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UEG Week 2014 Poster Presentations

United European Gastroenterology Journal


2(1S) A132A605
! Author(s) 2014
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DOI: 10.1177/2050640614548980
ueg.sagepub.com

MONDAY, OCTOBER 20, 2014


9:0017:00
POSTER PLUS VIDEO I POSTER EXHIBITION HALL XL_____________________
P0001 EUS GUIDED TRANSMURAL DRAINAGE OF WOPN;
COMPARISON BETWEEN A NEW FULLY COVERED LARGE BORE
WIDE FLARE METAL STENT (NAGI STENT) VS MULTIPLE
PLASTIC STENTS: A SINGLE CENTRE RETROSPECTIVE STUDY
N. Dubale1,*, A. Bapaye2, S.K. Davavala1, H. Gadhikar1, S. Dhadpahale1,
S. Date1, J. Bapaye3
1
Digestive Diseases and Endoscopy, 2Digestive Diseases and Endoscopy, Deenanath
Mangeshkar Hospital and Research Centre, Pune, 3Shreemati Kashibai Nawale
Medical College, Pune, India
Contact E-mail Address: amolbapaye@gmail.com
INTRODUCTION: WOPN is a frequent sequel of acute necrotizing pancreatitis.
The best approach for drainage of these collections is still controversial. We
present our retrospective data comparing the two endoscopic methods for drainage of WOPN.
AIMS & METHODS: Outcomes of patients undergoing EUS guided transmural
drainage (EUTMD) using a newly designed fully covered large-bore wide-flare
metal stent (Nagi stent) (Gr I) were compared to the outcomes of patients who
underwent placement of multiple plastic stents (Gr II). The pre-op CECT confirmed suitability of endoscopic drainage based on location, wall thickness &
contents. Visual quantification of necrosis (450% solid debris) by EUS excluded
8 patients (3 in Gr I and 5 in Gr. II). The procedure in both groups is done by
standard technique by a single endoscopist. The difference between the two
groups was tract dilatation (6 mm in Gr I vs. 18 mm in Gr II). Placement of
NCT and subsequent necrosectomy was done whenever necessary. Follow-up
imaging was done at 72 hrs and thereafter at 2, 4, & 6 weeks. The outcomes
were compared in terms of clinical success, need for surgery, complications,
hospital stay and mortality.
RESULTS: N: 21(Gr. I), 61(Gr. II). The two groups were comparable in terms of
demographics, etiology of pancreatitis, cyst location, size and amount of debris.
Placement of NCT, need of necrosectomy and no of sessions required were also
not different between the two groups. Clinical success defined as resolution of
symptoms was seen in 100% of Gr. I patients vs. 73% in Gr. II (p 0.048). None
of the patients in Gr I required subsequent surgery vs 20/61 (32.7%) in Gr. II
(p 0.025). Complications: 15% in Gr. I vs 37% in Gr. II (p 0.016)
Mean hospital stay was 4 days (1-33) in Gr. I vs 8 (4-65) in Gr II (p 0.012).
Mortality was none in Gr. I vs. 6.5% (4/61) in Gr. II (p 0.22)
CONCLUSION: The Nagi stentTM is effective and safe for EUTMD of WOPN.
It permits rapid clinical resolution with 100% technical and clinical success rates.
It offers distinct advantage over plastic stents although further prospective studies are warranted.
Disclosure of Interest: None declared
P0002 ENDOSCOPIC ESOPHAGEAL RECONSTRUCTION FOR THE
TREATMENT OF A TOTAL AND EXTENSIVE DISRUPTION OF
THE ESOPHAGUS USING A RENDEZ-VOUS TECHNIQUE
J.-M. Gonzalez1,*, G. Vanbiervliet2, M. Barthet1
1
Gastroenterology, Aix-Marseille University, North Hospital, Marseille,
2
Gastroenterology, Nice Hospital, Nice, France
INTRODUCTION: Complete esophageal obstruction leads to definitive fasting.
The rendez-vous endoscopic approach had already been described for complex
stenoses as an alternative to surgery that has high morbid-mortality.
AIMS & METHODS: This is a case series report about six patients referred for
complete esophageal disruption classified in two groups: 1/ Long disruption (4
5cm), one after caustic ingestion and two due to an esophageal stripping during
SEMS removal. Two had an associated loss of the SES; 2/ Short disruption (5
5cm), consecutive to radiation therapy for a neck neoplasia. They had been
fasting for 3 to 18 months. All the procedures were performed according the
anterograde retrograde approach, under anesthesia and with CO2 insufflation
and X-rays guidance.
RESULTS: There were 3 men and women between 25 and 71 years old. All the
reconstructions have been successful in one to three endoscopic sessions, using
the non hydrophilic tip of a guide wire passed through a straight catheter in 5
cases and a EUS needle in only one case. In 2 cases, a neo-SES had to be created,
by transillumination (n 1) or head and neck surgery (n 1). In order to guide
the reconstruction, SEMS was used in one case, NGT in one case, and both were
used in one patient. The first dilation was performed with a CRE balloon
(12-15mm). All the patients could eat mixed after 2 POD. There was no intraoperative or post-operative complication. Then, the patients underwent 3 to 18
dilations sessions during 1.5 to 15 months; two are still undergoing dilations and
all eat normally.
CONCLUSION: Endoscopic rendez-vous for esophageal reconstruction is safe
and effective in case of esophageal disruption even with loss of SES, avoiding
surgery.
Disclosure of Interest: None declared

P0003 ENDOSCOPIC SUBMUCOSAL DISSECTION


GASTRIC CANCERS USING THE CLUTCH CUTTER

OF

EARLY

K. Akahoshi1,*, Y. Motomura1, M. Kubokawa1, J. Gibo1, N. Kinoshita1,


S. Osada1, Y. Shimokawa1, K. Tokumaru1, Y. Otsuka1, T. Hosokawa1,
N. Tomoeda1, R. Utsunomiya1, T. Miyazaki1, K. Miyamoto1, M. Oya1
1
Gastroenterology, ASO IIZUKA HOSPITAL, Iizuka, Japan
Contact E-mail Address: kakahoshi2@aol.com
INTRODUCTION: To reduce the risk of complications related to ESD using
conventional knives, we developed the Clutch Cutter (CC), which can grasp and
incise the targeted tissue using electrosurgical current.
AIMS & METHODS: From June 2007 to March 2014, 325 consecutive patients
(228 men, 97 women; mean age 74 years, range 35-95) with a diagnosis of intramucosal or superficial submucosal gastric cancer without lymph node involvement, that had been confirmed by preliminary endoscopy, EUS, and endoscopic
biopsies, were enrolled into this prospective study. The CC was used for all steps
of ESD (marking, circumferential marginal incision, submucosal dissection, and
hemostatic treatment). The therapeutic efficacy and safety were assessed.
RESULTS: The mean size of the early gastric cancers and resected specimens was
17.3 mm and 46.7 mm, respectively. The mean operating time was 97.2 minutes.
The rate of en-bloc resection was 99.7% (324/325), and en-bloc resection with
tumor-free lateral/basal margins (R0 resection) was 95.1% (309/325), respectively. The R0 resection rates according to tumor size and location were 97.4%
(229/235) in less than 20 mm, 88.9% (80/90) in larger than 20 mm; 96.9%
(127/131) in lower portion, 91.9% (91/99) in middle portion, and 94.7% (91/
95) in upper portion. The mean operating time according to tumor size and
location was 93.4 min in less than 20 mm, 140 min in larger than 20 mm; 73.9
min in lower portion, 108.8 min in middle portion, and 117.2 min in upper
portion. Perforation during ESD occurred in one case (0.3%), which was managed with conservative medical treatment after endoscopic closure of the perforation. Post ESD bleeding occurred in 11 cases (3.4%), which were successfully
treated by endoscopic hemostatic treatment.
CONCLUSION: ESD using CC is a safe and technically efficient method for
resecting early gastric cancers.
REFERENCES
1) Akahoshi K, Akahane H, Murata A, et al. Endoscopic submucosal dissection
using a novel grasping type scissors forceps. Endoscopy 2007; 39: 1103-1105.
2) Akahoshi, K, Akahane H, Motomura Y, et al. A new approach: endoscopic
submucosal dissection using the clutch cutter for early stage digestive tract
tumors. Digestion 2012: 85: 80-84.
Disclosure of Interest: K. Akahoshi Other: Kazuya Akahoshi and FUJIFILM
have applied for the patent in Japan, Europe, and USA for the Clutch Cutter
described in this article. China has already granted the patent., Y. Motomura:
None declared, M. Kubokawa: None declared, J. Gibo: None declared, N.
Kinoshita: None declared, S. Osada: None declared, Y. Shimokawa: None
declared, K. Tokumaru: None declared, Y. Otsuka: None declared, T.
Hosokawa: None declared, N. Tomoeda: None declared, R. Utsunomiya:
None declared, T. Miyazaki: None declared, K. Miyamoto: None declared, M.
Oya: None declared
P0004 ENDOSCOPIC MYOTOMY FOR ACHALASIA USING A
COMBINATION OF NESTIS WATER JET SYSTEM AND HOOK
KNIFE: EVALUATION OF THE SAFETY AND THE EFFECTIVENESS
M. Pioche1,2,*, S. Roman3, M. Ciocirlan4, F. Mion3, T. Ponchon5
Gastroenterology and endoscopy, Hopital Edouard Herriot, 2Inserm U1032,
3
Functional disorders unit, Hopital Edouard Herriot, Lyon, France,
4
Gastroenterology and endoscopy unit, Institut Carol Davila, Bucharest, Romania,
5
Gastroenterology and endoscopy unit, Hopital Edouard Herriot, Lyon, France
Contact E-mail Address: mathieupioche@free.fr
1

INTRODUCTION: The peroral endoscopic myotomy (POEM) is a promising


method for the treatment of the esophageal achalasia. But the precise technique
can be refined. We developed a combined technique of water jet system for
tunnelling and hook knife section for myotomy and we evaluated its results in
a prospective study.
AIMS & METHODS: The patients presented with an achalasia without any
prior instrumental treatment. The submucosal tunnel was created 12 cm over
the cardia and 3 cm below, and then the endoscopic myotomy was performed
using the Olympus Hook Knife by a single operator with CO2 insufflation,
beginning 8 cms over the cardia and finishing 2 cms below. The clinical evaluation was realized before and then after the procedure at 1, 3, 6 and 12 months
(score of Eckardt, score of quality of life GIQLI). A high-resolution manometry
was realized before POEM and 3 months later to classify the achalasia (classification of Chicago) and to measure basal pressure and pressure of relaxation
integrated (PRI) of the lower esophageal sphincter. Then an esophageal
pHmetry of 24 hours was performed at 3 months to diagnose GERD. The

A133

United European Gastroenterology Journal 2(1S)


data are expressed in median (extremes) and compared before and later myotomie by paired t-test.
RESULTS: 21 patients (13 men, average age 61 years) were included. 18 procedures were complete, 1 was not realized because of a large esophageal diverticulum, 2 were interrupted (1 sub-mucosal fibrosis preventing the realization of the
tunnel and 1 mucosal injury of the tunnel in the cardia). 2 other mucosal injuries
occurred but did not prevent to continue the procedure after mucosal closure by
clips. Dual Knife (n 7) or the water jet Nestis Enki 2 (n 11) were used for
the tunnel. No mucosal injuries were observed with the water-jet system. Hook
Knife was used for all myotomies. The average time of procedure was 94.2 min
with a clear learning curve (135-35 min). A pneumoperitoneum was exsufflated
with a needle during the procedure in 13 cases without any visible perforation.
CT scan at day 1 showed a pneumomediastinum (n 14/18), a pneumoperitoneum (n 14/18) and/or a peumothorax (n 3/18). No sepsis was observed.
Feeding was always possible with liquids at day 1. All patients noted a clinical
improvement. At 3 months, the basal pressure of the SIO was decreased for all
patients (8 mmHg (0-15) against 23 mmHg (7-48) initially, p50.01) as well as the
PRI (8 mmHg (0-16) against 23 mmHg (9-28), p50.01). pH metry showed a
pathological GERD (esophageal pH 4 during more than 5% of time in 3 cases.
Inclusion

1 month

3 months

6 months

1 year

n
21
17
14
10
3
Eckardt 6 (3-11)
1 (0-3)*
1 (0-3)*
0 (1-4)*
0 (0-0)*
GIQLI 82 (50-114) 115 (66-135)* 115 (82-140)* 131 (94-143)* 140 (130-142)

CONCLUSION: Water-jet injection allows rapid and safe tunneling of the submucosa and myotomy with hook knife is very precise. Safety and effectiveness of
mytomy is reinforced using these technical refinements.
Disclosure of Interest: None declared
P0005 COMPUTER-AIDED DECISION SUPPORT SYSTEM IN HIGHMAGNIFICATION AND NARROW-BAND IMAGING ENDOSCOPY
FOR DIFFERENTIATION OF GASTRIC LESIONS
R. Kuvaev1,*, S. Kashin1, H. Edelsbrunner2, M. Machin3, O. Dunaeva3,
E. Nikonov4, V. Kapranov5, A. Rusakov6
1
Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation,
2
Institute of Science and Technology Austria (IST Austria), Klosterneuburg,
Austria, 3Delone Laboratory of Discrete and Computational Geometry, P. G.
Demidov Yaroslavl State University, Yaroslavl, 4Administration, Polyclinic 1 of
the Business Administration for the President of Russian Federation, Moscow,
5
Internet Center, 6Administration, P. G. Demidov Yaroslavl State University,
Yaroslavl, Russian Federation
Contact E-mail Address: kuvaev_roman@mail.ru
INTRODUCTION: High-magnification endoscopy with narrow-band imaging
(HME-NBI) has been used for diagnosis of gastric pathology because of its high
accuracy. Nevertheless, the application of these advanced techniques in clinical
practice is difficult due to the presence of various histological changes of gastric
mucosa with different modifications of microvascular and microsurface patterns.
Newly developed computer-aided decision support systems are designed to detect
and/or classify abnormalities and thus assist a medical expert in improving the
accuracy of medical diagnosis. However, there is lack of data for computer-aided
devices for classification of gastric lesions with HME-NBI.
AIMS & METHODS: The aim of this study was to evaluate the effectiveness of
computer-aided classifier of endoscopic magnification images of gastric lesions.
We analyzed our database contains 78 endoscopy NBI magnification images of
gastric lesions (Olympus Exera GIF Q160Z, Lucera GIF Q260Z). All images
were classified into three classes: oval (13 images), tubular (31 images), and
destroyed with vessel network (34 images). Initially we divided images of every
class into two sets training set and test set. Then we selected uniformly distributed random points with fixed density (one random point for every 300
pixels) at every picture, which were analyzed by extracting topological features
for building the classifier. Training set images were used for classifier training
with Adaboost algorithm and testing set images of each group were utilized for
testing with previously trained classifier. We repeated the procedure described
above for the estimation of classifier quality.
RESULTS: From 78 database images there were 50 images (66.6%) with the
success rate of correct classification exceeding 80%. In 14 images (17.9%) all
points (100%) were recognized correctly. The mean percentage of points with the
correct classification was 79%.
CONCLUSION: Topological features were successfully used for description of
endoscopic magnification images. The combination of topological features analyzed with Adaboost algorithm allowed for creating and effective training of
computer-aided classifier of endoscopic magnification images of gastric lesions.
Disclosure of Interest: None declared

P0006 NOVEL NARROW-BAND IMAGING SYSTEM WITH DUAL


FOCUS MAGNIFICATION IN ENDOSCOPIC MAPPING OF THE
GASTRIC MUCOSA IN PATIENTS WITH PRECANCEROUS
CONDITIONS AND LESIONS OF THE STOMACH
R. Kuvaev1,*, S. Kashin1, E. Nikonov2, A. Nadezhin3
1
Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, 2Administration,
Polyclinic 1 of the Business Administration for the President of the Russian
Federation., Moscow, 3Pathology, Yaroslavl Regional Cancer Hospital, Yaroslavl,
Russian Federation
Contact E-mail Address: kuvaev_roman@mail.ru
INTRODUCTION: Endoscopic mapping of the entire stomach with advanced
techniques has been recommended as an important step of surveillance of premalignant gastric conditions/lesions [1]. Although current imaging technologies,
such as narrow-band imaging (NBI) and high-magnification endoscopy, allow
enhanced visualization of gastric mucosa, their application is still limited due to
low contrast and brightness of endoscopic view and complexity of usage. Newly
developed NBI system with dual focus (DF) magnification might be a promising
tool to overcome this challenge.
AIMS & METHODS: The aim of this study was to evaluate diagnostic accuracy
of new NBI-DF system in detection, characterization of gastric lesions in patients
with extensive atrophy and/or intestinal metaplasia. A total of 43 patients (mean
age 51.3 years, SD 12.1) were initially examined by conventional white light
endoscopy (WLE) followed by NBI overview. Afterwards chromoendoscopy
(CE) with indigocarmine was performed as the gold standard for detection
of lesions. Any suspicious areas detected by NBI or CE were subsequently further
assessed with NBI with DF (Olympus Exera III GIF H190) and characterized
accordingly. Biopsies were taken from all lesions for histological assessment.
RESULTS: From 93 detected gastric lesions there were 75 non-neoplastic
(chronic gastritis, intestinal metaplasia), 3 low-grade dysplasia, and 15 highgrade dysplasia/early gastric cancer. All lesions (100%) detected by CE were
found with NBI observation. Endoscopic histology prediction was successful in
88 cases (94.6%) Endoscopic misdiagnosis was found in 5 cases (5.4%): overestimation in 3 cases, underestimation in 2 cases; sensitivity, specificity, positive
predictive value and negative predictive value were 80%, 97.4%, 85.7% and
96.2% respectively for early gastric cancer/high-grade dysplasia.
CONCLUSION: Observation of gastric mucosa with a novel NBI system was at
least as effective as CE with indigocarmine in detection of suspicious gastric
lesions in patients with precancerous conditions and lesions of the stomach.
Dual focus magnification provides sufficient assessment of microvascular and
microsurface patterns in order to differentiate gastric lesions. Further randomized controlled studies are needed to be performed for clarifying the role of
novel endoscopic system in diagnosis of gastric pathology.
REFERENCES
1. Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous
conditions and lesions in the stomach (MAPS): guideline from the European
Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study
Group (EHSG), European Society of Pathology (ESP), and the Sociedade
Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.
Disclosure of Interest: None declared
P0007 DEVELOPMENT
OF
A
PROTOTYPE
OF
VIDEO
SYNCHRONISATION FOR RELOCALISATION OF BIOPSY SITES
DURING ENDOSCOPIC EVALUATION OF BARRETTS
OESOPHAGUS: PRELIMINARY EXPERIMENTAL AND CLINICAL
STUDY
S. Adrien1,*, V. Anant1, H. Jerome1, N. Stephane2, S. Luc2, D. Michel1
1
CHU Strasbourg, 2IRCAD, Strasbourg, France
Contact E-mail Address: adrien.sportes@free.fr
INTRODUCTION: The prevalence of Barretts oesophagus (BE) is 5 to 6% in
the general population, with a progression from dysplasia to adenocarcinoma 0.6
to 0.7 patient-years. Hence, endoscopic surveillance is justified to detect early
lesions accessible to endoscopic treatment. However, the relocalisation of lesions
detected by biopsies may be difficult during follow-up endoscopies. The purpose
of this study was to evaluate the prototype of a magnetic probe for accurate
location of the position of the endoscope, allowing the relocalisation of this
position in a subsequent endoscopy. We report the results of a feasibility study
in pigs and the use of this device in two patients with BE.
AIMS & METHODS: The system consists of an electromagnetic (EM) field
transmitter and an EM probe constituting the electromagnetic tracking system
(EMS) (NDI, Aurora). The EM probe is inserted through the operating channel
of a double channel gastroscope. The EM field generator is positioned on the
patients chest wall. The system also includes new software developed at IHU/
IRCAD, which performs simultaneous recording of the video from the endoscope alongwith its corresponding position, as measured by the EMS. During a
second endoscopy, this software allows automatic synchronisation of the
recorded video to provide relocalisation of the endoscope in front of previous
biopsy sites in the oesophagus.
The system was tested in 5 anesthetised pigs. During the first endoscopy, ten
markings were performed by argon plasma electrocoagulation (ERBE Tubingen,
Germany) in the distal oesophagus. The position of each marking was recorded
by the system. A second operator to then performed a blind endoscopy on the
same pigs and was asked to follow the system implicitly as a guide to relocate the
markings.
In 2 patients with BE, the system was then tested to facilitate relocalisation of the
biopsy sites.
RESULTS: Ten markings were made in the distal oeosphagus of 5. After withdrawal of the endoscope the second operator found 48 of the 50 markings (96%)

A134
using the guidance provided by the system. The positioning of the endoscope
provided by the EMS system was within a 2mm range from the initial positionning. In the evaluation of BE patients, the system relocalised the biospy sites
within a range of 3mm.
CONCLUSION: This preliminary study shows the feasibility of the EMS prototype to relocalise the endoscope in the oesophagus within an acceptable range.
The clinical usefulness of this system should be evaluated further during the
follow-up of patients with BE.
Disclosure of Interest: None declared
P0008 THE UTILITY OF ROUTINE CHROMOENDOSCOPY FOR
DETECTION OF DYSPLASTIC LESIONS DURING SURVEILLANCE
COLONOSCOPY IN PATIENTS WITH COLONIC INFLAMMATORY
BOWEL DISEASE. DOES RESEARCH TRANSLATE TO CLINICAL
PRACTICE?
U. Javaid1, R. Thethi1, P. Luthra1, N. Mohammed2,*, J. Hamlin1,
B. Rembacken1, V. Subramanian2
1
Gastroenterology, St James University Hospital, Leeds Teaching Hospital NHS
Trust, 2Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences,
University of Leeds, Leeds, United Kingdom
Contact E-mail Address: v.subramanian@leeds.ac.uk
INTRODUCTION: Dysplasia in colonic inflammatory bowel disease (IBD) is
often multifocal and flat. Chromoendoscopy (CE) has been shown in prospective
studies to improve dysplasia detection rates by improving the ability to detect
subtle mucosal changes. (1) The utility of CE in dysplasia detection in patients
with IBD during routine clinical practice has not been reported so far. We aimed
to compare the yield of dysplastic lesions detected by CE with standard white
light endoscopy (WLE).
AIMS & METHODS: Retrospective cohort study of patients with long standing
(47 years) colonic IBD undergoing surveillance colonoscopy at Leeds Teaching
Hospital NHS Trust between January 2012 to December 2013. Details of diagnosis, duration of disease and outcomes of the colonoscopy were collected from
the endoscopy database, electronic patient records and patient notes.
RESULTS: There were 120 colonoscopies in the CE group and 220 colonoscopies in the WLE group. The groups were well matched for all demographic
variables. 27 dysplastic lesions were detected in 20 patients in the CE group
and 9 dysplastic lesions were detected in 6 patients in the WLE group. All the
lesions were detected on targeted biopsy and harboured low grade dysplasia. The
adjusted prevalence ratio (on a per patient basis) for detecting any dysplastic
lesion was 4.6 (95% CI 1.6-13.7) in favour of CE.
CONCLUSION: CE colonoscopy improves detection of dysplastic lesions
during surveillance colonoscopy of patients with colonic IBD even in routine
clinical practice, confirming data from prospective trials. CE should be the standard of care for all IBD surveillance procedures as advocated by both BSG and
ECCO guidelines.
REFERENCES
(1) Subramanian V, Mannath J, Ragunath K, et al. Meta-analysis: the diagnostic
yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33: 304-312.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
LIVER & BILIARY I POSTER EXHIBITION HALL XL_____________________
P0009 INVOLVEMENT OF B-CELLS IN HEPATIC INFLAMMATION
DURING NONALCOHOLIC STEATO-HEPATITIS (NASH)
A. Jindal1,*, S. Sutti1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1 on
behalf of Laboratory of General Pathology, Prof. Albano, Novara, Italy
1
Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy
Contact E-mail Address: aastha.jindal@med.unipmn.it
INTRODUCTION: Growing evidence indicates that adaptive immunity contributes to the process leading to chronic hepatic inflammation in NASH. However,
the mechanisms involved are still incompletely characterized. Recently, B-lymphocytes have emerged as players in orchestrating adipose tissue inflammation in
obesity contributing to the development of insulin resistance.
AIMS & METHODS: We investigated the possible role of B-cell responses in the
pathogenesis of NASH. NASH was induced by feeding four weeks C57BL/6 mice
with a methionine-choline deficient (MCD) diet.
RESULTS: In mice receiving the MCD diet the development of steatohepatitis
was associated with an increased hepatic infiltration by B220 (CD20) positive Blymphocytes and by the detection of circulating IgG targeting oxidative stressderived antigens such as malonildialdehyde- (MDA) and 4-hydroxynonenal-protein adducts. Moreover, immunohistochemistry showed the presence of IgG
deposits within the hepatic inflammatory infiltrates that co-localized with
MDA-derived antigens, indicating the formation of immunocomplexes. To substantiate the role of oxidative stress in triggering B-cell responses in NASH, mice
were immunized with MDA-adducted bovine serum albumin (MDA-BSA)
before feeding the MCD diet. In MCD-fed, but not in control mice, MDABSA immunization promoted liver B-cell expansion and enhanced transaminase
release, lobular inflammation and the hepatic production of the pro-inflammatory cytokines TNF-, IFN-, IL-12. Among immunized MCD-fed mice there
were also positive correlations between the individual expression of the B-cell
marker B220 and those of macrophage M1 activation markers IL-12p40 and
iNOS (r 0.87 and 0.71 respectively; p50.02).
This effect was likely mediated by B-cell interaction with CD4 T-cells as in the
same animals B220 expression also positively correlated with that of IFN-
(r 0.76; p50.03) and of the co-stimulatory molecule CD40 (r 0.72;

United European Gastroenterology Journal 2(1S)


p50.05). Furthermore, depleting CD4 T-cells in MCD-fed immunized mice
by using an anti-CD4 monoclonal IgG did not affected B220 expression, but
significantly lowered the hepatic mRNAs IFN-, iNOS and IL-12p40 and ameliorated lobular inflammation and focal necrosis.
CONCLUSION: These results indicate that B-cell responses triggered by oxidative stress can contribute to inflammation in NASH by stimulating T-cellular
responses.
Disclosure of Interest: None declared
P0010 GENERATION OF A VECTOR CONTAINING AN SHRNA FOR
THE RECEPTOR CB1 AS AN ANTIFIBROGENIC STRATEGY IN
LIVER DISEASE
A. D az Rivera1,*, V. Chagoya de Sanchez 2, G. Velasco Loyden 2, L. Garc a
Benavides 3, J. Armendariz Borunda 1, A. Sandoval Rodr guez1
1
Molecular Biology and Gene Therapy Institute, Guadalajara, 2Cellular Physiology
Institute, Mexico, D. F, 3Institute of Experimental and Clinical Therapeutics,
Guadalajara, Mexico
Contact E-mail Address: adrianadiaz.riv@gmail.com
INTRODUCTION: Blockade of cannabinoid type I receptor (CB1) by pharmacological antagonist has demonstrated antifibrogenic effects in models of cirrhosis. Gene therapy with a shRNA molecule for CB1 wthinin an adenovirus has the
advantage of hepatic tropism, which will reduce side effects and increase the
transduction efficiency.
AIMS & METHODS: Design a shRNA that efficiently inhibit the expression of
CB1, evaluate its antifibrogenic effect in an experimental model of liver cirrhosis
and generate an adenoviral vector coding for the shRNA-CB1.
shRNA sequences were designed to blockade mRNA of CB1 at positions 877,
1232, 1501 (pshCB1-A, B, D). The effectiveness of the shRNA was evaluated by
inhibition of the mRNA-CB1 after transfection of the plasmids in primary culture rHSC. To determine the optimum dose for transfection in primary cultures,
lipofectamine 2000 and Fugene HD were tested using a GFP expressing plasmid (pITR-GFP). Later, we evaluated shRNA mediated-CB1 inhibition in cirrhotic rats intoxicated with CCl4. The plasmids were administrated by
hydrodynamic injection in a volume of 4 mL. Then, in animals transfected
with the most potent shRNA-CB1, mRNA levels of fibrogenic molecules
(TGF-1, Col 1 and -SMA) and percentage of fibrotic liver tissue was measured. Finally, Ad5 backbone coding for shRNACB1-1232 or shRNA-Irrelevant
was generated by homologous recombination between pshRNA and the pAd /
BLOCK-iT TM DEST.
RESULTS: In vitro shRNA designed to block position 877 and 1232 significantly inhibited mRNA (p4 0.05) CB1 gene expression in 77% and 91%, respectively using Fugene HD. The sequence of shRNA-Irrelevant did not affect
mRNA expression of CB1. Hydrodynamics-based transfection of shRNA-CB1
via iliac vein in the rat allows efficient and repeatable delivery to the liver. A
volume of 4 mL carrying 3 mg/kg was administered in 5-7 seconds. In CCl4
model shCB1-1232 showed major decrease in CB1 mRNA and protein
(p50.05), and in consequence fibrogenic molecules TGF-1, Col I, -SMA
also reduced (60%, 47% and 77% (p50.05); respectively). Fibrosis diminished
49% (p50.05) compared to untreated controls. Thus pshRNACB1-1232 was
selected for production of adenovector. Homologous recombination between
attL and attR regions between pshRNA-1232-CB1 and pAd / BLOCK-iT TM
DEST allowed the generation of Ad-shRNA1232-CB1 backbone.
CONCLUSION: shCB1-1232 demonstrates CB1 gene and protein silencing
in vitro and in vivo, decreasing mRNA levels of key fibrogenic molecules and
fibrosis, showing potential to be used as therapeutic strategy for liver fibrosis.
Recombinant adenovirus expressing this shRNA will have the advantage of high
titers production conserving efficient liver transduction, which will facilitate its
therapeutic application in experimental models of liver cirrhosis or even clinical
scenarios.
Disclosure of Interest: None declared
P0011 CORRELATION BETWEEN INDIRECT SERUM MARKERS AND
MORPHOMETRIC VALUES OF FIBROTIC TISSUE IN PBC
C. Stasi1,*, L. Leoncini1, M.R. Biagini1, S. Madiai1, F. Marra1, G. Laffi1,
S. Milani2
1
Department of Experimental and Clinical Medicine, 2Department of Biomedical,
Experimental and Clinical sciences, University of Florence, Florence, Italy
INTRODUCTION: The accuracy of non-invasive methods for the quantification
of liver fibrosis in patients with PBC is still debated. Moreover, the Ludwigs
PBC stages do not represent a measurement of quantitative fibrosis.
AIMS & METHODS: We determined the histomorphometrical measurement of
fibrotic tissue and analyzed the accuracy of a number of indirect markers of liver
fibrosis for the detection of different histological stages of PBC and the association between indirect serum markers and morphometric values (MV) of fibrotic
tissue.
Methods: Sections of liver tissue were stained with hematoxylin/eosin and
Sirius red. Only samples with a 4 25 mm length and including at least 11
complete portal tracts were considered adequate for the study.
Histomorphometrical measurement of fibrotic tissue was performed on sirius
red stained sections of liver biopsies. Area percentage measures of fibrotic
tissue were ranked into 4 groups reflecting Ludwigs staging and compared
with values of the following serum markers of liver fibrosis: APRI, LOK,
FORNS, FIB-4. The percentage of fibrosis was calculated with ImageJ. All
results were expressed as mean  standard deviation. The numerical comparison
of continuous data was performed using the Wilcoxon signed ranks test applied
to two-samples. Linear regression analysis between two variables was performed
by using Pearson correlation. Statistical significance was set at a value of p50.05.

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United European Gastroenterology Journal 2(1S)


RESULTS: We enrolled 50 patients with PBC (mean age, 5712.30 years; 43 F
and 7 M; 8 AMA negative, 42 AMA positive). There were 19 (38%) patients in
Ludwigs PBC stage I, 14 (28%) in stage II, 12 (24%) in stage III and 5 (10%) in
stage IV. The morphometric values (Table 1) of fibrotic tissue were significantly
different in the various Ludwigs stages of PBC (p50.05). Only LOK score was
statistically different between stage II and III (p 0.02). No other significant
differences were found in the various Ludwigs stages of PBC for APRI,
FORNS, FIB-4 and LOK scores (Table 1). A statistically significant correlation
was found between MV and Forns (R2 0.3643, p 0.0004), MV and FIB-4
(R2 0.3945, p 0.0002), MV and LOK (R2 0.3367, p 0.0010), MV and
APRI (R2 0.1476, p 0.0361).
Table 1.
Ludwigs
stages

Morphometric
values

FORNS

FIB-4

Stage
Stage
Stage
Stage

0.74%  0.65
3.87%  1.5
6.15%  1.68
14.06%  8.45

3.61
4.55
5.52
8.05

0.24
0.35
0.35
1.00

I
II
III
IV






1.62
1.8
2.06
1.76






LOK
0.26
0.39
0.16
0.76

0.20
0.22
0.38
0.69






APRI
0.16
0.18
0.19
0.34

0.61
0.49
0.67
1.24






0.76
0.35
0.44
0.79

CONCLUSION: Histomorphometric values of fibrotic tissue increase progressively in Ludwigs stages of PBC, where non-invasive markers do not, and correlate positively with indirect serum markers of liver fibrosis.
Disclosure of Interest: None declared
P0012 THE NGF RECEPTOR P75NTR LEADS TO
HYPERTROPHY DURING THE DEVELOPMENT OF LIVER
CIRRHOSIS AND MALIGNANT LIVER TUMORS

NEURAL

D. Hartmann1,*, S. Werscher1, R. Go1, S. Teller1, M. Schlitter2, K. Becker2,


H. Friess1, G.O. Ceyhan1
1
Department of Surgery, 2Institute of Pathology, Technische Universitat Munchen,
Munich, Germany
Contact E-mail Address: daniel.hartmann@tum.de
INTRODUCTION: The autonomic nervous system is the involuntary part of the
peripheral nervous system and regulates the intestinal motor activity, smooth
muscles and exocrine glands. Autonomic nerves that innervate the liver reach
the organ via the hepatic hilum and run together with the portal vein, the hepatic
artery and the bile duct. In the full clinical picture of liver cirrhosis, no parenchymal innervation can be detected. In addition, malignant liver tumors, such as
hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC), are
not innervated.
AIMS & METHODS: The aim of this work is the characterization of a possible
hepatic neuroplasticity, including responsible neurotrophic factors. In the present
work, a collective consisting of 103 patients (22 patients with normal liver tissue,
23 patients with liver cirrhosis, 45 patients with HCC and 13 patients with CCC)
was examined for variations in nerve number and nerve size. In addition, growth
factors, such as Growth-Associated Protein (GAP-43) and Nerve Growth Factor
(NGF), as well as their receptors TrkA and p75NTR were investigated by immunohistochemistry and qRT-PCR in terms of their involvement in a possible
hepatic neuroplasticity.
RESULTS: The multiple comparison of median nerve sizes of the examined
entities showed a clearly significant difference. The largest nerves were discovered
in HCC samples. However, no difference in neural density was detected.
Furthermore, significant differences were observed for the high affinity NGFreceptor TrkA and the low affinity NGF-receptor p75NTR with regards to
immunoreactivity and relative expression. The highest p75NTR expression was
found in normal liver tissue and both, relative expression as well as immunoreactivity, decrease with increasing nerve size.
CONCLUSION: The results of the present study suggest that the observed
neural changes in the liver are related to active neural remodeling processes.
The NGF receptor p75NTR seems to take on a key role in this context. Since
p75NTR binds all neurotrophins with low affinity, further research is warranted
concerning its involvement in the plasticity of hepatic nerves.
Disclosure of Interest: None declared
P0013 HIGH CONCENTRATION OF FIBROTIC AND INFLAMMATORY
MARKERS AMONG PATIENTS WITH SCHISTOSOMAL LIVER
DISEASES
E. Sinkala1,2, P. Kelly3,4, E. Sinkala1,2,*
Internal Medicine, University of Zambia, 2Internal Medicine, TROPGAN,
Lusaka, Zambia, 3Internal Medicine, Barts and London, Blizzard Institute,
London, United Kingdom, 4Internal Medicine, University Teaching Hospital,
Lusaka, Zambia, Lusaka, Zambia
Contact E-mail Address: sinkalaeddie@yahoo.com
1

INTRODUCTION: Worldwide the commonest cause of portal hypertension is


cirrhosis, but in tropics it is schistosomiasis. Some parts of Zambia are hyperendemic with prevalence of 77%. Hepatocellular function is preserved in hepatosplenic schistosomiasis hence prognosis is better than cirrhosis. Liver biopsy
can confirm fibrosis but it is invasive.
AIMS & METHODS: This is an ongoing case control study involving 70 cases
and 20 controls. All cases had varices and were negative for HIV, hepatitis B and
C viruses. Hyaluran was used as a marker of liver fibrosis while TNF receptor 1,
sCD14, IL1 beta, IL 6 and CRP were inflammatory markers.

We set out to investigate fibrotic and inflammatory makers in hepatosplenic


schistosomiasis patients at the University Teaching Hospital, Lusaka, Zambia.
RESULTS: Eighty patients were evaluated and serology for schistosomiasis was
positive in 74 (93%) and negative in 6 (7%). Hyaluran levels compared with
controls were higher, p50.001 (median 111.6ng/ml, IQR 39.1, 240.3).
Inflammatory markers were elevated: TNF receptor 1 concentrations compared
with controls were higher, p 50.001 (median 3150.1pg/ml (IQR 1703.2, 10460.0),
sCD14 values were higher than in controls p50.001, median 2365.0ng/ml
(IQR1744.9, 3128.6). IL 1 beta values were higher than in controls p 0.013,
median 4.3pg/ml (IQR 0.8, 13.2) and so were IL 6 values p 0.001 (median
15.26pg/ml, IQR 10.15, 38.13). Spearmans rank correlation of hyaluran and
TNF receptor 1 was positive (r 0.44, p 0.002) and so was hyaluran and IL6
(r 0.251, p 0.045).
CONCLUSION: Schistosomiasis is a leading cause of portal hypertension in
Zambia and induces a liver fibrotic marker which could be used to assess disease
severity. It seems hepatosplenic schistosomiasis also induces high levels of TNF
receptor 1, sCD14, IL1 beta and IL6. These elevated markers could be due to
bacterial translocation which needs to be confirmed by markers of bacterial
translocation such as LPS.
Disclosure of Interest: None declared
P0014 LIVER FIBROSIS PREVENTION AFTER INTRAMUSCULAR
ADMINISTRATION OF MATRIX METALLOPROTEINASE-8
ADENOVIRAL VECTOR IN A MODEL OF HEPATIC FIBROSIS
J. Garcia-Banuelos1,*, E. Eden Oceguera-Contreras1, D. Gordillo-Bastidas1,
A. Sandoval-Rodr guez1, B. Bastidas-Ram rez2, J. Gonzalez-Cuevas1, J. MaciasBarragan1, B. Belinda Gomez-Meda1, J. Armendariz-Borunda1 on behalf of
INNOVARE, Guadalajara, Jalisco, Mexico
1
Instituto de Biologa Molecular y Terapia Genica, Centro Universitario de
Ciencias de la Salud, 2Instituto de Enfermedades Cronico Degenerativas, Centro
Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara,
Mexico
INTRODUCTION: MMP-8 degrades preferentially collagen type I (collagen of
higher proportion of hepatic fibrosis). We delivered MMP-8 gene in to the
muscle, using an Adenovirus vector, protein is released systemically and is activated in the liver.
AIMS & METHODS: Our aim was to evaluate profibrogenic gene expression
pattern and liver fibrosis prevention.
We used four groups of rats (n 15): control; thioacetamide (TAA), inducedfibrosis; TAAAdGFP; TAAAdMMP8. At the beginning of the fifth week of
TAA intoxication, administration of vectors in soleum muscle was accomplished.
Sub-groups of rats (n 5) at the end of first, second and third week after vector
administration were sacrificed. Percentage of fibrosis, liver function, gene expression of MMP8, proinflammatory genes (IL1-beta, TNF-alpha), profibrogenic
genes (collagen 1(I), CTGF and TGF-beta) and antifibrogenic genes (MMP1
and MMP9), were determined.
RESULTS: After 3 weeks of treatment: In the liver and serum, amount of MMP8
protein was sustained, fibrosis decreased up to 48%, proinflammatory genes
expression was modified only at the end of the third week, profibrogenic gene
expression decreased (Col 1(I) 4 times, TGF-beta 3 times and CTGF 2 times),
antifibrogenic genes expression increased (MMP9 2.8 times and MMP1 10
times). According to Knodell score, a clearly diminution of inflammatory cells
infiltration in comparison with counterpart animals treated with AdGFP, could
be appreciated.
CONCLUSION: A single dose of AdMMP8 in muscle is enough in order to
obtain a stable liver MMP8 protein expression and activity during 21 days.
Degradation of collagen in the liver modifies pro and anti-fibrogenic gene expression allowing a restoration of hepatic architecture.
Disclosure of Interest: None declared
P0015 WHOLE-PROTEIN MASS SPECTROMETRY TO IDENTIFY
CONGENITAL DISEASE OF GLYCOSYLATION IN END-STAGE
LIVER DISEASE
J.C. Jansen1,*, M.van Scherpenzeel2, D.J. Lefeber2, J.P. Drenth1
1
Gastroenterology and Hepatology, 2Laboratory of Genetic, Endocrine and
Metabolic Disease, Radboud University Medical Center, Nijmegen, Netherlands
Contact E-mail Address: Jos. Jansen@radboudumc.nl
INTRODUCTION: Congenital disorders of glycosylation (CDG) are a heterogeneous group of autosomal recessive metabolic diseases with a wide spectrum of
clinical symptoms. Depending on localization of the defective protein, two types
are distinguished (CDG-I; endoplasmatic reticulum and CDG-II; Golgi apparatus). Liver involvement is frequent in both groups and can even be predominant
for some CDG-II variants. Abnormal glycosylation is seen in liver cirrhosis,
probably resulting from affected liver synthesis. We hypothesized that mass
spectrometry (MS) differentiates between secondary and bonafide genetic
causes in end-stage liver disease.
AIMS & METHODS: To determine the effect of a diminished liver function on
glycosylation we analyzed anonymous serum samples drawn from end-stage liver
disease patients prior to their liver transplantation. As a first step we used transferrin isoelectric focusing (tIEF) to detect abnormal glycosylation. Selected samples were further analyzed with transferrin whole-protein MS to obtain a
comprehensive readout of the glycosylation profile.
We also obtained serum from 100 patients with a presumed CDG. Patients with a
predominant liver phenotype were selected for further analysis using exome
sequencing for identification of the pathogenic mutation.
RESULTS: We collected 1065 serum samples and found an abnormal tIEF
pattern in 30%. All abnormalities were mild and resembled a CDG-II pattern.

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United European Gastroenterology Journal 2(1S)

MS of abnormal tIEF samples had increased fucosylation of transferrin and loss


of one sialic acid.
We identified 18 patients with a phenotype resembling Wilson disease with liver
fibrosis, elevated transaminases, low ceruloplasmin and liver copper accumulation. DNA is currently prioritized for exome sequencing. MS comparison of the
Wilson disease-like patients and liver transplant patients showed that desialization is more abundant in Wilson disease-like patients and transferrin fucosylation
is seen more often in liver transplant patients.
CONCLUSION: Whole protein MS enables differentiation between abnormal
glycosylation secondary to liver failure and bonafide CDG. This can aid in the
detection of CDG as a cause for liver pathology.
Disclosure of Interest: None declared
P0016 MICRORNA EXPRESSION PROFILE IN SIMPLE STEATOSIS
AND NON-ALCOHOLIC STEATOHEPATITIS
K. Okamoto1,*, T. Okamoto1, T. Onoyama1, K. Miyoshi1, M. Kishina1, J. Kato1,
S. Tokunaga1, T. Sugihara1, Y. Hara2, M. Koda1, K. Hino2, Y. Murawaki1
1
2nd. Dept. of Internal Medicine, Tottori Univ. School of Medicine, Yonago,
2
Department of Hepatology and Pancreatology, Kawasaki Medical School,
Kurashiki, Japan
Contact E-mail Address: okamotka@grape.med.tottori-u.ac.jp
INTRODUCTION: Simple steatosis (SS) and non-alcoholic steatohepatitis
(NASH) are regarded as histological subtypes of non-alcoholic fatty liver disease
(NAFLD). The distinctive pathological difference between SS and NASH is that
NASH induces chronic liver inflammation and fibrogenesis, which can lead to
liver cirrhosis. The difference in pathogenesis between SS and NASH is still not
clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that
regulate gene expression by repressing translation or degrading target mRNAs.
Accumulating evidence indicates that miRNAs play important roles in various
life functions including inflammation, metabolism, and fibrosis.
AIMS & METHODS: The purpose of this study was to examine the relationship
of miRNA expression profiles with SS and NASH in animal models and humans.
DD Shionogi (DS), Fatty Liver Shionogi (FLS), and FLS ob/ob mice were
subjected as the normal control, SS model, and NASH model, respectively.
Microarray analysis was used to assess 375 miRNA expression profiles in
mouse liver tissue. Normalized miRNA expression ratios over 2log2 between
FLS and FLS ob/ob were identified as candidates. Real time PCR was used to
check the reproducibility of the microarrays predicting miRNAs from 4 mice in
each group. The putative miRNA target genes were predicted using the webdriven software DIANA microT-CDS. DAVID 6.7 was used to perform gene
ontology annotation and KEGG pathway enrichment analysis. The putative
miRNA expression profiles in human serum were also examined in every 10
patients with asymptomatic gallbladder stones, SS, and NASH.
RESULTS: In microarray analysis, 18 miRNAs were identified as candidates.
Among the 18 miRNAs, 6 showed good expression ratio reproducibility in real
time PCR and were confirmed to express commonly between mice and humans.
The expression levels of miR-200a and miR-200b increased in the order of
normal control, SS, and NASH. miR-1 was downregulated in NASH. miR376c, miR-409, and miR-411 showed potent high expression in SS, over 30fold of DS. KEGG pathway analysis indicated that the strongly expressed
miRNAs in SS (miR-376c, miR-409, and miR-411) had multiple targets in the
TGF- signaling pathway including TGFR, smad 2, 3, and 4. The analysis
suggests that miR-376c, miR-409, and miR-411 may protect liver fibrosis
through silencing the TGF- signaling pathway. In human serum, hierarchical
clustering analysis of the putative miRNA expression also showed clearly different expression profiles between SS and NASH.
CONCLUSION: The expression profiles of 6 miRNAs were different between SS
and NASH models. Some potential target genes of the putative miRNAs were
found to be involved in the TGF- signaling pathway. Furthermore, the putative
miRNA expression profiles in human serum were also clearly different between
SS and NASH patients. These miRNAs have high potential as biomarkers to
distinguish the fate of NAFLD patients and contribute to further research in the
pathogenesis and treatment of NASH.
Disclosure of Interest: None declared
P0017 PROTECTIVE
EFFECTS
OF
MELATONIN
THIOACETAMIDE-INDUCED LIVER FIBROSIS IN RATS

ON

K. Celinski1,*, G. Czechowska 1, A. Korolczuk2, G. Wojcicka3, J. Dudka4,


A. Bojarska-Junak5, A. Ma dro1, H. Cicho_z-Lach1
1
Gastroenterology, 2Department of Clinical Pathomorphology, 3Department of
Clinical Pathophysiology, 4Medical Biology, 5Clinical Immunology, MEDICAL
UNIVERSITY OF LUBLIN, Lublin, Poland
Contact E-mail Address: celinski.krzysztof@gmail.com
INTRODUCTION: The aim of the present study was to determine the effect of
melatonin on liver fibrosis induced with long-term administration of thioacetamide (TAA) in an animal model. The antifibrotic effects of melatonin were
assessed by determining activity indirect markers of fibrosis, i.e. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
(AP), and direct markers represented by proinflammatory cytokines such as
interleukin 6 (IL-6), interleukin beta 1 (IL-beta1), tumour necrosis factor alpha
(TNF-alpha, transforming growth factor beta 1 (TGF-beta1) and plateletderived growth factor (PDGF- AB). Moreover, parameters of oxidative stress
were determined, i.e. concentrations of oxidised glutathione (GSSG) and reduced
glutathione (GSH), activity of paraoxonase 1 (PON-1), an enzyme of antioxidative properties. Inflammatory changes and extent of fibrosis were evaluated
histologically.

AIMS & METHODS: Experiments were carried out in Wistar rats. Animals
were divided into 4 groups, 8 individuals each: group I- controls receiving drinking water ad libitum for 12 weeks, group II TAA, 300 mg/L ad libitum for 12
weeks, group III- melatonin, 10 mg/kg b.w. administered intraperitoneally (IP)
daily for 4 weeks, group IV TAA, 300 mg/L ad libitum for 12 weeks followed
by melatonin, 10 mg/kg/b.w. administered IP daily for 4 weeks.
RESULTS: Results of serum determinations demonstrated significantly lower
activity of AST, ALT and AP in the group receiving TAA followed by melatonin
(IV) compared to the group receiving only TAA (II). Immunoenzymatic findings
regarding the effect of melatonin on concentration of proinflammatory cytokines
(Il-6, Il-beta1, TNF-alpha, TGF-beta 1, PDGF-AB) confirmed these data.
CONCLUSION: Biochemical examinations in liver homogenates revealed statistically significant improvement of oxidative stress parameters (concentration of
GSH increases and concentration of GSSG decreases) in animals with TAAinduced liver damage receiving melatonin (IV). Moreover, the activity of PON1 toward phenyl acetate and paraoxon was found to be increased in liver homogenates and serum in the group receiving TAA followed by melatonin (IV)
compared to the TAA group (II). Microscopic evaluation disclosed inhibitory
effects of melatonin on inflammatory changes and extent of liver fibrosis.
Disclosure of Interest: None declared
P0018 ROLE OF GAMMA-KETOALDEHYDES AS NOVEL MEDIATORS
OF EXPERIMENTAL FIBROGENESIS AND STELLATE CELLS
ACTIVATION
L. Longato1,*, K. Rombouts1, D. Dhar1, S. Davies2, J. Roberts2, T. V. Luong1,
M. Pinzani1, K. Moore1
1
UCL Institute for Liver & Digestive Health, University College London, London,
United Kingdom, 2Pharmacology, Vanderbilt University, Nashville, United States
Contact E-mail Address: l.longato@ucl.ac.uk
INTRODUCTION: Reactive lipid aldehydes formed during lipid oxidation such
as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSCs)
to a pro-fibrogenic phenotype. -Ketoaldehydes (-KAs) are highly reactive lipid
aldehydes formed during oxidation of arachidonic acid or as a by-product of the
cyclo-oxygenase pathway. -Ketoaldehydes are 100x more reactive than HNE,
and form protein adducts and cross-links. Increased circulating concentrations of
proteins cross-linked to -ketoaldehydes are present in patients with alcoholic
liver disease.
AIMS & METHODS: The aim of this study was to investigate whether one
specific -ketoaldehyde, namely levuglandin E2 (LGE2), can induce activation
of HSCs. Cultured activated, serum-starved primary mouse and human HSCs
were exposed to various concentrations (0.5 pM-5 mM) of levuglandin E2 (LGE2)
for up to 48 hours. Endpoints measured included proliferation (BrdU incorporation), cytotoxicity (lactate dehydrogenase (LDH) release and tetrazolium (MTS)
reduction), RNA expression (qRT-PCR), protein expression (Western Blot), and
collagen secretion in conditioned medium (SirCol assay).
RESULTS: HSCs exposed to LGE2 exhibited profound cytotoxicity at 5 M
concentration, as indicated by LDH leakage and reduced MTS. This was
mediated by an induction of apoptosis, indicated by an increase in PARP cleavage, occurring as early as 8 hours after LGE2 exposure. However, at lower, noncytotoxic doses (ranging from 50 pM-500 nM, with a maximum effect observed
at 0.5 nM), LGE2 promoted HSC activation as indicated by increased expression
of -smooth muscle actin and vimentin, as well as increased proliferation and
collagen secretion. In addition, LGE2 exposure promoted sustained activation of
signalling pathways, as indicated by the increased phosphorylation of the kinases
ERK1/2 and JNK, as well as an increase in mRNA levels of chemokines such as
IL-8 and MCP-1. We are currently investigating the potential protective action of
administration of a -ketoaldehyde scavenger in an animal model of hepatic
fibrosis.
CONCLUSION: -Ketoaldehydes represent a newly identified class of activators
of HSCs in vitro, which are biologically active at concentrations as low as 50 pM.
Disclosure of Interest: None declared
P0019 NONINVASIVE SERUM FIBROSIS MARKERS IN COMPARISON
WITH GRADING AND STAGING IN CHRONIC HEPATITIS
M. Abdollahi1,*, A. Pouri2, M. Somi2
Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University,
2
Liver and Gastrointestinal Diseases Research Center, Tabriz University of
Medical Sciences, Tabriz, Iran, Islamic Republic Of
Contact E-mail Address: Dr. M. R. Abdollahi@gmail.com
1

INTRODUCTION: Chronic hepatitis is defined as a necroinflammatory disease


of the liver continuing for at least six months. The aim of this study was to
evaluate the role of noninvasive fibrosis markers by assessing the association
among grading and staging and these diagnostic parameters in patients with
chronic hepatitis.
AIMS & METHODS: We retrospectively studied 221 patients with chronic
hepatitis between 2011 and 2013. Routine biochemical indices and serum fibrosis
indexes such as aspartate aminotransferase (AST)/alanine aminotransferase
(ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score
(FIB-4) were determined, and the histological grade and stage of the liver biopsy
specimens were scored according to the Ishak scoring system. Receiver operating
characteristic curve (ROC) analysis was conducted to compare diagnostic
accuracies of these markers for prediction of significant fibrosis.
RESULTS: We identified 221 liver biopsies from chronic hepatitis patients with
contemporaneous laboratory values for imputing AAR, APRI and FIB-4. From
all, 135 males (61.1%) and 86 females (38.9%), with the mean age of 39.614.4
were studied. FIB-4, APRI and AAR were correlated significantly with the stage
of fibrosis, with a higher correlation coefficient than other markers in the patients

United European Gastroenterology Journal 2(1S)


with Hepatitis B (r 0.46), C (r 0.58) and autoimmune hepatitis (r 0.28).
FIB-4 (AUROC 0.84) and APRI (AUROC 0.78) was superior to AAR at
distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest
diagnostic accuracy.
CONCLUSION: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among
patients with chronic hepatitis.
Disclosure of Interest: None declared
P0020 REVEALING THE MOLECULAR MECHANISM OF RAT LIVER
RESPONSE TO LONG-TERM OMEPRAZOLE TREATMENT WITH
BIOINFORMATICS APPROACH
S. Vakal1, E.A. Virag2, K. Dvorshchenko1, L. Ostapchenko1,*
1
ESC "Institute of Biology", Taras Shevchenko National University of Kyiv, Kyiv,
Ukraine, 2University of Pecs, Pecs, Hungary
Contact E-mail Address: sergii.vakal@univ.kiev.ua
INTRODUCTION: Omeprazole is a widely prescribed acid-suppressing drug
available for clinical use for 25 years. Despite well-studied adverse effects of
short-term omeprazole treatment, underlying mechanisms of some hepatotoxic
effects of long-term injection of high omeprazole doses (e.g. development of
oxidative stress and histopathologic changes [1]) are not understood.
Transcriptome analysis is a powerful tool for elucidation of possible mechanisms
of cellular response to different conditions on molecular level. Bioinformatics
approach is suitable for processing of large datasets, prediction of possible
regulatory circuits and generation of hypotheses on involved molecular mechanisms [2].
AIMS & METHODS: The purpose of the research was to find out possible
molecular mechanisms of rat liver cells response to long-term injection of
omeprazole.
GSE8858 dataset and GPL2454 platform description were downloaded from
NCBI Genome Expression Omnibus database. Gene expression data from
livers of rats treated with 30 mg/kg and 415 mg/kg for 1 and 25 days were
compared in order to reveal differentially expressed genes (DEGs). DEGs were
determined with GEO2R tool on the basis of t-criterion and adjusted p value.
Gene ontology (GO), pathway enrichment analyses and building of protein-protein interactions (PPI) network were performed with STRING 9.1. Prediction of
miRNAs and cis-elements for DEGs was carried out with WebGestalt toolkit.
Clusters were identified by K-means analysis in ClusterONE. All networks were
visualized using Cytoscape.
RESULTS: In total 79 DEGs (21 up- and 58 down-regulated) and 87 DEGs (41
up- and 46 down-regulated) were identified in samples of rat livers treated with
30 and 415 mg/kg during 25 days, respectively. At the same time 22 genes with
similar pattern of expression (9 up- and 13 down-regulated) were found for both
types of dosage. Among them are Arntl, Cdk1a, Chka, Gpam, Litaf, Slc2a5, Usp2
etc. Enrichment in such GO terms was revealed: cell cycle, mitosis, nuclear division, lipid metabolism. Only genes involved in lipid metabolism were upregulated, while others were suppressed. Genes involved in PPAR signalling
pathway were found to be differentially regulated upon 25-day treatment with
omeprazole. Most of DEGs (51 genes) were of cytoplasmic proteins (housekeeping genes). PPI networks were constructed for 98 proteins and 102 interactions revealed. The optimal amount of clusters was equal to 3. MiRNA-9, 17-5p,
20A, 20B, 106A, 106B, 200B, 200C, 429, 506 and 519D were found to be involved
in regulation of revealed DEGs. 24 probable cis-elements were predicted for
promotors of identified DEGs.
CONCLUSION: Thus, long-term treatment of rats with omeprazole is associated with changes in expression of housekeeping genes: down-regulation of
genes involved in cell-cycle process and cellular division, up-regulation of genes
involved in lipid metabolism, and changes in expression of PPAR signalling
pathway genes.
REFERENCES
1. Dvorshchenko KO, Bernyk OO, Dranytsyna AS, et al. Influence of oxidative
stress on the level of genes expression Tgfb1 and Hgf in rat liver upon long-term
gastric hypochlorhydria and administration of multiprobiotic Symbiter. Ukr
Biokhim Zh 2014; 85: 114-123.
2. Shen B, Zhou S, He Y, et al. Revealing the underlying mechanism of ischemia
reperfusion injury using bioinformatics approach. Kidney Blood Press Res 2013;
38: 99-108.
Disclosure of Interest: None declared
P0021 MORPHOLOGICAL AND FUNCTIONAL CHANGES OF LIVER
MACROPHAGES DURING THE PROGRESSION OF
NONALCOHOLIC STEATOHEPATITIS (NASH)
S. Bruzzi1,*, S. Sutti1, A. Jindal1, I. Locatelli1, M. Vacchiano1, C. Bozzola1,
E. Albano1
1
Health Sciences, University of Eastern Piedmont "A. Avogadro", Novara, Italy
Contact E-mail Address: stefania.bruzzi@med.unipmn.it
INTRODUCTION: Recent reports indicate that both human and experimental
NASH is characterized by an increase in hepatic monocyte infiltration and that
macrophages have an important role in regulating the disease evolution.
However, little is known about the functional changes occurring in liver macrophages during the progression of NASH.
AIMS & METHODS: NASH was induced in C57BL/6 mice by feeding a methionine-choline deficient (MCD) diet up to 8 weeks.
RESULTS: Mice receiving the MCD diet showed a progressive worsening of
parenchymal damage and lobular inflammation, while liver fibrosis was evident
only after 8 weeks of treatment. Hepatic F4/80-positive macrophages increased in
parallel with the disease progression. In the early phases of NASH after 4 weeks

A137
on the MCD diet these cells prevalently expressed markers of inflammatory
monocytes such as Ly6C and CD11b, but the prevalence of Ly6C/CD11b
cells decreased by extending the treatment up to 8 weeks. This paralleled with
a lowering in the monocyte chemokines CCL1/CCL2 and their receptors CCR8/
CCR2. We observed that the expression of the macrophage M1 activation markers iNOS and IL-12 also peaked at 4 weeks and declined thereafter. No appreciable changes were instead observed in the levels of M2 polarization markers
arginase-1 and MGL-1. Histology revealed that the macrophages accumulating
in advanced NASH (8 weeks MCD) were enlarged, vacuolized and formed small
aggregates. Immunofluorencesce showed that these cells contained lipid vesicles
positive for the apoptotic cell marker Annexin V suggesting that they have phagocytosed apoptotic bodies derived from dying fat-laden hepatocytes. At flow
cytometry, enlarged macrophages were characterized by a weak Ly6C/CD11b
expression and by a low IL-12 production. On the other hand, these cells showed
an enhanced expression of the anti-inflammatory mediators IL-10 and annexin
A1. The production of the pro-fibrogenic cytokine TGF- was increased in the
macrophages obtained from NASH livers, irrespective of the cell phenotype.
CONCLUSION: Altogether, these data indicate that during the progression of
NASH liver macrophages down-modulate their pro-inflammatory phenotype in
parallel with the phagocytosis of apoptotic hepatocytes and acquired anti-inflammatory properties.
This work has been supported by a grant from the Fondazione Cariplo (Milan).
Disclosure of Interest: None declared
P0022 MICRORNA-27B DEVELOP THE FATTY LIVER FORMATION
AND INSULIN RESISTANCE AT THE SAME ONSET
T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, Y. Eguchi2, K. Wada3,
A. Nakajima1
1
gastroenterology and hepatology, Yokohama city university, yokohama, 2internal
medicine, saga university, saga, 3 Pharmacology, Osaka University Graduate
School of Dentistry, Oosaka, Japan
Contact E-mail Address: takaomi-kesso@hotmail.co.jp
INTRODUCTION: Nonalcoholic fatty liver disease (NAFL) morbidity rate in
Asia Pacific region is close to 1224%, while in Western countries is about 20
30%1). And nonalcoholic fatty liver disease (NAFLD) can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. In spite of
its high prevalence, up till now there is no proven effective treatment for
NAFLD3). Along with the obesity epidemic, the worldwide prevalence of
NAFLD is increasing rapidly and is generally assumed to be a consequence of
obesity-induced insulin resistance 2). On the other hand, not all obese individuals
are insulin resistant, nor are all insulin-resistant individuals obese 4). MicroRNAs
(miRs) are a class of small non-coding RNAs that function to control gene
expression by inducing the degradation or inhibiting the translation of mRNA
through an association with its 3-untranslated region (3UTR). Although miRs
play a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)
and diabetes mellitus (DM), detailed mechanisms of this pathogenesis remain
unclear.
AIMS & METHODS: We found that miR-27b increased in liver biopsy specimens of NAFLD patients with DM using microarray analysis, as compared with
controls. The aim of this study was to investigate whether overexpression of miR27b in liver could cause fatty liver formation and insulin resistance, and to
examine the mechanism of NAFLD and DM onset in a murine model.
Five-week-old male C57BL/6J mice were randomized into 2 groups (n 16
mice): basal diet (BD)-fed control mimic (BD-Con, n 4), BD-fed miR-27bmimic (BD-miR-27b, n 4). In this study, miR-27b mimic is injected intravenously at 7mg/kg. We comfirmed the target genes of miR-27b using quantitative
RT-PCR analysis. Insulin serum concentrations were measured by a local laboratory for clinical examinations. As an alternative method for assessing insulin
resistance (IR), the homeostasis model assessment of IR (HOMA-IR) was calculated using the following formula: fasting insulin (mU/mL) plasma glucose (mg/
dL) / 405.
RESULTS: BD-miR-27b significantly showed steatosis using oil red o staining
and increased hepatic tryglyceride content, as compared with BD-Con. In the
analysis of fat accumulation-related gene expression, hepatic Peroxisome proliferator-activated receptor  (PPAR) and Microsomal triglyceride transfer protein (MTTP) are significantly decreased. At the same time, BD-miR-27b showed
hyperinsulinemia and insulin resistance. In the analysis of insulin resistancerelated gene expression, hepatic Insulin receptor substrate 1 (IRS-1) is significantly decreased.
CONCLUSION: miR-27b controls multiple gene levels that are involved in fat
accumulation and insulin resistance, resulting in the NAFL and DM pathology.
These results propose a therapeutic approach for NAFL and DM by targeting
miR-27b.
REFERENCES
1) Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and
management of non-alcoholic fatty liver disease in the AsiaPacific region: executive summary. J Gastroenterol Hepatol 2007; 22: 775777.
2) Clark JM, Brancati FL and Diehl AM. Nonalcoholic fatty liver disease.
Gastroenterology 2002; 122: 16491657.
4) Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in
obesity: European Group for the Study of Insulin Resistance (EGIR). J Clin
Invest 1997; 100: 11661173.
Disclosure of Interest: None declared

A138
P0023 EFFICACY OF ABSORBABLE EMBOLIZATION MATERIALS
FOR PORTAL VEIN EMBOLIZATION TO INDUCE LIVER
REGENERATION IN A RABBIT MODEL
F. Huisman1,*, K.P. van Lienden2, J. Verheij3, T.M. van Gulik1
1
Surgery, 2Radiology, 3Pathology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: f.huisman@amc.nl
INTRODUCTION: Unilateral portal vein embolization (PVE) is used to increase
future remnant liver volume in patients requiring extended resections. Reversible
PVE is of interest when generating sufficient hypertrophy while preserving the
embolized liver lobe. The concept of reversible PVE requires an absorbable
embolization material.
AIMS & METHODS: The aim of this study is to modulate lysis time of a fibringlue based embolization material while using different concentrations of
Aprotinin. Aprotinin inhibits fibrinolysis and thereby delays absorption of FG.
PVE of the cranial liver lobe was performed in twenty-four rabbits, divided into 5
groups:
 Fibrin glue with Aprotinin (FG1000 KIU (Kallikrein Inactivotor Unit), n 4)
 Fibrin glue with Aprotinin (FG700KIU, n 5)
 Fibrin glue with Aprotinin (FG500KIU, n 5)
 Fibrin glue with Aprotinin (FG300KIU, n 5)
 Fibrin glue without Aprotinin (FG-Aprot, n 5)
The rabbits were sacrificed after 7, 14 and 49 days, respectively. CT volumetry of
non-embolized lobe (NELVol), liver damage parameters, liver-to-body weight
ratio of NEL were evaluated.
RESULTS: Data were compared with a previous series using a permanent embolization material, i.e. polyvinyl alcohol coils (PVAc), showing complete and
permanent occlusion of the embolized portal vein branch in all rabbits after 7
days.
FG-Aprot was completely absorbed in 7 days and did not give any hypertrophy
response of the NEL. At sacrifice on day 7, the embolized portal vein in all 4 of
the FG1000KIU Aprotinin group was still occluded and showed a hypertrophy
response comparable to the PVAc group. The group of FG 700KIU Aprotinin
survived 14 days and in two of the five rabbits, the embolized portal vein was
recanalized at sacrifice. The hypertrophy response in these rabbits was not different from the PVAc group. The rabbits with FG 500KIU and 300KIU
Aprotinin were sacrificed at day 49. In the group with FG 500KIU Aprotinin,
4 out of 5 showed recanalization of the cranial portal branches. In the group with
FG 300KIU Aprotinin, 3 out of 5 rabbits showed recanalization. Both groups
showed hypertrophy response rates not different compared to the PVAc group.
CONCLUSION: Fibrin glue with the concentrations 300KIU and 500KIU
Aprotinin resulted in 70% reversible embolization with a hypertrophy response
comparable to the PVAc group.
Disclosure of Interest: None declared
P0024 TRANSPLANTATION
OF
HUMAN
AMNION-DERIVED
MESENCHYMAL STEM CELLS AMELIORATES CARBON
TETRACHLORIDE-INDUCED LIVER FIBROSIS IN RATS
K. Kubo1,*, S. Ohnishi1, N. Sakamoto1
Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan
Contact E-mail Address: sonishi@pop.med.hokudai.ac.jp
1

INTRODUCTION: Liver fibrosis is a progressed stage of chronic hepatic disease


caused by a variety of factors, such as viral infections, alcohol, drugs and chemical toxicity. The only effective available treatment for end stage liver fibrosis is
transplantation; however, due to the lack of donors, complications and transplant rejection, alternative treatment is needed. Mesenchymal stem cells (MSCs)
have been reported to be a valuable cell source in cell therapy. Recently, bone
marrow- or adipose tissue-derived MSCs have been reported to be effective in the
treatment of liver fibrosis. In addition, several studies have shown that MSCs can
be easily isolated from human amnion, and a large amount of cells can be
obtained. Therefore, we examined the effects of transplantation of human
amnion-derived MSCs (hAMSCs) in rats with liver fibrosis.
AIMS & METHODS: All pregnant women gave written informed consent, and
amnion was obtained at Cesarean delivery. hAMSCs were isolated by collagenase treatment, and expanded with culture medium containing fetal bovine
serum. Liver fibrosis was induced in 6-week-old male Sprague-Dawley rats by
intraperitoneal injection of 2 ml/kg of 50% carbon tetrachloride (CCl4) twice a
week for 7 weeks. At 3 weeks, hAMSCs (1106 cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative RT-PCR were performed.
RESULTS: Transplantation of hAMSCs significantly reduced the fibrotic area
and deposition of type I collagen. In addition, hAMSC transplantation significantly decreased the number of -SMA-positive hepatic stellite cells and and
CD68-positive Kupffer cells in the liver of hAMSC-treated rats. mRNA expression of -SMA was significantly decreased in the liver of hAMSC-treated rats,
and mRNA expression of type I collagen, TGF- and IL-1 tended to be
decreased by hAMSC transplantation.
CONCLUSION: Transplantation of hAMSCs provided significant improvement
in a rat model of liver fibrosis, possibly through inhibition of inflammatory
reaction. hAMSC would be considered as a new cell source for the treatment
of liver fibrosis.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0025 VITAMIN D: HYPOTHESIS OF TROPHIC EFFECT ON LIVER
CELLS IN AN ANIMAL MODEL OF NAFLD
V. Lembo1,*, G. Mazzone1, G. DArgenio1, M. DArmiento2, F. Morisco1,
N. Caporaso1
1
Department of Clinical Medicine and Surgery, 2Department of Advanced
Biomedical Science, University of Naples Federico II, Naples, Italy
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the most
common liver disease in Western countries, is pathogenetically related to a sedentary lifestyle as well as to poor quality diet characterized by an excessive energy
intake including high fatty foods and high amounts of fructose, the so-called
Western Diet (WD). The hallmark of NAFLD is hepatic accumulation of triglycerides. Vitamin D in addition to the effects on lipid metabolism, plays other
biological functions, among which a trophic effect on human cultured cells.
AIMS & METHODS: To evaluate, in a rat model of NAFLD induced by
Western Diet, the relationship between body weight, liver weight and grade of
steatosis; and if these parameters are modified by vitamin D supplementation.
Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats.
The 3 groups were fed respectively with Standard Diet (SD); Western Diet (WD);
WDVitD: WD supplemented with 23 IU/day/rat of vitamin D3. The experiment
was conducted for 6 months. Weekly, the rats, body weight was recorded. At
sacrifice, livers were excised and weighed and samples were stored at -80 C. Liver
histology was examined by haematoxylin/eosin and Oil Red-O staining. Steatosis
was numerically scored following semi-quantitative pathological standard.
RESULTS: During the experiment the increase of body weight was similar in the
three groups. In the two groups fed with WD liver weight was significantly higher
than SD group (p50.01). A positive correlation between body weight and liver
weight was observed in WD groups (p50.0001). The liver/body weight ratio was
significantly higher in WD and WDVitD groups than SD: 2.90.05, 2.80.07
and 2.00.04, respectively; p50.001). Steatosis was present in 61% and 21% of
hepatocytes in WD group and WDVitD group, respectively, and absent in SD
group. No correlation was found between the grade of steatosis and liver or body
weight nor between the grade of steatosis and liver/body weight ratio. Although
vitamin D supplementation reduced the degree of steatosis, liver/body weight
ratio in WDVitD group was similar to WD group.
CONCLUSION: In a rat model of NAFLD induced by WD the presence and
extent of steatosis are independent from body weight. Interestingly and unexpectedly, in WD groups the supplementation with vitamin D reduces liver steatosis but not liver weight: this sustains the hypothesis of a trophic effect of
vitamin D on liver cells.
Disclosure of Interest: None declared
P0026 VITAMIN D PREVENTS STEATOSIS AND DIABETES IN A RAT
MODEL OF NAFL
G. Mazzone1,*, V. Lembo1, G. DArgenio1, M. Guarino1, M. DArmiento2,
F. Morisco1, N. Caporaso1
1
Department of Clinical Medicine and Surgery, 2Department of Advanced
Biomedical Science, University of Naples Federico II, Napoli, Italy
Contact E-mail Address: giovanna.mazzone@gmail.com
INTRODUCTION: The last decade has seen nonalcoholic fatty liver disease
(NAFLD) rise to become the most common cause of chronic liver disease in
Western countries. It is known that insulin resistance and type 2 diabetes mellitus
(T2DM) have an important role in the pathogenesis of obesity and NAFLD. A
growing body of evidence points to a linked and potentially causative relationship between serum 25-hidrossivitamin D3 [25-(OH)D] levels and NAFLD.
AIMS & METHODS: Aim of this study was to evaluate whether daily vitamin
D3 supplementation is able to modulate the liver effects and glucose homeostasis
of a westernized diet, high in fat and fructose, in an animal model of NAFL
without vitamin D deficiency. Methods: Eighteen male Wistar rats were divided
into 3 groups, each of 6 rats. Group 1: Standard Diet (SD); Group 2: Western
Diet (WD) containing 13 IU/day/rat of vitamin D3; Group 3: WD containing 23
IU/day/rat of vitamin D3 (WDVitD). The experiment was conducted for 6
months. Liver histology was examined by haematoxylin/eosin and Oil Red-O
staining. Insulin resistance was determined according to the Homeostasis
Model of Assessment (HOMA-IR) method. Grade of liver steatosis was evaluated according to Brunt EM et al.
RESULTS: In SD group, livers were normal and no hepatocytes contained fat; in
WD group the percentage of hepatocytes with steatotic vacuoles was 61%, while
in WDVitD group only 27% of hepatocytes contained fat. In WD group
HOMA-IR was significantly higher than in SD (41.98.9 vs 6.171.3, p50.01)
and it was reduced by vitamin D supplementation in WDVitD group (41.98.9
vs 19.45.2, p50.05). Interestingly SD and WDVitD rats were not diabetic
(98.78.0 and 103.26.1, respectively) while all rats in WD group were diabetic
(1399.6) with glycemic values significantly higher than SD (p50.01) and
WDVitD (p50.05).
CONCLUSION: These results suggest that a daily supplementation of vitamin
D3 is able to improve insulin sensitivity and to prevent the development of
diabetes and hepatic steatosis in WD rats.
Disclosure of Interest: None declared

A139

United European Gastroenterology Journal 2(1S)


P0027 INVOLVEMENT OF SPHINGOMYELIN METABOLISM IN THE
DEVELOPMENT OF NAFLD AND INSULIN RESISTANCE
S. Ohnishi1,2,*, S. Mitsutake3, H. Hanamatsu3, K. Yuyama3, S. Sakai3,
H. Takeda4, Y. Igarashi3, S. Hashino2, N. Sakamoto1
1
Gastroenterology and Hepatology, 2Health Care Center, 3Frontier Research
Center for Post-genome Science and Technology, 4Pathophysiology and
Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo,
Japan
Contact E-mail Address: sonishi@pop.med.hokudai.ac.jp
INTRODUCTION: Sphingomyelin (SM) is a major component in lipid microdomains, and SM is synthesized from ceramide by the action of SM synthase
(SMS). We have recently reported that mice deficient for SMS2 are resistant to
high fat diet-induced obesity, fatty liver and insulin resistance (J Biol Chem
2011:286;28544). In this study, we examined the relationship between SM and
ceramide molecular species and the development of NAFLD and insulin resistance in human.
AIMS & METHODS: Non-alcoholic students of our university with body mass
index (BMI)  35 kg/m2 at the regular physical checkup in 2013 were enrolled,
and volunteer students with BMI of 20-22 kg/m2 were set as a control group.
Serum levels of SM and ceramide containing saturated (C14:0, C16:0, C18:0,
C20:0, C22:0 and C24:0) and unsaturated (C16:1, C18:1, C20:1, C22:1 and
C24:1) fatty acids were measured using LC/MS/MS. Serum levels of liver
enzymes, lipids and insulin resistance were measured by blood examination.
Abdominal ultrasound was performed to confirm the existence of fatty liver,
and body composition including percent body fat (PBF) was measured by bioimpedance analysis.
RESULTS: The levels of total SM and ceramide were not altered in obese group
(19-28 y.o., n 12), compared with control group (18-27 y.o., n 11). The concentrations of SM C18:0 and C24:0 in the obesity group were significantly higher
than in the control group. Moreover, in the obese group, SM C20:0 and C22:0
tended to be higher than in the control group. In the analysis of total 23 cases, the
serum levels of SM containing saturated fatty acids positively correlated with
PBF, ALT, ChE, LDL-C, TG and HOMA-R. However, SM species containing
unsaturated acyl chain and almost all ceramide species did not correlate with
those items.
CONCLUSION: The present study demonstrated that the serum levels of SM
species containing saturated fatty acids (C18:0, C20:0, C22:0 and C24:0) are
correlated with liver function and insulin resistance, suggesting that distinct
SM species are involved in the development of NAFLD and insulin resistance.
Disclosure of Interest: None declared
P0028 GOOD CORRELATION BETWEEN PLASMA CYTOKERATIN-18
AND CONTROLLED ATTENUATION PARAMETER (CAP) IN
HEALTHY POPULATION
S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e
metabolismo, FML, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon,
Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. Plasma caspase-generated cytokeratin-18 fragments (CK-18)
have been proposed as a non-invasive alternative for the diagnosis of NAFLD,
especially NASH.
AIMS & METHODS: Aims: compare CK-18 serum levels in apparently healthy
individuals with and without steatosis. Methods: Recruitment from a prospective
epidemiological study of the general Portuguese adult population. Steatosis evaluated using CAP and ultrasound. Performance of CK-18 for diagnosing steatosis
compared with US and CAP was assessed using AUROC.
RESULTS: 146 individuals studied (60% male), mean age and BMIs (body mass
index) were 52.617.1 years and 28.24.9 kg/m2, respectively; 25% had a
normal BMI, 46% were overweight and 29% were obese. Prevalence of steatosis
on ultrasound was 52.1%.
The mean (SD), median (minimum-maximum), and 5th and 95th percentile
values of CK-18 values were 73.4 (67.7), 57.6 (25-508), 25 and 220.1 U/L, respectively. Median CK-18 were elevated in patients with vs. without hepatic steatosis
by ultrasound: 33.4 [IQR: 25151] vs. 73.7 [IQR: 25508] U/L, p 50.0001.
CK-18 significantly correlated with steatosis ( 0.40), ALT ( 0.40), CAP
( 0.38), triglyceride ( 0.32), waist circumference ( 0.30), HDL ( 0.28), AST ( 0.27), LDL ( 0.26), total cholesterol ( 0.21) and the
number of metabolic syndrome criteria ( 0.29), but not with LSM or BMI.
The CK-18 AUROC to predict steatosis using ultrasound and CAP (cut-offs of
243 dB/m) were 0.78 (95% CI 0.710.86) and 0.74 (95% CI 0.650.82),
respectively.
CONCLUSION: In the absence of steatosis, CK-18 serum levels were below 151,
with a very large range. It showed a good discriminating capacity for diagnosing
steatosis.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared

P0029 PREVALENCE OF HEPATIC STEATOSIS IN THE GENERAL


PORTUGUESE POPULATION: USING FATTY LIVER INDEX (FLI)
AND ULTRASOUND
S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, A. Carvalho3, H. CortezPinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutricao e
Metabolismo, FML, IMM, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA,
Lisbon, Portugal
INTRODUCTION: The fatty liver index (FLI) derived from an Italian population includes serum triglycerides, serum gamma-glutamyltransferase, body mass
index (BMI) and waist circumference. It has been used as a noninvasive measure
of hepatic steatosis (HS), but has not been widely validated and not examined in
the Portuguese population.
AIMS & METHODS: Estimate the prevalence of HS in the Portuguese adult
population by fatty liver index (FLI) and correlate with the ultrasound findings;
validate FLI for prediction of fatty liver in the Portuguese population.
Methods: Recruitment from a prospective epidemiological study of the general
Portuguese adult population. Steatosis evaluated using ultrasound (US) and FLI.
Performance of FLI for diagnosing steatosis compared with US was assessed
using AUROC.
RESULTS: We studied 950 subjects, 50.5% men. The mean age, waist circumference and BMIs were 50.518.4 years, 94.412.7 cm and 26.94.7 kg/m2,
respectively; 43% were overweight and 22% were obese. The median of FLI
was 38.1. Ultrasound was performed in 411 subjects, showing fatty liver in 35%.
Using the FLI, 27.6% of subjects had HS (FLI 4 60), 41.8% had no HS (FLI 5
30) and 30.6% were not classifiable (FLI 30-60). However, these cut-offs proposed by Bedogni appears to be inappropriate as 11.5% of subjects with FLI
530 exhibited HS on ultrasound and 13.4% of subjects with FLI 4 60 showed
no steatosis. For the FLI, the area under the ROC curve was 0.88 for the
diagnosis of HS.
There was a significant correlation (p 5 0.01) between the FLI and the following
variables: weight ( 0.80), waist circumference ( 0.74), presence of steatosis
( 0.65), triglycerides ( 0.58), BMI ( 0.51), ALT ( 0.43), GGT
( 0.39), HDL ( -0.36), age ( 0.33), female sex ( -0.33), insulin
( 0.29), AST ( 0.28), LDL ( 0.24) and total cholesterol ( 0.22). No
correlation was found with physical activity.
CONCLUSION: FLI could accurately identify hepatic steatosis in the general
Portuguese population. The calculation of FLI may be useful to suggest the
possibility of the presence of steatosis and indicate the need for an abdominal
ultrasound.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
P0030 NORMAL CONTROLLED ATTENUATION PARAMETER (CAP)
VALUES: A POPULATION-BASED STUDY OF HEALTHY SUBJECTS
S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutricao e
Metabolismo, FML, IMM, Lisbon, 3Internal Medicina, CHUC, Coimbra, 4INSA,
Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
1

INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. The normal range of controlled CAP values needs to be
explored in clinical and anthropometrically diverse healthy subjects. A recent
study has shown an association of CAP with BMI and the number of metabolic
syndrome criteria.
AIMS & METHODS: Aim: define the normal range of CAP values in healthy
subjects and evaluate the associated factors.
Methods: Recruitment from a prospective epidemiological study of the general
Portuguese adult population. CAP was performed using Fibroscan in 134 healthy
subjects, without fatty liver on ultrasonography or positivity serology for
HBsAg, anti-HBc and anti-HCV, and normal aminotransferase levels.
RESULTS: From 134 consecutive individuals studied (66 males), 4 were
excluded due to failure/unreliable liver stiffness measurements (LSM). The
mean age and BMIs (body mass index) were 46.918.0 years and 24.93.5 kg/
m2, respectively; 50% had a normal BMI, 43% were overweight and 7% were
obese. The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CAP values were 202.29 (48.4), 205.5 (100.0-297.0), 108.2 and 276.3
dB/m, respectively. Men had a higher mean CAP value than women (meanSD:
213.147.1 dB/m versus 191.847.8 dB/m, respectively; p 0.012).
CAP significantly correlated with gender ( 0.22), age ( 0.22), waist circumference ( 0.33), BMI ( 0.22), alcohol consumption ( 0.25), systolic blood
pressure ( 0.27), ALT ( 0.27), fasting glucose ( 0.24) and the number of
metabolic syndrome criteria.
After allowance for potential confounders, CAP was not independently associated with BMI or other risk factors for nonalcoholic fatty liver disease.
CONCLUSION: CAP values vary between 108.2 and 276.3 dB/m in healthy
subjects and is not associated with BMI or the number of metabolic syndrome
criteria.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared

A140

United European Gastroenterology Journal 2(1S)

P0031 EFFECT OF LANREOTIDE ON POLYCYSTIC LIVER AND


KIDNEY GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT
POLYCYSTIC KIDNEY DISEASE: AN OBSERVATIONAL TRIAL
T.J. G. Gevers1,*, J.C. Hol1, R. Monshouwer2, H.M. Dekker3, J.F. Wetzels4,
J.P. Drenth1
1
Gastroenterology and Hepatology, 2Radiation Oncology, 3Radiology,
4
Nephrology, RadboudUMC, Nijmegen, Netherlands
Contact E-mail Address: tom.gevers@radboudumc.nl
INTRODUCTION: Several trials have demonstrated that somatostatin analogues decrease liver volume in mixed populations of patients with autosomal
dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of
lanreotide and possibly enhances risk for adverse events.
AIMS & METHODS: The aim of this open-label clinical trial (RESOLVE trial)
was to assess efficacy of 6 months lanreotide treatment 120 mg subcutaneously
every 4 weeks in ADPKD patients with symptomatic polycystic liver disease. We
excluded patients with an estimated glomerular filtration rate (eGFR) 5 30 ml/
min/1.73m2. Primary outcome was change in liver volume, secondary outcomes
were changes in kidney volume, eGFR, symptom relief and health-related quality
of life (Euro-Qol5D). We used the Wilcoxon signed-rank test or paired two-sided
t-test to analyze within-group differences.
RESULTS: We included 43 ADPKD patients with polycystic liver disease (84%
female, median age 50 years, mean eGFR 63 ml/min/1.73m2). Median liver
volume decreased from 4,859 ml to 4.595 ml (-3.1%;p50.001), and median
kidney volume decreased from 1.023 ml to 1.012 ml (-1.7%;p 0.006). eGFR
declined 3.5% after the first injection and remained stable up to study end.
Lanreotide significantly relieved postprandial fullness, shortness of breath and
abdominal distension, but had no effect on any of the EuroQol-5D dimensions.
Three participants had a suspected episode of hepatic or renal cyst infection
during the study.
CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and
decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely
after starting lanreotide, but stabilized thereafter.
Disclosure of Interest: None declared
P0032 THE EFFECTS OF POLY-UNSATURATED FATTY
(PUFAS) IN A RODENT NUTRITIONAL MODEL OF NONALCOHOLIC STEATOHEPATITIS (NASH)

ACIDS

V. Smid1,2,*, K. Dvorak1, B. Stankova2, A. Zak1, L. Vitek1,2, R. Bruha1


1
4th Department of Internal Medicine, General University Hospital and 1st Faculty
of Medicine, 2Institute of Medical Biochemistry and Laboratory Diagnostics,
General University Hospital and 1st Faculty of Medicine, Charles University in
Prague, Prague, Czech Republic
INTRODUCTION: NAFLD and subsequent NASH are probably the most
common chronic liver diseases in western countries and have a high risk of
development of liver cirrhosis associated with high morbidity and mortality.
AIMS & METHODS: The aim of the study was to determine effects of administration of PUFAs in the MCD dietary model of NASH and to assess the
potential anti-inflammatory role of PUFAs in the pathogenesis of NASH.
For 6 weeks were male mice fed either with MCD or with chow. There were 4
groups of animals. Both experimental and control groups received from the
beginning either PUFAs or saline. Detailed liver histology, serum biochemistry,
total lipid and fatty acids compound, adiponectin and leptin levels were determined. Expressions of mRNA of key pro- and anti-inflammatory cytokines were
measured.
RESULTS: Feeding with MCD resulted in histopathological changes of
NAFLD/NASH and these changes were ameliorated in PUFAs-group (MP).
Administration of PUFAs led to significant decreases of total animal and liver
weight in MP. PUFAs also decreased cholesterol levels (P50.001), ALT
(P50.01) and AST levels (P50.01). MP developed significantly less pro-inflammatory cytokine profile, had lower leptin (P50.01) and higher adiponectin levels
(P50.01) than controls. Administration of PUFA led also to lower serum concentrations of saturated and monounsaturated FA and to higher serum concentrations of polyunsaturated FA in MP. Total lipid content of liver was
significantly lower in MP.
CONCLUSION: We conclude that PUFAs may play a causal role in the pathophysiology of NASH. In summary, PUFAs have favorable effects on histopathological changes, serum markers of liver damage, fatty acid compound and show
anti-inflammatory properties. We expect that PUFAs may represent a promising
way in prevention and treatment of this increasingly common disorder.
Disclosure of Interest: None declared
P0033 DYSBIOSIS SIGNATURE OF FECAL MICROBIOTA IN HUMANS
WITH NON-ALCOHOLIC FATTY LIVER DISEASE
W. Jiang1, N. Wu2, X. Wang1, Y. Zhang1, Y. Chi2, Y. Hu1, X. Qiu1, J. Li1,
Y. Liu1,*
1
Department of Gastroenterology, 2Institute of Clinical Molecular Biology &
Central Laboratory, Peking University Peoples Hospital, Beijing, China
Contact E-mail Address: liuyulan@pkuph.edu.cn, wuna1030@163.com
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized
by a broad spectrum of hepatic pathology that is closely linked to obesity and
ranges from simple steatosis (SS), to non-alcoholic steatohepatitis (NASH) and
even cirrhosis. NAFLD is recently believed to be under the influence of the gut
microbiota, which may have toxic effects on the human host after intestinal
absorption and delivery to the liver via the portal vein.

AIMS & METHODS: We explored the composition of gut bacterial communities of NAFLD and healthy subjects using 16S ribosomal RNA Illumina nextgeneration sequencing.
RESULTS: Partial least-squares discriminant analysis (PLS-DA) indicated that
most of the microbiota samples were clustered by disease status. Differences were
abundant at phylum, family, and genus levels between NAFLD and healthy
subjects. Lentisphaerae at phylum level was significant higher in NAFLD microbiota. Among those taxa with greater than 0.1% average representation in all
samples, five genera including Alistipes and Prevotella were the genus types
exhibiting significant higher level in healthy microbiota, while genera
Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in
NAFLD microbiota. In addition, lymphocyte profiles (CD4T cell and
CD8T cell) and proinflammatory cytokines (TNF-, IL-6 and IFN-) in gut
biopsies of patients and healthy controls was analyzed to monitor the inflammation caused by dysbiosis microbiota. The levels of CD4 T cells and CD8 T cells
were lower in NAFLD patients compared with healthy subjects, and the proinflammation cytokine TNF-, IL-6 and IFN- showed high level in NAFLD
patients. What was more, irregular arrangements of microvilli and widening of
the tight junction were observed in gut mucosa of the NAFLD patients by
transmission electron microscope.
CONCLUSION: The increased abundance of dysregulated bacteria in NAFLD
microbiota, decreased numbers of CD4T cells and CD8T cells, and increased
levels of TNF-, IL-6 and IFN- in gut mucosa of NAFLD patients suggest a
role for gut microbiota in the gut inflammation and the dysregulated gut immunity, which promote pathogenesis of NAFLD. We postulate that the distinct
composition of the gut microbiome among NAFLD and healthy controls
could offer a target for intervention or a marker for disease.
REFERENCES
1 Moschen AR, Kaser S and Tilg H. Non-alcoholic steatohepatitis: a microbiotadriven disease. Trends Endocrinol Metab 2013; 24: 537-545.
2 Mouzaki M, et al. Intestinal microbiota in patients with nonalcoholic fatty liver
disease. Hepatology 2013; 58: 120-127.
Disclosure of Interest: None declared
P0034 ASCITIC FLUID LACTOFERRIN
SPONTANEOUS BACTERIAL PERITONITIS

FOR

DIAGNOSIS

OF

A.A. Ghweil1,*
1
TROPICAL MEDICINE AND GASTROENTEROLOGY, QenaFACULTY
OF MEDICINE EGYPT, Qena, Egypt
Contact E-mail Address: alimena1@yahoo.com
INTRODUCTION: The diagnosis of spontaneous bacterial peritonitis (SBP) is
based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This
procedure is operator-dependent and lysis of PMNs during transport to the
laboratory may lead to false-negative results. Furthermore, ascitic fluid culture
is insensitive and leads to delays in diagnosis. The aim of this study was to assess
the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to
identify a cut-off level that can be used for future development of a rapid bedside
test.
AIMS & METHODS: Sixty ascites samples from cirrhotic patients were examined for PMN count, bedside culture, and lactoferrin concentration. AFLAC
concentrations were determined using a polyclonal antibody-based enzymelinked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or
greater with or without a positive culture was used for diagnosis of SBP.
RESULTS: Fifteen (25%) samples fulfilled diagnostic criteria for SBP. Samples
with SBP had a significantly higher lactoferrin concentration (median, 3200 ng/
mL; compared with non-SBP samples (median, 39 ng/mL P 5 .001). The sensitivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%,
respectively. The area under the receiver operating characteristic curve was 0.98.
Conclusions: AFLAC can serve as a sensitive and specific test for diagnosis
CONCLUSION: AFLAC can serve as a sensitive and specific test for diagnosis
of SBP. Qualitative bedside assays for the measurement of AFLAC can be developed easily and may serve as a rapid and reliable screening tool for SBP in
patients with cirrhosis.
Disclosure of Interest: None declared
P0035 MODULAR COMPUTER-AIDED DIAGNOSIS AND PREDICTION
SYSTEM FOR EARLY HEPATOCELLULAR CARCINOMA IN
CIRRHOTIC PATIENTS
C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, L. Streba1, D.
I. Gheonea1, I. Rogoveanu1
1
Gastroenterology, UMF CRAIOVA, Craiova, Romania
Contact E-mail Address: costinstreba@gmail.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most complex
treatable malignancies as its management is dependent on the stage of the underlying condition liver cirrhosis. An early diagnosis assures best curative chances,
as liver resection or transplantation have good survival rates in the general
population. Computer aided diagnostic and prognosis (CADP) models are currently being developed for a number of malignancies to help clinicians manage
cases based on individual needs of the patients rather than general statistics.
AIMS & METHODS: Our aim was to develop a CADP based on our previous
work involving artificial neural networks (ANN) [1] for successfully diagnosing
early HCC cases and better prognosticate their evolution, based on a set of
criteria in accordance with current guidelines.
Ethical clearance was obtained from the local board and 107 consecutive patients
with previously diagnosed liver cirrhosis signed informed consents for entering
the study, between January 2009 and February 2010. Clinical and demographic
parameters (age, sex, body mass index, waist circumference, type of viral

A141

United European Gastroenterology Journal 2(1S)


infection, alcohol consumption, smoking, clinical ascites, jaundice), laboratory
data (AST, ALT, GGT, alkaline phosphate, bilirubin, triglycerides, thrombocyte
count, prothrombin time, alpha fetoprotein), ultrasound data (portal vein thrombosis, size and number of possible tumors), elastography data (strain ratio, complexity, kurtosis, skewness, contrast, entropy, inverse difference moment, angular
second moment, correlation) and stiffness value (FibroScan) were collected and
imputed in the CADP. For patients with clear liver tumors contrast-enhanced
ultrasound was performed and time-intensity curve parameters were calculated
and fed to the ANN system: peak enhancement, time to peak, rise time, fall time,
mean transit time, area under the curve. We have followed the 4-year incidence of
HCC patients in tumor-free cases and assessed the evolution when any formation, either regeneration nodule or early HCC was found.
RESULTS: We found liver tumors in 21 patients; 12 were regeneration nodules
[median number of tumors per patient: 2 (min: 1, max: 5), median size 1.1 cm
(min: 0.4, max: 1.6)] and 9 were early HCC [median number of tumors per
patient: 1 (min: 1, max: 2), median size 1.8 cm (min: 0.7, max: 2.4)]. The
CADP system correctly diagnosed HCC in all 9 cases and in 8/12 regeneration
nodules based on clinical, laboratory and imaging data. A total of 28 patients
also developed HCC in the four-year follow-up period; the system correctly
predicted high possibility for HCC occurrence in 26 of these patients (92.85%),
while giving high estimates for HCC in another 16 patients that remained cancerfree until now.
CONCLUSION: We could successfully predict the rate of malignancy in cirrhotic patients by using a novel CADP system. We believe that such tools may
become worthy aids to clinical management of patients with various types of
digestive pathologies.
REFERENCES
1. Streba CT, et al. Using contrast-enhanced ultrasonography time-intensity
curves as classifiers in neural network diagnosis of focal liver lesions. World J
Gastroenterol 2012; 18: 44274434.
Disclosure of Interest: None declared
P0036 POSTOPERATIVE RESOURCE UTILIZATION AND SURVIVAL
AMONG LIVER TRANSPLANT RECIPIENTS WITH A MELD
SCORE GREATER THAN OR EQUAL TO 40: A RETROSPECTIVE
COHORT STUDY
F.S. Cardoso1,2,*, C. Karvellas2, N. Kneteman3, G. Meeberg3, P. Fidalgo2,4,
B. Sean2
1
Gastroenterology, Hospital Professor Doutor Fernando Fonseca, Amadora,
Portugal, 2Intensive Care, 3Transplantation, University of Alberta, Edmonton,
Canada, 4Nephrology, Hospital Professor Doutor Fernando Fonseca, Amadora,
Portugal
Contact E-mail Address: desousac@ualberta.ca
INTRODUCTION: Cirrhotic patients with Model for End-stage Liver Disease
(MELD) score 40 have high risk of death without liver transplant (LT). This
study aimed to evaluate these patients outcomes after transplant.
AIMS & METHODS: The retrospective cohort included 519 adult cirrhotic
patients who underwent LT at one Canadian center between 2002 and 2012.
Primary exposure was severity of end-stage liver disease measured by MELD
score at transplant (40 vs. 540). Primary outcome was duration of first intensive care unit (ICU) stay after LT. Secondary outcomes were duration of first
hospital stay after LT, rate of ICU readmission, re-transplant rate, and survival
rates.
RESULTS: On the day of LT, 5% (28/519) of patients had a MELD score 40.
These patients had longer first ICU stay after LT (14 vs. 2 days; p 50.001).
MELD score 40 at transplant was independently associated with first ICU stay
after transplant 10 days (OR, 3.21). These patients had longer first hospital stay
after LT (45 vs. 18 days; p 50.001); however, there was no significant difference
in the rate of ICU readmission (18% vs. 22%; p 0.58) or re-transplant rate (4%
vs. 4%; p 1.00). Cumulative survival at 1 month, 3 months, 1 year, 3 years, and
5 years was 98%, 96%, 90%, 79%, and 72%, respectively. There was no significant difference in cumulative survival stratified by MELD score 40 vs. 540
at transplant (p 0.59).
CONCLUSION: Cirrhotic patients with MELD score 40 at transplant utilize
greater postoperative health resources; however, derive similar long-term survival
benefit with LT.
REFERENCES
Shawcross DL, Austin MJ, Abeles RD, et al. The impact of organ dysfunction in
cirrhosis: survival at a cost? J Hepatol 2012; 56: 1054-1062.
Alexopoulos S, Matsuoka L, Cho Y, et al. Outcomes after liver transplantation
in patients achieving a model for end-stage liver disease score of 40 or higher.
Transplantation 2013; 95: 507-512.
Oberkofler CE, Dutkowski P, Stocker R, et al. Model of end stage liver disease
(MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients. Crit Care 2010; 14: R117.
Disclosure of Interest: None declared
P0038 DISTINGUISHING NASH CIRRHOSIS FROM NON-CIRRHOTICS
BY URINE VOLATILE ORGANIC COMPOUND ANALYSIS - A PILOT
STUDY
J. Covington1, E. Daulton1, E. Westenbrink1, M. McFarland2,*, C. Bailey2,
N. OConnell2, C. Nwokolo2, K. Bardhan3, R. Arasaradnam4
1
Engineering, University of Warwick, 2Gastroenterology, UHCW NHS Trust,
Coventry, 3Gastroenterology, Rotherham NHS Trust, Rotherham, 4CSRI,
University of Warwick, Coventry, United Kingdom
Contact E-mail Address: r.arasaradnam@warwick.ac.uk

INTRODUCTION: There is a quest for biomarker discovery in liver disease


especially to detect cirrhosis at an early stage. Current methods are invasive,
more often requiring a liver biopsy to confirm the diagnosis. For patients with
Non-alcohol related Steatohepatitis (NASH), the use of fibroscan whilst generally helpful, is unable to confirm the presence of fibrosis particularly in the
presence of fat within the liver which is inevitable in most cases with NASH.
The gut microbiome is altered in several gastrointestinal disorders, resulting in
altered gut fermentation patterns, which we (and others) have been able to
recognise by analysis of volatile organic compounds (VOC) in urine, breath
and faeces1. The altered structure of the small intestinal mucosa and increased
gut permeability (noted in liver disease), we hypothesised, would also change the
microbiome, hence recognisable by its unique fermentome pattern, making
NASH distinguishable from controls.
AIMS & METHODS: To determine if NASH results in an altered VOC pattern
in the urine, detectable by ion mobility spectrometry (FAIMS), and distinguishable from cirrhotics vs non-cirrhotics.
33 patients were recruited; 8 with NASH cirrhosis; (confirmed histologically), 8
with non-cirrhotic NASH; 5 with NAFLD (non-alcohol fatty liver disease) and
12 controls (normal synthetic liver function). Urine was collected and 10 ml
aliquots were stored frozen in universal containers. For assay, the containers
were first heated to 40  0.1oC. The headspace (the air above the sample) was
then pumped from the containers and analysed by Field Asymmetric Ion
Mobility Spectrometry (FAIMS). Linear discriminant analysis (LDA) was used
for initial statistical evaluation, with a re-classification using a leave one out
for calculating sensitivity and specificity.
RESULTS: LDA showed that FAIMS is able to distinguish the VOC pattern in
these different groups of liver disease. The control group was significantly different to all of the other groups with a sensitivity of 100%. Of the disease groups,
NASH and NASH with cirrhosis had sensitivity of 83% and 77% respectively
with specificity of 80%. NAFLD however had sensitivity of 50% but specificity
of 80%.
CONCLUSION: This pilot study suggests the IMS (FAIMS technology) offers
a novel non-invasive approach to separate not only NASH from controls but
also those with established cirrhosis using urine. It offers the potential for early
non-invasive tracking of NASH and its complications.
REFERENCES
1. Arasaradnam RP, Covington JA, Harmston C, et al. Next generation diagnostic modalities in gastroenterology gas phase volatile compound biomarker
detection. Aliment Pharmacol Ther 2014; 39: 780-789.
Disclosure of Interest: None declared
P0039 ELASTOGRAPHY PLUS PLATELET COUNT RATHER THAN
ENDOSCOPY TO SCREEN FOR LARGE OESOPHAGEAL VARICES
N. Ding1,*
Gastroenterology, St Vincents Hospital, Melbourne, Australia
Contact E-mail Address: dingnik@gmail.com
1

INTRODUCTION: Endoscopic screening for gastro-oesophageal varices (GOV)


is currently recommended for all cirrhotic patients. Noninvasive methods for
liver fibrosis assessment are identifying increasing numbers of patients with cirrhosis-range liver stiffness measurements (LSM), increasing the number of
referrals for screening endoscopy. The identification of simple non-invasive markers for the presence/absence of large gastroesophageal varices (GOV) would be
clinically useful. We evaluated the performance of liver stiffness measurement
(LSM)  platelet count to identify the presence of large GOV in patients with
Child Pugh (CP) A cirrhosis.
AIMS & METHODS: Data were collected retrospectively. The presence of cirrhosis was defined by LSM 4 13.6 kPa using elastography. We performed a
database search for patients with LSM 4 13.6 kPa who underwent screening
gastroscopy (2010 2013). Only patients with compensated liver disease were
included. Large GOV were defined by diameter 4 5mm or the presence of high
risk stigmata. We assessed the accuracy of LSM, platelet count (Pl) or the combination of these factors to identify patients with large GOV. A training set of 71
patients was used, and results were validated using a second cohort of 201
patients from two independent centres.
RESULTS: The combination of LSM and Pl was more accurate for identifying
CSPH than either marker alone (training cohort AUROC: 0.87 [0.77-0.94] vs.
0.78 [0.66 0.87] and 0.77 [0.66-0.86] for LSM or Pl alone). The optimal risk
score was 0.11 (Sens 0.88, Spec 0.77, PPV 0.33, NPV 0.98,
accuracy 78%). Results in the validation cohort confirmed the discriminatory
power of this model (AUROC: 0.76 [0.68-0.83]). We then tested clinically relevant cut-offs to improve the negative predictive value (NPV) for large GOV. The
NPV for the combination of LSM 5 25 kPa and Pl  100 and was 100% in both
the training cohort and validation cohort. 82 (42%) of patients overall met this
criteria.
CONCLUSION: The combination of LSM 5 25 kPa and Pl  100 can be used
to identify patients with compensated cirrhosis who do not have large GOV.
These patients do not benefit from endoscopic screening, but could be followed
with annual LSM and full blood count.
REFERENCES
1. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to
portal hypertension. American College of Gastroenterology Practice Parameters
Committee. Am J Gastroenterol 1997.
2. de Franchis R. Revising consensus in portal hypertension: report of the
Baveno V consensus workshop on methodology of diagnosis and therapy in
portal hypertension. J Hepatol 2010; 53: 762768.
3. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet
count identify portal hypertension in patients with compensated cirrhosis.
Gastroenterology 2013; 144, 102111.e1.

A142
4. Stefanescu H, Grigorescu M, Lupsor M, et al. Spleen stiffness measurement
using Fibroscan for the noninvasive assessment of esophageal varices in liver
cirrhosis patients. J Gastroenterol Hepatol 2011; 26: 164170.
Disclosure of Interest: None declared
P0040 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC
ENCEPHALOPATHY HAVE INCREASING RISK OF SUBSEQUENT
EPISODES. A POST HOC ANALYSIS OF RIFAXIMIN-A OPEN
LABEL STUDY DATA
C.A. Bannister1, P. Conway2,*, A. Radwan2, K. Nanuwa2, C.L. Morgan1,
E. Berni3, C.J. Currie1
1
Cochrane Institute of Primary Care & Public Health, Cardiff University, Cardiff,
2
Norgine, Uxbridge, 3Global Epidemiology, Pharmatelligence, Cardiff, United
Kingdom
Contact E-mail Address: PConway@norgine.com
INTRODUCTION: Hepatic encephalopathy (HE) is a chronic complication of
cirrhosis. In recurrent, overt, episodic HE, which is the most common subcategory, its seriousness is due to the chronic debilitating effects of the recurrent
episodes.
AIMS & METHODS: The aim of this study was to characterise the impact of the
number of prior HE episodes on the risk of future HE episodes. A post-hoc
analysis was carried out using data from 322 patients with a history of HE
from a phase 3, open-label study evaluating the long-term safety and tolerability
of rifaximin- 550mg BID. All eligible patients had a Conn score of 02 at
enrolment, and had either successfully participated in a previous HE study
with rifaximin- (RFHE3001), or they were new patients enrolled with 1 verifiable episode of HE within the preceding 12 months.
RESULTS: 319 of 322 patients (647 observations) aged 18 years had all the
information required for analysis. Median duration of follow-up was 17 months
(IQR 8.925.4). Stratifying patient observations by number of prior HE episodes
and using the Kaplan Meier method the probability of being event free at year
one was 0.644 (95% CI; 0.543-0.763), 0.615 (0.541-0.700), 0.396 (0.303-0.518) and
0.302 (0.246-0.371) and the probability at year two was 0.579 (0.469-0.713), 0.539
(0.455-0.638), 0.292 (0.1999-0.428) and 0.218 (0.163-0.290) for one, two, three
and four or more prior HE episodes, respectively. Plotting the Kaplan Meier
curves of time to next HE episode, stratified by the number of prior HE episodes,
a clear association between decreased time to next HE episode and increased
number of prior episodes was seen. Using log-rank tests, there was no significant
difference between the survival curves of one prior and two prior HE episodes
(2 0 on 1 degree of freedom (d.f.), p 0.899), however there were significant
differences between survival curves of one prior or two prior episodes and greater
numbers of prior episodes (2 72 on 3 d.f., p50.001).
CONCLUSION: This study supports the current understanding of the natural
history of end-stage encephalopathy; as the number of prior HE episodes
increased, the risk of subsequent HE episodes increased.
Disclosure of Interest: C. Bannister Consultancy for: Norgine, P. Conway Other:
Employee of Norgine, A. Radwan Other: Employee of Norgine, K. Nanuwa
Other: Employee of Norgine, C. Morgan Consultancy for: Norgine, E. Berni
Consultancy for: Norgine, C. Currie Consultancy for: Norgine
P0041 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY
CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS
WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS
AND PORTAL HYPERTENSION
P. Schwabl1,*, S. Bota1, P. Salzl1, M. Mandorfer1, B.A. Payer1, A. Ferlitsch1,
J. Stift2, F. Wrba2, M. Trauner1, M. Peck-Radosavljevic1, T. Reiberger1 on
behalf of Vienna Hepatic Hemodynamic Lab
1
Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Clinical
Institute of Pathology, Medical University of Vienna, Vienna, Austria
Contact E-mail Address: philipp.schwabl@meduniwien.ac.at
INTRODUCTION: Transient elastography (TE) is a non-invasive, easily repeatable tool to assess liver fibrosis and portal hypertension (HVPG). Recently, new
quality criteria for TE measurements have been proposed (Boursier et al.
Hepatology 2013): very reliable: IQR/M 50.1; reliable: IQR 0.10.3, or IQR/
M 40.3 if TE 57.1 kPa; poor reliable: IQR/M 40.3 if TE 47.1 kPa.
AIMS & METHODS: We evaluated the diagnostic power and accuracy of TE
measurements according to these new quality criteria (accurate very reliable
reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal
hypertension. Therefore we retrospectively identified patients undergoing TE,
HVPG measurement and liver biopsy within 3 months at our tertiary care center.
RESULTS: Among 278 patients (48.713.1 years, 74.7% male, 75.7% viral
etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable
measurements, while new criteria yielded in 83.2% accurate LS measurements
(23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional
or new criteria were all significantly and similarly strong correlated with fibrosis
stage (R 0.648 vs. R 0.636) and HVPG (R 0.836 vs. R 0.846). The accuracy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0%
for traditional and new TE criteria, respectively. The positive (PPV) and negative
(NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For
predicting HVPG 10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and
89.8% using traditional or new criteria, respectively. Both criteria resulted in
AUCs for diagnosis of HVPG 10mmHg of over 0.95 with a PPV and NPV
of 76% and 97%, respectively.
CONCLUSION: Applying new quality criteria for TE measurements significantly increases the number of valid TE measurements without affecting accuracy of TE for diagnosis of liver cirrhosis and portal hypertension.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0042 EVALUATION OF A NOVEL, PORTABLE, PROBE-BASED
TRANSNASAL ENDOSCOPE: SUPERIOR PATIENT PREFERENCE
AND ACCEPTABLE DIAGNOSTIC ACCURACY FOR
OESOPHAGEAL VARICES COMPARED TO CONVENTIONAL
ENDOSCOPY
S.S. Sami1,*, E. Wilkes1, M. James1, R. Mansilla-Vivar2, J. Fernandez-Sordo1,
J. White1, A. Khanna1, M. Coletta1, S. Samuel1, G. Aithal1, K. Ragunath1,
I. N. Guha1
1
Digestive Diseases NIHR Biomedical Research Unit, University of Nottingham,
UK, Nottingham, United Kingdom, 2Department of Gastroenterology, Pontifical
Catholic University of Chile, Santiago, Chile
INTRODUCTION: Conventional oesophagogastroduodenoscopy (C-OGD)
remains the gold standard test to screen for oesophageal varices (OV) in patients
with liver cirrhosis. However, it has many limitations in terms of costs, accessibility and tolerability. Hence, there is a need for less invasive and simple techniques to replace C-OGD in this setting.
AIMS & METHODS: We aimed to compare the accuracy and acceptability of a
portable, disposable, office-based, unsedated transnasal video endoscope (EG
ScanTM II) with C-OGD for the detection of OV.
This was a prospective diagnostic study. Consecutive adult patients with confirmed liver cirrhosis, scheduled for screening or surveillance of OV, were invited
to participate in this study. We excluded patients with recurrent epistaxis (more
than once a week); nasal obstruction; disease of the nasal cavity; history of
variceal bleeding or band ligation therapy in the past 12 weeks. All subjects
underwent two procedures on the same day (EG Scan followed by C-OGD),
performed by two different operators blinded to the findings of the other test.
Patients completed validated tolerability (10-point visual analogue scale (VAS))
and adverse events questionnaires on day 0 and day 14.
The primary outcome measure was diagnostic accuracy of EG scan (performed
by one operator) against C-OGD (reference standard). In addition, interobserver
agreement of the EG scan was calculated using the kappa (k) statistic, by nine
blinded endoscopists, evaluating video recordings of 47 EG Scan procedures.
RESULTS: 50 patients were recruited to the study (mean age 59 years /-11,
70% males). The majority (78%) had compensated cirrhosis. 45 patients (90%)
completed both procedures (3 failed EG Scan (6%) and 2 failed C-OGD (4%),
p 0.882). OV prevalence was 48.9%.
Sensitivity, specificity and area under the receiver operating characteristic curve
(AUROC) of the EG Scan for the diagnosis of any varices were 0.82 (95%
confidence interval (CI) 0.60-0.95), 0.78 (95%CI 0.56-0.93), and 0.80 (95%CI
0.68-0.92), respectively. Corresponding values for the diagnosis of medium/large
varices were 0.92 (95%CI 0.62-1.0), 0.97 (95%CI 0.84-1.0), and 0.94 (95%CI
0.86-1.0), respectively. Interobserver agreement was modest for the diagnosis
of any size OV (K 0.45, 95%CI 0.40-0.49) and medium/large OV (K 0.47,
95%CI 0.42-0.52).
Patients reported better experience (mean VAS/-standard deviation (SD)) and
higher preference (percentage) with EG Scan compared to C-OGD at day 0
(7.8/-2.2 vs. 6.8/-3.0, p 0.058; 76.5% vs. 23.5%, p50.001, respectively)
and day 14 (7.0/-2.3 vs. 5.5/-3.2, p 0.0013; 77.8% vs. 22.2%, p50.001,
respectively). There was no association between procedure preference and sedation use for C-OGD (day 0: odds ratio (OR) 0.16, 95%CI 0.02-1.49, p 0.106;
day 14: OR 0.24, 95%CI 0.02-2.56, p 0.238). 4 patients (8.5%) experienced
minor self-limiting epistaxis. No serious adverse events occurred.
CONCLUSION: EG Scan was accurate for the diagnosis of any varices and
clinically significant OV. Interobserver agreement was modest. More importantly, patients experience and preference remained significantly higher for EG
Scan 14 days after procedures independent of sedation use.
Disclosure of Interest: S. Sami Financial support for research from: Intromedic
Ltd, Seoul, South Korea, E. Wilkes: None declared, M. James: None declared,
R. Mansilla-Vivar: None declared, J. Fernandez-Sordo: None declared, J.
White: None declared, A. Khanna: None declared, M. Coletta: None declared,
S. Samuel: None declared, G. Aithal: None declared, K. Ragunath Financial
support for research from: Intromedic Ltd, Seoul, South Korea and Olympus
Keymed UK., I. N. Guha: None declared
P0043 NONINVASIVE PREDICTIVE MODEL FOR DETECTION OF
HIGH-RISK ESOPHAGEAL VARICES IN B-VIRAL LIVER
CIRRHOSIS: THE PH RISK SCORE AND VARICES RISK SCORE
S.H. Shin1,*, B.K. Kim1
Department of Internal Medicine, Institue of Gastroenterology, Yonsei University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: earth-peace@yuhs.ac
1

INTRODUCTION: Periodic endoscopic screening for esophageal varices (EVs)


and prophylactic treatment for high-risk EVs ((HEVs); (1) medium/large EVs
and (2) small EVs with red sign or decompensated cirrhosis) are currently recommended for all cirrhotic patients. Recently, two new liver stiffness measurement
(LSM)-based statistical equation models (PH risk score and Varices risk score)
were introduced as a noninvasive, simple, accurate models for identifying presence of EVs and clinically significant portal hypertension [1].
AIMS & METHODS: We aimed to validate predictive value of the two models for
detection of HEVs comparing with LSM alone or LSM-spleen diameter to platelet
ratio score (LSPS) [2]. We tried to suggest a cutoff of the two models, as well.
Between November 2004 and October 2011, we recruited 675 B-viral cirrhosis
patients. All underwent laboratory workups, endoscopy, LSM, and ultrasonography. LSM was measured by transient elastography; endoscopy was used as
the standard for detection of EVs. PH risk score, Varices risk score and LSPS
were calculated in all cases as follows: PH risk score -5.953 0.188 x LSM
1.583 x sex (1: male; 0: female) 26.705 x spleen diameter/platelet count ratio,

A143

United European Gastroenterology Journal 2(1S)


Varices risk score -4.364 0.538 x spleen diameter 0.049 x platelet count
0.044 x LSM 0.001 x (LSM x platelet count).
RESULTS: Among all the patients, 239 (35.4%) patients had EVs and 172
(25.5%) had HEVs. The area under the receiver-operating characteristic curve
(AUROC) of PH risk score was 0.951 (95% CI 0.934-0.968) and LSPS was 0.950
(95% CI 0.931-0.970), showing superiority of diagnostic accuracy over other
factors: Varices risk score (0.907, 95% CI 0.876-0.939, p50.001), LSM alone
(0.873, 95% CI 0.842-0.904, p50.001). At PH risk score 5 4.0, 94.6% negative
predictive value (NPV) was provided (481 patients), whereas 94.3% positive
predictive value (PPV) was achieved (70 patients) at PH risk score 4 10.0. In
the same way, at Varices risk score 5 -2.5, 95.6% NPV was provided (413
patients), whereas 91.7% PPV was achieved (72 patients) at Varices risk score
4 1.3. Overall, the likelihood of HEVs was correctly diagnosed in 551 patients
(81.6%) and 485 patients (71.9%), respectively.
CONCLUSION: The PH risk score is a reliable, noninvasive predictive model
for detection of HEVs. Furthermore, the LSPS is considered as more simply
applicable model having similar predictive value. Patients with PH risk score
5 4.0 may avoid endoscopy safely, whereas those with 4 10.0 should be considered for appropriate prophylactic treatments.
REFERENCES
1. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet
count identify portal hypertension in patients with compensated cirrhosis.
Gastroenterology 2013; 144: 102-111.e101.
2. Kim BK, Han KH, Park JY, et al. A liver stiffness measurement-based, noninvasive prediction model for high-risk esophageal varices in B-viral liver cirrhosis. Am J Gastroenterol 2010; 105(6): 1382-1390.
Disclosure of Interest: None declared
P0044 PLALA
SCORE
PREDICT
CIRRHOSIS
NONALCOHOLIC FATTY LIVER DISEASE

PATIENT

IN

T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, M. Yoneda1, A. Nakajima1 on


behalf of JSG-NAFLD
1
gastroenterology and hepatology, Yokohama city university, yokohama, Japan
Contact E-mail Address: takaomo-kesso@hotmail.co.jp
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an important
cause of chronic and progressive liver injury in many countries1). NAFLD
includes a wide spectrum of liver diseases that range from simple steatosis,
which is generally a nonprogressive condition, to nonalcoholic steatohepatitis
(NASH), which can progress to liver cirrhosis and hepatocellular carcinoma
(HCC), despite the absence of significant alcohol consumption. If NAFLD
patients have liver cirrhosis, they need to be kept under surveillance for early
detection of hepatocellular carcinoma and gastroesophageal varices. Liver biopsy
is the gold standard for diagnosis and staging of fibrosis in patients with
NAFLD2). However, ad the number of NAFLD patients has reached 80100
million in the United States and about 10 million NAFLD patients are estimated
in Japan, it is virtually impossible to enforce in all patients.
AIMS & METHODS: To develop a mass screening system for general physicians, which can be used for predicting liver cirrhosis in NAFLD patients, using
routine laboratory parameters.
A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from
nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3,
190; stage 4, 38). Statistical analysis was conducted using SPSS version 12.0.
Continuous variables were expressed as mean  SD.
RESULTS: Platelet counts, serum albumin levels, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio were selected as independent variables associated with cirrhosis in NAFLD patients by multiple logistic regression
analysis. The optimal cutoff value of platelet count, serum albumin, and AST/
ALT ratio was set at 515.3 104/l (sensitivity; 81.6% specificity; 88.6%), 54.0
g/dl (sensitivity; 84.2% specificity; 84.6%), and 40.9 (sensitivity; 78.9%, specificity; 82.0%), respectively, by the receiver operating characteristic curve. These
three variables were combined in an unweighted sum (platelet count 1 point,
serum albumin 1 point, AST/ALT ratio 1 point) to form an easily calculated
composite score for predicting cirrhosis in NAFLD patients, called the PLALA
(platelet, albumin, AST/ALT ratio) score. The diagnosis of PLALA 2 had
sufficient accuracy for detecting liver cirrhosis in NAFLD patients (86.8% sensitivity, 90.8% specificity, 99.4% negative predictive value, 26.1% positive predictive value).
CONCLUSION: The PLALA score may be an ideal scoring system for detecting
cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.
REFERENCES
1) Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 12211231.
2) Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in
patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-1362.
Disclosure of Interest: None declared
P0045 CARVEDILOL VERSUS NON-SPECIFIC BETABLOCKERS AND
MORTALITY IN ALCOHOLIC CIRRHOSIS. A NATIONWIDE
RETROSPECTIVE STUDY
U.C. Bang1,*, T. Benfield2, L. Hyldstrup3, J.-E. B. Jensen3, F. Bendtsen1
1
Gastrounit, 2Infectious Diseases, 3Endocrinology, Hvidovre Hospital, Hvidovre,
Denmark
Contact E-mail Address: ulrichbangbang@gmail.com
INTRODUCTION: Carvedilol may have a greater effect on portal and systemic
hypertension than propranolol although reports are conflicting 1, 2. The impact

of carvedilol versus non-specific betablockers (NSBB) on mortality on patients


with cirrhosis remains to be evaluated.
AIMS & METHODS: We wanted to compare the impact on mortality of carvedilol versus NSBB in patients with cirrhosis. We identified patients with alcoholic
cirrhosis from the Danish National Patient Register during the period 1995
through 2010. We used the anatomical therapeutic chemical (ATC) classification
to identify the user of NSBB (C07AA) or carvedilol (C07AG02). We defined risk
time as the time from the first prescription of either carvedilol or NSBB until
death or end of follow-up (December 31, 2010). We adjusted for gender, age,
heart disease, variceal bleeding, socioeconomic status, Charlson score, and use of
diuretics. We used univariate and multivariate Cox proportional hazard models
to assess the HR. Persons with missing data were excluded from the analyses
(0.03%). All analyses were done using SAS 9.3 (SAS Institute Inc., Cary, NC,
USA).
RESULTS: We identified 83 and 2.060 patients, who were treated with carvedilol
and NSBB, respectively. Three patients had received both carvedilol and NSBB
and were excluded. Patients from the carvedilol group were mainly classified with
uncomplicated cirrhosis without a history of laparocentesis (96%). Hence, we
only included patients with uncomplicated cirrhosis in our mortality analysis (80
versus 1.857 patients). Significantly fewer patients in the carvedilol group died
during follow-up compared with the NSBB group (20.5% vs. 46.5%, Chi-square
p50.0001). We found the un-adjusted HR for carvedilol vs. NSBB to be 0.45
(95% CI 0.3-0.7) and the HR adjusted for covariates was 0.46 (95% CI 0.3-0.7).
The prevalences of variceal bleeding (11% vs. 40%) or heart disease (70% vs.
14%) prior to cohort entry were un-evenly distributed between users of carvedilol
and NSBB. We did a sub-analysis where we matched patients on the presence of
heart disease and variceal prior to cohort entry. In this sub-analysis we compared
80 patients using carvedilol with 240 patients (1:3 ratio) using NSBB and found
an adjusted HR of 0.38 (95% CI 0.2-0.7).
CONCLUSION: The use of carvedilol compared with NSBB in patients with
cirrhosis was associated with lower mortality in this retrospective study.
REFERENCES
1. Hobolth L, Bendtsen F, Hansen EF, et al. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: a randomised study.
Dig Liver Dis 2014; 46: 251-256.
2. Banares R, Moitinho E, Matilla A, et al. Randomized comparison of longterm carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology 2002; 36: 1367-1373.
Disclosure of Interest: None declared
P0046 RESULTS OF THE UK MULTI-REGIONAL AUDIT OF BLOOD
COMPONENT USE IN CIRRHOSIS
V. Jairath1,*, M. Desborough2, B. Hockley2, M. Sekhar3, S. Stanworth2,
A. Burroughs3
1
Nuffield Department of Medicine, University of Oxford, 2NHS Blood and
Transplant, Oxford, 3Royal Free Hospital, London, United Kingdom
INTRODUCTION: Cirrhosis is a complex acquired disorder of coagulation with
a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombotic disorder. It is a frequent indication for transfusion of blood components, both
for prophylaxis and for treatment of bleeding, although indications and patterns
of blood use are poorly characterised.
AIMS & METHODS: All NHS trusts with representation on the British Society
of Gastroenterology membership list were invited to take part in a national audit.
Data were collected prospectively on consecutive admissions with a confirmed
diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/
death/day 28. Specific information was requested on use of blood components,
including indication, type of component and laboratory indices prior to transfusion. Standards were defined against guidelines on the use of red blood cells
(RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitate.
RESULTS: Data on 1313 consecutive patients with cirrhosis (mean age 58 years,
65% male) were collected from 85 hospitals. The predominant aetiology was
alcohol (70%; 921/1313); 74% of admissions were for features of decompensation; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all
admissions were transfused a blood component; in 61% (238/391) this was for
treatment of bleeding and in 39% (153/391) for prophylaxis. In patients transfused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238)
received RBCs, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238)
cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold
was 48g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis
the majority (61%, 94/153) received transfusion in the absence of a planned
procedure. In patients transfused for prophylaxis prior to a procedure (59/
153): 19% (3/16) received FFP at an INR 1.5 for high risk procedures and
33% (6/18) received FFP at an INR2 for low risk procedures; 36% (9/25)
received platelet transfusion at a platelet count450 prior to a procedure. The
most frequent procedures resulting in prophylactic transfusion were paracentesis
(18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboembolism was documented in 2% (29/1313) cases. Case fatality during follow up
was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the
most frequent cause of death.
CONCLUSION: Patients with cirrhosis are frequently transfused during hospitalisation. This audit highlights areas where greater scrutiny of blood component
use is required, particularly in the group transfused for prophylaxis of bleeding.
Further work is needed to improve patterns of blood use in cirrhosis to ensure
patients are not exposed to unnecessary transfusion and its attendant harms.
Disclosure of Interest: None declared

A144

United European Gastroenterology Journal 2(1S)

P0047 SVR12 OF 99% ACHIEVED WITH A RIBAVIRIN-FREE REGIMEN


OF ABT-450/R/OMBITASVIR AND DASABUVIR IN HCV GENOTYPE
1B-INFECTED PATIENTS
A. Maieron1,*, M. Puoti2, J. V. Enejosa3, P. Andreone4, Z. Ben Ari5,
G. Norkrans6, M. Romero-Gomez7, W. Xie3, D.E. Cohen3, T. Podsadecki3
1
Elisabeth Hospital, Linz, Austria, 2A. O. Ospedale Niguarda Ca Granda, Milan,
Italy, 3AbbVie Inc., North Chicago, United States, 4University of Bologna,
Bologna, Italy, 5The Chaim Sheba Medical Center, Tel Hashomer, Israel,
6
Sahlgrenska University Hospital, Goteborg, Sweden, 7Hospital Universitario
Nuestra Senora De Valme, Seville, Spain
INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor (identified
by AbbVie and Enanta) dosed with ritonavir (r). Ombitasvir (formerly ABT-267)
is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is a non-nucleoside
NS5B RNA polymerase inhibitor. We report the sustained virologic response
12 weeks post-treatment (SVR12) achieved in HCV genotype 1b-infected patients
after treatment with these 3 direct-acting antivirals (3D regimen) with or without
ribavirin (RBV).
AIMS & METHODS: Five hundred ninety-nine treatment-na ve and prior
pegIFN/RBV-experienced HCV genotype 1b-infected patients without cirrhosis
were enrolled and received study drugs in the PEARL-II and PEARL-III randomized phase 3 studies. Patients were randomized 1:1 to co-formulated ABT-450/
r/ombitasvir (150 mg/100 mg/25 mg once daily) and dasabuvir (250 mg twice
daily) with or without weight-based RBV (1000 1200 mg daily).
RESULTS: The combined SVR12 rate from PEARL-II and PEARL-III was
99.3% in 301 patients who received 3D regimen without RBV vs. 98.7% in 298
patients who received 3D RBV. Two patients (0.7%) receiving 3D without RBV
did not achieve SVR12, both due to missing week 12 post-treatment follow-up.
Four 3D RBV patients did not achieve SVR12: 1 (0.3%) due to virologic breakthrough, 1 (0.3%) due to missing SVR12 data, and 2 (0.7%) due to study drug
discontinuation for adverse events. SVR12 rates did not differ between 3D and 3D
RBV by baseline factors including IL28B genotype, sex, age, race, ethnicity,
BMI, fibrosis stage, and HCV RNA viral load. No patients receiving 3D and 0.7%
of patients receiving 3D RBV discontinued due to adverse events.
SVR12 by baseline factors, n/N (%)

3D

3D RBV

Overall
Treatment-na ve
PegIFN/RBV Treatment-experienced
IL28B non-CC genotype
Female
Age 65
Black race
BMI  30 kg/m2
Fibrosis stage, F3

299/301 (99.3)
208/210 (99.0)
91/91 (100)
249/250 (99.6)
160/160 (100)
34/34 (100)
16/16 (100)
62/64 (96.9)
31/33 (93.9)

294/298 (98.7)
209/210 (99.5)
85/88 (96.6)
240/244 (98.4)
147/149 (98.7)
29/29 (100)
13/13 (100)
44/45 (97.8)
33/34 (97.1)

CONCLUSION: Irrespective of previous pegIFN/RBV treatment response and


other baseline factors, HCV genotype 1b-infected patients achieved high SVR
rates after 12 weeks of 3D without RBV. Overall, only 1 (3D RBV) of 599
(0.2%) patients experienced virologic breakthrough and none experienced
relapse. Both regimens were well tolerated. ABT-450/r/ombitasvir and dasabuvir
without RBV achieves optimal treatment efficacy in HCV genotype 1b-infected
patients without cirrhosis.
Disclosure of Interest: A. Maieron Financial support for research from: Roche,
MSD, Consultancy for: MSD, Janssen Therapeutics, AbbVie, Boehringer
Ingelheim, Gilead Sciences, BMS, Rottapharm-Madaus, M. Puoti: None
declared, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, P. Andreone
Financial support for research from: Roche, Merck, Gilead, Consultancy for:
Roche, Merck, Janssen Cilag, AbbVie, Boehringer Ingelheim, Gilead, MSD,
BMS, Z. Ben Ari Consultancy for: MSD, Janssen, AbbVie, Boehringer
Ingelheim, BMS, GSK, G. Norkrans: None declared, M. Romero-Gomez
Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz,
BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead
Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, W. Xie
Shareholder of: AbbVie, Other: AbbVie, D. Cohen Shareholder of: AbbVie,
Other: AbbVie, T. Podsadecki Shareholder of: AbbVie, Other: AbbVie
P0048 ADHERENCE TO PRESCRIBED DOSES OF ABT-450/R/
OMBITASVIR, DASABUVIR, AND RIBAVIRIN IN THE PHASE 3
PEARL-II, PEARL-III, AND PEARL-IV TRIALS
D. Bernstein1, R. Marinho2,*, D. Cohen3, F. Bredeek4, F. Schneider5,
G. Norkrans6, M. Curescu7, M. Bennett8, M. Maevskaya9, J. Fessel10, W. Xie3,
Y. Luo3, J. Enejosa3
1
Hofstra North Shore- LIJ School of Medicine, Manhasset, United States, 2Centro
Hospitalar Lisboa Norte, Medical School of Lisbon, Lisbon, Portugal, 3AbbVie
Inc., North Chicago, 4Metropolis Medical Group, San Francisco, United States,
5
Markusovszky Hospital, Szombathely, Hungary, 6Sahlgrenska University
Hospital, Goteborg, Sweden, 7Life Search SRL, Timisoara, Romania, 8Medical
Associates Research Group, San Diego, United States, 9First Moscow State
Medical Universita n.a. I. M. Sechenov, Moscow, Russian Federation, 10Kaiser
Permanente, San Francisco, United States
INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor identified by
AbbVie and Enanta, dosed with ritonavir(r); ombitasvir(ABT-267) is an NS5A

inhibitor; dasabuvir(ABT-333) is an NS5B RNA polymerase inhibitor. The


phase 3 PEARL trials examined the efficacy and safety of all-oral, interferonfree, 12-week regimens of ABT-450/r/ombitasvirdasabuvir(3D) with or without
ribavirin(RBV) in HCV genotype(GT) 1a- and 1b-infected patients(pts). We
report pt adherence to the regimens in these trials.
AIMS & METHODS: Pts were randomized to co-formulated ABT-450/r/ombitasvir(150mg/100mg/25mg QD)dasabuvir(250mg BID) with either weightbased RBV or placebo (PBO)/no RBV. Adherence was calculated by pill
counts as the percentage of capsules/tablets taken relative to the total capsules/
tablets expected to be taken.
RESULTS: In each trial, mean pt adherence to every study drug was
498.5%(Table). Adherence was comparable in those who received 3D with
RBV, 3D with PBO, or 3D alone. SVR12 rates were 96.6-100% in treatmentexperienced and treatment-na ve HCV GT1b-infected pts receiving 3D/-RBV.
SVR12 rates were 97.0% and 90.2%, respectively, in treatment-na ve GT1ainfected pts receiving 3DRBV or 3DPBO. Only 1 GT1b-infected pt had
virologic failure. Pts with virologic failure had adherence rates comparable to
the overall rates, but the majority was GT1a-infected and did not receive RBV.
Five pts had adherence rates580% for one or more study drugs, none of whom
had virologic failure. Among 401 pts receiving 3D with RBV and 509 pts receiving 3D without RBV, 2(0.5%) and 2(0.4%), respectively, discontinued study drug
due to adverse events.
PEARL-III
PEARL-II
Treatment-experienced* Treatment-na ve
GT1b
GT1b
3DRBV
Adherence, Mean % (SD)
ABT-450/r/ ombitasvir 99.7 (2.3)
n 87
dasabuvir
RBV
SVR12, % (n/N)

99.0(3.2)
n 90
99.1 (6.5)
n 87
96.6
(85/88)

PEARL-IV
Treatment-na ve
GT1a

3D

3DRBV 3DPBO 3DRBV 3DPBO

100.0 (2.6)
n 92

99.8 (1.2) 100.0 (1.1) 99.7 (1.9) 99.7 (3.3)


n 205
n 205
n 98
n 190

99.2 (1.6)
n 94
NA

99.8 (1.2)
n 205
99.6 (2.1)
n 205
99.5
(209/210)

100
(91/91)

99.9 (1.1)
n 205
99.6 (2.6)
n 203
99.0
(207/209)

99.2 (2.0)
n 98
98.6 (3.2)
n 90
97.0
(97/100)

99.1 (3.6)
n 190
98.7 (3.6)
n 181
90.2
(185/205)

Adherence data for each capsule/tablet not available for all pts.
In PEARL-II, 7 randomized patients were excluded from the intent-to-treat
efficacy population because they received non-coformulated ABT-450/r/ombitasvir (N 6) or could not be genotyped (N 1).
CONCLUSION: Participants in these phase 3 trials had excellent adherence
(498.5%) to doses of ABT-450/r/ombitasvir, dasabuvir, and RBV. Low adherence rates, while infrequent, were not associated with virologic failure.
Disclosure of Interest: D. Bernstein Financial support for research from: AbbVie,
BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie,
Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen,
Vertex, Merck, R. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche,
Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen,
D. Cohen Shareholder of: AbbVie, Other: AbbVie, F. Bredeek Financial support
for research from: AbbVie, BMS, Gilead, Janssen, Merck, Sumagen, ViiV,
Lecture fee(s) from: Merck, ViiV, Consultancy for: Merck, ViiV, F. Schneider:
None declared, G. Norkrans: None declared, M. Curescu: None declared, M.
Bennett Shareholder of: AbbVie, M. Maevskaya: None declared, J. Fessel: None
declared, W. Xie Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder
of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie
P0049 ASSOCIATION BETWEEN TLR-3 GENE POLYMORPHISM
RS3775291 AND PROGRESSION OF HEPATITIS C VIRUS
INFECTION
F.-Z. Fakhir1,2,*, M. LKHIDER1
1
Faculte des Sciences, Chouaib Doukkali University, El Jadida, 2Viral Hepatitis
Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco
Contact E-mail Address: fatimazohra.fakhir@gmail.com
INTRODUCTION: Hepatitis C virus (HCV) is a major global health problem
with about 210 million people infected worldwide, and constitutes the most
important cause of chronic liver disease. HCV is an enveloped positive-strand
RNA virus belonging to the genus Hepacivirus of the family Flaviviridae. During
the viral replication cycle, double-stranded RNA (dsRNA), produced as an intermediate, is sensed by several pattern recognition receptors (PRRs) of the innate
immune system including Toll-like receptors (TLR). TLRs constitute a family of
receptors playing a key role in innate and adaptive immune response, among
them TLR3,-7 and -8, which are expressed on endosomal membrane, and have
been suggested to play an important role in antiviral immune responses based on
their recognition of dsRNA and single-stranded RNA (ssRNA). Single nucleotide polymorphisms (SNPs) may shift balance between pro- and anti-inflammatory cytokines, contributing to successful resistance to infection or leading to
chronic inflammation and cancer. The aim of this study was to investigate the
association between the TLR-3, -7 and -8 polymorphism and the outcome of
HCV infection.
AIMS & METHODS: 517 patients were enrolled in the study and genotyped for
the TLR3, -7 and -8 SNPs. Logistic regression was used to assess the association
between the polymorphisms and the outcome of the infection.
RESULTS: A significant association between TLR-3 SNP at rs3775291 and risk
of advanced liver disease was identified. The rs3775291-A/A genotype was more
common in subjects with advanced liver disease than subjects with mild chronic

A145

United European Gastroenterology Journal 2(1S)


hepatitis C (OR 3.81; 95% CI, 2.16-6.72; p 0.000004) and this difference was
higher with healthy controls (OR 5.34; 95% CI, 2.70-10.58; p 0.000002).
CONCLUSION: Our findings indicate that a TLR-3 SNP rs3775291 is associated with progression of HCV infection to cirrhosis and hepatocellular
carcinoma.
Disclosure of Interest: None declared

Shareholder of: AbbVie, Other: AbbVie, M. Colombo Financial support for


research from: Merck, Roche, BMS, Gilead, Lecture fee(s) from: Tibotec,
Roche, Novartis, Bayer, BMS, Gilead Sciences, Vertex, Consultancy for:
AbbVie, Merck, Roche, Novartis, Bayer, BMS, Gilead Sciences, Tibotec,
Vertex, Janssen Cilag, Achillion, Lundbeck, Abbott, Boehringer Ingelheim,
GSK, GenSpera

P0050 LOW INCIDENCE OF HYPERBILIRUBINAEMIA EVENTS WITH


ABT-450/R/OMBITASVIR AND DASABUVIR WITH OR WITHOUT
RIBAVIRIN IN HCV GENOTYPE-1 INFECTED PATIENTS

P0051 SUSTAINED VIROLOGIC RESPONSE 12 WEEKS


POST-TREATMENT WITH ABT-450/RITONAVIR/OMBITASVIR AND
DASABUVIR WITH RIBAVIRIN (SAPPHIRE I AND II) IS
INDEPENDENT OF PATIENT SUBGROUPS

M. Romero-Gomez1,*, R.T. Marinho2, R. Planas Vila3, D. Bernstein4,


F. Rodriguez-Perez5, T. Hassanein6, K.R. Reddy7, N. Tsai8, S. Lovell9, J.
V. Enejosa9, Y. Luo9, D.E. Cohen9, M. Pedrosa9, M.G. Colombo10
1
Hospital Universitario Nuestra Senora De Valme, Seville, Spain, 2Centro
Hospitalar Lisboa Norte, Medical School of Lisbon, Lisboa, Portugal, 3Hospital
Germans TrasiPujol, CIBERehd, Badalona, Spain, 4Hofstra North Shore-LIJ
School of Medicine, Manhasset, United States, 5Gastroenterology and Hepatic
Wellness Center, Santruce, Puerto Rico, 6Southern California Liver Centers and
Southern California Research Center, Coronado, 7University of Pennsylvania,
Philadelphia, 8The Queens Medical Center Liver Center, Honolulu, 9AbbVie
Inc., North Chicago, United States, 10University of Milan, Milan, Italy
INTRODUCTION: Ribavirin (RBV) is known to cause haemolytic anaemia that
can lead to hyperbilirubinaemia. In addition, the NS3/NS4A protease inhibitor
ABT-450 can increase unconjugated bilirubin levels due to transporter inhibition.
We report the rate of hyperbilirubinaemia in HCV genotype 1-infected patients
treated with ABT-450/r/ombitasvir (formerly ABT-267) and dasabuvir (formerly
ABT-333) (3D regimen) with or without RBV.
AIMS & METHODS: Data from 910 patients randomized in 3 phase 3 trials
(PEARL-II, PEARL-III, and PEARL-IV), which examined the contribution of
RBV to the safety and efficacy of the 3D regimen, were used to evaluate the
incidence and severity of clinical events related to bilirubin (hyperbilirubinaemia,
jaundice) during 12 weeks of treatment. Total, direct, and indirect bilirubin were
assessed at baseline and every 1-2 weeks per protocol.
RESULTS: Total bilirubin elevations of 43X ULN occurred in 23/401 (5.7%)
3DRBV patients and in 2/509 (0.4%) patients receiving the RBV-free 3D regimen. The majority of patients in each group (490%) had normal total bilirubin
levels at the end of treatment. Mean total bilirubin levels were significantly higher
at each treatment visit in the RBV-containing treatment groups. Mean total
bilirubin peaked at week 1 in both treatment groups (predominantly indirect),
and declined to baseline by week 2 in the RBV-free group. Events of hyperbilirubinaemia and jaundice were mostly mild, occurred within the first 2 weeks of
treatment and did not result in study drug discontinuation. One patient underwent RBV dose modification and one interrupted study drug due to hyperbilirubinaemia; both patients achieved sustained virologic response 12 weeks posttreatment. Two patients receiving 3DRBV experienced ALT 3X ULN and
total bilirubin 2X ULN, however, the timing and predominance of indirect
bilirubin were not consistent with drug induced liver injury. No serious adverse
events related to hyperbilirubinaemia were reported.

M.R. Brunetto1,*, M. Makara2, H. Hinrichsen3, J. Hanson4, M. Bennett5,


E. Lawitz6, J. Xiong7, E. Coakley7, T. Baykal7, G. Neff7
1
Liver Unit, University Hospital of Pisa, Pisa, Italy, 2Saint Laszlo Hospital,
Budapest, Hungary, 3Gastroenterologisch-Hepatologisches Zentrum, Kiel,
Germany, 4Charlotte Gastroenterology & Hepatology, PLLC, Charlotte, 5San
Diego Digestive Diseases, San Diego, 6Texas Liver Institute, University of Texas
Health Science Center, San Antonio, 7AbbVie, North Chicago, United States
Contact E-mail Address: brunetto@med-club.com, laurinda.cooker@abbvie.com
INTRODUCTION: ABT-450 is a potent hepatitis C virus (HCV) protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta;
ombitasvir (ABT-267) is an NS5A inhibitor and dasabuvir (ABT-333) is a nonnucleoside polymerase inhibitor. In phase 3 trials of this 3 direct-acting antiviral
(3D) regimen with ribavirin (RBV) in non-cirrhotic HCV genotype 1-infected
patients, 96.3% of treatment-na ve patients (SAPPHIRE-I trial) and 96.2% of
pegINF/RBV-experienced patients (SAPPHIRE-II trial) achieved SVR12 (HCV
RNA 525 IU/mL at post-treatment week 12).
AIMS & METHODS: Patients in the SAPPHIRE-I and -II trials were randomized to receive the 3D regimen of co-formulated ABT-450/r/ombitasvir
(150mg/100mg/25mg QD) and dasabuvir (250mg BID) with weight-based RBV
(1000 or 1200 mg daily divided BID), or placebo, for 12 weeks. Data from the
two trials were pooled, and SVR12 rates were calculated overall and according to
race, ethnicity, and region.
RESULTS: 770 patients assigned to the 3DRBV regimen received 1 dose of
study drug. The overall SVR12 rate in the combined studies was 96.2%; high
SVR rates were achieved regardless of race, ethnicity, or region (Table).
Tolerability was similar across populations. Most adverse events were mild or
moderate; the 3 most common adverse events were headache (34.3%), fatigue
(34.2%) and nausea (22.3%). Few patients discontinued due to adverse events (6/
770, 0.8%).
3DRBV
% with SVR12 (n/N)
Overall
Race
Ethnicity

Bilirubin-related events, n (%)

3DRBV (N 401)

3D (N 509)

Any bilirubin-related event


Hyperbilirubinaemia
Jaundice
Total bilirubin 43X ULN

21
13
11
23

4
3
1
2

(5.2)
(3.2)
(2.7)
(5.7)

(0.8)
(0.6)
(0.2)
(0.4)

CONCLUSION: Low rates of hyperbilirubinaemia were observed with both 3D


regiments but was less frequent in the RBV-free 3D regimens, suggesting that
increases in bilirubin associated with ABT-450-containing regimens are enhanced
by RBV-induced haemolysis. Bilrubin-related adverse events were infrequent
with both regimens and did not affect treatment response.
Disclosure of Interest: M. Romero-Gomez Lecture fee(s) from: AbbVie, Roche,
Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK,
Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS,
Boehringer Ingelheim, GSK, R. T. Marinho Lecture fee(s) from: AbbVie, Gilead,
BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche,
Merck, Janssen, R. Planas Vila Financial support for research from: Roche,
MSD, BMS, Gilead, Janssen, Lecture fee(s) from: Roche, MSD, BMS, Gilead,
Janssen, Boehringer Ingelheim, Consultancy for: Roche, MSD, BMS, Gilead,
Janssen, D. Bernstein Financial support for research from: AbbVie, BMS,
Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie,
Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen,
Vertex, Merck, F. Rodriguez-Perez Lecture fee(s) from: BMS, Merck,
Consultancy for: AbbVie, Gilead, Janssen, Merck, T. Hassanein Financial support for research from: AbbVie, Boehringer-Ingelheim, BMS, Eisai, Gilead,
Janssen, Idenix, Ikaria, Mochida, Takeda, Mochida, Roche, Ocera, Sundise,
Salix, Taigen, Takeda, Vertex, Lecture fee(s) from: BMS, Genentech, Gilead,
Salix, Consultancy for: AbbVie, BMS, K. R. Reddy Financial support for
research from: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, GenentechRoche, Genfit, Consultancy for: AbbVie, BMS, Gilead, Vertex, Janssen,
Merck, Genentech-Roche, Idenix, N. Tsai Financial support for research from:
AbbVie, Janssen, Genentech-Roche, Vertex, BMS, Lecture fee(s) from: Gilead,
Genentech-Roche, BMS, Vertex, Merck, Janssen, Consultancy for: AbbVie,
Gilead, Janssen, S. Lovell Shareholder of: AbbVie, Other: AbbVie, J. Enejosa
Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other:
AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, M. Pedrosa

Region

SAPPHIRE-I and SAPPHIRE-II


Black
Non-black
Hispanic/Latino
Non-Hispanic/Latino
Australia/New Zealand
Europe
North America

96.2
96.0
96.3
93.9
96.4
95.5
95.8
96.7

(741/770)
(48/50)
(693/720)
(46/49)
(695/721)
(42/44)
(346/361)
(353/365)

CONCLUSION: High pooled SVR12 rates were achieved in non-cirrhotic HCV


GT1 treatment-na ve and pegINF/RBV-experienced patients in the SAPPHIREI and SAPPHIRE-II trials, regardless of the baseline demographics assessed in
this analysis.
Disclosure of Interest: M. Brunetto Lecture fee(s) from: AbbVie, BMS, Gilead,
Janssen, MSD, Roche, Novartis, M. Makara: None declared, H. Hinrichsen
Lecture fee(s) from: AbbVie, Gilead, Janssen, BMS, MSD, Roche, J. Hanson:
None declared, M. Bennett Shareholder of: AbbVIe, E. Lawitz Financial support
for research from: AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals,
Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead
Sciences, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera
Pharmaceuticals, Inhibitex Pharmaceuticals, Intercept Pharmaceuticals,
Janssen, Medarex, Medtronic, Merck & Co., Novartis, Pharmasset, Presidio,
Roche, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals,
Vertex Pharmaceuticals, ViroChem Pharma, ZymoGenetics, Lecture fee(s)
from: Gilead, Kadmon, Merck, Vertex, Consultancy for: AbbVie, Achillion
Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, BioCryst,
Biotica; Enanta; GlobeImmune,
Idenix Pharmaceuticals,
Inhibitex
Pharmaceuticals, Janssen, Merck & Co., Novartis, Pharmasset, Santaris
Pharmaceuticals, Tibotec, Theravance, Vertex Pharmaceuticals, J. Xiong
Shareholder of: AbbVIe, Other: AbbVie, E. Coakley Shareholder of: AbbVIe,
Other: AbbVIe, T. Baykal Shareholder of: AbbVIe, Other: AbbVIe, G. Neff
Shareholder of: AbbVIe, Other: AbbVIe

A146

United European Gastroenterology Journal 2(1S)

P0052 SAFETY OF ABT-450/R/OMBITASVIR DASABUVIR WITH OR


WITHOUT RIBAVIRIN IN HCV GENOTYPE 1-INFECTED PATIENTS:
RESULTS FROM PEARL II, PEARL III, AND PEARL IV
R. Aspinall1,*, J. Lalezari2, Y. Luo3, R. Pruitt4, V. Luketic5, G. Gaeta6,
I. Olszok7, W. King8, S. Gurel9, Y. Hu3, J. Enejosa3, D. Cohen3, N. Shulman3
1
Queen Alexandra Hospital, Portsmouth, United Kingdom, 2Quest Clinical
Research, San Francisco, 3AbbVie Inc., North Chicago, 4Nashville Gastrointestinal
Specialists, Inc./Nashville Medical Research Institute, Nashville, 5Virginia
Commonwealth University, Richmond, United States, 6A. O. U. Seconda
Universita` degli Studi di Napoli, Naples, Italy, 7Szpital Rejonowy, Oddzial
Obeserwacyjno-Zakazny, Raciborz, Poland, 8Trial Management Associates; LLC,
Wilmington, United States, 9Uludag University, Bursa, Turkey
INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor dosed with
ritonavir (r) 100mg, identified by AbbVie and Enanta. Ombitasvir (formerly
ABT-267) is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is an
NS5B RNA polymerase inhibitor. The phase 3 trials PEARL II, PEARL III,
and PEARL IV examined the efficacy and safety of 12 week regimens of ABT450/r/ombitasvir dasabuvir (3D) with or without ribavirin (RBV) in non-cirrhotic patients with HCV genotype (GT) 1a and 1b infection. Safety outcomes in
patients receiving RBV-containing and RBV-free regimens in these trials are
reported.
AIMS & METHODS: GT1b-infected treatment-experienced patients (PEARL
II), GT1b-infected treatment-naive patients (PEARL III), and GT1a-infected
treatment-naive patients (PEARL IV) were randomized to co-formulated ABT450/r/ombitasvir (150mg/100mg/25mg QD) dasabuvir (250mg BID) with
weight-based RBV or placebo/no RBV. Adverse event (AE) assessment and
clinical laboratory testing occurred at study visits during treatment and followup and included all randomized patients who received at least one dose of study
drug.
RESULTS: In PEARL II, PEARL III, and PEARL IV, respectively, 186, 419,
and 305 patients were randomized and received at least one dose of study drug.
In total across the 3 trials, 401 patients received 3DRBVand 509 received 3D.
Treatment-emergent AEs and laboratory values of note are in the Table. In both
the 3DRBV and 3D groups, the majority of AEs were mild. AEs occurring in
420% of patients in both the 3DRBV and 3D groups were fatigue (29.9% and
26.5%) and headache (24.4% and 25.3%). 8.5% of patients receiving 3DRBV
had an AE leading to RBV dose modification; all of these patients achieved
SVR12. The rate of discontinuation due to AEs was 0.5% or less among patients
treated with 3DRBV or 3D.

Any AE, n (%)


Any AE leading to study drug discontinuation, n (%)
Any serious AE, n (%)
Any AE leading to RBV/placebo dose
modification, n (%)
RBV/placebo dose modification due to
decrease in hemoglobin, n (%)
Hemoglobin (g/dL), n (%)
Total bilirubin 43X ULN, n (%)
ALT 45X ULN, n (%)

3DRBV
N 401

3D
N 509

332 (82.8)
2 (0.5)

383 (75.2)
2 (0.4)

9 (2.2)
34 (8.5)

7 (1.4)
1* (0.2)

25 (6.2)

209 (52.1)/
23 (5.7)/2 (0.5)
23 (5.7)
3 (0.7)

34 (6.7)/0/0
2 (0.4)
1 (0.2)

P0054 ABERRANT EXPRESSION OF KERATIN 7 IN HEPATOCYTES AS


A PREDICTIVE MARKER OF RAPID PROGRESSION TO HEPATIC
FAILURE IN ASYMPTOMATIC PRIMARY BILIARY CIRRHOSIS
H. Seki1,*, F. Ikeda1, S. Nanba1, K. Yamamoto1
1
Department of Gastroenterology and Hepatology, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, okayama, Japan
Contact E-mail Address: jhare25@yahoo.co.jp
INTRODUCTION: Routine testing for antimitochondrial antibodies has
increased the identification of patients with asymptomatic primary biliary cirrhosis (PBC). A predictive marker of the rapid progression to hepatic failure is
desired for patients with asymptomatic PBC.
AIMS & METHODS: We performed a systematic cohort analysis of 101 patients
diagnosed as having asymptomatic PBC and the rapid progression to liver failure, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin
(CK) 7 expressions in the patients hepatocytes.
RESULTS: Intralobular expressions of CK-7 were found in nine of the 101
patients (9%). The grades of CK-7 expression was significantly associated with
the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin
(p 0.0060, 0.020, and 0.0015, respectively), but not with bile duct loss or cholestasis in orcein staining. The stepwise logistic regression analysis revealed that
high grades of CK-7 expression in hepatocytes had positive correlations with
high levels of total bilirubin (p 0.0020). During the follow-up period, eight
patients developed jaundice, and the mean period until the development of jaundice was 5.2 years. The proportional hazards models for the risk of developing
jaundice identified only high grades of aberrant CK-7 expression in hepatocytes
as significant risk factor (hazards ratio 8.7, p 0.019).
CONCLUSION: Aberrant CK-7 expression in hepatocytes can be used as an
additional marker to predict the rapid progression to liver failure in patients with
asymptomatic PBC at the time of diagnosis.
Disclosure of Interest: None declared
P0055 THE VALUE OF 2D SHEAR WAVE ELASTOGRAPHY (2D-SWE)
IN THE EVALUATION OF ESOPHAGEAL VARICES IN PATIENTS
WITH LIVER CIRRHOSIS

CONCLUSION: In the PEARL II, PEARL III, and PEARL IV trials, ABT-450/
r/ombitasvir dasabuvir was well tolerated either with or without RBV.
Comparable low rates of discontinuation were observed in patients receiving
the RBV-containing and RBV-free regimens. Clinically significant hemoglobin
reductions and bilirubin elevations were infrequent and not treatment-limiting.
Disclosure of Interest: R. Aspinall: None declared, J. Lalezari: None declared, Y.
Luo Shareholder of: AbbVie, Other: AbbVie, R. Pruitt: None declared, V.
Luketic: None declared, G. Gaeta Consultancy for: Merck, Roche, BMS,
Gilead, BI, AbbVie, I. Olszok: None declared, W. King: None declared, S.
Gurel Lecture fee(s) from: Roche, MSD, BMS, Johnson and Johnson,
Consultancy for: Roche, MSD, BMS, Johnson and Johnson, Y. Hu
Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie,
Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, N.
Shulman Shareholder of: AbbVie, Other: AbbVie
P0053 ALBENDAZOLE CAN ENHANCE THE RESOLUTION
EOSINOPHILIC LIVER ABSCESS ASSOCIATED WITH
TOXOCARIASIS

albendazole treatment remains uncertain in this condition. We aimed to evaluate


whether albendazole can enhance the radiologic resolution of ELA-T.
AIMS & METHODS: We retrospectively reviewed the medical records of the
patients diagnosed with ELA-T at our institution between January 2008 and
December 2011. ELA-T was diagnosed based on the imaging findings on computed tomography or magnetic resonance imaging and the presence of positive
serum IgG antibody for Toxocara canis. Among a total of 163 patients, 32
patients received albendazole (albendazole group) and 131 did not (control
group). Baseline characteristics and fate of liver nodules were compared between
the two groups.
RESULTS: Baseline characteristics (age, sex, number and maximal size of
lesions, eosinophil count) were similar between the two groups. Median duration
for achieving radiologic resolution in the albendazole group was significantly
shorter than in control group (207 days [range 186-228] vs. 302 days [range
224-380], p 0.023). Cox regression analysis of the cumulative rates of radiologic
resolution showed that hazard ratio for albendazole treatment was 1.99 (95%
confidence interval: 1.22-3.23).
CONCLUSION: Radiologic resolution of ELA-T can be accelerated with albendazole treatment. Hence, inconvenience associated with long-term follow-up and
unnecessary worries among the patients can be eliminated with albendazole
treatment.
Disclosure of Interest: None declared

OF

E.-Y. Jang1,*, M.S. Choi1, W. Sohn1, G.-Y. Gwak1, K.C. Koh1, S.W. Paik1, Y.H. Paik1, B.C. Yoo1
1
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea, Republic Of
Contact E-mail Address: hand1@dreamwiz.com
INTRODUCTION: Visceral larva migrans, which is caused by Toxocara canis
and Toxocara cati, has emerged as a significant cause of eosinophilic liver abscess
(ELA). It is sometimes difficult to differentiate ELA associated with toxocariasis
(ELA-T) from metastasis or primary liver malignancy. However, the role of

O. Gradinaru Tascau1, A.S. Popescu1,*, I. Sporea1, R. Sirli1, M. Popescu1,


S. Bota1, M. Danila1, R. Sirli1, I. Ratiu1, on behalf of Flavia Mot;iu, Athena
Plaian
1
Department of Gastroenterology and Hepatology Timisoara, Emergency County
Hospital of Timisoara, Timisoara, Romania
Contact E-mail Address: bluonmyown@yahoo.com
INTRODUCTION: 2D-SWE is a new elastographic technique for the evaluation
of chronic liver disease.
AIMS & METHODS: To evaluate the feasibility of 2D-SWE in cirrhotic patients
with esophageal varices and the performance of 2D-SWE for predicting the
presence of esophageal varices.
The study group included 71 subjects diagnosed with cirrhosis by clinical, biological, ultrasound and/or endoscopic criteria. All subjects underwent 2D-SWE
with an AixplorerTM ultrasound system (SuperSonic Imagine S. A., Aix-enProvence, France). In each patient we aimed to perform three liver stiffness
measurements, with the patient in supine position and then a mean value was
calculated and expressed in kiloPascals (kPa).
RESULTS: The study included 71 subjects, 65.2% men and 34.8% women with a
median age of 60.5 years (ranging between 22-82 years). The etiology of liver
cirrhosis was: HCV-22.2%, HBV- 12.5%, HCV and HBV-2.7%, ethanol-13.8%
and other etiologies-47.2%. Esophageal varices were present in 39.4% of cases
and significant esophageal varices (grade II and III) in 22.5% of cases. 2D-SWE
had similar feasibility in patients with and without esophageal varices: 85.7% vs.
88.3%, (p 0.90). The mean 2D-SWE values (kPa) were not statistically different
in patients with and without esophageal varices: 3013.5 vs. 24.812.7, (p 0.1).
The mean 2D-SWE values (kPa) were also not statistically different in patients
with significant esophageal varices (grade II and III) vs. those without or grade I
esophageal varices: 32.413.4 vs. 25.314 kPa, (p 0.1).

United European Gastroenterology Journal 2(1S)


CONCLUSION: 2D-SWE is a feasible method in patients with cirrhosis and
esophageal varices but seems unable to predict the presence of esophageal
varices. Further studies, in a larger number of patients, are still needed.
Disclosure of Interest: None declared
P0056 IMPLEMENTING
A
VIRTUAL
PALPATION
MODEL
COMBINING SPIRAL CT AND ELASTOGRAPHY DATA INTO
MEDICAL TRAINING A PILOT STUDY
C.T. Streba1,*, I.A. Gheonea2, L. Sandulescu1, S. Adrian1, D. I. Gheonea1
Gastroenterology, 2Radiology, UMF CRAIOVA, Craiova, Romania
Contact E-mail Address: costinstreba@gmail.com

INTRODUCTION: There are inherent problems in providing training to novices


in any safety critical task. In particular, teaching medical clinicians to perform
procedures poses challenges and possible risk to patients. A palpation procedure
involves the examination of a patient through direct contact. That means that
palpation is traditionally restricted to organs in direct contact with the outer
layers of the body.
AIMS & METHODS: Our aim was to implement a previously described virtual
reality model for palpation of liver tumors based on combined spiral CT and
real-time elastography (RT-E) data in a haptic simulator used by medical students in a pilot study. After clearing all ethical concerns with the local committees
and obtaining written consent, we acquired spiral CT and full RT-E imaging data
stored in DICOM format from 15 patients with primary liver cancers scheduled
for surgery. By using previously described methods [1] we created a three-dimensional model of the liver and the tumor using the CT data and integrated elasticity information by superimposing the RT-E data on the stiffness of each
tumor. We thus obtained 15 distinct virtual models containing segmented
color-map data superimposed on a high-fidelity representation of the tumors.
These computerized models were later integrated in a virtual reality system which
projected a three-dimensional image of the tumor to the operator and allowed
physical interaction through haptic devices attached to the students body. We
tested the system on a pilot group of 60 medical students in the fifth year of
training. Students were presented with the experimental design and were asked to
perform a series of tasks involving spatial manipulation and virtual palpation of
the virtual model. They were also presented with data on the real tumor (size,
shape, location). After completion, a standardized questionnaire was given to
each student and results were quantified using descriptive statistics and intergroup analysis.
RESULTS: All students considered the model to be accurate in both size and
shape with the actual image of the tumor (60/60, 100%). The general impression
was that it increased knowledge on tumoral pathology of the liver and students
agreed that it provided useful insights otherwise unobtainable through standard
teaching techniques. The main issue with the physical haptic system were related
with the optical system for virtual reality, which the students found hard to wear
and interact. The tactile feedback device was however well accepted by the test
group.
CONCLUSION: We successfully tested a haptic medical simulator in a pilot
study involving medical students with already acquired clinical knowledge. The
general consensus was that the haptic simulator is useful for increasing knowledge on liver tumors and provide additional data otherwise unobtainable
through traditional methods.
REFERENCES
1. Streba CT, Gheonea IA, Sandulescu LD, et al. Virtual Palpation Model
combining spiral CT and elastography data: a Proof-of-Concept study.
Gastroenterology 2013; 144: S992-S993.
Disclosure of Interest: None declared
P0057 COMPARISON OF THE ACCURACY OF SHEAR WAVE
ELASTOGRAPHY AND ACOUSTIC RADIATION FORCE IMPULSE
IN DETERMINING LIVER FIBROSIS AMONG PATIENTS WITH
CHRONIC LIVER DISEASE
J.-A. V. Bisnar1,*, J. Gopez-Cervantes1, J. Bocobo1, I.H. Cua1
1
Institute of Digestive and Liver Disease, St. Lukes Medical Center, Quezon City,
Philippines
Contact E-mail Address: joannebisnar@gmail.com
INTRODUCTION: The prognosis of chronic liver diseases (CLD) depends on
the extent of liver fibrosis. Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic
liver diseases.
AIMS & METHODS: The study aims to compare the accuracy of Shear Wave
Elastography (SWE) and Acoustic Radiation Force Impulse (ARFI) in determining liver fibrosis among patients with chronic liver disease.
Cross-sectional study conducted between March-July 2012. SWE, ARFI and
ultrasound-guided liver biopsy were performed on 120 patients. Liver fibrosis
using Knodells histologic activity index and AUROC were determined for F0-F1
vs. F2-F4, F0-F2 vs. F3-F4, and F0-F3 vs. F4. SPSS 16.0, OpenEpi 2.3.1, and
Stata 11.0 software were utilized in the statistical analysis.
RESULTS: AUROCs were 0.858 (ARFI) and 0.893 (SWE), 0.944 (ARFI) and
0.95 (SWE), and 0.919 (ARFI) and 0.965 (SWE), between F0-F1 vs. F2-F4, F0F2 vs. F3-F4, and F0-F3 vs. F4, respectively. ARFI has a sensitivity and specificity of 87.5% (64-96.5) and 84.6% (76.5-90.3), 95.8% (79.8-99.3) and 78.1%
(68.9-85.2), 91.3% (79.7 96.6) and 43.2% (32.6-54.6) for F4 vs. F0-F3, F3-F4
vs. F0-F2, and F2-F4 vs. F0-F1. SWE has a sensitivity and specificity of 100%
(80.6-100) and 83.7% (75.4-89.5), 95.8% (79.7-99.3) and 85.4% (77-91.1), and
78.3% (64.4-87.7) and 86.5% (76.9-92.5).
CONCLUSION: SWE is more accurate in assessing liver cirrhosis. Both sensitivity and specificity of ARFI and SWE increased with the severity of liver

A147
fibrosis. SWE is more sensitive between F4 vs. F0-F3 and more specific between
F3-F4 vs. F0-F2 and F2-F4 vs. F0-F1. ARFI is more specific between F4 vs. F0F3 and more sensitive between F2-F4 vs. F0-F1. Differences in estimates between
SWE and ARFI were statistically significant between F0-F1 and F2-F4. Thus,
both SWE and ARFI can be used as non-invasive tools in detecting liver fibrosis.
REFERENCES
[1] Bataller R. Liver fibrosis. J Clin Invest 2005; 115: 209-218.
[2] Rockey DC. Liver biopsy. AASLD Position Paper. Hepatology 2009: 10171044.
[3] Pol S. Non-invasive staging of liver fibrosis with shearwave elastography
imaging. Aixplorer Multiwave White Paper; pp. 1-12.
[4] Rahn SB. Liver biopsy interpretation in chronic hepatitis. J Insur Med 2001;
33: 110-113.
[5] Ferraioli G. Accuracy of real-time shearwave elastography for assessing liver
fibrosis in chronic hepatitis C: a pilot study. Hepatology 2012; 1-9.
[6] Poynard T. Prospective analysis of discordant results between biochemical
markers and biopsy in patients with chronic hepatitis C. Clin Chem 2004; 50:
1344-1355.
Disclosure of Interest: None declared
P0058 NON-INVASIVE ASSESSMENT OF PORTAL HYPERTENSION
USING ELASTOGRAPHY OF SPLEEN
K. Dvorak1,*, V. Smid1, R. Sroubkova1, A. Novotny1, J. Mengerova1, J. Petrtyl1,
R. Bruha1
1
4TH DEPARTMENT OF MEDICINE, GENERAL UNIVERSITY
HOSPITAL AND 1ST MEDICAL FACULTY CHARLES UNIVERSITY IN
PRAGUE, Prague 2, Czech Republic
Contact E-mail Address: k2dvorak@gmail.com
INTRODUCTION: The degree of portal hypertension is one of crucial prognostic factors in patients with liver cirrhosis. Standard method used for the assessment is measurement of hepatic venous pressure gradient (HVPG) during liver
vein catheterisation. Being an invasive procedure this approach is not common,
has complications and moreover it does not enable monitoring of changes in the
long term. Recently non-invasive approaches have been increasingly employed in
evaluation of liver fibrosis; one such method is elastography.
AIMS & METHODS: The aim of our study was to evaluate the possibility of
assessment of portal hypertension with elastography of the spleen in patients with
various etiology of liver cirrhosis. Elastography of liver and spleen was assessed
using ARFI (Acoustic Radiation Force Impulse) measurement with ultrasound
system Siemens Acuson S2000 and then HVPG was measured in all patients. A
total of 20 patients was examined (13 men, 7 women), average age 5910.9, with
different etiology of liver cirrhosis (10 ethylic, 4 viral hepatitis, 6 other).
Diagnosis of cirrhosis was confirmed by liver biopsy or with presence of portal
hypertension. There was a control group of 20 healthy individuals without signs
of liver disease.
RESULTS: Clinically significant portal hypertension was diagnosed in 15 from
20 examined patients. The HVPG values were (mmHg; median, IQ range) 15 (326), ARFI of liver (m/s; median, IQ range) 2.96 (1.31-3.54), ARFI of spleen 3.13
(1.99-3.74). The value of ARFI of spleen significantly correlated with the degree
of portal hypertension (p 0.038), the ARFI of liver did not (p 0.251).
CONCLUSION: Spleen elastography which is simple, reproducible and easy to
repeat, could enable assessing portal hypertension in cirrhotic patients
noninvasively.
Supported by IGA MZCR NT 12290/4, SVV 260032-2014
Disclosure of Interest: None declared
P0059 OUR PRELIMINARY EXPERIENCE WITH ELASTOPQ SHEAR
WAVE ELASTOGRAPHY TECHNIQUE AND DOPPLER INDICES IN
THE NON-INVASIVE ASSESSEMENT OF LIVER FIBROSIS
M. Garcovich1,*, M.A. Zocco1, L. Riccardi1, M.E. Ainora1, E.B. Annicchiarico1,
D. Roccarina1, G. Caracciolo1, A. Grieco1, G.L. Rapaccini1, M. Siciliano1,
M. Pompili1, A. Gasbarrini1
1
Internal Medicine, Catholic University of Sacred Heart, Rome, Italy
INTRODUCTION: Real-time shear wave elastography (RTE) is a novel noninvasive technique that assesses liver fibrosis by measuring liver stiffness (in kPa).
The purpose of this study was to determine the efficacy and the feasibility for the
assessment of hepatic fibrosis as compared with the histological grade in patients
undergoing liver biopsy (LB).
AIMS & METHODS: Consecutive patients scheduled for LB were studied by
using the iU22 Philips ultrasound system with ElastPQ technique. In addition,
Doppler indices at various sites, hepatic vein and portal venous blood velocity
and flows were evaluated. The correlations between these quantitative parameters and the Metavir score were analyzed using Spearman correlation and
ROC curve analyses were performed to calculate AUC for F42, F43, and
F 4.
RESULTS: We enrolled 60 patients (39/21 males/females) who underwent LB for
viral or non-viral chronic hepatitis (HCV 58%; NASH 30%). Liver stiffness
measurements performed on the right lobe were reliable in almost all cases, while
15% of left lobe measurements were not obtainable/unreliable. Median kPa
values were 4.43(range 2.984.82) and 3.92(2.51-6.73) for F0-F1, 7.65(4.2812.9) and 8.21(5.43-12.3) for F2-F3, 15.12(9.9-29.16) and 18.54(9.31-31.34) for
F4 in the right and left lobe, respectively. AUCs calculated for the right lobe were
0.90(0.840.92;95%CI) for F42, 0.84(0.730.88;95%CI) for F43 and
0.92(0.900.96;95%CI) for F 4. Adding Doppler indices to liver stiffness
increased no further the diagnostic accuracy of RTE.

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CONCLUSION: RTE with ElastPQ appears to be a useful tool for non-invasive
evaluation of fibrosis in patients with viral and non-viral chronic hepatitis,
although these findings need to be confirmed in larger studies.
Disclosure of Interest: None declared
P0060 LIVER FIBROSIS ASSESSED BY TRANSIENT ELASTOGRAPHY
IN LONG-TERM METHOTREXATE-TREATED PATIENTS
R. Shah1,*, M. Petrova1, S. Redhead1, P. Berry1, A. ALA1,2
1
DEPARTMENT OF GASTROENTEROLOGY AND HEPATOLOGY,
FRIMLEY PARK NHS FOUNDATION TRUST, FRIMLEY,
2
GASTROENTEROLOGY, FACULTY OF HEALTH SCIENCES AND
HEALTH CARE MANAGEMENT AND STATERGY, UNIVERSITY OF
SURREY, GUILDFORD, United Kingdom
Contact E-mail Address: rahulhshah@hotmail.com
INTRODUCTION: Methotrexate (MTX) is among most commonly used immunosupressive agents but requires careful monitoring due to risks of hepatotoxicity. The amino-terminal of type III pro-collagen peptide (serum P3NP) is used
as a surrogate of collagen turnover. Its measurement has been proposed as a
marker for ongoing hepatic fibrogenesis. Liver stiffness measurement (LSM) is a
simple non-invasive method for assessment of liver fibrosis (LF). Currently, only
liver biopsy for assessment of liver fibrosis in long-term (424weeks) MTX-treated patients is used. Our aim was to evaluate the presence of liver fibrosis by
transient elastography (TE) in patients treated with MTX in a long-term clinical
practice.
AIMS & METHODS: We consecutively enrolled 34 patients with rheumatoid
arthritis or psoriasis taking MTX between 2011 and 2012. We only included
patients with normal liver function and no history of underlying chronic liver
disease. All patients had P3NP measurements close to TE. Liver stiffness was
evaluated by TE (single operator). Cut-off of LSM to predict liver fibrosis was
7.1 KPa.
RESULTS: The study population consists of 34 patients (12 males, 35%) at
mean age of 65.2 years (range 34-77, SD 11.04). Seven patients (20%) had psoriasis, 23 (68%) had RA and the remaining were with SLE. Mean MTX cumulative dose was 5320 (SD 3682) mg, and mean treatment duration was 427 weeks
(range 104-670). Mean hepatic stiffness was 7.4 KPa (SD 4.46) and mean level of
P3NP was 6.7 mcg/l (SD 2.25). In six patients abdominal ultrasound was suggestive of fatty liver disease and they were excluded from further analysis. The
remaining 28 patients had mean LSM of 7.4 KPa (SD 4.74), which correlated
significantly with serum P3NP (Pearson r 0.46, p50.02). Ten patients had
LSM 4 7.2 KPa, suggestive of significant fibrosis. Patients age, steroids, treatment duration or cumulative doses of MTX were not associated with LF.
CONCLUSION: In our series, 33% of long-term MTX treated patients developed liver fibrosis, as assessed by LSM. Transient elastography may be potentially useful in evaluation and follow-up of liver fibrosis in long-term MTXtreated patients. Further work is required to evaluate the diagnostic yield of
TE as a predictor of liver fibrosis in these patients.
REFERENCES
Laharie D, Seneschal J, Schaeverbeke T, et al. Assesment of liver fibrosis with
transient elastography and fibrotest in patients on methotrexate in chronic
inflammatory conditions.
Disclosure of Interest: None declared
P0061 XL VS. M PROBE FOR LIVER FIBROSIS ASSESSMENT BY
TRANSIENT ELASTOGRAPHY
O. Gradinaru Tascau1, R. Sirli1,*, I. Sporea1, A. Deleanu1, A. Popescu1,
M. Danila1 on behalf of Laura Culcea, Milana Szilaski, Cristian Ivascu-Siegfried
1
Department of Gastroenterology and Hepatology Timisoara, Emergency County
Hospital of Timisoara, Timisoara, Romania
Contact E-mail Address: roxanasirli@gmail.com
INTRODUCTION: Liver stiffness measurement (LSM) using Transient
Elastography (TE) for liver fibrosis assessment is difficult to perform in obese
and overweight patients by standard M probe, thus the XL probe was developed.
AIMS & METHODS: The aim of our paper was to compare the LS values
obtained by the XL probe vs. M probe in daily clinical practice.
Our study included 88 difficult to evaluate patients (mean BMI 29.63.4 kg/m2)
with chronic hepatopathies, in which paired measurements were made with the M
(3.5MHz) and XL (2.5 MHz) probes in the same session. In each patient 10 valid
LSM were acquired with each probe, a median was calculated, expressed in
kiloPascals (kPa). Unreliable TE measurements were considered: fewer than 10
valid shots; with a success rate (SR)560% and/or interquartile range interval
(IQR)30%. We used published cut-offs for M probe (7.6kPa) to divide p with
no significant fibrosis (F52 Metavir) from those with significant fibrosis (F2),
and those with no cirrhosis (F54) vs. cirrhosis (F4) (15kPa)*.
RESULTS: XL LS values strongly and significantly correlated with those
obtained by M probe (Spearman r 0.782, p50.0001), but were significantly
lower [median 6.3 kPa (range 3.152.3) vs. 7.2 kPa (range 3.757.3), Wilcoxon
paired t test p50.001)]. XL LS values were also lower in the F52 group (47
patients): median 5.1 kPa (range 3.112.7) vs. 5.9 kPa (range 3.77.4), Wilcoxon
paired t test p 0.0006); in the F2-F3 group (23 patients): median 7.3 kPa (range
5.116.3) vs.10.5 kPa (range 7.714.1), Wilcoxon paired t test p 0.0154); and in
the cirrhotic group (18 patients): median 18.2 kPa (range 13.352.3) vs. 21.3 kPa
(range 15.957.3), Wilcoxon paired t test p50.0001.
CONCLUSION: LSM by XL probe are significantly correlated, but lower, than
those obtained by M probe in patients with no significant fibrosis (F52), in
patients with moderate and severe fibrosis (F2,F3) and in patients with cirrhosis
(F4).

United European Gastroenterology Journal 2(1S)


REFERENCES
Tsochatzis EA, Gurusamy KS, Ntaoula S, et al. Elastography for the diagnosis
of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol 2011; 54: 650-659.
Disclosure of Interest: None declared
P0062 THE USEFULNESS OF SPLEEN STIFFNESS EVALUATED BY
2D-REAL TIME SHEAR WAVE ELASTOGRAPHY (2D-SWE) FOR
PREDICTING THE PRESENCE OF LIVER CIRRHOSIS
S. Bota1,*, R. Paternostro1, A. Etschmaier1, R. Schwarzer1, M. Mandorfer1,
M. Ferlitsch1, C. Kienbacher1, T. Reiberger1, M. Trauner1, M. PeckRadosavljevic1, A. Ferlitsch1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
III, Medical University of Vienna, Vienna, Austria
Contact E-mail Address: bota_simona1982@yahoo.com
INTRODUCTION: Recently, spleen stiffness (SS) assessed by various elastographic methods was evaluated for predicting liver fibrosis. Recently (LeungRadiology, 2013) good results were published for predicting liver cirrhosis byusing SS by 2D-SWE.
AIMS & METHODS: Our aim was to validate this cut-off in an independent
cohort, considering liver stiffness (LS) by Transient Elastography (TE) as the
reference method.
We analyzed 89 patients with chronic liver disease. In each of the patients, in the
same session LS was evaluated by TE (FibroScan, Echosens, Paris, France) and
SS by 2D-SWE (Aixplorer, SuperSonic Imagine S. A., Aix-en-Provence, France).
TE reliability criteria defined as: median of 10 valid LS measurements with a
SR60% and IQR530%. 2D-SWE results were recorded as median value of 3
valid SS measurements. For predicting the presence if liver cirrhosis, we used the
LS cut-off proposed in the most recently published meta-analysis (Tsochatzis-J
Hepatol 2011): 14.5 kPa. For SS the following cut-off was analyzed (LeungRadiology2013): 22 kPa.
RESULTS: Reliable LS measurements by TE were obtained in 71 (79.7%)
patients and valid SS measurements by 2D-SWE in 63/71 (88.7%) patients,
who were included in the final analysis. According to the pre-specified cut-off
values for LS and SS, the performance of SS assessed by 2D-SWE for predicting
the presence of liver cirrhosis was: 58.3% sensitivity, 82.3% specificity, 43.7%
positive predictive value (PPV), 89.3% negative predictive value (NPV) and
77.7% accuracy.
CONCLUSION: In our patient cohort, SS by 2D-SWE was a good method for
excluding liver cirrhosis, with a very good NPV (89.3%), but less useful for
predicting cirrhosis, with a rather poor PPV(only 43.7%).
Disclosure of Interest: None declared
P0063 COMPARISON BETWEEN 2D-REAL TIME SHEAR WAVEELASTOGRAPHY (2D-SWE) AND SIMPLE SEROLOGICAL SCORES
FOR LIVER FIBROSIS ASSESSMENT FOR CLINICAL ROUTINE,
CONSIDERING TRANSIENT ELASTOGRAPHY (TE) AS REFERENCE
METHOD
S. Bota1,*, R. Paternostro1, A. Etschmaier1, R. Schwarzer1, P. Salzl1,
M. Mandorfer1, T. Purevsambuu1, M. Ferlitsch1, C. Kienbacher1, T. Reiberger1,
M. Trauner1, M. Peck-Radosavljevic1, A. Ferlitsch1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
III, Medical University of Vienna, Vienna, Austria
INTRODUCTION: 2D-Shear Wave elastography (2D-SWE) is a new method
for non-invasive assessment of liver fibrosis.
AIMS & METHODS: Our aim was to assess the performance of 2D-SWE and
simple serological scores for liver fibrosis assessment, considering TE as reference
method.
Our study included 127 consecutive patients with chronic liver disease undergoing
both TE (FibroScan, Echosens, Paris, France) and 2D-SWE (Aixplorer,
SuperSonic Imagine S. A., Aix-en-Provence, France). Biochemical parameters
were recorded to calculate the noninvasive fibrosis scores. TE reliability criteria
defined as: median of 10 valid LS measurements with a SR60% and IQR530%.
2D-SWE results were recorded as median value of 3 valid LS measurements. TE
cut-offs to stage liver fibrosis were used according to a recent meta-analysis
(Tsochatzis-J Hepatol 2011): F1: 6kPa, F2: 7.2kPa, F3: 9.6kPa and F4: 14.5kPa.
RESULTS: Reliable LS measurements by TE and 2D-SWE were obtained in
74.8% and 98.4% of patients (p50.0001), respectively. The following noninvasive fibrosis scores were correlated in univariate analysis with fibrosis estimated
by TE: 2D-SWE (r 0.699; p50.0001), Forns (r 0.534; p50.0001), Kings
(r 0.512; p50.0001), APRI (r 0.373, p 0.001) Fibrosis Index score
(r 0.363; p 0.0008) and Lok score (r 0.316, p 0.006), while FIB-4
(r 0.195; p 0.09) was not correlated. In multivariate analysis only LS by
SWE was significantly correlated with fibrosis estimated by means of TE
(p50.0001).
The best LS cut-off by 2D-SWE for predicting different stages of liver fibrosis,
considering TE as the reference method, are presented in the table.
Table to abstract P0063

Fibrosis

SWE
Cut-off (kPa)

AUC

Se
(%)

Sp
(%)

PPV
(%)

NPV
(%)

Accuracy
(%)

F2
F3
F4

4 8.03
4 9.2
4 13.1

0.832
0.919
0.915

77.1
88.2
76.2

76.1
85
94.5

77.1
76.9
80

76.1
92.7
93.2

76.5
86.1
90.4

United European Gastroenterology Journal 2(1S)


CONCLUSION: 2D-SWE results in a higher rate of successful liver stiffness
measurements than TE and is superior to simple serological scores for non-invasive liver fibrosis assessment.
Disclosure of Interest: None declared
P0064 THE CONTROLLED ATTENUATION PARAMETER (CAP)
EVALUATED WITH TRANSIENT ELASTOGRAPHY ACCURATELY
ESTIMATES THE SEVERITY OF STEATOSIS INDEPENDENT OF
FIBROSIS AND DISEASE ETIOLOGY IN PATIENTS WITH
CHRONIC LIVER DISEASE
Y. Yilmaz1,2,*, A. Yesil3, F. Gerin4, R. Ergelen5, H. Akin2, C.A. Celikel4,
N. Imeryuz2
1
Institute of Gastroenterology, 2Department of Gastroenterology, Marmara
University, School of Medicine, 3Department of Gasdtroenterology, Haydarpasa
Numune Education and Research Hospital, 4Department of Pathology,
5
Department of Radiology, Marmara University, School of Medicine, Istanbul,
Turkey
Contact E-mail Address: dryusufyilmaz@gmail.com
INTRODUCTION: Currently only liver biopsy can accurately establish the diagnosis and severity of hepatic steatosis. Few studies to date have addressed the
feasibility of the Controlled Attenuation Parameter (CAP) measured by transient
elastography for measuring hepatic fat content. However, the effects of hepatic
fibrosis and disease etiology on the accuracy of CAP values for grading the
severity of liver steatosis are still unclear.
AIMS & METHODS: The aims of this study were (1) to determine whether CAP
values can discriminate grades of steatosis in a sample of consecutive patients
with a spectrum of liver disease etiology and steatosis severity, and (2) to evaluate
the effect of hepatic fibrosis and disease etiology on the quantification of steatosis
by CAP measurements. The study involved 50 sequential patients (64% males;
mean age, 47.4 years; range, 19-70 years) who had undergone a percutaneous
liver biopsy and CAP measurements. The causes of liver disease were nonalcoholic fatty liver disease (n 20), chronic viral hepatitis (n 23), autoimmune
hepatitis (n 3), and others (n 4). A pathologist scored the specimens in a
four-graded scale as follows: 55% steatosis S0, 5-33% S1, 33-66% S2,
and 466% S3. All liver biopsy specimens were at least 20 mm long and/or
contained more than 11 complete portal tracts.
RESULTS: The pathology results showed that 16 (32%) patients had S0, 12
(24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. Overall a close relationship
was observed between the CAP values and histology steatosis scores (r 0.709, P
5 0.001). There was a stepwise increase in CAP with increasing stages of hepatic
steatosis: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m.
Regression analysis, that included a number of potential confounders, was performed to determine the influence of hepatic fibrosis and disease etiology on the
relationship between CAP values and the histological assessment of steatosis.
However, neither liver fibrosis (p 0.58) nor disease etiology (p 0.96) were
found to have an interaction between CAP and the stage of steatosis.
CONCLUSION: Liver fibrosis or disease etiology does not impact on the accuracy of CAP for the assessment of steatosis. The results of this study strengthen
the role of CAP measured by transient elastography as a non-invasive alternative
to liver biopsy for the evaluation of liver fat content in subjects with liver disease.
Given its accuracy and lack of confounding by fibrosis and disease etiology, CAP
assessment is an attractive method to evaluate the presence and severity of steatosis in clinical practice and may also be a useful tool to monitor change in
steatosis in subjects undergoing an intervention.
Disclosure of Interest: None declared
P0065 FOCAL LIVER LESIONS CLASSIFICATION BY ARTIFICIAL
NEURAL NETWORKS AND SUPPORT VECTOR MACHINES
EMPLOYING DYNAMIC IMAGING DATA
C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, D. I. Gheonea1,
L. Streba1, I. Rogoveanu1
1
Gastroenterology, UMF CRAIOVA, Craiova, Romania
Contact E-mail Address: costinstreba@gmail.com
INTRODUCTION: Early diagnostic of liver malignancies is essential for therapy
efficiency; differentiating hepatocellular carcinoma (HCC) from intrahepatic
cholangyocarcinoma, liver metastases or benign lesions is therefore essential
even in early phases. Successful classification of liver lesions by computerized
methods is currently possible and artificial neural networks emerged as optimal
tools for independent diagnostic.
AIMS & METHODS: Our aim was to test the validity of two separate decision
making systems an artificial neural network (ANN) and a support vector
machine (SVM) in classifying focal liver lesions (FLLs) by using dynamic imaging data.
Expanding on our previous work involving ANN use in interpreting imaging
data for HCC [1], we now proposed a comparative approach between two different machine learning systems, one based on ANNs and contrast-enhanced
ultrasound (CEUS) quantitative data and one employing a SVM and spiral
computed tomography (CT). After obtaining ethical clearance and signing individual consent forms, we prospectively included 191 patients who underwent
both spiral CT and CEUS as part of their clinical work-up at the University
County Hospital of Craiova between January 2009 September 2013. Final
diagnosis was based on post-treatment evaluation, follow-up and pathology,
when available. Imaging data from CEUS was obtained through time-intensity
curve (TIC) analysis and the main parameters (time to peak, rise time, fall time,
mean transit time, area under the curve) were fed to an ANN. Spiral CT data was
obtained through manually segmenting the tumor and a tumor-free parenchyma
portion in distinctive images and obtaining Gray Level Co-occurrence Matrix

A149
GLCM parameters (entropy, correlation and contrast) by using the free ImageJ
software and a dedicated plug-in. These parameters were then fed to a SVM.
RESULTS: We included 54 cases of HCC, 9 intrahepatic cholangiocarcinomas,
71 liver metastases (41 hypervascular), 38 liver hemangiomas and 19 focal fatty
changes. The SVM classified lesions into malignant or benign, obtaining 141
correct classifications (malignant: 113/134, benign: 28/57). Overall, the ANN in
correlation with TIC-derived parameters proved to be a superior combination to
SVM and GLCM.
CONCLUSION: ANNs are superior to SVMs when employed in medical classification problems. Established quantitative parameters improve the diagnostic
accuracy. The differences shown here were not given by the quality of the two
investigations, showing rather the adequacy of the chosen parameters and the
diagnostic yields of the computer methods employed.
REFERENCES
1. Streba CT, et al. Computer aided differentiation model for automatic classification of focal liver lesions based on contrast enhanced ultrasound (CEUS)
time-intensity curve (TIC) analysis. J Hepatol 56(Suppl. 2): S296.
Disclosure of Interest: None declared
P0066 LONG-TERM OUTCOMES AFTER TREATMENT OF SINGLE
SMALL HEPATOCELLULAR CARCINOMA IN ELDERLY
PATIENTS WITH WELL-PRESERVED LIVER FUNCTION AND
GOOD PERFORMANCE STATUS
G. Lee1, M.S. Choi1,*, D.H. Sinn1, G.-Y. Gwak1, Y.H. Paik1, J.H. Lee1,
K.C. Koh1, S.W. Paik1, B.C. Yoo1
1
Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of
Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: iamann81@gmail.com
INTRODUCTION: Aging of general population and advances in diagnostic
imaging have led to more frequent detection of small hepatocellular carcinoma
(HCC) in elderly adults. However, long-term outcome and its predictive factors
after treatment of small HCC in these patients have not been established.
AIMS & METHODS: Between 2006 and 2009, 897 patients who had Eastern
Cooperative Oncology Group (ECOG) score 0-1 and Child-Pugh class A liver
function were diagnosed with single small HCC (size3 cm) at Samsung Medical
Center. They were divided into elderly group (age65 years, n 186) and young
group (age565 years, n 711). We compared baseline characteristics, initial
treatment modality, and treatment outcomes between the two groups.
RESULTS: At baseline, male patients were less common, and HCV infections
and alcoholic liver disease were more common in elderly group. Elderly group
underwent surgical resections less frequently but TACE more frequently compared to young group (21.5% vs. 38.8% for surgery and 26.9% vs. 12.9% for
TACE, p50.001). One-, 3-, and 5-year overall survival (OS) rates (OSR) of
elderly group were lower than those of young group (96.7%, 81.4%, and
60.5% vs. 97.3%, 87.9%, and 82.4%, respectively, p50.001).
One-, 3-, and 5-year OS rates were after surgery, RFA, and TACE were 94.9%,
89.7%, and 86.6% vs. 97.9%, 79.6%, and 56.7% vs. 96.0%, 80.0%, and 50.6%,
respectively in elderly group (p 0.014); 98.2%, 91.8%, and 89.5% vs. 98.2%,
87.6%, and 80.3% vs. 92.3%, 79.0% and 70.5%, respectively in young group
(p50.001). Although OS rates after surgery and TACE were comparable
between the two groups, elderly group showed lower 1-, 3-, and 5-year OS
rates than young group after RFA. In addition, 1-, 3-, and 5-year recurrencefree survival (RFS) rates of elderly subgroup were lower than those of young
group (63.2%, 30.5%, and 23.0% vs. 75.7%, 48.0%, and 36.6%, respectively,
p50.001).
One-, 3-, and 5-year RFS rates after surgery, RFA, and TACE were 74.4%,
61.5%, and 52.5% vs. 70.2%, 23.5% and 13.8% vs. 40.8%, 18.4%, and
16.3%, respectively in elderly group (p50.001); 81.4%, 63.5%, and 51.5% vs.
75.1%, 41.4%, and 29.9% vs. 59.2%, 23.6%, and 11.7%, respectively in young
group (p50.001). RFS rates after surgery and TACE were comparable between
the two groups, whereas elderly group showed lower 1-, 3-, and 5-year RFS rates
than young group after RFA. Multivariate analysis showed that sex and initial
treatment modality were the significant predictive factor for OS and RFS.
CONCLUSION: Although long-term outcomes after treatment of single small
HCC in elderly group were lower than those in young group, adoption of curative treatment modality was an independent predictive factor for the better outcomes irrespective of age. Therefore, in elderly patients with well-preserved liver
function and good performance status, curative treatment including surgery
should be more positively considered for single small HCC.
REFERENCES
Arii S, et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas. The Liver Cancer Study Group of Japan. Hepatology
2000; 32: 1224-1229.
Mirici-Cappa F, et al. Treatments for hepatocellular carcinoma in elderly
patients are as effective as in younger patients. Gut. Mar 2010; 59: 387-396.
Disclosure of Interest: None declared
P0067 EFFICACY OF SORAFENIB ACCORDING TO THE NUMBER OF
PRIOR TACE PROCEDURES IN HCC PATIENTS
R. Sacco1,*, A. Romano1, V. Mismas1, M. Bertini1, M. Bertoni1, G. Federici1,
G. Parisi1, A. Scaramuzzino1, S. Metrangolo1, E. Tumino1, G. Bresci1 on behalf
of ITA.LiCA Group
1
Gastroenterology, Pisa University Hospital, Pisa, Italy
Contact E-mail Address: r.sacco@ao-pisa.toscana.it
INTRODUCTION: It has been recently suggested that sorafenib should be
initiated as early as possible in patients with hepatocellular carcinoma (HCC)
who failed transarterial chemoembolization (TACE); however, the correlation

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United European Gastroenterology Journal 2(1S)

between the efficacy of sorafenib and the number of prior TACE procedures has
not been documented. We analyze here the correlation between the efficacy of
sorafenib and the number of prior TACE procedures in HCC patients included in
the Nation-wide Italian database ITA. LI. CA.
AIMS & METHODS: The ITA. LI. CA. database contains data of 5136 HCC
patients treated at 18 Italian Centers. All patients treated with sorafenib were
included in this analysis. The following endpoints were considered: overall survival (OS), time to progression (TTP) and disease control rate (DCR). These
endpoints were compared in patients with no TACE, one and 2 prior TACE
procedures.
RESULTS: In total, 321 patients had received sorafenib (271 males; age 6511
years; 225 in BCLC-C stage). Of these, 201 received no TACE (187 were in
BCLC-C stage), 60 one TACE and 60 2 TACE procedures. Median OS was
significantly longer in patients who received one single TACE procedure, with
respect to those with no or 2 TACE procedure(s) (19 months with one TACE
versus 11 months with no TACE and 12 months for 2 TACE; p50.05). No
differences among groups were observed in TTP (one TACE: 4 months; no
TACE: 4 months; 2 TACE: 5 months; p not significant), but patients with
only one TACE prior to sorafenib treatment had an improved DCR (one TACE:
34%; no TACE: 24%; 2 TACE: 28%; p50.05).
CONCLUSION: Although with all the limitations of any observational study,
this analysis, conducted in a large field-practice database, suggests that HCC
patients who start sorafenib after one single TACE procedure present improved
OS and DC with respect to those who received TACE 2 TACE procedures.
Disclosure of Interest: None declared
P0068 CORRELATION BETWEEN LDH LEVELS AND RESPONSE TO
SORAFENIB IN HCC PATIENTS
R. Sacco1,*, A. Romano1, V. Mismas1, M. Bertini1, M. Bertoni1, G. Federici1,
G. Parisi1, A. Scaramuzzino1, S. Metrangolo1, E. Tumino1, G. Bresci1 on behalf
of ITA.LiCA Group
1
Gastroenterology, Pisa University Hospital, Pisa, Italy
Contact E-mail Address: r.sacco@ao-pisa.toscana.it
INTRODUCTION: Lactate dehydrogenase (LDH) is a predictor of clinical outcome in hepatocellular carcinoma (HCC) patients. However, the predictive role
of LDH on the clinical outcomes of sorafenib treatment has been poorly documented. The correlation between LDH levels and clinical outcomes in HCC
patients treated with sorafenib included in the Nation-wide Italian database
ITA. LI. CA is investigated here.
AIMS & METHODS: The ITA. LI. CA. database contains data of 5136 HCC
patients treated at 18 Italian Centers. All patients treated with sorafenib treatment and with available LDH values were considered. A ROC analysis was
performed to find a suitable threshold for baseline LDH levels. Overall
Survival (OS) and time to progression (TTP) were compared in patients with
LDH above and below the identified threshold. Study endpoints were also evaluated according to different patterns of LDH levels during treatment.
RESULTS: Baseline LDH levels were available for 97 patients (85 males, 61 in
BCLC-C stage); data on LDH levels during sorafenib were reported for 10
patients. Mean baseline LDH concentration was 324141 U/L. The most accurate cut-off value for LDH concentration was 297 U/L. Both study endpoints
were equal in patients with LDH values 297 U/L (n 47) and in those with
lower LDH concentrations (n 52) (OS: 12.0 months in each population; TTP:
4.0 months in each group). During treatment, LDH values decreased in three
patients (mean difference -219 U/L). Patients with decreased LDH concentrations have a prolonged OS versus those with unmodified/increased values
(p 0.0083; all patients with decreasing LDH are alive, median OS for patients
with increasing LDH was 8.0 months). Median TTP was 19.0 months in patients
with decreasing LDH and 3.0 months in those with increasing values (p 0.008).
CONCLUSION: The clinical benefits of sorafenib do not seem influenced by
baseline LDH. However, a decreased LDH concentration during sorafenib might
be associated with improved clinical outcomes.
Disclosure of Interest: None declared

P0070 SAFETY AND EFFICACY OF SORAFENIB IN ELDERLY


PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
S. Nakashita1,*, T. Otsuka1, Y. Eguchi2, S. Kawazoe3, K. Yanagita4, K. Ario5,
K. Kitahara6, S. Iwane7, H. Kato8, T. Mizuta1 on behalf of the Saga Liver
Cancer Study Group
1
Internal Medicine, 2Liver Disease Control and Assistance Task Force, Saga
University Hospital, 3Hepato-Biliary and Pancreatology, Saga-Ken Medical
Centre Koseikan, Saga, 4Internal Medicine, Saiseikai Karatsu Hospital, Karatsu,
5
Internal Medicine, NHO Ureshino Medical Center, Ureshino, 6Surgery, Saga
University Hospital, Saga, 7Internal Medicine, Karatsu Red Cross Hospital,
Karatsu, 8Internal Medicine, NHO Saga Hospital, Saga, Japan
INTRODUCTION: The average age of patients with hepatitis and hepatocellular
carcinoma (HCC) in Japan is increasing. Sorafenib is approved for the treatment
of advanced HCC; however, its safety and efficacy for elderly patients is not
established by published studies. Therefore, we aimed to evaluate the safety
and efficacy of sorafenib for elderly patients (80 years of age) included in the
Saga Liver Cancer Study Group.
AIMS & METHODS: We conducted a retrospective study between July 2008
and August 2013 that included 134 patients with advanced HCC who received
sorafenib in Saga, Japan until disease progression or treatment intolerance. We
divided the patients into two groups comprising 36 patients 80 years of age or
greater (80 group) and 98 patients less than 80 years of age (580 group). We
compared antitumour effect [objective response rate (ORR), disease control rate
(DCR), time to tumour progression (TTP)], overall survival (OS), and adverse
events (AEs) of the two groups.
RESULTS: Baseline characteristics were not significantly different between the
two groups. The median ORRs were 6.9% and 8.3%, and the median DCRs
were 37.9% and 46.4% in the 80 and 580 groups, respectively. These values
were not significantly different between the two groups (p 0.81, p 0.43). The
median TTPs were 2.9 months for both groups, and the median OSs were 14.7
and 9.2 months for the 80 and 580 groups, respectively, which were not significantly different. The frequencies of AEs were 97.2% and 96.6% in the 80
and 580 groups. The frequencies of grade 3 AEs between the 80 and 580
groups were significantly different (69.4% and 49.0% respectively, p 0.036).
CONCLUSION: Sorafenib treatment is equally effective for elderly and non
elderly patients with advanced HCC. However, the high frequency of AEs in
elderly patients is problematic and requires close attention.
Disclosure of Interest: None declared
P0071 HEPATOCELLULAR CARCINOMA INCIDENCE IN CHRONIC
HEPATITIS C PATIENTS ACCORDING TO SUSTAINED
VIROLOGIC RESPONSE (SVR) AND FLUCTUATION OF ALFA
FETO-PROTEIN LEVELS DURING ANTIVIRAL TREATMENT
T. Purevsambuu1,*, S. Bota1, H. Florian1, H. Hofer1, P. Ferenci1, W. Sieghart1,
M. Peck-Radosavljevic1
1
Gastroenterology and Hepatology, Internal Medicine III, Medical University of
Vienna, Vienna, Austria
Contact E-mail Address: tuulaigirl@yahoo.com
INTRODUCTION: Chronic hepatitis C (CHC) is an important risk factor for
progression of liver disease to advanced fibrosis and hepatocellular carcinoma
(HCC) and the published studies showed that the kinetics of alfa feto-protein
(AFP) levels in cirrhotic patients are more valuable than single AFP values for
predicting the HCC.
AIMS & METHODS: Our aim was to assess the HCC incidence in relation to
antiviral treatment response and fluctuation of AFP levels during antiviral treatment
in a large number of patients from a single institution. We retrospectively collected
data of HCV patients, who were diagnosed and treated between 1989-2011. We
analyzed the HCC incidence according to AFP fluctuation (baseline vs. end of
treatment-EOT) in the entire Cohort of patients and in SVR and non-SVR patients.
RESULTS: We identified 2627 patients diagnosed with chronic hepatitis C. We
excluded 975 patients because they did not receive antiviral therapy, 5 because
they were diagnosed simultaneously with HCV/HCC and 321 patients due to lack

Table to abstract P0071


Table 1. HCC incidence in different groups, according to AFP levels at baseline and EOT (P0071 table)

Cohort

Group A: n50 (3.8%)


AFP410/ AFP410
(ng/ml,baseline/EOT)

Group B: n81 (6.1%)


AFP410 /AFP510
(ng/ml, baseline/EOT)

Group C: n1167 (88%)


AFP510 /AFP510
(ng/ml,baseline/EOT)

Group D: n28 (2.1%)


AFP510/AFP410
(ng/ml,baseline/EOT)

All

24%

9.8%

1.8%

17.8%

SVR

30.7%

Non-SVR

21.6%

p0.77

7.1%

11.3%

p0.83

0.5%

4.7%

p50.0001

12.5%

20%

p0.93

P value
A vs. B: p0.004
Avs.C:p50.0001
A vs. D: p0.72
B vs.C: p50.0001
B vs. D: p0.42
C vs.D: p50.0001
A vs. B: p0.12
A vs.C: p50.0001
A vs. D: p0.67
B vs. C: p0.003
B vs. D: p0.81
C vs. D: p0.04
A vs. B: p0.30
A vs.C: p0.0002
A vs. D: p0.84
B vs. C: p0.10
B vs. D: p0.56
C vs. D: p0.01

A151

United European Gastroenterology Journal 2(1S)


of AFP values at baseline and EOT. We included in the final analysis 1326
patients. The median follow-up time was 10 years (0.2-25 years). The overall
HCC incidence was 3.5% and the median time between HCV and HCC diagnosis
was 7 years (0.5-15 years). According to baseline fibrosis stage, HCC incidence
was: 0.9% in F(0-2) patients, 1.8% in F3 and 10.1% in F4 patients.
The HCC incidence was significantly higher in non-SVR as compared with SVR
patients: 7.4% vs. 1.2%, p50.0001.
AFP values 4 10 ng/ml at baseline, EOT and the increase of AFP values during
the antiviral treatment are associated with high HCC incidence in both SVR and
non-SVR patients (Table 1). The decrease of AFP values during the antiviral
treatment is associated with reduced HCC incidence, comparative to the cases
with high AFP at baseline and EOT. AFP levels 5 10 ng/ml in both baseline and
EOT are protective against HCC development exclusively in the SVR group.
CONCLUSION: The fluctuation of AFP levels during antiviral treatment plays
an important role on HCC development. The patients with AFP 4 10 ng/ml at
both baseline and EOT had the highest risk to HCC, however they achieved
SVR. Hence, an intensified HCC surveillance should be performed in these
patients.
Disclosure of Interest: None declared
P0072 INFLUENCE OF HBV REACTIVATION ON THE RECURRENCE
OF HEPATITIS B-RELATED HEPATOCELLULAR CARCINOMA
AFTER CURATIVE RESECTION IN PATIENTS WITH LOW VIRAL
LOAD
W. Sohn1,*, Y.-H. Paik1, J.Y. Cho1, G.-Y. Gwak1, M.S. Choi1, J.H. Lee1,
K.C. Koh1, S.W. Paik1, B.C. Yoo1
1
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea, Republic Of
Contact E-mail Address: hand1@dreamwiz.com
INTRODUCTION: It is unclear whether the reactivation of hepatitis B virus
(HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the
effect of HBV reactivation on the recurrence of hepatitis B-related HCC after
curative resection in patients with low viral load (HBV DNA 52.000 IU/mL).
AIMS & METHODS: We retrospectively analyzed a total of 130 patients who
underwent curative resection for HBV-related early-stage HCC (single nodule;
55 cm / two or three nodules; 53 cm) with preoperative HBV DNA level
52.000 IU/mL and serial check-up on HBV DNA. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative
resection were investigated. HBV reactivation was deEned as the reemergence
or an increase of more than 10-fold in serum HBV DNA as compared with the
level before resection.
RESULTS: Fifty-three patients (41%) had HBV reactivation after resection
among 130 patients. HBV reactivation was observed in 22 of 53 patients with
undetectable baseline HBV DNA and in 31 of 77 patients with detectable HBV
DNA. Cumulative recurrence rates after resection at 1, 2, and 3 years were
17.0%, 23.3%, and 31.4%, respectively. The multivariable analysis demonstrated
that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, p 0.003), multi-nodularity (HR 4.61, p 0.005),
HBV reactivation after resection (HR 2.03, p 0.032), and HBeAg positivity
(HR 2.06, p 0.044).
CONCLUSION: HBV reactivation after curative resection was associated with
the recurrence of HBV-related HCC in patients with low viral load. This study
suggests that aggressive viral suppression by anti-viral therapy can help to reduce
the recurrence of HCC after resection in chronic hepatitis B with low viral load.
Disclosure of Interest: None declared
P0073 A STUDY OF PLASMA PROLIDASE ACTIVITY IN CASES WITH
AND WITHOUT HEPATOCELLULAR CARCINOMA IN THE
SETTING OF UNDERLYING CIRRHOSIS
1
_
S. Uygun Ilikhan
, M. Bilici1, H. Sahin1, I. I. Oz2, M. Can3, M.C. Buyukuysal4,
Y. Ustundag5,*
1
Internal Medicine, 2Radiology, 3Biochemistry, 4Biostatistics, 5Gastroenterology,
Bulent Ecevit University Medical Faculty, Zonguldak, Turkey
Contact E-mail Address: yucelustundag@yahoo.com.tr
INTRODUCTION: Cancer cell prolidase enzyme activity has been reported to
be important for tumor invasiveness and metastasis. As far as we know, plasma
prolidase activity (PPA) has not been studied in patients with hepatocellular
carcinoma (hcc).
AIMS & METHODS: We aim to assess the correlation between the PPA and
AFP levels in patients with hepatocellular carcinoma. A total of 51 patients with
cytopathological diagnosis of HCC in the setting of cirrhosis, 31 patients with
cirrhosis without HCC and 33 cases as healthy volunteers were enrolled in this
study. There were no significant differences with respect to gender and age of the
study cohort with the healthy group. The patients with HCC were divided into
groups according to tumor size, number and presence of vascular invasion.
Barcelona-Clinic Liver Cancer (BCLC) criteria was used for staging of patients
with hcc. PPA was measured spectrophotometrically. AFP level was measured
with immunoassay method.
RESULTS: PPA was significantly higher in cases with HCC than cases with
cirrhosis without HCC and, healthy controls (1182 U/L versus 932 U/l and
880 U/l, respectively). Patients with cirrhosis had PPA similar to those of healthy
controls (p40.05). PPAs differed significantly in the group of tumor diameters
less than 3 cm (n:13), compared to the group of tumor diameters between 3-5 cm
(n:9) and more than 5 cm (n: 29) ((p 0.003) According to the tumor number, a
significant difference has been seen in the group which has more than two tumors
compared to the group which has one (p 0.001) and two tumors (p 0.027).

PPA also differed in patients with regard to BCLC staging classification


(p 0.003). However, prolidase levels showed no statistically significant difference with presence of macrovascular invasion in patients with HCC (p 0.898).
There was a significant positive correlation between PPA and serum AFP values
(r 0.731; p50.001)
CONCLUSION: To our knowledge, this is the first study reporting increased PPA
in patients with HCC, and it was found to be significantly associated with size,
number and BCLC stage of the tumor. This was not seen in patients with cirrhosis
without HCC. Furthermore, PPA significantly associated with serum AFP levels.
However, further studies should be done to clarify clinical significance and pathophysiological role of augmented prolidase activity in cases with HCC.
REFERENCES
Myara I, Myara A, Mangeot M, et al. Plasma prolidase activity: a possible index
of collagen catabolism in chronic liver disease. Clin Chem 1984; 30: 211215.
Peng SY, Chen WJ, Lai PL, et al. High alpha-fetoprotein level correlates with
high stage, early recurrence and poor prognosis of hepatocellular carcinoma:
significance of hepatitis virus infection, age, p53 and beta-catenin mutations.
Int J Cancer 2004; 112: 44-50.
Lu XY, Xi T, Lau WY, et al. Pathobiological features of small hepatocellular
carcinoma: correlation between tumor size and biological behavior. J Cancer Res
Clin Oncol 2011; 137: 567-575.
Disclosure of Interest: None declared
P0074 VALUE
OF
ESOPHAGOGASTRODUODENOSCOPY
PATIENTS REFERRED FOR CHOLECYSTECTOMY: A
SYSTEMATIC REVIEW AND META-ANALYSIS

IN

M. Lamberts1,2,*, C. Ozdemir3, W. Kievit3, G. Westert4, C.van Laarhoven1,


J. Drenth2
1
Surgery, 2Gastroenterology and Hepatology, 3Health Evidence, 4Scientific
Institute for Quality of Healthcare (IQ healthcare), Radboud University Medical
Center, Nijmegen, Netherlands
Contact E-mail Address: Mark. Lamberts@Radboudumc.nl
INTRODUCTION: Up to 33 percent of patients with symptomatic cholelithiasis
report persisting abdominal pain after cholecystectomy, suggesting alternative
causes for these symptoms. Esophagogastroduodenoscopy (EGD) may serve as
a tool to identify additional symptomatic abdominal disorders beforehand, in
order to avoid unnecessary gallbladder surgery. There is controversy whether
routine EGD prior to cholecystectomy is appropriate.
AIMS & METHODS: We performed a systematic review and meta-analysis to
assess the value of EGD prior to cholecystectomy. A systematic literature search
was conducted in Pubmed, Embase, Web of Science, ClinicalTrials.gov, and the
Cochrane library. All studies were included that reported the proportion of
patients who were referred for cholecystectomy, but in whom surgery could be
avoided after treatment of abnormalities detected with EGD. Pooled estimates
were calculated using a random effects model.
RESULTS: Twelve eligible studies were included with a total of 6.317 patients
with cholelithiasis receiving EGD. The pooled estimate of abnormalities detected
with EGD was 36.3% (95% CI, 28.0-45.0). Treatment of these findings avoided
cholecystectomy in 11.0% (95% CI, 3.9-21.1) of patients. In a total of 3.8%
(95% CI, 1.4-7.6) of patients referred for cholecystectomy who underwent
prior EGD, gallbladder surgery was avoided.
CONCLUSION: Our study indicated that the value of prior EGD in preventing
gallbladder surgery is limited. EGD should only be considered selectively in
patients with cholelithiasis referred for cholecystectomy.
Disclosure of Interest: None declared
P0075 REFERENCE RANGES OF SERUM BILE ACID IN CHILDREN
AND ADOLESCENTS
E. Zohrer1,*, B. Stering1, G. Fauler2, H. Scharnagl2, J. Jahnel1, A. Hauer 1,
T. Stojakovic 2
1
Department of Paediatrics and Adolescent Medicine, 2Clinical Institute of Medical
and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria
Contact E-mail Address: evelyn_zoehrer@gmx.at
INTRODUCTION: Serum total bile acid (tBA) concentrations are prognostic
and predictive markers for hepatic disorders. Due to the lack of data on normal
value ranges of tBA in children and adolescents we aimed to determine such
ranges as well as the composition of BA in this age group.
AIMS & METHODS: tBA concentration was measured in 194 healthy children
and adolescents (0 - 19 years). Unconjugated and taurine or glycin conjugated
BA were measured by using high performance liquid chromatography tandem
mass spectrometry (HPLC MS/MS). Patients were classified in five groups
according to their age: 0-5 months (n 17), 6-24 months (n 13), 3-5 years
(n 22), 6-11 years (n 44), and 411 years (n 98), respectively.
RESULTS: tBA values found in children were significantly higher compared to
reference ranges in adults (0.28 6.50 mmol/l). Serum tBA increased constantly
after delivery (0-5 months: 3.85 6.32 mmol/l) and reached a peak at the age of 624 months (6.61 9.43 mmol/l). Henceforward tBA decreased continuously (3-5
years: 4.27 6.43 mmol/l, 6-11 years: 3.61 5.14 mmol/l and 411 years: 3.10
4.12 mmol/l). In neonates levels of taurine conjugated BA were elevated; however,
after 6 months glycine conjugated clearly predominated.
CONCLUSION: This study shows that serum tBA levels vary substantially in
the first years of life indicating age-dependent reference ranges for tBA and the
BA profile; the causes of the variations need further clarification.
REFERENCES
Barbara L, Lazzari R, Roda A, et al. Serum bile acids in newborns and children.
Pediatr Res 1980; 14: 1222-1225.
Chiang JY. Bile acids: regulation of synthesis. J Lipid Res 2009; 50: 1955-1966.

A152
Hofmann AF. The continuing importance of bile acids in liver and intestinal
disease. Arch Intern Med 1999; 159: 2647-2658.
Niijima S. Studies on the conjugating activity of bile acids in children. Pediatr
Res 1985; 19: 302-307.
Polkowska G, Polkowski W, Kudlicka A, et al. Range of serum bile acid concentrations in neonates, infants, older children, and in adults. Med Sci Monit
2001; 7(Suppl 1): 268-270.
Disclosure of Interest: None declared
P0076 EUS-GUIDED DRAINAGE WITH A LUMEN APPOSING METAL
STENT IS FEASIBLE FOR THE TREATMENT FOR ACUTE
CHOLECYSTITIS IN HIGH RISK PATIENTS
D. Walter1,*, A.Y. Teoh2, T. Itoi3, M. Perez-Miranda4, A. Larghi5, A. SanchezYague6, P.D. Siersema1, F.P. Vleggaar1
1
Dept. of Gastroenterology and Hepatology, University Medical Center Utrecht,
Utrecht, Netherlands, 2Dept. of Surgery, Prince of Wales Hospital, Chinese
University of Hong Kong, Hong Kong, China, 3Dept. of Gastroenterology and
Hepatology, Tokyo Medical University, Tokyo, Japan, 4Dept. of Gastroenterology,
Unit of Gastrointestinal Endoscopy, University Hospital Rio Hortega, Valladolid,
Spain, 5Dept. of Gastroenterology, Digestive Endoscopy Unit, Catholic University,
Rome, Italy, 6Dept. of Digestive Disease, Endoscopy Unit, Agencia Sanitaria Costa
del Sol, Marbella, Spain
Contact E-mail Address: d.walter@umcutrecht.nl
INTRODUCTION: Percutaneous gallbladder drainage is the treatment of choice
in high-risk surgical patients with acute cholecystitis. However, it is associated
with discomfort and risk of inadvertent drain removal which may lead to bile
leakage and recurrent cholecystitis. Recently, EUS-guided drainage has been
introduced as an alternative treatment option.
AIMS & METHODS: Our aim was to determine the feasibility and safety of
EUS-guided gallbladder drainage with a lumen apposing metal stent (AXIOS) in
patients with acute cholecystitis at high risk for surgery. We performed a prospective, multicenter study. Stent removal was scheduled after 3 months and
patients were followed until 9 months after removal. Study endpoints included
safety, recurrent symptomatic cholecystitis, clinical and technical success.
RESULTS: Between June 2012 and Feb 2014, 30 patients were included (11 men
(37%), mean age 857 years). Median time between onset of symptoms and stent
placement was 2 days (range 1-28 days). The majority of patients (87%) presented with calculous cholecystitis. In 11 patients (37%) a transgastric approach
and in 19 patients (63%) a transduodenal approach was used. Stent placement
was technically successful in all patients (100%), but in 4 patients (13%) a second
stent was placed due to problems with stent deployment. Clinical success was
achieved in all but one patient (97%) after a median of 3 days (IQR 3-5 days). In
one patient with ongoing fever for 14 days, endoscopic irrigation was successfully
performed through the stent to drain large amounts of pus from the gallbladder.
Stent removal was successfully performed in 12 patients (40%) after a median of
91 days (range 15-133), of which one was evaluated as being difficult due to tissue
overgrowth (125 days). In 18 patients (60%) no stent removal was performed,
including 2 patients (2%) with significant tissue overgrowth (105 and 150 days), 5
patients (17%) with follow-up 53 months, 5 unrelated deaths 53 months
(17%), 4 patients (13%) with a poor clinical condition, 1 patient (3%) with a
polypoid lesion in the gallbladder and 1 patient (3%) with lingering stones.
Causes of death included urosepsis (n 1), pneumonia (n 1), myocardial
infarction (n 1) and progression of pancreatic adenocarcinoma (n 2). Major
complications were reported in 4 patients (13%). One patient presented with
melena due to mucosal gangrene of the gallbladder for which endoscopic irrigation of the gallbladder was performed. One patient developed fever due to food
contents in the gallbladder for which stent removal was performed. This patient
also developed acute biliary pancreatitis 21 days later. Two patients developed
symptoms of cholestasis due to common bile duct stones for which ERCP was
performed. During a mean follow-up of 212 days (95% CI 149-274) none of the
patients developed recurrent cholecystitis.
CONCLUSION: EUS-guided gallbladder drainage with a lumen apposing stent
was found to be feasible in high-risk surgical patients with a high clinical success
rate. Difficulties with stent deployment was seen in approximately 15% of
patients. The overall number of major complications was low, but tissue overgrowth may complicate stent removal.
Disclosure of Interest: D. Walter: None declared, A. Teoh: None declared, T. Itoi
Consultancy for: Xlumena Inc. (Mountain View, CA, USA), M. Perez-Miranda:
None declared, A. Larghi: None declared, A. Sanchez-Yague: None declared, P.
Siersema: None declared, F. Vleggaar: None declared
P0077 THE EFFECT OF PERIAMPULLARY DIVERTICULUM ON THE
CLINICAL PRESENTATION OF CHOLEDOCHOLITHIASIS AND
OUTCOME AFTER ERCP
F. Benjaminov1,*, A. Stein1, V. Bieber1, T. Naftali1, F.M. Konikoff1
Gastroenterology and Hepatology, Meir medical center, Kfar Saba, Israel
Contact E-mail Address: fabianabenjaminov@gmail.com
1

INTRODUCTION: Periampullary diverticulum (PAD) is an incidental finding in


up to 20% of ERCPs. Its incidence increases with age. PAD is associated with
CBD stones and is considered a risk factor for obstructive jaundice, cholangitis
and pancreatitis even in the nascence of CBD stones. However, the impact of
PAD on the presentation and consequences in patients with CBD stones is
unclear.
AIMS & METHODS: The aim of our study was to investigate the effect of PAD
on
the
clinical
presentation
and
course
of
patients
with
suspectedcholedocholithiasis.

United European Gastroenterology Journal 2(1S)


All ERCPs performed in our unit from 1/2010 to 7/2013 were reviewed. Studies
performed for documented or suspected choledocholithiasis were included in the
study. Patients were divided into two groups. Group I- patients without PAD
and group II- with PAD. The following data were recorded: Age, gender, comorbidities, indication for ERCP, previous imaging studies, liver function tests, presence of gallbladder, prior sphincterotomy, CBD diameter,ERCP success and
complications, as well as the presence, size and type of PAD.
RESULTS: Three hundred and two patients met the inclusion criteria. Mean age
was 66.4  20.5y (range 19-98), 173 (57.3%) women. Altogether, 86 patients
(28.4%) had PAD. Ninety-nine percent of ERCPs were successful. Two hundred
and fifty-three patients (83.8%) had CBD stones on ERCP. Significant complications (pancreatitis, perforation, death) were recorded in 14 patients (6.5,3,
respectively) (4.6%). Patients with PAD were older (73.416.2y Vs
63.621.4y) and predominantly male (53.5% Vs 38.4%), p50.01. Patients
with PAD presented more often with cholangitis compared to those without
PAD (58.1% Vs 34.6%, p5 0.001). There were no differences between the two
groups regarding imaging findings, laboratory tests, presence of gallbladder,
comorbidities, procedural success, prior ERCP, inadvertent pancreatic duct cannulation, presence of CBD stones, number and size of CBD stones, procedure
related complications and their severity, or number of ERCPs for stone
clearance.
CONCLUSION: PAD is a risk factor for infectious complications ofcholedocholithiasis. However, the presence of PAD does not predispose patients to misinterpretation of imaging studies, procedural difficulty, failure or complications of
ERCP.
REFERENCES
1) Zoepf T, Zoepf DS, Arnold JC, et al. The relationship between juxstapapillary
duodenal diverticula and disorders of the biliopancreatic system: analysis of 350
patients. Gastrointest Endoscopy 2011: 54; 56-61.
2) Wu SD, Su Y, Fan Y, et al. Relationship between intraduodenal periamoullary diverticulum and biliary disease in 178 patients undergoing ERCP.
Hepatobiliary Pancreat Dis Int 2077: 6; 299-302.
3) Egawa N, Anjiki H, Takuma K, et al. juxstapapillary duodenal diverticula and
pancreaticobiliary disease. Dig Surg 2010: 27; 105-109.
4) San-Roman AL, Moreira VF, Garcia M, et al. Dirrect compression by duodenal diverticulum causing biliary obstruction. Endoscopy 1994: 26; 334.
5) Castilho Netto JM and Speranzini MB. Ampullary duodenal diverticulum and
cholangitis. Sao Pablo Med J 2003; 121: 173-175.
Disclosure of Interest: None declared
P0078 MULTICENTER TRIAL FOR EFFICACY OF MAGNESIUM
TRIHYDRATE OF UDCA AND CDCA (CNU)FOR GALLSTONE
DISSOLUTION
H.S. Lee1,*, C.D. Kim1, S.O. Lee2, T.N. Kim3, J. Lee4, J. Ryu5, E.T. Park6,
I.S. Lee7, D.H. Lee8, S.H. Dong9, J.H. Kim10 on behalf of Korean Gallstone
Study Group
1
Division of Gastroenterology, Dept. of Internal Medicine, Korea University
College of Medicine,Dept. of Gastroenterology, Seoul, 2Division of
Gastroenterology, Dept. of Internal Medicine, Cheonbuk University, Cheonjoo,
3
Division of Gastroenterology, Dept. of Internal Medicine, Youngnam University,
Deagu, 4Division of Gastroenterology, Dept. of Internal Medicine, Hanllym
University, 5Division of Gastroenterology, Dept. of Internal Medicine, Seoul
National University, Seoul, 6Division of Gastroenterology, Dept. of Internal
Medicine, Gosin University, Busan, 7Division of Gastroenterology, Dept. of
Internal Medicine, Catholic University, Seoul, 8Division of Gastroenterology, Dept.
of Internal Medicine, Inha University, Inchon, 9Division of Gastroenterology, Dept.
of Internal Medicine, Kyunghee University, Seoul, 10Division of Gastroenterology,
Dept. of Internal Medicine, Ajou University, Suwon, Korea, Republic Of
Contact E-mail Address: hslee60@korea.ac.kr
INTRODUCTION: The gallstone is still a most prevalent medical issues in the
pancreatobiliary system. Laparoscopic cholecystectomy is a treatment of choice;
however, oral litholysis with bile acids has been an attractive alternative therapeutic option for asymptomatic or mild symptomatic subgroups.
Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) or both
had been investigated for their effectiveness on stone dissolution. Recently, the
prevalence of gallstones has increased due to the wide availability of sonographic
examination and dietary habit modification. We conducted a prospective, multicenter, phase IV clinical study to evaluate the efficacy of magnesium trihydrate of
UDCA and CDCA for gallstone dissolution at present.
AIMS & METHODS: The objects of this study are to evaluate the effects of
CNU on GB stone dissolution and to assess the improvement of stone associated symptoms and to find out predictive factors for gallstone dissolution.
In total 10 medical centers in Korea participated in the investigation from Jan
2011 to June 2013. Inclusion criteria were; GB stone (diameter 515mm) in
sonography, GB EF  50% in DICIDA biliary scan, radiolucent on Plain Xray and asymptomatic or mild symptomatic patients. Exclusion criteria were: age
under 18 years, complicated GB stones, patients with severe co-morbidity, abnormal LFT (ALT 42x N). The treatment consisted of 1 tablet (114mg of UDCA
and 114mg of CDCA) at morning and 2 tables at bedtime. Patients were followed
up at 1Mo, 3Mo and 6Mo for LFT, symptom score and ultrasonography (6Mo)
RESULTS: Total 236 cases were enrolled and 196 cases (Male 87, Female 109,
mean age 54.812.8)) were finished the study and were analyzed. Complete
dissolution was achieved in 13.3% after 6 months administration of CNU.
Partial dissolution (defined as reduction in volume more than 25%) was
32.1%. Overall response rate was 45.4%. Stone size and BMI are factors for
predicting gallstone dissolution. Gallbladder ejection fraction is not a predictive
factor for dissolution. CNU treatment showed significant symptomatic improvements regardless of stone dissolution.

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CONCLUSION: Magnesium trihydrate of UDCA and CDCA (CNU) is a well
tolerated and effective agent for gallstone dissolution. However, a substantial
portion of gallstones are still ineffectively treated with CNU. This group may
have pigment stones rather than cholesterol stones. Further study is needed to
evaluate effect of longer Tx duration and recurrent rate after cessation of Tx.
Development of methods for predicting chemical composition of gallstones is
warrant for selecting good candidates for medical dissolution Tx.
Disclosure of Interest: None declared

CONCLUSION: In patients with acute cholecystitis and a high suspicion of


CBD stones, the single-step approach through ERCP and simultaneous ETGD
could be an effective alternative treatment modality to the two-step approach
through PTGBD followed by ERCP.
Disclosure of Interest: None declared

P0079 SIZE OF RECURRENT SYMPTOMATIC COMMON BILE DUCT


STONES AND FACTORS RELATED TO RECURRENCE

K. Sekine1,*, N. Nagata1, K. Watanabe1, S. Mikami1, Y. Nozaki1, T. Sakurai1,


C. Yokoi1, Y. Kojima1, M. Kobayakawa1, J. Akiyama1, M. Yanase1
1
National Center for Global Health and Medicine, Tokyo, Japan
Contact E-mail Address: hawaiiantuberider@gmail.com

J.H. Chang1,*, M. Park1, C.W. Kim1, S.W. Han1


1
Internal Medicine, The Catholic University of Korea, Bucheon, Korea,
Republic Of
INTRODUCTION: Common bile duct (CBD) stones can be treated successfully
by endoscopic stone extraction. Unfortunately, 4% to 24% of patients have
recurrent CBD stones after the initial extraction of CBD stones. Some patients
even have multiple recurrences. Unfortunately, little information is available on
the size and recurrence interval of recurrent symptomatic CBD stones or on ways
to prevent recurrence.
AIMS & METHODS: Between January 2007 and December 2011, 481 consecutive patients undergoing endoscopic extraction of CBD stones at a single institute
were enrolled. We selected 34 patients with recurrent symptomatic CBD stones
and 63 patients who were followed up more than five years without recurrence.
We evaluated the role of endoscopic papillary large-balloon dilation (EPLBD) (
10 mm) in preventing the recurrence of CBD stones while identifying risk factors
related to recurrence. Furthermore, the characteristics of symptomatic recurrent
CBD stones and the interval of recurrence were investigated in patients with the
first, second, and third recurrences of CBD stones.
RESULTS: The sizes of the CBD stones increased during the recurrences: 10.1 
5.2 mm, 13.5  7.3 mm, and 16.8  7.8 mm at the initial presentation, the first
recurrence, and the second recurrence, respectively (P 0.016). Among CBD
stone recurrences, 50% occurred within 2.3 years, and 80% occurred within
5.3 years. The recurrence group had a smaller proportion of patients under 50
years of age, larger CBD diameters, fewer histories of more than 10 mm EPLBD,
and more type I periampullary diverticula, compared with the non-recurrence
group (P 5 0.05). Multivariate analysis revealed that EPLBD more than 10 mm
and smaller CBD diameter were independently related to less recurrence of CBD
stones (P 0.001 and 0.012, respectively).
Table. Multivariate analysis of the factors related to the recurrence of common
bile duct stones
Factors

OR (95% CI)

P value

Endoscopic papillary largeballoon dilation ( 10 mm)


CBD diameter
Type I periampullary
diverticulum
Age (5 50)

0.161 (0.055 0.473)

0.001

1.126 (1.027 1.235)


3.322 (0.608 18.17)

0.012
0.166

0.314 (0.073 1.360)

0.122

CONCLUSION: The sizes of CBD stones increased during recurrences. EPLBD


more than 10 mm and smaller CBD diameter were related to less recurrence of
CBD stones.
Disclosure of Interest: None declared
P0080 A COMPARATIVE STUDY BETWEEN PTGBD AND ETGD AS A
BRIDGE TO SURGERY IN PATIENTS WITH ACUTE
CHOLECYSTITIS AND A SUSPICION OF CBD STONE
J.H. Kim1,*, M.J. Yang1, B.M. Yoo1
1
Gastroenterology, Ajou Unversity School of Medicine, Suwon, Korea, Republic Of
INTRODUCTION: To compare the technical feasibility, clinical and surgical
outcomes between a single-step approach of endoscopic removal of CBD
stones with endoscopic transpapillary gallbladder drainage (ETGD group) and
a two-step approach of endoscopic removal of CBD stones and percutaneous
transhepatic gallbladder drainage (PTGBD group) as a bridge treatment before
cholecystectomy, in patients with acute cholecystitis and a high suspicion of
common bile duct (CBD) stones.
AIMS & METHODS: From March 2006 to May 2013, a total of 79 patients
were enrolled in this study retrospectively. The PTGBD group (n 39) was
compared with the ETGD group (n 40, ENGBD: 22, ERGBD: 18) in terms
of technical and clinical success rates, adverse events, and surgical outcomes of
surgery time and rate of conversion to open surgery in the non-inferiority
analysis.
RESULTS: PTGBD and ETGD groups had similar outcomes in terms of technical success rate (97.4% 38/39 vs 92.5% 37/40; 95% 1-sided confidence interval
(CI) lower limit, -14.6%; p 0.028 for noninferior margin of 15%) and clinical
success rate (94.7% 36/38 vs 91.9% 34/37; 95% 1-sided CI lower limit, -12.9%;
p 0.045 for noninferior margin of 15%). The two groups did not differ significantly in the rates of adverse events (5.1% 2/39 vs 7.5% 3/40; p 1.000), surgery
time (59.3 vs 55.7 min; p 0.361), rates of conversion to open cholecystectomy
(5.2% 2/38 vs 0% 0/37; p 0.135). There was no significant differences in the
technical, clinical, and surgical outcomes between ENGBD and ERGBD groups
respectively.

P0081 VISCERAL ABDOMINAL FAT MEASURED BY CT SCAN IS


ASSOCIATED WITH AN INCREASED RISK OF SYMPTOMATIC
GALLSTONE DISEASE

INTRODUCTION: Previous studies have shown that obesity measured as BMI


is a causal risk of gallstone disease. Visceral fat promotes systemic inflammation
by secreting adipokines and inflammatory cytokines.
AIMS & METHODS: This study aims to investigate whether visceral fat measured by computed tomography (CT) is a risk factor for symptomatic gallstone
disease (cholangitis or cholecystitis). A total of 582 participants (451 without
gallstone and 131 symptomatic gallstone disease) who underwent CT and
abdominal ultrasonography were analyzed. The associations between body
mass index (BMI), visceral adipose tissue (VAT) area, subcutaneous adipose
tissue (SAT) area, and symptomatic gallstone disease were estimated using
odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, sex,
dyslipidemia, and diabetes mellitus.
RESULTS: In multivariate analysis, symptomatic gallstone disease was significantly associated with VAT area and SAT area (P for trend 50.001, and 0.045,
respectively), but not BMI (P for trend 0.40). When the obesity indices were
considered simultaneously, symptomatic gallstone disease remained significantly
associated with VAT area for both categorical data and trend (P for trend 0.003),
but not BMI (P for trend 0.536). The adjusted ORs for the highest quartile of the
VAT area in gallstone disease were 3.2, compared with the lowest quartile.
CONCLUSION: Abdominal visceral tissue measured by CT, rather than BMI, is
a better predictor for risk of symptomatic gallstone disease.
Disclosure of Interest: None declared
P0082 POSITIVE
PREDICTIVE
VALUE
OF
ENDOSCOPIC
ULTRASOUND (EUS) FOR THE DETECTION OF INTRALUMINAL
FILLING DEFECTS IN THE COMMON BILE DUCT (CBD) IN A
LARGE NON-ACADEMIC TEACHING HOSPITAL
L.Van Driel1,*, R. Quispel1, B. Veldt1, M. Bruno2
1
Reinier de graaf hospital, Delft, 2Erasmus medical centre, Rotterdam, Netherlands
Contact E-mail Address: L.vandriel@rdgg.nl
INTRODUCTION: In small academic studies, endoscopic ultrasound has been
shown a reliable and safe method to assess the presence of common bile duct
stones.
AIMS & METHODS: The aim of this study was to calculate the positive predictive value (PPV) for the presence of CBD stones with EUS. For this we
retrospectively included all patients in whom CBD stones were detected with
EUS and who subsequently underwent endoscopic retrograde cholangiography
(ERC). This study was performed in a large non-academic teaching hospital in
The Netherlands between November 2006 and January 2011. PPV was calculated
by dividing the number of true positives by the total number.
RESULTS: EUS detected CBD stones in 99 patients who subsequently underwent ERC. The median time-interval between EUS and ERC was 5 days (interquartile range 1-15 days). The PPV for the total group was only 56% (57/99).
However, the PPV depended on the time-interval between EUS and ERC, being:
80% (8/10) within 24 hours, 63% (32/51) within 1-6 days, and 47% (18/38) after
one week. Moreover, the PPV differed substantially depending on the type and
number of intraluminal filling defects in the CBD, namely sludge (10/21, PPV
48%), or one stone (29/51, PPV 58%), or more than one stone (18/24, PPV 75%),
or more than one stone with acoustic shadow (8/10, PPV 80%).
CONCLUSION: EUS performed in a large non-academic teaching hospital has
a lower PPV for detection of CBD stones than overall reported in literature. This
seems to be explained at least in part by the large variation in time-intervals
between EUS and ERC indicating that ERCP should promptly follow a positive
EUS and may be delayed a few days after the onset of symptoms to allow for
spontaneous stone passage. Sludge in the CBD as finding on EUS has the lowest
PPV when compared with stones with or without an acoustic shadow.
Disclosure of Interest: None declared
P0083 WHICH IS A BETTER PROCEDURE: SINGLE SESSION VERSUS
MULTIPLE SESSIONS OF ERCP FOR COMMON BILE DUCT
STONES WITH OR WITHOUT ACUTE CHOLANGITIS?
R. Maeshima1,*, M. Asano1, H. Kobashi1, H. Himei1, S. Inoo1, M. Omori1,
S. Ando1, E. Yoshimura1, M. Shigetoshi1, J. Toshimori1, M. Inoue1,
M. Yokoyama1
1
Gastroenterology and hepatology, Japanese Red Cross Okayama Hospital,
Okayama city, Japan
INTRODUCTION: Tokyo guidelines (TG13) for management of acute cholangitis (AC) and acute cholecystitis were revised and published in 2013. TG13
recommend the elective, early or urgent biliary drainage using endoscopic retrograde cholangiopancreatography (ERCP), followed by treatment of etiology
such as common bile duct (CBD) stones after the resolution of AC. However,

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the usefulness of completion of endoscopic clearance of CBD stones with biliary


drainage in a single session, remains unclear.
AIMS & METHODS: The aim of this study is to clarify which of these, a single
session or multiple sessions of ERCP, is better for the patients with CBD stones
with and without AC. This is a retrospective study. Between August 2012 and
March 2014, a total of 411 ERCPs were performed in 252 patients with biliary
and pancreatic diseases in our hospital. The patients with CBD stones with or
without AC treated with ERCP-related procedure were eligible for the study. The
patients with recurrent disease were excluded. Finally 116 consecutive patients
(56 males and 60 females) were included in the study. They were divided into two
groups; Group A for the patients in a single session of ERCP, and Group B for
those in multiple sessions of ERCP. Groups A and B were compared with each
other for the clinical outcomes, namely total duration of hospitalization (DH)
and frequency of adverse events. The grade of AC, Grade I (mild), Grade II
(moderate) and Grade III (severe), were also taken into account. Wilcoxon/
Kruskal-Wallis test and Kaplan-Meier analysis were used as statistics. This
study was approved by the local committee of ethics.
RESULTS: Group A and Group B was consisted of 84 and 32 patients, respectively. Mean age was 72.4 in Group A and 78.8 in Group B. The sphincterotomy
and the maneuver using retrieval basket or balloon were performed more frequently in Group A (p50.001). In total, 74 patients were complicated with AC;
grade I in 44, grade II in 17 and grade III in 13, and 42 patients were without AC.
In Group A, grade I in 35, grade II in 10 and Grade III in 5, and without AC in
34 patients, respectively. In Group B, grade I in 9, grade II in 7 and grade III in 8,
and without AC in 8 patients, respectively. The mean DH was 12.7 days in total.
It was significantly shorter in Group A (9.9 days), as compared with Group B
(20.1 days) (p50.001). In total, DH was incrementally longer according to the
degree of AC grade (p50.0001); it was significantly longer (32.0 days) in grade
III, as compared with Grade I (11.3 days), grade II (15.6 days) and without AC
(7.0 days). In the patients with AC grade III, DH was significantly shorter in
Group A (18.0 days) as compared with Group B (40.75 days) (p 0.0437). Also
in the patients without AC, DH was significantly shorter in Group A (6.4 days)
as compared with Group B (9.9 days) (p 0.033). As for adverse events, post
ERCP pancreatitis was occurred in 4 patients in Group A and in 1 patient in
Group B, and there was no significant difference between both groups (p 0.69).
CONCLUSION: A single session of ERCP for completion of clearance of CBD
stones with biliary drainage is superior to multiple sessions of ERCP, especially
for the patients complicated with AC grade III and those without AC.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
PANCREAS I POSTER EXHIBITION HALL XL_____________________
P0084 THE ROLE OF PROINFLAMMATORY CYTOKINES
ADHESION MOLECULES IN VASCULAR DISORDERS AND
ORGAN DYSFUNCTION IN ACUTE PANCREATITIS PATIENTS

AND

I. Osmilovska1,*, S. Chooklin1, O. Usach1


1
Regional Clinical Hospital, Lviv, Ukraine
Contact E-mail Address: docihor@ukr.net: chooklin_serge@hotmail.com
INTRODUCTION: The main component in the pathogenesis of acute pancreatitis is the transition from local to the system inflammation that causes the
severity of disease. Changes of microcirculation and endothelial dysfunction
are an important step from mild to severe disease.
AIMS & METHODS: The study involved 53 acute pancreatitis patients (28 severe, 25 - mild). We measured interleukin-6, interleukin-18, ICAM-1 and Eselectin in the blood plasma. Flow in the visceral arteries was assessed with the
help of the Doppler sonography.
RESULTS: A significant increase of both pro-inflammatory cytokines and adhesion molecules was determined only in severe acute pancreatitis. We determined
that the level of IL-6 significantly correlated with the appearance of liver dysfunction. There was a significant correlation between the concentration of IL-18,
ICAM-1, E-selectin and the appearance of multiple organ dysfunction syndrome.
There was a significant direct correlation concentrations of IL-6 with peak systolic velocity in the superior mesenteric artery (R 0.502941, p 0.047063), with
an index of resistance in common hepatic (R 0.532845, p 0.033574), splenic
(R 0.511125, p 0.043028) and superior mesenteric (R 0.563200,
p 0.023107) arteries. The level of IL-18 was significantly correlated with peak
systolic velocity in the common hepatic artery (R 0.589102, p 0.016342),
splenic artery (R 0.547865, p 0.028022) and superior mesenteric artery
(R 0.504783, p 0.046131), as well as the resistance index in the common
hepatic artery (R 0.524375, p 0.037051) and superior mesenteric artery
(R 0.573230, p 0.020271). The level of ICAM-1 was significantly correlated
with changes in blood flow in the visceral vessels, in particular, peak systolic
velocity in the common hepatic artery (R 0.802061, p 0.000186), splenic
(R 0.764581, p 0.000,562) and the superior mesenteric artery (R 0.768212,
p 0.000509), as well as the resistance index (R 0.527422, p 0.035770;
R 0.608824, p 0.012315; R 0.736152, p 0.001148, respectively) in them.
The level of soluble E-selectin may also affect splanchnic flow in patients with
acute pancreatitis, defined as a significant direct correlation between the concentration dependence of E-selectin and peak systolic velocity of blood flow in the
common hepatic (R 0.838249, p 0.000095) and splenic (R 0.689902,
p 0.004424) arteries and resistance index in the common hepatic
(R 0.710321, p 0.003002) and superior mesenteric (R 0.759862,
p 0.001012) arteries.
CONCLUSION: It was determined that the levels of proinflammatory cytokines
and adhesion molecules increase in the blood of acute pancreatitis patients. Their
level correlates with the organ dysfunction and disturbances in splanchnic blood
flow.
Disclosure of Interest: None declared

P0085 TIMING OF INTERVENTION IN INFECTED NECROTIZING


PANCREATITIS: AN INTERNATIONAL MULTIDISCIPLINARY
SURVEY AND CASE VIGNETTE STUDY
J.van Grinsven1,2,*, S.van Brunschot3, O. Bakker3, T. Bollen4, M. Boermeester5,
M. Bruno6, K. Dejong7, M. Dijkgraaf8, C.van Eijck9, P. Fockens1,
H.van Goor10, H. Gooszen11, K. Horvath12, K.van Lienden13, H.van Santvoort3,
M. Besselink5 on behalf of Dutch Pancreatitis Study Group
1
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,
2
Research and Development, St. Antonius Hospital, Nieuwegein, 3Surgery,
University Medical Center Utrecht, Utrecht, 4Radiology, St. Antonius Hospital,
Nieuwegein, 5Surgery, Academic Medical Center, Amsterdam, 6Gastroenterology
and Hepatology, Erasmus Medical Center, Rotterdam, 7Surgery, Maastricht
University Medical Center, Maastricht, 8Clinical Research Unit, Academic
Medical Center, Amsterdam, 9Surgery, Erasmus Medical Center, Rotterdam,
10
Surgery, 11OR/Evidence Based Surgery, Radboud University Medical Center,
Nijmegen, Netherlands, 12Surgery, University of Washington Medical Center,
Seattle, United States, 13Radiology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: j.vangrinsven@pancreatitis.nl
INTRODUCTION: It is unclear whether there is consensus regarding the timing
of intervention in patients with infected necrotizing pancreatitis (INP).
AIMS & METHODS: We evaluated the current expert opinion regarding timing
of intervention in INP. An anonymous digital survey was sent to 118 expert
pancreatologists (surgeons, gastroenterologists, radiologists) from all continents.
The survey consisted of 18 questions and 10 clinical cases including CECT images
of varying disease stages. Diagnostic and therapeutic options included fine needle
aspiration (FNA), antibiotics, (percutaneous or endoscopic) catheter drainage
and necrosectomy.
RESULTS: Response rate was 74% (N 87). The step-up approach, initial
catheter drainage if needed followed by necrosectomy, was accepted by most
experts (87%). Consensus was lacking regarding the use of FNA to diagnose
INP: 0% used FNA routinely, 40% only in case of clinical suspicion, 45% rarely
and 15% never. After definitively diagnosing INP, 55% would postpone an
intervention and await the effect of antibiotics, whereas 45% would immediately
perform an intervention. Walled-off necrosis was not considered a technical
prerequisite for percutaneous catheter drainage by 88% of experts whereas
66% considered it essential for endoscopic transluminal drainage. More experts
would intervene in case of proven INP (gas in the (peri)pancreatic necrotic collection on CECT) vs. clinical signs of INP: i.e. day 7: 34% vs 2%, day 14: 57% vs
25%, day 30: 89% vs 72%.
CONCLUSION: Although the step-up approach is well accepted as routine
management strategy of INP, consensus regarding the timing of initiating this
approach is lacking. Proof of infection and disease duration influence the timing
of intervention. This study highlights the need for a randomized trial on timing of
intervention in INP.
Disclosure of Interest: None declared
P0086 PREDICTION OF POST-ERCP PANCREATITIS BY 4-HOUR
POST-ERCP SERUM AMYLASE AND LIPASE LEVEL
J.H. Kim1,*, M.J. Yang1
1
Gastroenterology, Ajou Unversity School of Medicine, Suwon, Korea, Republic Of
INTRODUCTION: Acute pancreatitis is the most common and serious complication of endoscopic retrograde cholangiopancreatography (ERCP). Early prediction of possible post-ERCP pancreatitis (PEP) could allow for an earlier safe
discharge of a patient on the same day after ERCP.
AIMS & METHODS: The aim of this study was to investigate a predictive cutoff value of 4-hour post-ERCP serum amylase and lipase levels for the PEP. In
patients who underwent ERCP procedures and had tests for serum amylase and
lipase levels of 4-hour post-ERCP and the next morning at Ajou Medical Center
from January 2012 to August 2013, patient demographics, the procedure reasons,
performance of pancreatograms, serum amylase and lipase levels were retrospectively evaluated.
RESULTS: PEP occurred in 16 (3.1%) after 516 ERCP procedures. Its severity
was mild in 4 (25%), moderate in 9 (56.3%), and severe in 3 (18.8%). The mean
4-hour amylase level was significantly higher in patients with PEP, compared
with those without PEP (965 U/L vs. 158 U/L, p 0.001). There were no statistically significant differences in age, gender, and the procedure reasons between
both groups. The sensitivity, specificity and negative predictive value (NPV) of a
4-hour post-ERCP amylase level with a cut-off value of 2.5 times of its normal
upper limit (290 U/L) was 75.0%, 88.0% and 99.1%, respectively. The sensitivity,
specificity and negative predictive value (NPV) of a 4-hour post-ERCP lipase
level with a cut-off value of 8 times of its normal upper limit (480 U/L) was
75.0%, 91.3% and 99.1%, respectively. The patient group undergoing pancreatogram revealed high incidence of post-ERCP pancreatitis, but no significant
difference in the 4-hour post-ERCP serum amylase and lipase level, compared
to its counterpart group.
CONCLUSION: The 4-hour post-ERCP serum amylase level and lipase level
with cut-off value of 2.5 times and 8 times of their normal upper limit have so far
proven to be useful predictive values for an earlier safe discharge of a patient on
the same day after ERCP.
Disclosure of Interest: None declared

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P0088 PREDICTING SUCCESS OF CATHETER
INFECTED NECROTIZING PANCREATITIS

DRAINAGE

IN

R.A. Hollemans1,*, T.L. Bollen2, S.van Bruschot3, U. Ahmed Ali4, O.J. Bakker4,
H.van Goor5, M.A. Boermeester6, H.G. Gooszen7, M.G. H. Besselink6, H.C.
van Santvoort4 on behalf of Dutch Pancreatitis Study Group
1
Surgery / Research and Development, University Medical Center Utrecht / St
Antonius Hospital Nieuwegein, Utrecht / Nieuwegein, 2Radiology, St Antonius
Hospital, Nieuwegein, 3Gastroenterology and Hepatology, Academic Medical
Center, Amsterdam, 4Surgery, University Medical Center Utrecht, Utrecht,
5
Surgery, Radboud University Medical Center, Nijmegen, 6Surgery, Academic
Medical Center, Amsterdam, 7Operating Rooms / Evidence Based Surgery,
Radboud University Medical Center, Nijmegen, Netherlands
Contact E-mail Address: H.vanSantvoort@umcutrecht.nl
INTRODUCTION: Catheter drainage as the first treatment step of infected
necrotizing pancreatitis is successful in at least 30% of patients. It is currently
not possible to predict which patients will also need necrosectomy. We evaluated
predictive factors for success of catheter drainage in infected necrotizing
pancreatitis.
AIMS & METHODS: We performed a post-hoc analysis of 130 prospectively
included patients who underwent primary catheter drainage for (suspected)
infected necrotizing pancreatitis. Using logistic regression we evaluated the association between success of catheter drainage (i.e. survival without necrosectomy)
and 22 factors regarding demographics, disease severity (e.g. CRP, APACHE-II
score and organ failure), morphologic characteristics on CT (e.g. percentage and
distribution of necrosis and CTSI) and drainage criteria (e.g. timing of drainage
and type of drain).
RESULTS: Drainage was performed percutaneously in 113 patients and endoscopically in 17 patients. Infection was confirmed in 116 patients (89%). Catheter
drainage was successful in 45 patients (35%). In multivariable regression, the
following variables were associated with success of drainage: female gender
(odds ratio[OR] 4.84; 95%4 confidence interval[CI] 1.89-12.4; p 0.001),
absence of multi-organ failure (OR 6.19; 95%4CI 1.50-25.53; p 0.012), percentage of pancreatic necrosis (530%/30-50%/450%: OR 2.29; 95%4CI 1.214.36; p 0.011), primarily left-sided pancreatic necrosis (OR 13.35; 95%4CI 1174; p 0.048) and homogeneity of the collection (OR 5.23; 95%4CI 1.6017.05; p 0.006). A prognostic nomogram including these factors yielded probability of success ranging from 99% (all factors present) to 1% (none of the
factors present).
CONCLUSION: Female gender, absence of multi-organ failure, low percentage
of necrosis, left-sided pancreatic necrosis and a homogeneity of the collection are
independent predictors for success of catheter drainage in infected necrotizing
pancreatitis. The constructed nomogram can easily predict success in clinical
practice.
Disclosure of Interest: None declared
P0089 FUNGAL INFECTION IN PATIENTS WITH WALLED-OFF
PANCREATIC NECROSIS IS ASSOCIATED WITH A POOR
PROGNOSIS
S. Roug1,2,*, M. Werge1, S. Novovic1, P.N. Schmidt 1, E. Feldager1,
B. Sndergaard1, J.D. Knudsen3
1
Department of Gastroenterology and Gastrointestinal Surgery Copenhagen
University Hospital, Hvidovre, 2Department of Medical Gastroenterology, Kge
Hospital, 3Department of Clinical Microbiology Copenhagen University Hospital,
Hvidovre, Denmark
Contact E-mail Address: stineroug@dadlnet.dk
INTRODUCTION: Patients with necrotizing pancreatitis and infected necrosis
have a worse prognosis than patients with sterile necroses. While there is clear
evidence that bacterial infection in pancreatic necrosis increases mortality and
morbidity, studies on the influence of fungal infections have been conflicting.
AIMS & METHODS: To evaluate the impact of fungal infections in patients
with walled-off pancreatic necrosis (WON) treated by endoscopic, transmural
drainage and necrosectomy (ETDN). In addition, to evaluate the effect of antifungal treatment.
We retrospectively retrieved medical charts of 123 patients who underwent
ETDN for WON in our department between November 2005 and December
2013.
RESULTS: Fifty-seven out of the 123 patients (46%) had fungus in their necrosis. The median time from the symptom debut to the first fungal finding was 61
days (range 8-195). In 20 patients (35%) the first fungal finding was at the index
endoscopy, in 24 patients (42%) it was at the second endoscopy, and in 9 patients
(16%) at the third endoscopy. The prevailing fungal finding at both the index and
secondary endoscopy was Candida albicans (55% and 56%, respectively).
Ten of the 57 patients (18%) with fungal infection died during admission, and 18
(32%) developed organ failure. The mortality in patients infected with bacterial
infection, only, was 6.5% (p 0.046). Concomitant fungemia was found in 6
patients. Three patients with concomitant fungemia died, as opposed to seven
with fungi in the necrosis, only (50% vs. 14%, respectively p 0.027).
Thirty-nine of the 57 patients (70%) were treated with antifungals. There was no
significant difference in mortality or occurrence of organ failure between this
group and the group that was not treated with antifungals.
Culturing from the necrosis was repeated in 35 out of 57 patients (61%), of which
17 patients were positive for fungus. The same fungal species on both the first
and the second culture was found in 15 out of the 17 patients (88%) despite
adequate antifungal treatment based on the susceptibility pattern.
CONCLUSION: Fungal infection in WON, especially with concomitant fungemia, is associated with a poor prognosis. Whether the outcome may be explained
by the fungal infection per se or it is merely a consequence of a prolonged disease

course is, however, at present unknown. Only about one-third of all cases with
fungal infection in necrosis were found at the index endoscopy, which is why
continuous culturing should be mandatory throughout the disease course
Disclosure of Interest: None declared
P0090 EFFECT OF INTRAVENOUS FLUID RESUSCITATION ON
INFLAMMATORY MARKERS OF ACUTE PANCREATITIS AND ITS
CLINICAL OUTCOME
Y.R. Reddy1,*, S. Talukder2, T.D. Yadav2, P.K. Siddappa1,1, R. Kochhar1
1
Gastroenterology, 2General surgery, Postgraduate Institute of Medical Education
and Research (PGIMER), Chandigarh, India
Contact E-mail Address: dr_kochhar@hotmail.com
INTRODUCTION: Early in the course of acute pancreatitis (AP) management
revolves primarily around supportive care and fluid resuscitation remains the
cornerstone. Inflammatory cytokines play a crucial role in extravascular fluid
sequestration. Recent evidence shows the superiority of Ringer lactacte (RL) over
normal saline (NS) as the fluid of resuscitation patients with AP.
AIMS & METHODS: To study the effect of two different types of resuscitation
fluids viz. normal saline (NS) and Ringers lactate (RL) on inflammatory markers
IL-6 and IL-10 and on the clinical course and outcome of patients with acute
pancreatitis (AP).
Consecutive adult patients with AP who presented within 5 days of onset of
symptoms between July 2012 and June 2013 were randomized to receive NS or
RL. The patients were classified as having mild, moderate or severe AP and
managed in a high dependency unit as per a uniform protocol. Intravenous
fluid was infused initially as 20ml/kg bolus till a base line CVP of 8 cm of
water and a urine output of 4 0.5ml/kg/hr. was established. Further fluids
were infused to maintain urine output as mentioned above. Serum samples
were obtained at admission days 0, 3 and 7. IL-6 and IL-10 were estimated on
the cryo-preserved serum samples using a Diaclone ELISA kit. Patients were
monitored for the development of organ failure, sepsis, local complications,
duration of hospital stay and final outcome till 28 days of admission. Data
was recorded using Microsoft excel and analyzed using SPSS software v17.0.
RESULTS: 50 patients of AP with a mean age of 45.8216.46 years (56% males)
were included. NS and RL groups included 25 patients each who were well
matched for age and sex. There was no significant difference in the severity of
AP between the 2 groups (p 0.77). IL-6 levels on day 0, day 3 and day 7 were
significantly elevated in patients with severe AP (SAP) compared to those without severe disease [183.6643.92, 178.2036.28, 143.8547.21 pg/ml vs
145.9060.93, 119.9958.86, 86.4438.50 pg/ml (p50.05)] and remained persistently elevated at the end of first week in SAP group. No such correlation was
seen with IL-10 level (p40.05). The cumulative fluid infused over first 7 days of
admission was not statistically significant between the 2 groups (13.564.93 liters
vs. 13.994.58 liters, p40.05). There was no statistically significant difference in
the serum IL-6 levels noted between the NS and RL groups but among patients
with severe disease (n 29), those who received RL had significantly lower serum
IL-6 levels at the end of first week than those in RL group; p 0.043. Patients
receiving NS had significantly longer duration of hospitalisation (2212.45 days
versus 147.17 days; (p 0.015), higher incidence of infective complication
(p 0.037) and a higher need for intervention (p 0.050). Patients receiving
RL were found to show a greater magnitude of reduction in their organ failure
score on day 3 and 7 in comparison to those receiving NS (p 0.012 and 0.001).
CONCLUSION: There was no significant reduction in cytokine levels among
patients resuscitated with RL or NS. However, patients receiving RL had an
early organ failure resolution, fewer infections and shorter hospital stay,
making RL the preferred fluid for resuscitation.
Disclosure of Interest: None declared
P0091 A
C-REL/NFTAC2/COX-2
PATHWAY
RESISTANCE IN PANCREATIC CANCER

CONFERS

TRAIL

C. Geismann1, F. Grohmann1, R. Hasler2, S. Zeissig1, H. Schafer1,


P. Rosenstiel2, S. Schreiber1, A. Arlt1,*
1
1st Deparment of Medicine, Universityhospital Schleswig-Holstein, Campus Kiel,
2
IKMB, CAU Kiel, Kiel, Germany
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) represents one
of the deadliest malignancies with an overall life expectancy of six months despite
current therapies. NF-kB signalling has been shown to be critical for this profound cell-autonomous resistance against chemotherapeutic drugs and deathreceptor induced apoptosis, but little is known about the role of the c-Rel subunit
in solid cancer and PDAC apoptosis control.
AIMS & METHODS: In the present study, by analysis of genome-wide patterns
of NF-kB dependent gene expression we investigated the role of c-Rel in apoptosis resistance of PDAC.
RESULTS: TRAIL resistant Panc1 and Patu8988 cells exhibited a strong
TRAIL inducible NF-kB activity, whereas TRAIL sensitive MiaPaca2 cells displayed only a small increase in NF-kB binding activity. Transfection with siRNA
against c-Rel sensitized the TRAIL resistant cells in a comparable fashion to
siRNA targeting the p65/RelA subunit. Gel shift analysis revealed that c-Rel is
part of the TRAIL inducible NF-kB complex in PDAC. Array analysis identified
NFATc2 as a c-Rel target gene amongst the 12 strongest TRAIL inducible genes
in apoptosis resistant Panc1 cells. By database search and chromatin immunoprecipitation we were able to funcionally characterize one regulatory element for
c-Rel in the NFATc2 promoter. In line, siRNA targeting c-Rel strongly reduced
TRAIL induced NFATc2 activity in TRAIL resistant PDAC cells. Furthermore,
siRNA targeting NFATc2 sensitized these PDAC cells against TRAIL induced
apoptosis. Finally, TRAIL induced expression of COX-2 was diminished

A156

United European Gastroenterology Journal 2(1S)

through siRNA targeting c-Rel or NFATc2 and pharmacological inhibition of


COX-2 with celecoxib enhanced TRAIL apoptosis.
CONCLUSION: In conclusion, we were able to delineate a novel c-Rel, NFATc2
and COX-2 dependent anti-apoptotic signalling pathway in PDAC with broad
clinical implications for pharmaceutical intervention strategies.
Disclosure of Interest: None declared

with shorter survival, indicating that this genetic variant is not a clinically relevant prognostic factor. Supported by TAMOP and OTKA.
Disclosure of Interest: None declared

P0092 THE MICROARRAY TISSUE ANALYSIS OF GENES INVOLVED


IN PANCREATIC ADENOCARCINOMA

E. Tieftrunk1,*, I.E. Demir1, S. Schorn1, M.U. Kurkowski2, E. Costello3,


H. Algul2, H. Friess1, G.O. Ceyhan1
1
Department of Surgery, 2Department of Internal Medicine II, Klinikum rechts der
Isar, Munchen, Germany, 3Liverpool NIHR Pancreas Biomedical Research Unit,
Liverpool, United Kingdom
Contact E-mail Address: elke.tieftrunk@tum.de

A. Seicean1,*, O. Balacescu1, I. Berindan1, R. Stan-Iuga1, R. Redis1,


L. Balacescu1, R. Seicean1
1
UNIVERSITY OF MEDICINE AND PHARMACY IULIU HATIEGAN,
CLUJ-NAPOCA, Romania
Contact E-mail Address: andradaseicean@gmail.com
INTRODUCTION: The pathogenesis of pancreatic ductal adenocarcinoma
involves the multi-stage development of molecular aberrations affecting signaling
pathways that regulate cancer growth and progression. Tissue microarray analysis of pancreatic tumors allows simultaneous assessment of genetic disorders,
which can lead to identification of biomarkers of poor prognosis.
AIMS & METHODS: To characterize the gene expression of pancreatic adenocarcinoma compared to normal tissue from the same patient. We investigated
sixteen samples of T3 pancreatic adenocarcinoma obtained intraoperatively and
compared them to normal pancreatic tissue from the same patients. RNA was
extracted and assessed qualitatively and quantitatively, followed by amplification
of cDNA using reverse transcriptase, cRNA synthesis, and hybridization of
microarray slides. For each sample 1000 ng of total RNA was available. The
overexpressed and underexpressed genes were classified by their known function
in the cell. We selected genes over- or underexpressed three times compared to
normal adjacent tissue some described previously in pancreatic pathology, and
used RT-PCR for validation.
RESULTS: On microarray tissue analysis 41 genes were overexpressed and 402
were underexpressed in the pancreatic adenocarcinoma samples. There were
selected genes involved in transcription process as ZNF 428, MIXL1, SEPT 1,
genes involved in intracellular signaling as FLJ21865, AGRP and genes involved
in transmembranar and intracellular transport as CCDC88, UTP14A,VPS11,
LLRC21,CHRM3, Marveld3. Validation by qRT-PCR confirmed the involvement of AGRP and MIXL1 gene in pancreatic adenocarcinoma tissue.
CONCLUSION: Microarray tissue analysis of pancreatic adenocarcinoma
showed more underexpressed than overexpressed genes. After validation, the
overexpressed gene AGRP was shown to be one possible factor responsible for
anorexia and perineural invasion. The possible role in pancreatic cancer of
MIXL1, known to play a role in cellular proliferation and differentiation,
should be further clarified.
Disclosure of Interest: None declared
P0093 CCK-B RECEPTOR GENE VARIANT IS NOT ASSOCIATED WITH
INCREASED RISK, NOR WITH DECREASED SURVIVAL IN
PANCREATIC ADENOCARCINOMA
A. Balazs1,*, B.C. Nemeth2, E. Hegyi1,3, I. Hritz4, F. Izbeki5, J. Gervain5,
A. Szepes6, G. Gyimesi6, Z. Dubravcsik6, D. Kelemen7, A. Csiszko8,
Z. Szentkereszty9, B. Bod10, R. Szmola11, J. Sumegi12, J. Novak13, G. Farkas14,
L. Czako1, T. Takacs1, Z. Rakonczay1, A. Pap11, M. Sahin-Toth15, P. Hegyi1 on
behalf of Hungarian Pancreatic Study Group
1
First Department of Medicine, University of Szeged, Szeged, Hungary,
2
Department of Molecular and Cell Biology, Boston University, Boston, United
States, 32nd Department of Pediatrics, University Childrens Hospital, Comenius
University Medical School, Bratislava, Slovakia, 4First Deoartment of Medicine,
University of Szeged, Szeged, 5Fejer Megyei Szent Gyorgy Hospital,
Szekesfehervar, 6Bacs-Kiskun County Municipality Hospital, Kecskemet,
7
Department of Surgery, University of Pecs, Pecs, 8Department of Surgery,
University of Debrecen, 9Department of Surgery, University of Debrecen,
Debrecen, 10Dr. Bugyi Istvan Hospital, Szentes, 11National Institute of Oncology,
Budapest, 12B-A-Z County Hopspital, Miskolc, 13Pandy Kalman County Hopsital,
Gyula, 14Department of Surgery, University of Szeged, Szeged, Hungary,
15
Department of Molecular and Cell Biology, Boston University, Boston, United
States
Contact E-mail Address: anitabalazs@outlook.com
INTRODUCTION: Cholecystokinin-B (CCK-B) receptor is often overexpressed in pancreatic ductal adenocarcionoma (PDAC); stimulation of the
receptor promotes tumor growth. An intronic mutation (c.81137C4A) in the
CCKBR gene causes retention of intron-4, resulting in a new spliceform, which
was previously shown to correlate with higher PDAC risk and a more aggressive
phenotype.
AIMS & METHODS: Our aim was to test the effect of the c.81137C4A
mutation on PDAC risk and prognosis in a Hungarian population. 122 subjects
with PDAC (cases) and 106 subjects with no pancreatic disease (controls) were
recruited from the Hungarian National Pancreas Registry. Genomic DNA was
isolated from peripheral blood. Intron-4 of the CCKBR gene, including exonintron boundaries, was amplified and sequenced.
RESULTS: We found the c.81137C4A intronic mutation in 35 heterozygous
and 5 homozygous cases and in 32 heterozygous and 3 homozygous controls
(allele frequency 18.4% and 17.9% respectively). One case subject carried a p.
R319Q and one control subject a p. R319W missense mutation. Survival analysis
showed no significant difference in median survival between wild type cases and
carriers for the mutation (8.7 months and 6.9 months respectively)
CONCLUSION: In our cohort, the c.81137C4A intronic mutation was not
associated with increased risk for PDAC. Also, the mutation was not associated

P0094 HYPOXIA AND NEUROINFLAMMATION LEAD TO


INTERLEUKIN-6-INDUCED SCHWANN CELL ACTIVATION IN
PANCREATIC CANCER

AN

INTRODUCTION: Pancreatic cancer (PCa) is characterized by prominent intrapancreatic neuropathy and neuropathic pain. Up to now, the impact of glia cells
on the development of the pancreatic neuropathy has not yet been investigated.
AIMS & METHODS: We studied whether there is an activation of peripheral
glia cells (Schwann cells, SC) in PCa and what signalling pathways might be
responsible for intrapancreatic glial activation. SC were cultured under hypoxia,
in pancreatic cancer cell (PCC) supernatants or co-coltured with PCC and Tlymphocytes and investigated via immunoblotting, MTT viability assay,
Multiplex-Luminex-ELISA and cell area measurement. Nerves in PCa and
normal pancreas (NP) were analysed for their immunoreactivity for glial fibrillary acidic protein (GFAP), hypoxia inducible factor 1 alpha (HIF-1) and
carboanhydrase IX (CA-IX). The SC distribution and frequency in conditional
PCa knock-out mice was assessed after in-vivo blockade of the IL-6 signalling
pathway.
RESULTS: Hypoxia leads to upregulation of the intermediate filaments GFAP,
Nestin and Vimentin and pro-inflammatory cytokines in SC. The nerves in PCa
were immunoreactive for HIF-1 and CA-IX, and the extent of neuro-immunoreactivity for HIF-1 and CA-IX correlated to the intraneural GFAP amount.
PCC supernatants led to upregulation of GFAP and Nestin in SC, cellular
hypertrophy (stellation) and higher proliferation rate. The serverity of pancreatic
neuritis correlated with the intraneural GFAP amount. The blockade of IL-6, but
not of IL-1 in PCC supernatants abolished the upregulation of GFAP and
Nestin. GFAP/SOX10 double positive SC were found around pancreatic intraepithelial neoplasia (PanIN) of Ptf1a-Cre;KrasG12D, but not around PanINs of
Ptf1a-Cre;KrasG12D;IL6-/- mice. The blockade of IL-6 transsignalling in Ptf1aCre;KrasG12D;sgp130tg mice had no influence on the SC distribution around
PanINs.
CONCLUSION: SC in PCa show typical features of reative gliosis, which is
induced via the classical IL-6 signalling.
Disclosure of Interest: None declared
P0095 DIAGNOSTIC
EFFICIENCY
OF
CELL-BLOCK
IMMUNOSTAINING, SMEAR CYTOLOGY, LIQUID-BASED
CYTOLOGY IN EUS-FNA ON PANCREATIC LESIONS: AN
INSTITUTIONS EXPERIENCE

WITH

H. Jiang1,*, S.-Y. QIN1, L. TAO1, W. LUO1, S.-B. SU1, X.-P. LU1, R.-E. LEI1
1
The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Contact E-mail Address: lihuan@erbechina.com
INTRODUCTION: The diagnostic efEciency of endoscopic ultrasound-guided
fine needle aspiration (EUS-FNA) cytology varies largely depending on the processing methods of specimens.
AIMS & METHODS: The present study aimed to evaluate the diagnostic efficiency of cell block (CB) with methods of immunostaining, smear cytology (SC)
and liquid-based cytology (LBC) without on-site cytopathologist in patients with
pancreatic lesions. 72 patients with pancreatic lesions were prospectively enrolled
in this study. After EUS-FNA, specimens were determined by SC, LBC and CB
with immunostaining, respectively. Diagnostic efEciency of SC was compared
with that of LBC and CB. The final diagnosis was conErmed by surgically
resected specimens, diagnostic imaging and clinical follow-up.
RESULTS: 60 malignant and 12 benign pancreatic lesions were determined. The
diagnostic sensitivity, negative predictive value and accuracy (90.0%, 66.7% and
91.7%) of CB with immunostaining were significantly higher than those of SC
(70.0%, 30.0% and 75.0%, P 5 0.05), LBC (73.3%, 31.6% and 77.8%, P 5
0.05). The combination of CB and SC, or CB and LBC did not significantly
increase the efficiency compared to CB with immunostaining alone (P 4 0.05).
Table: Diagnostic efficiency of SC, LBC and CB methods in pancreatic lesions
SC

LBC

CB

SCCB

LBCCB

Sensitivity,% (n)

70.0 (42/60)

73.3 (44/60)

90.0 (54/60)*

91.7 (55/60)

93.3 (56/60)

Spcificity, % (n)
PPV, % (n)
NPV, % (n)
Accuracy, % (n)

100 (12/12)
100 (42/42)
30.0 (12/40)
75.0 (54/72)

100 (12/12)
100 (44/44)
31.6 (12/38)
77.8 (56/72)

100 (12/12)
100 (54/54)
66.7 (66/72)*
91.7 (66/72)*

100 (12/12)
100 (55/55)
70.6 (12/17)
93.1 (67/72)

100 (12/12)
100 (56/56)
75.0 (12/16)
94.4 (68/72)

CONCLUSION: The CB with immunostaining technique presents a higher diagnostic efficiency than both of SC and LBC without on-site cytopathologist in
patients with pancreatic lesions who had undergone EUS-FNA.

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: None declared
P0096 EFFECT OF TELOMERASE PEPTIDE VACCINATION, GV 1001
COMBINED WITH GEMCITABINE IN PANCREATIC DUCTAL
ADENOCARCINOMA
J.K. Park1,*, H. Kim2, Y. Kim2, S.-H. Lee1, J.K. Ryu1, W.J. Lee2, J.S. Kang2
Internal Medicine, Seoul National University Hospital College of Medicine,
2
Anatomy, Seoul National University College of Medicine, Seoul, Korea, Republic
Of
Contact E-mail Address: mdsophie@gmail.com
1

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) shows dismal


prognosis due to early metastasis, frequent recurrence and chemo-resistance.
However, there is no effective treatment to overcome these problems. GV1001
is a telomerase-based cancer vaccine made of a 16-mer TERT peptide and human
telomerase reverse transcriptase (hTERT), the rate-limiting subunit of the telomerase complex, is therefore an attractive target for cancer vaccination.
AIMS & METHODS: AIMS: The aim of this study was to evaluate the combination benefit of telomerase peptide vaccination, GV1001 combined with
Gemcitabine in PDAC.
METHODS: Human PDAC cell lines (Panc-1 and AsPC-1) and PDAC stem
cells (CD133) were used in in vitro experiments. Also, a PDAC xenograft mice
model was established using PDAC cell lines (Panc-1 and AsPC-1) and PDAC
stem cells (CD133). Treatment groups were divided as follows; control,
Gemcitabine alone, GV 1001 alone and Gemcitabine and GV 1001 combination.
The changes of weight and tumor size were evaluated in regular intervals before
and after the treatment. The inflammatory cytokines (IL-6, TNF-, INF-),
leptin and ghrelin were measured from the serum of xenograft PDAC mice
model.
RESULTS: In vitro experiments: GV1001 alone did not affect the proliferation of
PDAC cells.
Almost 100% of the population of each PDAC cell line was positive for
Epithelial Specific Antigen (ESA, Epithelial Cellular Adhesion Molecule). The
positive results in PDAC cells ranged from as few as 0.5% to as many as 3% for
ESACD133 cells.
In vivo experiments: Mean tumor volume and size were decreased in treatment of
Gemcitabine only group and Gemcitabine with GV 1001 group, and there were
no significant differences between the two groups. However, Gemcitabine only or
Gemcitabine with GV 1001 treatment groups had significantly small tumor size
and volume compared to control group (P 5 0.001). Interestingly, there was
significant difference in mean body weight between the groups with
Gemcitabine only vs. Gemcitabine with GV 1001 combination groups. Mice of
Gemcitabine with GV 1001 treatment group did not have significant weight loss
compared to Gemcitabine only group although they have decreased tumor size
and volume. There was no mortality of mice until the end of the treatment.
CONCLUSION: GV1001 showed beneficial effects combined with Gemcitabine
in the PDAC xenograft mice model, preventing emaciation and increasing antiinflammatory effects. Moreover, GV 1001 combined with Gemcitabine treatment
showed significant loss of fibrosis in tumor tissue. Therefore, further investigation of GV1001s effect may give us useful insights to understand the biology of
PDAC progression and the synergistic effects of anti-cancer drug delivery in
PDAC treatment.
Disclosure of Interest: None declared
P0097 PRDX1 PROMOTES PANCREATIC CANCER CELL MOTILITY
AND INVASION BY MODULATING P38 MAPK ACTIVITY
K. Taniuchi1,*, M. Furihata1, S. Iwasaki1, S. Shimizu1, T. Shimizu1, M. Saito1,
T. Saibara1
1
Kochi Medical School, Kochi University, Nankoku, Japan
Contact E-mail Address: ktaniuchi@kochi-u.ac.jp
INTRODUCTION: Previous reports describe that Prdx1 is an antioxidant
enzyme that participates in the regulation of hydrogen peroxide-mediated
signal transduction, and is also implicated in the immune response, cell proliferation, differentiation, and apoptosis. Prdx1 interacts with apoptosis signalregulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase
kinase kinase (MAPKKK) family that activates both MKK4/MKK7-JNK and
MKK3/MKK6-p38 MAPK signaling cascades, via the thioredoxin-binding
domain of ASK1; the redox-sensitive catalytic activity of Prdx1 is required for
the interaction with ASK1.
AIMS & METHODS: Pancreatic ductal adenocarcinoma (PDAC) is among the
deadliest cancers because PDAC cells are highly invasive, they easily invade
surrounding tissues, and they metastasize at an early stage. Since the role of
Prdx1 in migration and invasion of cancer cells, including pancreatic cancer
cells, has not been reported, the aim of this study was to investigate the role of
Prdx1 in invasiveness of pancreatic cancer cells. This study describes new and
unique findings regarding the molecule Prdx1.
RESULTS: Prdx1 plays a role in promoting cell motility and invasion by regulating the activity of p38 MAPK, a member of the MAPK family protein. Prdx1
interacts with active forms of p38 MAPK, and complexes of Prdx1 and phosphorylated p38 MAPK localize at the leading edges of migrating PDAC cells.
Suppression of Prdx1 decreases active p38 MAPK and inhibits cell motility and
invasion. Treatment of PDAC cells with a p38 MAPK inhibitor decreases invasiveness. The peroxidase activity of Prdx1 was likely not associated with cell
motility and invasion in PDAC. Thus, Prdx1-dependent promotion of cell motility and invasion is likely associated with increased active p38 MAPK.
Suppression of Prdx1 inhibits membrane ruffling and protrusions and decreases
peripheral actin structures in membrane protrusions. The p38 MAPK inhibitor

A157
also inhibits the formation of membrane protrusions via inhibition of accumulation of Prdx1 in cell protrusions.
CONCLUSION: Prdx1 regulates actin-cytoskeleton rearrangements at membrane protrusions through modulation of the activity of p38 MAPK, which in
turn promotes pancreatic cancer cell motility and invasion. Inhibition of binding
of Prdx1 with active p38 MAPK may be effective for targeted molecular therapy,
because any such therapy would inhibit the formation of cell protrusions and
consequently limit cell motility and invasion of pancreatic cancer cells.
Disclosure of Interest: None declared
P0098 TIME-RESTRICTED ACTIVATION OF PROTEIN KINASE D2
DIRECTS VASCULOGENESIS DURING MOUSE EMBRYONIC
STEM CELL DIFFERENTIATION
M. Muller1,*, J. Schroer1, N. Azoitei1, F. Genze2, A. Illing1, T. Seufferlein1,
S. Liebau3, A. Kleger1
1
Department of Gastroenterology, 2Department of Urology, Universitatsklinikum
Ulm, Ulm, 3Institute of Anatomy, Universitat Tubingen, Tubingen, Germany
INTRODUCTION: The protein kinase D (PKD) isoenzymes PKD1, -2, and -3,
are prominent downstream targets of PKCs and phospholipase D in various
biological systems. Recent data from our laboratory identified PKD isoforms
as novel, essential mediators of tumour cell-endothelial cell communication but
also as regulators of tumour cell motility and metastasis formation. The role of
PKD isoforms during vascular development remains elusive.
AIMS & METHODS: In the current study, we aimed to dissect the contribution
of PKDs to vasculogenesis and angiogenesis in early embryonic development
using mouse embryonic stem (ES) cells as bona fide tool.
RESULTS: First, we identified Protein Kinase D2 as the predominant isoform in
undifferentiated ES cells leading us to particularly focus on this isoform. Timerestricted PKD2 activation using an inducible knock-in allele in differentiating
mouse ES cells prevented cardiac mesoderm but activated a vascular differentiation program as shown by gene and protein regulation. Interestingly, the proliferative capacity is strongly diminished as a consequence of forced PKD2
expression. Finally, we aimed to underpin our findings in two independent
in vivo models: First, embryoid bodies were transplanted on the chorioallantois
membrane (CAM) of fertilised chicken eggs, a widely used model to study proand anti-angiogenesis. In line, with our in vitro data pronounced vessel formation
was evident in the tumour-like structures arising at day 4 of the CAM assay.
Second, we used the teratoma assay and induced PKD2 in immunodeficient mice
during teratoma formation. While there was no difference in teratoma weight or
size, a strong increase of CD31 expression as an indicator of vasculogenesis was
observed in teratoma lysates.
CONCLUSION: Our data obtained in murine ES cells demonstrate that PKD2
contributes to the regulation of angiogenesis during early development and
ascribes a vascular fate in two independent embryonic tumorgenesis models.
Disclosure of Interest: None declared
P0099 GENISTEIN POTENTIATES THE ANTITUMOR EFFECT OF 5FLUOROURACIL BY INDUCING APOPTOSIS AND AUTOPHAGY
IN HUMAN PANCREATIC CANCER CELLS
R. Suzuki1,2,*, Y. Kang3, D. Roife3, X. Li3, J.B. Fleming3
1
Gastroenterology and Rheumatology, Fukushima Medical University School of
Medicine, Fukushima, Japan, 2Gastroenterology, Hepatology and Nutrition,
3
Surgical Oncology, UT MD Anderson Cancer Center, Houston, United States
Contact E-mail Address: rs197857@gmail.com
INTRODUCTION: Although 5-fluorouracil (5-FU)-based combination chemotherapy (e.g. FOLFIRINOX) has demonstrated effectiveness against pancreatic cancer, novel therapeutic strategies must be developed to enhance increase the
therapeutic window of these cytotoxic agents. Genistein is a soy-derived isoflavone with pleiotropic biologic effects that can enhance the antitumor effect of
chemotherapeutic agents.1-3
AIMS & METHODS: To understand how genistein potentiates the antitumor
effects of chemotherapeutic agents, we examined apoptosis and autophagy in the
MIA PaCa-2 human pancreatic cancer cell line and subcutaneous pancreatic
tumor xenograft model. Apoptosis was evaluated using DNA fragmentation
assay and Western blot of poly (ADP ribose) polymerase and caspase-3.
Meanwhile, autophagy was evaluated using Western blot of microtubule-associated protein light chain 3 (LC3)-I/II and fluorescent microscopy observation of
green fluorescent protein-LC3B puncta and acidic vesicular organelle formation.
In animal study, induction of apoptosis and autophagy was assessed by TUNEL
assay and immunohistochemistry staining of LC3B, respectively.
RESULTS: We observed that genistein enhanced 5-FU-induced apoptosis by
down-regulating B-cell lymphoma 2 (bcl-2). Moreover, gensitein enhanced 5FU-induced autophagy and triggered autophagic cell death by decreasing bcl-2
while inducing beclin-1. In vivo treatment studies demonstrated that the combination of 5-FU and genistein significantly decreased final tumor volume comparing to genistein alone or 5-FU alone by inducing apoptosis as well as autophagy.
CONCLUSION: Genistein can potentiate the antitumor effect of 5-FU by inducing apoptotic cell death as well as autophagic cell death. These results demonstrate the potential of genistein as an adjuvant therapeutic agent to enhance the
antitumor effects of current first-line cytotoxic agents against pancreatic cancer.
REFERENCES
1. Banerjee S, Zhang Y, Ali S, et al. Molecular evidence for increased antitumor
activity of gemcitabine by genistein in vitro and in vivo using an orthotopic
model of pancreatic cancer. Cancer Res 2005; 65: 9064-9072.
2. Banerjee S, Zhang Y, Wang Z, et al. In vitro and in vivo molecular evidence of
genistein action in augmenting the efficacy of cisplatin in pancreatic cancer. Int J
Cancer 2007; 120: 906-917.

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3. Hwang KA, Kang NH, Yi BR, et al. Genistein, a soy phytoestrogen, prevents
the growth of BG-1 ovarian cancer cells induced by 17beta-estradiol or bisphenol
A via the inhibition of cell cycle progression. Int J Oncol 2013; 42: 733-740.
Disclosure of Interest: None declared
P0100 CHARACTERIZATION OF THE NERVE-STELLATE
INTERACTIONS IN PANCREATIC CANCER

CELL

S. Teller1,*, D. Dischl1, R. Go1, I.E. Demir1, H. Friess1, G.O. Ceyhan1


1
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU Munchen,
Munchen, Germany
Contact E-mail Address: Steffen. Teller@tum.de
INTRODUCTION: Pancreatic stellate cells (PSC) emerged in recent years as the
main actor for the generation of pancreatic fibrosis in pancreatic cancer (PCa).
Subsequent to their activation, PSC start to proliferate, migrate, and produce
several extracellular matrix (ECM) components as well as cytokines. In this
context, neural invasion and pancreatic neuroplasticity is most prominent in
the desmoplastic areas.
AIMS & METHODS: The present study aims at elucidating the characterisation
of the interactions of nerves, carcinoma cells and PSC and the potential impact of
PSC during the generation of neuropathic alterations in PCa.
PSC were isolated from Wistar rats and cultivated under hypoxia, stimulated
with TGF or left untreated as controls. After cell lysis, the expression of neurotrophic factors and their receptors (GFR) was determined by Immunoblotting
and by qRT-PCR. For neuroplasticity assays, dorsal root ganglia (DRG) were
isolated from newborn Wistar rats and treated with supernatants of quiescent
and activated PSC. Changes in neurite length, axonal branching, perikaryonal
diameter and glial density were determined.
RESULTS: PSC produce neurotrophic factors as well as their receptors and alter
the expression pattern of neurturin and artemin after activation towards their
active forms, whereas the GFR expression remains unchanged. After treatment
of PSC with hypoxia or TGF, PSC are activated. Cell culture supernatants of
activated PSC lead to an increased neurite and glial density in isolated DRG.
CONCLUSION: Activated PSC alter their expression pattern of neurotrophic
factors, influence neuroplasticity of isolated DRG and therefore may play a
seminal role in the generation of pancreatic neuropathy and pain in PCa.
Disclosure of Interest: None declared
P0101 THE METASTASIS-PROMOTING ROLES OF EXTRAVASATED
PLATELET AGGREGATION IN PANCREATIC CANCER AND
STROMA
T. Miyashita1,*, H. Tajima1, I. Makino1, H. Nakagawara1, H. Kitagawa1,
T. Ohta1
1
Department of Gastroenterological Surgery, KANAZAWA UNIVERSITY
HOSPITAL, Kanazawa, Japan
Contact E-mail Address: tomoharumiya@gmail.com
INTRODUCTION: The last decade has focused attention on the central role of
platelets interacting with tumor cells and the immune system in promoting tumor
progression and distant spread through release of growth factors, such as transforming growth factor beta (TGF-), vascular endothelial growth factor A
(VEGF-A) and plasminogen activator inhibitor-1 (PAI-1), into the tumor microenvironment. We focused on the potential metastasis-promoting role of extravasated platelet aggregation (EPA) in pancreatic cancer and stroma.
AIMS & METHODS: Resected pancreatic cancer specimens from 40 patients
were used in this study. To examine the expression and localization of platelet
aggregation in the epithelial-mesenchymal transition (EMT) region in cancer and
stroma, CD42b, Snail1 and E-cadherin were assessed using immunohistochemistry. We determined the correlation of these expressed proteins with clinical
features and overall survival.
RESULTS: CD42b expression was detected at the invasive front of the tumor,
which was in 73% of the EMT portion, but not in the region of tubular formation. Increased Snail1 and loss of E-cadherin expression were noted in 85% and
75% of the EMT portion, respectively. There was a significant correlation
between CD42b and Snail1 expression (p 0.02) and CD42b and loss of Ecadherin expression (p 0.008). No prognostic impact of CD42b, Snail1 or
loss of E-cadherin expression on overall survival was identified using Kaplan
Meier survival analysis.
CONCLUSION: We demonstrate that EPA is associated with the first step in the
formation of the EMT. These data suggest a potential role for antiplatelet agents
to suppress EMT and metastasis by changing the tumor microenvironment.
Disclosure of Interest: None declared
P0102 CATHEPSIN B AND D DRIVE THE FIBROGENIC POTENTIAL OF
PANCREATIC STELLATE CELLS AND MODULATE THE STROMAL
COMPARTMENT IN PANCREATIC DUCTAL ADENOCARCINOMA
(PDAC)
U.M. Mahajan1,*, T. Schwaiger1, F.-U. Weiss1, M. Lohr2, M.M. Lerch1,
J. Mayerle1
1
Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University,
Greifswald, Greifswald, Germany, 2CLINTEC, Karolinska Institutet, Stockholm,
Sweden
Contact E-mail Address: mayerle@uni-greifswald.de
INTRODUCTION: Remodelled extracellular matrix (ECM) has been implicated
in the resistance of cancer cells to chemotherapy. Stromal-cell-derived proteases,
e.g. cathepsins, are involved in tumorigenesis and tissue invasion but their role in
regulating pancreatic stellate cells (PSCs) and thus ECM formation is unknown.

We studied whether cathepsin B and D, lysosomal proteases both highly


expressed in pancreatic cancer, contribute to fibrogenesis by activating PSCs.
AIMS & METHODS: Cathepsin B and D activity was measured in serum of
PDAC patients. PSCs were isolated by Nycodenz-gradient from mouse pancreas
for immunoblotting and immunofluorescence staining. TGF1 was measured
using ELISA and LC/MS-mass-spectroscopy.
RESULTS: Serum cathepsin D activity was increased and correlated with poor
survival of patients with PDAC. Expression of cathepsin B and D was negligible
in quiescent PSCs but increased in parallel with PSC trans-differentiation to
myofibroblasts. Silencing or inhibition (Pepstatin, CA074Me) of cathepsin B
and D decreased phenotypic markers of PSC activation. Moreover, latent
TGF1 was cleaved to TGF1 leading to an increase in the PSC fibrogenic
potential in a time-dependent manner. Cathepsin D activated cathepsin B and
both acted directly on latent TGFb1. TGFb1 increased proliferation, invasion
and extracellular matrix remodedelling of PSCs.
CONCLUSION: We show that Cathepsin D activity correlates with poor survival in PDAC patients. Cathepsin B and D expression increases during PSC
activation in vitro and both modulate ECM-formation via proteolytic cleavage
of latent TGF1. Via PSC activation cathepsins B and D regulate fibrogenesis
and stroma development in pancreatic cancer and therefore represent a promising treatment target.
Disclosure of Interest: None declared
P0103 SRC/STAT3 SIGNALING PATHWAYS ARE INVOLVED IN KAI1REDUCED VEGF-C DOWN-REGULATION IN PANCREATIC
CANCER
X. Guo1,*, X. Liu1
1
General Hospital of Shenyang Military Area, Shenyang, China
Contact E-mail Address: guoxiaozhong1962@163.com
INTRODUCTION: To investigate the signaling pathways involved inKAI1reduced vascular endothelial growth factor C (VEGF-C) down-regulation and
lymphatic metastasis in MIA PaCa-2 pancreatic cancer cells.
AIMS & METHODS: MIA PaCa-2 pancreatic cancer cells were transfected with
KAI1 by liposomes. The expression level of VEGF-C was assessed by Western
blot. Levels of vascular endothelial growth factor (VEGF)-C secreted by cells
measured by enzyme-linked immunosorbent assay (ELISA). Src and STAT3
phosphorylation was detected by Western blot. Signaling transduction inhibitors,
PP2 and AG490, were used to block Src and STAT3 signaling pathways,
respectively.
RESULTS: KAI1 overexpression decreased VEGF-C expression and inhibited
Src and STAT3 phosphorylation. PP2 pretreatment efficiently reversed the upregulation of Src and STAT3 phosphorylation and VEGF-C expression. AG490
pretreatment efficiently reversed the upregulation of STAT3 phosphorylation
and VEGF-C expression, but not the upregulation in Src phosphorylation.
CONCLUSION: This study identified that Src/STAT3 signaling pathways were
involved in KAI1-reduced VEGF-C down-regulation and suggested their important roles in lymphatic metastasis in pancreatic cancer.
REFERENCES
1 Qian CN, Berghuis B, Tsarfaty G, et al. Preparing the "soil": the primary tumor
induces vasculature reorganization in the sentinel lymph node before the arrival
of metastatic cancer cells. Cancer Res 2006; 66: 10365-10376.
2 Stacker SA, Achen MG, Jussila L, et al. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer 2002; 2: 573-583.
3 Miranti CK. Controlling cell surface dynamics and signaling: how CD82/KAI1
suppresses metastasis. Cell Signal 2009; 21: 196-211.
4 Cheng P, Jin G, Hu X, et al. Analysis of tumor-induced lymphangiogenesis and
lymphatic vessel invasion of pancreatic carcinoma in the peripheral nerve plexus.
Cancer Sci 2012; 103: 1756-1763.
5 Liu X, Guo XZ, Zhang WW, et al. KAI1 inhibits HGF-induced invasion of
pancreatic cancer by sphingosine kinase activity. Hepatobiliary Pancreat Dis Int
2011; 10: 201-208.
6 Stacker SA and Achen MG. The VEGF signaling pathway in cancer: the road
ahead. Chin J Cancer 2013; 32: 297-302.
7 Ischenko I, Seeliger H, Camaj P, et al. Src tyrosine kinase inhibition suppresses
lymphangiogenesis in vitro and in vivo. Curr Cancer Drug Targets 2010; 10: 546553.
Disclosure of Interest: None declared
P0104 TP53 CODON 72 AND MDM2 SNP309 POLYMORPHISMS IN
PANCREATIC CANCER
Y. Hori1,*, K. Miyabe1, M. Yoshida2, T. Nakazawa1, K. Hayashi1, I. Naitoh1,
S. Shimizu1, H. Kondo1, Y. Nishi1, S. Umemura1, A. Kato1, H. Ohara3, T. Joh1
1
Department of Gastroenterology and Metabolism, Nagoya City University
Graduate School of Medical Sciences, Nagoya, Japan, Nagoya, Japan, 2Division of
Digestive Diseases, Emory University School of Medicine, Atlanta, United States,
3
Department of Community-based Medical Education, Nagoya City University
Graduate School of Medical Sciences, Nagoya, Japan, Nagoya, Japan
Contact E-mail Address: horinei_40847357@yahoo.co.jp
INTRODUCTION: Single-nucleotide polymorphisms (SNPs) of TP53 gene
(codon 72, rs1042522) and mouse double minute 2 (MDM2) promoter
(SNP309, rs2279744), have been associated with increased risk of various
human cancers. However, few studies have analyzed these polymorphisms in
pancreatic cancer.
AIMS & METHODS: We investigated TP53 codon 72 and MDM2 SNP 309
polymorphisms in 32 patients with pancreatic ductal carcinoma (PDAC) and 21
patients with controls (non-neoplastic pancreatic epithelium attached to resected
specimens without pancreatic disease), using paraffin-embedded tissue sections.

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RESULTS: The frequencies of TP53 codon72 arginine (Arg)/Arg, Arg/proline
(Pro), and Pro/Pro were 6, 28, and 66% in PDAC and 29, 52, and 19% in
controls, respectively. The ratio of Pro/Pro genotype to Arg/Arg genotype was
significantly higher in PDAC than controls [p 0.004, adjusted odds ratio
(OR) 15.75; 95% confidence interval (CI) 2.30-107.9]. On the other hand,
those of MDM2 SNP309 TT, TG, and GG genotypes were 22, 44, and 34% in
PDAC and 38, 33, and 29% controls, respectively. There were no significant
differences among them.
CONCLUSION: This is the first study to evaluated the significance of TP 53
codon 72 and MDM2 SNP 309 polymorphism using paraffin-embedded pancreas tissue. The proportion of Pro/Pro genotype was significantly higher in
PDAC, while the proportion did not differ in MDM2. This finding indicates
that TP53 codon 72 polymorphism is likely to be correlated with increased risk
for pancreatic cancer.
REFERENCES
Grochola LF, et al. Single-nucleotide polymorphisms in the p53 signaling pathway cold spring. Harb Perspect Biol 2010; 2: a001032.
Disclosure of Interest: None declared
P0105 POSTRANSCRIPTIONAL REGULATION OF HO-1 AND COX-2
EXPRESSION AS NOVEL THERAPEUTIC TARGETS IN
PANCREATIC CANCER
A. Jakstaite1,*, Z. Dambrauskas1, A. Gulbinas1, G. Barauskas2, J. Pundzius2
1
Institute for Research of Digestive System, 2Department of Surgery,
LITHUANIAN UNIVERSITY OF HEALTH SCIENCES, Kaunas, Lithuania
Contact E-mail Address: zilvinas.dambrauskas@gmail.com
INTRODUCTION: Pancreatic cancer is a rapidly invasive, metastatic tumor,
which is resistant to standard therapies, thus only 1015% of patients are candidates for potentially curative surgery. None of the currently available chemotherapeutic agents have an objective response rate of over 10%. Recent studies show
that RNA binding proteins regulate post transcriptional gene expression and
play a critical role in RNA stability andtranslation, thus they potentially could
become an important group of new therapeutic targets.
AIMS & METHODS: We examined the association of this postranscriptional
regulation pathway (CUGBP2 and HuR) and the expression of COX-2 and HO1, which are known to be associated with inhibition of apoptosis, increased
tumor invasiveness and resistance to oxidative stress and/orchemotherapy, and
promotion of angiogenesis. Western blot analysis, immunohiostochemistry and
quantitative RT-PCR were employed to show the expression of mRNA and
protein in normal pancreas (from organ donors), cancer tissue (surgical
specimens).
RESULTS: RT-PCR analysis showed 10.3 and 14 fold lower HuR and CUGBP2
mRNA levels in pancreatic cancer compared to normal tissue (p50.05), COX-2
levels were 1.5 times higher and HO-1 expression on average was upregualted 6fold in the pancreatic cancer samples, compared to the normal pancreatic tissue
(p50.05). Western blot analysis showed very low levels of HuR and CUGBP2 in
pancreatic cancer compared with the normal tissue (p 5 0.05). Expression of
COX-2 protein levels was 2-fold higher in pancreatic cancer. Western blot analysisrevealed 3.5 times higher (p50.017) expression of HO-1 in pancreatic cancer.
CONCLUSION: The decreased or altered activity of CUGBP2 and HuR could
be associated with high chemoresistance and early dissemination of pancreatic
cancer through the HO-1 and COX-2 mediated cytoprotective and carcinogenesis
pathways. These results mandate further functional studies and evaluation of
postranscriptional regulation as a new potential therapeutic target.
Disclosure of Interest: None declared
P0106 DIAGNOSTIC VALUE OF A PANCREATIC MASS
COMPUTED TOMOGRAPHY IN PATIENTS UNDERGOING
PANCREATODUODENECTOMY FOR PRESUMED PANCREATIC
CANCER

ON

A. Gerritsen1,2,*, T.L. Bollen3, C.Y. Nio4, I.Q. Molenaar1, M.G. Dijkgraaf5, H.C.
van Santvoort6, G.J. Offerhaus7, L.A. Brosens8, K. Biermann9, E. Sieders10, K.P.
de Jong10, R.M. van Dam11, E.van der Harst12, H.van Goor13,
B.van Ramshorst14, B.A. Bonsing15, I.H. de Hingh16, M.F. Gerhards17, C.H.
van Eijck18, D.J. Gouma2, I.H. Borel Rinkes1, O.R. Busch2, M.G. Besselink2 on
behalf of the Dutch Pancreatic Cancer Group
1
Dept of Surgery, University Medical Center Utrecht, Utrecht, 2Dept of Surgery,
Academic Medical Center, Amsterdam, 3Dept of Radiology, St Antonius Hospital,
Nieuwegein, 4Dept of Radiology, 5Clinical Research Unit, Academic Medical
Center, Amsterdam, 6Department of Surgery, 7Dept of Pathology, University
Medical Center Utrecht, Utrecht, 8Dept of Pathology, Academic Medical Center,
Amsterdam, 9Dept of Pathology, Erasmus Medical Center, Rotterdam, 10Dept of
Surgery, University Medical Center Groningen, Groningen, 11Dept of Surgery,
Maastricht University Medical Center, Maastricht, 12Dept of Surgery, Maasstad
Ziekenhuis, Rotterdam, 13Dept of Surgery, Radboud University Medical Center,
Nijmegen, 14Dept of Surgery, St Antonius Hospital, Nieuwegein, 15Dept of
Surgery, Leiden University Medical Center, Leiden, 16Dept of Surgery, Catharina
Hospital, Eindhoven, 17Dept of Surgery, OLVG, Amsterdam, 18Dept of Surgery,
Erasmus Medical Center, Rotterdam, Netherlands
Contact E-mail Address: a.gerritsen@dpcg.nl
INTRODUCTION: Preoperative differentiation between malignant and benign
pancreatic tumors can be difficult. Consequently, some 5-14% of patients undergoing pancreatoduodenectomy for suspected malignancy are ultimately diagnosed with benign disease.
AIMS & METHODS: We aimed to determine the diagnostic value of a pancreatic mass on computed tomography (CT) in patients with presumed pancreatic
cancer and the additional value of reassessment by expert-radiologists.

We performed a multicenter retrospective cohort study in 1629 consecutive


patients undergoing pancreatoduodenectomy for suspected malignancy (20032010). All patients with unexpected benign disease at postoperative pathological
diagnosis were included in a 1:3 ratio with random patients with (pre)malignant
disease. The preoperative CT scan was reassessed by two expert-radiologists
separately and subsequently (after defining a mass as a measurable space occupying soft tissue density, except for an enlarged papilla or focal steatosis) in
consensus.
RESULTS: 86 patients with benign and 258 patients with (pre)malignant disease
were included. A mass was reported in the original CT report in 66% of patients
versus 48% and 50% on reassessment by the two expert-radiologists, respectively. Interobserver agreement among expert-radiologists was moderate
(kappa 0.47, 95%CI 0.38-0.56); they disagreed on the presence of mass in
29% of patients. The incidence of mass decreased to 44% after consensus reading
(P50.001 vs. original report). 167/212 (79%) masses identified in the original
report proved to be malignant after pancreatoduodenectomy versus 139/150
(93%) masses identified by expert-radiologists in consensus (P50.001). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of masses identified in the original CT report were 68%, 42%, 79%, 7%,
and 67%, respectively. For masses identified by expert-radiologists in consensus
these were 54%, 87%, 98%, 12%, and 56%, respectively.
CONCLUSION: In patients with presumed pancreatic cancer, the diagnostic
value of a pancreatic mass on CT is high, whereas the absence of a mass
cannot rule out malignancy. Expert-radiologists less frequently identified a pancreatic mass as compared to the original CT-report, with doubled specificity for
malignancy.
Disclosure of Interest: A. Gerritsen Financial support for research from:
Unrestrictred grant from Ipsen Farmaceutica B. V., T. Bollen: None declared,
C. Y. Nio: None declared, I. Q. Molenaar: None declared, M. Dijkgraaf: None
declared, H. van Santvoort: None declared, G. J. Offerhaus: None declared, L.
Brosens: None declared, K. Biermann: None declared, E. Sieders: None declared,
K. de Jong: None declared, R. van Dam: None declared, E. van der Harst: None
declared, H. van Goor: None declared, B. van Ramshorst: None declared, B.
Bonsing: None declared, I. de Hingh: None declared, M. Gerhards: None
declared, C. van Eijck: None declared, D. Gouma: None declared, I. Borel
Rinkes: None declared, O. Busch: None declared, M. Besselink: None declared
P0107 FARNESOID X RECEPTOR (FXR) EXPRESSION IN HUMAN
PANCREATIC ADENOCARCINOMA: ASSOCIATIONS WITH
CLINICOPATHOLOGICAL PARAMETERS, TUMOR
PROLIFERATIVE CAPACITY, PATIENTS SURVIVAL AND
RETINOID X RECEPTORS (RXRS) EXPRESSION
I. Koutsounas1,*, K. Giaginis2, A. Zizi3, G. Kouraklis4, E. Patsouris1,
S. Theocharis1
1
First Department of Pathology, Medical School, National and Kapodistrian
University of Athens, Athens, 22Department of Food Science and Nutrition, School
of the Environment, University of the Aegean, Myrina, Lemnos, 3Department of
Pathology, Tzanion General Hospital, Piraeus, 42nd Department of Propedeutic
Surgery, Laikon General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
Contact E-mail Address: john_koutsounas@yahoo.gr
INTRODUCTION: Farnesoid X Receptor (FXR) belongs to the group of
nuclear receptors (NRs). As a transcription factor, it binds to DNA either as a
monomer or as an heterodimer with Retinoid X Receptor (RXR). FXR affects
several metabolic pathways, including development of atherosclerosis, intestinal
bacterial growth and liver regeneration. Additionally, FXR is involved in the
pathogenesis of cholestatic diseases, non-alcoholic fatty liver disease, inflammatory bowel disease and cancer. Although many studies have investigated FXR
expression in various cancer types, a few data exist, so far, on the clinical significance of this receptor in pancreatic cancer.
AIMS & METHODS: The expression levels of FXR and its heterodimeric partners RXR-, - and - were assessed immunohistochemically on histopathological samples obtained from pancreatic adenocarcinoma patients, and associated
with various clinicopathological parameters, tumor proliferative capacity (Ki-67
labeling index), and patients survival.
RESULTS: Moderate/strong FXR expression was noted in 27 (49.1%) out of 55
pancreatic adenocarcinoma cases, being at borderline level associated with earlier
histopathological stage (p 0.054). Moderate/strong FXR/RXR- expression
was significantly correlated with low tumour histopathological grade of differentiation (p 0.017). Moderate/strong FXR/RXR- and FXR/RXR- expression was significantly correlated with smaller tumor size (p 0.037, p 0.005,
respectively) and earlier histopathological stage (p 0.017, p 0.004, respectively), while moderate/strong FXR/RXR- expresssion was also significantly
correlated with the absence of lymph node metastases (p 0.018).
Furthermore, patients presenting moderate/strong FXR expression showed significantly longer survival times compared to those with negative/weak (log-rank
test, p 0.013). In multivariate analysis, FXR expression and histopathological
stage were identified as independent prognostic factors for patients survival
(Cox-regression analysis, p 0.044 and p50.001). Patients presenting moderate/strong FXR/RXR- or FXR/RXR- expression showed significantly
longer survival times compared to those with negative/weak (log-rank test,
p 0.021, p50.001, respectively).
CONCLUSION: FXR, FXR/RXR-, FXR/RXR- and FXR/RXR- expression levels in pancreatic cancer are associated with important histopathological
parameters and better patients outcome.
Disclosure of Interest: None declared

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P0108 CLINICAL SIGNIFICANCE OF PREGNANE X RECEPTOR (PXR)


AND RETINOID X RECEPTORS (RXRS) EXPRESSION IN HUMAN
PANCREATIC ADENOCARCINOMA: AN
IMMUNOHISTOCHEMICAL STUDY
I. Koutsounas1,*, K. Giaginis2, A. Zizi3, G. Kouraklis4, E. Patsouris1,
S. Theocharis1
1
First Department of Pathology, Medical School, National and Kapodistrian
University of Athens, Athens, 2Department of Food Science and Nutrition, School
of the Environment, University of the Aegean, Myrina, Lemnos, 3Department of
Pathology, Tzanion General Hospital, Piraeus, 42nd Department of Propedeutic
Surgery, Laikon General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
Contact E-mail Address: john_koutsounas@yahoo.gr
INTRODUCTION: Pregnane X Receptor (PXR) is a member of the nuclear
receptor (NR) superfamily, expressed mainly in the liver and intestine, exerting
its transcriptional regulation by binding to DNA response elements as an heterodimer with Retinoid X Receptor (RXR). PXR is involved in the homeostasis of
numerous endobiotics, as well as in inflammatory bowel disease, bone homeostasis, liver steatosis and antifibrogenesis. Additionally, PXR has a multifactorial impact on cancer, either by directly affecting cell proliferation and apoptosis
or by inducing chemotherapy resistance. Even though many studies have investigated PXR implication in various types of cancer, data on the clinical significance of this receptor in pancreatic cancer are still very limited.
AIMS & METHODS: The expression levels of PXR and its heterodimeric partners RXR-, - and - were assessed immunohistochemically on histopathological samples obtained from pancreatic adenocarcinoma patients, and associated
with various clinicopathological parameters, tumor proliferative capacity (Ki-67
labeling index), and patients survival.
RESULTS: Moderate/strong PXR expression was noted in 24 (43.6%) out of 55
pancreatic adenocarcinoma cases, being positively correlated with tumour histopathological grade of differentiation (p 0.023). Moderate/strong PXR/RXR-
and PXR/RXR- expression was significantly correlated with smaller tumor size
(p 0.005, p 0.012, respectively) and earlier histopathological stage (p 0.003,
p 0.014, respectively). Additionally, pancreatic adenocarcinoma patients presenting moderate/strong PXR/RXR- or PXR/RXR- expression showed longer
survival times compared to those with negative/weak, at non significant levels
though (log-rank test, p 0.278, p 0.053, respectively).
CONCLUSION: In our study, PXR and PXR/RXRs expression was for the first
time examined in human pancreatic cancer cases, being correlated with favourable histopathological parameters and associated with longer patients survival.
Disclosure of Interest: None declared
P0109 UROKINASE-TYPE
PLASMINOGEN
ACTIVATOR
POSSIBLE PANCREATIC CANCER DIAGNOSTIC AND
PROGNOSTIC MARKER?

(UPA)-

K. Winter1,*, M. Pawlowski2, P. Szczes niak3, A. Ga siorowska1, D. OrszulakMichalak3, E. Malecka-Panas1


1
Department of Digestive Tract Diseases, 2Department of Diabetes and Internal
Diseases, 3Biopharmacy Institution, Medical University of Lodz, Lodz, Poland
Contact E-mail Address: katarzyna.winter@vp.pl
INTRODUCTION: Urokinase-Type Plasminogen Activator (uPA) is a serine
proteinase, which transforms inactive plasminogen to the active plasmin. UPA
is involved in cancer progression, growth and metastasis through degradation of
extracellular matrix (ECM), growth factors FGF, IGF, VEGF release and cellular migration activation. UPA overexpression was confirmed in many human
cancers including pancreatic cancer and was connected to the poor survival. UPA
expression was found in the vessels of tumor stroma, which suggests that it can be
detected in serum.
AIMS & METHODS: The aim of this study was to evaluate the uPA serum
concentration in patients with pancreatic cancer (PC) and chronic pancreatitis
(CP) in order to determinate its possible diagnostic and prognostic value.
The study group included 90 patients: 40 with pancreatic cancer, 30 with chronic
pancreatitis and 20 healthy individuals (control group). Serum level of uPA was
analyzed using an enzyme-linked immunosorbent assay (ELISA). Pancreatic
cancers were classified according to the TNM classification. Criteria for resectability included: absence of distant metastases, lack of evidence of tumor involvement of major arteries, and (if there is venous invasion) a suitable segment of
portal vein (above) and superior mesenteric vein (below) the site of venous
involvement to allow for venous reconstruction.
RESULTS: We revealed threefold increase in uPA serum level in patients with
pancreatic cancer (3.23ng/ml) and twofold increase in patients with chronic pancreatitis (2.18ng/ml), with was significant higher than in control group (1.01ng/
ml) (p50.05 PC vs CP; PC vs control; CP vs control). We observed significantly
higher level of uPA in patients with pancreatic cancer and CA19-94 500 IU/l
compared to patients with CA19-9 5500 IU/l 3.98 ng/ml vs 2.8 ng/ml
(p50.03). We noticed lower level of uPA in patients with resectable pancreatic
cancer: 2.28 ng/ml vs 3.4 ng/ml in patients with unresectable pancreatic cancer
but difference was not significant (p 0.14). In addition there was no correlation
between uPA level and pancreatic cancer stage. We found the significant correlation between high serum uPA concentration and shorter survival (p50.05); mean
survival in patients with uPA 4 2 was 181 days 155.11 and in patients with
uPA 5 2 ng/ml- 335 days 313.75 (p 0.04).
CONCLUSION: The results suggest the possible use of serum uPA in pancreatic
cancer diagnosis and differentiation from chronic pancreatitis. Significant correlation between serum uPA concentration and decreased survival, may indicate on
the role of uPA as a prognostic marker in pancreatic cancer.
Disclosure of Interest: None declared

P0110 PARTIAL COVERED BILIARY METALLIC STENT WITH/


WITHOUT DUODENUM METAL STENT AND NEOADJUVANT
CHEMORADIATION THERAPY PROVIDES SYMPTOMATIC
BORDERLINE RESECTABLE PANCREATIC HEAD CANCER WITH A
CHANCE FOR R0 SURGERY
Y. Sekino1, K. Kubota1, K. Hosono1, A. Nakajima1, Y. Fujita1,*
1
Gastroenterology, Yokohama City University, Yokohama, Japan
Contact E-mail Address: kubotak@yokohama-cu.ac.jp
INTRODUCTION: Neoadjuvant chemradiationtherapy (NACRT) may lead to
successful margin-negative resection (R0) in pts with borderline resectable pancreatic head cancer (BRPHC). NACRT using a covered metallic biliary stent has
been attempted in pts with BRPHC, however, the efficacy of this therapy with/
without metallic duodenal stent (MDS) and the influence of using partially covered metallic stent (PCMS) for its delivery in the treatment of BRPHC has not
been evaluated.
AIMS & METHODS: To evaluate the efficacy of and complications associated
with the use of PCMS with/without MDS during NACRT and the surgical
period.
We reviewed the outcomes of consecutive pts with BRPHC had histopathologically proven pancreatic adenocarcinoma, who presented with symptomatic biliary obstruction, and divided the patients chronologically, in terms of the period
of stent placement into two groups: group A; plastic stent (PS) deployment plus
NACRT between August 2009 and October 2010; group B; prospectively PCMS
deployment with/without MDS plus NACRT between November 2010 and
December 2013. The pts were categorized as having borderline resectable
cancer based on the NCCN clinical practice guideline established in 2013.
Data on the pts demographics, complications, non re-intervention rate (NRR),
surgical time, operative blood loss, length of hospital stay, complications after
resection, the rate of R0 and prognosis were studied. Safe R0 surgery was defined
as R0 surgery without the need for re-intervention or postoperative
complications.
RESULTS: There were a total of 57 pts with LAPHC (group A and B: 29 and 28
pts, respectively). The median time from stent placement to surgery in the overall
subject population were 130.5 Days in group A and 130.7 days in group B. MDS
was deployed in one pts with group A and three pts with group B. NPR for the 1st
30 days in group A (PS) and B (PCMS) were 48% and 96%, respectively. NPR
for the 2nd 30 days in group A and B were 23% and 92%, respectively. NPR for
the 3rd 30 days in group A and B were 15% and 92%, respectively. Regarding
NPR, PCMS is superior to group using PS (p50.05). No severe complications
including gastrointestinal bleeding after irradiation were noted in any pts. There
were no significant differences between groups regarding surgical time, operative
blood loss, length of hospital stay. The rates of achievement of R0 surgery in
groups A and B were 68.9% (20/29) and 89.3% (25/28), respectively. The PCMS
and MDS did not interfere with the conduct of the NACRT and pancreaticoduodenectomy in any patients. The rates of achievement of safe R0 surgery in
groups A and B were 10.3% (3/29) and 70.4% (20/28), respectively (p50.05).
Multivariate analysis showed that odds ratio for safe R0 surgery was 18.426
(p50.0001) for PCMS placement.
CONCLUSION: Insertion of PCMS should be considered for the relief of biliary
and/or duodenum obstruction in pts with BRPHC scheduled to receive NACRT,
in view of the minimize need for re-intervention for recurrent biliary obstruction,
and a potentially high rate of achievement of safe R0 surgery, as compared to the
results obtained with PS deployment.
Disclosure of Interest: None declared
P0111 BRANCH DUCT INTRADUCTAL PAPILLARY NEOPLASMS
WITH CYSTS LARGER THAN 3 CM WITHOUT HIGH-RISK
STIGMATA: SHOULD WE RESECT THESE NEOPLASMS OR NOT?
K.T. Lee1,*, M.J. Lee1, Y.J. Lee1, J.K. Lee1, K.H. Lee1
1
Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: happymap@skku.edu
INTRODUCTION: In 2012, revised international consensus guidelines were
published, and they suggested a more conservative approach for the management
of BD-IPMN with cysts larger than 3 cm without other high-risk stigmata.
But, several recent studies have challenged the safety of this guideline. The aim of
this study is to compare the prognosis in patients who underwent surgical resection because of the cyst size and the prognosis in patients who chose close
observation.
AIMS & METHODS: We retrospectively reviewed the data of 48 BD-IPMN
patients with a cyst size  3cm, without any other suspicious features, between
March 1995 and October 2013. We divided the patients into 2 groups (21 patients
underwent surgery, and 27 patients chose close observation), and compared the
patients characteristics and prognosis.
RESULTS: The patients in the observation group were older than the patients in
the surgery group and they had severe co-morbidities (2 ACE-27 co-morbidity
score (moderate)). None of the patients developed new worrisome features or
high-risk stigmata during the follow-up period, and the causes of death were
not related to IPMN. Among the 21 patients who underwent resection; 4 patients
(19%) were diagnosed with invasive carcinoma, and 1 patient (4.8%) was diagnosed with intestinal type of invasive carcinoma. No surgery-related death and
major postoperative complications were noted.
CONCLUSION: While making a decision regarding the management of BDIPMN with a cyst size  3cm in the absence of high-risk stigmata, we should
consider the risk of surgery in patients, but we should not hesitate to perform
resection in surgically fit patients especially in high-volume centers with experienced surgeons.
Disclosure of Interest: None declared

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P0112 FOLLOW UP HIGH-RISK INDIVIDUALS
DETECTION OF PANCREATIC CANCER

FOR

EARLY

R. Ashida1,*, T. Ioka1, N. Ishida1, H. Sueyoshi2, R. Takada2, N. Fukutake2,


H. Uehara2, K. Katayama1
1
Departments of Cancer Survey and Gastrointestinal Oncology, 2Department of
Hepato-Biliary and Pancreato Oncology, Osaka Medical Center For Cancer And
Cardiovascular Disease, Osaka, Japan
Contact E-mail Address: rashida@goo.jp
INTRODUCTION: For the detection of pancreatic cancer in early stage, it is
important to identify high-risk individuals and follow up those patients periodically. We have started an early detection system for pancreatic cancer since 1998,
and revealed that individual with either pancreatic cyst (45mm) or dilated main
pancreatic duct (42.5mm) is high-risk for pancreatic cancer. Follow up of highrisk individuals (HRIs) with imaging tests, such as trans abdominal ultrasound
which is specialized to pancreato-billiary area (pancreatic US: pUS), endoscopic
ultrasound (EUS) and computed tomography (CT) or magnetic resonance imaging (MRI), can lead to the detection and treatment within asymptomatic
patients, however usefulness of the optimal imaging approach is not known.
AIMS & METHODS: Between June 2007 and January 2014, 535 asymptomatic
HRIs were examined periodically at single center, using pUS (every 3 or 6 month)
and CT or MRI (once a year). EUS was performed when any changes such as
hypoechoic mass, new nodule or rapid change in cyst size were detected by pUS.
ERCP was recommended for cytology when the size of cyst become bigger than
3cm or main pancreatic duct was dilated bigger than 3mm or a newly narrowed
part appeared, or the size of cyst or main pancreatic duct changed rapidly. EUSFNA was performed when an invasive nodule or hypoechoic mass was detected.
Contrast harmonic pUS/EUS was also performed if necessary.
RESULTS: Sixteen patients with pancreatic cancer have been confirmed as
malignancy during follow up (2.99% incidence rate), 8 males and 8 females
(mean age 69.1 yrs). Eight patients had an intraductal papillary mucinous
neoplasms (IPMNs) with an associated carcinoma (2: invasive, 6: non-invasive),
six had an invasive ductal adenocarcinoma, and two had ductal carcinoma in situ
(PanIN3). Mean total follow up period until the detection of cancer was 34.8
months (range 6.6 - 64 mo). Fourteen patients were asymptomatic. The number
of patients with cancer stage of 0, IA, IIA, IIB, III, was 7, 4, 2, 1 and 2, respectively. Ten cases were brought to further examination by the findings detected by
pUS, two with symptoms such as abdominal pain, one with tumor marker elevation, one with MRI finding, one with CT finding and one with EUS finding
which was found by chance during further examination for another lesion. All
invasive pancreatic cancers (smaller than 10mm) were detected only by either
pUS or EUS but not by CT nor MRI. Invasive cancer showed hypo-vascularity
in pUS/ CE-EUS. Three cases were comfirmed as malignant by EUS-FNA and
twelve cases by ERCP. Thirteen cases had surgical resection and three cases had
chemotherapy.
CONCLUSION: Periodical examination of asymptomatic HRIs frequently
detects small pancreatic cancer with early stage. EUS and pUS could detect
invasive pancreatic cancer in early stage better than CT or MRI and are thought
to be important modalities in surveillance.
Disclosure of Interest: None declared
P0113 THE INFLUENCE OF NEURAL INVASION ON SURVIVAL AND
TUMOR RECURRENCE IN PATIENTS WITH PANCREATIC DUCTAL
ADENOCARCINOMA A SYSTEMATIC REVIEW AND METAANALYSES
S. Schorn1,*, I.E. Demir1, B. Haller2, H. Friess1, G.O. Ceyhan1 on behalf of
Pancreatic Neuropathy and Pain
1
Department of Surgery, 2Institute of Statistics and Epidemiology, Klinikum
Rechts der Isar der TU Munchen, Munchen, Germany
Contact E-mail Address: Stephan. Schorn@tum.de
INTRODUCTION: The aim of this study is to assess the true impact of perineural invasion/Pn on survival and tumor recurrence in pancreatic ductal adenocarcinoma/PDAC.
Pn is a histopathological hallmark of PDAC, which affects overall survival/OS
and tumor recurrence. Until now, recent studies could demonstrate that Pn
influences disease-free-survival-time/DFS and progression-free-survival-time/
PFS. However, at this time point, there is still no consensus on the real impact
of Pn in PDAC.
AIMS & METHODS: Pubmed, Cochrane library, Ovid and Google Scholar
were scanned for the terms pancreatic ductal adenocarcinoma, pancreatic
cancer, survival, tumor recurrence and perineural invasion. Using the
Preferred Reporting Items for Systematic review and Meta-Analysis/PRISMA
guidelines, a systematic review/SR and meta-analyses was performed. All articles
meeting the predefined criteria were critically analyzed on relevance and metaanalyses were performed by pooling univariate and multivariate hazard ratios/
HR.
RESULTS: 23 studies for the influence of Pn on tumor recurrence and a total of
101 studies analyzing the influence of Pn on survival were identified by the SR.
The performed analyses revealed the prognostic influence of Pn on PDAC
patients. The pooled HR of the univariate (1.86; CI 1.67-2.08; p50.00001) and
multivariate analyses (1.50; CI 1.36-1.65; p50.00001) showed a strong negative
impact of Pn on OS in PDAC. Interestingly, Pn was also closely linked to
decreased DFS (HR: 2.23, CI 1.13-4.41; p50.05) and PFS (HR: 2.82; CI 1.974.04; p50.00001) in the pooled multivariate analyses.
CONCLUSION: This is the first systematic review and meta-analyses focusing
on the prognostic impact of Pn on OS, DFS and PFS in PDAC. Here we could
demonstrate that Pn is an independent prognostic factor among PDAC patients,
which decreases OS, PFS and DFS. Therefore, Pn should receive increased

attention for improved patient stratification and be considered much more intensively in the development of novel therapeutic algorithms in PDAC.
Disclosure of Interest: None declared
P0114 OBESITY
IS
A
RISK
PRECANCEROUS LESIONS

FACTOR

FOR

PANCREATIC

V. Rebours1,*, S. Gaujoux2, G. dAssignies3, A. Sauvanet2, P. Levy1,


P. Ruszniewski1, A. Couvelard4
1
Pancreatology Unit, 2Surgery Unit, 3Radiology Unit, Beaujon Hospital, Clichy,
4
Pathology Unit, Bichat Hospital, Paris, France
Contact E-mail Address: vinciane.rebours@bjn.aphp.fr
INTRODUCTION: Obesity was described as a risk factor of pancreatic cancer in
combination with metabolic abnormalities. The respective roles of intravisceral
and subcutaneous fat are unknown and the prevalence of precancerous lesions in
obese patients was never evaluated.
AIMS & METHODS: To characterize the frequency and severity of pancreatic
intraepithelial neoplasia (PanIN) in patients with fatty pancreas, to correlate
pathological findings with metabolic abnormalities, tobacco intake and type of
fat. Consecutive pancreatic specimens of patients operated on for benign neuroendocrine tumors were analyzed. The pancreatic parenchyma was analyzed at
least 2 cm apart from the tumor. Fatty infiltration and fibrosis of the parenchyma in intra- and extralobular locations were assessed. Dysplastic lesions were
described according to the PanIN classification. General characteristics of the
patients were collected, including body mass index (BMI), diabetes and tobacco
intake. Liver steatosis was assessed by CT scan (mean of 3 regions of interest,
threshold 458UH). The subcutaneous and intravisceral fat (% of the total area)
was estimated on CTscan by the ImageJ software (1.47, NIH, USA).
RESULTS: 110 patients (males: 57%) were included (median surface of pancreatic specimen: 7.5 cm2). Median age at surgery was 53.8 [17-85] years. Arterial
hypertension, diabetes, tobacco intake were found in 19, 9 and 23%, respectively.
Median BMI was 24 [16-37], (BMI525: 45%, 25-530: 24%, 430: 11%).
Overall, PanIN lesions were found in 65% of the patients, Type 1, 2 and 3
PanIN were observed in 62, 38 and 1% of the cases, respectively. Fibrosis and
fatty pancreas (intra- and extralobular locations) were found in 1% and 24% and
in 30% and 51%, respectively. Liver steatosis was observed in 27%. A correlation was observed between the presence of PanIN lesions on one hand and fatty
pancreas [extra- (0.01) and intralobular (50.0001)], intralobular fibrosis (0.003),
high BMI (p 0.02), liver steatosis (p 0.03) and subcutaneous (p 0.02) and
intravisceral fat (p 0.02) on the other. Presence of PanIN was not influenced by
tobacco intake or diabetes. The number of PanIN lesions was correlated with the
severity of liver steatosis (r -0.25, p 0.02), the percentage of intravisceral fat
(r 0.22, p 0.04) but not with the percentage of subcutaneous fat (r 0.14,
p 0.22) or patient age at surgery.
CONCLUSION: Obesity -and especially android obesity with increased intravisceral fat- is a risk factor for precancerous lesions of the pancreas. These results
suggest that fatty infiltration per se plays a specific role in pancreatic oncogenesis.
Disclosure of Interest: None declared
P0115 MUCIN PHENOTYPE PREDICTS THE SITE OF METASTASIS
AFTER RESECTION OF PANCREATIC DUCTAL
ADENOCARCINOMA
Y. Hamada1,*, K. Maeshiro2, Y. Nakayama3
1
Pathology, FUKUOKA UNIVERSITY, Fukuoka, 2Surgery, St. Maria Hospital,
Kurume, 3Laboratory Medicine, National Medical Center, Fukuoka, Japan
Contact E-mail Address: yhamada@fukuoka-u.ac.jp
INTRODUCTION: Prognosis after surgical resection of pancreatic ductal adenocarcinoma remains poor because of the high incidence of recurrence. Some
studies have described the sites of metastasis after resection of pancreatic ductal
adenocarcinoma, but little is known about the relationship between clinicopathological features of the primary carcinoma and site of recurrence. Both normal
and malignant epithelial cells of a variety of organs contain mucous substances
that are rich in very high molecular weight glycoproteins called mucins, which
contain many serine- and threonine-linked carbohydrate chains. However, few
studies examine the relationship between mucin phenotype of primary pancreatic
ductal adenocarcinoma and the site of metastasis.
AIMS & METHODS: The current study focused on clinicopathological features,
including mucin phenotype, in primary pancreatic ductal adenocarcinoma and
their relationship to sites of metastasis after surgical resection. A total of 323
patients underwent pancreatic resection in our hospital from 1982 to 2003.
Seventy-four patients died from a known cause. Patients with intraductal papillary mucinous neoplasm were excluded. The follow-up period was 61 to 288
months. Clinical data were obtained from patients charts, and pathological
factors were assessed according to the WHO classification. A control group
comprised 13 patients who had survived more than 10 years after surgery for
carcinoma of the pancreas (10 group). Sections were stained with hematoxylin
and eosin and high iron diamine blue stain for detection of sulfomucin and
sialomucin. The staining pattern was classified into three groups: pure sialomucin
type (Si type), pure sulfomucin type (Su type), and mixed type. With regard to
immunohistochemical staining for MUC1, MUC2, MUC5AC and MUC6, staining of more than 10% of the carcinoma was defined as positive. Neurovascular
invasion was deemed to be present if involvement of more than five sites on a
typical section was seen.
RESULTS: Of the 74 patients with an obvious cause of death, 45 died of peritonitis carcinomatosa following local recurrence (P group), 25 died of liver metastasis (L group), 2 died of lung metastasis, and 2 died of bone metastasis. We
compared the clinicopathologic features between the L group, P group, and 10
group. Clinicopathologic features of each group are as follow: L group: frequent

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United European Gastroenterology Journal 2(1S)

Si type of carcinoma (vs. P group, p 5 0.0001; vs. 10 group, p 0.0002), high


rate of venous invasion (vs. P group, p 5 0.0001; vs. 10 group, p 5 0.0001), and
shorter prognosis (334 months, vs. P group, p 0.0257). P group: advanced pT
factor (vs. 10 group, p 0.0015) and high rate of R1 status (vs. L group,
p 0.0370; vs. 10 group, p 0.0243). 10 group: lower grade of pT factor (vs. L
group, p 0.0086; vs. 10 group, p 0.0015) and lower stage (vs. P group,
p 0.0037).
CONCLUSION: We might be able to predict the occurrence of liver metastasis
by preoperative histochemical mucin staining of carcinoma cells that were classified as Si type preoperatively using EUS-FNA or biopsy.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


ENDOSCOPY AND IMAGING
XL_____________________

POSTER

EXHIBITION

9:0017:00
HALL

P0116 EUS-FNA FOR SMALL GASTROINTESTINAL SUBMUCOSAL


LESIONS: USEFULNESS OF FORWARD-VIEWING
ECHOENDOSCOPE ATTACHED WITH CAP DEVICE
A. Yamabe1,*, A. Irisawa1, G. Shibukawa1, Y. Abe1, K. Imbe1, K. Hoshi1,
R. Igarashi1
1
Gastroenterology, Fukushima Medical University Aizu Medical Center,
Aizuwakamatsu, Japan
Contact E-mail Address: akaneko@fmu.ac.jp
INTRODUCTION: Previous reports demonstrated endoscopic ultrasoundguided fine-needle aspiration biopsy (EUS-FNA) for gastrointestinal submucosal
lesion (SML) is feasible and safe with high diagnostic yield. On the other hand,
since it is difficult to perform EUS-FNA for small SML especially less than
15mm, almost small SMLs are observed without EUS-FNA. However, because
SMLs include malignant lesions even though a tumor is small, it is desirable to
perform EUS-FNA when possible.
AIMS & METHODS: The aim of this study is to evaluate feasibility and safety
of EUS-FNA using forward-viewing echoendoscope attached with a cap device
to the tip of scope for the small SML. Eight patients who had small SML less
than 15mm I upper GI were enrolled in this study. EUS-FNA was done using
forward-viewing EUS scope (XGIF-UCT160J-AL5; Olympus, Tokyo, Japan)
and needle devices (22G, 25G), with rapid on-site evaluation. To fix the SML
at the needling, a cap device was attached to the tip of scope. We evaluated the
rate of sampling, accuracy, and complication.
RESULTS: Mean diameter of SMLs was 10.6 mm2.94mm (meanSD, range
8-15mm). The puncture could be done in all 8 cases, and mean number of FNA
passes was 4.61.59 (meanSD, range 3-7). The adequate materials were
obtained in 6 (87.5%) for cytology, in 4 (50%) for histological examination
with immunostaining. In 1 (12.5%) patient, adequate sample for both cytology
and histology was not obtained. As final diagnosis, 6 patients were gastrointestinal stromal tumor (2 in definition, 3 in suspicion), 2 patients were leiomyoma.
No complication was noted.
CONCLUSION: Although the rate of definitive diagnosis was 50%, EUS-FNA
using forward-viewing echoendoscope attached with a cap device for small SML
was feasible and safe.
Disclosure of Interest: None declared
P0117 ENDOSCOPIC CHARACTERISTICS OF EARLY GASTRIC
CANCERS MIXED WITH WELL AND POORLY DIFFERENTIATED
ADENOCARCINOMA
A. Takahashi1,*, T. Oyama1
1
Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan
Contact E-mail Address: aurevoireurope@yahoo.co.jp
INTRODUCTION: The risk of lymph node metastasis of superficial gastric
cancer depends on histological type, invasion depth and the size. Sometimes,
well differentiated gastric adenocarcinoma has poorly differentiated component
partially. And, the incidence of lymph node metastasis is higher than that of the
well differentiated type. Therefore, endoscopic diagnosis of histological type is
important. However, the endoscopic characteristics of such a histologically
mixed gastric adenocarcinoma are unknown.
AIMS & METHODS: The aim of this study is to investigate the endoscopic
characteristics of early gastric cancers partially with poorly differentiated type.
One hundred eighty-two gastric adenocarcinomas from 172 patients treated by
ESD from January to December 2012 were enrolled in this study. All of the
examination was performed by Olympus H260Z with Lucera. And, narrow
band imaging (NBI) magnified observation was performed after white light imaging (WLI) observation. Magnified endoscopic findings were divided into surface
and vascular pattern. Surface pattern was divided into villous, pit and unclear.
The gross type was classified into 0-I, 0-IIa, 0-IIb and 0-IIc type, and the number
was 9, 67, 7, and 99, respectively. The histology was classified into well and
poorly differentiated type. When the cancer had only well differentiated type,
it was classified as pure well differentiated type. And, when the well differentiated
adenocarcinoma had a poorly differentiated component, it was classified as
mixed type. And when the cancer was composed of only poorly differentiated
adenocarcinoma, it was classified as pure poorly differentiated type.
RESULTS: 1. The numbers of pure well differentiated type, mixed type and pure
poorly differentiated type were 157, 23 and 2, respectively.
2. 0-I type: Seven of 9 lesions were pure well differentiated type, and two of 9
lesions were mixed type. The size of these two lesions was more than 20mm.
3. 0-IIa type: Sixty three and 4 of 67 lesions were well differentiated and mixed
type, respectively. The incidence of mixed type has relationship with the size.
When the lesions were divided three groups depends on the size such as 1-9, 10-

19, 20-29, 30mm or bigger, the incidence of mixed type was 0% (0/15), 8% (2/24)
and 0% (0/15), 15% (2/13), respectively.
4. 0-IIb type: All of seven lesions were pure well differentiated type.
5. 0-IIc type: 80, 17 and 2 of 99 lesions was pure well, mixed and pure poorly
differentiated type, respectively. And when the size was subclassified into four
groups 2-9, 10-19, 20-29, 30mm or bigger, 0% (0/30), 25% (12/48), 27% (4/15)
and 50% (3/6) were mixed type.
6. The surface pattern of well differentiated adenocarcinoma observed by magnified endoscopy showed irregular villous or pit pattern. However, the surface
pattern of mixed type was unclear in some cases. However, sometimes the surface
was covered by thick mucus, and magnified endoscopic observation was
impossible.
CONCLUSION: The incidence of mixed type depends on the size and macroscopic type of the superficial gastric cancer. Magnified endoscopy was sometimes
useful to detect mixed type from the surface pattern.
REFERENCES
NONE
Disclosure of Interest: None declared
P0118 SUBMUCOSAL FIBROSIS AFFECTS THE OUTCOME
ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR GASTRIC
NEOPLASMS

OF

A. Shimozato1,*, N. Ogasawara1, Y. Kondo1, Y. Ito1, H. Noda1, K. Yanamoto1,


M. Sasaki1, K. Kasugai1
1
Gastroenterology, Aichi Medical University, Nagakute City Aichi, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) is an effective
treatment for gastric neoplasms. However, because of its technical difficulty, it
takes longer, and there is a greater risk of complications such as bleeding and
perforation. The success of ESD depends on the technical proficiency of the
endoscopist and the condition of the gastric tumor. Even for a skilled endoscopist, however, submucosal fibrosis can be an obstacle to success of ESD.
Submucosal fibrosis, which usually results from inflammation or tumor invasion,
makes it harder to lift the tumor tissue from the muscle layer. This in turn
lengthens the procedure time, creates risk of complications such as perforations,
and reduces the success rate of complete en bloc resection. Despite its importance, there has been little investigation of the relationship between the degree of
submucosal fibrosis and outcomes of ESD in early gastric tumors. Accordingly,
the aims of this study were 1), to examine the association between endoscopic and
pathologic findings and submucosal fibrosis in gastric neoplasms; 2), to examine
the association between degree of submucosal fibrosis and outcomes of ESD.
AIMS & METHODS: Two hundred forty six patients with gastric neoplasms (52
cases of adenomas and 194 cases of early gastric cancers) were treated by ESD
from November 2008 to September 2013. Endoscopically, the degree of submucosal fibrosis was classified as follows, based on the findings obtained after a
solution including indigo carmine was injected under the submucosal layer: F0,
no fibrosis, which appeared as a blue transparent layer; F1, mild fibrosis, which
appeared as a white web-like structure in the blue submucosal layer; and F2,
severe fibrosis, which appeared as a white muscle-like structure without a blue
transparent layer.
RESULTS: The presence of endoscopic submucosal fibrosis was not significantly
related to tumor size, ulceration, histological findings, submucosal invasion, and
en bloc resection rates in univariate analysis. However, posterior walls of the
stomach harbored higher frequency of submucosal fibrosis compared with anterior wall regardless of upper, middle or lower portion of the stomach (p50.05).
The procedure time according to the degree of endoscopic submucosal fibrosis
were as follows (mean SD): F0, 82.142.1 minutes; F1, 146.681.6 minutes,
and F2, 171.4106.7 minutes, showing significant difference between groups (p
50.01). The severity of endoscopic submucosal fibrosis was associated with
abundant immediate bleeding which required hemostasis using hemoclips
during ESD procedure (p50.05). However, delayed bleeding was not significantly related to the degree of submucosal fibrosis.
CONCLUSION: Submucosal fibrosis of gastric neoplasms is closely related to
tumor location, procedure time, and severe bleeding during ESD. Moreover, the
more advanced the endoscopic submucosal fibrosis, the longer the time required
for ESD and the higher the frequency of immediate bleeding. Further development of endoscopic devices and peripheral equipments are needed for safe and
complete resection of lesions with severe fibrosis.
Disclosure of Interest: None declared
P0119 NEW
ENDOSCOPIC
TECHNIQUE
PLACEMENT OF VOICE PROSTHESIS
1,*

FOR

SECONDARY

A.M. Seraphim , A. Pelosof , L. Kowalski , J. Vartanian , C.Z. Sztokfisz1


1
endoscopy, 2head and neck surgery, AC Camargo Cancer Center, Sao Paulo,
Brazil
Contact E-mail Address: alvaroseraphim@yahoo.com.br
INTRODUCTION: The functional speech rehabilitation in laryngectomized
patients after total laringectomy remains as one of the most challenging matters
for head and neck surgeons and speech therapists.
The use of voice prostheses has been considered the gold standard in voice
rehabilitation for the last 25 years. Insertion can be performed either as a primary
procedure during laryngectomy or as a secondary procedure with rigid esophagoscope or trocar. In some patients these procedure became technically impossible due to some post treatment cervical abnormalities such as necks reduced
hyperextension (post surgery or radiotherapy) anastomotic reduced diameter
(post surgery), trismus and other impairments situations.
AIMS & METHODS: Objective: To present an endoscopic technique for secondary placement of Provox prosthesis using the flexible endoscope, a plastic

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United European Gastroenterology Journal 2(1S)


pliable overtube (to keep the virtual esophageal lumen open so the traqueoesophageal puncture could be performed safely, avoiding unexpected lesions on the
posterior esophageal wall), a 14 gauge intravenous catheter to perfomed the
puncture, and a flexible guidewire. Furthermore, using the flexible endoscope
instead of the rigid esophagoscope we can avoid some of the major complications
of the classical technique i.e.: mediastinitis, cervical cellulitis, fracture of cervical
vertebra, and esophageal perforation
Methods: 7 patients referred to voice rehabilitation with Provox II vocal prosthesis in a secondary placement, in which the classic technique could not be
performed, underwent a new surgical technique, performed with a flexible endoscope, a plastic pliable overtube, a 14 gauge intravenous catheter and a flexible
guidewire,
RESULTS: The procedure was successfully performed in all seven patients.
There were no complications related to the surgical technique.
CONCLUSION: In patients where the classic technique for secondary insertion
of the Provox prosthesis is technically impossible, this new technique could be a
good alternative
Disclosure of Interest: None declared
P0120 ARE
OUTCOMES
FOLLOWING
ENDOSCOPY
EMERGENCY UPPER GI BLEEDING WORSE AT NIGHT AND
WEEKENDS?

12% but was not directly related to the SEMS insertion. The 7-day readmission
rate following SEMS placement was 5% as result of symptoms caused by SEMS
including pain & vomiting. The median survival was 125 (range 4-910) days. 26
(35%) of the patients needed re-intervention due to recurrence of dysphagia due
SEMS migration or tumour overgrowth. The SEMS migration rate was 18%
(n 14/96) occurring after a median of 120 (range 10-365) days. 87% of the
migrated SEMS were from tumours of the lower oesophagus and GOJ.
Tumour overgrowth occurred in 16% (n 15/96) at a median of 120 (range
28-210) days. In 19/26 (73%) cases palliation was successfully achieved with
re-intervention; further SEMS placement in 17 & APC in 2. Interestingly, the
patients with recurrence of dysphagia had significantly (p00.5) prolonged survival (median 156 (range 30-790) days) compared to patients who did not need
any intervention (median 125 (range 4-910) days).
CONCLUSION: Fully covered SEMS are safe and offer extremely effective
palliation of malignant dysphagia for up to 3-4 months. Re-intervention
beyond this point is for recurrence of dysphagia due to SEMS migration and/
or tumour overgrowth that may be due to increased patient survival. The majority of patients can be re-palliated successfully with further endotherapy.
Disclosure of Interest: None declared

FOR

A. Rehman1,*, P. Mundre1, B. Rembacken1


1
Leeds teaching hospital Leeds, Leeds, United Kingdom
Contact E-mail Address: bjorn.rembacken@leedsth.nhs.uk
INTRODUCTION: Patients admitted out of hours or at weekends may have an
excess mortality due to the fact that they undergo emergency endoscopy by junior
staff. We retrospectively looked at the predictors of mortality in patients undergoing emergency endoscopy for severe bleeding in Leeds.
AIMS & METHODS: The survival of patients with the most significant upper
GI bleeding lesions who underwent emergency endoscopy in Leeds between end
of April 2008 and middle of June 2012 were selected for retrospective analysis
using data from our endoscopy reporting system and hospital records.
RESULTS: A total of 509 significant emergency gastroscopies were carried out
with the finding of 197 duodenal ulcers, 105 gastric ulcers, 161 oesophageal
varices, 26 gastric varices, 12 Dieulafoys and 9 other bleeding lesions (bleeding
biopsy site, bleeding EMR site, gastric lymphoma, 3 PHG, 3 angioectasia).
After 22% of procedures (114/509), the patient died within 30 days. As expected,
patients who died had a significantly higher Rockall score (7.6 vs. 6.0 p50.0001),
a higher ASA level (3.5 vs. 2.7 p50.001) and a lower systolic BP at the time of
the examination (94.8 vs 103 p 0.025). Patients who died following endoscopy
for bleeding ulcers were significantly older than those who survived (77.7 vs. 67.5
yrs, p 0.006). There was no significant difference in mortality with the type of
bleeding lesion, Hb (8.0 vs. 7.8) or heart rate (100 vs. 102 bpm) at the time of the
endoscopy between those who survived and those who died. Patients who died,
were transfused significantly more blood than those who survived (5.9 units vs
3.8). Of the patients who suffered a re-bleed, 52 patients died and only 62 survived. A total of 28 patients required emergency angiography and embolisation
of a bleeding vessel. This small group had suffered a significantly greater blood
loss (21 had suffered a re-bleed) and had an average Hb of only 6.9 in spite of
having received an average of 12.9 units of blood. In spite of this, 22 patients
survived following embolisation.
Undergoing an emergency gastroscopy at night or during the weekend or a bank
holiday was not associated with an increased risk of death (p 0.50, p 0.32
respectively). Whether the examination was carried out by a SpR or a Consultant
made no difference to the survival of the patient (p 0.40).
CONCLUSION: Our study had the statistical power to detect all the recognised
risk factors for death following admission with an acute upper GI bleed including
advancing age, increasing comorbidity, hypotension, re-bleeding and transfusion
requirement. We found no evidence that undergoing an emergency endoscopy at
night or during the weekend or a bank holiday had any adverse effect on outcomes. Similarly, the level of seniority of the endoscopist did not affect outcomes.
Disclosure of Interest: None declared
P0121 LONG-TERM OUTCOMES OF PATIENTS WITH MALIGNANT
DYSPHAGIA THAT HAVE UNDERGONE STENTING
A. Gaglia1,*, H. Smart2, P. OToole1, N. Haslam1, S. Sarkar1
1
Gastroenterology, 2Royal Liverpool University Hospital, Liverpool, United
Kingdom
Contact E-mail Address: gagliam2000@hotmail.com
INTRODUCTION: Oesophageal stenting with fully covered self-expanding
metal stents (SEMS) has transformed the care of patients with malignant dysphagia. SEMS are easily removable and have fewer reported long-term complications of tumour ingrowth although possibly more migration. However,
predictive factors for favourable outcomes are yet to be fully defined for those
with malignant dysphagia.
AIMS & METHODS: The aim of this retrospective study was to evaluate the
complications, the re-intervention rate and the survival after insertion of fully
covered SEMS for malignant dysphagia and to identify any predictive factors for
outcomes other than tumour stage. All SEMS procedure data were retrieved
from Royal Liverpool University Hospital patient database retrospectively in a
2-year inclusion period and analysed regarding SEMS characteristics, procedural
events, re-interventions and survival on a standard proforma.
RESULTS: A total of 96 fully covered SEMS were inserted in 74 patients (47
males) with a median age of 73 (range 36-89) years. Technical success was 99%
(95/96), with no complications of perforation or bleeding. Minor (n 6) complications included chest pain, vomiting & severe GORD. The 30-day mortality was

P0122 HIGH DIAGNOSTIC YIELD OF EUS-ASSISTED SINGLE


INCISION-NEEDLE KNIFE (SINK) BIOPSY FOR HISTOLOGICAL
ANALYSIS OF UPPER GASTROINTESTINAL STROMAL TUMORS
C.de la Serna- Higuera1,1,*, P. Diez- Redondo1, F. Santos1, I. Penas1, P. Gil1,
H. Nunez1, M. Perez-Miranda1
1
Gastroenterology, Rio Hortega Hospital, Valladolid, Spain
Contact E-mail Address: csernah@hotmail.com
INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most frequent type of mesenchymal neoplasms of the upper gastrointestinal tract and
may be malignant regardless their echopattern or size, therefore, histologic and
immunohistochemical (IH) analysis are crucial for diagnostic and pronostic purposes. EUS- guided FNA provides a low diagnostic yield, specially for smaller
GIST. EUS - assisted SINK biopsy is an alternative method with promising
preliminary results.
AIMS & METHODS: We aimed to evaluate the diagnostic yield of SINK samples for IH analysis and mitotic index (MI)assessement.
Retrospective evaluation of a prospectively-mantained database, including all
patients with upper gastrointestinal subepithelial tumors (SETs) who underwent
EUS-assisted SINK biopsy since April 2010 to March 2014. All patients underwent previous radial/linear EUS for size measurement and morphological characterization; then a needle-knife was used in blended current at 30W to 60W
settings and a 6 to 12 mm linear incision was made along the highest convexity
zone of the lesion. Then, 3 to 5 biopsy samples were obtained from the exposed
tissue with a standard biopsy forceps and included in formalin. When histologic
analysis revealed features of mesenchymal origin (spindle cells), specific IH markers for GISTs (cKit- CD 117, CD 34) and mitotic count per 50 high- power
fields (HPF) to assess malignant potential were performed.
RESULTS: 72 patients (M/F: 38/34) were included (mean age 63.66, range 2289). There were 27 mesenchymal lesions (27/72: 37.5%); GIST 23, leiomioma 4.
Median size: 3.53 mm (1.34-5.90). IH analyses for SINK samples was positive in
25/ 27 GISTs (92.59%) and MI determination was feasible in 21/ 27 (77.77%).
16/21 showed 5 5 mitoses per 50 HPF and were categorized as very low risk
according to the NIH classification-all these lesions with diameters under 30 mm.
There were no procedure-related complications.
CONCLUSION: EUS-assisted SINK-biopsy of upper GISTs appears to be an
easy and safe technique and provides sufficient tissue samples for IH diagnosis
and assessment of malignancy by means of an accurate MI calculation.
REFERENCES
1.-Philipper M, Hollerbach S, Gabbert HE, et al. Prospective comparison of
endoscopic ultrasound-guided fine needle aspiration and surgical histology in
upper gastrointestinal submucosal tumors. Endoscopy 2010; 42: 300-305.
2.-Fernandez-Esparrach G, Sendino O, Pellise M, et al. Endoscopic ultrasoundguided fine needle aspiration and trucut biopsy in the dignosis of gastric stromal
tumors: a randomized crossover study. Endoscopy 2010; 42: 292-299.
3.-Hoda KM, Rodriguez SA and Falgel DO. EUS-guided sampling of supected
GI stromal tumors. Gastrointest Endosc 2009; 69: 1218-1223.
4.-De la Serna C, Perez-Miranda M, Diez-Redondo P, et al. EUS-guided singleincision needle-knife biopsy: description and results of a new method for tissue
sampling of subepithelial GI tumors. Gastrointest Endosc 2011; 74: 672-676.
Disclosure of Interest: None declared
P0123 PENTAX I-SCANTM WITH MAGNIFICATION FOR THE
IDENTIFICATION OF UNDERDIAGNOSIS ORGANIC
ESOPHAGEAL LESIONS (BARRET ESOPHAGUS AND
ESOPHAGITIS) IN PATIENTS WITH FUNCTIONAL DYSPEPSIA: A
PROSPECTIVE STUDY
C. Robles-Medranda1,*, R. Del Valle1, M. Soria1, G. Bravo1, H. Lukashok1,
C. Robles-Jara1
1
ENDOSCOPY, INSTITUTO ECUATORIANO DE ENFERMEDADES
DIGESTIVAS, UNIVERSITY HOSPITAL OMNI, ESPIRITU SANTO
UNIVERSITY, Guayaquil, Ecuador
Contact E-mail Address: carlosoakm@yahoo.es
INTRODUCTION: Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by symptoms originating from the gastroduodenal
region in the absence of underlying organic disease as defined by Roma III
criteria. Upper endoscopy (UE) associated to digital chromoendoscopy (DC),
magnification (M) and high definition (HD) had shown excellent results for

A164

United European Gastroenterology Journal 2(1S)

the diagnosis of Barret esophagus (BE) and esophagitis. However, not all patients
are investigated with this kind of technology, where UE results are considered as
absence of organic lesions, thus diagnosed as FD.
AIMS & METHODS: Based on the hypothesis that HD UE associated to DC
and M can detect more mucosal details than standard UE, we evaluate the
effectiveness of i-ScanTM (HD UEDCM) in patients with functional dyspepsia for the identification of organic esophageal lesions. After approval by the
ethics committee and signing of an informed consent, a prospective study was
performed in consecutive patients undergoing for UE from Nov 2012 to June
2013. Inclusion criteria: Criteria of FD in accordance to ROMA III criteria,
normal standard UE in the last 3 months previous to the inclusion in this
study. Exclusion criteria: age 518, pregnancy, history of: gastritis, GERD, gastrointestinal cancer, H pylori infection, pancreatic disease, choledocolitiasis,
alcohol or smoke abuse, use of medications (IBP, NSAIDs, Antibiotics). HD
UEDC and M was performed using the EPK-i processors with i-ScanTM from
Pentax. Under sedation patients underwent HD UE, analyzing all the mucosa
aspects using initially white light (WL), with especial regard in the Z-line at the
level of the cardia. Then DC was performed using i-Scan. Any alteration in the
mucosa pattern (color, pitt or vascular pattern) was analyzed and then classified
as inflammation or BE using Los Angeles and Prague classifications respectively.
Finally acetic acid was performed and a target biopsy was done as the gold
standard method to confirm i-Scan findings.
RESULTS: 491 patients were included. 48% were men with a mean age of 47
(ranges: 18-87). 151/491 patients (30.7%) had an organic esophageal lesion
detected at i-Scan. 45/151 patients were detected initially by HD-UE-WL.
Biopsy confirm the esophageal lesions in 125 cases. i-Scan detect 94 cases of
short BE (C51,M51), 25 cases of esophagitis (Grade A), and 6 cases where
considered to have a mixed disease (BE and esophagitis). The accuracy to predict
BE for i-Scan was 95% and 100% for esophagitis.
CONCLUSION: HD UEMDC (i-ScanTM) could detect an important
number of organic esophageal lesions as BE and esophagitis in patients initially
overdiagnosed as a functional disease.
Disclosure of Interest: C. Robles-Medranda Consultancy for: Pentax Medical,
MaunaKea technologies, R. Del Valle: None declared, M. Soria: None declared,
G. Bravo: None declared, H. Lukashok: None declared, C. Robles-Jara: None
declared
P0124 COMPARATIVE STUDY OF ESD AND SURGICAL RESECTION
FOR GASTRIC SETS ORIGINATED FROM MUSCULARIS PROPRIA
C.B. Ryu1,*, M.S. LEE2, J.Y. BAE3, J.Y. SONG4
1
Department of Internal Medicine, Soon Chun Hyang University School of
Medicine, 2Department of Internal Medicine, SOON CHUN HYAN
UNIVERSITY SCHOOL OF MEDICINE, BUCHEON, 3SEOUL MEDICAL
CENTER, SEOUL, 4SUWON MEDICAL CENTER, SUWON, Korea, Republic
Of
INTRODUCTION: Endoscopic resection for gastric subepithelial tumors (SETs)
originated from the muscularis propria (GSET-PM) has offered less invasive
alternatives to surgical resection. The aims of this study were to compare endoscopic subtumoral dissection (ESD) with surgical resection for the removal of
GSET-PM.
AIMS & METHODS: This study involved 17 patients with GSET-PM removed
by ESD and 76 patients who underwent curative surgical resection. ESD was
attempted in GSET-PM with well marginated tumors which was below 5cm and
showed an endoluminal growth pattern according to endoscopic ultrasound
(EUS) finding.
RESULTS: ESD group were more likely to have upper portion (10/17, 58.8%)
and surgery group were more likely to have mid portion (41/76, 53.8%)
(p 0.039). ESD group had smaller median tumor size (25.6 mm vs 35.9 mm,
p 0.037) and higher endoluminal ratio (58.59.1% vs 45.815.4%, p 0.002).
ESD group mostly had Yamada type III (10/17, 58.8%) and the surgery group
were mostly Yamada type I (52/76, 68.4%) (p50.001). Complete resection by
ESD was lower than by surgical resection (82.4% vs 100%, p50.001). In ESD
group, 3 performed surgical resection after ESD (1 incomplete resection and 2
uncontrolled bleeding) and 1 showed perforation which was completely resected
with endoscopic closure. In the surgery group, complications occurred in 6
patients (1 leakage, 1 stricture, 1 hernia and bowel obstruction, 1 wound infection
and 2 worsened general condition after surgery). Although surgery group were
lower in complication rate than ESD group (p 0.006), severity of complications
were higher in the surgery group and there were no mortalities in the ESD group
compared with 2 in the surgery group. There was no statistical difference of
recurrence and the follow-up period between the two groups.
CONCLUSION: ESD can be a good option for the resection of endoluminal
GSET-PM and could replace treatment by surgical resection in Yamada type III
with a high endoluminal ratio.
Disclosure of Interest: None declared
P0125 NON-CURATIVE ENDOSCOPIC RESECTION DOES
ALWAYS LEAD TO GRAVE OUTCOMES IN SUBMUCOSAL
INVASIVE EARLY GASTRIC CANCER

NOT

C. Jun Young1,*, J. Seong Woo1, C. Kwang Bum2, P. Kyung Sik2, K. Eun Soo2,
P. Chang Keun3, C. Yun Jin3, K. Joong Goo4, J. Jin Tae4, K. Eun Young4,
K. Kyeong Ok5, J. Byung Ik5, L. Si Hyung5, P. Jeong Bae6, Y. Chang Hun6
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Kyungpook National University Medical Center, 2Internal Medicine, Keimyung
University College of Medicine, 3Internal Medicine, Fatima Hospital, 4Internal
medicine, Daegu Catholic University School of Medicine, 5Internal Medicine,
Youngnam University School of Medicine, Daegu, 6Internal Medicine, Dongkuk

University School of Medicine, Gyeongju, Korea, Republic Of


Contact E-mail Address: sentiwalk@naver.com
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely
performed for the treatment of early gastric cancer (EGC).
AIMS & METHODS: The aim of this study is to confirm the effectiveness of
ESD in submucosal invasive gastric cancers (SM-GC), with a special focus on
patients who underwent non-curative resection.
Data for 1,246 patients who underwent ESD for treatment of EGC at six medical
centers in Daegu-Gyeongbuk, Korea, between February 2003 and May 2010
were collected. After retrospective analysis of ESD databases, 118 patients
were enrolled in the study. The corresponding EGC lesions were classified into
three groups based on the results of pathological examination: 1) gastric cancers
with submucosal invasion less than 500mm (SM1-GC) that met the expanded
criteria (EC) (SM1 EC group, n 42); 2) SM1-GC that did not meet the EC
(SM1 non-EC group, n 38); and 3) gastric cancers with submucosal invasion
greater than 500mm (SM2-GC group, n 38).
RESULTS: The en bloc resection rate (SM1 EC group/SM1 non-EC group/
SM2-GC group: 85.7%/94.7%/97.4%, respectively) and complete resection
rate (SM1 EC group/SM1 non-EC group/SM2-GC group: 81.0%/81.6%/
71.1%, respectively) did not differ significantly among the three groups.
However, the curative resection rate was significantly better in the SM1 EC
group (69.0%) compared to that in SM1 non-EC and SM2-GC groups (0% in
both cases). Out of a total of 118 patients, 89 (75.4%) underwent non-curative
resection. Cancer recurrence was observed in 9 patients (9/89, 10.1%) during the
median follow-up period of 40 months (range: 3-99). We analyzed the overall
survival and disease-free survival in non-curative patients that underwent or did
not undergo additional surgery. The overall survival and disease-free survival did
not differ significantly between patients that were treated with additional surgical
resection and those that were simply followed up after ESD.
CONCLUSION: Non-curative resection in SM-GC does not always lead to
cancer recurrence. Thus, if additional surgery cannot be performed because of
the patients unsuitable condition (due to age, underlying disease, etc.) or refusal,
a close follow-up with endoscopy can be considered as an alternative for carefully
selected patients. Moreover, as the ESD technology continues to evolve, it might
be possible to expand the criteria for curative ESD in patients with SM-GC.
Disclosure of Interest: None declared
P0126 PROSPECTIVE LONG-TERM OBSERVATION TRIAL OF ARGON
PLASMA COAGULATION (APC) FOR SHORT-SEGMENT
BARRETTS ESOPHAGUS IN AN OUTPATIENT SETTING
D. Schadlich1,*
1
Universitat Erlangen-Nurnberg, Erlangen, Germany
Contact E-mail Address: e-mail@daniela-hascher.de
INTRODUCTION: Barretts esophagus (BE) is the only known precursor lesion
to esophageal adenocarcinoma of the distal esophagus. There are various endoscopic treatments to ablate BE to generate a neo-squamous epithelium such as
radiofrequency ablation (RFA), cryotherapy and argon plasma coagulation
(APC). However, there is limited data available for APC in an outpatient setting.
AIMS & METHODS: Prospective long-term observation trial of Argon Plasma
Coagulation in an outpatient setting.
Patients of a gastroenterology practice were considered for entry into this trial.
At the initial endoscopy a chromoendoscopy was undertaken and biopsies were
taken (bioptic mapping). Then the patients were treated with a high frequency
pulsed APC (16 boosts/sec) in order to ablate BE completely. One session was
necessary for tongue-shaped and complete covering epithelium, more than two
sessions for distal circular BE. Follow-ups were scheduled after six weeks, six
months, one and two years.
RESULTS: 73 patients (17% women, median age: 71 years, range: 34 -82 years)
were enroled but only 70 patients were finally included in this trial. Other than
rare minor retrosternal pain after large ablations there were no other treatmentassociated complications. Of all patients treated with APC-ablation 87.5%
showed a stable complete eradication with regenerated neo-squamous epithelium
in the follow up. During the 2-year follow up 4.3% showed a macroscopic and
histological recurrence. However, the clinical role of residual or recurrent BE in
form of so called Buried glands (10%) is still uncertain and worth discussing.
CONCLUSION: In this trial it was shown the first time that APC was a safe and
efficient endoscopic treatment to ablate short-segment non-dysplastic BE especially in an outpatient setting.
Disclosure of Interest: None declared
P0127 FUNCTIONAL ESOPHAGOSCOPY VIA TRANSNASAL ACCESS
ALLOWS NEW INSIGHTS IN PATIENTS WITH NEUROGENIC
DYSPHAGIA
D. Domagk1,*, P. Lenz1, K. Heuwing1, I. Suttrup2, H. Heinzow1, J. Wessling3,4,
R. Dziewas2, I.F. Herrmann5, T. Warnecke2
1
Department of Medicine B, 2Department of Neurology, University of Muenster,
3
Department of Radiology, Clemens Hospital Muenster, 4Department of Clinical
Radiology, University of Muenster, Muenster, 5Reflux Center Duesseldorf,
Duesseldorf, Germany
Contact E-mail Address: domagkd@uni-muenster.de
INTRODUCTION: Patients suffering from neurogenic dysphagia often get
caught in the trap: they find themselves somewhere in the space between different
specialists. This dilemma might be due to a lack of pathophysiological knowledge
of the complex swallowing process from the oral cavity to the stomach and an
inability to directly visualize the esophageal phase of deglutition.

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: In a multidisciplinary setting, 31 consecutive patients with
suspected neurogenic dysphagia were evaluated by transnasal access applying an
ultrathin video endoscope with an outer diameter of 3.8 mm (BF-3C160,
Olympus Europe). Patients were examined in sitting position while ingesting
water and food of different consistencies. Diagnostic was completed by videofluoroscopy and high-resolution manometry. The study was approved by the
local Ethics Committee.
RESULTS: Functional endoscopy was successfully performed in all patients. We
were able to show that functional endoscopy is a feasible and safe method; no
adverse events were noted. Endoscopic findings correlated well with the clinical
signs of the patients and the other diagnostic modalities. A variety of disorders
was documented by functional endoscopy and recorded as video files: Incomplete
and delayed closure of the upper esophageal sphincter (in retroflex view), clearance disturbance of tubular esophagus, esophageal hyperperistalsis and hypomotility. The most common findings in the oral and pharyngeal phase were bolus
leakage, delayed swallowing reflex, vallecular residues, and, aspiration during
food intake.
CONCLUSION: By interdisciplinary cooperation with additional assessment of
the esophageal phase of deglutition using the innovative method of functional
endoscopy, the diagnostic of neurogenic disorders including dysphagia may be
tremendously improved leading to a better clinical understanding of complex
dysfunctional patterns. To our best knowledge, this is the first study to show
that a retroflex view of the ultrathin video endoscope within the esophagus may
be safely performed. This diagnostic comprehensive approach should be helpful
to apply focused prophylactic and therapeutic actions.
Disclosure of Interest: D. Domagk Lecture fee(s) from: Olympus Europe,
Consultancy for: AbbVie, P. Lenz: None declared, K. Heuwing: None declared,
I. Suttrup: None declared, H. Heinzow: None declared, J. Wessling: None
declared, R. Dziewas: None declared, I. Herrmann: None declared, T.
Warnecke: None declared
P0128 REPEATED
BOLUS
INJECTION
VERSUS
SLOWLY
CONTINUOUS INFUSION OF PROTON PUMP INHIBITOR FOR
THE MANAGEMENT OF BLEEDING AFTER ENDOSCOPIC
SUBMUCOSAL DISSECTION
D.K. Kang1,*, D.H. Kang1, H.W. Kim1, C.W. Choi1, S.B. Park1, S.J. Kim1,
Y.S. Shin1, Y.Y. Choi1, H.K. Lim1, S.K. Oh1, H.S. Nam1
1
Division of Gastroenterology, Department of Internal Medicine, School of
Medicine Pusan National University, Pusan National University Yangsan Hospital,
Yangsan-si, Korea, Republic Of
Contact E-mail Address: shadam@naver.com
INTRODUCTION: Elevated intra-gastric pH is important in management of
bleeding and healing the artificial ulcer after endoscopic submucosal dissection.
The Proton Pump Inhibitor (PPI) has powerful acid suppression. At present, the
standard treatment of choice for the prevention of gastric ulcer bleeding is continuous infusion of PPI after intravenous bolus loading.
AIMS & METHODS: Our aim is to compare the effects of repeated bolus
injection and slowly continuous infusion of PPI for the management of delayed
bleeding after gastric ESD.
From March 2012 to Feb 2013, 273 patients with gastric superficial epithelial
neoplasm were enrolled. The group was divided into two. One is the repeated
bolus group, the other one the slowly continuous-infusion group. All patients are
undergod ESD. In slowly infusion group After initial pantoprazole 80mg bolus
loading for 30 min before ESD, 8mg/hr continuous infusion for 72 hours is done
after initial 80mg bolus loading for continous infusion group. For repeated bolus
group (n 136), pantoprazole 40mg bolus is injected q 12 hours for 72 hours.
After 72 hours, Oral pantoprazole 40 mg daily for 4 to 8 weeks. Follow-up
endoscopy is performed 2 days and 4 weeks after ESD. (In case of incomplete
ulcer healing, 8 week endoscopy and pantoprazole 8 wk medication was done.)
RESULTS: No difference on clinical characteristics were seen between two treatment groups. Bleeding events occurred in 8.4% (23/273) of all patients. In follow
up endoscopic findings, high risk of stigma was found in 15.8% (43/273) of all
patients. No difference in bleeing event was seen between repeated bolus group
and slowly continous infusion group. Submucosal invasive, gross type of lesion
and coronary disease were significant risk factors for rebleeding events rather
than the method of PPI administration.
CONCLUSION: The method of PPI administration was not significantly different to predict post ESD delayed bleeding. Submucosal invasive, gross type of
lesion and coronary disease were more important to predict post ESD delayed
bleeding.
Disclosure of Interest: None declared
P0129 A NOVEL STRATEGY IN THE ENDOSCOPIC TREATMENT OF
REFRACTORY UPPER GI-BLEEDING IN ANTICOAGULATED
PATIENTS WITH THE OVER-THE-SCOPE-CLIP (OTSC) ARE WE
ENTERING TO A NEW ARA IN THE TREATMENT OF UPPER GIBLEEDING?
E. Wedi1,*, A. Sportes2, T.M. Reiig2, J. Hochberger1
1
Departement of Gastroenterology and Interventional Endoscopy, 2University
Hospital Strasbourg, Strasbourg, France
Contact E-mail Address: edris1@web.de
INTRODUCTION: The OTSC (OVESCO, Germany) is a novel endoscopic
device successfully applied for severe GI bleedings, perforations, fistulas and
experimental NOTES procedures.
We performed a retrospective analysis of all OTSC applications for acute gastrointestinal bleeding from February 2009 to March 2014 using our endoscopy
database and individual patient records.

A165
AIMS & METHODS: Over a 5 year period 55 patients [median 73 y (29-97) 17
w, 38 m, ASA 2-4] with acute severe upper gastrointestinal bleeding (hemoglobin
5 7 g/dl at admission for acute bleeding or as emergency endoscopy for hospitalized patients) using 56 OTSCs (n 54 T-type 12/6 17.5 mm OD; n 2 T-type
14/6 21 mm OD).
RESULTS: In 48/55 cases (87.2%) acute bleeding was related to peptic ulcer
disease, in 2 cases due to bleeding from a malignant ulcer (1x gastric AC, 1x
gastric lymphoma), 2 cases due to recurrent bleeding after polypectomy and clip
in the stomach. In 1 case a heavily bleeding Mallory Weiss tear and in 1 case a
bleeding ulcer at a gastro-jejunal anastomosis was treated. One patient bled
heavily from a deep muscle laceration after balloon dilatation for achalasia.
18/55 (32.7%) were treated due to a failure of a previous hemostasis methods
(standard hemoclips, injection or radiologic embolization).
Of the 55 patients 44 (80%) were on pre-existing anticoagulation, 9/55 (16.4%)
took warfarin, 24/55 (43.6%) aspirin, 10/55 (18.2%) heparin/enoxaparin and 1
(1.8%) was anti-coagulated with a combination of aspirin plus clopidogrel.
In 46/55 of all cases, primary treatment with the OTSC was successful (83.6%), in
all the cases without re-bleeding events. In 7/55 (12.7%) surgical treatment was
necessary due to insufficient hemostasis. However, 4 of those 7 patients died
during the hospital stay. 2 multi-morbid patients not fit for surgery passed away.
CONCLUSION: The OTSC system is a promising new tool for the management
of acute severe GI-bleeding. Especially patients with pre-existing anticoagulation
and multi-morbidity seem to profit from this system.
Disclosure of Interest: None declared
P0130 CLINICAL OUTCOMES OF ENDOSCOPIC RESECTION FOR
GASTRIC NEOPLASMS IN THE PYLORUS
E.J. Gong1,*, D.H. Kim1, H.-Y. Jung1, H. Lim2, K.-S. Choi1, J.Y. Ahn1,
J.H. Lee1, K.D. Choi1, H.J. Song1, G.H. Lee1, J.-H. Kim1
1
Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center,
Seoul, 2Gastroenterology, Hallym University Sacred Heart Hospital, Anyang,
Korea, Republic Of
INTRODUCTION: Endoscopic resection (ER) for gastric neoplasms in the
pylorus is a technically difficult procedure.
AIMS & METHODS: We investigated clinical outcomes to determine the feasibility and effectiveness of ER for gastric neoplasm in the pylorus. Subjects who
underwent ER for gastric neoplasm in the pylorus at Asan Medical Center
between January 1997 and February 2012 were eligible. The clinical features of
patients and tumors, histopathologic characteristics, adverse events, results from
ER, and survival were investigated.
RESULTS: A total of 227 subjects underwent ER for 228 gastric neoplasms in
the pylorus. Median age was 62 years (interquartile range [IQR]: 53-68 years),
and the male to female ratio was 2.2:1. Median tumor size was 14 mm (IQR: 1022 mm), and median procedure time was 23 minutes (IQR: 15-33 minutes). En
bloc resection was achieved for 193 lesions (84.6%), including complete resection
(CR) of 195 lesions (85.5%), and curative resection (CuR) of 167 lesions (73.2%).
Rates of CR and CuR were significantly lower for pyloric and postpyloric lesions
than for prepyloric lesions (p 0.002 and p 0.006). Adverse events occurred in
19 patients, including delayed bleeding in 12 (5.3%) and stricture in 7 (3.1%).
During a median follow-up period of 79.0 months, local tumor recurrence was
detected in 2.6%. The 5-year overall and disease-specific survival rates in the 83
patients with gastric cancer were 81.5% and 96.9%, respectively.
CONCLUSION: ER appears to be a feasible and effective method for the treatment of gastric neoplasms in the pylorus, on the basis of these favorable clinical
outcomes.
Disclosure of Interest: None declared
P0131 THE ROLE OF NONCONTRAST COMPUTED TOMOGRAPHY
(CT) PRIOR TO THE ENDOSCOPIC INTERVENTION FOR THE
SUSPICIOUS ESOPHAGEAL FISH BONE (FB)
E.K. Choi1,*, S.U. Jeong1, H.U. Kim1, S.-J. Boo1, S.-Y. Na1, H.J. Song1, Y.K. Cho1, B.-C. Song1
1
Internal Medicine, Jeju National University Hospital, Jeju-Do, Korea, Republic
Of
Contact E-mail Address: suhmok@gmail.com
INTRODUCTION: Accidental foreign body ingestion is not uncommon among
patients of all ages. The immediate risk to the patient ranges from negligible to life
threatening. In Asian countries, fish bones (FB) are the most prevalent esophageal
foreign bodies and they are usually ingested accidentally together with food. The
FBs have sharp polygonal or pin-like pointed structure and they can perforate or
tear the esophageal wall. Therefore, endoscopic intervention should be performed
if FB is impacted in the esophagus. However, it is difficult to diagnose esophageal
FB with symptom, sign or plain radiography in most cases. Computed tomography (CT) has been proven to be accurate and noninvasive technique for evaluating
the structures of esophagus. There are few reports or practical guidelines for using
CT scan for the diagnosis of esophageal FB till now.
AIMS & METHODS: The aim of this study was to evaluate the usefulness of CT
scan for the diagnosis of esophageal FB. Between March 2009 and March 2014,
consecutive patients with suspected esophageal FB at Jeju National University
Hospital were identified. Among those, patients with normal plain radiography
were included, and medical records were abstracted for CT scan and endoscopy
with outcomes. In some patients, noncontrast neck CT scan was performed prior
to endoscopic intervention. We evaluated the outcome in two groups (pre-endoscopic CT or No CT).
RESULTS: During the study period, 134 patients (M:F 55:79) who were
strongly suspected of FB ingestion with normal plain radiography were enrolled.
The mean age was 54.515.6. Of those 134 patients, 91 (68%) underwent CT

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United European Gastroenterology Journal 2(1S)

scan, and 43 (32%) underwent endoscopic intervention without CT scan. Among


91 patients with pre-endoscopic CT scan, 57 patients had positive CT findings of
FB. The subsequent endoscopic procedure showed FB in 56 (98%), and FB was
removed in all patients successfully. Among 34 patients who had negative finding
of FB on the CT scan, 20 patients underwent endoscopy because of patients
request. However, FB was found in only 2 (10%) patients at the inlet of esophagus. In these two patients, artifacts which were made by dental prosthesis interfered with detecting FB on the CT scan. Among 43 patients without preendoscopic CT scan, 31 patients (72%) had esophageal FB in endoscopic examination. The sensitivity, specificity, positive predictive value, and negative predictive value of CT scan for the detection of FB was 98.2%, 90.1%, 96.5%, and
94.7%, respectively.
CONCLUSION: Pre-endoscopic CT scan is accurate and noninvasive diagnostic
modality for the detection of ingested esophageal FB. Moreover, CT scan prior
to endoscopic procedure is very useful to avoid unnecessary endoscopic procedure. Further studies are needed about the advantages of pre-endoscopic CT scan
for the evaluation of pre-endoscopic complication and for the planning of endoscopic removal method.
Disclosure of Interest: None declared
P0132 ENDOSCOPIC THERAPY IN UPPER GI BLEEDING: ARE WE
FOLLOWING THE GUIDELINES?
G. Goodchild1,*, S. Subramaniam1, K. Besherdas1
Gastroenterology, Barnet and Chase Farm NHS Trust, London, United Kingdom

INTRODUCTION: Acute upper gastrointestinal bleeding (UGIB) is a common


medical emergency that carries a 10% inpatient mortality. Acute peptic ulcer
disease is the most common aetiology followed by variceal bleeding. Mortality
has not significantly improved over the last 50 years, highlighting the need to
follow best practice guidelines in order to improve outcomes.
Upper GI endoscopy allows us to diagnose and treat the cause of UGIB as well
as to help prevent re-bleeding. The 2012 NICE guidance on the management of
non-variceal UGIB states that adrenaline as monotherapy should be avoided. It
suggests that only mechanical therapy (e.g clips) be used as monotherapy and
that adrenaline should always be used as dual therapy with either clips or thermal
coagulation (APC).
The aim of our study was to audit our practice and compliance with NICE
guidance in delivering appropriate endoscopic therapy for non variceal UGIB
and to ascertain the rate of re-bleeding.
AIMS & METHODS: A retrospective analysis of all patients who underwent
upper GI endoscopy for melaena or haematemesis as a primary symptom over an
eight year period (2006-2013) was performed within a large district general North
London NHS trust. Data was obtained from the Unisoft Endoscopy reporting
software. The therapies used at endoscopy for UGIB were scrutinized.
RESULTS: 3759 patients were referred for upper GI endoscopy with melaena or
haematemesis. 594 patients received endoscopic therapy (102 for variceal bleeds
and 492 for non-variceal bleeds).
Table 1: Therapies in non-variceal upper GI bleeding:
Therapy

Number of patients (%)

Adrenaline monotherapy
Adrenaline Endoclip*
APC monotherapy
Adrenaline APC*
Endoclip monotherapy*
Adrenaline APC endoclip*
Endoclip APC
Total

172 (34.9%)
117 (23.8%)
94 (19.1%)
53 (10.8%)
32 (6.5%)
18 (3.7%)
6 (1.2%)
492

A total of 26 patients (5.3%) diagnosed with non-variceal upper GI bleeding


experienced re-bleeding (defined as the re-appearance of melaena/haematemesis
with repeat endoscopy within 7 days). Of these patients 14 (53.8%) had received
optimal (NICE recommended) therapy whilst 12 (46.2%) had received sub-optimal therapy (7 had adrenaline monotherapy and 5 had APC monotherapy).
There was no associated increase in mortality compared to the national average.
CONCLUSION: This study demonstrates poor adherance to current NICE guidance on dual therapy in non variceal UGIB as only 45% of patients received
optimal intervention. Endoscopic monotherapy for acute UGIB either with
adrenaline (35%) or APC (19%), though no longer recommended was still evident within our trust. The type of therapy given did not influence the risk of rebleeding in our population and our overall mortality rates fell within expected
levels.
Disclosure of Interest: None declared

P0133 PRIMARY OBESITY SURGERY ENDOLUMENAL METHOD FOR


THE TREATMENT OF 162 OBESE PATIENTS WITH A FOLLOW UP
TIME OF 1 YEAR
G. Lopez-Nava1,*, I. Bautista-Castano1, A. Jimenez-Banos 1, T.de GradoManchado 1, J.P. Fernandez-Corbelle1
1
Bariatric Endoscopy Unit, Sanchinarro University Hospital, Madrid, Spain,
Madrid, Spain
Contact E-mail Address: inmaculadabautista60@gmail.com
INTRODUCTION: Obesity is at epidemic proportions and rising1. Bariatric
surgical procedures have demonstrated better durable weight loss than diet and
exercise. However risk may limit adoption of these procedures2. Endoscopic
procedures like the Primary Obesity Surgery Endolumenal (POSE), may offer
less risk and satisfactory results, however, limited safety and outcome data is
available3.
AIMS & METHODS: The objective of the study was to describe the POSE
procedure, perioperative care, one year safety and weight loss outcomes for a
single center.
Methods: 162 patients undergoing the POSE procedure between July 2011 and
April 2013 were followed for one year. Overall patient status and weight data was
collected at baseline and at 1 year (n 130). Outcomes included adverse events,
change in total body weight (TBWL), percentage of TBWL (%TBWL) and
percentage of excess weight loss (%EWL).
RESULTS: Patients tolerated the procedure well with no serious short or long
term adverse events. All but one patient was discharged within 24 hours of
procedure. Mean age was 43.711.0 years and baseline BMI was 38.0  4.9
kg/m2. Initial body weight (106.7 18.0 kg) was significantly reduced at 1
year: mean TBWL was 16.010.2 kg and mean % TBWL was 14.48.2%. At
1 year of follow up %EWL was 43.425.6%
CONCLUSION: The POSE method can be considered an effective, safe and well
tolerated for the treatment of patients with obesity, at least at 1 year of follow-up.
REFERENCES
1- World Health Organization. Obesity: preventing and managing the global
epidemic. Report of a WHO Consultation (WHO Technical Report Series
894),
http://www.who.int/nutrition/publications/obesity/WHO_TRS_894/en/
(accessed 5 March 2014).
2- Gloy VL, Briel M, Bhatt DL, et al. Bariatric surgery versus non-surgical
treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ 2013; 347: f5934.
3- Espinos JC, Turro R, Mata A, et al. Early Experience with the incisionless
operating platform (IOP) for the treatment of obesity: The primary obesity surgery endolumenal (POSE) procedure. Obes Surg 2013; 23: 1375-1383.
Disclosure of Interest: None declared
P0134 A KOREAN MULTI-CENTER STUDY TO EVALUATE THE
EFFICACY OF THE OTSC SYSTEM FOR TREATMENT OF GI
FISTULA, PERFORATION AND NOTES ENTRY SITE CLOSURE
H.L. Lee1,*, J.Y. Cho2, J.-H. Cho2, J.J. Park3, S.H. Kim4, J.-H. Han5
1
Gastroenterology, HANYANG UNIVERSITY HOSPITAL, 2Gastroenterology,
Soonchunhyang University, 3Gastroenterology, Korea University,
4
Gastroenterology, Eulji University, Seoul, 5Gastroenterology, Chungbuk National
University, Cheongju, Korea, Republic Of
Contact E-mail Address: alwayshang@hanyang.ac.kr
INTRODUCTION: Recently, a new over-the-scope clip (OTSC) (Ovesco
Endoscopy, Tuebingen, Germany) system has been developed and used for the
primary non-surgical closure of GI tract perforations and fistulas.
AIMS & METHODS: The aims of this study were to investigate the therapeutic
yield of endoscopic management by the OTSC system. We performed a multicenter prospective study. In total six experts (five centers) performed OTSC
procedure.
RESULTS: This study involved in total 17 patients (median age 55 years (range
32-77 years), 12 men) with GI leaks from anastomotic dehiscence, fistulas, and
esophageal perforation due to Boerhaaves syndrome: Three gastrojejunostomy
site, three esophagojejunostomy site, three esophagogastrostomy site, two
Boerhaave syndrome, two gastrobronchial fistula, one gastrocolonic fistula,
one endoscopic full thickness resection site closure, one jejuno-jejunal fistula,
one colonopseudocyst fistula. The diameter of leaks ranged between 5 and 20
mm. Mean procedure time was 18.3 min. Technically, all procedures were succssful. Complete sealing of leaks was achieved by using OTSC alone in 14 of 17
patients. For one OTSC fail patient, closure was completed by placing one
additional covered stent. Two fistula cases required surgical repair.
CONCLUSION: The OTSC system is very useful in the management of GI leaks
especially in case of anastomotic leakage after bowel surgery.
Disclosure of Interest: None declared
P0135 THE TISSUE EFFECT OF ARGON-PLASMA COAGULATION
WITH PRIOR SUBMUCOSAL INJECTION (HYBRID-APC) VERSUS
STANDARD APC: A RANDOMIZED EX-VIVO STUDY
H. Manner1,*, A. Neugebauer2, M. Scharpf3, K. Braun1, C. Ell4, F. Fend3,
M.D. Enderle2
1
HSK Wiesbaden, Wiesbaden, 2Erbe Elektromedizin, 3Institute of Pathology,
University Tuebingen, Tuebingen, 4Sana Klinikum, Offenbach, Germany
Contact E-mail Address: HSManner@gmx.de
INTRODUCTION: Thermal ablation for Barretts esophagus has widely been
established in gastrointestinal endoscopy during the last decade. The mainly used
methods of radiofrequency ablation (RFA) and argon-plasma coagulation

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United European Gastroenterology Journal 2(1S)


(APC) carry a relevant risk of stricture formation of up to 5-15%. Newer ablation techniques that are able to overcome this disadvantage would therefore be
desirable.
AIMS & METHODS: The aim of the present study was to compare the depth of
tissue injury of the new method of Hybrid-APC versus standard APC within a
randomized study in a porcine esophagus model. Using a total of 8 explanted pig
esophagi, 48 esophageal areas were ablated either by standard or Hybrid-APC
(APC with prior submucosal fluid injection) using power settings of 50 and 70W.
The depth of tissue injury to the esophageal wall was analysed macroscopically
and histopathologically.
RESULTS: Using 50 W, mean coagulation depth was 937469mm during standard APC, and 477271mm during Hybrid-APC (p 0.064). Using 70 W, coagulation depth was 1096320mm (standard APC) and 468136 mm (HybridAPC; p 0.003). During all settings, damage to the muscularis mucosae was
observed. Using standard APC, damage to the submucosal layer was observed
in 4/6 (50 W) and 6/6 cases (70 W). During Hybrid-APC, coagulation of the
submucosal layer occurred in 2/6 (50 W) and 1/6 cases (70 W). The proper muscle
layer was only damaged during conventional APC (50W: 1/6; 70W: 3/6).
CONCLUSION: Hybrid-APC reduces coagulation depth by half in comparison
with standard APC, with no thermal injury to the proper muscle layer. It may
therefore lead to a lower rate of stricture formation during clinical application.
Disclosure of Interest: H. Manner: None declared, A. Neugebauer Other:
Employee of Erbe Elektromedizin, M. Scharpf: None declared, K. Braun:
None declared, C. Ell: None declared, F. Fend: None declared, M. Enderle
Other: Employee of Erbe Elektromedizin
P0136 EVALUATION OF GASTRIC SUBMUCOSAL TUMORS BY
ENDOSCOPIC VISUALIZED FEATURES ON SUBMUCOSAL
ENDOSCOPY
H. Kobara1,*, H. Mori1, S. Fujihara1, N. Nishiyama1, T. Matsunaga1, M. Ayaki1,
T. Yachida1, T. Masaki1
1
Gastroenterology and Neurology, Kagawa University, Kagawa, Japan
Contact E-mail Address: kobara@med.kagawa-u.ac.jp
INTRODUCTION: Although the macroscopic characteristics of submucosal
tumors (SMTs), such as gastrointestinal stromal tumors (GISTs), have been
characterized, the assessment of SMTs by their endoscopic visualized features
(EVF; which are observed by endoscopic imaging under direct view) remains
unevaluated.
AIMS & METHODS: The aim of the present study was to investigate the
potential of endoscopic diagnostics for SMTs using EVF. The EVF of 26 gastric
SMT cases, in which the final pathological diagnosis was obtained by bloc biopsy
using the submucosal endoscopy with mucosal flap method, were retrospectively
reviewed. Each type of SMT was classified according to the following five EVF:
Color, clarity, shape, tumor coating and solidity. Additionally, the EVF of 13
low-risk GISTs and 13 benign submucosal tumors (BSTs) were comparatively
evaluated for the five abovementioned EVF.
RESULTS: Similar trends were identified between the low-risk GISTs, granular
cell tumors and the schwannoma with regard to EVF. While these tumors exhibited cloudy EVF, leiomyomas tended to exhibit clear EVF. Among SMTs of the
heterotopic pancreas type, the EVF demonstrated particularly small nodules of
the pancreatic tissue itself. Although the sample size included in the present study
is small, a classification system for gastric SMTs was proposed according to the
EVF. When compared with the BST group, the GIST group demonstrated a
significantly higher frequency of tumors that exhibited a combination of three
EVF (white, cloudy and rigid) that are consistent with all gastric GISTs
(P50.05).
CONCLUSION: Gastric SMTs may be classified based on the EVF, which
indicates that the EVF possess potential diagnostic value for the differentiation
of GISTs from BSTs.
REFERENCES
1. Kobara H, Mori H, Masaki T, et al. Bloc biopsy by tunneling method using
the endoscopic submucosal dissection for upper gastrointestinal submucosal
tumor. Endoscopy 2012; 44: E197-E198.
2. Kobara H, Mori H, Fujihara S, et al. Bloc biopsy by using submucosal endoscopy with a mucosal flap method for gastric subepithelial tumor tissue sampling
(with video). Gastrointest Endosc 2013; 77: 141-145.
3. Kobara H, Mori H, Masaki T, et al. Gastric heterotopic pancreas can be
identified by endoscopic direct imaging with submucosal endoscopy. J
Gastrointestin Liver Dis 2013; 22: 345-348.
Disclosure of Interest: None declared
P0137 MIXED HISTOLOGICAL-TYPE (INTESTINAL AND DIFFUSE
TYPE) EARLY GASTRIC CANCER PATIENTS TENDED TO BE
NON-CURATIVE RESECTION BY ENDOSCOPIC SUB-MUCOSAL
DISSECTION
H. Osumi1,*, J. Fujisaki1, M. Igarashi1
1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation
for Cancer Research, Tokyo, Japan
Contact E-mail Address: hiroki.osumi@jfcr.or.jp
INTRODUCTION: It is well known that the histological types of gastric cancer
are intestinal and diffuse type (by Lauren1). Intestinal type mucosal gastric
cancer will be cured by ESD. However, Diffuse type gastric cancers have
lymph node metastasis and even intramucosal cancer. Intestinal type was divided
into well (tub1) differentiated adenocarcinoma and moderately (tub2) differentiated adenocarcinoma according to their structure abnormality by Japanese
Classification of Gastric carcinoma (JCGC). Intestinal type is equal to differentiated adenocarcinoma and Diffuse type is equal to undifferentiated

adenocarcinoma by JCGC. Mixed-histological type (Intestinal and Diffuse)


early gastric cancer sometimes yields different results in pre-endoscopic submucosal dissection (ESD) biopsy diagnosis and post-operative ESD diagnosis.
This complicates the diagnosis of the cancer region using narrow band imaging
(NBI).
AIMS & METHODS: The purpose of this study is to evaluate the clinical characteristics and tendencies of mixed-histologic-type early gastric cancer, and bring
up points of consideration of pre-operative ESD diagnosis. 1259 patients who
were diagnosed with predominantly differentiated early gastric cancer (M: 1026
cases, SM: 233 cases) and who were treated with ESD between 2005 and 2012
without previously being treated at the Cancer Institute Hospital were retrospectively studied. The histological type of the cancer tissue, the criteria used to
determine the stump, and the degree of SM invasion were determined based on
the Japanese Classification of Gastric Carcinoma (JCGC). The Chi-square test
and logistic regression analysis were used as univariate and multivariate analysis
respectively to statistically compare the test groups.
RESULTS: Mixed-histologic-type early gastric cancer was defined as showing
10% or more undifferentiated adenocarcinoma in the post-operative ESD diagnosis. 94.6% of well (tub1) differentiated adenocarcinoma diagnosed by biopsy
accorded with final ESD specimens pathology. However, 68.2% of moderately
(tub2) differentiated adenocarcinoma diagnosed by biopsy accorded with ESD
specimens. Mixed-histologic-type adenocarcinoma tended to be bigger in size and
had a higher positive rate of sub-mucosal invasion than pure differentiated adenocarcinoma. (Size: 23.2 mm (13.2) vs14.7 mm (9.8), p50.05 SM: 45% vs
26%, p50.05) The rates of lateral margin involvement (LM), Lymphatic invasion (ly) and Lymph node metastasis (LN) were significantly different between
groups of pure differentiated adenocarcinoma and mixed-histologic-type
adenocarcinoma.(LM: 5.4% vs 1.0%, p 0.003 ly: 18% vs 3.1%, p50.05 LN:
3.6% vs 0.3%, p 0.003) In the multivariate analysis, all the above factors are
significantly different between groups.
CONCLUSION: If pre-operative histological diagnosis using biopsy specimens
before ESD shows tub2, there is the possibility that it is mixed-histologic-type
early gastric cancer. We consider it necessary in such a case to conduct a careful
pre-operative diagnosis of the cancer region using NBI or a biopsy of the surrounding area, while keeping in mind the clinical characteristics of mixed-histologic-type adenocarcinoma avoiding non- curative resection by ESD.
REFERENCES
1 Lauren T. The two histological main types of gastric carcinoma. Acta Pathol
Microbiol Scand 1965; 64: 34.
Disclosure of Interest: None declared
P0138 A MORPHOLOGICAL CLASSIFICATION OF WHITE OPAQUE
SUBSTANCE WITHIN GASTRIC NEOPLASIA VISUALIZED BY
MAGNIFYING ENDOSCOPY WITH NARROW-BAND IMAGING
H. Ueyama1,*, A. Nagahara1, K. Matsumoto1, Y. Nakagawa1, K. Matsumoto1,
T. Yao2, S. Watanabe1
1
Gastroenterology, 2Human Pathology, Juntendo University School of Medicine,
Bunkyo-Ku, Japan
Contact E-mail Address: psyro@juntendo.ac.jp
INTRODUCTION: White opaque substance (WOS) identified within gastric
neoplasias is a unique finding visualized in magnifying endoscopy with
narrow-band imaging (ME-NBI) and represents intramucosal accumulation of
lipid droplets. The morphological classification of WOS within gastric neoplasia
has not been investigated in detail.
AIMS & METHODS: The aim of the current study was to establish the morphological classification of WOS and investigate whether it can be used to discriminate between adenoma and early carcinoma. This study retrospectively
investigated two hundred twenty-seven patients with 242 gastric neoplasias (29
adenomas and 213 early carcinomas) who underwent ME-NBI before endoscopic
resection in our hospital between January 2010 and December 2013. We studied
the frequency of WOS within gastric neoplasias and identified the following
morphological patterns: 1) dotted pattern, scattered and distributed as dots; 2)
linear pattern, shaped like a line composed of aggregated dots; 3) reticular pattern, shaped like a honeycomb composed of connected lines; 4) speckled pattern,
mottled and composed of aggregated dots; and 5) diffuse pattern, diffusely distributed by dense WOS in the intervening part. We also investigated the irregularity of WOS within adenomas and early carcinomas. We defined irregular WOS
as disorganized and asymmetrical distribution of WOS in all patterns.
RESULTS: WOS was more frequently observed in adenomas (13/29: 44.8%)
than in early carcinomas (62/213: 29.1%). WOS within adenomas showed a
symmetrical distribution with a regular reticular pattern because the intervening
part has no severe structural abnormalities. The WOS within carcinomas showed
an asymmetrical distribution with an irregularly dotted or speckled pattern
because the intervening part has severe structural abnormalities.

Dotted pattern
Linear pattern
Reticular pattern
Speckled pattern
Diffuse pattern
Irregular WOS

Adenoma (13)

Carcinoma (62)

P value

2
5
8
4
1
3

30 (48.4%)
13 (21.0%)
9 (14.5%)
40 (64.5%)
8 (12.9%)
60 (96.8%)

50.05
NS
50.01
0.053
NS
50.01

(15.4%)
(38.5%)
(61.5%)
(30.8%)
(7.69%)
(23.1%)

A168
CONCLUSION: In gastric neoplasias containing WOS, the morphological classification of WOS is useful in discriminating between adenoma and early
carcinoma.
Disclosure of Interest: None declared
P0139 ESTABLISHMENT OF AN ENDOSCOPIC DIAGNOSIS FOR
GASTRIC ADENOCARCINOMA OF THE FUNDIC GLAND TYPE
(CHIEF CELL PREDOMINANT TYPE) USING MAGNIFYING
ENDOSCOPY WITH NARROW-BAND IMAGING
H. Ueyama1,*, K. Matsumoto1, A. Nagahara1, Y. Nakagawa1, K. Matsumoto1,
T. Yao2, S. Watanabe1
1
Gastroenterology, 2Human pathology, Juntendo University School of Medicine,
Bunkyo-Ku, Japan
Contact E-mail Address: psyro@juntendo.ac.jp
INTRODUCTION: Gastric adenocarcinoma of the fundic gland (chief cell predominant type, GA-FG-CCP) has recently been proposed as a new and rare
variant of gastric adenocarcinoma. We previously described the clinicopathoplogical and endoscopic features of GA-FG-CCP using conventional endoscopy
(CE) in 2010 and 20141-2. If this tumor type is not recognized by a physician,
it may be misdiagnosed as a submucosal tumor or fundic gland polyp or it may
be overlooked. Therefore, the endoscopic diagnosis of GA-FG-CCP using magnifying endoscopy with narrow-band imaging (ME-NBI) may be useful; however, this technique has not been investigated in detail.
AIMS & METHODS: The aim of the current study was to evaluate the endoscopic features of GA-FG-CCP using ME-NBI. A total of 17 GA-FG-CCPs were
evaluated retrospectively between January 2008 and December 2013. The endoscopic and clinicopathological features of the lesions were analyzed to provide
information of diagnostic value.
RESULTS: A total of 17 patients [median age 66 y (57-75), 10 men, 7 women]
with 17 lesions were treated as follows: 12 were treated with ESD, 3 were treated
with EMR, and 2 underwent surgery. Except for 2 cases that underwent additional surgery, all of the cases underwent an endoscopic removal without further
treatment. Twelve of the lesions were detected in the upper stomach, 4 in the
middle stomach, and 1 in the lower stomach. Macroscopically, 9 lesions were
submucosal tumors in shape, whereas 5 were depressed, 1 was flat-elevated, 1 was
protruded and 1 was flat in shape. The mean tumor size was 11.8 (3-39) mm.
Histopathologically, there were 5 intramucosal cancers and 12 submucosal invasive cancers. The mean depth of the submucosal invasion was 337.5 (50-1200)
mm. Lymph node metastasis was observed in one case (25%, 1/4). The most
common features of the 17 lesions with CE were 1)submucosal tumor shape in
10(58.8%) cases, 2) whitish color in 12(70.6%) cases, 3)dilated vessels with
branching architecture in 9(52.9%) cases and 4)background mucosa without
atrophic change in 15 (88.2%) cases. The endoscopic findings for a GA-FGCCP using ME-NBI did not meet the criteria for carcinoma. However, we
detected the four most frequently occurring features using ME-NBI to be 1)an
indistinct line of demarcation between the lesion and the surrounding mucosa 8/
8(100%), 2)a dilatation of the crypt opening 7/8(87.5%), 3)a dilatation of the
intervening part between the crypts 5/8(62.5%) and 4)the presence of microvessels without distinct irregularities 7/8(87.5%).
CONCLUSION: GA-FG-CCP has distinct endoscopic characteristics, especially
in terms of its shape, color, vessels and background mucosa using CE and in its
demarcation lines, the shape of the crypt opening, the shape of the intervening
part between the crypts and the microvessels observed with ME-NBI. Further
investigations should include collecting cases using CE and ME-NBI based on
these endoscopic features.
REFERENCES
[1] Ueyama H, et al. Gastric adenocarcinoma of fundic gland type (chief cell
predominant type): proposal for a new entity of gastric adenocarcinoma. Am J
Surg Pathol 2010; 34: 609619.
[2] Ueyama H, et al. Gastric adenocarcinoma of the fundic gland type (chief cell
predominant type). Endoscopy 2014; 46(02): 153-157.
Disclosure of Interest: None declared
P0140 DIAGNOSTIC AND THERAPEUTIC EFFICACY OF ENDOSCOPIC
ENUCLEATION FOR SMALL GASTRIC MUSCULARIS PROPRIA
LAYER TUMOR
H. Kim1,*, B. Bang1, K. Kwon1, Y. Shin1
1
Internal Medicine, Inha University Hospital, Incheon, Korea, Republic Of
INTRODUCTION: Gastric subepithelial tumors originated from muscularis
propria (MP) are partly benign tumors, but some gastric stromal tumors have
malignant potential, especially gastrointestinal stromal tumors (GISTs). PM
tumors are usually treated by surgical intervention and endoscopic treatment
remains controversial. The aim of this study was to retrospectively evaluate the
utility of endoscopic enucleation for diagnosis and treatment of MP tumors.
AIMS & METHODS: From January 2010 to June 2013, forty patients with
gastric MP tumor ( 20 mm) underwent endoscopic enucleation. Before endoscopic resection, all patients performed endoscopic ultrasound to determine the
layer of origin and the accurate size. Small PM tumor (512 mm) was resected by
using band ligation method and PM tumor (range 12-20 mm size) was enucleated
by endoscopic submucosal resection (ESD) technique using various endo-knifes.
Tumor characteristics, tumor size, procedure technique, complete resection rate
and recurrence were analyzed.
RESULTS: A total 40 patients (16 men, 24 women; mean age 50.3 years) were
eligible for inclusion in this study. The histologic diagnosis was leiomyoma
(n 24), GIST (n 15) and schwanoma (n 1). Band ligation method was
used in 20 patients. Median procedure time was 8 min (5-26) and complete
resection rate was 95% (19/20). Two patients developed perforation, which

United European Gastroenterology Journal 2(1S)


was closed by endoscopic methods with metallic clips. ESD method was used
in 20 patients. The mean procedure time was 41.1 minutes (range 10 260) and
complete resection rate was 60% (12/20). Four cases were complicated by perforation, and the perforations were closed with metal clips. The mean follow-up
time was 9.8 months (range 3-35). No recurrence was developed during follow-up
period.
CONCLUSION: Endoscopic enucleation appears to be effective method for the
histologic diagnosis and removal of small MP layer tumors (52cm). Although
there is a risk of perforation which has become manageable endoscopically.
REFERENCES
Park YS, Park SW, Kim TI et al. Endoscopic enucleation of upper-GI submucosal tumors by using an insulated-tip electrosurgical knife. Gastrointest Endosc
2004; 59: 409-415.
Huang WH, Feng CL, Lai HC, et al. Endoscopic ligation and resection for the
treatment of small EUS-suspected gastric GI stromal tumors. Gastrointest
Endosc 2010; 71: 1076-1081.
Jeong ID, Jung SW, Bang SJ, et al. Endoscopic enucleation for gastric subepithelial tumors originating in the muscularispropria layer. Surg Endosc 2011; 25: 468474.
Disclosure of Interest: None declared
P0141 COMPARISON
OF
DEXMEDETOMIDINE
VERSUS
MIDAZOLAM FOR PROCEDURAL SEDATION DURING
ENDOSCOPIC SUBMUCOSAL DISSECTION OF GASTRIC TUMOR
I.-K. Sung1,*, H.S. Park1, J.H. KIM1, S.-Y. Lee1, S.-P. Lee1, C.S. Shim1
1
Konkuk university medical center, Seoul, Korea, Republic Of
Contact E-mail Address: inksung@kuh.ac.kr
INTRODUCTION: Endoscopic submucosal dissection (ESD) is nowadays commonly performed as a treatment for gastric tumor. However, the sedation with
midazolam (MDZ) often did not reach a satisfactory sedation during the procedure and the drug could suppress respiration and blood pressure also.
AIMS & METHODS: To investigate the safety and efficacy of dexmedetomidine
(DEX) in comparison with midazolam (MDZ) as a sedative during an endoscopic submucosal dissection (ESD) of gastric tumor.
Design: Prospective, randomized, double-blind study.
Setting: Tertiary-care institution.
Patients: Scheduled patients undergoing ESD of gastric tumor.
Main Outcome Measurements: The depth of sedation by using a MOAA/S score
(Modified Observers Assessment alertness/sedation), interfering actions of
patients, sedation related-adverse events, and the satisfaction degree of the
doctors.
RESULTS: Eighty patients were randomly assigned to one of two treatment
regimens (40 patients of each). There was no statistically significant difference
between the two groups regarding age, sex, body mass index, ASA classification,
and tumor characteristics. Appropriate sedation rate and the satisfaction degree
of the doctors were significantly high in the DEX group. There were more movements of patient leading to an interruption of the procedure in the MDZ group
than in the DEX group. There was no difference in the adverse events between
the two groups.
CONCLUSION: DEX for the sedation during gastric ESD is as safe as MDZ
and the sedation effect of DEX is superior to that of MDZ.
Key words: Procedural sedation; Endoscopic submucosal dissection; Sedative
agents; Dexmedetomidine; Midazolam
Disclosure of Interest: None declared
P0142 A NEW METHOD TO PERFORM DIRECT PERCUTANEOUS
ENDOSCOPIC JEJUNOSTOMY USING DOUBLE BALLOON
ENTEROSCOPY AND FLUOROSCOPY
J. Velazquez1,2,*, R. Beyer2, K. Kabir Baig2, K. Monkemuller2
1
ENDOSCOPY, UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO,
MEXICO, Mexico, 2ENDOSCOPY, UNIVERSITY OF ALABAMA,
Birmingham, United States
Contact E-mail Address: jacovelazquez@gmail.com
INTRODUCTION: Direct percutaneous endoscopic jejunostomy (DPEJ) is
usually performed using traditional push enteroscopes or pediatric colonoscopes.
The success rate of DPEJ in expert hands is about 68%. Herein we present a new
method to perform DPEJ using DBE and fluoroscopy.
AIMS & METHODS: To report on the efficacy and safety of DBE-assisted
DPEJ with simultaneous use of fluoroscopy.
The DBE was performed by using the standard push-pull-technique after the
balloon enteroscope was advanced beyond the ligament of Treitz. During
advancement, a site in the jejunum was sought for PEJ tube placement by transillumination and finger indentation. In addition we confirmed the site of indentation by placing a radio-opaque marker on the skin and verifying that the small
bowel loop was closed to the skin. After a suitable site was identified, DPEJ
placement was performed by using the Ponsky-method (pull-type-percutaneous
gastrostomy tube technique and 20 Fr PEG-kit.
After placing the DPEJ we administered water soluble contrast through the tube
to clearly confirm intraluminal jejunal positioning.
RESULTS: The study included 24 patients (11 females, 13 males, mean age 55
years, age range 31-79). The indications for DPEJ were feeding in 23 patients and
venting for malignant small bowel obstruction in one. The technical success was
91.6%. In two patients no transillumination was possible. The mean distance of
DPEJ was 74 cm (range 50 to 90 cm) past the pylorus or the anastomosis. One
jejunostomy site got infected (4.1%). There were no major complications associated with the procedure.

A169

United European Gastroenterology Journal 2(1S)


CONCLUSION: DBE-DPEJ using fluoroscopic assistance seems an efficacious,
safe and successful approach for patients requiring jejunal enteral feeding.
Nevertheless, studies comparing the double balloon enteroscopy technique to
the standard push enteroscopy technique are needed to establish potential advantages of this technique.
REFERENCES
1. Maple JT, Petersen BT, Baron TH, et al. Direct percutaneous endoscopic
jejunostomy: outcomes in 307 consecutive attempts. Am J Gastroenterol 2005;
100: 2681-2688.
2. Zhu Y, Shi L, Tang H, et al. Current considerations of direct percutaneous
endoscopic jejunostomy. Can J Gastroenterol 2012; 26: 92-96.
3. Kwon RS, Banerjee S, Desilets D, et al. Enteral nutrition access devices.
Gastrointest Endosc 2010; 72: 236-248.
4. Jovanovic I, Vormbrock K, Zimmermann L, et al. Therapeutic double-balloon
enteroscopy: a binational, three-center experience. Dig Dis 2011; 29: 27-31.
5. Monkemuller K, Vormbrock K, Kassalik M, et al. A. Direct percutaneous
endoscopic jejunostomy tube placement using double-balloon enteroscopy.
Gastrointestinal Endoscopy 2012; 75: 463465.
Disclosure of Interest: None declared
P0143 ENDOSCOPIC CLOSURE OF COMPLEX FISTULAS IN POSTBARIATRIC SURGERY PATIENTS USING THE OVER-THE-SCOPECLIP (OTSC) SYSTEM
J. Velazquez1,2,*, H. Neumann2, C. Diaz2, K. Monkemuller2
ENDOSCOPY, UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO,
MEXICO, Mexico, 2ENDOSCOPY, UNIVERSITY OF ALABAMA,
BIRMINGHAM, United States
Contact E-mail Address: jacovelazquez@gmail.com
1

INTRODUCTION: The novel over-the-scope-clip (OTSC) allows for excellent


apposition of tissue, potentially permitting closure of various types of GI defects.
AIMS & METHODS: To evaluate the usefulness and safety of OTSC for endoscopic closure of fistulas and leaks and perforations in patients with post-obesity
surgery altered upper GI anatomy
Case series of all patients with post-obesity surgery altered upper GI anatomy
referred for attempted endoscopic closure over a 14-months period. Data analysis included clinical characteristics, demographics, indication, and type of bariatric surgery, primary closure, recurrence, complications, and long-term follow-up
clinical outcome.
RESULTS: Seven consecutive patients with fistulas and leaks associated with
previous bariatric surgery, four men, three women, were included. The mean age
was 50.3 years (range 29-66), mean ASA score of 3 (range 2-4). The most
common surgery was gastric sleeve (n 4), followed by gastric bypass (n 3).
Four patients had a gastropleural fistula; three patients had a gastro-peritoneocutaneous fistula. Endoscopic closure was achieved in 6/7 (85.7%). Whereas 4
patients had resolution of the fistula after one endoscopic session, two patients
required two sessions and one patient required three sessions. On long-term
follow-up there was one recurrence, which was treated with another OTSC.
There were no complications associated with OTSC-applications.
CONCLUSION: This is the largest series reported so far on the utility of OTSC
for closure of fistulas associated with bariatric surgery. OTSC represents an
effective, easy to perform and safe endoscopic therapeutic modality for various
types of fistulas. This therapy should be added to the armamentarium of therapeutic endoscopists.
REFERENCES
1. Nishiyama N, Mori H, Kobara H, et al. Efficacy and safety of over-the-scope
clip: including complications after endoscopic submucosal dissection. World J
Gastroenterol 2013; 19: 2752-2760.
2. Junquera F, Mart nez-Bauer E, Miquel M, et al. OVESCO: a promising
system for endoscopic closure of gastrointestinal tract perforations.
Gastroenterol Hepatol 2011; 34: 568-572.
3. Kirschniak A, Subotova N, Zieker D, et al. The Over-The-Scope Clip (OTSC)
for the treatment of gastrointestinal bleeding, perforations, and fistulas. Surg
Endosc 2011; 25: 2901-2905.
4. Sandmann M, Heike M and Faehndrich M. Application of the OTSC system
for the closure of fistulas, anastomosal leakages and perforations within the
gastrointestinal tract. Z Gastroenterol 2011; 49: 981-985.
5. Weiland T, Fehlker M, Gottwald T, et al. Performance of the OTSC System in
the endoscopic closure of iatrogenic gastrointestinal perforations: a systematic
review. Surg Endosc 2013; 27: 2258-2274.
Disclosure of Interest: None declared
P0144 IMPROVING OUTCOMES FROM UPPER GASTROINTESTINAL
BLEEDING IN ENGLAND BETWEEN 2001 AND 2012
J. Rees1,*, F. Evison2, R. Vohra3, N. Trudgill1
1
Gastroenterology, Sandwell General Hospital, 2Health Informatics Department,
3
General Surgery, Queen Elizabeth Hospital, Birmingham, United Kingdom
Contact E-mail Address: jamesrees@doctors.org.uk
INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a common medical emergency with significant mortality. UGIB management has changed in
recent years with early therapeutic endoscopy and interventional radiology
(IR) rather than surgery for uncontrollable bleeding. We have therefore examined outcomes for patients with UGIB over the last decade in England.
AIMS & METHODS: Hospital attendances in England are collated using
Hospital Episode Statistics (HES). ICD-10 coding was used to identify admissions to hospital with UGIB between 2001 and 2012. Death in hospital, 30 day
mortality, emergency readmission within 30 days, median time to endoscopy,
need for surgery or IR and length of stay were examined.

RESULTS: 679,505 episodes were examined involving 378057 men and 301448
women. 51.9% were coded as undergoing inpatient endoscopy. The overall inhospital mortality and 30-day mortality for UGIB was 12.2% and 16.1% respectively. Both in hospital and 30-day mortality fell over the 10 year period examined (2001-2003 14.4% and 18.1% vs. 2009-2012 10.2% and 14.3%, p50.001).
There has been a large fall in age-adjusted in-hospital mortality (81.7 per 1000
(95% CI 79.1-84.3) in 2001-2002 vs. 56.5 (95% CI 56.5-58.3) in 2011-2012). Ageadjusted 30-day mortality has also fallen from 102.9 per 1000 (95% CI 99.9105.9) in 2001-2002 to 79.9 (95% CI 77.7-82.1) in 2011-2012. In-hospital mortality for bleeding varices has fallen by 21.8% from 235.6(95% CI 207.8-265.5)
per 1000 in 2001-2003 to 184.3 (95% CI 165-205) in 2009-2012 and for bleeding
peptic ulcer it has fallen by 18% from 82.2 per 1,000 in 2001-2003 (95% CI 76.788) to 67.4 (95% CI 62.4-72.7) in 2009-2012. For patients who were not coded as
undergoing endoscopy, overall in-hospital and 30-day mortality was higher
(16.4% and 21% respectively) but also fell over the decade. During the same
period there has been a significant fall in the number of patients undergoing
surgery (2001-2003 1.84% vs. 2009-2012 0.75%, p50.001) and a rise in the
proportion of patients undergoing an IR procedure (2001-2003 0.04% vs.
2009-2012 0.18% p50.001). Median time to endoscopy did not change significantly (2001-2003 1(IQR 1-3) days vs. 2009-2012 1(IQR 0-3)days) and the percentage of patients undergoing endoscopy within 48 hours of admission remained
55% over the same time period. Average length of stay fell from 5 (range 2-12)
days in 2001-2003 to 4 (range 1-9) days in 2009-2012 but rates of emergency
readmission within 30 days have significantly increased (2001-2003 18.2% vs.
2009-2012 27.8% p50.001).
CONCLUSION: Outcomes for patients with UGIB have improved over the past
decade with significant reductions in associated mortality and age-adjusted mortality. There has been a reduction in surgery and increase in IR for UGIB.
Disclosure of Interest: None declared
P0145 ROUTINE CONFOCAL ENDOMICROSCOPY IN A CLINIC
SPECIALIZED IN THE MANAGEMENT OF THE DIGESTIVE
PATHOLOGY WITH MUCOSECTOMY, SUBMUCOSAL
DISSECTION, PROSTHESIS AND PUNCTURE: RESULTS OF THE
FIRST MONTHS OF USE
J.M. Canard1,*
1
Gastro Enterology, Clinique du Trocadero, Paris, France
Contact E-mail Address: jm.canard@hotmail.fr
INTRODUCTION: Probe-based Confocal Laser Endomicroscopy (pCLE) is an
imaging technique that allows the achievement of an extemporaneous microscopic exam of a lesion before the treatment or to control the quality of the
endoscopic treatment.
The aim of the study is to appreciate the real indication of Cellvizio in routine in
a clinic specialized in the management of the digestive pathology.
AIMS & METHODS: In 5 months of practice (from May 16th until November
23rd 2013) during 436 endoscopies, 51 procedures of pCLE were performed. In
all cases, the pathologist exam supports the conclusions of the probe-based
microscopic exam.
Among these 51 procedures, 6 are presented:
- One in the esophagus showing the utility of pCLE to find a dysplasia area on a
Barretts Esophagus before mucosectomy followed by a BARRX destruction.
- One in the colon showing the utility of pCLE to differentiate serrated polyps
from hyperplasic polyps so as to realize an immediate resection.
- One in the stomach showing the utility of pCLE to find a gastric dysplasia area
inside relief abnormalities and treat it by submucosa dissection.
- One in the duodenum showing the utility of pCLE to differentiate an inflammatory granuloma from an adenomatous residue which would justify an
ARGON treatment and/or a mucosectomy on a duodenal scare or a right
colic that could initiate major complications.
- One in the biliary duct showing the utility of pCLE for the immediate diagnosis
of cholangiocarcinoma (1) allowing to choose the most appropriate prosthesis.
- One in the pancreas showing the utility of pCLE for the differential diagnosis of
pancreas cysts (serous, mucinous, pseudocysts, cystic forms of neuroendocrine
tumors)
RESULTS: For the first 51 procedures the repartition was: 2 cases in the esophagus (4%), 3 in the cardia (6%), 3 in the stomach (6%), 2 in the duodenum
(4%), 1 in the small bowel (2%), 3 in the biliary duct (6%), 3 in the Vater papillia
(6%), 1 in the pancreas and 33 in the colon (64%).
In 43 cases (84%), the pCLE diagnosis was consistent with those of the pathologist. In 6 cases (12% of cases, 1 in cardia BE, 1 in the stomach, 1 in colonic
mucosectomy scares, 1 at the Vater papillia and 2 colonic polyps). pCLE over
evaluated the lesion. In 2 cases (4% of cases, 2 cases with colon polyp) pCLE
didnt concur with the diagnosis of the pathologist.
CONCLUSION: Optical biopsies have been useful in the management of the
lesions in the whole digestive tract in 51 cases out of 436 (11.7% of cases) before
E. M. R, E. S. D., installation of biliary prosthesis, pancreatic cysts treatment
and to control the nature of potential residues on an E. M. R or E. S. D. scares.
REFERENCES
(1) Giovannini M, et al. Emid study: final results of a prospective bicentric study
assessing Probe-Based Confocal Laser Endomicroscopy (pCLE). Impact in the
management of biliary strictures. Gastrointest Endosc 2013.
Disclosure of Interest: None declared

A170

United European Gastroenterology Journal 2(1S)

P0146 HIGH-PRESSURE
INJECTION
OF
GLYCEROL
WITH
HYBRIDKNIFE FOR ESD IS FEASIBLE AND INCREASES THE
EASE AND SPEED OF THE PROCEDURE: AN IN VIVO STUDY IN
PIGS
J. Jacques1,*, D. SAUTEREAU1, P. CARRIER1, C.-Y. COUQUET2,
M. DEBETTE-GRATIEN1, A.L.-sidaner1, T. TABOURET1,
V. VALGUEBLASSE1, V. LOUSTAUD-RATTI1, R. LEGROS1
1
Hepato-gastro-enterology, CHU Limoges, 2laboratoire departemental, conseil
general de haute vienne, Limoges, France
Contact E-mail Address: jeremiejacques@gmail.com
INTRODUCTION: The HybridKnife water-jet system (ERBE, Tubingen,
Germany) has been shown to increase dissection speed and decreased the risk
of perforation during endoscopic submucosal dissection (ESD). Glycerol mixture
is a viscous, long-lasting solution preferentially used by Japanese ESD experts.
The combination of the HybridKnife system with a glycerol solution has not
been evaluated to date.
AIMS & METHODS: A prospective non-randomised comparative study of ESD
with HybridKnife injecting of either a glycerol mixture or normal saline was
performed. Twenty dissections (ten per group) were performed on four anaesthetised domestic mini-pigs. Dissection speed (mm2/min), size of the specimen
(mm2), duration (min), en bloc resection rate, and bleeding and perforation rates
were prospectively recorded. An evaluation of operator comfort and perception
of safety (dissection score) was performed using a visual analogue scale with 0
being the worst score and 10 the best.
RESULTS: High-pressure injection of the glycerol mixture and dissection with
the HybridKnife was feasible without complications. Dissection was significantly
more rapid (1.67-fold) with glycerol injection than normal saline injection (27.44
vs. 16.44 mm2/min; p50.001). The dissection score was significantly higher in the
glycerol group than in the normal saline group (5.9 vs. 2.9; p50.001) indicating
that both operators felt more comfortable and safe performing ESD with the
glycerol mixture injection. No differences were observed in the rates of en bloc
resection, bleeding and perforation.
Table 1: Results
Solution
2

Mean surface (mm )


Mean time (min)
Mean speed (mm2/min)
Perforation
Bleeding
En bloc resection
Dissection score
Preliminary incision

Glycerol (n 10)

NaCl 0.9% (n 10)

1495 (/- SD 430.3)


54 (/- SD 9.43)
27.44 (/- SD 5.70)
0%
20%
100%
5.9 (/- SD 0.7)
5

976 (/- SD 117.8)


62.6 (/-SD 17.08)
16.44 (/- SD 3.43)
0%
20%
100%
2.9 (/- SD 0.78)
4

0.0127
0.082
50.001
NS
NS
NS
50.001
NS

CONCLUSION: In an in-vivo pig model, high-pressure jet injection of glycerol


with HybridKnife for ESD is feasible and increases the speed and safety of the
procedure compared with use of normal saline.
REFERENCES
Lingenfelder T et al. Combination of water-jet dissection and needle-knife as a
hybrid knife simplifies endoscopic submucosal dissection. Surg Endosc 2009; 23:
15311535.
Pioche M, et al. High-pressure jet injection of viscous solutions for endoscopic
submucosal dissection: a study on ex vivo pig stomachs. Surg Endosc. Epub
ahead of print 3 January 2014.
Disclosure of Interest: None declared
P0147 VALIDATION OF A FRENCH TRAINING PROGRAM OF
ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) IN LIVE PIGS
AIMING TO START EFFICIENT AND SAFE HUMAN RECTAL ESD
J. Jacques1,*, R. LEGROS1, C.-Y. COUQUET2, V. VALGUEBLASSE1,
F. BOULANGER1, A.L.-Sidaner1, R. DALOKO1, A. BOUYGUES1,
P. CARRIER1, M. DEBETTE-GRATIEN1, V. LOUSTAUD-RATTI1,
D. SAUTEREAU1
1
Hepato-gastro-enterology, CHU Limoges, 2laboratoire departemental, conseil
general de haute-vienne, Limoges, France
Contact E-mail Address: jeremiejacques@gmail.com
INTRODUCTION: ESD is a beneficial procedure that allows higher rates of en
bloc and complete resection for large precancerous lesions or superficial cancer.
However, training in ESD requires numerous sessions to become efficient, and so
takes time and patience especially in Western countries. A well-structured training program is essential, because the outcome of ESD is dependent of the experience of the endoscopist. European experts recommend structured training
programs with animal models to overcome the initial learning curve.
Afterwards, constant practicing of ESD is required to increase success and
decrease the procedure time and complications. We report the sucessful experience of a standardized local training program for ESD in a french tertiary center
with a starting recruitment.
AIMS & METHODS: Between March and December 2013, 31 pig gastric ESD
were performed by two operators. After the 11 initial pig gastric ESD, operators
began human rectal ESD and 8 rectal human ESD were performed during the
same period. The 20 next animals ESD were performed in parallel in order to
keep a constant exposure to ESD cases. All procedures were performed with a
hybridknife type T (Erbe medical, Erlangen, Germany). Glycerol mixture and
physiologic serum were used for submucosal injection. Live, 20 kg, domestic

mini-pigs, fasted for 48h prior to the procedure, were used. The duration of
the procedure, size of the specimen, speed of the dissection, en bloc resection
rate, complete resection rate and complications rate were prospectively recorded.
RESULTS: In the pig model, the en bloc resection rate was 96.7% (29/30). The
speed of dissection increased with the experience of the operator to reach a
plateau (30 mm2/min) after 10 dissections. The speed of dissection for the 15
last ESD was significantly higher than the 16 first ESD (16.6 vs 28.2 mm2/min;
p50.001). The mean size of the resected specimen was 1072.8 mm2, the mean
dissection time was 47.9 min and the mean speed of dissection was 22.4 mm2/min.
Only 1 perforation occurred and 6 (19.3%) per procedure bleedings imposed the
use of a coagulation forceps.
In human rectal ESD, en bloc and complete resection rate were 100%. The mean
specimen size was 1909.2 mm2, the mean procedure time was 256 min. The
average speed of dissection was 8.6 mm2/min: 5.8 mm2/min for the first 4
cases vs 10.9 mm2/min for the last 4 cases (p 0.03) No perforation occurred
and 2 patients presented per procedure bleeding considered as a complication. 2
patients presented post procedure bleeding at day 7 and day 17 successfully
treated with hemoclips.
CONCLUSION: A local training program with a pig model allows starting
human dissection with high safety and efficiency. Initial training accelerates the
learning curve and the continuous practice in pig model allows maintaining
constant training until the recruitment of patients becomes sufficient.
REFERENCES
Deprez P, et al. Current practice with endoscopic submucosal dissection in
Europe: position statement from a panel of experts. Endoscopy 2010; 42: 853
858.
Disclosure of Interest: None declared
P0148 BURIED BUMPER SYNDROME - MANAGEMENT BASED ON
ACCURATE STAGING
J. Cyrany1,*, R. Repak1, T. Douda1, S. Rejchrt1, M. Kopacova1, J. Bures1
1
2nd Department of Internal Medicine - Gastroenterology, Charles University in
Prague, Faculty of Medicine in Hradec Kralove; University Hospital Hradec
Kralove, Hradec Kralove, Czech Republic
Contact E-mail Address: jiri.cyrany@fnhk.cz
INTRODUCTION: Buried bumper syndrome (BBS) is one of the major complications of percutaneous endoscopic gastrostomy (PEG). Until now there is no
universal diagnostic and therapeutic algorithm based on the degree of disc
submersion.
AIMS & METHODS: to assess safe and effective algorithm for diagnosis and
therapy of BBS based on easy-to-use classification of severity. Methods: retrospective analysis of an endoscopic database, composition and evaluation of BBS
severity scale
RESULTS: We have identified 40 cases of BBS in 38 patients (pts.) out of 1248
procedures of PEG performed from 01.01.2002 to 31.12.2012 at our endoscopy
unit. The cohort consisted of 27 men and 11 women of 22-84 years of age (mean
age 64 years). The most frequent indications for gastrostomy were neoplasma (18
cases) and neurological impairment (16 cases). Duration of gastrostoma to the
diagnosis of BBS varied from 2 weeks to 64 months (mean 13 month). The
incidence of BBS was 3.2% and it has almost tripled between subsequent fiveyear intervals - from 1.8% in group A (year 2003-2007) to 5% in group B (year
2008-2012). Potential reasons for the increase we found in more frequent detection of asymptomatic BBS (0 in group A, 8 in group B, p 0.05), often in
patients with already minimal or no use of the stoma (0 in group A, 9 in
group B, p 0.03). New classification of the depth of disc migration was composed based on clinical examination, gastroscopy and abdominal ultrasound
(Table). Endoscopic component of this classification was validated with a high
inter-rater agreement ( 0.93) and abdominal ultrasound showed favourable
parameters in the localisation of the buried bumper inside the stomach (sensitivity, specificity, positive and negative predictive value were 100%, 90%, 92%
and 100%, respectively). Spectrum of severity in our cohort according to this
classification was: grade 1 - 6 pts., grade 2 - 5 pts., grade 3 - 15 pts., grade 4 - 0
pt., grade 5 - 13 pts., grade 6 - 1 pt. 13 patients with grade 3 were treated
endoscopically by various techniques of dissection, only one case was complicated by pneumoperitoneum. From 13 patients with BBS grade 5, six underwent
laparotomy - bumper was localized outside the stomach in all cases.
STAGE

gastroscopy/abdominal ultrasound (US)/clinical finding

0
1

normal
ulcer below the disc and/or partial overgrowth of the disc (less than a
half of disc area covered)
disc components still visible (more than a half of disc area covered)
disc completely covered, guide wire can be introduced; US: disc
localized inside the stomach
disc completely covered, guide wire cannot be introduced; US: disc
localized inside the stomach
disc completely covered; US: disc localized out of the stomach
disc protrudes out of the skin or palpable just below the skin

2
3
4
5
6

CONCLUSION: Incidence of BBS in our series was 3.2% with significant rise
during 11 year period. New BBS severity classification based on gastroscopy and
abdominal ultrasound is easy tool for stratification of patients for surgical and
endoscopic therapy. Acknowledgement: Supported by the project PRVOUK 3708.
Disclosure of Interest: None declared

A171

United European Gastroenterology Journal 2(1S)


P0149 ENDOSCOPIC
SUBMUCOSAL
RESECTION
FOR
METACHRONOUS TUMOR IN THE REMNANT STOMACH AFTER
SUBTOTAL GASTRECTOMY

P0151 ENDOSCOPIC
SUBMUCOSAL
DISSECTION
IN
TREATMENT OF GASTROINTESTINAL NEOPLASIAS: INITIAL
RESULTS IN 31 PATIENTS

J. Lee1,*, B.-H. Min1, J.H. Lee1, J.J. Kim1, P.-L. Rhee1, K.-M. Kim2
1
Department of Internal Medicine, 2Department of Pathology, Samsung Medical
Center, Seoul, Korea, Republic Of

A. Herreros de Tejada1,2,*, M. Hernandez Conde1, J.L. Calleja1,2, A. Sanchez


Movilla1, C. Salas1, P. Matallanos1, E. Blazquez1, J.C. Fernandez-Rial1,
S. Gonzalez2, J.F. Garc a2, L. Abreu1,2
1
Hospital Universitario Puerta de Hierro Majadahonda, 2M. D. Anderson Cancer
Center, Madrid, Spain
Contact E-mail Address: marta.hernandez.conde@gmail.com

INTRODUCTION: Subtotal gastrectomy is one of the most common procedures


to resect gastric cancer curatively. However, if the patients have a remnant
stomach after the surgery, the risk of metachronous gastric tumor remains.
Because early gastric cancer (EGC) patients have a good prognosis after curative
surgery, the incidence of metachronous tumor in the remnant stomach is now
problematic. When the metachronous gastric tumor is detected, endoscopic submucosal dissection (ESD) can be considered as an alternative treatment option
than an additional operation.
AIMS & METHODS: Little information exists concerning the optimal treatment
of metachronous tumor in the remnant stomach. The aim of this study was to
assess the clinical outcomes and safety of ESD for this lesion. We retrospectively
enrolled patients who had undergone ESD for metachronous tumor in the remnant stomach after subtotal gastrectomy from December 2007 to January 2013 at
the Samsung Medical Center in Seoul, Korea. A total of 18 lesions in 12 patients
with EGC and 6 patients with high grade dysplasia (HGD) were treated by ESD.
The patient characteristics, endoscopic findings and histopathological features
and technical outcomes of ESD were investigated.
RESULTS: A total of 18 patients had previously undergone 17 Billoth-I (94%), 1
Billoth-II (6%) gastrectomies. The median period from the previous gastrectomy
to the subsequent ESD for metachronous tumor in the remnant stomach was
71months (range 13-207 months), the median tumor size was 13mm (range
4-22mm). En block resection with curative resections achieved for 16 lesions
(88.9%). Adverse events showed 1 case of perforation (5.6%) and there was
neither case of requiring emergent surgery nor treatment-related mortality
during this study period. The patients who requiring additional surgery for curative treatment due to deep submucosal invasion were 2 (11.2%).
CONCLUSION: ESD for the metachronous tumor in a remnant stomach after
subtotal gastrectomy showed a high en bloc resection rate and very low complication rate. Therefore, we suggest that ESD is an effective and safe treatment
method for metachronous tumor in the remnant stomach if it is performed by
highly qualified experts. It is less invasive than additional surgery. Therefore, it
can give a better quality of life to the patients, and the treatment outcome is
excellent, with no treatment-related mortality in this study.
Disclosure of Interest: None declared
P0150 EFFICACY OF REBAMIPIDE IN THE HEALING OF IATROGENIC
ULCERS POST ENDOSCOPIC SUBMUCOSAL DISSECTION: A
META-ANALYSIS
J.-A. V. Bisnar1,*, I.H. Cua1
Institute of Digestive and Liver Disease, St. Lukes Medical Center, Quezon City,
Philippines
Contact E-mail Address: joannebisnar@gmail.com
1

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a treatment


option for early gastric cancer (EGC). It is less invasive, however, it is associated
with larger, deeper ulcers post-procedure. Combined use of mucosal protective
anti-ulcer drugs such as rebamipide and proton pump inhibitors (PPI) was
reported to promote ulcer healing.
AIMS & METHODS: The study aims to determine the efficacy of rebamipide in
the healing of post ESD associated ulcers.
PubMed, Cochrane Database and bibliographies of retrieved articles were
searched for eligible articles. Randomized controlled trials involving patients
with EGC who underwent ESD and were given rebamipide monotherapy or as
adjunct to PPI were included in this meta-analysis. 2 reviewers extracted the data
and assessed the quality of the studies included. Review Manager 5 software was
used to analyze data from the studies included. Random effects model was used
for combining quantitative data.
RESULTS: 6 studies with a total population of 758 were included in the review.
356 patients were randomized to the treatment group (rebamipide alone or as an
adjunct to PPI). 354 patients were randomized to the control group (PPI or H2RA). Rebamipide monotherapy or as an adjunct to a PPI compared to placebo
(PPI or H2-RA) significantly improved healing with a p value of 0.0002 (RR
1.50, 95% CI 1.21-1.87).
CONCLUSION: Rebamipide improves the healing of post ESD associated
ulcers especially when administered with PPI for 4 weeks.
REFERENCES
Rembackes BJ, et al. Endoscopic mucosal resection. Endoscopy 2001; 33: 709-718.
Uedo N, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on
prevention of bleeding from ulcer after endoscopic submucosal dissection of early
gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol
2007; 102: 1610-1616.
Terano A, et al. Rebamipide, a gastro-protective and anti-inflammatory durg,
promotes gastric ulcer healing following eradication therapy for Helicobacter
pylori in Japanese population: a randomized, double-blind, placebo-controlled
trial. J Gastroenterol 2007; 42: 690-693.
Park SH, et al. Comparison of prevention of NSAID-induced gastrointestinal
complications by rebamipide and misoprostol: a randomized, multicenter, controlled trial STORM STUDY. J Clin Biochem Nutr 2007; 40: 148-155.
Kato, et al. Clinical trial: rebamipide promotes gastric ulcer healing by proton
pump inhibitor after endoscopic submucosal dissection a randomized controlled study. J Gastroenterol 2010; 45: 285-290.
Disclosure of Interest: None declared

THE

INTRODUCTION: Endoscopic submucosal dissection (ESD) is an advanced


technique used for en-bloc curative resection of early neoplasms of the gastrointestinal tract. Main advantages are high rate of curative resection and low
recurrence rate, avoiding in most cases the need of surgery.
AIMS & METHODS: Initial training on Animal Research facilities was carried
out for 2 years before starting ESD in humans. Prospective analysis of ESD
performed for suspected early neoplasia of GI tract. The interventions were
performed mostly in the endoscopy suite, full equipped to provide general anaesthesia in selected cases (all cases on the oesophagus and stomach, as selected
colorectal cases). Flush knife BT (Fujifilm Co. Japan) was the main knife used,
both in versions BT 1.5mm (oesophagus, colon and rectum) and 2.0mm (stomach); occasionally other knifes were applied, such as Hook-knifeand DualKnife (Olympus Co, Japan)
RESULTS: From January 2012 to February 2014 ESD was completed in 31
patients. The mean age was 64.4 years (SD12), with a male proportion of
55%. Over 60% of the cases were performed in colorectal location (colon 12
(39%); rectum 7 (22%)); other locations were stomach (9 (29%)) and oesophagus
(3 (10%)). Initial success of ESD was 93.5%, with 2 cases requiring surgery due
to failure or severe complication (both colonic cases). The en-bloc resection rate
was 96.5%, the average specimen size 18.1 cm2 (max. length on average 46.4mm),
with a median of 114 minutes (34-256) to complete the procedure. Regarding the
morphology, 16 cases were 0-IIa, 5 cases 0-Is, 3 cases 0-IIa/0-IIc, 2 cases 0-IIb, 2
cases 0-Is/IIa 1 case 0-IIa/0-IIb and 1 case 0-IIb/0-IIc. Lateral spreading tumors
(LSTs) distribution was: LST granular mixed type 5 cases, LST granular homogeneous type 7 cases, and 1 case of LST non-granular type. The R0 resection rate
for successful ESD was 90% (26 cases). There were 12 cases (39%) with perforation (38%), of which 10 (80%) were managed successfully with local endoscopic
treatment (closure with clips). There were 2 cases of late complications (splenic
rupture and mild lower gastrointestinal bleeding), with no mortality associated.
We analyzed the population according to chronological inclusion and divided
into 3 similar periods. The average dissection speed during the initial phase was
0.36mm/min, compared to 0.49mm/min and 0.44mm/min during the intermediate and the final phase respectively, with no statistically significant differences
(p 0.2) due to the small sample size.
CONCLUSION: ESD is an effective technique in the treatment of early neoplastic lesions in the digestive tract, particularly in cases of flat-depressed morphology, with a size greater than 20mm and/or the presence of submucosal fibrosis.
The technical difficulty, along with the prolonged time of endoscopy and the risk
of serious complications (essentially perforation) are the main constraints of
ESD. However, in our own experience, high en-bloc and R0 resection rate can
be achieved, along with remarkable technical progress during the learning curve
and successful endoscopic management of perforation. Our results demonstrate
the possibility of successful adoption of ESD in Europe after completing proper
training.
Disclosure of Interest: None declared
P0152 ENTONOX DURING COLONOSCOPY; HOW SHOULD IT
BE USED?
A. Ball1,*, S. Din1, M. Donnelly1, K. Smith1, S.A. Riley1
Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield,
United Kingdom
Contact E-mail Address: alex.ball@sth.nhs.uk
1

INTRODUCTION: Entonox can be used to ease the discomfort associated with


colonoscopy but the optimal mode of administration is unknown. We have
compared continuous and as required Entonox use during screening colonoscopy
examinations.
AIMS & METHODS: Patients attending for screening colonoscopy were invited
to participate. Eligible patients were randomised to using Entonox as required or
continuously. Procedural and demographic details including HADS score were
collected. Examinations were performed by three experienced colonoscopists.
Patients rated pain on a 10 point numerical ratings scale (0 no pain and
10 extreme pain) every 2 minutes during colonoscopy, prior to discharge and
1-3 days following colonoscopy. The colonoscopist and specialist screening practitioner (SSP) also rated the patients overall pain severity and the technical
difficulty of colonoscopy.
Continuous and categorical data were compared using a t test and chi-squared
test respectively. Correlations were assessed using Pearsons correlation coefficient and the agreement between observers was assessed using the intra-class
correlation coefficient (ICC).
RESULTS: 157 patients were screened and 49 were excluded (34 opted for intravenous sedation, 13 declined and 2 had a cardiac pacemaker). 108 patients were
randomised and 8 patients were withdrawn (7 had a cancer and 1 was unable to
activate Entonox). Study participants had a mean age of 67 years and 75% were
male. 46 patients were randomised to continuous and 54 to as required use.
15/54 (27.7%) patients in the as required group did not use Entonox and 7/46
(15.2%) of patients in the continuous group reverted to as required use due to side
effects. The number of patients requiring additional analgesia was not significantly
different between continuous use and as required use (4/46 vs 3/54, p 0.54).

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United European Gastroenterology Journal 2(1S)

There was no significant difference in the overall pain scores given by patients
who used Entonox continuously and as required (mean score 2.4 vs 3.2,
p 0.08 and peak score 4.2 vs 4.8, p 0.26). Overall patient satisfaction was
high with the continuous and as required methods (mean 9.9 vs 9.7, p 0.23) as
was willingness to undergo a repeat examination (mean 9.2 vs. 9.7, p 0.09).
A HADS anxiety score of 7 was associated with higher overall pain scores
(mean score 2.1 vs 3.6, p 0.004 and peak scores 3.7 vs 5.6, p 0.003).
Patient with a HADS anxiety score 57 who were allocated to continuous
rather than as required use had lower pain scores (mean 1.4 vs 2.5,
p 0.045) but there were no significant differences between strategies in the
patients with a HADS score 7 (3.3 vs 3.8, p 0.6) There was no significant
difference in the pain ratings according to gender.
Patients overall rating of pain prior to discharge correlated highly with the mean
intra-procedural pain score (r 0.84) and peak rating of pain (r 0.84). There
was also a very high correlation between the patients overall pain rating prior to
discharge and 1-3 days later (r 0.94). There was good agreement between the
patients and the SSPs (ICC 0.79) and endoscopists (ICC 0.76) overall pain
rating.
CONCLUSION: Overall, the method of Entonox administration did not influence pain ratings. However, continuous Entonox use was more effective in
patients with a low anxiety level.
Disclosure of Interest: None declared
P0153 NON-ANAESTHESIOLOGIST ADMINISTERED PROPOFOL IN
COLONOSCOPY INTERIM ANALYSIS OF A RANDOMIZED
CONTROLLED TRIAL
A.O. Ferreira1,2,*, J. Torres1, S. Pereira1, S. Dias1, M. Rocha1, R. Pinto3,
V. Schuler3, M. Neves3, C. Castanheira3, A.A. Santos3, F. Silva3, M. Cravo1
1
Department of Gastroenterology, Hospital Beatriz Angelo, Loures, 2Department
of Gastroenterology, Centro Hospitalar do Algarve, Portimao, 3Department of
Anesthesiology, Hospital Beatriz Angelo, Loures, Portugal
Contact E-mail Address: alex.gastrohep@gmail.com
INTRODUCTION: Propofol allows the best sedation in colonoscopy. There is
only one Randomized Controlled Trial (RCT) comparing Non-Anaesthesiologist
Administered Propofol (NAAP) with sedation by an anaesthesiologist.
AIMS & METHODS: Our goal was to compare the incidence of sedation-related
adverse events (AE), colonoscopy quality, and patient satisfaction between
NAAP and anaesthesiologist sedation. We performed a single blinded RCT
with two parallel intervention groups (group A NAAP; group B anaesthesiologist sedation). In group A, a 40-60 mg propofol bolus was administered
followed by 10-20 mg bolus as needed. In group B propofol was administered
under the anesthesiologist indication. The primary endpoint was the incidence of
AE as defined by the World SIVA International Task Force on Sedation.
Secondary endpoints were propofol dose, patient satisfaction, and pain assessed
by a 10-point visual analogue scale, procedure and recovery time, and colonoscopy quality indicators (cecal intubation rate, withdrawal time, adenoma detection rate). A sample size of 330 (1:1) cases was calculated for a power of 90% at a
5% level of significance, and based on the AE incidence in our preliminary
experience. Patients aged 18-80 with low anaesthetic risk (ASA I-II) were
included (patients characteristics presented in table 1). Herein we present the
interim analysis of the first 100 cases. Statistical analysis was performed with
SPSS version 21. Chi-square, Fischers exact, t-tests and logistic regression were
used as appropriated.
RESULTS: The incidence of AE was 34.3% on group A and 42.4% on group B
(odds ratio 0.709; 95% CI 0.302-1.668; p 0.43). There were no severe (sentinel)
AE events. The following interventions were necessary: atropine administration
(0% vs 6.1%); airway repositioning (14.9% vs 9.1%); increase in O2 administration (8.9% vs 6.1%); increase in fluids rate (4.5% vs 0%). Mean propofol
dose: group A 222  84 mg vs group B 245  118mg (p 0.276). Procedure times
were 22.24  13.12 and 21.39  10.78 min (p 0.75), withdrawal time was 11.97
 10.36 vs 11.84  6.15 min (p 0.949) and recovery time was 62  44 vs 61  22
min (p 0.856) in group A and group B respectively. Patients had no pain (0) in
84.5% vs 88.5% (p 0.946) and reported complete satisfaction with the sedation
in 84.8% vs 81.2% (p 0.58). Procedural amnesia was reported in 88 vs 93.8%
(p 0.49). All the patients were willing to repeat the colonoscopy under propofol
sedation. Cecal intubation rates were 95.5% vs 93.9% (p 1.0), adenoma detection rates were 30.4% vs 31.3% (p 0.93).
Patient characteristics

Group A(n 67)

Group B(n 33)

Male sex, n (%)


Mean age, years (sd)
ASA I/II, n
Cardiovascular disease, n (%)
Smoking, n (%)
Snoring history, n (%)

24(35.8)
57(14)
6/61
10(14.9)
15(22.4)
4(8.0)

14(42.5)
51(18)
7/26
5(15.2)
5(15.2)
2(6.0)

n.s.
n.s.
n.s.
n.s.
n.s.
n.s.

CONCLUSION: In the interim analysis NAAP was equivalent to anaesthesiologist sedation in the rate of adverse events in a low risk population.
Clinicaltrials.gov (NCT02067065).
Disclosure of Interest: None declared

P0154 MACROSCOPIC
COLONOSCOPY
FINDINGS
COLLAGENOUS COLITIS; A THREE-CENTRE EXPERIENCE

OF

A. Koulaouzidis1,*, K. Sjoberg2, L. Bartzis1, M. MacNeill3, A. Nemeth2,


G. Wurm Johansson2, P. Finneron3, A.J. Lucendo4, E. Toth2
1
Endoscopy Unit, Centre for Liver & Digestive Disorders, The Royal Infirmary of
Edinburgh, Edinburgh, United Kingdom, 2Endoscopy Unit, Department of
Gastroenterology, Skane University Hospital, Malmo, Sweden, 3Pathology
Department, Western General Hospital, Edinburgh, United Kingdom, 4Endoscopy
Unit, Hospital General de Tomelloso, Tomelloso, Spain
INTRODUCTION: Microscopic colitis (MC) encompasses 2 entities, collagenous colitis (CC) and lymphocytic colitis (LC).1 Although (by definition) a histopathological diagnosis, there are occasions when colonoscopy reveals findings
such as alteration of the vascular mucosal pattern/innominate grooves, mucosal
nodularity and a sequence of mucosal changes from defects/lacerations to cicatricial lesions that are thought to be characteristic of MC, and especially CC.1,2
The aim of this study was to evaluate the frequency and type of endoscopic
findings in patients diagnosed with CC in two University Hospitals.
AIMS & METHODS: Retrospective study. The database of the Pathology
Department of 2 university hospitals in Edinburgh (Scotland) and Malmo
(Sweden), and a district general hospital in Spain (general Hospital de
Tomelloso) were searched for patients who have been diagnosed with CC
between May 2008 and August 2013. Endoscopy reports & endoscopic images
were retrieved and reviewed; data on lesions, sedation, bowel preparation (type
and effect) and endoscopists experience were abstracted. Categorical data are
reported as mean SD. The Fischers exact, the chi-square and the t (unpaired)
tests were used to compare datasets. A two-tailed P value of 50.05 was considered statistically significant.
RESULTS: A total of 416 patients (96M/320F; mean age: 67.112.1 years) case
notes, who were diagnosed with CC, were collected and reviewed.
The colonoscopies had been carried out by senior medical/surgical staff (consultants or associate specialists) in 331 (79.6%). A total of 81 (19.5%) patients had a
mix of findings, previously described as being suggestive of CC in endoscopy,
such as mucosal erythema/oedema (mosaic pattern): 65, colonic mucosa linear
defects (lacerations, tears, ulcers/fractures, mucosal furrows): 10, cat-scratch
mucosa: 4, and cicatricial lesions: 3.
Although the use of polyethylene glycol (PEG) offer superior quality of bowel
prep effect (as compared to other pre-colonoscopy preparations; P50.0001), this
was not associated with higher detection rate of (all types) macroscopic findings
and/or colonic mucosal defects in specific (P 1.0). Furthermore, mucosal colonic defects had no association with either the experience of the colonoscopist
(P 0.812), or the use of general anaesthesia/propofol (P 0.53), and/or the use
spasmolytic (hyoscine butylbromide/glucagon), P 0.568.
CONCLUSION: A substantial minority of patients with CC (19.5%) had endoscopic findings indicative of CC. The presence of these findings is not associated
with procedural factors such as endoscopists experience, quality of bowel prep,
and/or use of spasmolytic during colonoscopy.
REFERENCES
1. Koulaouzidis A and Saeed AA. Distinct colonoscopy findings of microscopic
colitis: not so microscopic after all? World J Gastroenterol 2011; 17: 4157-4165.
2. Suzuki et al. Usefulness of colonoscopic examination with indigo carmine in
diagnosing microscopic colitis. Endoscopy 2011; 43: 1100-1104.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
Given Imaging ESGE research grant 2011, Lecture fee(s) from: Dr
FalkPharmaUK, Other: Travel support: Dr FalkPharma, Abbott, MSD, K.
Sjoberg: None declared, L. Bartzis Other: Grant from the Hellenic Society of
Gastroenterology, M. MacNeill: None declared, A. Nemeth: None declared, G.
Wurm Johansson: None declared, P. Finneron: None declared, A. Lucendo:
None declared, E. Toth: None declared
P0155 A TAILORED SEDATION FOR COLONOSCOPY BY NONANESTHESIOLOGISTS: USE OF PROPOFOL TARGET
CONTROLLED INFUSION FOR SAFELY ERASE PATIENTS PAIN
A. Della Rocca1,*, A. Scatto2, P. Tresin3, S. Gallo1, E. Rosa-Rizzotto1,
L. Peraro1, E. Guido1, D. Caroli1, B. Licata3, F. De Lazzari1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital,
2
Anesthesiology, Azienda Ospedaliera, 3Anesthesiology, St Anthony Hospital,
Padua, Italy
INTRODUCTION: Pharmacokinetics and pharmacodinamic of both
Midazolam(M) and Pethidine(P) (the most common drugs for procedural sedation) dont allow during colonoscopy to rapidly adjust dosage according to
patient response and to the complexity and length of the procedure. As result
patients may be too much or not enough sedated. Propofol sedation overcomes
these limitations but may expose the patient to dangerous side effetcs such as
hypotension and respiratory depression.
AIMS & METHODS: Demonstrate that Propofol Target Controlled Infusion
(PTCI) enables properly modified infusion rate (ie total drug dose) in order to
perform a zero pain colonoscopy and without affecting safety. 3 types of sedation
were utilized in this trial: PTCI, MP, Propofol titration (PT). Propofol infusion
was controlled by a TCI pump set on Schnider protocol. Propofol administration
and monitoring was performed by a nurse trained on recognizing adverse effects
and on basic resuscitation maneuvers; an anesthesiologist was always on call.
Colonoscopy started 1 min after infusion was begun. Initial Effect Site Target
Concentration was 2.5 mg/ml, increments of 0.5 mg/ml/min were allowed until
total pain relief. We monitored pts ETCO2, SpO2, NIBP, ECG. At the end of the
procedure pts were transferred to recovery room only when Observers
Assessment of Altertness/Sedation (OAA/S) scale was 4 3 and then discharged
when ALDRETE score was 4 8. Satisfaction was established by Numeric Visual

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United European Gastroenterology Journal 2(1S)


Scale (NVS, pain evaluation from 1 to 10). A control group (treated with MP)
followed the same protocol.
RESULTS: 721 consecutive pts undergoing both diagnostic and operative colonoscopy were included. No exclusion critheria were stipulated. 345 pts PTCI at
an average drug dosage (ADD) of 156.869.6 mg; 376 pts MP at an ADD,
respectively, of 4.181.3 mg and 47.55.5 mg; The 2 groups were clinically
homogeneus (M 55.4%; F 44.6%; ASA 1-2 90%, ASA 3 10%) Adverse
events: Hypoxemia (So2590%): PTCI 0.Mp 8 (p50.05); Apnea:
PTCI 3, Mp 26 (p50.001); Hypotension (SBP590mmHg): PTCI 44,
Mp 36 (p ns); Bradycardia (540 bpm) PTCI 5, Mp 11 (p ns).
Apnea was treated successfully with neck extension. Outcome and satisfaction:
mean NVS (all procedures) PTCI 0.361.2 vs 1.072.1 MP (p50.001); mean
NVS (only difficult proceures) PTCI 0.241 vs 1.972.8 MP (p50.001); mean
cecal intubation time (intubation rate was 98.4%) PTCI 6.143.6 min vs MP
7.524.8 min (p50.01), mean time for the entire procedure (colonoscopy
recovery time): PTCI 38.7615.1 min vs MP 53.9514.6 min (p50.001).
PTCI total mean dosage was compared with the mean dosage of 50 colonoscopies in propofol titration, at the univariate analysis less total propofol (adjusted
for BMI, Sex, Age, Endoscopist, Abdominal surgery) was administered using
PTCI than the titration method: 156.8569.63 vs 212.5085.70 (p50.0001).
CONCLUSION: Propofol TCI provide a extremely flexible technique which
ensures a sedation tailored to the individual patient and gives the possibility to
guarantee an effective sedation for long lasting procedures without affecting
recovery time. The final results are the opportunity to totally relieve pain, high
performance (time length and quality of recovery) and less operator-dependent
process.
Disclosure of Interest: None declared
P0156 HOW WELL DOES RADIOLOGY PREDICT
CORRELATING IMAGING WITH ENDOSCOPY; A
RETROSPECTIVE STUDY

COLITIS?

A. Sinha1, J. Gulliver1,*, M. Shaw2, R. Makins1


1
Gastroenterology, 2Radiology, Gloucestershire Hospitals NHS Trust,
Cheltenham, United Kingdom
Contact E-mail Address: ashish.sinha@glos.nhs.uk
INTRODUCTION: A common indication for endoscopic assessment of the large
intestine is to clarify an abnormal finding on either cross sectional or contrast
radiological imaging. Our aim was to assess how often a positive diagnosis of
colitis of any form was made following either CT scanning or barium enema. We
then aimed to correlate these radiological findings with those seen at a subsequent endoscopy.
AIMS & METHODS: The endoscopy database at Gloucestershire Hospitals
NHS Foundation Trust was reviewed for procedures performed between
January 2008 and June 2013. Cases where endoscopy was performed for the
indication of abnormal radiological findings were selected. The patients radiology reports were reviewed and the cases where colitis or inflammation was
described as possible differentials were selected. We then compared these radiological findings with those seen on endoscopy for positive correlation. The
endoscopic finding of diverticular disease was taken as a positive correlation
where relevant. Histology reports from the biopsies taken during the endoscopic
procedures were also reviewed to confirm the endoscopic findings.
RESULTS: Between January 2008 and June 2013, 562 colonoscopies or flexible
sigmoidoscopies were performed as a result of an abnormality seen on radiological imaging. In 168 (30%) a positive diagnosis of colitis was mentioned on the
radiology report. Demographics showed a fairly even sex distribution with 53%
of patients female, 47% male. The ages ranged from 22-98 with a mean age of
60.9 years. A total of 5 cases were excluded, with the colonoscopy failing to reach
the region of interest in 4 cases.
Endoscopy confirmed mucosal inflammation in 60 of the 163 cases (37%)
whereas the endoscopy was reported as normal in the remaining 103 cases (63%).
In patients with positive endoscopic correlation, biopsies were taken in 34 (57%)
of cases. Biopsies were not taken in cases where diverticular disease was identified
and considered a positive diagnosis.
In those with histological specimens 28 of the 34 (82%) showed histology consistent with an inflammatory process. Of these the majority (57%) showed
Crohns disease. 6 specimens showed no inflammatory change on histology
despite a macroscopic impression of inflammation.
Interestingly 2 biopsy series were taken despite negative endoscopic correlation,
of which 1 was confirmed as lymphocytic colitis on histology. Another showed
features of Crohns on histology (this patient had known Crohns).
CONCLUSION: 37% of the cases in our series referred for endoscopic evaluation after the finding of colitis on radiological imaging were confirmed to have
colonic inflammation at endoscopy. This suggests that there is a limited correlation between radiological and endoscopic imaging when a diagnosis of colitis is
being considered.
Further studies are required to determine whether a number of parameters considered together to create a scoring system would increase the likelihood of a
positive pick up at endoscopy following colitis identified on radiological imaging,
thereby improving diagnostic yield and reducing the number of unnecessary
procedures. Interestingly, with one diagnosis of lymphocytic colitis made on
samples from endoscopically normal colon, an argument could be made for
taking biopsy series in all cases to exclude microscopic colitis.
Disclosure of Interest: None declared

P0157 SHORT MESSAGE SERVICE (SMS) IN COLONOSCOPY


PREPARATION - PERICLES-I -A FEASIBILITY STUDY
B.M. Walter1,*, P. Klare1, B. Neu1, R.M. Schmid1, S.von Delius1
II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munchen,
Germany
Contact E-mail Address: benjamin.walter@lrz.tum.de
1

INTRODUCTION: High quality preparation is essential for colonoscopy. A


sufficient colon cleaning improves adenoma detection rate and reduces rates of
necessary re-colonoscopies due to invalid preparation. Several studies showed
importance of patients education and correct pre-colonoscopy diet. Only few
studies have evaluated feasibility of using new media such as SMS in high quality
preparation. The PERICLES-project (prospective studies for improvement of
colonscopy preparation by optimized visualisation) aims to optimize patient guidance by reminding the most important steps during colonoscopy preparation.
AIMS & METHODS: Objective: To assess the feasibility of colonoscopy preparation using SMS (short message service) starting 4 days prior colonoscopy
appointment and to assess sufficient colonoscopy preparation.
Design: A feasibility study Setting: Tertiary care center, university hospital.
Subjects: Patients scheduled for out-patient colonoscopy at a university hospital.
Interventions: Patients enrolled in the SMS study group get SMS information at
different timepoints according to the next step of colonoscopy preparation and
diet information. Data of out-patient colonoscopies with regular preparation
procedure were collected as control group during time of SMS study.
RESULTS: Colonoscopy could be performed in all patients included in the study.
Overall patient satification receiving SMS based information was high. Asked if
the SMS reminder system was helpful to get the colonoscopy preparation done (1
not helpful to 10 very helpful) an average score of 7.8 was counted (n 18). On the
contrary asked if the SMS reminder system was inhibitory (1 not inhibitory to 10
very inhibitory) an average of 1.1 was counted (n 19). The average total BBPS
was significantly higher than in the control group (MeanSEM 7.316  0.2967
(SMS-group), MeanSEM 6.269  0.1925 (control group); good bowel preparation for colonoscopy 5). BBPS calculated for the different colon regions.
LC Left colon (MeanSEM 2.5000.1357 (SMS group) MeanSEM
2.1380.06530 (control group)), TC transverse colon (MeanSEM
2.4000.1124 (SMS group) MeanSEM 2.1150.06875 (control group)),
RC right colon (MeanSEM 2.4000.1124 (SMS group) MeanSEM
2.0150.07325 (control group)) were higher than in the control group.
CONCLUSION: A SMS (short message service) system in colonoscopy preparation works is stable and effective. Quality of colonoscopy preparation was higher
than in regular preparation procedure. Patients were highly satisfied by using the
SMS system during colonoscopy preparation.
Disclosure of Interest: None declared
P0158 WHY DONT WE RETRIEVE ALL THE ENDOSCOPIC RESECTED
POLYPS?
C. Fernandes1,*, R. Pinho1, S. Leite1, L. Proenca1, A. Rodrigues1, L. Alberto1,
I. Ribeiro1, T. Pinto-Pais1, A. Ponte1, J. Silva1, J. Fraga1, J. Carvalho1
1
Gastroenterology, C. HOSPITALAR VILA NOVA GAIA, V N Gaia, Portugal
INTRODUCTION: Colonoscopy is able to diagnose, resect and retrieve colonic
polyps. The latter is of major importance to allow an accurate histological evaluation. Factors associated with failed polyp retrieval are not yet clear.
AIMS & METHODS: To evaluate the prevalence of failed polyp retrieval; to
define factors associated with polyp retrieval failure.
A single center retrospective study that considered all the resected polyps by
snare in consecutive colonoscopies performed between September 2011 and
December 2012. Eleven gastroenterology specialists and 3 residents were considered as endoscopists. Demographic and endoscopic data obtained through the
colonoscopy report.
Statistical analysis (SPSS v.19): Chi-square, t-student.
RESULTS: 496 colonoscopies were evaluated, corresponding to 484 patients
(male gender 66.1%, mean age 63.4 years [10.2]). Considering a total of 1111
resected polyps, 52 (4.7%) were not retrieved. A deficient bowel preparation
(p 0.0006), a coloretal surgery history (p 0.008), a higher number of resected
polyps (p50.0001), a smaller size of resected polyps (p50.0001), a right-side
location (p 0.0006) and a cold snare resection versus current snare resection
(p 0.0007) were factors associated with failed polyp retrieval. Colonoscopy
performed by a resident (p 0.81), under deep sedation (p 0.94) or with diverticulum (p 0.44) were not related with failed polyp retrieval.
CONCLUSION: In our study the polyp retrieval failure prevalence was 4.9%. A
1) deficient bowel preparation, 2) a colorectal surgery history, 3) a greater number
of resected polyps, 4) a smaller size of the resected polyps, 5) a righ-side location
and 6) a cold snare resection were associated with polyp retrieval failure.
Disclosure of Interest: None declared
P0159 FUSE COLONOSCOPY YIELDS HIGHER DETECTION OF
ADVANCED AND MULTIPLE ADENOMAS AS COMPARED TO
STANDARD FORWARD VIEWING COLONOSCOPY: A POST-HOC
PER PATIENT ANALYSIS FROM A RANDOMIZED COMPARATIVE
TRIAL
C. Hassan1,*, I. Gralnek2
1
ONRM Hospital, Rome, Italy, 2Rambam Health Care Campus, Haifa, Israel
Contact E-mail Address: cesareh@hotmail.com
INTRODUCTION: As compared with Standard Forward Viewing (SFV) colonoscopy, Full Spectrum Endoscopy (Fuse) colonoscopy has been shown to significantly increase the yield of adenomas detected (per lesion analysis) [1].

A174
However, the accuracy of FUSE based upon a per-patient analysis has not fully
been addressed.
AIMS & METHODS: We performed a post-hoc analysis of the data from a
recently completed international, multicentre, randomized trial (NCT01549535)
in which 197 patients underwent same-day, back-to-back tandem colonoscopy
with SFV- and FUSE-colonoscopes. The per-patient detection rate of polyp/
advanced adenoma was calculated for each of the two colonoscopy techniques
according to polyp size and multiplicity (3 polyps). The relative detection rate
was defined as the ratio between the number of patients classified by either SFV
or FUSE colonoscopy in each lesion category and the cumulative detection with
both of the colonoscopy techniques (SFVor FUSE) for the same lesion category.
Statistical analysis was performed by Chi-square test.
RESULTS: We found 111, 23 and 9 patients presenting with at least one 5mm,
6-9mm, or 10mm polyp respectively, while 22 and 27 additional patients had as
their most severe lesion an advanced adenoma or multiple adenomas, respectively. The relative sensitivity of SFV and FUSE for each type of lesion is
shown in Table 1. In detail, the sensitivity of FUSE was statistically significantly
superior to SFV for all categories except for polyps 10mm. As compared to
SFV colonoscopy, FUSE detected an additional 9 patients with multiple adenomas, resulting in a relative per-patient sensitivity of 94%, as compared with 27%
for SFV colonoscopy.
CONCLUSION: As compared to SFV colonoscopy, FUSE colonoscopy appears
to be more effective in identifying patients with multiple polyps and polyps up to
9 mm in size, including 6-9mm advanced adenomas. These data appear to further
demonstrate the clinical relevance of the additional adenoma detection of FUSE
as previously shown at a per lesion level [1].
REFERENCES
[1] Gralnek IM, et al. Standard forward-viewing colonoscopy versus full-spectrum endoscopy: an international, multicentre, randomised, tandem colonoscopy
trial. Lancet Oncol 2014; 15: 353-360.
Disclosure of Interest: None declared
P0160 DISCRETE DYSPLASTIC LESIONS IN ULCERATIVE COLITIS
MAY BE ADEQUATELY MANAGED ENDOSCOPICALLY: A LONG
TERM FOLLOW-UP STUDY
C.H. R. Choi1,*, A. Ignatovic-Wilson1, A. Askari1, J. Warusavitarne1,
M. Moorghen1, S. Thomas-Gibson1, B. Saunders1, A.L. Hart1
1
Academic Institute, St. Marks Hospital, London, United Kingdom
Contact E-mail Address: pacoblue@gmail.com
INTRODUCTION: While there is evidence to support endoscopic resection of
adenoma-like mass (ALM) occurring in patients with ulcerative colitis (UC), its
long-term follow up data is currently limited. The aim of this study is to evaluate
the long-term outcomes of patients with UC who have had an endoscopic resection of dysplasia within segment of bowel affected by colitis.
AIMS & METHODS: All patients who had their dysplastic lesions resected
endoscopically between 1998 and 2008 were retrospectively identified from the
endoscopic and histology databases. Patients who were immediately referred to
colectomy were excluded. Medical records, endoscopy and histology reports were
reviewed to determine the primary study outcome, which was defined as no
further dysplasia episode, recurrence of dysplasia, or development of colorectal
cancer (CRC).
RESULTS: A total of 100 patients underwent endoscopic resection for 121 discrete dysplastic lesions during the study period (table 1). The median follow-up
duration from the time of dysplasia resection was 70 months (interquartile range
(IQR), 53 89 months). The Paris classifications of the resected lesions were: Ip
(60 lesions, 50.4% of 121 lesions), Is (36, 29.8%), IIa (3, 2.5%), IIb (4, 3.3%),
IIa/c (1, 0.8%), and lateral spreading tumour (1, 0.8%). Remaining 16 lesions
(13.2%) were described as appearance suspicious for dysplasia associated lesion
or mass (DALM), where Paris classification was not recorded. Median size of
the resected lesions was eight millimetres (IQR, 4 15 millimetres). Lesions were
removed using snare polypectomy (66 lesions, 54.5% of 121 lesions), EMR (30,
24.8%), hot biopsy (21, 17.4%) or ESD (4, 3.3%) techniques. Histology showed
low-grade dysplasia (LGD) in 111 (91.7% of 121 lesions) and high-grade dysplasia (HGD) in 10 lesions (8.3%). Pathologists interpretations on the lesions were
as follows: histological features favour DALM (36 of 121 lesions, 29.8%) favour
sporadic adenoma (56, 46.3%), or distinction not possible on histological
grounds alone (29, 23.9%). Overall, 23 patients (23% of study population)
had developed recurrent episode of dysplasia in median of 41 months since the
time of resection (IQR, 16 55 months). Seven of these patients underwent
colectomy: cancer was detected in two patients (Dukes A and C), but no
other patients had HGD or CRC in surgical specimen. The patient who developed Dukes C cancer did not have surveillance colonoscopy for five years prior
to the cancer diagnosis. The cumulative incidence of recurrent episode of dysplasia following endoscopic resection was 3.1% in 1 year, 7.4% in 2 years, 11.9% in
3 years, 16.7% in 4 years and 22.0% in 5 years.

United European Gastroenterology Journal 2(1S)


Table to abstract P0160
Patient demographics
Sex (%)
Male
Female
Disease extent (%)
Extensive
Left-sided
Disease duration (years) (Median,
interquartile range)
Age at the time of dysplasia diagnosis
(years) (Median, interquartile range)

66 (66%)
34 (34%)
87 (87%)
13 (13%)
24 (13 33)
61 (54 69)

CONCLUSION: Patients with endoscopically resectable, well-circumscribed


dysplastic lesions within the segment of colitis may be appropriately managed
with endoscopic resection. However, close surveillance is necessary given the
relatively high rate of recurrence.
Disclosure of Interest: None declared
P0161 LOW-GRADE DYSPLASIA IN ULCERATIVE COLITIS: IMPACT
OF LESION SHAPE AND SIZE ON PROGRESSION TO HIGHGRADE DYSPLASIA OR COLORECTAL CANCER
C.H. R. Choi1,*, A. Askari1, A. Ignatovic-Wilson1, J. Warusavitarne1,
M. Moorghen1, S. Thomas-Gibson1, B. Saunders1, T. Graham2, A.L. Hart1
1
Academic Institute, St. Marks Hospital, 2Tumour biology, Barts Cancer Institute,
Queen Mary University of London, London, United Kingdom
Contact E-mail Address: pacoblue@gmail.com
INTRODUCTION: One of the most challenging aspects of managing low-grade
dysplasia (LGD) in ulcerative colitis (UC) is the identification of patients who
will progress to high-grade dysplasia (CRC) or colorectal cancer (CRC). The aim
of this study was to identify risk factors associated with progression to HGD or
CRC in UC patients diagnosed with LGD.
AIMS & METHODS: Patients with UC who were diagnosed with LGD between
1990 and 2012 were identified from the UC surveillance database of a large
tertiary centre in the UK and followed up to 1st January 2013. Data on patient
demographics, endoscopic and histological variables at the time of the first LGD
episode were collected and correlated with progression to HGD or CRC, our
primary outcome measure. Time to event analysis was performed using Cox
proportional hazards methods with a Bonferroni adjusted significance level
(p 0.0022).
RESULTS: A total of 189 patients were evaluated during 1,100 patient-years of
follow up from the date of the first LGD diagnosis (median, 53 months; interquartile range, 19 92 months). Overall, 38 (20.1% of study population) had
progressed to HGD (16 patients) or CRC (22 patients). Table 1 shows the variables
significantly associated with progression to HGD or CRC on univariate analysis.
A statistically non-significant trend towards the progression to HGD or CRC was
observed in those patients with history of primary sclerosing cholangitis (hazard
ratio (HR), 3.54; p 0.018), a shortened colon (HR, 2.75; p 0.024), multiple
episodes of dysplasia (HR, 2.59; p 0.005), and histological active inflammation
in the segment of LGD (HR, 2.20; p 0.025). At the multivariate level, only nonpolypoid shape (HR, 7.3; 95% confidence interval (CI), 2.4 21.8; p50.001),
lesion size one centimeter (cm) or bigger (HR, 4.2; 95% CI, 1.3 13.3;
p 0.015) remained significant variables contributing to HGD or CRC.

Variables

Categories

Hazards 95% confidence


ratio (HR) interval (CI)
P

Lesion shape

Polypoid x
Non-polypoid
Invisible]

1
24.1
5.8

10.0 58.1
1.5 22.6

50.001

Lesion size

51cm
1cm
No
Yes
No
Yes
Adenoma more likely
Distinction not
clear
UC associated dysplasia more likely
No
Yes

1
14.1
1
7.1
1
4.0
1
12.2
37.2

4.8 41.3

50.001

2.4 21.1

50.001

Stricture
Previous indefinite
dysplasia
Pathologists interpretation
on histological features

Multifocal dysplasia

1
3.1

1.9 8.4

50.001

1.4 109.4
5.1 273.6

50.001

1.6 6.0

.001

Table 1: Results of Univariate Analysis (only significant variables are shown). x:


Discrete pedunculated or sessile polyps (Paris classification type I). : Flat,
depressed (Paris type II), irregular, diffuse, plaque-like or lesions with poorly
defined edges. ]: LGD with no evidence of endoscopic abnormality.
CONCLUSION: Low-grade dysplastic lesions that are non-polypoid or large
(1cm) have a high-risk of progression to HGD or CRC in patients with UC.
Patients harboring these lesions require careful counseling of management
options including colectomy. Conversely, small polypoid low-grade dysplastic

A175

United European Gastroenterology Journal 2(1S)


lesions may be appropriately managed with endoscopic resection and close
surveillance.
Disclosure of Interest: None declared
P0162 A PILOT STUDY OF FLUORESCENT IMAGING
COLORECTAL TUMOR USING -GLUTAMYL-TRANSPEPTIDASE
(GGT) FLUORESCENCE ACTIVITY PROBE

OF

C. Sato1,*, S. Abe1, E. So1, M. Yamada1, M. Makazu1, H. Takamaru1,


H. Sasaki1, Y. Matsuyama1, T. Sakamoto1, T. Nakajima1, T. Matsuda1,
R. Kushima2, M. Kamiya3, Y. Urano3,4, Y. Saito1
1
Endoscopy Division, 2Pathology Division, National Cancer Center Hospital,
3
Laboratory of Chemical Biology and Molecular Imaging, University of Tokyo,
4
Accelerated research enhancement program of Japan Science and Technology
Agency (JST), Tokyo, Japan
Contact E-mail Address: csato@ncc.go.jp
INTRODUCTION: New endoscopic technologies improve visibility of early colorectal cancers. However, flat lesions especially in lateral spreading tumor of the
non-granular type (LST-NG) are sometimes hard to detect even with such modalities. -glutamyl-transpeptidase (GGT) is poorly expressed in normal tissue,
but overexpressed on the cell membrane of various cancer cells in vivo. The
use of -glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been
reported to show specific and immediate fluorescence activity with overexpressed
GGT in tumor. This fluorescence active probe is expected to be applied to a new
modality for cancer-selective fluorescence imaging1).
AIMS & METHODS: This pilot study aimed to evaluate ex-vivo fluorescent
imaging of colorectal tumor using the GGT fluorescence activity probe. 30
endoscopically resected colorectal tumors from March 2013 to March 2014
were included in this study. 1000l of gGlu-HMRG in a concentration of
either 50M or 500M was sprayed on the freshly resected specimen fixed on
a black board. Fluorescent images of the resected specimen were taken after
spraying gGlu-HMRG every 30 seconds for 15 minutes using a dedicated imaging machine providing 550nm of blue excitation light (Discovery; INDEC Inc.).
The fluorescence image 7 minutes after spraying (when fluorescence activity had
almost reached equilibrium) was evaluated by 3 endoscopists. The fluorescence
activity was judged positive or negative. Lesions showing partial fluorescence
activity were considered positive. This pilot study assessed the proportion of
lesions positive for fluorescence and correlation with their clinicopathological
characteristics.
RESULTS: The clinicopathological features were; mean age was 687, male/
female 15 /15, mean tumor size: 3913mm, macroscopic type: lateral spreading
tumor of the granular type (LST-G)/LST-NG 20/10, adenoma/ carcinoma in
adenoma 13/17. 20 (67%) of images after 7 minutes were positive for fluorescence activity and 10 (33%) were negative. The mean tumor size of lesions
positive for fluorescence activity was 42mm and that of negative was 32mm.
Of 13 adenoma, 7 (54%) lesions were positive and 6 (46%) were negative. Of
17 carcinoma in adenoma, 13 (76%) lesions showed positive and 4 (24%) were
negative. 16 LST-G lesions (80%) and 4 LST-NG lesions (40%) revealed positive. 18 (75%) of 24 lesions in 50M gGlu-HMRG and 2 (33%) of 6 lesions in
500M revealed positive.
CONCLUSION: Topically spraying gGlu-HMRG to identify GGT activity in ex
vivo colorectal tumors provides rapid and selective fluorescent imaging.
REFERENCES
1) Urano Y et al. Sci Transl Med 2011.
Disclosure of Interest: None declared
P0163 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GIANT
COLORECTAL LATERAL SPREADING TUMORS LARGER THAN
10 CM: IS IT FEASIBLE?
D.H. Jung1,*, Y.H. Youn1, J.-H.K. 1, J.J. Park1, H. Park1
1
Yonsei University College Of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: leah1004@yuhs.ac
INTRODUCTION: Colorectal endoscopic submucosal dissection (ESD) has
recently been used for the resection of large colorectal neoplasms that could
not be completely resected by conventional endoscopic mucosal resection
(EMR). The colorectal ESD technique has an advantage of high en bloc resection
rates, but is not accepted as a standard procedure due to several limitations, such
as relatively high perforation rate and very high technical difficulty. However,
ESD was applied to the lesions such as the giant colorectal lateral spreading
tumor (LST) larger than 10 cm by some expert ESD-endoscopist. Thus, we
investigated the feasibility and safety of ESD of giant colorectal LST over 10 cm.
AIMS & METHODS: A total of 133 patients received colorectal ESD between
March 2009 and August 2013 by a single expert ESD-endoscopist at Gangnam
Severance Hospital, Seoul, Korea. Among them, 7 patients had giant colorectal
LSTs larger than 10cm. The tumor features, complete resection rate, and complications of ESD of giant colorectal LST were evaluated. We compared the
clinicopathologic factors of ESD between giant colorectal LSTs and others. All
patients underwent regular follow-up to evaluate for any local recurrence or
distant metastasis.
RESULTS: The colorectal LSTs larger than 10cm were categorized as the giant
colorectal LST. The locations of the 7 giant colorectal LST lesions as follows:
cecum (n 1), sigmoid colon (n 2), and rectum (n 4). The average maximal
diameter of the giant colorectal LST lesions was 124.3 mm (range: 110-160 mm),
and the procedure time was 294.3 min (range: 146-570 min). 2 lesions were whole
nodular types and 5 lesions were focal nodular lesions by the Japanese
Classification of Colorectal Carcinoma. According to the World Health
Organization classification system, histologic diagnosis determined that 1
lesion was low grade dysplasia, 2 lesions were high grade dysplasia, and 4 lesions

were carcinoma. Profound bleeding occurred in 1 patient with whole nodular


type LST, who changed to piecemeal resection and was needed transfusion
during ESD. Perforations developed in 2 patients after ESD, which were managed by endoscopic clipping treatment. The duration of hospitalization in the
giant colorectal LST was 5.6 day (range: 2-12 day). During a mean follow-up
period of 18.5 mo (range: 5.9-27.4 mo), no local recurrence and distant metastasis
occurred. The complication rate was higher in giant colorectal LST than others
(42.9% vs 8.7%, p 0.026). The en-bloc resection and curative resection rate of
ESD for the giant colorectal LST was 85.7% and 100%, respectively, and these
rates were comparable with that of ESD for LST smaller than 10 cm. (en-bloc
resection rate 92.1%, and curative resection rate 92.9%)
CONCLUSION: The ESD of giant colorectal LSTs appears to be a feasible and
curative treatment, even if, it endure the higher complication rate, higher technical difficulty and longer procedure time.
Disclosure of Interest: None declared
P0164 ANALYSIS OF THE BLEEDING AFTER THE ENDOSCOPIC
SUBMUCOSAL DISSECTION (ESD) AND THE ENDOSCOPIC
MUCOSAL RESECTION (EMR) OF COLORECTAL NEOPLASMS
FOR THE PATIENTS TAKING ANTI-THROMBOTIC AGENTS
D. Okamoto1,*, M. Tosa1, D. Komazawa1, H. Ito1, N. Dairaku1, T. Ikeda1, S.I. Ikeya1, H. Nakayama1, N. Hiwatashi1, S. Takahashi1
1
Gastroenterology, Iwaki Kyoritsu General Hospital, Iwaki city, Fukushima, Japan
Contact E-mail Address: oka1572@gmail.com
INTRODUCTION: Recently, EMR and ESD for the patients with many complication has been increasing. Anti-thrombotic therapy is usually provided to
prevent cerebro-cardiovascular events. In 2012, the endoscopic treatment guidelines for the patients taking anti-thrombotic agents were published from Japan
Gastroenterological Endoscopy Society. Thereafter, in our institution, we perform endoscopic treatment in accordance with the guidelines. Delayed bleeding is
one of the major complications of EMR and ESD, but little is known about the
influence of anti-thrombotic therapy.
AIMS & METHODS: In this study, we analyzed the delayed bleeding rate after
colorectal EMR and ESD for the patients taking anti-thrombotic agents. This is
a retrospective study for the consecutive patients treated in our center from
February 2014 to January 2013. Furthermore, we divided the patients taking
anti-thrombotic agents into three groups, and compared the bleeding rate and
the clinical background with control group. [A]: anti-coagulant continuation
group, [B]: heparin or anti-coagulant single agent replacement group, [C]:anticoagulant discontinuation group. Statistical analysis was made by Chi-squared
test (significance: p50.01).
RESULTS: We treated 328 patients with 633 colorectal neoplasms by EMR, and
the delayed bleeding rate was 1.9% (12/633). Male/Female ratio was 237:91 and
the mean age was 64.5 years. 63 patients (19.2%) with 129 neoplasms (20.4%)
received anti-thrombotic therapy and divided into three groups, [A]:16/28, [B]:21/
45, [C]:26/56 (patients/neoplasms). Patients taking the anti-coagulant agents were
significantly older than control group (P50.01). The delayed bleeding rate was 1/
28(3.6%) in group A, 2/45(4.4%) in group B and none (0/56) in group C. We
found no significant differences about the delayed bleeding rate when we compared each group with the control group (9/504; 1.9%). On the other hand, we
treated 47 patients with 47 neoplasms by ESD. Male/Female ratio was 32:15 and
the average age was 68.7 years. 11 patients (23.4%) received anti-thrombotic
agent and divided into three groups, [A]:4, [B]:2, [C]:5. In ESD, patients taking
anti-thrombotic agents were significant older (P50.01), and the delayed bleeding
was not recognized in all cases. In addition, cerebro-cardiovascular events did not
occur in all cases during the clinical course of EMR and ESD.
CONCLUSION: We found no significant differences about the delayed bleeding
rate between patients taking anti-thrombotic agents and control group. Although
this is a single institutional study, we thought that EMR and ESD for the patients
taking anti-thrombotic agents could be performed without increased risk of
delayed bleeding in accordance with the guidelines.
Disclosure of Interest: None declared
P0165 SESSILE SERRATED ADENOMA (SSA): QUALITATIVE
ENDOSCOPIC IDENTIFICATION USING ACETIC ACID, FICE AND
IMAGE MAGNIFICATION
L.A. R. Oliveira1, D.S. D. Oliveira2,*, R. Delisa3
1
Endoscopic Advanced Center (CEA), 2Pontifica Universidade Catolica de
Campinas, 3Pathology, Endoscopic Advanced Center (CEA), Campinas, Brazil
Contact E-mail Address: uniendolix@terra.com.br
INTRODUCTION: Sessile Serrated Adenoma may be the precursor of 30% of
colorectal cancers. The colonoscopy finding and identification of this type of
lesion can reduce the incidence of colorectal cancer.
The correct approach on the search of this specific type of lesion is known to be a
true challenge for the colonoscopists nowadays, and the precise identification, in
number and type, of these lesions is associated to the quality of the colonoscopy
exam.
Not much can be found in the literature about the combined use of acetic acid,
FICE and image magnification in the identification of this specific type of lesion.
AIMS & METHODS: 150 lesions in the right colon were prospectively evaluated: the lesions were larger than 10mm, had a mucus cap and their morphology
suggested sessile serrated adenoma, by the analysis of these lesions, crypts pattern. The study was performed by an endoscopist with extensive experience in
chromoendoscopy and magnification and a single pathologist with extensive
experience in this type of lesion. The lesions were classified into three types of
Pits: type II Classic (Pit II - C), Pit II Open Shape (Pit II - O), and Pit II Fat

A176
Shape (Pit II - F). The crypts were evaluated after instillation of acetic acid,
chromoscopy (FICE), and image magnification.
RESULTS: From all the 150 lesions, 122 were classified as SSA. The Pit pattern
II C was found in all of the lesions analyzed, revealing a low specificity in the
association of this pattern with SSA. However, the Pit II O pattern was found
in 120 lesions, and 118 of these were classified as SSA form, showing a stronger
association of this pattern and SSA than the Pit II- C pattern. When it comes to
the Pit II F, it was found in 122 lesions, and 120 of these were classified as SSA.
All lesions containing the association of Pit II- O and Pit II F pattern, were
classified as SSA.
CONCLUSION: The strong correlation between the colonoscopic findings of
SSA with the use of acetic acid, FICE and image magnification and histological/
molecular alterations of the suspicious lesions, reveals the importance of this
technique in this type of lesions management decision and in the participation
on the colorectal cancer prevention.
REFERENCES
A novel pit pattern identifies the precursor of colorectal cancer derived from
sessile serrated adenoma. Am J Gastroenterol 2012; 107: 460469.
Serrated lesions of the colorectum: Review and recommendations from an expert
panel. Am J Gastroenterol 2012; 107: 13151329.
Disclosure of Interest: None declared
P0166 THE USEFULNESS OF INTRAVENOUS CIMETROPIUM
BROMIDE ON POLYP/ADENOMA DETECTION DURING
COLONOSCOPY WITHDRAWAL
D.K. Kang1,*, D.H. Kang1, H.W. Kim1, C.W. Choi1, S.B. Park1,1, S.J. Kim1,
B.J. Song1, Y.Y. Choi1, Y.S. Shin1, H.K. Lim1
1
Division of Gastroenterology, Department of Internal Medicine, School of
Medicine Pusan National University, Pusan National University Yangsan Hospital,
Yangsan-si, Korea, Republic Of
Contact E-mail Address: shadam@naver.com
INTRODUCTION: Colorectal cancer can be prevented effectively by colonoscopy, because it can detect polyps and adenoma. It can miss from 5 to 32% of
polyps, and proximal colon cancers are not efficiently prevented by colonoscopy
screening. Cimetropium bromide has antispasmodic activity and improves polyp
detection, especially in the right side colon.
AIMS & METHODS: We studied the effect of cimetropium bromide on detection of adenoma in colonoscopy.
Patients undergoing colonoscopy for screening and diagnostic examinations were
included and received 5 mg cimetropium bromide at cecal intubation in Pusan
National University Yangsan Hospital during 2 months in 2013 and 2014, respectively. We studied retrospectively polyp detection rate (PDR), adenoma detection
rate (ADR), advanced adenoma detection rate (AADR), and sessile serrated
adenoma detection rate (SADR) in right side colon as well as in whole
colorectum.
RESULTS: A total of 1025 patients were analyzed in this study. Cimetropium
group consisted of 214 patients and control group consisted of 811 patients.
ADR, AADR in whole colorectum were significantly higher in cimetropium
group, respectively (38.2% vs 28.4% (p 0.03), 10.5% vs 5.3% (p 0.026)).
Also, PDR, ADR, and AADR in right side colon were significantly higher in
cimetropium group, respectively (25.6% vs 19.4% (p 0.015), 23.4% vs 15.6%
(p 0.023), 7.2% vs 3.5% (p 0.024)). But, PDR in whole colorectum and
SADR in right side colon between two groups were not different. In non-right
side colon, PDR and ADR were not significantly higher in cimetropium group,
respectively (31.6% vs 27.8% (p 0.487), 25.0% vs 21.0% (p 0.154)).
CONCLUSION: Cimetropium bromide can improve ADR and AADR in right
side colon as well as colorectum in colonoscopy.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


10  2.5 months and 17 patients did not relapse with a mean Rutgeerts score 0.4
 0.5 after 8  3 months. 5, 2 and 2 patients presented a Rutgeerts score i2, i3, i4,
and 10 and 7 presented a Rutgeerts score i0 and i1, respectively. The mean
percentage of gaps was 11.5  17 (range 0 to 55). Watson score was 1.7  0.9
(range 0 to 3). The mean HB was 1  1.1 (range 0 to 4). Mean Gomes score was
1.1  0.9 (range 0 to 3). Mean CRP, calprotectine and neopterine were 5.4  9.3
(range 52 to 44 mg/l), 811  2207 (range 35 and 9200) and 553  287 (range 142
and 992), respectively. The correlation was significantly positive between
Rutgeerts and Watson score and percentage of gaps (Rho 0.65). The correlation
was positive but not significantly with CRP, Gomes and calprotectine (Rho 0.47,
0.35 and 0.27, respectively). However, in 5/10 and 2/7 patients with i0 and i1
Rutgeerts score, respectively, CLE detected inflammation (Watson score 2).
CONCLUSION: There is a good correlation between CLE score and Rutgeerts
but CLE detected inflammation in 5 patients without endoscopic relapse. The
follow-up of these patients would be interesting to evaluate CLE in predicting
relapse in CD patients.
Disclosure of Interest: None declared
P0168 ENDOSCOPIC SELF-EXPANDABLE METAL STENTS IN ACUTE
MALIGNANT LARGE BOWEL OBSTRUCTION SINGLE CENTER
EXPERIENCE
E. Rodrigues-Pinto1,*, P. Pereira1, A. Peixoto1, S. Lopes1, A. Ribeiro1,
G. Macedo1
1
Gastroenterology, Centro Hospitalar Sao Joao, Porto, Portugal
Contact E-mail Address: edu.gil.pinto@gmail.com
INTRODUCTION: Endoscopic self-expanding metal stents (SEMS) may be
used in acute malignant large bowel obstruction (AMLBO) emerging as an alternative to surgery.
AIMS & METHODS: Characterize the population of patients with AMLBO
that placed endoscopic SEMS in clinical practice. Cross-sectional study of
patients with AMLBO that placed SEMS in a tertiary center in a 3 year period.
RESULTS: We placed SEMS in 47 patients, with a mean age of 7113 years.
The distal top of the tumor was located in the descending colon in 12.8%, in the
sigmoid colon in 61.7% and in the rectum in 25.5%. Eighty-one percent of
patients had lymph node invasion and 68.1% had metastasis. The location of
the tumor did not influence the presence of lymph node involvement (p 0.764),
metastasis (p 0.885) nor the extent of the stent used (p 0.511). Fluoroscopy
was used in 57.4% of the procedures. There was need for placement of a second
stent in 6.4% of patients due to migration during the opening. The rate of early
complications was 11% and late complications was 4.6%. The use of fluoroscopy
did not influence the occurrence of immediate complications (p 0.385), early
complications (p 0.950) or late complications (p 0.057). Thirty-three percent
of patients underwent surgery at a later time, with neo-adjuvant therapy in
17.8%. The median time of follow-up was 150 days (P25-75: 23 437), with a
mortality rate at first year of 60.6%. The survival was significantly higher in
patients submitted later to combined therapy in relation to chemotherapy, surgery or symptomatic treatment (838.5 days [ 35.0] vs 387.6 days [ 87.7] vs
354.3 days [ 80.2] days vs 222.3 [ 104.6 therapy], p50.001).
CONCLUSION: The majority of patients with AMLBO had advanced disease.
SEMS have a high success rate with a low complication rate, reducing the high
morbidity and mortality associated with emergency surgery and creation of a
stoma.
Disclosure of Interest: None declared
P0169 COLONIC CHICKEN SKIN MUCOSA IS AN INDEPENDENT
ENDOSCOPIC PREDICTOR OF DISTALLY LOCATED ADVANCED
COLORECTAL ADENOMA
E.J. Chung1,*, J.Y. Lee1, S.-J. Myung2
Health promotion and screening center, 2Gastroenterology, Asan medical center,
Seoul, Korea, Republic Of
1

P0167 CORRELATION
BETWEEN
ENDOSCOPIC
AND
ENDOMICROSOPIC SCORES IN CROHNS DISEASE PATIENTS IN
DETECTING RELAPSE AFTER SURGERY
D. Moussata1,2,*
1
Gastroenterology, Lyon Sud Hospital, Pierre Benite, 2CREATIS, CNRS,
Villeurbanne, France
Contact E-mail Address: driffa.moussata@chu-lyon.fr
INTRODUCTION: As clinical relapse risk is well correlated with the endoscopic
appearance in operated Crohns disease (CD) patients, its recommended to perform an endoscopy in the year following the surgery in order to adapt treatment.
In endoscopy, the relapse is based on Rutgeerts score superior to i2 defined by
the presence of more than 5 ulcerations. Confocal Laser Endomicroscopy (CLE)
can detect inflammation on a macroscopic healing mucosa (whereas macroscopically the mucosa appears normal). Inflammation is evaluated by CLE according to percentage of gaps reported to total villous perimeter and to Watsons
score based on shedding and luminal signal.
AIMS & METHODS: Aim: To evaluate inflammation with CLE into the ileum
above the anastomosis (ileocolic anastomosis) and compare with Rutgeerts score.
Patients and methods: In the year following the surgery, under sedation, an
endoscopy with CLE (EC3870K Pentax, Tokyo) was performed after 3 ml fluorosceine injection. Relapse was scored endoscopically with Rutgeerts score and
endomicroscopically with percentage of gaps and Watsons score, which were
quantified as calprotectine in stools, urinary neopterine and C-reactive protein
(CRP). We compared Harvey Bradshaw score, Watsons score, calprotectine,
neopterine, CRP and histology (Gomes score) with Rutgeerts score.
RESULTS: 26 patients (12 men, mean age 36  11 years ( SD)) were included
prospectively. The endoscopy was performed in 9  3 (range 6 to 13) months
after the surgery. 9 patients relapsed with a mean Rutgeerts score 2.7  0.8 after

INTRODUCTION: Chicken skin mucosa (CSM) surrounding colorectal adenoma is described as an endoscopic finding with pale yellow-speckled mucosa
and aggregations of lipid-filled macrophages in the lamina propria noted on
histopathology. However, its clinical significance is unknown.
AIMS & METHODS: The aim of this study was to evaluate the prevalence,
clinical characteristics of CSM, and association between colorectal carcinogenesis
and CSM. This cross-sectional study was performed on 733 consecutive patients
who underwent endoscopic polypectomy for colorectal adenoma after screening
colonoscopy at the Asan Health Promotion Center between June 2009 and
December 2011. The colonoscopic and pathological findings of colorectal adenoma including number, size, location, dysplasia, and morphology, and clinical
parameters were reviewed.
RESULTS: The prevalence of CSM was 30.7% (225 of 733 patients), and most
CSM-related adenomas were located in the distal colon (93.3%). Histological
analysis revealed lipid-laden macrophages in the lamina propria of the mucosa.
According to multivariate analyses, CSM was significantly associated with
advanced pathology, including villous adenoma, high-grade dysplasia, and carcinoma in situ (OR 2.078, 95% CI 1.191-3.627, p 0.010), multiple adenomas
(i.e.,  2 adenomas; OR 1.692, 95% CI 1.143-2.507, p 0.009), and a protruding
morphology (OR 1.493, 95% CI 1.027-2.170, p 0.036). There were no significant differences found in terms of polyp size or clinical parameters between
patients with and without CSM.
CONCLUSION: CSM-related adenoma was mainly observed in the distal colon.
CSM was associated with advanced pathology and multiple adenomas. CSM
may be a potential marker of the carcinogenetic progression of distally located
colorectal adenomas.
Disclosure of Interest: None declared

A177

United European Gastroenterology Journal 2(1S)


P0170 PREVALENCE OF COLORECTAL POLYPS IN A GROUP OF
SUBJECTS WITH AVERAGE-RISK OF COLORECTAL CANCER
UNDERGOING COLONOSCOPIC SCREENING IN TEHRAN, IRAN
BETWEEN 2008 AND 2013
M. Sohrabi1, F. Zamani1,*, M. khonsari1, H. Ajdarkosh1, N. Rakhshani1,
G. Hemmasi1
1
Gastrointestinal and Liver Disease Research Centre, Iran University, Tehran,
Iran, Islamic Republic Of
Contact E-mail Address: sohrab_r@yahoo.com
INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of
death in different countries. Due to slow progression of GC, detection of CRC
in early stage is important issue. There have been no high quality studies from the
Middle East.
AIMS & METHODS: We aimed to investigate the prevalence of preneoplastic
and neoplastic lesions of the colon in the average risk population.
Eligible asymptomatic, average risk adults between 2008 and 2012, aged older
than 40 years old, in Firoozgar general hospital were involved. They underwent
screening colonoscopy. All polypoid lesions were removed and examined by an
expert gastrointestinal pathologist. The lesions were classified by size, location,
numbers and pathologic findings. Size of lesion was also measured by
endoscopists.
RESULTS: One thousand and eight subjects were enrolled in this study. The
mean age of participants was 56.45  9.59 years and 51.6% subjects were male.
Overall polyp detection rate was 199/1208 (16.5%). Of them 26 subjects had nonneoplastic polyps including hyperplastic polyps, and 173/1208 (14.3%) subjects
had neoplastic polyps of which, 26 (2.15%) were advanced neoplastic lesion. The
prevalence of colorectal neoplasia was more common among 50-59 years old
(p ); although, prevalence of adenoma was noticeable in 40-49 years old
group. The advanced adenoma was also more frequent among age over 50
years old. Majority of adenomas were detected in distal colon, but a quarter of
advanced adenomas were detected in proximal colon. Most colorectal adenoma
was detected beyond sigmoid. The increasing age and male gender were associated with presence of adenoma.
CONCLUSION: It seems that CRC screening among average-risk population
might be recommended in countries such as Iran. However, sigmioidoscopy
alone would have missed many colorectal adenomas. Furthermore, the 50-59
age group could be considered as an appropriate target population for this
purpose.
Disclosure of Interest: None declared
P0171 STANDARD QUALITY ENDOSCOPY REPORT: DELPHI
CONSENSUS TO IDENTIFY QUALITY MEASURES FOR UPPER
AND LOWER GI ENDOSCOPY
F. Iacopini1,*, A. Bella2, G. Costamagna3, L. Baiocchi4, M. Angelico5, A. Kohn6,
M.C. Di Paolo7, L. Tammaro8, E. Grasso4 on behalf of Lazio AIGO-SIEDSIGE members
1
Gastroenterology and Endoscopy Unit, Ospedale S. Giuseppe, Albano L, Rome,
2
National Center for Epidemiology, Surveillance and Health Promotion, Istituto
Superiore di Sanita`, 3Surgical Digestive Endoscopy, Catholic University,
4
Gastroenterology, Policlinico Tor Vergata, Rome, 5Gastroenterology, Policlinico
Tor Vergata, Roma, 6Gastroenbterology, Ospedale S. Camillo-Forlanini,
7
Gastroenterology and Endoscopy Unit, 8Gastroenterology and Endoscopy,
Ospedale S. Giovanni-Addolorata, Rome, Italy
Contact E-mail Address: federico.iacopini@gmail.com
INTRODUCTION: Efforts to improve quality in endoscopy are ongoing and
quality measures determined by examining the procedure report have been proposed as a mechanism for meeting this goal. Complete documentation is necessary for patient care and appropriate use of endoscopy. However, quality
measures are very numerous and it is undetermined which are really critical for
quality of cure.
AIMS & METHODS: To identify the quality measures to be included in the
upper and lower GI endoscopy report of standard quality. Quality measures were
extracted from the Quality Assurance Task Groups of the US Gastroenterology
Societies (ASGE, AGA, ACG). Measures included in the questionnaire were
divided in three categories: 1) pre-procedural with patient demographics (n.
15); 2) procedural (n. 27); 3) post-procedural (n. 9). A Rand Delphi method
was used to reach the consensus. Participants were asked to label each measure
using a 6 point Likert scale from 0 (not required) to 5 (absolutely required). The
questionnaire was iteratively proposed to via a web-based application with a
feedback of the results observed at the preceding round (median value; % of
patients expressing the median value). Consensus was reached when no significant change was observed between values of the last two rounds (median, IRQ
range, P value by Wilcoxon test). Measures with a score-5 were considered to
characterize the standard (minimum) quality.
RESULTS: A total of 72 participants completed the 3 Delphi rounds required to
reach the consensus: mean age 48; working experience (yrs) 11; n. endoscopy/
week 415 in 61%; public employment 61%. A strong consensus was obtained
for 33 (61%) out of 51 metrics. A score-5 was achieved for the following measures: patient name and birth date; exam indication; date and findings of the
previous endoscopy for follow-up; anti PLT/coagulants use; informed consensus
collection; assistants/anesthesiologist names; sedation drugs and doses; antibiotic
prophylaxis use; causes of incomplete examination; stricture lumen according to
the endoscope diameter; photographic documentation of landmark and findings;
findings localization and biopsies; operative interventions: description of technique and completeness; definition of complete EGD retroversion manouvre; definition of complete colonoscopy: ileoscopy and retroversion in the rectum;
indications after endoscopy in case of adverse events and follow-up.

CONCLUSION: The availability of a huge number of measures may be one of


the causes of the poor report quality. The identification of the list of measures
defining the endoscopy report of standard quality could provide endoscopists
with an improvement tool and referring physicians with a report that use standard terms and provide follow-up recommendations. The identification of mandatory quality measures within their long list will ensure a fair accounting of the
procedure and may encourage broader adoption of quality improvement efforts.
Disclosure of Interest: None declared
P0172 SELF-EXPANDABLE MESH METAL STENTS (SEMS) FOR
ACUTE COLONIC OBSTRUCTION - EXPERIENCE OF A UK
CENTRE
G.H. El Sayed1,*, J. Deepak1, B. Paranandi1, P. Patel1, M. Ryde1, S.P. Pereira1,
M.H. Chapman1, G.J. Johnson1, A. Obichere2, M.J. Obichere3, G. Webster1
1
Gastroenterology & Hepatobiliary medicine, 2Colorectal surgery, University
College London Hospitals, London, 3Colorectal surgery, Luton & Dunstable,
Luton, United Kingdom
Contact E-mail Address: ghassanovii@yahoo.co.uk
INTRODUCTION: Acute intestinal obstruction occurs in up to 30% of patients
with colorectal carcinoma. Historically, emergency surgical decompression was
the treatment of choice. Self-expandable mesh metal stents (SEMS) have been
increasingly used for malignant colonic obstruction. Several studies showed its
efficacy in relieving obstruction, offering good palliation, avoiding emergency
surgery and reducing the need for stoma creation.
AIMS & METHODS: A password-protected database of prospectively recorded
endoscopic activity in our UK centre was analysed. Endoscopic records of
patients undergoing SEMS for colonic obstruction from April 2007 to April
2014 were assessed. Data parameters included: patient demographics; site and
pathology of obstruction; SEMS details; technical success of SEMS placement
(correct placement of the stent across the stricture); clinical success (colonic
decompression, with relief of obstructive symptoms and no significant complication); complications and the need for further intervention.
RESULTS: 107 SEMS insertion procedures were performed on 95 patients
during the study period. M: F 46%:54%; median age 70 years (range 20 95);
50% were tertiary referrals. Causes of obstruction were primary colorectal cancer
(CRC) (78%), extrinsic compression (18%) due to other malignancy mainly
gynaecological; unspecified (4%). Obstruction occurred in left colon (distal to
mid transverse) in 87% of cases. The majority of patients (97%) had sedation and
only 3% were done under general anaesthesia. 3 stent types were used: 98%
uncovered (Boston Wallflex (n 27), Cook Evolution (n 78)), 2% fully covered
(Taewoong Medical (n 2)). The median length of SEMS was 80mm (range
60mm 120 mm). A single SEMS was inserted in 92% of patients, with 2
SEMS in the same session in 8 patients, and 3 SEMS in one patient. All
SEMS were inserted under combined endoscopic and fluoroscopic guidance.
Technical success was achieved in 98% of patients, with clinical success in 76%.
Complication

Number (%)

Post perforation management

Perforation

5/107 (5%)

4/5 (80%)-emergency laprotomy


1/5 (20%)- palliated

Obstruction due
to flat valving
stent migration
Stent occlusion

2/107 (2%)
6/107 (6%)
3/107 (3%)

Median time to perforation from stent insertion was 4.5 days (range 1 15 days).
Median time to death from stent insertion was 8.5 months; 6/107 (6%) died 5 30
days from stent insertion, with one attributed to stent-related perforation. Stent
migration noted to occur more in non-CRC extrinsic obstruction (2/19 (11%))
than primary CRC (4/88 (4.5%)).
CONCLUSION: Our data demonstrate that SEMS insertion for acute colonic
obstruction is technically highly successful. However, technical success does not
guarantee clinical success in all cases, and non-CRC extrinsic compression may
be associated with higher rates of SEMS migration. The 5% perforation rate was
similar to other reported studies, and needs to be considered in conjunction with
the risks of emergency surgery in this patient group. The results of large randomised multicentre trials of SEMS vs surgery in palliating acute colonic obstruction are awaited.
Disclosure of Interest: None declared
P0173 LEARNING CURVE IN MUCOSAL HEALING (MH)
INFLAMMATORY ACTIVITY ASSESSMENT BY USING THE
ERLANGEN MH SCORE FOR CONFOCAL LASER
ENDOMICROSCOPY (EMHS) IN INFLAMMATORY BOWEL
DISEASES

AND

G. Hundorfean1,*, M.T. Chiriac1, A. Nagel1, H. Albrecht1, C. Janson1, R. Gortz1,


C. Weber1, S. Jungbauer1, L. Merkl1, F. Zoicas1, T. Kukiolka1, A.E. Kremer1,
J. Siebler1, M.F. Neurath1
1
Medical Clinic 1, University of Erlangen-Nuremberg, Erlangen, Erlangen,
Germany
Contact E-mail Address: gheorghe.hundorfean@uk-erlangen.de
INTRODUCTION: Confocal laser endomicroscopy (CLE) is a modern imaging
technique that enables real time histology in vivo, during endoscopy, providing
new insights of mucosal pathology. Monitoring histological activity to assess

A178
MH is important in evaluating the therapy response and management of inflammatory bowel diseases (IBD). Our group has recently validated an endomicroscopic mucosal healing score (eIBD-MHs), which has to be interpreted by skilled
endoscopists.
AIMS & METHODS: Our first aim was to analyze the learning curve (LC) of
MH assessment by CLE in endoscopists na ve to the CLE technique. Secondly,
we comparatively investigated the LC between endoscopists and residents (i.e.
physicians acquainted neither to endoscopic nor to CLE techniques).
Therefore, 4 study groups were established: a.) senior endoscopists (n 3), board
certified (42000 procedures, 42 years of experience); b.) junior endoscopists
(n 3) (significant endoscopic skills, 52 years of experience); c.) internal medicine residents (n 4) without endoscopic experience, and d.) a skilled endomicroscopist (n 1). Initially, all attendees received a random set of 20 CLE images
from 10 IBD patients with different inflammatory activity and a table with the
eIBD-MHs (9 criteria) for a spontaneous offline assessment (based only on histologic knowledge from medical school and interdisciplinary medical-histopathology meetings). Thereafter, all physicians participated in a short training
session including explanation of the CLE technique, terminology, elementary
CLE lesions, and assessment of IBD cases based on the eIBD-MHs before and
after therapy). Subsequently, the same set of 20 CLE pictures was re-assessed (in
a modified, paired succession, grouped per patient, before and after therapy). All
physicians were blinded regarding patients identity, diagnosis and disease activity. Assessment scores and duration from the pre- and post-teaching evaluation
were statistically analyzed.
RESULTS: The average evaluation times before and after training for the groups
a; b; c and d were: 25 vs. 12,33; 23 vs. 15; 24,5 vs. 15,25; 14 vs. 9 minutes,
respectively). Overall, the evaluation time before the CLE instruction session
was significantly longer (p50.001) compared to second evaluation times. No
significant differences were observed between the physicians with or without
endoscopic experience regarding assessment duration and quality.
Interobserver agreement of the MH evaluation in the groups (compared to the
assessment results of the skilled endomicroscopist) for group a; b and c were:
0.72; 0.52 and 0.75, respectively.
CONCLUSION: In conclusion, the LC for MH and inflammatory activity
assessment by CLE is fast, can be easily learned and is independent of basic or
advanced endoscopic skills or experience.
Disclosure of Interest: None declared
P0174 COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION:
RESIDUAL/RECURRENT LESIONS VERSUS PRIMARY LESIONS
G. Andrisani1,*, L. Petruzziello1, G. Vitale1, S. Greco1, I. Costamagna1,
C. Spada1, G. Costamagna1
1
Digestive Endoscopy Unit, Catholic University, Rome, Italy
Contact E-mail Address: gianluca.andrisani@gmail.com
INTRODUCTION: Residual/locally recurrent lesions may occur after endoscopic resection: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) or after transanal endoscopic microsurgery (TEM) for
rectal lesions. ESD may be useful for resection of scar-embedded lesions, not
lifted by standard injection of saline solution, but may be more technically difficult. We evaluated the feasibility and safety of ESD, as a salvage therapy for
residual/locally recurrent lesions compared to primary lesions.
AIMS & METHODS: From January 2012 to March 2013 we performed 30
colonic ESD. Fifteen patients were on the first endoscopic treatment and the
remaining fifteen had residual/recurrent lesions (median diameter of 21 mm) and
have received at least an attempt at endoscopic resection using standard techniques including snare polypectomy, EMR or argon plasma coagulation, or TEM
(5/15). The tumor size, the procedure duration, complications and early recurrence rate were compared between the two groups.
RESULTS: Procedure time was similar between groups (7022 min vs 7235
min). The lesions were significantly smaller (239 mm vs 35 15 mm; P 5 0.05)
in the residual/ locally recurrent group, compared with primary lesions.
Immediate bleeding rate was significantly higher in primary lesions group
(46.6% vs 6.6%; P 5 0.05). However, there were no cases of delayed bleeding
in both groups. Intraprocedural perforations were observed only in residual/
locally recurrent group (3/15: 20%): surgery was needed in one patient, while
two patients were managed using endoclips. Early recurrence, evaluated at three
months, was similar between groups (20%)
CONCLUSION: Endoscopic submucosal dissection for residual/locally recurrent lesions was more difficult with higher risk of perforation due to presence
of scar. However, the presence of lesions of smaller size and the low risk of intraprocedural bleeding, may recommend this procedure for scar-embedded lesions
instead of surgical resection.
REFERENCES
1. Kuroki Y, et al. Endoscopic submucosal dissection for residual/locally recurrent lesions after endoscopic therapy for colorectal tumors. J Gastroenterol
Hepatol 2010; 25: 1747-1753.
2. Azzolini F, et al. Endoscopic submucosal dissection of scar-embedded rectal
polyps: a prospective study (Esd in scar-embedded rectal polyps). Clin Res
Hepatol Gastroenterol 2011; 35: 572-579.
3. Hayashi N, et al. Predictors of incomplete resection and perforation associated
with endoscopic submucosal dissection for colorectal tumors. Gastrointest
Endosc 2014; 79: 427-35.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0175 THE USE OF DOUBLE CHANNEL GASTROSCOPE REDUCED
THE PROCEDURAL TIME IN LARGE LEFT-SIDED ENDOSCOPIC
MUCOSAL RESECTIONS
V. Evangelos1, G. Tribonias1, A. Tavernaraki1, A. Theodoropoulou1,
E. Vardas1, G. Chlouverakis2, G. Paspatis1,*
1
Gastroenterology, Venizeleion Hospital, Heraklion, Crete, 2Department of Social
Medicine, University of Crete, Heraklion, Greece
Contact E-mail Address: gpaspatis@gmail.com
INTRODUCTION: Endoscopic mucosal resection (EMR) of large colorectal
lesions is associated with an increased procedural time. Usually the inject and
cut EMR technique is applied for large sessile or flat colorectal lesions. The use
of double channel gastroscope (DCG) might reduce the procedural time in the
rectosigmoid area.
AIMS & METHODS: To evaluate the effect of DCG use in the procedural time
of injection-assisted EMR performed in the rectosigmoid area. To the best of our
knowledge this is the only comparative study on this subject. All EMRs for
sessile or flat rectosigmoid lesions larger than 2cm performed from July 2012
to September 2013 were retrospectively analyzed. The use of DCG was mainly
dependent on the availability.
RESULTS: There were 55 lesions 2cm or larger in the rectosigmoid area in 55
patients, of which 26 were removed by EMR using a DCG (DC group) and 29 by
using an ordinary colonoscope or gastroscope (OS group). The mean size of the
removed polyps was not statistically different between the two groups (4.3cm
1.86 & 3.9 cm  1.9 in DC and OS group respectively). The Paris classification
was similar between the two studied groups. The mean procedural time in the DC
group (24.418.3 min) was significantly lower compared to that of OS group
(36.324.4 min) (p50.05). Moreover, in the subgroup of patients with polyps
larger than 40mm the statistical difference in the mean procedural time between
the DC group (3321min) and OS group (58.720.6 min) (p50.01) was even
more pronounced. Outcome parameters such as recurrence rate (12 months
follow-up), post-procedural bleeding rate and hospital stay were similar between
the two groups. No case of perforation was observed. Multivariate linear regression analysis revealed that the polyp size (b 0.92, p50.001) and use of DCG
(b 15.5, p50.001) were significantly associated with the procedural time.
CONCLUSION: Our data suggest that the use of DCG for large sessile or flat
rectosigmoid lesions significantly reduces the procedural time. The use of DCG
seems to be more effective in larger polyps. These results should be confirmed in
a prospective study.
Disclosure of Interest: None declared
P0176 ADENOMATOUS
HISTOLOGY
IN COLONIC
INFLUENCE OF POLYP LOCATION, SIZE AND PARISCLASSIFICATION

POLYPS:

H.F. Hammer1,2, J.L. Klein1,*, M. Okcu3, K.H. Preisegger3


Gastroenterology and Hepatology, Medical University Graz, 2Privatklinik,
Kastanienhof, 3IMAH, Graz, Austria
Contact E-mail Address: heinz.hammer@medunigraz.at
1

INTRODUCTION: Published data on the likelihood of a polyp being an adenoma in relation to its location in the colon, size and form are incomplete.
AIMS & METHODS: To evaluate these factors in a consecutive patient group
all histologically verified colonic adenomas which were removed by one endoscopist between 01-01-2011 and 31-12-2013 were included into this analysis.
Before polypectomy polyps were classified as protruded (Paris classification
type I) or flat (Paris type II), their size was estimated as compared to an open
biopsy forceps, and the location in the colon was noted. Polyps were grouped
according to their diameter using groups of sizes published in the literature. In
the study period 698 patients were colonoscoped by one of the authors (mean
patient age 62 years, 392 female). Visibility was reduced by fecal residues in 43
patients (6.2%). In 12 patients (1.7%) the cecum was not reached. In 8 patients
(1.1%) the polyp could not be retrieved.
RESULTS: 1877 polyps were removed and histologically assessed. In 8 patients
(1.1%) the polyp could not be retrieved for histological analysis. In 7 patients
(1.0%) the location of the polyp was not described. In 34 polyps (6% of polyps)
the estimated diameter was not described. Carcinoma of the sigmoid colon was
detected in one patient. Adenoma was detected in 565 polyps (n 222 Paris type
I lesion; n 343 Paris type II lesion). 13% of all adenomas were located in the
coecum (18 Paris I; 56 Paris II), 23% in the ascending colon (52 Paris I; 79 Paris
II), 27% in the transverse colon (71 Paris I; 79 Paris II), 7% in the descending
colon (19 Paris I; 22 Paris II), 22% in the sigmoid colon (43 Paris I; 80 Paris II)
and 8% in the rectum (19 Paris I; 27 Paris II). The table shows the total number
of adenomas in 5 groups according to lesion diameter, and the likelihood of a
polyp having adenomatous histology in % of all removed polyps, again in relation to diameter and to Paris-classification of the lesion.
Table to abstract P0176

Diameter

minute small
large
55 mm 6-7 mm 8-9 mm 410 mm

Total

Number of adenomas 270

189

40

Adenoma, %
of all polyps
Adenoma in Paris I
Adenoma in Paris II

23%

39.5%

51.3%

10-19 mm 20 mm 531


27
5
82%
100%

58%
20%

61%
29%

64%
32%

91%
75%

62%
23%

United European Gastroenterology Journal 2(1S)


CONCLUSION: Summary: 63% of adenomas are located oral to the left colonic
flexure. 61% of adenomas are flat lesions. Both in the right and in the left colon
the majority of adenomas are flat. However, in polyps of all sizes protruding
lesions have a significantly higher likelihood of being adenomatous as compared
to flat lesions. In flat and protruding lesions the likelihood of a polyp being
adenomatous increases with polyp size, from 58% to 91% in protruding and
from 20% to 75% in flat lesions. Conclusion: Almost two thirds of colonic
adenomas are flat or are located oral to the left colonic flexure. Although only
a minority of small and flat polyps are adenomatous, they comprise the majority
of adenomas. The high number of lesions in the right sided colon has not been
reported before and may be related to excellent colonoscopy preparation with
only 6% of colonoscopies having been influenced by fecal residues. The clinical
role of the right sided and the small polyps needs to be determined.
Disclosure of Interest: H. Hammer: None declared, J. Klein: none, M. Okcu:
none, K. Preisegger: none
P0177 A HAND-HELD METAL DETECTOR IS AN ACCURATE, LOW
COST ASSESSMENT OF FLEXIBLE SIGMOIDOSCOPY
COMPLETION TO THE SPLENIC FLEXURE
H.C. Matthews1,2,*, G. Sadler2, R. Leicester3
1
Gastroenterology, Kingston Hospital Foundation Trust, 2Gastroenterology,
3
Endoscopy, St Georges NHS Trust, London, United Kingdom
Contact E-mail Address: h.matthews1@nhs.net
INTRODUCTION: Flexible sigmoidoscopy (FS) is a validated screening test to
reduce the incidence of colorectal cancer. Bowel scope screening is due to be
implemented in the UK by 2016. There is variability in FS performance between
operators; internal colonoscopic markings are unreliable for colonoscope posiTM
tion. Three dimensional (3D) magnetic imaging systems eg Scopeguide
(Olympus, UK) represent real time instrument position but are not widely available. Hand-held metal detectors (HHMD) can easily localise metal objects within
the body. We assessed use of HHMD to confirm flexible endoscopic tip placement at the splenic flexure (SF).
AIMS & METHODS: Adult subjects undergoing outpatient FS/colonoscopy
were eligible and gave consent. When the operator judged examination complete
to the SF, an independent observer placed the HHMD at the left 10th intercostal
space, anterior-axillary line (corresponding to the internal fixation of the colon at
the SF). A positive resultTMwas recorded if the HHMD beeped. Position was then
assessed by Scopeguide . If the SF could not be reached, the patient was
excluded. We evaluated 3 different HHMD from different manufacturers.
Patient experience was also studied. Ethical review NREC Ref no 13/LO/1065;
IRAS Project ID 121224.
RESULTS: 44 subjects were recruited consecutively: mean age 64 years (range
17-74), 50% male (n 22), mean BMI 27 kg/m2 (range 20-41 kg/m2). Endoscopic
TM
confirmation of position at SF showed concordance with Scopeguide in 95%
(42/44). Subjects 1-6 were examined using BDS200 (Black & Decker) HHMD.
Despite promising results on colonoscopic training models, this proved insensitive in humans and was abandoned. For subjects 7-30 (n 24) studied with
GMS120 (Bosch) HHMD, positive reading at the correct
anatomical marking
TM
was recorded in 88% of examinations with Scopeguide validation. Of the 3
2
failures, 2 had a BMI of 430 kg/m . Use of an X-Ray screening trolley improved
specificity. For subjects 31-44, n 14, a detector with increased sensitivity and
directional capabilities, GPP (Garrett Metal Detectors USA), was used on standard endoscopy trolleys. This showed concordance with 3D imaging in 100% of
cases (n 14) including 4 patients with BMI 430kg/m2. ThereTMwas one true
negative versus endoscopic assessment confirmed by Scopeguide . The technique was further validated by loss of signal on scope withdrawal. Patient questionnaires showed high acceptability.
CONCLUSION: Use of HHMD in FS has shown excellent concordance with
ScopeguideTM for colonoscope localisation at SF. Specificity and sensitivity are
improved by adapting the specifications of the HHMD. A HHMD is an accurate
and very cheap (E100 per unit) means of assuring quality during FS and further
studies may confirm its role as a useful training tool especially during future
service expansion.
REFERENCES
Atkin W et al. BMJ 2010.
Leicester R et al. Lancet 1981.
Disclosure of Interest: None declared
P0178 CONFOCAL LASER ENDOMICROSCOPY (CLE) DEMASKS
SUBTLE MUCOSAL CHANGES IN PATIENTS WITH IRRITABLE
BOWEL SYNDROME (IBS)
H. Neumann1,*, G.E. Tontini1,2, M. Vieth3, C. Gunther1, S. Zopf1,
M.F. Neurath1, Y. Zopf1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany, 2IRCCS
Policlinico San Donato, San Donato Milanese, Italy, 3Klinikum Bayreuth,
Bayreuth, Germany
INTRODUCTION: IBS is a symptom-based diagnosis characterized by chronic
abdominal pain, bloating, and alterations of the bowel habits without any
organic cause. CLE allows in vivo visualization of microscopic features of the
intestinal epithelium in real time during endoscopy.
AIMS & METHODS: To assess whether CLE is able to demask microscopic
alterations of the small and large bowel mucosa in patients with established
diagnosis of IBS.
Patients with established diagnosis of IBS according to Rome-III criteria and
control patients underwent ileocolonoscopy. Fluoresceine guided CLE was performed in the terminal ileum and random optical biopsies were additionally
performed in the colon and rectum. Attention was paid to presence or absence

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of epithelial gaps, intramucosal bacteria, crypt and vessel morphology, goblet
cells and cellular infiltrate within the lamina propria. Physical biopsies were
additionally taken for histopathological analysis.
RESULTS: Epithelial gap density and the microvascular pattern were increased
in a subgroup (44%) of patients with IBS according to Rome-III as compared to
control patients suggesting an altered intestinal permeability. No differences were
observed regarding the presence of intramucosal bacteria, colonic crypt morphology, presence of goblet cells or the cellular infiltrate within the lamina propria (P
40.05).
CONCLUSION: Confocal imaging revealed subtle changes of the mucosa in
patients with IBS. These findings were not visible in every patient with IBS
according to Rome-III criteria suggesting that some IBS patients may have an
organic cause of the disease.
Disclosure of Interest: None declared
P0179 IN VIVO ASSESSMENT OF PORTAL HYPERTENSIVE
COLOPATHY AND CLINICAL OUTCOME OF PATIENTS WITH
LIVER CIRRHOSIS WITH CONFOCAL LASER ENDOMICROSCOPY
(CLE)
H. Neumann1,*, G.E. Tontini2, C. Gunther1, M. Vieth3, Y. Zopf1, M.F. Neurath1,
S. Zopf1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany, 2IRCCS
Policlinico San Donato, San Donato Milanese, Italy, 3Klinikum Bayreuth,
Bayreuth, Germany
INTRODUCTION: Recent data has highlighted the role of mucosal integrity for
bacterial translocation in the gut which is also discussed as a major cause for
development of spontaneous bacterial peritonitis (SBP) and/ or hepatic encephalopathy (HE) in patients with liver cirrhosis. CLE has emerged as a valuable tool
for real time diagnosis of mucosal integrity and allows in vivo imaging of commensal bacteria in the gut.
AIMS & METHODS: To prospectively assess the value of CLE for in vivo
diagnosis of portal hypertensive colopathy and its association to Child-Pugh
class, Model for End Stage Liver Disease (MELD), HE and development of
SBP. Patients with established diagnosis of liver cirrhosis and portal hypertension
were prospectively included. Clinical, biochemical, and ultrasound criteria,
including portal vein thrombosis, ascites and collateral portosystemic vessels
were assessed in addition to endoscopic criteria (e.g. esophageal varices, portal
gastropathy) and beta-blocker intake. Fluoresceine aided CLE was performed in
every patient in the sigmoid colon, rectosigmoid junction, and rectum.
Afterwards biopsies were taken, unless contraindicated, for corresponding histopathological analysis.
RESULTS: Overall, more than 14,700 CLE images were collected. Confocal
imaging revealed dilation and/or ectasia of microvessels, congestion of blood
flow, edema, and a non-specific increase of the cellular infiltrate within the
lamina propria. These findings were directly correlated to Child-Pugh class and
MELD score with patients at higher scores showing more distinct changes of the
microarchitecture. Of note, disturbed mucosal integrity, as observed by CLE, was
strongly correlated with occurrence of HE and SBP, even in the follow-up of the
patients. The procedure was well tolerated by the patients, and no adverse events
were observed.
CONCLUSION: Fluoresceine guided CLE in patients with liver cirrhosis and
portal hypertensive colopathy is safe and well tolerated. In vivo imaging revealed
similar microscopic changes of portal colopathy as conventional histology without the need of physical biopsies. Of note, confocal imaging corresponds to
clinical outcome parameters, including development of HE and/or SPB.
Disclosure of Interest: None declared
P0180 HIGH-DEFINITION ENDOSCOPY WITH COMPUTED VIRTUAL
CHROMOENDOSCOPY FOR PREDICTION OF FOOD ALLERGY IN
REAL-TIME A PROSPECTIVE, RANDOMIZED STUDY WITH
CROSS-OVER DESIGN
H. Neumann1,*, M. Vieth2, G.E. Tontini1,3, S. Zopf1, C. Gunther1,
M.F. Neurath1, Y. Zopf1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, 2Klinikum
Bayreuth, Bayreuth, Germany, 3IRCCS Policlinico San Donato, San Donato
Milanese, Italy
INTRODUCTION: Food allergy is mediated via IgE and non-IgE mediated
mechanisms. White-light endoscopy is not feasible to detect any specific mucosal
alterations in patients with intestinal food allergy.
AIMS & METHODS: To access the value of advanced endoscopic imaging using
high-definition colonoscopy with computed virtual chromoendoscopy (CVC) for
prediction of mucosal changes in patients with suspected food allergy.
Patients suffering from recurrent abdominal pain and diarrhea were consecutively included. At baseline, patients underwent a standardized clinical interview
in order to contain the diagnosis. Afterwards, patients underwent ileocolonoscopy with high-definition white-light endoscopy alone followed by CVC or
the reverse. The mucosa of the terminal ileum, caecum and at the rectosigmoid
junction was carefully inspected with or without CVC. Following the endoscopic
inspection, a diagnostic lavage examination was performed at the above mentioned locations and analysed by measuring 13 different allergic markers, including TNF-alpha, IgE, and eosinophilic cationic protein. Finally, biopsies were
obtained for additional histopathological analysis of the tissue.
RESULTS: 46 patients were randomized of which 39 patients (31 female, mean
age 50 years; Range 21-78 years) completed the study protocol. Based on the
clinical presentation, histopathological results and the lavage diagnosis 61% (24/
39) of patients were diagnosed with intestinal food allergy. High-definition imaging with CVC visualized lymphoid hyperplasia, slight mucosal edema and

A180
blurred mucosal vascular pattern. No mucosal changes were observed with highdefinition endoscopy alone. CVC allowed correct diagnosis in 21 of 24 intestinal
food allergy cases as compared with the criterion standards, giving a sensitivity,
specificity and accuracy of 88%, 87%, and 87%, respectively. Positive and negative predictive value of CVC to predict food allergy was 91% and 81%,
respectively.
CONCLUSION: High-definition endoscopy with CVC could mimic slight mucosal changes in patients with intestinal food allergy which were highly predictive
for the disease. Therefore, advanced endoscopic imaging could add valid new
criteria for diagnosis of intestinal food allergy.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


(group A) had a thick fibrosis (F2) after severe radiation colitis and resulted in
a delayed perforation the following day.
CONCLUSION: The size or location of tumors will not be related to dissection
speed. This study showed a severe fibrosis was only a predictor, which was
independent of the tumor size, of decelerating a dissection speed during colorectal ESD. In a case with severe fibrosis, an operation will take much time
because of the difficulty, so an experienced physician should perform ESD.
Additional cases, while considering dissection speed, will probably be a good
reference for a predictor of the difficulty of colorectal ESD.
REFERENCES
(1) Matsumoto A, et al. Outcome of endoscopic submucosal dissection for colorectal tumors accompanied by fibrosis. Scand J Gastroenterol 2010; 45: 1329-1337.
Disclosure of Interest: None declared

P0181 UNDERWATER ENDOSCOPIC MUCOSAL RESECTION OF


LARGE COLORECTAL LESIONS IN A SWEDISH CENTRE
N. Uedo1, A. Nemeth1, E. Toth1, G. Wurm Johansson1, H. Throlacius2,*
1
Department of Gastroenterology, Skane University Hospital, 2Department of
Surgery, Skane University Hospital, Lund University, Malmo, Sweden
Contact E-mail Address: henrik.thorlacius@med.lu.se
INTRODUCTION: Underwater endoscopic mucosal resection (UEMR) without
submucosal injection has recently been reported to be a useful to remove large
colorectal polyps in one single institution (1). The aim of this study was to
examine if UEMR is a safe and effective procedure for removing large colorectal
lesions in our institution.
AIMS & METHODS: Two experienced interventional endoscopists performed
all UEMR cases after observing UEMR procedures. UEMR was performed by
use of a colonoscope with hood and the polyp was fully immersed in water during
the entire procedure. All polyps were removed by en bloc or piecemeal resection
and without submucosal injection. The size of the snare (15 or 33 mm) depended
on lesion size. Patient data were collected prospectively.
RESULTS: A total of 13 consecutive patients (8 men, mean age 74 years, range
52-84) referred for polyp removal of colorectal lesions underwent UEMR.
Totally 16 lesions with a mean size of 17 mm (range 7-30) were removed by
UEMR. Lesions were located in the cecum (n 8), ascending colon (n 2),
transverse colon (n 4) and rectum (n 2). 56% of the polyps were removed
en bloc and the rest by piecemeal technique. All lesions were radically removed as
judged endoscopically. Minor bleeding events occurred during three procedures
which were easily managed with coagulation forceps and clips. No complications,
such as perforation or delayed bleeding, occurred.
CONCLUSION: UEMR seems to be an effective and safe method for removing
colorectal polyps and should be incorporated into the therapeutic arsenal of
institutions managing large colorectal lesions.
REFERENCES
1. Binmoeller KF, Weilert F, Shah J, et al. "Underwater" EMR without submucosal injection for large sessile colorectal polyps (with video). Gastrointest
Endosc 2012; 75: 1086-1091.
Disclosure of Interest: None declared
P0182 A PREDICTOR OF THE DIFFICULTY OF COLORECTAL ESD
FROM THE STANDPOINT OF DISSECTION SPEED
H. Chiba1,*, D. Kurihara1, T. Suto1, K. Ashikari1, N. Kawano1, S. Seki1,
S. Tsuruta1, A. Takahashi1, T. Ida1, T. Morohashi1, T. Goto1
1
gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
Contact E-mail Address: h.chiba04@gmail.com
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been applied
to the treatment of large colorectal tumors in Japan. However, the rate of complications is still higher than conventional endoscopic resection. For a management of complications, it is so important that we try to predict the difficulty of
ESD in advance. Dissection speed during ESD will be related to the stability of
the intraoperative visual field or ESD procedure itself.
AIMS & METHODS: To evaluate the difficulty of ESD from the dissection
speed, we retrospective analyzed 94 patients who underwent colorectal ESD in
Omori Red Cross Hospital from 2012 April to 2014 March. Because the mean
dissection speed of total cases was 29.415.5(mm2/min), we divided the patients
into two groups: a low speed group (514 mm2/min) (group A) and a control
group (=15 mm2/min) (group B). The two groups were compared with respect to
their clinical background and tumor characteristics predicted as a difficult case.
In this study, for keeping uniform the quality of ESD, ESD procedure with a
needle type device was done by one experienced ESD physician who under took
more than 150 colorectal ESD before this study. In addition, the degree of submucosal fibrosis was classified into three types (F02) (1) (F0: no fibrosis, F1:
mild fibrosis, F2: whitish submucosa or severe fibrosis). Independent and significant predictors were determined by multivariate analysis.
RESULTS: 94 lesions (male/female: 51/43) underwent ESD procedures; 14 in
group A and 80 in group B. In a low speed group (group A), tumor location was
C1/A2/T3/D3/S4/R1, and the mean tumor size was 25.39.8mm (15-50), and 5
cases had a fibrosis (F1; 2 cases and F2; 3 cases), and the rate of en bloc and
curative resection was 100% and 13/14 (92.9%), and the mean operation time
was 73.3min. The mean age, sex, the number of having antithrombotic agents
was similar between two groups. The statistical analysis showed that severe
fibrosis (F2) was predictor of a low speed (OR 36.0; 95%CI 2.46-527.1;
p 0.009), but tumor size (=30mm), depressed tumor (IIc or LST-NG-PD),
total fibrosis, location of tumors in the rectum or cecum, and the straddle of
the fold did not have any significant differences. With respect to the postoperative course, there was also no differences in WBC, CRP, a number of having a
high fever (=38 C), using antibiotic agents, taking a painkiller, and a hospital
period. Otherwise, there was one complication case in all lesions. This case

P0183 PREDICTIVE FACTORS OF AN INCOMPLETE EN BLOC


RESECTION IN ENDOSCOPIC MUCOSAL RESECTION FOR
COLORECTAL TUMORS
H. Minamino1,*, M. Shiba1, K. Hayashi2, M. Ominami1, S. Fukunaga1,
Y. Nagami1, T. Hayakawa2, K. Aomatsu2, S. Sugimori1, H. Machida3,
T. Watanabe1, K. Tominaga1, Y. Fujiwara1, T. Arakawa1
1
Osaka City University Graduate School of Medicine, Osaka, 2Izumiotsu
Municipal Hospital, Izumiotsu, 3Machida gastrointestinal hospital, Osaka, Japan
Contact E-mail Address: piacere_minaminohiroaki@yahoo.co.jp
INTRODUCTION: En bloc resection by the procedure of endoscopic mucosal
resection (EMR) for colorectal tumors over 2 cm in diameter is difficult according to previous reports. However, predictive factors of difficulty of en bloc resection are not indicated in colorectal EMR.
AIMS & METHODS: The aim of this study is to clarify predictive factors of an
incomplete en bloc resection in EMR for colorectal tumors. From January 2012
to December 2013, a total of 277 patients with 370 colorectal tumors larger than
10 mm in diameter except pedunculated type tumors underwent EMR at
Izumiotsu Municipal Hospital (Osaka, Japan). Age (mean): 70 years, sex: male
169 / female 108, location: right hemicolon 183 / left hemicolon (including the
rectum) 187, macroscopic type: protruding type including sessile (Is) 43 / semipedunculated (Isp) 151 / flat-elevated type (IIa) 156 / IIaIs 20. DRAGONEA
bipolar snare (ZEON Medical Co., Tokyo, Japan) was used and selected width of
snare 13 mm or 26 mm in diameter in reference to the lesion size in EMR
procedures. Standard saline solution was injected into the submucosa in all
cases. We retrospectively analyzed predictive factors of an incomplete en bloc
resection on age, sex, tumor size, location, macroscopic type, and histological
findings by multivariate analysis.
RESULTS: With crude-OR, location was 1.98 (95% Confidence Interval (CI),
1.12 to 3.48) and tumor size 1.11 (95% CI, 1.05 to 1.18) were associated with the
incomplete en bloc resection. Regarding the location, the multivariate-adjusted
OR of the incomplete en bloc resection for the right hemicolon was 1.9 (95% CI,
1.06 to 3.38) compared with the left hemicolon. Regarding the tumor size, the
multivariate-adjusted OR of the incomplete en bloc resection for the highest
tertile was 2.97 (95% CI, 1.53 to 5.75) compared with the lowest tertile (p for
trend 5 0.01, cutoff value: 16 mm).
CONCLUSION: Size (cutoff: 16 mm in diameter) and location (right hemicolon)
of the colorectal tumors are indicated to be predictive factors for an incomplete
en bloc resection by EMR. Especially, when lesion over 16 mm in diameter or
located in right hemicolon is treated by EMR, the consideration of EMR-precutting technique or endoscopic submucosal dissection may be needed.
REFERENCES
Disclosure of Interest: None declared
P0184 SUBMUCOSAL DISSECTION IN THE COLORECTUM: LOW
RATE OF PIECEMEAL RESECTION AND RECURRENCE
H. Kashida1,*, T. Adachi1, T. Sakurai1, Y. Asakuma1, M. Takayama1, H. Mine1,
S. Matsui1, M. Kudo1
1
Department of Gastroenterology and Hepatology, Kinki University Faculty Of
Medicine, Osaka-sayama, Japan
Contact E-mail Address: kashi-md@xf6.so-net.ne.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) for colorectal neoplasms was developed in Japan but is now spreading rapidly. The technique was
started in our institute in the year 2010.
AIMS & METHODS: The aim of this study is to evaluate the results of colorectal ESD procedures for the first 4 years. The subjects are 205 consecutive
lesions in 180 patients which were treated with ESD technique. The indications
for ESD in our hospital are; 1. Neoplasms larger than 20mm but confined to the
mucosa or invading minimally to the submucosal layer, 2. Those smaller than
20mm but unable to be lifted by injection due to fibrosis. The instruments used
are PCF-Q260AZI or JI (Olympus), Short ST Hood and Flush Knife (Fujifilm)
and VIO 300D (Erbe).
RESULTS: Male: female ratio was 86:94 and the average age was 68.0 (39-90)
years old. The location was the cecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum in 36, 51, 48, 6, 24 and 40 of the lesions,
respectively. The final pathological diagnosis was sessile serrated adenoma/polyp
(SSA/P) in 18, adenoma in 63, mucosal cancer in 101, minimally invasive cancer
(SM1) in 15 and deeply invasive cancer (SM2) in 7, and neuroendocrine tumor in
1. The gross appearance of the adenomas and cancers was flat or laterally spreading tumor (LST) in 174, sessile or 0-Is in 9, and depressed or 0-IIc in 3. The LSTs
were subdivided into 53 lesions of homogeneous granular-type (LST-GH), 41
mixed-nodular type (LST-GM), 41 flat-elevated type (LST-NGF), and 39
pseudo-depressed type (LST-NGPD). The average size in LST-GH, LST-GM,
LST-NGF, LST-NGPD, 0-Is, 0-IIc, and SSA/P was 41.1mm, 39.7mm, 30.7mm

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United European Gastroenterology Journal 2(1S)


and 25.7mm, 36.4mm, 10.3mm, and 23.9mm respectively. Invasive rates in these
subtypes in order was 1.9%, 14.6%, 9.8%, 20.5%, 22.2%, 33.3%, and 0%. Postprocedure bleeding occurred in 2 cases (0.98%). Minor intra-procedure perforation was encountered in 6 cases (2.93%), but no emergency operation was
required. Delayed pneumoperitoneum was witnessed in one case, but it was
attributable to the ileus caused by anal stricture. If we divide the cases into
1st, 2nd, 3rd, and 4th fifty lesions, the en bloc resection rate was 78%, 88%,
98% and 98%. Local recurrence was witnessed in 3 cases (1.46%) in all of which
the ESD procedure had resulted in piecemeal resection due to fibrosis, but the
recurrent lesions were all small and removed endoscopically.
CONCLUSION: Submucosal dissection in the colorectum was successful with
low rate of piecemeal resection and recurrence, but without serious
complications.
Disclosure of Interest: None declared

was 0.79-0.96, BBPS, 0.73-0.89. Intra-observer kappa for AC was 0.51-0.79 and
for HCS, 0.36-0.92.
CONCLUSION: Inter-observer agreement values were high in OS and BBPS.
This validation analysis showed that OS and BBPS are reliable, coherent scales so
that they can provide better standardization to evaluate bowel preparation in
both study and clinical practice.
REFERENCES
Thomas-Gibson S, Rogers P, Cooper S, et al. Judgement of the quality of bowel
preparation at screening flexible sigmoidoscopy is associated with variability in
adenoma detection rates. Endoscopy 2006; 38: 456-460.
Brotz C, Nandi N, Conn M, et al. A validation study of 3 grading systems to
evaluate small-bowel cleansing for wireless capsule endoscopy: a quantitative
index, a qualitative evaluation, and an overall adequacy assessment.
Gastrointest Endosc 2009; 69: 262-270.
Disclosure of Interest: None declared

P0185 COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION


(ESD) PERFORMED BY EXPERTS IN COLONOSCOPY WITH
LITTLE EXPERIENCE OF GASTRIC ESD

P0187 MANAGEMENT OF LARGE COLONIC POLYPS IN A BOWEL


CANCER SCREENING PROGRAMME

H. Shiga1,*, M. Kuroha1, K. Endo1, J. Kusaka1, T. Tadano1, K. Matsushita1,


Y. Kakuta1, Y. Kinouchi1, T. Shimosegawa1
1
TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, Sendai,
Japan

H.Y. Lee1,*, W. Gashau1, R. Willert1


Department of Endoscopy, Central Manchester University Hospitals NHS
Foundation Trust, Manchester, United Kingdom
Contact E-mail Address: huiyann.lee@cmft.nhs.uk

INTRODUCTION: The efficacy of colorectal endoscopic submucosal dissection


(ESD) has been reported mainly from Japanese referral centers. However, it is
technically difficult and is associated with a higher risk of adverse events than
endoscopic mucosal resection (EMR), especially for novices in colorectal ESD
with little experience in gastric ESD.
AIMS & METHODS: We aimed to evaluate the results of colorectal ESD during
the clinical learning curve. Colorectal ESD was performed by 2 endoscopists who
had expertise in colonoscopy and colonic EMR but had experience of fewer than
5 cases of gastric ESD. A total of 120 cases consisting of the first 60 cases of each
endoscopist were retrospectively investigated. The main outcome measurements
were procedural time, en bloc resection rate with tumor-free margins (R0 resection rate) and adverse events rate. From among the clinical characteristics
obtained before the ESD procedure, factors that affected the main outcome
measurements were identified.
RESULTS: (Clinical characteristics) Tumors were located at the rectum, left
colon, right colon and junction (dentate line, SD junction, hepatic flexure, splenic
flexure, ileocecal valve) in 22, 19, 51 and 28 cases, respectively. With regard to the
macroscopic type, 44, 23, 5 and 8 cases were granular-type laterally spreading
tumor (LST), nongranular-type LST, depressed and protruding type, respectively. Of the 120 cases, 20 cases had factors which reflected fibrosis of the
submucosal layer (sporadic localized lesions with ulcerative colitis, local residual
tumors after EMR, etc.). The mean tumor diameter was 38.518.3 mm. The
histological analysis showed 59 adenocarcinomas and 61 adenomas.
(Outcomes) The mean procedural time was 101.765.9 min. A total of 113
cases (94.2%) were resected en bloc, and the R0 resection rate was 80.0% (96/
120). Perforation and postoperative hemorrhage occurred in 8 (6.7%) and 2
(1.7%) cases, respectively. Multivariate analyses revealed that lesions in junction
and lesions with factors reflecting fibrosis were significantly associated with
longer procedural time (90 min) and a lower en bloc resection rate. Larger
lesions (40 mm) and lesions resected in the first half (up to 60 cases) were
also associated with longer procedural time.
CONCLUSION: Colorectal ESD is feasible and safe when performed by experts
in colonoscopy with little experience of gastric ESD. For novices in colorectal
ESD, beginning with lesions in junction and lesions with factors reflecting fibrosis may not be advisable.
Disclosure of Interest: None declared

INTRODUCTION: Bowel cancer is the third most common cancer in the United
Kingdom forming up to 13.6% of all newly diagnosed cancers(1). Bowel cancer
screening colonoscopy allows early polyp detection at a curable stage. Complete
resection and follow-up of large polyps is crucial to prevent malignant
progression.
AIMS & METHODS: The aim of this study was to review the management of
polyps with diameters  2 cm, particularly of sessile polyps, to assess the enbloc
resection rates, completeness of resection using endoscopic mucosal resection
(EMR) vs surgery and the incidence of malignant polyps.
Patients were identified retrospectively from a regional bowel screening programme database. Details of index colonoscopy including polyp characteristics,
method of resection and complications were recorded. Histology results were
reviewed for all polyps. Outcomes from follow-up endoscopic surveillance were
analysed.
RESULTS: One hundred and fifty-eight patients (102 males, 56 females, mean
age 66.2 years) with polyps  2 cm were identified from 2182 screening colonoscopies from January 2010 to August 2013. Caecal intubation rate was 96.8% in
this group.
Largest polyp size for each patient ranged from 20 to 60 mm (mean 26.6 mm).
The incidence of adenocarcinoma was 11.9% (n 19), all located within the left
colon, with 12 requiring surgical resection.
One hundred thirty nine patients (n 139) had 155 non-malignant large polyps,
mostly tubulovillous or villous histology (n 110, 79%).
Thirty-six patients had 37 sessile polyps which underwent primary resection by
EMR (n 26) or surgery (n 11).
Polyp diameter was larger in the surgery group with mean polyp diameter of 40.4
mm vs 28.0 mm (p50.05).
EMR enbloc resection rate was 11.5% (n 3 out of 26). Completeness of excision
was 38.4% (n 10) at 3 months and 92.3% (n 24) at 1 year. EMR complications included 1 perforation, 1 post polypectomy syndrome and 1 bleed.
Surgical resection included: anterior resection in 2, TEMS excision in 7 and right
hemicolectomy in 3.
CONCLUSION: Sessile polyps  2 cm are relatively uncommon in an asymptomatic bowel cancer screening programme (37 in 2182 colonoscopies). They can
be successfully resected by EMR without recurrence in 92.3% at 1 year providing
a 3 month site check is performed in all piecemeal polypectomies.
REFERENCES
(1) Cancer for National Statistics. Office for national statistics, http://www.ons.gov.uk/ons/dcp171778_263537.pdf (2010).of InterestDisclosure: None declared

P0186 A VALIDATION STUDY OF 4 TYPE BOWEL CLEANSING SCALE:


ARONCHICK, BOSTON BOWEL PREPARATION, OTTAWA,
HAREFIELD SCALE
S.H. Kim1,1, I.K. Yoo1, J.M. Lee1, S.J. Nam1, H.S. Choi1, E.S. Kim1, B. Keum1,
Y.T. Jeen1, H.S. Lee1,*, H.J. Chun1, C.D. Kim1
1
Department of Internal Medicine, Division of Gastroenterology and Hepatology,
Korea University Anam Hospital, Seoul, Korea, Republic Of
Contact E-mail Address: kimseunghan09@gmail.com
INTRODUCTION: Total colonoscopy is a potent tool for assessing the large
bowel. There are various bowel preparation scale, but few bowel preparation
scale have been validated. Diversity in bowel preperation scales can cause a lot
of confusion on decisions in the clinical environment and much confounding of
results within clinical studies. However there have been no clinical trials that
compared 4 types of bowel preparation scales. The aim of this study is to
assess the compatibility and reliability of 4 different types of bowel preparation
scales.
AIMS & METHODS: This study compared 4 types of bowel preparation scales:
Aronchick scale (AC), Boston bowel preparation scale (BBPS), Ottawa scale
(OS), Harefield cleansing scale (HCS). 5 trainees read 20 total colonoscopy studies twice, with an interval of 1 month. We used Intraclass correlation coefficient
(ICC) to evaluate Intra-observer (test-retest) consistency and inter-observer reliability of the BBPS and the OS. The unweighted kappa statistic was used to assess
the reliability of the AC and the HCS.
RESULTS: Total 400 ratings were completed in this study. Inter-observer and
intra-observer reliability were assessed by ICC and kappa statistic. ICC for OS
was 0.73 (95% CI, 0.52-0.87, p 5 0.0001), BBPS 0.76 (95% CI, 0.59-0.88, p 5
0.0001), inter-observer kappa for AC was 0.29 (95% CI, 0.19-0.42, p 5 0.0001),
HCS 0.27 (95% CI, 0.15-0.41, p 5 0.0001). Intra-observer scores for OS, ICC

P0188 ARE THERE ANY PARAMETERS TO PREDICT BILE DUCT


STONES IN BILIARY PANCREATITIS BEFORE ERCP
A. Sayilir1,*, B. Odemis1, E. Parlak1, S. Disibeyaz1, Y. Beyazit1, N. Sasmaz1
1
Gastroenterology, TURKIYE YUKSEK IHTISAS TEACHING AND
RESEARCH HOSPI, ANKARA, Turkey
Contact E-mail Address: drabdurrahim@gmail.com
INTRODUCTION: The role of endoscopic retrograde cholangiopancreaticography (ERCP) for the management of acute biliary pancreatitis (ABP) remains a
controversial topic. Pre-ERCP detection of biliary stones in patients with ABP
may strengthen the indication for a subsequent ERCP.
AIMS & METHODS: The aim of this study was to determine the value of
several clinical and laboratory parameters as non-invasive pre-ERCP indicators
_
of bile duct stones. Patients presenting to Turkiye Yuksek Ihtisas
Teaching and
Research Hospital (TYIH) between 1 January 2010 and 31 August 2011 with
ABP, who underwent ERCP within 72 hours of the onset of symptoms were
screened, and eligible patients were enrolled in the study. Receiver operating
characteristic (ROC) curve analysis was used to determine the optimal cut-off
value of several parameters, such as AST, ALT, GGT, ALP, bilirubin, common
bile duct (CBD) width on USG and duration of syptoms, with the highest sensitivity and specificity for predicting the presence of CBD stones.
RESULTS: A total of 59 patients [20 (33.89%) males and 39 (66.1%) females]
were included in the final analysis. Areas under the curve for CBD width, timing
of ERCP, AST, ALT, GGT, ALP and bilirubin were 0.753, 0.630, 0.548, 0.370,
0.577, 0.568 and 0.495, respectively. As a predictor of the presence of a biliary
stone(s), CBD width was found to have the highest sensitivity, specificity,

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United European Gastroenterology Journal 2(1S)

negative predictive value (NPV), positive predictive value (PPV) and general
accuracy. With a cut-off value of 8.55 mm for CBD width, sensitivity and specificity were 75% with a NPV of 47.4%, PPV of 90.9% and general accuracy of
75. A summary of ROC analyses for the other parameters is provided in table 1.
Table 1. ROC analysis for the value of several labortory and clinical parameters
as pre-ERCP indicators of the presence of bile duct stones.
Sensitivity Specificity NPV PPV
Cut-off AUC (%)
(%)
(%) (%) Accuracy
CBD width (mm)
Duration (hours)
AST (u/L)
ALT (u/L)
GGT (u/L)
ALP (u/L)
Bilirubin (mg/dl)

8.55
25.5
224.5
156.2
263
153
1.54

0.753
0.630
0.548
0.370
0.577
0.568
0.495

75
60.9
56.5
43.2
69.8
56.8
54.8

75
61.5
53.8
40.0
70
60
50

47.4
30.8
25.9
13.8
35
24
20.8

90.9
84.8
81.3
76
90.9
86.2
82.1

75
61
55.9
42.6
69.8
57.4
53.8

CBD, common bile duct; AST, Aspartat Aminotransferase; ALT, Alanin


Aminotransferase; GGT, Gama-Glutamyl Transferase; ALP, Alkaline phosphatase; AUC, area under the curve; NPV, negative predictive value; PPV: positive
predictive value
CONCLUSION: Determination of CBD width on ultrasonography and serum
GGT levels are important parameters that may help predict the presence of
biliary stones prior to endoscopic intervention.
Disclosure of Interest: None declared
P0189 PROCEDURAL DESCRIPTION AND CLINICAL OUTCOMES OF
A NOVEL COMBINED RETROGRADE-ANTEGRADE ENDOSCOPIC
APPROACH USING ERCP AND EUS FOR THE MANAGEMENT OF
POSTOPERATIVE BILE-DUCT TRANSECTIONS
A.L. Vargas1,*, N. Aleman1, I. Penas Herrero1, C. De la Serna-Higuera1,
C. Almohalla1, F. Garc a-Pajares1, G. Sanchez-Antolin1, M. Perez-Miranda1
1
Gastroenterology & Hepatology, Hospital Universitario Ro Hortega, Valladolid,
Spain
Contact E-mail Address: mpmiranda5@hotmail.com
INTRODUCTION: Postoperative Bile-duct Transections (POBT) are not amenable to endoscopic therapy. Preliminary data from combined percutaneous-endoscopic approaches are encouraging. Isolated reports of successful retrograde
canalization are intriguing. We hypothesized that aggressive retrograde
(ERCP) and/or antegrade (EUS) attempts at recanalization may salvage
POBTs for endotherapy, and subsequent serial stenting would induce remodeling
and durable resolution as seen in partial strictures.
AIMS & METHODS: To assess the feasibility, safety and efficacy of an endoscopic treatment algorithm of POBTs and to characterize the heterogeneous
techniques used to attempt recanalization.
Since September 2010, 248 consecutive ERCPs were performed at a tertiary Unit
for postoperative complications (strictures/leaks) in 150 patients (69 Liver
Transplant, 81 Other). POBTs were identified in 17 patients (9 Female;
age 59.6 [43-79] years) following liver transplant (LT) /cholecystectomy
(CCx) /Other in 7/7/3. Clinical records were retrospectively reviewed for procedural data (success, antegrade Vs retrograde, technique) and clinical outcome
(immediate POBT remodeling and mid-term clinical resolution).
RESULTS: Recanalization was achieved in 12/17 POBT (70%), by means of
ERCP alone in 5 (4 LT, 1CCx), of ERCP combined with EUS-guided antegrade
approach in 6 (2 LT, 3CCx, 1 Other), and EUS alone in 1. Lack of upstream
biliary dilation precluded EUS attempts in 4, and recanalization failed in 1
despite EUS-hepaticogastrostomy (EUS-HG). 5 initial failures underwent surgical repair with/without interval external PTBD. 10/12 recanalizations required
forced antegrade/retrograde techniques: using the hard end of a stiff guidewire,
needle-knife, puncture with intraductal hollow needles, transhepatic peritoneoscopy or magnetic compression anastomosis. A mean (range) of 1.5 (1-5) ERCPs
were needed to achieve recanalization. Coincidental bilomas were drained in 2
POBTS (one transpapillary by ERCP and one transmural by EUS each). 11
Patients have completed 12 treatment courses of serial stenting (2 plastic alone
& 10 covered metal with/without plastic) after 323(180-503) days of stents in
place. After a mean follow-up of 353(30-900) days, there were 3 recurrences (1
surgery, 1 currently undergoing stenting, 1 successfully remodeled endoscopically). Post-procedural or stent related mild cholangitis ensued in 4, and moderate post-sphincterotomy bleeding in 1.
CONCLUSION: 70% of POBTs can successfully be recanalized endoscopically
by means of forced mechanical (guidewires, needles), thermal or magnetic techniques. Antegrade EUS approaches allow salvage of 60% of ERCP failures. Midterm treatment ouctomes using this algorithm for POBTs appear comparable to
those seen with partial postoperative strictures.
Disclosure of Interest: None declared

P0190 VALIDATION OF A RISK SCORE FOR PREDICTING POST-ERCP


PANCREATITIS BASED ON THE EUROPEAN GUIDELINE
A. Mariani1,*, M. Di Leo1, A. Ambrosi2, M.L. Grazie1, A. Giussani1,
P.A. Testoni1
1
Division of Gastroenterology and Gastrointestinal Endoscopy Vita-Salute San
Raffaele University Scientific Institute San Raffaele, Milan, Italy, 2Vita-Salute
San Raffaele University Scientific Institute San Raffaele, Milan, Italy, Milan,
Italy
Contact E-mail Address: mariani.alberto@hsr.it
INTRODUCTION: Post-ERCP pancreatitis (PEP) is an important complication
in biliopancreatic endoscopy, associated with morbidity and mortality. While
clinical and technical risk factors for PEP have been elucidated, the identification
of a simple and valid risk score to predict PEP remains a challenge.
AIMS & METHODS: To develop a model to predict the risk of PEP in patients
undergoing endoscopic retrograde cholangiopancreatography (ERCP).
Methods: A risk score was created based on the prognostic factors for PEP
identified on the basis of the ESGE Guideline (1) and validated on 1823
ERCPs from an independent, prospectively assembled database (validation
cohort). The predictive performance of the models was tested by ROC analysis
to identify patients at low and high risk of PEP.
RESULTS: A score proportional to its regression coefficient was assigned to
each independent prognostic factor: suspected sphincter of Oddi dysfunction
(SOD) (4.1 points), female sex (2.2 points), previous pancreatitis (2.5 points),
young age (2 points), no chronic pancreatitis (1.9 points), normal serum bilirubin
(1.9 points), precut sphincterotomy (2.7 points), pancreatic injection (2.2 points),
large number of cannulation attempts (2.9 points), pancreatic sphincterotomy
(3.1 points), biliary balloon sphincter dilation (4.5 points), failure to clear bile
duct stones (3.4 points). The AUC of the ROC curve showed a predictive score
performance of 0.9268 (95% C. I. 0.90-0.95 p50.0001). We identified 9.5 as the
cut-off between low- and high-risk classes, with 88.5% specificity, 81.6% sensitivity. Considering only severe PEP (n 12), there was a significant difference
between the two risk classes (p 0.001).
CONCLUSION: We developed and validated a simple risk score to predict PEP.
It could be useful to clinicians for predicting the individual risk of PEP and
directing prophylactic measures, to researchers for designing and interpreting
clinical trials, and to policy-makers for saving healthcare resources.
REFERENCES
1. Dumonceau JM, Andriulli A, Deviere J, et al. European Society of
Gastrointestinal Endoscopy (ESGE) Guideline: prophylaxis of post-ERCP pancreatitis. Endoscopy 2010; 42: 503-515.
Disclosure of Interest: None declared
P0191 MONITORING
RADIATION
EXPOSURE
IN
PROFESSIONALS DURING ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY

HEALTH

A.R. Alves1,*, D. Gomes1, P. Mendes2, T. Laranjeiro2, G. Paulo2, J. Santos2,


N. Almeida1, S. Mendes1, R. Mesquita1, E. Camacho1, F. Portela1, C. Sofia1
1
Gastroenterology Department, Coimbra Hospital and University Centre,
2
Coimbra College of Health Technology, Polytechnic Institute of Coimbra,
Coimbra, Portugal
Contact E-mail Address: alvess.anarita@gmail.com
INTRODUCTION: Use of radiation in endoscopic procedures has been increasing in Gastroenterology, particularly during endoscopic retrograde cholangiopancreatography (ERCP). Safety radiation limits have been defined for
persons with occupational exposure to ionizing radiation. Monitoring the efficacy of protection measures and quality of x-ray systems are recommended.
AIMS & METHODS: The objectives of this study were to measure occupational
radiation doses during ERCP in a Gastroenterology department and evaluate the
impact of a real time individual dosimeter system in staff behavior. A prospective
study was performed, during three phases, in which radiation doses were measured with individual dosimeters in health professionals: gastroenterologist,
endoscopy and circulating nurses, radiology technician and anesthesiologist.
Phase 1 25 procedures, dosimeter placed under the protection apron, at thoracic level. Phase 2 18 procedures, dosimeter placed outside the protection
apron, at cervical level, simulating absence of radiation protection. Phase 3
12 procedures, dosimeter placed in second phase position, but with real time
exposure levels displayed in a monitor and staff being able to adapt their
position.
RESULTS: In phase 2, the following doses were registered: gastroenterologist
6.785.99 Sv, endoscopy nurse 7.6312.88Sv, radiology technician
6.866.27Sv, anesthesiologist 6.5811.75Sv and circulating nurse
4.565.45Sv. In phase 1, protection equipment allowed a significant reduction
in exposure doses: gastroenterologist 3.374.00 Sv, endoscopy nurse
0.090.16Sv,
radiology
technician
0.701.55Sv,
anesthesiologist
0.430.95Sv and circulating nurse 1.153.03Sv (p50.05). In phase 3, with
the change of health professionals position, according to real time values, there
was a reduction of 44-71% in radiation levels, except for the gastroenterologist
whose change of position was limited by his role in ERCP.
CONCLUSION: The present study showed occupational exposure doses within
the recommendations, proving the efficacy of radiation protective equipments.
Real time knowledge of radiation doses may have a positive impact in professionals behavior.
Disclosure of Interest: None declared

A183

United European Gastroenterology Journal 2(1S)


P0192 PALLIATIVE BILIARY DRAINAGE FOR KLATSKIN TUMORS:
ENDOSCOPIC OR PERCUTANEOUS?
A.T. Oliveira1,1,*, S. Campos1, S. Giestas1, N. Almeida1, S. Mendes1,
E. Camacho1, R. Mesquita1, D. Gomes1, A.G. Agostinho2, V. Carvalheiro2,
C. Sofia1
1
Gastroenterology, 2Radiology, Centro Hospitalar e Universitario de Coimbra,
Coimbra, Portugal
INTRODUCTION: At the time of the diagnosis only 20% of patients with
Klatskin Tumors have resectability criteria. Thus, the majority will require palliative procedures for maintenance of biliary drainage.
AIMS & METHODS: The aim of this study is to compare two palliative nonsurgical methods (endoscopic and percutaneous approach) in terms of therapeutic efficacy and complications.
We performed a retrospective study of patients newly diagnosed with Klatskin
Tumors, in the period betwen 2010-2012, undergoing endoscopic biliary drainage
(EBD) and/or percutaneous transhepatic biliary drainage (PTHBD). We analyzed the patient characteristics, technical success (insertion of drain/stent
through the stenosis), therapeutic success (total bilirubin  4mg/dL after the
procedure), duration of patency, complications and need for reintervention.
RESULTS: We included 70 patients with a mean age of 7111 years and a male
predominance (67.1%), of which 32 were submitted exclusively to PTHBD, 30 to
EBD and 8 at both. These eight were initially submitted to EBD, but by impossibility of access to the biliary tract they needed PTHBD, so we considerer 40
patients in the PTHBD group and 30 in the EBD group. The two groups differed
regarding the mean age (PTHBD 68 years; EBD 74 years; p 0.006). No difference was found in the Bismuth Classification (Type III/IV: PTHBD 82.5%, EBD
70.0%) and technical success rate (PTHBD 75%; EBD 79%). The rate of therapeutic success was PTHBD 57.5%; ERCP 79.3% (p 0.07). The terapheutic
failure was more common in Bismuth III/IV types, in both groups (PTHBD
48.5%; EBD 30.0%). The complication rate was in the PTHBD group 47.5%
(cholangitis in eleven patients and hemorrhage in 8 patients) and in the EBD
group 23.3% (cholangitis in four, pancreatitis in two and perfuration in one)
p 0.038. The patency time was similar: PTHBD 136 days; EBD 133 days. The
reintervention rate was 32.4% in the PTHBD group and 48.3% in the EBD
group (p 0.191).
CONCLUSION: Palliative biliary drainage is possible by endoscopic or percutaneous route, although the success rate is limited, especially in patients with
Bismuth types III/IV. Endoscopic biliary drainage seems to show a trend
toward greater treatment success, and it is associated with fewer complications.
Disclosure of Interest: None declared
P0193 ERCP CANNULATION; EVALUATION OF A WIRE-LED
TECHNIQUE FOR BILIARY ACCESS IN A TRAINING CENTRE
C. Shekhar1,*, S. Shetty1, N.C. Fisher1
1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom
Contact E-mail Address: drcshekhar@gmail.com
INTRODUCTION: A range of techniques have been described to achieve successful cannulation at ERCP, and when training in ERCP it is often difficult to
select the optimum approach 1. There are potential advantages to a wire-led
approach and we have evaluated this in our unit in a training setting.
AIMS & METHODS: To evaluate cannulation success rates for trainers and
trainees using a wire-led technique as the default approach.
A prospective evaluation was done with 2 experienced trainers and 2 trainees
(previous experience of 50-100 ERCPs each). The sphincterotome was pre-loaded
with a hydrophilic wire (in limited cases loop tip wire was used) and cannulation
started with the wire extending 3-5mm out of cannula. Attempts were then made
to advance the wire deep into the bile duct before injecting any contrast or
pushing the cannula through the ampulla. Trainees were allowed 6 minutes for
cannulation attempts. If the wire-led approach failed then other techniques were
used. Wire-led cannulation was considered successful only if no other techniques
were required. Only cases with a virgin ampulla were including in this study.
RESULTS: 100 cases were included over a 5 month period. Trainees were present
in 62 (62%) cases. Overall biliary cannulation success was 93 (93%). Success rate
was 54/62 (87%) if a trainee was present and 37/38 (97%), if no trainee was
present. Independent success for trainees was 34/62 (55%), mostly using the wireled technique 29/34 (85%). In cases where a trainer took over from a trainee, the
wire-led approach was still successful in 14/28 (50%). Overall success with the
wire-led approach alone was 31 (69%); other approaches used in remaining cases
included pre-cut sphincterotomy, locked PD wire, and PD stent. A peri-ampullary diverticulum was the most common cause for failure of wire-led technique;
other common causes included stricture, floppy ampulla, or an impacted stone.
Median cannulation time was 6.5 minutes (IQR 4-10min) overall and 5 minutes
(IQR 3-10min) for consultant-only cases. Immediate complications included false
passage of wire (1 case, no further clinical events) and late complications: post
ERCP pancreatitis (1 case, hospital stay 3 days, no further clinical events).
CONCLUSION: Wire-led biliary cannulation, with selective usage of additional
techniques, may allow a cannulation rate of 490% in cases with a virgin
ampulla. The technique appears to be a useful training tool and has a low
complication rate.
REFERENCES
1.Gastrointest Endosc Clin N Am 2012; 22: 417-434.
Disclosure of Interest: None declared

P0194 DOUBLE-BALLOON OVERTUBE-ASSISTED ENTEROSCOPY


ERCP IN PATIENTS WITH BILLROTH II GASTRECTOMY: A
LARGE SERIES REPORT
C.-L. Cheng1,*, C.-H. Lin1, J.-H. Tang1, M.-C. Yu2, Y.-N. Tsui1, N.-J. Liu1
Gastroenterology, 2General Surgery, Chang Gung Memorial Hospital, Taoyuan
County, Taiwan, Province of China
Contact E-mail Address: chiliang.cheng@gmail.com
1

INTRODUCTION: Data on double-balloon overtube-assisted enteroscopy to


facilitate ERCP (DBE-ERCP) in patients with Billroth II gastrectomy is limited.
AIMS & METHODS: The primary aim was to evaluate DBE-ERCP success in
patients with Billroth II gastrectomy and suspected pancreaticobiliary disease.
The seconday aim was to examine the safety and efficacy of DBE-ERCP.
Patients with Billroth II gastrectomy in whom standard ERCP techniques had
failed underwent ERCP by using DBE with initial therapeutic intent were identified retrospectively. DBE success was defined as visualizing the papilla, while
ERCP success as completing the intended pancreaticobiliary intervention.
Clinical success was delineated as a greater than 50% reduction in abdominal
pain or level of hepatic enzyme elevations or resolution of cholangitis or complete
extraction of bile duct stone.
RESULTS: From April 2006 through December 2011, 77 patients (59-male,
mean age 73.5 years, range 50-95 years) had 92 DBE-assisted ERCPs. Overall
DBE-ERCP success was 69 of 77 (90%). DBE success was 73 of 77 (95%), of
whom 69 of 73 (95%) achieved ERCP success. Reasons for DBE- ERCP failure
(n 8): tumor obstruction within afferent limb (n 2), peritoneal adhesion
(n 2), cannulation failure (n 3), and bowel perforation (n 1). Diagnosis in
patients with DBE-assisted ERCP success (n 69): choledocholithiasis (n 50),
biliary dilatation (n 9), malignant biliary stricture (n 9), normal study (n 1).
Selective interventions included biliary sphincteroplasty (dilation  cautery,
n 76), stone extraction (n 57), stenting (n 20), nasobiliary drainage
(n 6), and rendezvous (n 3). Complications occurred in 5 of 77 (6.5%). In
those patients who underwent therapeutic ERCP (n 68), 66 patients (97%)
achieved clinical success.
CONCLUSION: DBE permits diagnostic and therapeutic ERCP in patients with
Billroth II gastrectomy with a high success and acceptable complication rates.
DBE-assisted ERCP should be considered as an effective alternate when standard ERCP failed in such patients.
REFERENCES
1. Lin CH, Tang JH, Cheng CL, et al. Double balloon endoscopy increases the
ERCP success rate in patients with a history of Billroth II gastrecotmy. World J
Gastroenterol 2010; 16: 4594-4598.
2. Shah RJ, Smolkin M, Yen R, et al. A multicenter US experience of singleballoon, double-balloon, and rotational overtube-assisted enteroscopy ERCP in
patients with surgically altered pancreaticobiliary anatomy (with video).
Gastrointest Endosc 2013; 77: 593-600.
Disclosure of Interest: None declared
P0195 OUTCOMES
OF
THE
ENDOSCOPIC
DRAINAGE
PANCREATIC COLLECTIONS ACCORDING TO THE NEW
ATLANTA CLASSIFICATION

OF

D. Ruiz-Clavijo 1,*, B. Gonzalez de la Higuera1, C. Prieto1, E. Sainza1, M. Casi1,


F. Bolado1, J. Urman1, I. Fernandez Urien1, F.J. Jimenez1, J.J. Vila1
1
Complejo Hospitalario de Navarra, Pamplona, Spain
Contact E-mail Address: davidruizcla@gmail.com
INTRODUCTION: Endoscopic drainage is considered a minimally invasive
first-line treatment of pancreatic collections (PC). A revision of the Atlanta
classification has been recently published but outcomes of endoscopic therapy
according to this new classification are scarce.
AIMS & METHODS: Our objective was to evaluate the outcomes of the endoscopic drainage procedures of PC performed in our center during the last 5 years,
assessing results with regard to morphological characteristics of the PC, technique used, and type of stent placed. A retrospective review of all endoscopically
drained PC at our center from January 2009 to December 2013 was made.
Indications for endoscopic drainage were symptomatic or complicated PC. PC
were retrospectively classified according to the new Atlanta 2012 classification.
Variables analyzed: 1) general variables: sex, underlying pancreatic pathology,
PC type, 2) endoscopic technique: endoscopic intervention, type of stent, technical success (successful placement of draining stents), number of endoscopic interventions (including the session to retrieve the stents after PC resolution),
complications, and 3) other variables: clinical success (symptom resolution),
morphological success (resolution of the PC on computed tomography), and
need for subsequent surgery. All drainage procedures were performed under
endoscopic ultrasound guidance. Chi-squared and Fishers exact test were used
for analysis.
RESULTS: Endoscopic drainage was performed in 39 PC in 37 patients (33
men). 46.2% of PC developed in the setting of acute pancreatitis, 38.5% in
chronic pancreatitis, and 12.5% after pancreatic surgery. PC included 17 pseudocysts (2 infected) and 19 walled-off necrosis (15 infected). We were unable to
retrospectively classify 3 PC according to Atlanta 2012. The endoscopic
approach was transgastric in 61%, transpapillary in 28%, and mixed in 7.7%.
In 50% of transgrastric drainages a covered biliary metallic stent was deployed
while the others underwent pigtail stents placement. The treatment approach and
stent used were associated with the type of PC since walled-off necrotic PC were
preferentially drained via a transgastric approach (17 of 19) and with metallic
stents (13 of 19) (p50.05). Nasocystic lavage was performed in 38.5% of drainages (13 infected walled-off necrotic PC and 2 infected pseudocysts).
Endoscopic necrosectomy was required in 2 patients. Technical, clinical and
morphological success was achieved in 94.9%, 76.9% and 66.7% of cases per

A184
intention to treat analysis. Type, location, or etiology of PC, drainage technique
and type of stent did not show a significant influence on technical, clinical, or
morphological success. The median number of endoscopic sessions performed
were 2 (range:1-6). There were 30% of complications after the endoscopic drainage including migration of the stents in 7 patients, infection in 2, and perforation in 1 case. 3 stent migrations and the perforation required surgery while the
infections resolved after new endoscopic drainage procedure.
CONCLUSION: In our series, endoscopic treatment of PC achieved 95% technical success, 76.9% clinical success per intention to treat, and 66.7% morphologic success. The type of PC according to Atlanta classification determined the
treatment approach and stent placed.
REFERENCES
Disclosure of Interest: None declared
P0196 CAN INITIAL PRECUT FISTULOTOMY IMPLEMENTATION
REDUCE ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHYRELATED COMPLICATION RISK?
D. Kim1,1,*, G. Song1, B. Lee1, D. Baek1, J. Seo1, S. Lee1, T. Kim1, K. Lee1, J. Lee
1
1
Department of Internal Medicine, Pusan National University School of Medicine,
Busan, Korea, Republic Of

INTRODUCTION: Precut fistulotomy allows biliary access when standard cannulation methods fail. Precut fistulotomy is considered a risk factor for endoscopic retrograde cholangiopancreatography (ERCP)related complications;
however whether the complication risk is due to precut fistulotomy itself or to
the prior prolonged attempts is still debated. We aimed at assessing success of
cannulation and complications of an initial precut fistulotomy vs. a classic strategy of precut fistulotomy after a difficult biliary cannulation.
AIMS & METHODS: We conducted a retrospective study from January 2011 to
December 2012. A total of 152 patients without prior sphincterotomy were
enrolled. The patients were classified into two groups: an initial precut fistulotomy (Group A, n 72) or a late precut fistulotomy only after a failed difficult
biliary cannulation (precut fistulotomy after 4 10 cannulation attempts, 4 10
minutes, and 4 3 accidental pancreatic duct cannulations, Group B, n 80).
RESULTS: During the study period, total of 1412 ERCPs were performed. Of
these, 152 cases (10.7%) underwent precut fistulotomy. Both groups were comparable, with no differences for age, gender or indications and findings. The
overall success of cannulation for Group A and Group B was 95.9% vs 95%;
mean cannulation time: 5.7 vs. 13.0 minutes (p50.001). The overall frequency of
postERCP pancreatitis was 3 patients in Group A vs. 11 patients in Group B
(p 0.041). Other complications developed with 1 perforation and 2 bleeding
presenting in the Group A and Group B, respectively. All resolved conservatively. Finally, the overall complication rates for Group A and Group B were
8.3% (6 cases out of 72 patients) and 17.5% (14 cases out of 80 patients),
respectively.
CONCLUSION: Initial precut fistulotomy provides a higher cannulation success
with significantly less time than late precut fistoltomy, although final overall
success is similar. Initial precut fistulotomy implementation reduces post
ERCP pancreatitis risk but not the overall complication rate.
Disclosure of Interest: None declared
P0197 ENDOSCOPIC TREATMENT OF PANCREATIC FISTULAS DUE
TO ETIOLOGIES OTHER THAN PANCREATITIS
E. Parlak1,*, S. Disibeyaz2, A.S. Koksal1, B. Odemis2, S. Okten3, O. Aydinli2,
N. Sasmaz2, B. Sahin2
1
Gastroenterology, Sakarya University, Sakarya, 2Gastroenterology, 3Radiology,
_
Turkiye Yuksek Ihtisas
Hospital, Ankara, Turkey
Contact E-mail Address: koksalas@yahoo.com
INTRODUCTION: Endoscopy is effective in the treatment of pancreatic fistulas
due to pancreatitis.
AIMS & METHODS: We aimed to determine the effectivity of endoscopic
treatment in patients with pancreatic fistulas due to etiologies other than
pancreatitis.
RESULTS: The study group consisted of 44 patients (28 male, 6-80 years).
Etiologies were surgery in 30 and trauma in 14 patients. Thirty-seven patients
were presented with drainage through the drain, 5 with pancreatic ascites, and 2
with pseudocyst. Pancreatic fistulas were located in the blind end in 22 (50%)and
lateral side of the pancreas in 9 (20.5%) patients. Pancreatic fistula could not be
visualized during pancreatography in 6 (13.6%) patients. Six patients had disconnected pancreatic duct syndrome. Endoscopic treatments were pancreatic
sphincterotomy (PES) stenting in 35, PES alone in 6, and PES nasopancreatic drain insertion in 2 patients. The success of endoscopic treatment could not be
determined in 9 patients due to lost to follow up in 6 and exitus in 1 patient.
Endoscopic treatment was unsuccessfull in 7 patients due to disconnection in 6
and failure of cannulation in 1 patient. Endoscopic treatment was successfull in
29 patients (65%) and surgically placed drains were withdrawn after a mean time
of 27.3 days (5-90) in fistulas located in the blind end, 11.9 (3-28) days in fistulas
located in the lateral side, and 9.7 (3-18) days in fistulas with undefined location.
CONCLUSION: Endoscopy is effective in the treatment of pancreatic fistulas
due to etiologies other than pancreatitis if the pancreatic duct is not
disconnected.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0198 THE RESULTS OF ERCP IN PATIENTS WITH A HISTORY OF
FAILED CANNULATION
E. Parlak1,*, S. Disibeyaz2, A.S. Koksal1, B. Odemis2, B. Cicek3, H. Yildiz2,
N. Sasmaz2, B. Sahin2
1
Gastroenterology, Sakarya University, Sakarya, 2Gastroenterology, Turkiye
_
Yuksek Ihtisas
Hospital, Ankara, 3Gastroenterology, Acbadem University,
_
Istanbul,
Turkey
Contact E-mail Address: koksalas@yahoo.com
INTRODUCTION: Cannulation of common bile or pancreatic ducts is a prerequisite for biliopancreatic interventions.
AIMS & METHODS: To determine the reasons of failed cannulations and
suggest ways to increase the success rate.
We reviewed the data of the patients who were referred to our ERCP unit after
failed cannulation at another center.
RESULTS: The study group included 71 patients (40 male, mean age:57.2 years).
Sixty-nine patients had biliary and 2 pancreatic pathologies. On admission, 2
patients had retroperitoneal perforation, 1 patient had pancreatitis and cholangitis, each due to the previous ERCP attempt. The reasons of failed cannulation
were unsuccessfull pre-cut in 31 (43.6%), failure to reach papilla due to apical
stenosis in 8, presence of a peripapillary diverticula in 6, altered anatomy in 6 (3
with Billroth II), distal location of the papilla in 2, and failure to identify papilla
in 1 patient. Fifteen patients had no reasons to explain failed cannulation.
Cannulation was not attempted in the patient with retroperitoneal perforation.
Of the remaining 70 patients, cannulation could be achieved in all of them (68/70,
97.1%) other than 2 with Billroth II gastroenterostomy. Cannulation could be
achieved selectively in 50, after pre-cut in 14, dilation of the apical stenosis in 4,
and by using either one channel two accessory method or leaving a guidewire in
the pancreatic channel in 2 (2.9%) patients with peripapillary diverticula.
CONCLUSION: Performing pre-cut in the appropriate direction, realising the
anatomic alterations and anomalies in the location of papilla, and applying
advanced cannulation techniques are required to increase the success rate of
cannulation.
Disclosure of Interest: None declared
P0199 PREVENTION
OF
POST-ERCP
PANCREATITIS:
RANDOMIZED CLINICAL TRIAL USING RECTAL DICLOFENAC

G.W. Lua1,*, R. Muthukaruppan1, J. Menon1


Medical Department, Ministry of Health Malaysia, Kota Kinabalu, Sabah,
Malaysia
Contact E-mail Address: guanway@hotmail.com
1

INTRODUCTION: Pancreatitis is one of the commonest post ERCP complications. Preliminary research has evaluated several pharmacologic agents for prevention of post-ERCP pancreatitis (PEP) but none has been proven to be
effective. Non steroidal anti-inflammatory drugs (NSAIDs) have been shown
to reduce the incidence of PEP via inhibition of phospholipase A2. There were
various trials using different routes and dosages of NSAIDs. Meta analysis of
these trials was carried out but the results were inconsistent. Hence, we conducted
a clinical trial to evaluate the efficacy of prophylactic rectal diclofenac for the
prevention of PEP in high-risk patients.
AIMS & METHODS: This was a randomized, open-label, two-arm, prospective
clinical trial.
Only patients at high risk of developing PEP were selected. This was determined
by validated patient- and procedure-related risk factors. All procedures were
performed by gastroenterology trainees under the supervision of senior consultants. They were then assigned to either receive 100mg rectal diclofenac or no
intervention immediately after ERCP. After the procedure, the patients were
admitted to the ward for further observation.
The primary outcome of the trial was the development of PEP, which consisted
of new onset of upper abdominal pain, an increase in pancreatic enzymes to at
least three times the upper limit of the normal range after the procedure, and
requiring at least 2 nights of hospital stay. The patients were also reviewed 1
month after discharge to exclude the occurrence of any adverse event related to
the study drug and ERCP procedure. The difference in incidence of post-ERCP
pancreatitis between the 2 study groups was analysed using Fisher exact test
(2-tailed), with P 50.05 indicating a significant difference.
RESULTS: Among 107 patients who were enrolled and completed follow-up, 62
(57.9%) received diclofenac and 45 (42.1%) were in the control group. Among all
the patients, 4 (3.7%) developed PEP, in which 3 were in the diclofenac group (a
pancreatic stent was deployed for 1 of the patient in this group) and 1 was in the
control (p 0.31). Every cases of PEP was mild. After ERCP, 5 (4.7%) developed cholangitis and 1 (0.9%) had a perforation in which they were treated
conservatively. No drug related complications or adverse event were noted for
both groups of patients.
CONCLUSION: Among patients at high risk for developing PEP, rectal diclofenac did not significantly decrease the incidence of PEP.
REFERENCES
1. Elmunzer BJ, Scheiman JM, LehmanGA, et al. Arandomized trial of rectal
indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012; 366: 14141422.
2. Ding XW. Nonsteroidal anti-inflammatory drugs for prevention of postERCP pancreatitis: a meta-analysis. Gastrointest Endosc 2012; 76: 1152-1159.
Disclosure of Interest: None declared

A185

United European Gastroenterology Journal 2(1S)


P0200 EUS AND ERCP COMBINED WITH IDUS IN THE DIAGNOSIS OF
BILE DUCT STRICTURE
H. Jiang1,*, S.-Y. QIN1, L. TAO1, W. LUO1, S.-B. SU1, X.L.1, H.-J. NING1,
X.-P. LU1, R.-E. LEI1
1
The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Contact E-mail Address: lihuan@erbechina.com
INTRODUCTION: A variety of cholongioscopes have been emerged as a new
tools for diagnosis of different biliary strictures. But these new techniques are not
widely applied clinically because of high price and too easy to damage.
AIMS & METHODS: We evaluated the value of endoscopic ultrasonography
(EUS) and endoscopic retrograde cholangiopancreatography (ERCP) combined
with intraductal ultrasonography (IDUS) in the diagnosis of bile duct stricture.
36 patients with bile duct stenosis were recruited. The findings by endoscopic
ultrasonography and endoscopic retrograde cholangiopancreatography combined with intraductal ultrasonography and the results of bile duct brushing
cytology and liquid-based cytology of these patients were analyzed. The final
diagnosis was based on clinical data, histopathology and follow-up results (6
months).
RESULTS: All of the 36 patients, in whom 21 were diagnosed malignant biliary
diseases, including 9 biliary tract carcinomas, 4 duodenal papilla carcinomas, 4
pancreatic cancers infiltrating common bile duct and 4 liver cancers infiltrating
common bile duct; 15 were diagnosed as benign biliary diseases, including 9 bile
duct stones, 4 liver fluke diseases, 1 cholangitic stenosis and 1 external compression, were shown to have bile duct stricture. The accuracy rate of EUS, ERCP,
IDUS and EUSERCPIDUS in the differential diagnosis of bile duct stricture
disease were 77.8%, 88.9%, 91.7% and 94.4%, respectively. The accuracy rates
of differential diagnosis of bile duct stricture disease between EUS and ERCP
were similar; while the accuracy rate of EUS and ERCP combined with IDUS
was significantly higher than both EUS and ERCP (P50.05). The sensitivity,
specificity, positive predictive value (PPV) and negative predictive value (NPV) of
EUSERCPIDUS were 95.2%, 93.3%, 95.2%, 93.3%, respectively; the sensitivity, PPV, NPV in EUS ERCP IDUS were higher than that of EUS, ERCP
and IDUS. All of the 36 patients received bile duct brushing cytology and the
liquid-based cytology tests, 19 of which were diagnosed as malignant biliary
diseases, while 17 were diagnosed as benign biliary diseases. The sensitivity,
specificity and accuracy of differential diagnosis of bile duct stricture disease
were 90.5%, 100% and 94.4%, respectively.
Table. Comparison of ERCP and EUS in the diagnosis of bile duct stricture

Tokyo, Japan). Pancreatic interventions were successful in 9 patients (75%).


Three of 6 patients with anastomotic stricture were treated successfully with
balloon dilation, and the remaining 3 patients required repeated balloon dilation
and long-term pancreatic stent placement. Two patients with pancreatic fistula
were treated successfully with endoscopic nasopancreatic drainage. Pancreatic
duct stones were successfully removed in 4 patients. Complications occurred in
3 (25%) patients, including retroperitoneal air (n 1) and hyperamylasemia
(n 2), but all were asymptomatic.
CONCLUSION: Endoscopic pancreatic interventions using short DBE,
although technically demanding, are effective and safe in patients with surgically
altered anatomy.
Disclosure of Interest: None declared
P0202 SHORT SINGLE-BALLOON VERSUS DOUBLE-BALLOON
ENDOSCOPE FOR PANCREATICOBILIARY INTERVENTIONS IN
PATIENTS WITH SURGICALLY ALTERED ANATOMY
H. Kogure1,*, A. Yamada1, H. Isayama1, N. Takahara1, R. Uchino1,
T. Hamada1, K. Miyabayashi1, D. Mohri1, T. Sasaki1, S. Matsubara1,
N. Yamamoto1, Y. Nakai1, K. Hirano1, M. Tada1, K. Koike1
1
Department of Gastroenterology, Graduate School of Medicine, The University of
Tokyo, Tokyo, Japan
Contact E-mail Address: kogureh-tky@umin.ac.jp

CONCLUSION: EUS and ERCP combined with IDUS can improve the diagnostic accuracy of bile duct disorders. IDUS is carried out under the guidance of
a guide wire, and the operation is simple. It can also make up for the inadequacy
of EUS. With the help of ERCP and IDUS, the bile duct could be directedly
brushed, which could improve the diagnostic positive rate.
Disclosure of Interest: None declared

INTRODUCTION: With the advent of short double-balloon endoscope (DBE),


therapeutic pancreaticobiliary interventions are possible with surgically altered
anatomy. However, because the channel diameter of short DBE is 2.8 mm, only
limited ERCP devices are available and the exchange of devices is both timeconsuming and cumbersome. Recently, a prototype short single-balloon endoscope (SBE) with passive bending and high force transmission, which has a 3.2
mm working channel and a 152 cm in length, was specifically developed for
ERCP (SIF-Y0004-V01; Olympus Medical Systems, Tokyo, Japan).
AIMS & METHODS: The aim of this study was to compare the insertability and
procedural efficiency of short SBE and short DBE for pancreaticobiliary interventions in patients with surgically altered anatomy. Between March 2013 and
Jan 2014, we performed endoscopic pancreaticobiliary interventions using a short
SBE in 20 patients who have successfully undergone short DBE-assisted ERCP.
Previous surgeries included Roux-en-Y (R-Y) gastrectomy (n 7), hepaticojejunostomy (n 5), pancreaticoduodenectomy with R-Y reconstruction (n 3),
Billroth II (B-II) gastrectomy with Brauns anastomosis (n 2), pancreaticoduodenectomy with B-II reconstruction and Brauns anastomosis (n 2), and liver
transplantation with hepaticojejunostomy (n 1).
RESULTS: Access to the papilla or anastomosis with SBE failed in 3/20 patients
(15%). Among successful patients, the median time (IQR) required to reach the
target orifice was 26 min (1132.5 min) with SBE and 16 min (1121 min) with
DBE (P 0.10). Pancreaticobiliary interventions with SBE were successful in 17/
17 patients (100%). Therapeutic procedures using SBE included stone extraction
(n 11), biliary plastic stenting (n 5), papillary large balloon dilation (n 3),
balloon dilation of anastomotic stricture (n 3), pancreatic stenting (n 3), biliary metallic stenting (n 1), balloon dilation of biliary stricture (n 1), and
endoscopic naso-pancreatic drainage (n 1). Although almost the same procedures with prior DBE, the median ERCP procedure time (IQR) was shorter with
SBE than with DBE [29 min (2355.5 min) vs 63 min (46.593.5 min), P 0.03].
Aspiration pneumonia as procedure-related complication occurred in 1 patient.
CONCLUSION: Insertability of a short SBE is slightly inferior to that of a short
DBE. However, a short SBE with a 3.2 mm working channel allows most conventional ERCP devices to be used and reduces ERCP procedure time compared
to a short DBE with an only 2.8 mm working channel.
Disclosure of Interest: None declared

P0201 ENDOSCOPIC PANCREATIC INTERVENTIONS USING SHORT


DOUBLE-BALLOON ENDOSCOPE IN PATIENTS WITH
SURGICALLY ALTERED ANATOMY

P0203 INTER-OBSERVER AGREEMENT AND ACCURACY


PREOPERATIVE EUS-GUIDED BIOPSY FOR HISTOLOGIC
GRADING OF PANCREATIC CANCER

H. Kogure1,*, A. Yamada1, H. Isayama1, N. Takahara1, R. Uchino1,


T. Hamada1, K. Miyabayashi1, D. Mohri1, T. Sasaki1, S. Matsubara1,
N. Yamamoto1, Y. Nakai1, K. Hirano1, M. Tada1, K. Koike1
1
Department of Gastroenterology, Graduate School of Medicine, The University of
Tokyo, Tokyo, Japan
Contact E-mail Address: kogureh-tky@umin.ac.jp

A. Larghi1,*, R. Ricci2, I. Abdulkader3, G. Monges4, J. Iglesias-Garcia 5,


M. Giovannini6, F. Attili1, G. Vitale 1, C. Hassan1, G. Rindi2, G. Costamagna1
1
Digestive Endoscopy Unit, 2Department of Pathology, Catholic University, Rome,
Italy, 3Department of Pathology, University Hospital of Santiago de Compostela,
Santiago de Compostela, Spain, 4Department of Pathology, Paoli-Calmettes
Institute, Marseille, France, 5Gastroenterology Department, University Hospital of
Santiago de Compostela, Santiago de Compostela, Spain, 6Endoscopic Unit, PaoliCalmettes Institute, Marseille, France
Contact E-mail Address: albertolarghi@yahoo.it

EUS

ERCP

IDUS

EUSERCPIDUS

sensitivity
specificity
PPV

71.4%(15/21)
86.7%(13/15)
88.2%(15/17)

85.7%(18/21)
93.3%(14/15)
94.7%(18/19)

90.5%(19/21)
93.3%(14/15)
95%(19/20)

95.2%(20/21)
93.3%(14/15)
95.2%(20/21)

NPV
diagnosis
misdiagnosis
Accuracy rate (%)

68.4%(13/19)
28
8
77.8

82.4%(14/17)
32
4
88.9

87.5%(14/16)
33
3
91.7

93.3%(14/15)
34
2
94.4

INTRODUCTION: In patients with surgically altered anatomy, endoscopic


treatment of pancreatic disease such as pancreaticojejunostomy stricture, pancreatic fistula, and pancreatic duct stones can be challenging.
AIMS & METHODS: We evaluated the efficacy and safety of endoscopic pancreatic interventions using short double-balloon endoscope (DBE) for the treatment of pancreatic disease in patients with surgically altered anatomy.
Between October 2009 and April 2014, we performed endoscopic pancreatic
interventions in 12 patients using a short DBE (152 cm in length with a 2.8
mm working channel; EC-450BI5/EI-530B, Fujifilm Medical, Tokyo, Japan),
enabling conventional ERCP accessories. Previous surgeries included pancreaticoduodenectomy with Billroth II reconstruction (n 7), pancreaticoduodenectomy with Roux-en-Y reconstruction (n 3), and Roux-en-Y gastrectomy (n 2).
Indication for pancreatic interventions were anastomotic stricture (n 8; with
pancreatic duct stones [n 5]), pancreatic fistula (n 3), and pancreatic duct
stones (n 1).
RESULTS: Access to the papilla or the end of afferent loop successful in all 12
patients, but anastomosis site could not be identified in 3 patients. Pancreatic
duct cannulation was achieved using a straight cannula (0.025-inch ERCP-catheter, MTW Endoskopie, Wesel, Germany) and a 0.035-inch hydrophilic guidewire
(Radifocus, Terumo, Tokyo, Japan), or a metal tip cannula (PR-132Q, Olympus,

OF

INTRODUCTION: Post-surgical poor differentiation/high grade of pancreatic


cancer (PADC) appears to accurately predict an early unfavourable outcome,
these patients possibly deserving neo-adjuvant treatment. EUS-guided pancreatic
tissue core biopsy (EUS-PTCB) may in theory allow a pre-operative assessment
of PADC-grading. To assess inter-observer pathological agreement and accuracy
of preoperative PADC-grading based on EUS-PTCB.
AIMS & METHODS: 42 post-surgical PADC-cases with preoperative EUSPTCB were chosen. Four expert pathologists independently reviewed the EUSPTCB slides, reporting tumour grading (well-/moderate-/poor-degree of differentiation). Agreement among pathologists for reporting PADC-grading on preoperative EUS-PTCB material was expressed by using Cohens/Fleiss kappa
statistic, as appropriate. Post-surgical PADC-grading was used as gold-standard
to assess the cumulative accuracy of EUS-PTCB in preoperatively predicting
PADG grade.
RESULTS: The k values for PADC-grading on EUS-PTCB material ranged
from 0.09 to 0.41. The total agreement among the four pathologists was only
fair (k 0.27; 95% CI: 0.14-0.38). When tumor grades were grouped as well-/

A186
moderately differentiated versus poorly differentiated, kappa values ranged from
0.19 to 0.50, with only a fair overall agreement (k 0.27; 95% CI: 0.21-0.49).
Preoperative EUS-PTCB-based accuracy of preoperative staging was 56% (75/
134 readings; 95% CI: 40-65%), with mean sensitivity and specificity to detect a
high grade poorly differentiated tumor of 41% (95% CI: 19-54%) and 78% (53/
68 readings; 95% CI: 60-99%), respectively.
CONCLUSION: Preoperative EUS-PTCB-based pathological grading of PADC
is unreliable, arguing against the use of this information in clinical practice. This
appears to be related with both a suboptimal inter-observer agreement among
pathologists and an overall low accuracy in predicting post-surgical staging.
Disclosure of Interest: None declared
P0204 PERFORMANCE OF THE PROCORE 25 GAUGE NEEDLE IN
OBTAINING SAMPLES FOR HISTOLOGICAL EXAMINATION IN A
LARGE AND HETEROGENOUS COHORT OF PATIENTS: A TWO
CENTERS STUDY
A. Larghi1,*, F. Attili1, G. Petrone2, I. Abdulkader3, F. Inzani 2, J. IglesiasGarcia 4, C. Hassan1, G. Rindi2, G. Costamagna1
1
Digestive Endoscopy Unit, 2Department of Pathology, Catholic University, Rome,
Italy, 3Department of Pathology, 4Gastroenterology Department, University
Hospital of Santiago de Compostela, Santiago de Compostela, Spain
Contact E-mail Address: albertolarghi@yahoo.it
INTRODUCTION: A new 25-gauge Procore biopsy needle has become
recently available. Scanty data on its performance are available. We evaluate
the yield of this needle in obtaining samples for histologic evaluation (EUSFNB), its diagnostic accuracy and inter-observer agreement between three
pathologists in a large cohort of patients with heterogenous indication.
AIMS & METHODS: Consecutive patients who underwent EUS-FNB using the
Procore 25G were retrospectively retrieved. The collected material was placed
directly in formalin or in cytolit and sent for histologic evaluation. All samples
were independently reviewed by three pathologists and scored for: (i) presence of
an histologic, cytologic specimen or no specimen; (ii) presence or absence of
neoplasia; (iii) diagnostic or not diagnostic. Diagnostic accuracy and interrater concordance among pathologists in the evaluation of the above mentioned
parameters were calculated.
RESULTS: 94 patients (median age 71 years; 55 male) underwent EUS-FNB of
101 sites. Mass lesions were located in the pancreas (49 patients), abdomen (6),
liver (8), common bile duct (3 masses and 3 wall thickening), stomach (1 subepithelial lesion and 2 wall thickening), mediastinum (2), lung (1), and adjacent to
the rectum (1). All the remaining 25 sampled lesions were mediastinal (14) and
abdominal (11) lymph nodes. The median lesion size was 30 mm (range, 15-67
mm) and a mean of 2.5 FNA passes (range, 1-6; median, 3; IQR, 2-3) per lesion
was done. A total of 41 (40.6%) lesions were classified as having a histologic
specimen either by at least two of the three pathologists. A presence of a cytologic
specimen was found by at least two of the three pathologists in 29 (28.7%) cases.
In the remaining 31 lesions no specimen was present according to all three
pathologists. There was good agreement among pathologists in determining if
EUS-FNB provided cytologic vs. histologic samples (kappa index, 0.82; 95%
CI:0.74-0.90). When considering non-diagnostic samples as false negative, the
pooled sensitivity of the EUS-FNB for neoplasia was 65% (154 of 237 readings;
95% CI: 54.8-75.1%), whereas specificity was 98% (50 of 51 readings; 95% CI:
89-100%). The pooled accuracy of the procedure was 70.8 (204 of 288 readings;
95% CI: 62.1-79.6%). In the per-protocol analysis, the overall sensitivity and
accuracy of the procedure for malignancy was 93.8 (150 of 160 readings; 95% CI:
88.8-96.9) and 93.9% (170 of 181 reading; 95% CI: 89.3-96.9%), respectively.
Substantial agreement on the presence (or absence) of neoplasia resulted (kappa
index, 0.94; 95% CI: 0.83-1.00). Substantial agreement was seen across the three
reviewers in describing diagnostic accuracy, with an overall kappa value of 0.95
(95% CI: 0.85-1.00). At multivariate analysis, histologic samples were more likely
than cytologic one to lead to a correct diagnosis (OR, 4.1; 95% CI: 1.2, 15.0;
p 0.027).
CONCLUSION: EUS-guided FNB with the Procore 25G needle provided samples for histologic examination in about 40% of the cases and showed excellent
results in term of interobserver variability.
Disclosure of Interest: None declared
P0205 COMBINED ENDOBRONCHIAL AND TRANSESOPHAGEAL
APPROACH OF AN ULTRASOUND BRONCHOSCOPE FOR TISSUE
DIAGNOSIS OF MEDIASTINAL LYMPHADENOPATHY
A. Strunina1,*, R. Kuvaev1, S. Kashin1, A. Levina2, V. Chernyaeva2,
N. Akhapkin3
1
Endoscopy, 2Cytology, 3Administration, Yaroslavl Regional Cancer Hospital,
Yaroslavl, Russian Federation
Contact E-mail Address: kuvaev_roman@mail.ru
INTRODUCTION: Morphological evaluation of mediastinal masses is essential
for diagnostic confirmation and treatment planning of patients (pts) with mediastinal abnormalities. EBUS-TBNA and EUS-FNA is a safe and efficacy
method to obtain tissue for morphological diagnosis. The combined approach
reduces the need for additional equipment, the operating costs, and the duration
of the procedure. However it could be difficult to select the order of preference if
both of the techniques are available.
AIMS & METHODS: The aim was to determine the diagnostic value of EBUSEUS combined approach by using single ultrasound bronchoscope for evaluation
mediastinal lymphadenopathy. EUS FNA and EBUS TBNA (Olympus Exera
II BF-UC160F, Olympus 21g needles) were compared in 166 patients for tissue
diagnosis from enlarge (40.9cm) 7 and 4L group lymph nodes. 110 lesions were
sampled from the respiratory tract under moderate sedation as first step. For 56

United European Gastroenterology Journal 2(1S)


lesions fine needle aspiration was performed initially from the esophagus under
local anesthesia. Cytology examination of the fine needles aspirates was made on
site. If EUS-FNA (8pts) gives a negative result (8pts) in the on-site cytological
analysis, EBUS-TBNA was performed once.
RESULTS: Diagnosis was proved in 87.3% of cases in EBUS-TBNA group and
in 85.7% of cases in EUS-FNA group. Definitive morphology diagnosis was
made in 96.4% by the combined approach with rapid on-site evaluation of the
fine needles aspirates.
CONCLUSION: Two procedures can be performed with single ultrasound
bronchoscope and the combined approach with cytology examination on site
has better diagnostic value than either alone. But EUS-FNA with ultrasound
bronchoscope is easy, safe and doesnt request moderate sedation. Therefore it
can be performed for patients for tissue diagnosis from enlarge 7 and 4L group
lymph nodes as the first step of examination.
Disclosure of Interest: None declared
P0206 RESULTS AND LEARNING FROM A THERAPEUTIC
ENDOSCOPIC ULTRASOUND PRACTICAL WORKSHOP ON A
SWINE LIVING MODEL
A. Teran Lantaron1,2,*, B. Castro Senosiain1,2, P. Iruzubieta Coz1,2, G. De las
Heras Castano1,2, J.C. Manuel-Palazuelos2, J.B. Gornals Soler3, J.J. Vila Costa4,
M. Perez-Miranda5, J. De la Pena Garcia1,2
1
GASTROENTEROLOGY AND HEPATOLOGY, HOSPITAL
UNIVERSITARIO MARQUES DE VALDECILLA, 2HOSPITAL VIRTUAL
VALDECILLA, SANTANDER, 3GASTROENTEROLOGY AND
HEPATOLOGY, HOSPITAL UNIVERSITARI BELLVITGE, BARCELONA,
4
GASTROENTEROLOGY AND HEPATOLOGY, COMPLEJO
HOSPITALARIO DE NAVARRA, PAMPLONA, 5GASTROENTEROLOGY
AND HEPATOLOGY, HOSPITAL UNIVERSITARIO RIO HORTEGA,
VALLADOLID, Spain
Contact E-mail Address: altelan@hotmail.com
INTRODUCTION: Therapeutic endoscopic ultrasound (T-EUS) has been
undergoing extensive development in recent years. Although previous experience
on EUS-FNA and ERCP is considered to be needed, data on learning curves and
the potential benefit of animal models training are lacking.
AIMS & METHODS: To train some different T-EUS techniques and to estimate
their difficulties and the potential benefit of the swine model in this context.
Prospective data analysis from a T-EUS practical workshop on a biliary obstruction porcine model by OTSC clip, addressed to endoscopists with previous
EUS-FNA and ERCP experience. There were four different T-EUS procedures
trained: common bile duct drainage (CBDD), cholecysto-gastrostomy (CGS),
transrectal urinary bladder drainage (TUBD), simulating a fluid collection drainage, and gastro-jejunostomy (GJS). All animals were sacrificed after T-EUS
procedures and necropsy studies were performed. Local Ethics Committee
approval was obtained.
RESULTS: Thirty three procedures were analyzed (11 CBDD, 5 CGS, 7 TUBD,
10 GJS), performed by 12 endoscopists in 10 pigs (2.83  0.58 proc./endoscopist;
3.3  1.42 proc./animal). Main results are shown in Table 1. Together TUBD
and GJS were the procedures more frequently and successfully completed versus
CBDD and CGS (100% vs. 62.5%, p 0.007 and 82.4% vs. 37.5%, p 0.011).
Among the different procedural steps, guidewire management (31.8%), stent
insertion (25%) and cystotome use (20%) were the most troublesome ones.
Table 1. Results by procedure

N
Mean time duration (min.)
Completed
Final succes
Trainer intervention needed
Inmediate complications

CBDD

CGS

TUBD

GJS

Total

11
51.3 
14.5
63.6%
45.5%
18.8%
10%

5
48 
7.6
60%
20%
20%
40%

7
31.3 
5.9
100%
85.7%
14.3%
14.3%

10
21.2 
17.2
100%
80%
20%
10%

33
34.7 
18.5
81.8%
60.6%
18,8%
15.6%

*p

0.000
0.007
0.011
0.608
0.437

CONCLUSION: Our model appears to mirror the challenges of T-EUS even for
endoscopists experienced in EUS-FNA and ERCP.
Ethical and cost concerns can be minimized by optimizing the number of T-EUS
drainage procedures, up to 4 per animal.
CGS and CBDD, both longer and with higher number of steps and instrument
requirements, are more challenging than TUBD or GJS, which suggests more
demanding training is needed.
This kind of training based on animal model simulation may allow a safer and
probably quicker learning curve on T-EUS.
Disclosure of Interest: A. Teran Lantaron Financial support for research from:
The workshop reported in this abstract was sponsorized by Boston Scientific, B.
Castro Senosiain: None declared, P. Iruzubieta Coz: None declared, G. De las
Heras Castano: None declared, J. Manuel-Palazuelos: None declared, J. Gornals
Soler: None declared, J. Vila Costa: None declared, M. Perez-Miranda: None
declared, J. De la Pena Garcia: None declared

A187

United European Gastroenterology Journal 2(1S)


P0207 COMPLICATIONS AND HISTOPATHOLOGICAL ASSESSMENT
OF THE PANCREAS IN A PORCINE MODEL AFTER EUS
RADIOFREQUENCY ABLATION

P0209 ENDOSCOPIC ULTRASONOGRAPHY-GUIDED DRAINAGE OF


HEPATIC ABSCESSES AND BILOMAS BY USING SELFEXPANDABLE METAL STENTS (SEMS). A PILOT STUDY

B.S. Ungureanu1,*, L. Sandulescu1, C. Margaritescu1, D. Pirici2, A. Saftoiu1


1
Gastroenterology, Research Center in Gastroenterology and Hepatology,
2
Gastroenterology, Morphopatology, Craiova, Romania
Contact E-mail Address: boboungureanu@gmail.com

C. De La Serna Higuera1,*, P. Diez- Redondo1, I. Penas1, F. Santos1, P. Gil1,


H. Nunez1, M. Perez-Miranda1
1
Gastroenterology, Rio Hortega Hospital, Valladolid, Spain
Contact E-mail Address: csernah@hotmail.com

INTRODUCTION: Treating pancreatic cancer represents a major objective in


research, as it still remains the fourth leading cause of cancer deaths among men
and women, with approximately 6% of all cancer-related deaths. Radiofrequency
ablation uses electromagnetic energy deposition causing thermal lesions and
overheating tissue which leads in a final stage to necrosis.
AIMS & METHODS: We studied the assessment of an EUS-guided RFA probe
through a 19-gauge needle, in order to achieve a desirable necrosis area in the
pancreas. Radiofrequency ablation of the head of the pancreas was performed
using a RITA Medical System device on 10 Yorkshire pigs with a weight between
25 to 35 kg. Using an EUS-guided RFA experimental probe we ablated an area
of 2 to 3 cm wide at 5-10-15-20 watts for one minute a time.
RESULTS: No major complications were noted. High levels of amylase, lipase,
aspartate transaminase and alanine transaminase were found within 3 days from
the ablation. Necropsy pointed out a very well limited area with minimal invasion and inflammatory tissue at about 2 cm surrounding the lesion. No nearby
fibrosis or adhesions were found and no major vessel injuries or adjacent organ
damage was produced. The pathology examination revealed coagulative necrosis,
a local acute inflamatory reaction with structured necrosis of the glandular parenchyma, steatonecrosis, and recent thrombosis of blood vessels.
CONCLUSION: EUS-Guided RFA of the pancreas may be a feasible procedure,
however more studies are necessary.
Disclosure of Interest: None declared

INTRODUCTION: Liver abscesses and bilomas are conventionally managed by


means of percutaneous drainage or surgical approach. However, both procedures
have been reported on high morbi-mortality rates. Transgastric EUS-guided drainage of both entities with plastic stents or nasocystic catheters have been exceptionally performed. We describe our experience using self expandable metal stents
(SEMS) tubular and lumenapposing metal stents (LAMS) in this setting.
AIMS & METHODS: The aim of the study was to assess the technical feasibility
and clinical outcomes of EUS-guided drainage of liver abscesses and bilomas
using SEMS under mixed fluoroscopic, endoscopic and ultrasonographic
guidance.
Retrospective analysis involving eight consecutive patients (March12 to Oct 13)
with liver abscesses/bilomas not accesible to percutaneous approach and/or discarded for surgery by means of age or comorbidities (Table 1). Procedures were
performed by using linear echoendoscopes, 19G needles under EUS & fluoroscopic control, 0.035 guidewires, 8.5F cystotome and tract dilation with 4 mm
biliary balloon. Aspiration of fluid was routinelly performed for culture. Finally,
cSEMS were placed, either tubular or lumen-apposing metal stents (LAMS:
AXIOSTM- Xlumena Inc).
RESULTS: Six patients with liver abscesses and 2 bylomas were included (Table
1) EUS-guided transgastric approach was performed in 6/8 cases (75%) in correspondence with abscesses located on the left hepatic lobe. 6 patients were
managed with LAMS (5 abscesses, 1 biloma). Median diameter of abscesses
was 80.05 mm (range 52.70 - 99). Drainages were successful in all cases and
there were no procedure-related complications. Stents were removed after a
mean of 7 weeks (range 4-12). There were no relapses after a mean follow-up
of 7.5 months (range 1-18)
CONCLUSION: EUS-guided drainage of hepatic abscesses and bilomas by
means of SEMS appears to be a safe, effective and useful procedure in patients
not suitable for radiologic drainage or surgery. However, larger, prospective and
multicenter studies are needed.
Disclosure of Interest: None declared

P0208 ROLE OF ENDOSCOPIC ULTRASONOGRAPHY IN


SELECTION FOR NEOADJUVANT TREATMENT OF GASTRIC
ADENOCARCINOMA

THE

B.M. Goncalves1,*, P. Bastos1, J.-B. Soares1, D. Fernandes1, E. Couto2,


J. Cunha2, C. Rolanda1, R. Goncalves1
1
Gastroenterology, 2Oncology, Hospital de Braga, Braga, Portugal
Contact E-mail Address: brunommgoncalves@gmail.com
INTRODUCTION: Gastric remains one of the most common causes of cancerrelated death. Recent studies reveal that neoadjuvant treatment of locally
advanced gastric cancer improves survival of these patients. Endoscopic ultrasonography (EUS) staging is recommended in several guidelines, particularly in
the assessment of the T and N stages. However, its role in identifing patient
candidates to neoadjuvant therapy is not known.
AIMS & METHODS: The purpose of the study was to evaluate the accuracy of
EUS in selecting patients for neoadjuvant therapy of gastric adenocarcinoma.
We conducted a retrospective analysis of patients with gastric adenocarcinoma
who underwent EUS staging and were submitted to primary gastrectomy
between 2011 and 2013. We determined the agreement (kappa k) between
EUS and pathological TNM staging and the accuracy (AUROC, sensitivity
and specificity) of EUS to identify patients with indication for neoadjuvant
therapy (defined as stages II and III in the pathological analysis of the surgical
specimen).
RESULTS: Between 2011 and 2013 were performed 141 USE, of which 66 were
excluded (37 patients did not undergo underwent gastrectomy, 16 patients underwent neoadjuvant therapy, 7 USE were re-staging examinations and 6 cases
werent adenocarcinomas). Of the 75 patients enrolled, the median age was 66
years, 65% were male and 60% had intestinal type adenocarcinoma. The distribution of patients according to the EUS and pathological staging was: 50.7%
and 46.6% for stage I, 31.1% and 33.3% for stage II, 16% and 21.3% for stage
III. The agreement between EUS and pathologic stages for T, N and TNM was
good (k 0.61), moderate (k 0.44) and fair (k 0.36), respectively, while for
stages II III was good (k 0.63). The accuracy of EUS for stages II III was
high (AUROC 0.82, sensitivity 78% and specificity 86%), especially for intestinal
type adenocarcinoma (AUROC 0.84, sensitivity 86% and specificity 85%).
CONCLUSION: Endoscopic ultrasonography has an important role in the staging of gastric cancer, showing a good performance in the selection of patients
for neoadjuvant treatment, especially in intestinal type adenocarcinoma.
Disclosure of Interest: None declared

P0210 COULD
QUANTITATIVE
AND
QUALITATIVE
EUSELASTOGRAPHY RESULTS BE AFFECTED BY THE
COMPRESSION RATE AND THE DIAMETER OF THE REGION OF
INTEREST?
C. Robles-Medranda1,*
ENDOSCOPY, INSTITUTO ECUATORIANO DE ENFERMEDADES
DIGESTIVAS, UNIVERSITY HOSPITAL OMNI, ESPIRITU SANTO
UNIVERSITY, Guayaquil, Ecuador
Contact E-mail Address: carlosoakm@yahoo.es
1

INTRODUCTION: EUS-elastography (EUS-e) is an alternative method to evaluate tissue stiffness (elasticity-index) of solid pancreatic masses, which may be
related to histopathology tissue features (hard blue neoplastic / soft redyellow-green non-neoplastic). Recently publications show different results
using EUS-e and a lack of data exist regarding the compression rate of the
probe (CRP) and the diameter of the region of interest (d-ROI) under analysis.
AIMS & METHODS: Based on the hypothesis that EUS-e could be affected by
CRP and the d-ROI this study aimed to evaluate the quantitative strain ratio (qSR) and qualitative color (q-C) EUS-e results determined by the CRP and the dROI in normal pancreatic tissue (NPT). After approval by the ethics committee
and signing of an informed consent, a prospective study was performed in 45
patients undergoing for upper-EUS from Oct-Nov 2013. Inclusion criteria: EUS
for evaluate submucosal tumors. Exclusion criteria: age518 or 4 55; pregnancy,
history of: pancreatic disease, choledocolitiasis, symptoms of maldigestion, alcohol abuse, increased serum levels of pancreatic enzymes, smokers and EUS signs
of chronic pancreatitis (Rosemont classification). EUSe was performed using
linear Pentax-EUS and Hitachi-Avius. The q-SR and q-C EUS-e was measured
in the body of the pancreas taking in consideration the curve of the CRP high:
0.4 (H-CRP), middle: 0 (M-CRP), low: -0.4(L-CRP) in the largest (LROI) and
smaller ROI (SROI) diameters. Analysis for q-C was obtained by the predominant color of the pancreatic area studied. Pictures where recorded and q-SR data

P0209
Collection
type

Age/ Sex

Size
(mm)

Approach

Stent
type

Complications

Retrieval
(weeks)

Follow-Up
(months)

Outcome

1
2
3

Abscess
Abscess
Abscess

71/M
92/M
65/M

74
91,6
85

Transgastric
Transgastric
Transgastric

AXIOS 15 x 10
AXIOS 15 x 10
HotAXIOS 15 x 10

NO
NO
NO

8
12
9

6
14
3

Resolution
Resolution
Resolution

4
5
6
7

Abscess
Abscess
Abscess
Biloma

34/M
84/F
49/F
74/F

99
52,7
78
72

Transgastric
Transgastric
Trans-duodenal
Trans - duodenal

NO
NO
NO
NO

4
6
9
4

2
1
3
13

Resolution
Resolution
Resolution
Resolution

Biloma

53/F

69.4

Transgastric

AXIOS 10 x 10
AXIOS 10 x 10
Tubular SEMS 60 X 10
AXIOS 15 x 10
Plastic pig-tail
Tubular SEMS 60 x 10
Plastic pigtail

NO

18

Resolution

A188
were calculated comparing EUS-e of pancreatic tissue with soft tissue (normal
mucosal layer: red). Finally, a comparative analysis was performed between the
results with the mean normal value (NV) of 1.68 for q-SR previously published
for NPT, and between the different CRP.
RESULTS: 60 images were analyzed and 10 patients were included, 6 females,
mean age 50 (ranges: 32-55). LROI q-C analysis: showed a predominant green
(G) color in H-CRP in 90%, M-CRP in 50% and L-CRP in 70% of cases. SROI
q-C analysis: showed a predominant G-color in H-CRP in 100%, L-CRP in 50%
and M-CRP in 66.6% of cases. In LROI-quantitative showed a mean SR of 7.2
(range: 2.7-24) for H-CRP, 11.03 (range: 3.3-42) for M-CRP and 8.8 (range: 2.636) for L-CRP being p50.05 for H-CRP and L-CRP when compared with NV qSR, and for H-CRP when comparing with M-CRP. For SROI q-SR analysis
showed a mean SR of 6 (range: 5.5-6.6) for H-CRP; 8 (range: 5-12) for M-CRP
and 77 (ranges: 2.3-224) for L-CRP, being p50.05 in all cases when compared
with NV q-SR.
CONCLUSION: EUS-e (q-C and q-SR) results in NPT could be affected by
CRP and d-ROI. These data suggest that a standardization of the measurements
parameters is required to determine the best results and application of this technology in pancreatic diseases.
REFERENCES
Dawwas MF, Taha H, Leeds JS, et al. Diagnostic accuracy of quantitative EUS
elastography for discriminating malignant from benign solid pancreatic masses: a
prospective, single-center study. Gastrointest Endosc 2012; 76: 953-961.
Disclosure of Interest: C. Robles-Medranda Consultancy for: Pentax Medical,
MaunaKea technologies, Other: Key Opinion Leader for Pentax Medical
P0211 ENDOSCOPIC
ULTRASOUND-GUIDED
FINE
NEEDLE
ASPIRATION (EUS-FNA) IN PANCREATIC LESIONS: PREDICTIVE
FACTORS OF ACCURATE DIAGNOSIS
C. Leitao1,*, A. Santos1, H. Ribeiro1, J. Pinto1, A. Caldeira1, E. Pereira1,
A. Banhudo1
1
Servico de Gastrenterologia, Hospital Amato Lusitano - Unidade Local de Saude
de Castelo Branco, Castelo Branco, Portugal
Contact E-mail Address: catia.f.leitao@gmail.com
INTRODUCTION: Endoscopic ultrasound (EUS) has taken on an important
role in the diagnosis of benign and malignant pancreatic disease. Due to the
proximity of the transducer and reduced acoustic interference, EUS provides
high-resolution ultrasound images of the pancreas with subtle anatomical
detail and has the unique ability to obtain specimens of the pancreas and peripancreatic structures for cytohistological diagnosis.
AIMS & METHODS: The aim of this study is to identify the predictive factors
for an accurate EUS-FNA diagnosis. Methods: Retrospective analysis of medical
records of patients submitted to an EUS-FNA for evaluation of a pancreatic
mass, from January of 2008 to December of 2013. All procedures were performed
by 2 operators, using a linear echoendoscop Pentax EG3870UTK and Hitachi
HI Vision Preirus or EUB-6000 US. Collection of demographic data, ultrasonographic characteristics, technical information on EUS-FNA and cytohistological
results.
RESULTS: A total of 1420 EUS examinations were performed during the
period. 88 patients (with a mean age of 6414 years; 54.5% female) diagnosed
with pancreatic masses underwent EUS-FNA. 81.8% of them had this symptoms: epigastric pain (34%), weight loss (23.9%) and jaundice (23.9%). 51.5% of
the lesions were located in head of pancreas and 67% were solid masses. The
median size of the lesion was 31.812.5mm. The mean number of passages was
2.350.97. EUS-FNA was performed with 19 G needle in 7.1% of patients, 22G
needle in 70.6% and with 25G needle in 22.4% of patients. The overall diagnostic
accuracy was 82.9%. In 10 patients procore needle (19G-1;22G-1;25G-5) was
used and the diagnostic accuracy was 100%, although not a statistically significant difference. Adenocarcinoma was the most common cytological diagnosis
(62.9%), followed by inflammatory pancreatic disease (21%), endocrine neoplasm (6.5%), mucinous neoplasm cystic (6.5%) and IPMN (1.6%). There
were no procedure-related complications. The predictors of diagnostic accuracy
(p5 0.05) were: appearance of lesion (solid mass 90.6% vs. cystc mass 54.4%),
size of lesion (diagnostic 32.6 mm vs non diagnostic 23.6 mm) and location of the
lesion (body 100% vs. head 86.6% vs. neck 70.2% vs. tail 40%). The size of
needle and number of passages did not significantly influenced the diagnostic
accuracy of the procedure.
CONCLUSION: EUS-guided FNA is a safe and reliable technique for establishing a diagnosis in pancreatic mass lesions, especially in solid mass, located in
body or head and with a greater dimension.
REFERENCES
(1) Hewitt MJ et al. EUS-guided FNA for diagnosis of solid pancreatic neoplasms: a meta-analysis. Gastrointest Endosc 2012; 75: 319-331.
(2) Iglesias-Garcia J, et al. Influence of on-site cytopathology evaluation on the
diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration
(EUS-FNA) of solid pancreatic masses. Am J Gastroenterol 2011; 106: 17051710.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0212 LEARNING CURVE FOR ENDOSCOPIC ULTRASONOGRAPHY
IN GASTRIC CANCER T STAGING USING CUMULATIVE SUM
METHOD
C.H. Park1,*, J.C. Park1, E.H. Kim1, D.H. Jung1, H. Chung1, S.K. Shin1,
S.K. Lee1, Y.C. Lee1
1
Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea, Republic Of
INTRODUCTION: One of the most studied tools for the loco-regional staging
of gastric cancer is endoscopic ultrasonography (EUS). The American Society for
Gastrointestinal Endoscopy guideline set 75 examinations as a minimum number
of EUS procedures for mucosal cancer including esophageal, gastric, and rectal
cancer before competency can be determined. The learning curve in the staging of
gastric cancer, however, has not been evaluated.
AIMS & METHODS: We retrospectively reviewed the clinical records of
patients who underwent EUS examinations for gastric cancer, which were performed by trainees, at Severance Hospital, Seoul, Korea, between March 2011
and February 2012. Cumulative summation analysis was applied to assess the
learning curve for EUS T staging in each trainee.
RESULTS: A total of 553 initial EUS examinations for na ve gastric cancer
performed by 4 trainees were enrolled in the study. Final EUS T staging was
determined by experts in 332 gastric cancers, while EUS T staging of other 221
lesions was determined by trainees. Accuracies of EUS examinations performed
by trainees and experts were 72.6% and 84.3%, respectively. Required EUS
examinations for reaching a 1st plateau in each trainee were 20, 41, 60, and 65,
respectively. In addition, poor predictive factors for accurate T staging of gastric
cancer were 2030 mm and 3050 mm of size compared to 20 mm or less of size,
pT2pT4 stages compared to pT1 stage, and EUS T staging by trainees.
CONCLUSION: A threshold number of 75 which is suggested by guidelines may
be acceptable for achieving competency of gastric cancer T staging by EUS.
Disclosure of Interest: None declared
P0213 PROGNOSTIC SIGNIFICANCE OF EUS NON-TRAVERSABILITY
IN PATIENTS WITH LOCALLY ADVANCED SQUAMOUS
ESOPHAGEAL CANCER RECEIVING PREOPERATIVE
CHEMORADIOTHERAPY
C.J. Cho1,*, H.J. Song1, J.S. Lee1, J.Y. Ahn1, J.H. Lee1, D.H. Kim1, K.-S. Choi1,
K.D. Choi1, G.H. Lee1, H.-Y. Jung1, J.-H. Kim1
1
Division of Gastroenterology, Department of Internal Medicine, University of
Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: formidable1981@gmail.com
INTRODUCTION: Although endoscopic ultrasonography (EUS) is the most
accurate loco-regional staging modality for squamous esophageal cancer (EC),
approximately 30% of patients cannot complete EUS due to malignant stenosis
(EUS non-traversability). Malignant stenosis has reportedly been associated with
advanced tumor stage. However, to date, no study has assessed clinical implications of EUS non-traversable EC stenosis in patients with locally advanced EC
receiving preoperative chemoradiotherapy (CRT).
AIMS & METHODS: This study aimed to examine the clinical implications and
prognostic significance of EUS non-traversability in locally advanced EC
patients treated with preoperative CRT. Data from 89 consecutive patients
with locally advanced and resectable EC (stage II or III) planning preoperative
CRT followed by esophagectomy were retrieved. Relevant clinical and cancerspecific parameters were reviewed retrospectively. Univariate and multivariate
analysis with a Cox model were performed to determine significant factors for
survival.
RESULTS: EUS scope could not pass through EC in 26 of 89 (29.2%) patients.
Between EUS non-traversable and traversable group, dysphagia (88.5% vs.
52.4%; P 0.001), need for stent insertion (30.8% vs. 1.6%; P50.001),
median serum albumin level (3.6 vs. 3.9 g/dL; P 0.028), tumor length (6.0 cm
vs. 4.0 cm; P 0.002), and percentage of stage III disease (65.4% vs. 38.1%;
P 0.019) were significantly different. 79 (88.8%) patients completed preoperative CRT; 22 (84.6%) in non-traversable group and 57 (90.5%) in traversable
group (P 0.426). 70 (78.7%) attained CR or PR. CRT response rates were not
different between non-traversable and traversable group (76.9% vs. 79.4%;
P 0.798). 53 (59.6%) patients underwent esophagectomy; 16 (61.5%) in nontraversable and 37 (58.7%) in traversable group (P 0.806). Median OS of all
patients was 32.8 months (95% CI, 068.2 months) with 5-YSR of 43.8%. Stage
III (P 0.079), non-response to preoperative CRT (P50.001), incompletion of
esophagectomy (P50.001), weight loss 10% (P 0.047), serum albumin level
53.8 g/dL (P 0.035), EUS non-traversability (P 0.025) and tumor length 5
cm (P 0.069) were negative prognostic factors on univariate analysis. Weight
loss 10% (P 0.042), EUS non-traversability (P 0.007), non-response to preoperative CRT (P 0.003), and incompletion of esophagectomy (P 0.002)
remained significant negative prognostic factors of survival in multivariate analysis. EUS non-traversable EC patients had a significantly lower 5-YSR than
those with EUS traversable EC (30.8% vs. 49.3%, P 0.023). 5-YSR was
50.0% for EUS non-traversable EC patients who attained a clinical response
to CRT and also underwent esophagectomy (vs. 64.5% in EUS traversable EC
patients; P 0.153).
CONCLUSION: EUS non-traversability is a significant negative prognostic
factor in patients with locally advanced, resectable EC receiving preoperative
CRT. The clinical implication may arise from incomplete loco-regional EC staging and larger tumor burden. We suggest that treatment should not be discontinued for the patients with EUS non-traversable EC stenosis, given the
acceptable compliance to multimodality therapy and the survival of the patients
who attained a clinical response to CRT and underwent surgery.
Disclosure of Interest: None declared

A189

United European Gastroenterology Journal 2(1S)


P0214 IS THE CORE BIOPSY NEEDLE (PROCORE TM COOK NEEDLE)
THE ALMIGHTY SOLUTION FOR EUS-GUIDED TISSUE
ACQUISITION? A COMPARISON WITH STANDARD EUS-FNA
NEEDLES
C. De Angelis1,*, S. Gaia1, S.F. Manfre1, A. Andrealli1, M. Bruno1, P. Carucci1,
D. Pacchioni1, A. Cassenti1, R. Senetta1, L. Molinaro1, G. Gatti1, A. Sapino1,
M. Rizzetto1
1
Citta` della Salute e della Scienza, Turin, Italy
Contact E-mail Address: eusdeang@hotmail.com
INTRODUCTION: Fine Needle Aspiration (FNA) under Endoscopic
UltraSound (EUS) guidance is an efficient and safe method to obtain tissue
samples from gastro-intestinal tract and from the nearest structures. Whereas
EUS-FNA provides samples of cells without any tissue structure information,
EUS-Fine Needle Biopsy (FNB) has the theorethical advantage to collect tissue
specimens for histological evaluation. The aim of this study is to compare feasibility and diagnostic yield of the newly-developed FNB device (Cook EchoTip
ProCore) with the standard FNA needles.
AIMS & METHODS: 134 patients (75/59 M/F; 6213.5 years) were consecutively enrolled between April 2011 and June 2013, for a total of 137 lesions (mean
size 33.516 mm, range: 6-100 mm): 81 pancreas, 31 lymph nodes, 8 stomach, 7
gut (including 1 papilla), 4 esophagus, 5 aspecific abdominal masses, 1 nervous
ganglia. For each lesion EUS-guided tissue sampling was performed both with
standard needle and with ProCore needle. An expert cytopathologist evaluated
the material giving out a score (0-4) about the adequacy of the samples and
assessing the feasibility of the diagnosis on the samples from the two types of
needle.
RESULTS: A mean of 3.21.1 (range 1-6) and 2.81.1 (range 1-7) needle passes
per lesion were performed with standard needles and ProCore respectively (p:ns).
A core sample adequate for histological assessment from ProCore biopsy was
achieved in 29% lesions (mean length 1.370.7 mm, range 0.5-3.0 mm), with no
difference among the 22, the 19 and the 25 Gauge needle (25%, 46.7% and
33.3% respectively; p: ns). 37% of lesions however fitted for cytological evaluation, whereas 34% were inadequate. There were no statistical difference in the
pathologists adequacy score between the standard needle and the ProCore
needle (2.31.4 and 2.31.4 respectively, p:ns). A final diagnosis was reached
84% cases; 66% of the ProCore samples and 67% of the standard needle samples
(p:ns; Standard Echo alone versus both: p 0.009; ProCore alone versus both: p
0.005). In 16.5% the diagnosis was reached only on the ProCore sample. No
complications were observed.
CONCLUSION: EUS-FNB is feasible and safe, but only in 29% of cases a core
sample adequate for histological evaluation was obtained. The success rate in
reaching the diagnosis is similar with standard needles and with ProCore needles.
However the best results could be reached significantly better with the combination of the 2 type of needle than with EchoTip alone or with ProCore alone (p:
0.009 and p:0.005 respectively) and it seems that the ProCore needle could be
useful especially on fibrotic or hard lesions.
Disclosure of Interest: None declared
P0215 NATURAL HISTORY OF PANCREATIC INTRADUCTAL
PAPILLARY MUCINOUS NEOPLASMS: CLINICAL EVALUATION
OF SENDAI CRITERIA IN A LARGE COHORT OF PATIENTS
E. Dabizzi1,*, M.C. Petrone1, M.E. Traini1, S.G. G. Testoni1, P.A. Testoni1,
P.G. Arcidiacono1
1
Gastroenterology and Digestive Endoscopy, San Raffaele Scientific InstituteUniversita` Vita e Salute, Milano, Italy
Contact E-mail Address: dabizzi.emanuele@hsr.it
INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMN) are
mucin-producing, pancreatic cystic tumors, with a long-term potential for progression to adenocarcinoma. The revised Sendai criteria, based on imaging
features, can differentiate the lesions into high and low risk of progression,
influencing the patient management. However, few data are still available
about clinical management and a better understanding in natural history is
critical.
AIMS & METHODS: To evaluate the natural history of IPMN throughout
clinical follow-up. Second end-point was to assess the clinical correlation between
endoscopic ultrasound features and malignant histology, in order to validate the
Sendai Criteria in our clinical practice. All the patients with pancreatic IPMN,
referred to our tertiary referral center between March 2003 and April 2013 were
enrolled in the study. We divided patients into 3 groups, according to Sendai
criteria: patients with cysts without signs of malignancy (1), patients with cysts
with worrisome features (2) and patients with cysts with high risk stigmata (3).
Data were analyzed using uni variate and multivariate logistic regression, to
assess the risk factors of malignant progression at diagnosis (T0) and at 2
years of follow up (T2).
RESULTS: 371 patients were enrolled in the study period (171 M, mean age 67
years), with a mean follow up of 38 months from 1 up to 106 months (mean 38
mo). 191/371 (52%) pts presented cysts without signs of malignancy, 105/371
(28%) pts cysts with worrisome features and 75/371 (20%) pts cysts with high
risk of malignancy. At multivariate analysis, the features significantly associated
with a higher risk of progression at diagnosis included mass size, pancreatic duct
dilation (p50.001), with an accuracy of 78% and a specificity of 88%. Whereas,
the features with a significantly higher risk of progression at 2 year-follow up
included the pancreatic dilation and the presence of mural nodules (OR 40.01)
(P50.001), with an accuracy of 84% and a specificity of 93%.
CONCLUSION: Our results validated Sendai Criteria in clinical practice.
Therefore, patients with no sign of malignancy and unchanged EUS imaging
can be followed up with a lengthened interval. Due to a high progression rate,

a strict follow up is recommended in pts with worrisome features. Patients with


high risk stigmata need surgery at diagnosis.
Disclosure of Interest: None declared
P0216 AUTOMATIC DETECTION
ENDOSCOPY VIDEO SEGMENTS

OF

SUSPICIOUS

CAPSULE

A. Koulaouzidis1,*, S. Tsevas2, D.K. Iakovidis3


1
Centre for Liver & Digestive Disorders, The Royal Infirmary of Edinburgh,
Edinburgh, United Kingdom, 2Department of Computer Engineering, Technogical
Educational Institute of Central Greece, 3Department of Computer Engieering,
Technological Educational Institute of Lamia, Lamia, Greece
INTRODUCTION: Manual review and annotation of capsule endoscopy (CE)
videos requires a considerable amount of reviewing time. Furthermore, the diagnostic accuracy of this process over lengthy reviewing sessions may decrease
due to reviewers tiredness. Recent studies showed an average detection rate for
the clinically significant findings as low as 40%.[1] We present a generic computational framework for automatic detection of abnormalities in CE videos.
AIMS & METHODS: A CE video (MiroCam, InrtoMedic Co Ltd, Seoul,
Korea), depicting inflammatory changes (aphthae, mucosal breaks, ulcers,
erythema) was reviewed and manually annotated by experienced CE reader. A
total of 1,984 frames, depicting any type of pathology, were thumbnailed. The
proposed framework considers video frames as members of a vector space represented by their colour information. An unsupervised data reduction algorithm,[2]
which does not require any prior knowledge about the data, was then applied on
each segment. This algorithm clusters together frames that exhibit similar characteristics e.g. colour distributions. Its output is a subset of video frames
extracted from each cluster by applying a threshold to the clustering result.
The extracted frames are characteristic of the particular video segment and as
a result representative of possible lesions.
RESULTS: The evaluation of the proposed framework aimed to determine its
accuracy, in terms of the ratio of the neighbourhoods represented by at least one
frame in the systems output and the neighbourhoods that were manually annotated as suspicious for containing lesions. The parameters considered include
clustering from 2 to 6 clusters and thresholds[2] varying from 0.004 to 0.6. The
obtained accuracy ranged between 76% and 98% depending on the desired
sensitivity level of the algorithm, controlled by the threshold. Furthermore, the
automatic selection of the representative CE video segments performed by the
proposed approach, the number of video frames to be thoroughly examined can
be reduced from 30% to 60% of the original video, depending on the clustering
and threshold settings.
CONCLUSION: The application of the proposed framework to the evaluation
of CE videos may reduce the rate of false negative evaluations by attracting the
attention of the reviewer to automatically identified video segments (or single
frames) of interest which are likely to contain lesions.
REFERENCES
1. Zheng Y, Hawkins L, Wolff J, et al. Detection of lesions during capsule
endoscopy: Physician performance is disappointing. Am J Gastroenterol 2012;
107: 554-560.
2. Iakovidis DK, Tsevas S and Polydorou A. Reduction of capsule endoscopy
reading times by unsupervised image mining. Comput Med Imaging Graph 2010;
34: 471478.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
Given Imaging ESGE research grant 2011, Lecture fee(s) from: Dr
FalkPharma, S. Tsevas: None declared, D. Iakovidis: None declared
P0217 WIRELESS CAPSULE ENDOSCOPE LOCALIZATION BASED ON
VISUAL ODOMETRY
A. Koulaouzidis1,*, D.K. Iakovidis2, E. Spyrou2
Endoscopy Unit, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom,
2
Dept of Computer Engineering, Technological Educational Institute of Central
Greece, Lamia, Greece
1

INTRODUCTION: The localization of a wireless capsule endoscope (WCE)


within the small-bowel is typically performed by wearable radiofrequency sensors
triangulation. The accuracy of this approach is low.[1] Only a few approaches
have been proposed for localisation of WCE based on visual features. These
include methods addressing the estimation of the rotation angle of the capsule
[2,3] & temporal video segmentation methods.[4] We present a WCE localization
method, based only on visual information extracted from conventional WCE
recording.
AIMS & METHODS: to check the accuracy of visual odometry in WCE with exvivo data.
Methods: Automatic detection of points of interest (POI) in WCE video frames,
matching of the detected POI between consecutive frames, and determination of
actual correspondences between subsets of these POI based on the random
sample consensus (RANSAC) algorithm was performed. Instead of the speeded
up feature extraction (SURF) algorithm, a maximally stable extremal regions
(MSER) algorithm was used. Based on the scaling & the rotation of the content
of the consecutive WCE frames, it is possible to estimate the displacement & the
rotation of the capsule within the GI tract.
For the ex-vivo experiment a standard simulated intestinal environment was
created. Markers were sewn onto the luminal surface of porcine small-bowel
through which a capsule endoscope (MiroCam, IntroMedic Co Ltd, Seoul,
Korea) was propelled.
RESULTS: Comparative experiments using both SURF and MSER features,
which indicated the superiority of the former over the latter, were conducted.
We worked on a corpus of 1070 WCE frames (634 indicating forward motion,
436 indicating backward motion). The accuracy using SURF features was 81.5%

A190
(87.2% on forward motion, 73.2% on backward motion), while using MSER was
67.2% (79.8% on forward motion, and 48.9% backward motion). Noteworthy,
the proposed algorithm often fails when using MSER (6.7% of frames while
50.1% when using SURF) and a transform is not estimated due to the lack
of adequate correspondences between POI.
CONCLUSION: Visual odometry is a promising technique and -potentially- a
feasible alternative to other localization approaches in WCE.
REFERENCES
1. Than TD, et al. A review of localization systems for robotic endoscopic capsules. IEEE Trans Biomed Eng 2012; 59: 2387-2399.
2. Spyrou E and Iakovidis D. Homography-based orientation estimation for
capsule endoscope tracking. In: Imaging Systems and Techniques (IST), 2012
IEEE International Conference on, 2012, pp. 101105.
3. Mackiewicz M, et al. Wireless capsule endoscopy color video segmentation.
IEEE Trans Med Imaging 2008; 27: 1769-1781.
4. Spyrou E and Iakovidis DK. Video-based measurements for wireless capsule
endoscope tracking. Meas Sci Technol 2014; 25: 015002.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
Given Imaging ESGE research grant 2011, Lecture fee(s) from: Dr
FalkPharmaUK, Other: Material support for research from SynMedUK, D.
Iakovidis: None declared, E. Spyrou: None declared
P0218 UTILITY
OF
THREE-DIMENSIONAL
IMAGE
RECONSTRUCTION IN THE DIAGNOSIS OF OESOPHAGEAL
VARICES
A. Koulaouzidis1,*, A. Karargyris2, Y.L. Ang3, S. Douglas1, E. Rondonotti4,
A.J. Bathgate1, P.C. Hayes3, J.N. Plevris1,3
1
Endoscopy Unit, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom,
2
National Library of Medicine, National Institutes of Health, Bethesda, MD,
United States, 3Medical School, The University of Edinburgh, Edinburgh, United
Kingdom, 4Gastroenterology Unit, Ospedale Valduce, Como, Italy
INTRODUCTION: Oesophagogastroduodenoscopy (OGD) remains the gold
standard for the diagnosis of oesophageal varices (OVs). Oesophageal capsule
endoscopy (OCE) is a non-invasive alternative. However, recent studies showed
that OCE is lagging behind OGD in diagnostic accuracy [1]; it can be an acceptable alternative though in certain situations such as those who cannot tolerate
OGD or are at risk of variant CreutzfeldtJakob disease (vCJD)[2]. Application
of innovative 3D reconstruction software may improve OCE accuracy in the
diagnosis of OVs [3].
AIMS & METHODS: 14 patients, intolerant or with contraindications for conventional OGD e.g. risk for vCJD (for public health purposes), underwent OCE
with PillCamESO1/2. The OCE video recordings (from one of the 2 CE domes)
from the entry in the oesophagus to exit in the stomach were deconstructed to
individual frames. Following 3D reconstruction, the frames were stitched back to
3-D videos. Ten reviewers; 6 GI trainees (novice in CE review), 3 GI specialists
with experience between 20 and 100 CE reviews and 3 expert CE reviewers read
the OCE first in 2-D and then in a GUI (graphic user interface) offering (side-toside) 2-D & 3-D. Furthermore, the consensus opinion of 3 senior hepatologists,
with wide endoscopy experience in patients with liver disease, who reviewed the
OCEs with the GUI was used as reference standard (RS). Interobserver agreement for each of the above groups was checked with kappa () statistics.
When the RS for C2 (i.e. varices requiring treatment) was taken into account, the
negative predictive value (NPV) of the entire group (10 reviewers) for C2 variceal
diagnosis with2-D and 2D3D was calculated.
RESULTS: The interobserver agreement for the entire group, novice, experienced and experts CE reviewers with 2-D was 0.145, 0.118, 0.125 and 0.025,
respectively. The interobserver agreement for the entire group, novices, experienced and expert reviewers with 2-D & 3-D was 0.215, 0.104, 0.222 and 0.372,
respectively. For C2 varices diagnosis (RS), the NPV of 2-D and 2-D & 3-D
review was 66.6% and 80%, respectively.
Limitations: the use of subjective RS.
CONCLUSION: In oesophageal capsule endoscopy, the use of a GUI that
incorporates 2-D and 3-D reconstructed videos leads to improved diagnostic
agreement; furthermore, it improves significantly he NPV of OCE for C2 varices.
Acknowledgement: we thank all those in the 3-D in capsule endoscopy assessment group.
REFERENCES
1. Laurain A, et al. Oesophageal capsule endoscopy versus oesophago-gastroduodenoscopy for the diagnosis of recurrent varices: a prospective multicentre
study. Dig Liver Dis 2014 Mar 12.
2. Millar CM, et al. Risk reduction strategies for variant Creutzfeldt-Jakob disease transmission by UK plasma products and their impact on patients with
inherited bleeding disorders. Haemophilia 2010; 16: 305-315.
3. Rondonotti E, et al. Utility of three-dimensional image reconstruction in the
diagnosis of small-bowel masses in capsule endoscopy. Gastrointes Endosc 2014,
in press.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
ESGE-Given Imaging Research grant 2011, Lecture fee(s) from: Dr
FalkPharmaUK, Other: Material support for research from SynMedUK, A.
Karargyris: None declared, Y. L. Ang: None declared, S. Douglas: None
declared, E. Rondonotti: None declared, A. Bathgate: None declared, P.
Hayes: None declared, J. Plevris: None declared

United European Gastroenterology Journal 2(1S)


P0219 LATERAL-VIEWING CAPSULE ENDOSCOPY
FROM AN ACADEMIC CENTRE IN SCOTLAND

EXPERIENCE

A. Koulaouzidis1,*, L. Bartzis1, S. Douglas1, J.N. Plevris1,2


Endoscopy Unit, The Royal Infirmary of Edinburgh, 2Medical School, The
University of Edinburgh, Edinburgh, United Kingdom
1

INTRODUCTION: CapsoCamSV1 represents a major departure from conventional wireless capsule endoscopy (CE). This CE system utilises on-board data
storage, which necessitates retrieval of the device for data collection. Four lenses
in the middle of the device, offering panoramic views of the bowel lumen, have
replaced a forward-facing lens. Battery life is also increased to 15h by virtue of
a variable image capture rate. Furthermore, the reviewing software provides 4
rectangular panels in a linear sequence, departing from conventional CE reading
software.
AIMS & METHODS: Aim: To report our experience on the clinical use of
CapsoCamSV1 CE.
Setting: An academic hospital, tertiary referral-centre for CE for the South-East
of Scotland.
Methods: Retrospective, single centre, observational study.
RESULTS: Since May 2012, 12 patients (4M/8F, mean age: 67.75 13.5 years; 8
inpatients) underwent CE with CapsoCam following the standard protocol of
our unit. In 80% of patients, the examination was performed for obscure GI
bleeding.
The mean time from capsule ingestion to data upload was 5.6 8.5 days. Two
patients underwent successful endoscopic placement with the AdvanCE delivery
device. The gastric transit time (GTT), small-bowel transit time (SBTT) was 50.9
51.2 min and 5.46 3.15 h, respectively. The mean total working time for
CapsoCam was 14 3 h. Caecal entry was confirmed in 10/12 examinations.
The ampulla of Vater (AoV) was visualised in 2/12 i.e. 20% of cases after correcting for quality of bowel prep (10 good). Diagnostic yield for findings was
33.3%.
CONCLUSION: A significant time interval between capsule ingestion and data
upload is noted. However, capsule retrieval eliminates the need for radiologic
confirmation of capsule excretion in cases of incomplete enteroscopy. The
AdvancCE delivery can be used for CapsoCam endoscopic placement. The
diagnostic yield and the rate of identification of the AoV is comparable to forward-viewing CE devices.
REFERENCES
1. Friedrich K, et al. First clinical trial of a newly developed capsule endoscope
with panoramic side view for small bowel: a pilot study. J Gastroenterol Hepatol
2013; 28: 1496-1501.
2. Pioche M, et al. French Society of Digestive Endoscopy (SFED). Prospective
randomized comparison between axial- and lateral-viewing capsule endoscopy
systems in patients with obscure digestive bleeding. Endoscopy. Epub ahead of
print 27 November 2013.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
ESGE Given Imaging research grant 2011, Lecture fee(s) from: Dr
FalkPharma UK, Other: Dr FalkPharmaUK, Abbott, MSD,Almiral, L.
Bartzis Other: grant from the Hellenic Society of Gastroenterology, S.
Douglas: None declared, J. Plevris: None declared
P0220 OPTIMAL TIMING OF VIDEO CAPSULE ENDOSCOPY IN
OVERT OBSCURE GI BLEEDING PATIENTS
S.H. Kim1, I.K. Yoo1, J.M. Lee1, S.J. Nam1, H.S. Choi1, E.S. Kim1, B. Keum1,
Y.T. Jeen1,*, H.S. Lee1, H.J. Chun1, C.D. Kim1
1
Department of Internal Medicine, Division of Gastroenterology and Hepatology,
Korea University Anam Hospital, Seoul, Korea, Republic Of
Contact E-mail Address: kimseunghan09@gmail.com
INTRODUCTION: Video capsule endoscopy (VCE) is crucial examination for
diagnosis of small bowel bleeding. But diagnostic yield of VCE is 38% to 83% in
overt obscure gastrointestinal bleeding (OGIB). For an accurate diagnosis of
cause of overt OGIB, the timing to perform VCE is the valuable factor. This
study is to investigate the diagnostic yield, rate of therapeutic intervention, and
prognosis according to the timing of VCE in the overt OGIB patients.
AIMS & METHODS: We conducted a single center, retrospective study at
Korea University Medical Center Anam Hospital from April 2008 to February
2014. Patients who presented overt OGIB with negative result of initial upper and
lower endoscopy were enrolled. We compared the diagnostic yield, rate of therapeutic intervention, length of hospital stay, and rate of re-bleeding between
patients with VCE performed in 48hrs and 448hrs after the occurrence of
overt OGIB. We defined positive finding as active bleeding or any cause of
small bowel bleeding.
RESULTS: In 111 patients, VCE were performed to evaluate overt OGIB during
the period. Among them, 90 patients were included and 21 patients who lacked of
medical records were excluded. Diagnostic yield was 65.51% in 48hrs group
and 35.59% in 448hrs group (p 0.037). Therapeutic intervention was done in
45% of the 48hrs group and 14% of 448hrs group (p 0.006). The average
day of hospital stay was 5.48 days in 48hrs group and 8.18 days in 448hrs
group (p 0.005). Re-bleeding rate between the 48-hrs group and 448-hrs
group was not significantly different.
CONCLUSION: Early VCE deployment within 48hrs of last overt OGIB may
improved the diagnostic yield, rate of therapeutic intervention and decreased the
length of hospital day.
REFERENCES
Yamada A, Watabe H, Kobayashi Y et al. Timing of capsule endoscopy influences the diagnosis and outcome in obscure-overt gastrointestinal bleeding.
Hepato-gastroenterology 2012; 59: 676-679.

A191

United European Gastroenterology Journal 2(1S)


Singh A, Marshall C, Chaudhuri B, et al. Timing of video capsule endoscopy
relative to overt obscure GI bleeding: implications from a retrospective study.
Gastrointes Endosc 2013; 77: 761-766.
Disclosure of Interest: None declared
P0221 THROMBOCYTOSIS AND HIPOALBUMINEMIA: A PRIORITY
PASS FOR CAPSULE ENDOSCOPY IN CROHNS DISEASE?
B. Rosa1,*, H. Cardoso2, M.J. Moreira1, P. Boal Carvalho1, S. Lopes2,
S. Rodrigues2, M. Marques2, F. Magro2, C. Dias3, G. Macedo2, J. Cotter1
1
Gastroenterology, Centro Hospitalar do Alto Ave, Guimaraes, 2Gastroenterology,
Hospital Sao Joao, 3Biostatistics and Medical Informatics, Faculty of Medicine of
Porto University, Porto, Portugal
Contact E-mail Address: bruno.joel.rosa@gmail.com
INTRODUCTION: Small bowel capsule endoscopy (SBCE) may identify small
bowel lesions in a large proportion of patients with Crohns disease (CD).
AIMS & METHODS: To identify predictive factors of small bowel involvement
in a cohort of patients with CD. Transversal multicenter study including consecutive patients with CD affecting the small bowel over a period of eight years.
Small bowel inflammatory activity at SBCE was assessed with the Lewis Score
(LS), and it was considered clinically relevant if LS135. Univariate analysis and
multivariate regression of patients baseline clinical, analytical and endoscopic
(index ileocolonoscopy) variables were performed to identify pre-test predictors
of relevant (LS135) lesions at SBCE in patients with known or suspected CD.
RESULTS: A total of 158 patients were included, 58% female, mainly with ileal
(42%) or ileocolic (39%) location at ileocolonoscopy, non-stricturing non-penetrating behaviour in 74% of cases. SBCE lesions were non-significant (LS5135)
in 34 (22%) patients, mild (135LS5790) in 68 (43%) and moderate to severe
(LS4790) in 55 (35%). Lesions were located in the first tertile of the small bowel
in 38 (24.1%) patients, second tertile in 48 (30.4%) and third tertile in 113
(71.5%) patients. Multivariate regression identified thrombocytosis [OR 1,012
(95% CI: 1.002-1.022), p 0.019] and low serum albumin [OR 0.803 (95% CI:
0.663-0.971), p 0.023] as independent variables predictive of small bowel CD,
[ROC 0.846 (0.767-0.925)]. Clinical features, endoscopic distribution of the
disease at ileocolonoscopy, and biomarkers such as anaemia or C-reactive protein were not predictive of SBCE lesions.
CONCLUSION: In patients with known or suspected CD, thrombocytosis and/
or hipoalbuminemia are predictive of active small bowel inflammation at SBCE.
Whether these biomarkers should play a role in the selection of patients for
SBCE warrants further prospective evaluation.
Disclosure of Interest: None declared
P0222 DOES CAPSULE ENDOSCOPY WITH
VISIBILITY OF SMALL BOWEL LESIONS?

ALICE

IMPROVE

C.B. Ryu1,1,*, M.S. LEE1, J.Y. BAE2, J.Y. SONG3


Department of Internal Medicine, Soon Chun Hyang University School of
Medicine, Bucheon, 2SEOUL MEDICAL CENTER, SEOUL, 3SUWON
MEDICAL CENTER, SUWON, Korea, Republic Of
Contact E-mail Address: ryuchb@gmail.com

P0223 UTILITY OF FECAL CALPROTECTIN IN THE EVALUATION OF


PATIENTS WITH CROHNS DISEASE CANDIDATES FOR CAPSULE
ENDOSCOPY: PRELIMINARY RESULTS
C. Romero Mascarell1,*, C. Rodriguez De Miguel1, I. Ordas Jimenez1, E. Ricart
Gomez1, A. Jauregui Amezaga1, A. Ramirez Morros1, M. Gallego Barrero1,
J. Llach Vila1, J. Panes D az1, B. Gonzalez Suarez1
1
Gastroenterology, Hospital Clinic de Barcelona, Barcelona, Spain
Contact E-mail Address: bgonzals@clinic.ub.es; crromero@clinic.ub.es
INTRODUCTION: Small bowel capsule endoscopy (SBCE) is an expensive but
useful imaging method in the diagnosis and extension of Crohns disease (CD).
Symptomatology and acute phase reactants (CRP and ESR) are not correlated
with the presence of endoscopic activity in small Bowel. Fecal calprotectin (FC)
is a biomarker that correlates well with small bowel inflammation.
AIMS & METHODS: The aim of our study is to assess if fecal calprotectin
correlates with the presence of endoscopic activity in small Bowel, evaluated
by capsule endoscopy (Lewis Score).
We included prospectively patients with suspected or diagnosed Crohns disease
referred for capsule endoscopy. All of them were submitted to SBCE and a
measure of FC, ESR, and CRP. CDAI was also registered.
RESULTS: For this preliminary analysis, 30 patients were included (17 females and
13 males), mean age 38 /- 13 years. The indication for capsule endoscopy was
suspected CD (7 patients), extension study of the illness and/or lack of response to
treatment (21 patients) and mucosal healing assessment (2 patients). One patient was
excluded for the analysis because of the capsule was retained in stomach temporarily.
Only 10% of patients had FC levels less than 100 mcg/g, two of them with no
lesions in capsule endoscopy. FC levels higher than 100 mcg/g correlated more
closely with the presence of lesions in capsule endoscopy (p 0.006).
In our study, there is a slight but positive correlation between FC levels and
Lewis Score (r 0.4; p 0.02). There is no correlation between clinical symptoms, CRP or ESR, and the presence of lesions in the capsule endoscopy.
CONCLUSION: Fecal Calprotectin seems to be useful in identifying patients
with Crohns Disease and small bowel involvement. It can be a good tool to select
patients for performing capsule endoscopy
Disclosure of Interest: None declared
P0224 ABSENCE OF MUTUAL INTERFERENCE BETWEEN MIROCAM
CAPSULE ENDOSCOPY, PACEMAKERS AND IMPLANTABLE
CARDIAC DEFIBRILLATORS: A CLINICAL
ELECTROPHYSIOLOGICAL STUDY
D. Moneghini1,*, A. Lipari2, G. Missale1, L. Minelli1, G. Cengia1, L. Bontempi2,
A. Curnis2, R. Cestari1
1
Digestive Endoscopy, 2Electrophysiology and Electrostimulation Lab, SPEDALI
CIVILI - UNIVERSITY OF BRESCIA, Brescia, Italy
Contact E-mail Address: dario.moneghini@spedalicivili.brescia.it

INTRODUCTION: ALICE (Augmented Live-body Image Color-spectrum


Enhancement) refers to a spectral imaging technique for the MiroView (TM)
system to perform medical tests through capsule endoscope (CE) system,
where light of specific blue, green, and red wavelength is used to enhance the
detail of certain aspects of the surface of the mucosa, but the data was limited.
AIMS & METHODS: This study is to evaluate the visibility of CE-ALICE
depending on type of small bowel lesions.
A total of 50 patients who underwent CE at Soon Chun Hyang Bucheon
Hospital from August 2008 to November 2011 were enrolled in this study. The
lesions were classified as elevated (tumor and polyp, n 5), flat (angiodysplasia
and erosion, n 18), depressed (ulcer, n 27) lesions. Two experienced endoscopists analyzed CE-ALICE images obtained at setting 1-10 (setting 1: red 415 nm,
green 415 nm, blue 540 nm; setting 2: red 415 nm, green 445 nm, blue 500 nm;
setting 3: red 420 nm, green 470 nm, blue 500 nm; setting 4: red 400 nm, green 445
nm, blue 450 nm; setting 5: red 420 nm, green 480 nm, blue 540 nm; setting 6: red
420 nm, green 480 nm, blue 500 nm; setting 7: red 400 nm, green 500 nm, blue 450
nm; setting 8: red 455 nm, green 455 nm, blue 500 nm; setting 9: red 500 nm,
green 455 nm, blue 455 nm; setting 10: red 455 nm, green 500 nm, blue 455 nm)
compared with conventional images. Physicians rated the visibility of the lesions
on ALICE images as follows: _2(improved visibility), _1 (somewhat improved
visibility), 0 (visibility equivalent to that of conventional video CE visibility), _1
(somewhat decreased visibility), and _2 (decreased visibility). Scores for each
lesion were totaled (per ALICE setting) and evaluated. Intraobserver agreement
was also examined.
RESULTS: In elevated lesion (n 5), with setting 2, 3, 4, 5, 6, 7, 9, 10, improvement was achieved but not significantly statistical (NS). In flat lesion (n 18),
with setting 3, 5, 10, improvement was achieved statistically for 100% (18/18),
100% (18/18), 100% (18/18) (p50.01). In depressed lesion (n 27), with setting
2, 3, 6, 10, improvement was achieved statistically for 89% (24/27), 93% (25/27),
93% (25/27), 85% (23/27)
CONCLUSION: CE-ALICE improves visibility of flat and depressed lesion in
small bowel.
Disclosure of Interest: None declared

INTRODUCTION: Capsule endoscopy (CE) has recently become one of the


most important tools for small bowel investigation. Once swallowed by the
patient, Mirocam capsule transmits images from the gut to an external recorder
by the Human Body Communication (HBC) system. HBC uses the capsule itself
to generate an electrical field and uses the human body as the conductor for data
transmission. Because of the creation of an electric field, a potential electromagnetical interference with implantable cardiac devices has been postulated, so their
presence is considered a relative contraindication for CE. Whereas some safety
data are available about Given M2A capsule in patients with pacemakers (PM)
and automatic implantable cardiac defibrillators (AICD), studies in this field
regarding Mirocam capsule are lacking.
AIMS & METHODS: We report the use of Mirocam video capsule system
(Intromedic Co Ltd, Seoul, Korea) in 6 patients with PM and in a patient with
AICD over a 2-years period. Patients swallowed the capsule in the morning after a
overnight fast; a bowel cleansing with 2 litres of polyethylene glycol (PEG) solution
was administered in the afternoon before the procedure. All patients gave their
written informed consent. Three different type of PM from 2 manufacturers
(Altura and Insignia Ultra from Boston Scientific Corporation, Esprit from Sorin)
and Atlas AICD from St. Jude Inc. were tested. A full technical control of the cardiac
devices was performed by electrophysiologists before CE examination, using a manufacturer-specific programmer. This technical control included the evaluation of the
following parameters: battery charge, shock impedance, leads impedance and sensing, leads pacing threshold, arhythmic events. After a cardiac visit and electrocardiogram (ECG), each patient was placed in Cardiac Care Unit. AICD electrical
therapies were switched off just before capsule ingestion. During CE the patients
were continuously monitored with cardiac telemetry, performed by Mortara X12
device (Mortara Instrument Inc., U. S. A.). At the end of the endoscopic procedure,
before discharge, the patients repeated cardiac evaluation, ECG and a complete
cardiac device check. The following characteristics were analyzed: changes in
device parameters, inappropriate shocks, inappropriate anti-tachycardia therapy,
inappropriate sensing or pacing, noise detection, device reset, programming changes,
permanent electrical damages. CE records were reviewed by a skilled endoscopist.
RESULTS: For 6 patients indication for CE was obscure gastrointestinal bleeding (OGIB), in one was follow up of intestinal polyposis. Mean age was 74 years;
all the patients were males. Capsule reached ileo-cecal valve in all except two
cases. No complications related to capsule transit were observed. No technical
problems related to imagine transmission were recorded. Causes of OGIB were
found in 50% of cases. No polyps were found in patient with polyposis. No
cardiac devices malfunctions nor interference in sensing or pacing were recorded;
conversely, no malfunctions of CE caused by PM or AICD were registered.
CONCLUSION: Our results suggest that Mirocam capsule endoscopy can be
safely performed in patients with different types of implantable cardiac devices.
Disclosure of Interest: None declared

A192
P0225 SELF-EXPANDABLE METAL STENTS VERSUS PLASTIC
STENTS FOR MALIGNANT BILIARY OBSTRUCTION: CLINICAL
OUTCOME AND COST-EFFECTIVENESS IN POLISH ECONOMIC
CIRCUMSTANCES
A. Budzynska1,*, E. Nowakowska-Dulawa1, T. Marek1, M. Hartleb1
1
Dept. of Gastroenterology&Hepatology, Medical University of Silesia, Katowice,
Poland
Contact E-mail Address: budzynskaagnieszka@poczta.onet.pl
INTRODUCTION: Most patients with malignant biliary obstruction are suited
only for palliation of jaundice by endoscopic placement of a plastic stents (PS) or
self-expandable metal stents (SEMS). The initial higher cost of the SEMS is
considered to be balanced by a decreased need for repeated interventions.
AIMS & METHODS: To compare the clinical outcome and costs of biliary
stenting with SEMS and PS in patients with malignant biliary strictures. A
total of 114 pts (63F, 51M) who underwent 366 endoscopic retrograde biliary
drainage (ERBD) for palliation of unresectable malignant biliary obstruction
between 2009 and 2014 were retrospectively enrolled into the study.
RESULTS: ERBD with placement of PS was performed in 80 patients, with onestep SEMS insertion (direct placement without a prior plastic stent) in 20 patients
and two-step SEMS insertion (placement of SEMS at second or consecutive
endoscopic retrograde cholangiopancreatography following plastic stent placement, e.g. SEMS after PS) in 14 patients. Significantly less endoscopic procedures
were performed in patients with one-step SEMS than PS alone and two-step
SEMS technique (2.01.12, 3.11.7 and 5.72.1 respectively, p50.0001). The
median hospitalization time was similar for three groups of patient. The patients
survival was longest in SEMS after PS group in comparison to SEMS group and
PS group (596.2270d, 276.1141d and 207.5219d, p50.001). Overall median
stent patency was 89.3159 d for PS and 120.6101 for SEMS (p 0.01). Stent
dysfunction occurred more frequently in PS group than in SEMS groups (76.8%
vs. 62.8%, p 0.05). No significant difference between the two stent types in
terms of technical success and complications was observed. The mean total
cost of hospitalization with drainage procedures was higher for SEMS group,
then for SEMS after PS group and finally for PS group (1448312E, 1152135E
and 977156E, p50.0001). Estimated annual cost of subsequent ERBD due to
recurrent biliary obstruction would be still higher for SEMS group than for PS
group (4618E vs. 3995E). Metal stents would be cost-effective if their patency
exceed 202 days.
CONCLUSION: Biliary decompression by metal stents in patients with malignant jaundice is associated with longer patency and reduced number of additional biliary procedures, but repeated plastic stents drainage is still more costeffective strategy.
Disclosure of Interest: None declared
P0226 OUTCOMES OF PRIMARY AND REVISION EFFICACY OF
COMBINED METALLIC STENTS IN MALIGNANT DUODENAL
AND BILIARY OBSTRUCTIONS
D.F. B. Carvalho1,*, J. Canena1,2, J. Coimbra1, C. Rodrigues2, M. Silva1,
M. Costa1, D. Horta2, A. Mateus-Dias1, I. Seves1, G. Ramos1, L. Ricardo2,
A. Pereira Coutinho3, C. Romao3
1
Gastroenterology, Hospital Santo Antonio dos Capuchos - Centro Hospitalar
Lisboa Central, Lisbon, 2Gastroenterology, Hospital Professor Doutor Fernando
Fonseca, Amadora, 3Gastroenterology, Hospital Pulido Valente - Centro
Hospitalar Lisboa Norte, Lisbon, Portugal
Contact E-mail Address: dianafbcarvalho@gmail.com
INTRODUCTION: Self-expandable metal stents (SEMSs) can be used for palliation of combined malignant biliary and duodenal obstructions. However, the
results of the concomitant stent placement for the duration of the patients lives,
as well as the need for and efficacy of endoscopic revision, are unclear.
AIMS & METHODS: This study evaluated the clinical effectiveness of SEMS
placement for combined biliary and duodenal obstructions throughout the
patients lives and the need for endoscopic revision. This study is a retrospective
multicenter study of 50 consecutive patients who underwent simultaneous or
sequential SEMS placement for malignant biliary and duodenal obstructions.
The data were collected to analyze the sustained relief of obstructive symptoms
until the patients death and the efficacy of endoscopic revision, as well as stent
patency, adverse events, survival and prognostic factors for stent patency.
RESULTS: Technical and immediate clinical success was achieved in all of the
patients. Duodenal stricture occurred before the papilla in 35 patients (70%),
involved the papilla in 11 patients (22%) and was observed distal to the papilla in
4 patients (8%). Initial biliary stenting was performed endoscopically in 42
patients (84%) and percutaneously in 8 patients. After combined stenting, 30
patients (60%) required no additional intervention until the time of their
death. The remaining 20 patients were successfully treated using endoscopic
stent reinsertion: 9 patients needed biliary revision, 3 patients needed duodenal
restenting and 8 patients needed both biliary and duodenal reinsertion. The
median duodenal stent patency and median biliary stent patency were 34
weeks and 27 weeks, respectively. The median survival after combined stent
placement was 12 weeks. A Cox multivariate analysis showed that duodenal
stent obstruction after combined stenting was a risk factor for biliary stent
obstruction (Hazard ratio 6.85; 95% CI 1.43-198.98; P 0.025).
CONCLUSION: Endoscopic bilio-duodenal bypass is clinically effective, and the
majority of the patients need no additional intervention until their death.
Endoscopic revision is feasible and has a high success rate.
Disclosure of Interest: D. Carvalho: None declared, J. Canena Consultancy for:
Boston Scientific, J. Coimbra: None declared, C. Rodrigues: None declared, M.
Silva: None declared, M. Costa: None declared, D. Horta: None declared, A.
Mateus-Dias: None declared, I. Seves: None declared, G. Ramos: None declared,

United European Gastroenterology Journal 2(1S)


L. Ricardo: None declared, A. Pereira Coutinho: None declared, C. Romao:
None declared
P0227 TEMPORARY ENDOSCOPIC INSERTION OF UNILATERAL OR
BILATERAL COVERED SELF-EXPANDABLE METAL STENTS
(CSEMS) ABOVE THE HEPATIC DUCT CONFLUENCE FOR BENIGN
BILE-DUCT DISEASE
P. Gil-Simon1, N. Aleman2, I. Penas Herrero1,*, A. Vargas2, R. Sanchez-Ocana2,
F. Santos1, C.de la Serna1, M. Perez-Miranda2
1
endoscopy, 2Hospital Universitario Ro Hortega, Valladolid, Spain
Contact E-mail Address: pgpaula@hotmail.com
INTRODUCTION: cSEMS appear to enhance therapeutic efficacy for benign
distal bile-duct strictures and leaks. Concerns over the use of cSEMS above the
hepatic duct confluence remain since clinical data are very limited. Aim: To
assess the feasibility and efficacy of cSEMS placement proximal to the hepatic
duct confluence in benign disease.
AIMS & METHODS: Retrospective analysis of prospectively databased patients
undergoing ERCP over a 10-month period at referral Unit. 34 Consecutive
Patients (17 female; age 59 [32-87] years) underwent biliary cSEMS placement
across the hilum for benign disease. Underlying diagnosis, number and type of
cSEMS, presence of associated plastic stents, indication for cSEMS (primary vs.
failed prior plastic stenting), duration of stenting, ease of removal, procedural &
stent related complications, and final therapeutic outcome were determined.
RESULTS: Diagnoses: 28 biliary strictures (13 postcholecystectomy, 11 postliver transplant, 4 undetermined) and 6 miscellaneous (2 high output fistulas, 2
with prior embedded uncovered SEMS, 1 sump syndrome, 1 primary sclerosing
cholangitis). In 19.4%, 2 or 3 biliary cSEMS were placed. The contralateral
hepatic duct was stented with a plastic stent in 80.6%. Transhilar biliary
cSEMS were indicated primarily in 14 (41%) and as salvage of prior standard
plastic stenting in the remainder 20. CSEMS used were all 10mm in diameter,
Hanaro 23, Wallflex 8, Bonastent 2, Taewoong 1. There were 2 procedural
complications related to cSEMS, one moderate cholangitis secondary to hepatic
branch occlusion (requiring cSEMS removal), and one mild (pain requiring IV
analgesia 424 hours). After a mean duration of stenting of 5.3 (1-15) months,
removal was attempted in 64.3% and was technically successful in all 20 cases
despite 4 partial migrations (3 proximal/ 1 distal; 2 with cholangitis, 2 asymptomatic). Strictures/leaks were successfully remodeled/controlled upon removal in
19/20 (1 persistent leak), pending long-term follow-up. 11 patients are still undergoing cSEMS replacement. Transient enlargement of the intrahepatic bile-duct
was documented in 12/31, without any adverse clinical consequences. Overall
complication & short-term success rates are 13% & 95%.
CONCLUSION: If the contralateral hepatic duct is stented and ipsilateral secondary radicals spared, transhilar cSEMS placement appears safe. Refractory
benign disease can successfully be salvaged with this aggressive approach, with
an acceptable safety profile. Transient intrahepatic duct enlargement was noted.
This encouraging preliminary data warrant further study as the long-term efficacy and reproducibility of this approach remain in question.
Disclosure of Interest: None declared
P0229 PREOPERATIVE BILIARY DRAINAGE WITH A MODIFIED
FULLY COVERED SELF-EXPANDABLE METALLIC STENT FOR
POTENTIALLY RESECTABLE DISTAL MALIGNANT BILIARY
OBSTRUCTION
J.H. Moon1,*, H.J. Choi1, Y.N. Lee1, H.J. Jung1, M.H. Choi1, T.H. Lee1, S.W. Cha1, Y.D. Cho1, S.-H. Park1, S.-J. Kim1
1
Department of Internal Medicine, SoonChunHyang University School of
Medicine, Bucheon, Digestive Disease Centerand Research Institute, Bucheon,
Korea, Republic Of
Contact E-mail Address: 95970@schmc.ac.kr
INTRODUCTION: Early biliary decompression is indicated for cholangitis in
patients with malignant biliary obstruction (MBO). However, preoperative biliary
drainage using plastic stents may increase the need of reintervention and perioperative complications. We evaluated the usefulness of a removable fully covered selfexpandable metallic stent (FCSEMS) modified to minimize stent-induced complications in preoperative biliary drainage for potentially resectable distal MBO.
AIMS & METHODS: From January 2009 to Agust 2013, a total of 51 patients
underwent biliary drainage using a modified FCSEMS (BONASTENT MIntraductal, Standard Sci Tech Inc, Seoul, Korea) for suspicious distal MBO
that was potentially resectable or on stage work-up. Further treatment was
decided according to the final assessment; (1) curative intent surgery, (2) neoadjuvant chemoradiation, (3) palliative treatment with/without chemoradiation, or
(4) removal of stent for finally proved benign biliary stricture.
RESULTS: The overall technical and clinical success rates of the biliary drainage
using a modified FCSEMS were 100% (51/51). Complications related with stenting were developed in 5 patients (1 mild pancreatitis and 4 stent migrations).
Final diagnosis was 46 MBS (24 pancreatic head cancers, 18 CBD cancers, 3
gallbladder cancers and 1 ampullay cancer) and 5 benign biliary strictures (3
chronic pancreatitis and 2 autoimmune pancreatitis). 19 patients had undergone
curative intent pancreaticoduodenectomy. 3 patients had undergone surgical
resection after neoadjuvant chemotherapy. No stent-induced postoperative complication occurred. The median stent patency in patients who had undergone
palliative treatment was 148 days (range, 73-256). Removal of the stent was
successful in all patients confirmed finally benign biliary strictures.
CONCLUSION: The modified FCSEMS may be effective for first line of biliary
drainage in patients with potentially resectable distal MBO without interfere for
further intervention.
Disclosure of Interest: None declared

A193

United European Gastroenterology Journal 2(1S)


P0230 DOES CHEMOTHERAPY PROLONG THE STENT PATENCY IN
MALIGNANT DISTAL BILIARY STRICTURE?
M. Kida1,*, S. Miyazawa1, S. Tokunaga1, H. Yamauchi1, K. Okuwaki1, T. Iwai1,
M. Takezawa1, M. Watanabe1, H. Imaizumi1, W. Koizumi2
1
Endoscopy Center, 2Gastroenterology, KITASATO University Hospital,
Sagamihara, Japan
Contact E-mail Address: m-kida@kitasato-u.ac.jp
INTRODUCTION: Metallic stents for malignant distal biliary stricture have
become one of the best palliative treatments in inoperative cases who were generally treated by chemotherapy; however its influence in stent patency has not
been investigated and consensus is not established.
AIMS & METHODS: From 2002 to 2013, we have inserted metallic stents in
totally 259 cases with malignant distal biliary stricture, and treated 164(63%)
caes with chemotherapy and remaining 95(37%) cases with best supportive care
(BSC). We investigated the efficacy of chemotherapy in its stent patency etc.
retrospectively.
RESULTS: Subjects in this study were consisted of 206 (80%) pancreas cancers,
45(14%) biliary cancers, and 8(3%) papillary cancers. Metallic stents we used
were 152(59%) partially covered Wallstents (P-WS), 54(21%) partially covered
Wallflexs (P-WF), 34(13%) fully covered Wallflexs (F-WF), and 19(7%) fully
covered Bonastents (F-BS). There was no significant difference on base line
characteristics between chemotherapy group and BSC group except for age (68
vs 74 years olds). Chemotherapy we employed was Gemcitabine (GEM) alone,
GEM TS-1, and GEMTS-1CDDP etc. The median stent patency was 328
days in total, and the median stent patency of chemotherapy group was significantly longer (354 days vs188 days in BSC, p 0.001). The median stent patency
of biliary cancer in chemotherapy group was significantly longer (341 days vs 119
days in BSC, p 50.001), whereas the median stent patency of pancreas cancer
in chemotherapy group was not significant.
CONCLUSION: We concluded that chemotherapy prolong the stent patency in
malignant distal biliary stricture, especially biliary cancers.
Disclosure of Interest: None declared
P0231 ENDOSCOPIC DOUBLE SELF-EXPANDING METAL STENT
PLACEMENT FOR THE TREATMENT OF MALIGNANT BILIARY
AND GASTRODUODENAL OBSTRUCTION: A LARGE SERIES OF
TREATED PATIENTS FROM A REFERRAL HOSPITAL FOR
PALLIATIVE CARE
R. Di Mitri1,*, F. Mocciaro1, G.M. Pecoraro1
1
Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli
Hospital, Palermo, Italy
Contact E-mail Address: fmocciaro@gmail.com
INTRODUCTION: Patients with malignant gastroduodenal obstruction often
have coexistent biliary obstruction and require simultaneous endoscopic treatment. The use of self-expandable metal stents (SEMS) is an effective palliative
treatment in patients with unresectable malignant gastroduodenal and biliary
obstructions.
AIMS & METHODS: The aims of this study are to evaluate the efficacy and
safety of double SEMS placement in a large consecutive series of patients with
malignant inoperable gastroduodenal and biliary obstruction. From March 2007
to March 2014 we collected data on all consecutive patients treated with double
SEMS placement (Wallflex Enteral and Biliary by Boston Scientific, Niti-S
Biliary by Taewoong). SEMS were placed under fluoroscopic and endoscopic
guidance. First the scope was allowed to reach the duodenal stricture, then a
guidewire equipped with an imaging catheter was passed through the stricture
allowing the deployment of the duodenal SEMS. The duodenoscope was passed
through the duodenal stent for accessing the papilla through the mesh of the
SEMS. After common bile duct cannulation and cholangiography a guidewire
was placed across the papilla. A balloon dilation to enlarge the spacing of the
tight mesh of the duodenal stent was performed allowing the placement of the
biliary SEMS. If possible balloon dilation of the duodenal stricture was performed allowing the deployment of the biliary SEMS before duodenal SEMS
placement. Technical and clinical success, and adverse events were recorded.
RESULTS: 31 patients (20 male [65%]), with a mean age of 73.69.8 year, were
treated: 27 had pancreatic head cancer (87%), 2 antro-bulbar cancer (7%), 1
cholangiocarcinoma (3%), 1 duodenal obstruction due to colon cancer (3%).
The mean baseline bilirubin level and the median gastric outlet obstruction scoring system (GOOSS) score were 16.73.8 mg/dL and 1 (range 0-3) respectively.
Technical success was achieved in all patients with significant reduction in bilirubin levels (8.43.2 mg/dL) and a satisfactory oral feeding at discharge (GOOSS
score 3 [range 2-3]). No complications related to the SEMS placement were
recorded. Biliary stent occlusion occurred in 2 patients (6%) after 3 and 10
months. In 1 patient (3%) migration of the biliary stent was recorded after 5
months. The median hospital stay was 4 days (range 3-8) with a median survival
time of 6 months (range 3-8). All deaths were due to the natural course of underlying malignancy.
CONCLUSION: Endoscopic management of malignant gastroduodenal and
biliary obstructions with double SEMS placement is the treatment of choice in
advanced unresectable gastroduodenal tumors with biliary involvement too. It is
a safe procedure and it enhances patients quality of life. In advanced diseases or
in frail patients palliative surgery should be considered only in case of endoscopic
failure.
Disclosure of Interest: None declared

P0232 COMPARISON OF OUTCOMES BETWEEN INTERNAL STENT


PLACEMENT AND PTBD IN PATIENTS WITH PLANNED CRT FOR
PERIHILAR CHOLANGIOCARCINOMA
S.W. Yi1,*, J.H. Cho2, J.B. Chung3, S.W. Park3, S.Y. Song3, S. Bang3
1
Internal medicine, Division of Gastroenterology, International St. Marys
Hospital, 2Internal medicine, Gachon University Gil Medical Center, Incheon,
3
Internal medicine, Division of Gastroenterology, Yonsei University College of
Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: sinbbori97@naver.com
INTRODUCTION: The optimal biliary decompression method in resectable
perihilar-cholangiocarcinoma has been authorized as percutaneous transhepatic
biliary drainage (PTBD). In case of locally advanced perihilar-cholangiocarcinoma, malignant biliary obstruction is judged to have palliation of jaundice by
placement of an internal stents or PTBD. We aimed to investigate the efficacy of
internal placement of biliary stent compared with PTBD for patients planned
CRT in locally advanced perihilar-cholangiocarcinoma.
AIMS & METHODS: The patients who are histologically proven locally
advanced perihilar-cholangiocarcinoma between Jan. 1995 and Dec. 2013 at
single tertiary medical center in Korea, analyzed as prospective observational
study. The perihilar cholangiocarcinoma was defined as disease occurring above
the junction of the cystic duct up to the secondary branches of the hepatic duct.
RESULTS: Among one hundred seventy six locally advanced perihilar-cholangiocarcinoma patients, CRT was performed in 79 patients; endoscopic biliary
decompression was forty six patients (26.14%), and PTBD was thirty three
patients (18.75%). The mean period of internal stent indwelling is 152 days
whereas 222 days in PTBD group (p 0.675). The R0 operative rate after the
CRT was 23.9% in endoscopic stenting group, and 12.1% in PTBD group
(p 0.174). The median overall survivals were 463 days at endoscopic stenting
group and 439 days in PTBD group, respectively (p 0.874). Repeated biliary
decompression procedure was performed at endoscopic decompression group 26
patients (56.5%), 12 patients in PTBD group (36.4%) (p 0.077).
In the subgroup analysis of endoscopic stenting group, there were 25 cases of
SEMS, and 21 cases of biliary drainage using the plastic stent. The stent dysfunction was found in 20 patients (80.0%) with plastic stent and 6 patients (28.6%) in
SEMS group (p 0.001). Median stent patency time was 111 days and 402 days
in the plastic stent and SEMS, respectively (p 0.002). Post-operative major
complications were not seen in both cases.
CONCLUSION: The endoscopic placement of internal stent might be useful
method for biliary decompression in patients with planed CRT for locally
advanced perihilar-cholangiocarcinoma, compared to PTBD. In case of biliary
endoscopic drainage, the pre-CRT SEMS had lower rate for repeated endoscopic
procedure than plastic stent in perihilar-cholangiocarcinoma.
Disclosure of Interest: None declared
P0233 ENDOSCOPIC
OESOPHAGEAL
STRICTUROTOMY
PROMISING MODALITY IN THE TREATMENT OF BENIGN
RESISTANT OESOPHAGEAL STRICTURES

AS

A.A. Monged1,*, G. Mohamed1, C.B. OSuilleabhain2, M. Buckley1 on behalf of


Gastroenterology depatment, mercy university hospital, cork, Ireland
1
Gastroenterology, 2Mercy University Hospital, Cork, Ireland
Contact E-mail Address: amongid@yahoo.com
INTRODUCTION: The majority of benign oesophageal strictures result from
long-standing gastroesophageal reflux disease. Treatment usually involves dilation combined with acid-suppressive therapy. Other causes of resistant strictures
include post radiation, oesophageal sclerotherapy, caustic ingestions and surgical
anastomosis. In the majority of patients, this can be accomplished with oesophageal dilation, though in cases of refractory strictures, additional therapy is
required. There is little published data on the treatment of resistant esophageal
strictures (ROS).
AIMS & METHODS: To describe our experience with Endoscopic Oesophageal
Stricturotomy (EOS) for resistant oesophageal strictures. From January 2012 to
July 2013 all patients with oesophageal strictures resistant to treatment with balloon
dilatation /- bougienage were selected for EOS. Data on Age, sex, co-morbidity,
clinical presentation, procedural details, and outcome were retrospectively collected,
anonymized, and analized. Endoscopic Oesophageal Stricturotomy procedures
were exclusively done by an experienced endoscopist (M. B.). Patient with resistant
strictures were assessed for suitability for Stricturotomy. Using Needle knife stricturotome (RX Needle Knife Boston scientific/ 5.5 F/1.8mm) Four quadrant incisions were made and tissue excised. Stricturotomy was followed by hydrostatic
balloon dilatation if residual stenosis was present.
RESULTS: A total of five male dysphagic patients, median age 58, (range 29-81),
with resistant oesophageal strictures were treated with EOS, during the study
period. Two patients had strictures due to peptic fibrosis, two due to exposure to
radiotherapy, and one had post surgery for oesophageal atresia. 80% (4/5) had
multiple previous trials of unsuccessful balloon. One session of Stricturotomy
was enough for 80% of patients, however, for one patient (20%) EOS were
needed to be repeated 5 times. Only 40% (2 patients) needed balloon dilatation
following the EOS. In all patients, successful response following initial EOS was
obtained.
CONCLUSION: EOS is highly effective in treating selected patients with resistant benign oesophageal strictures. Initial response has been achieved to all five
patients, refractory oesophageal stricture was noted in one patient, that has
finally showed good response after the 5th Stricturotomy session. Short focal
strictures may be more suitable for EOS. The risk of perforation following
EOS is not yet known, and needs to be elucidated in longer studies.
Stricturotomy is a valuable method in the treatment of patients with resistant
oesophageal strictures.

A194
REFERENCES
Patterson DJ, Graham DY, Smith JL, et al. Natural history of benign esophageal
stricture treated by dilatation. Gastroenterology 1983; 85: 346.
Marks RD and Richter JE. Peptic strictures of the esophagus. Am J
Gastroenterol 1993; 88: 1160.
Riley SA and Attwood SEA. Guidelines on the use of oesophageal dilatation in
clinical practice. Gut 2004; 53(Suppl. I): i1i6.
Standards of Practice Committee, Egan JV, Baron TH, et al. Esophageal dilatation. Gastrointest Endosc 2006; 63: 755.
Hernandez LV, Jacobson JW and Harris MS. Comparison among the perforation rates of Maloney, balloon and Savary dilation of esophageal strictures.
Gastrointest Endosc 2000; 51: 460462.
Disclosure of Interest: None declared
P0234 LONG-TERM COMPLICATIONS OF SELF-EXPANDABLE
METALLIC STENT IN PATIENTS WITH ADVANCED
ESOPHAGEAL CANCER
B.C. Martins1,*, M.S. I. Ribeiro1, F.A. Retes1, M.S. Lima1, A. V. SafatleRibeiro1, C.C. Gusmon1, C.M. Pennacchi1, F.S. Kawaguti1, R.S. Uemura1,
U. Ribeiro Jr2, F. Maluf-Filho1
1
Endoscopy, 2Gastroenterology, Cancer Institute of the University of Sao Paulo,
Sao Paulo, Brazil
Contact E-mail Address: bcm.bruno@gmail.com
INTRODUCTION: Self-expandable metallic stents (SEMS) are considered the
best palliative treatment of dysphagia of patients with advanced esophageal
cancer. Complications are a major concern, especially in patients with better
prognosis and longer survival.
AIMS & METHODS: The aim of this study was to assess the prevalence of
SEMS-related complications in the follow-up of patients with advanced esophageal cancer who survived longer than 6m. We performed a retrospective analysis
of a prospective collected database of patients with advanced esophageal cancer
submitted to SEMS palliation between February 2009 and December 2012 at the
Cancer Institute of the University of Sao Paulo. Patients with follow-up longer
than 180 days were included in this study.
RESULTS: Of the 145 patients from the database, 32 were selected. There was a
predominance of male patients (78.1%), mean age of 60 years with squamous cell
carcinoma (78.1%). The lesions were mainly located in the middle esophagus
(53.1%). Twenty-nine stents were partially covered (90.6%) and three completely
covered (9.4%). Twenty-two (68.7%) patients received chemo and/or radiotherapy before and 26 (81.2%) patients after SEMS insertion. Complications
occurred in 20 patients (62.5%): migration (n 9), overgrowth (n 8), ingrowth
(n 4), fistula (n 3), pulmonary infection (n 2), food impaction (n 2),
GERD (n 1), bleeding (n 1) and intractable pain (n 1). Most complications
could be managed endoscopically. Fatal complications occurred in 2 (6.2%)
patients: 1 bleeding and 1 pulmonary infection. The median survival after prosthesis was 305 days (range 182-630 days). A mean of 0.9 procedures per patient
(range 0-10) were performed to maintain stent patency. At the end of the followup, 20 patients still had a functional stent, while 12 patients had either retrieved
the stent or received a nasogastric tube.
CONCLUSION: The use of SEMS in patients with advanced esophageal cancer
who live longer than 6m is associated with high complication rate. Most complications are usually nonfatal and are managed endoscopically.
REFERENCES
1. Schoppmann SF, Langer FB, Prager G, et al. Outcome and complications of
long-term self-expanding esophageal stenting. Dis Esophagus 2013; 26: 154-158.
2. Park JJ, Lee YC, Kim BK, et al. Long-term clinical outcomes of self-expanding metal stents for treatment of malignant gastroesophageal junction obstructions and prognostic factors for stent patency: effects of anticancer treatments.
Dig Liver Dis 2010; 42: 436-440.
Disclosure of Interest: None declared
P0235 RISK FACTORS FOR METALLIC STENTS MIGRATION IN
PATIENTS WITH ADVANCED ESOPHAGEAL CANCER
B.D. C. Martins1,*, F.A. Retes1, M.S. Lima1, A. V. Safatle-Ribeiro1, M.S.
I. Ribeiro1, C.M. Pennacchi1, F.S. Kawaguti1, R.S. Uemura1, U. Ribeiro Jr2,
M.C. Franco1, J.T. Rios1, F. Maluf-Filho1
1
Endoscopy, 2Gastroenterology, Cancer Institute of the University of Sao Paulo,
Sao Paulo, Brazil
Contact E-mail Address: bcm.bruno@gmail.com
INTRODUCTION: Migration is one of the most common complications after
stent placement to palliate dysphagia in patients with inoperable esophageal
neoplasia. It occurs in up to 36% of the cases, so it would be useful to recognize
risk factors associated with this complication as preventive measures could be
taken to prevent it.
AIMS & METHODS: The aim of this study was to identify risk factors for
esophageal stents migration in patients with advanced esophageal cancer.
From 2009 to 2012, patients with advanced esophageal neoplasia who underwent
SEMS placement were followed prospectively and data were collected to evaluated risk factors associated with stent migration. Patients with less than 1 month
follow-up were excluded from the study.
RESULTS: A total of 145 patients with a median age of 63 years (SD10) and
male predominance (79.3%) were enrolled in the study. The most common histology was squamous cell carcinoma (109 cases, 75%) followed by adenocarcinoma (24 cases, 16.5%), and extra-esophageal cancer (12 cases, 8.5%). The lesion
was located in the distal third of the esophagus in 54 (37.2%), in the mid-esophagus in 70 (48.3%) and in the proximal esophagus in 21 (14.5%) patients.
Mean tumors length was 7.5cm (SD 2.8cm). Fifty-nine (40.7%) patients

United European Gastroenterology Journal 2(1S)


received chemoradiation prior and 13 (9.0%) after the stent implantation.
Partially covered stents were placed in 135 (93%) pts and fully covered SEMS
were placed in 10 (7%) pts. Evolution (n 69, 47.5%), Hanaro (n 44, 30.3%),
Endoflex (n 13, 9%), Wallflex (n 12, 8.2%), Plastimed (n 6, 4.2%) and
Ultraflex (n 1, 0.8%) stents were used. After a median follow-up of 156 days
(range: 31 630 days), the migration rate was 13.1% (19 patients, range: 1-323
days). The mean survival rate after the procedure was 146 days. Univariate
analysis showed that fully covered stents (p 0.049) and body stent diameter
measuring less than 20mm (p 0.004) were significantly associated with higher
migration rate.
CONCLUSION: Fully covered stents and stents with body diameter measuring
less than 20mm are associated with higher migration rate.
REFERENCES
Verschuur EM, Homs MY, Steyerberg EW, et al. A new esophageal stent design
(Niti-S stent) for the prevention of migration: a prospective study in 42 patients.
Gastrointest Endosc 2006; 63: 134-140.
Langer FB, Schoppmann SF, Prager G, et al. Temporary placement of selfexpanding oesophageal stents as bridging for neo-adjuvant therapy. Ann Surg
Oncol 2010; 17: 470-475.
Disclosure of Interest: None declared
P0236 ENDOSCOPIC ULTRASOUND (EUS) GUIDED SELF EXPANDING
METAL STENTS (SEMS) PLACEMENT FOR GASTRIC OUTLET
OBSTRUCTION
C. Shekhar1,*, S. Hebbar2, B. Mahon1
1
Radiology, Queen Elizabeth Hospital, Birmingham, 2Gastroenterolgoy, University
Hospital of North Staffordshire, Stoke on Trent, United Kingdom
Contact E-mail Address: drcshekhar@gmail.com
INTRODUCTION: SEMS placement is an effective way of relieving gastric
outlet obstruction, majority of them done endoscopically under fluroscopy guidance. This is known to be superior to surgical bypass with lower morbidity,
mortality, and shorter hospital stay1,2. At times, despite direct vision through the
endoscope and fluroscopy guidance, it can be difficult or unmanageable to position a SEMS
AIMS & METHODS: To evaluate use of EUS as an adjunct to safely and
effectively delineate lumen through the obstructing lesion and place SEMS
through EUS scope with / without fluroscopy guidance. All procedures were
done using Olympus linear scope (GF-UCT240) and Evolution (Cook
Medical) SEMS were used (22x 60-120mm).
RESULTS: Between February 2010 to November 2011, 15 patients had duodenal/enteral SEMS placement using EUS. All patients had prior CT scan and
endoscopy. All had successful stent placement using EUS technique, when it
was not possible to be done by endoscopic view supplemented with fluroscopy
guidance in previous or done as tandem procedures in same sitting. One patient
had 2 stents placed, one in afferent loop endoscopically and another one in
efferent loop with help of EUS.
One patient had perforation, stent was placed successfully across a tight angulated stricture but caused tear as it expanded across the angulated obstruction,
which was managed surgically.
Endoscopic implantation of SEMS in a malignant gastric outlet obstruction is a
safe and effective method. However, any obstruction beyond direct access of
scope, presence of food/liquid debris and some times contact bleeding obscuring
views are impediments in successful implantation of a stent. Most of the time this
is due to inability to visualise/delineate the lumen beyond direct vision even with
help of fluroscopy. There is high risk of false passage formation/perforation if
wire/catheter are advanced blindly. EUS has an added advantage of visualising
lumen even in above circumstances, especially when endoscopic views are poor.
CONCLUSION: This is first ever case series reporting use of EUS in gastroduodenal SEMS placement. We believe this is useful adjunct to existing techniques. However, this needs to be evaluated further in larger comparative studies.
As with any other complex intervention, this is highly dependent on experience of
the operator in endoscopic stent placement as well as EUS modality.
REFERENCES
1. Endoscopy 2004; 36: 73-78.
2. Surg Endosc 2002; 16: 310-312.
Disclosure of Interest: C. Shekhar: None declared, S. Hebbar: None declared, B.
Mahon Financial support for research from: Cook
P0237 EFFICACY AND SAFETY OF A PARTIALLY COVERED
DUODENAL STENT FOR MALIGNANT GASTRODUODENAL
OBSTRUCTION
D. Oh1,*, S.S. Lee1, T.J. Song1, D.H. Park1, D.W. Seo1, S.K. Lee1, M.-H. Kim1
Division of Gastroenterology, Department of Internal Medicine, University of
Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Seoul, Korea,
Republic Of
Contact E-mail Address: dongwook.oh1@gmail.com
1

INTRODUCTION: Duodenal stent placement has emerged as an effective and


safe palliative treatment for patients with malignant gastroduodenal obstruction.
The uncovered enteral stent is susceptible to re-stenosis due to tumor ingrowth.
Although covering an enteral stent with a membrane almost solves the problem
of tumor ingrowth, stent migration continues to be a major unresolved problem.
Recently, a partially covered metallic stent was introduced for gastroduodenal
obstruction.
AIMS & METHODS: Duodenal stent placement has emerged as an effective and
safe palliative treatment for patients with malignant gastroduodenal obstruction.
The uncovered enteral stent is susceptible to re-stenosis due to tumor ingrowth.
Although covering an enteral stent with a membrane almost solves the problem

United European Gastroenterology Journal 2(1S)


of tumor ingrowth, stent migration continues to be a major unresolved problem.
Recently, partially covered metallic stent was introduced for gastroduodenal
obstruction. Twenty patients with malignant gastroduodenal obstruction
received palliative treatment with partially covered duodenal stents. Technical
success was defined as the placement of the stent successfully. Clinical success
was defined as the relief of obstructive symptoms and/or improvement of the
Gastric Outlet Obstruction Scoring System score to  2 after the procedure.
RESULTS: A total of 20 patients (11 men and 9 women; median age 64.5 years,
range 39-85 years) were enrolled in this study. Ten patients had pancreatic
cancer, four patients had gallbladder cancer, two had cholangiocarcinoma, one
had advanced gastric cancer, one had metastatic rectal cancer, one had liver
sarcoma, and one had ampulla of Vater cancer. Stent placement was successful
in 20 of 20 patients (technical success, 100%). Symptoms improved in 19 patients
after stent placement (clinical success, 95%). The Gastric Outlet Obstruction
Scoring System score improved significantly (P-value 5 0.001). Tumor overgrowth developed in eight patients during patients survival period (40%).
Stent migration did not occur in any case. Median stent patency was 79.5 days
(range 13-198 days). Adverse events occurred in 3 patients, comprising two cases
of transient bacteremia, and one of asphyxia due to impaction of food material
into the stent.
CONCLUSION: Partially covered duodenal stent was effective and safe for the
malignant gastroduodenal obstruction and can prevent tumor ingrowth and stent
migration.
REFERENCES
1. Didden P, Spaander MC, de Ridder R, et al. Efficacy and safety of a partially
covered stent in malignant gastric outlet obstruction: a prospective Western
series. Gastrointest Endosc 2013; 77: 664-668.
2. Tringali A, Didden P, Repici A, et al. Endoscopic treatment of malignant
gastric and duodenal strictures: a prospective, multicenter study. Gastrointest
Endosc 2013.
3. Kanno Y, Ito K, Fujita N, et al. Efficacy and safety of a WallFlex enteral stent
for malignant gastric obstruction. Dig Endosc 2013; 25: 386-391.
4. Jung GS, Song HY, Kang SG, et al. Malignant gastroduodenal obstructions:
treatment by means of a covered expandable metallic stent-initial experience.
Radiology 2000; 216: 758-763.
Disclosure of Interest: None declared
P0238 A NOVEL REINFORCEMENT METHOD FOR THE SURFACE OF
GASTOINTESTINAL METAL STENT: GAS PLASMA TREATMENT
H.S. Choi1,*, E.S. Kim1, B. Keum1, Y.T. Jeen1, H.S. Lee1, H.J. Chun1,
C.D. Kim1, J.-J. Park1, S.W. Lee1, H.B. Kim2
1
Internal Medicine, Korea University College of Medicine, Seoul, 2Institute of
Interventional Medicine, M. I. Tech Co., Ltd, Pyeongtaek, Korea, Republic Of
INTRODUCTION: A gastrointestinal (GI) stent, which is made of NickelTitanium (NiTi) alloy coating with a silicone polymer, has been using for the
relief of obstructive symptom in malignant stenosis of gastrointestinal tract. But
the corrosion and fatigue failures of nitinol devices have been constant subjects of
discussion. Recently, GI nitinol stent use is increasing abruptly, and fractures of
GI stents have been reported. Although coating with the silicone polymer on the
stent plays a key role in corroding, corrosion properties may differ along the
surface of the NiTi alloy wire. The surface modification with plasma etching
technology is a way to improve the physical properties of the target. We systematically investigated a reinforcement of nitinol alloy and surface modification to
stick the silicone employing gas plasma treatment.
AIMS & METHODS: The fifteen NiTi alloy stents were treated in a few conditions of the plasma treatment, in which mixture rates of Ar and O2 gas, applied
voltages and duration of exposing time were varied. We prepared three kinds of
stents; normal stent (product by normal process, sample 1), slightly etched
normal stent (product by plasma treatment, sample 2) and natural oxide layereliminated normal stent (product that removed natural oxide regions by plasma
treatment, sample 3). The stents were analyzed with a transmission electron
microscope (TEM) and scanning electron microscope (SEM) to examine surface
topographies of the stents and the interlocking state between wire and silicone
polymer. We performed a potentiodynamic test to compare the corrosion state of
each stent in GI state.
RESULTS: The surface profile of the samples showed that some content of the
oxide layer for the normal stent was formed in thickness of about 100nm, while
the others was 6070nm by TEM analysis. Moreover, the oxide layer for normal
product and slightly etched normal stent was likely to exhibit deposition of
oxygen without interlocking that enhances cohesion, whereas natural oxide
layer-eliminated normal stent showed behavior of strong interlocking between
oxide and nickel. SEM image showed effective modification of nitinol wire to
stick the silicone polymer by plasma etching technology. In a potentiodynamic
test, the sample 3 removed natural oxide regions by plasma treatment, indicating
the strongest corrosion resistance.
CONCLUSION: This result implies that an interlocking between nickel and
oxide layer plays a significant role in corrosion resistance. Natural oxide layer
by normal manufacture process induced micro-crack of nitinol GI, stent and
removing the natural oxide layer by plasma treatment improved reinforcement
and surface modification of nitinol GI stent. These results revealed that the
plasma treatment could be employed to improve the surface property of GI
stent for malignant outlet obstruction.
Disclosure of Interest: None declared

A195
P0239 ENDOSCOPIC ELECTROCAUTERY DILATION OF POSTSURGICAL BENIGN ANASTOMOTIC COLONIC STRICTURES: A
SINGLE CENTER EXPERIENCE
I. Bravi1,*, D. Ravizza1, G. Fiori1, D. Tamayo1, C. Trovato1, G. De Roberto1,
L. Laterza1, C. Crosta1
1
Division of Endoscopy, European Institute of Oncology, Milan, Italy
Contact E-mail Address: ivana.bravi@ieo.it
INTRODUCTION: Benign anastomotic colonic stenosis sometimes occur after
surgery and usually requires surgical or endoscopic dilation. Endoscopic dilation
of anastomotic colonic strictures by using balloon or bougie-type dilators has been
demonstrated to be safe and effective in multiple uncontrolled series. However, few
data are available on safety and efficacy of endoscopic electrocautery dilation.
AIMS & METHODS: Aim of our study was to retrospectively investigate safety
and efficacy of endoscopic electrocautery dilation of post-surgical benign anastomotic colonic strictures.
Patients with post-surgical benign anastomotic colonic strictures treated with
endoscopic electrocautery dilation between June 2001 and February 2013 were
considered. Anastomotic stricture was defined as a narrowed anastomosis
through which a standard colonoscope could not be passed. Only annular anastomotic strictures were considered suitable for electrocautery dilation which
consisted of radial incisions performed with a precut sphincterotome.
Treatment was considered successful if the colonic anastomosis could be
passed by a standard colonoscope immediately after dilation. Recurrence was
defined as anastomotic stricture reappearance during follow-up.
RESULTS: Sixty-eight patients (43 women and 25 men, median age 63.6 yrs
(22.6-81.7)) were included. Nine had undergone adiuvant radiotherapy and chemotherapy, 25 adiuvant chemotherapy only. Forty-four patients had a colorectal, 19 had a colo-colic and 5 an ileo-rectal anastomosis. Five patients had a
colostomy and 12 an ileostomy. Two patients were referred for subocclusive
symptoms, nine for stipsis and six for stool shape modification. The time-interval
between colorectal surgery and the first endoscopic evaluation or symptoms
development was 7.3 months (1.3-60.7). Electrocautery dilation was successful
in all the patients. There were no procedure-related complications. Median
follow-up was 35.5 months (2.0-144.0). Anastomotic stricture recurrence was
observed in two patients who were successfully treated with electrocautery dilation and Savary dilation, respectively.
CONCLUSION: Endoscopic electrocautery dilation is a safe and effective treatment for annular benign anastomotic post-surgical colonic strictures.
Disclosure of Interest: None declared
P0240 BIODEGRADABLE STENTS IN PATIENTS WITH ACUTE LARGE
BOWEL OBSTRUCTION SECONDARY TO A RECTAL TUMOR AND
INDICATION FOR FURTHER NEOADJUVANT THERAPY:
OUTCOMES AND SAFETY
J. Jimenez-Perez1,*, I. Fernandez-Urien1, J. Vila1, E. Albeniz1
1
GASTROENTEROLOGY, COMPLEJO HOSPITALARIO DE NAVARRA,
Pamplona, Spain
Contact E-mail Address: jjimenezpster@gmail.com
INTRODUCTION: Colorectal stenting is the first choice treatment in patients
with acute large bowel obstruction due to the presence of a malignant tumor in
the left colon. After colon decompresion, stenting allows accurate tumoral staging
and patient preparation for further surgery. However, stenting is controversial in
rectal tumors. The presence of a metallic stent in a patient undergoing neoadjuvant
therapy increases disperse radiation and collateral inflammation in surrounding
tissues, leading to a higher complication rate and poorer surgical results.
AIMS & METHODS: The aim of this study was to assess the outcomes of
biodegradable stents in patients with obstructing rectal tumors undergoing
neoadjuvant therapy. A prospective observational study was conducted including
patients with acute large bowel obstruction due to a rectal cancer and candidates
to neoadjuvant therapy. After large bowel obstruction was diagnosed, a CT scan
was performed to confirm the etiology of the obstruction and, in patients with a
rectal tumor, to characterize the lesion and to assess the indication of further
neoadjuvancy. A biodegradable stent was inserted in these cases. Patients were
followed until surgery or until death if surgical treatment was dismissed.
Technical success at stent insertion, clinical success, stenting complications and
surgical findings and outcomes (primary anastomosis and postoperative complications) were documented.
RESULTS: 8 patients [4 men/4 women; mean age: 62.6 yr (51-77)] were enrolled
in the study. Once further neoadjuvant therapy was considered indicated, a
polydioxanone monofilament biodegradable stent (Ella-CS. Czceh Rep) was successfully inserted in all patients (100%) [31/25/31 mm; 6 cm (n 2), 8 cm (n 6)
length]. Initial colon decompression was achieved in every case (100%) but the
stent migrated in one patient (12.5%) and a second stent was inserted. Patients
underwent neoajuvant therapy [RT: 50.4 Gy in 28 sessions capecitabine (825
mg/m2/12 h)] and were reevaluated with a CT scan at the end of treatment. 3
patients did not go for surgery after tumoral staging, received chemotherapy and
did not present occlusive symptoms until death (mean follow-up: 220 days). 5
patients were operated 96 days after stent insertion (66-123 days). Primary anastomosis was performed in 3 (60%) whereas colostomy was performed in 2 (40%)
due to severe local inflammation in one case and a silent perforation in the other.
The only post surgical complication was a pneumonia in one patient (12.5%). No
wound or anastomosis complications were registered
CONCLUSION: 1. Biodegradable stents are effective in patients with rectal
tumors and secondary large bowel obstruction. 2. Association with neoadjuvant
therapy causes local inflammation but allows primary anastomosis in 60% of
cases and is not followed by an increased post surgery complication rate.
Disclosure of Interest: None declared

A196
P0241 SELF-EXPANDABLE
COLONIC OBSTRUCTION

United European Gastroenterology Journal 2(1S)


METAL

STENTS

FOR

MALIGNANT

L.C. Meireles1,*, P. Sousa1, L.C. Freitas2, J. Lopes1, L.C. Ribeiro1, J. Velosa1


Department of Gastroenterology, Centro Hospitalar Lisboa Norte, Lisboa,
2
Department of Gastroenterology, Centro Hospitalar do Funchal, Funchal,
Portugal
Contact E-mail Address: lilianeenailil@gmail.com
1

INTRODUCTION: Tumoral obstructions in almost the entire gastrointestinal


tract can be treated with interventional digestive endoscopy techniques. The use
of self -expanding metal stents (SEMS) is a minimally invasive procedure providing a relatively simple and effective first- line treatment for the relief of obstructive symptoms.
AIMS & METHODS: To report data from a single center study on self-expandable metal stent (SEMS) placement for malignant colorectal obstruction. One
hundred and six patients (64 males, mean age of 7114 years), in a period of 96
months, were retrospectively evaluated and data on type and size of stent, complications, lesion location, and survival after the procedure were analyzed.
RESULTS: Most lesions were located in the rectum (50%, n 53), 36% (n 38)
in the sigmoid colon, descending colon in 8.4% (n 9) and 5.6%(n 6) in the
transverse colon. The mean length of the lesions was 65  36mm. Most procedures were performed with palliative intent and in 4 patients two or more stents
were placed. The stent was uncovered in 92% of cases and partially covered in
8% of the procedures. Complications were 4 neoplastic ingrowths, 3 stent migrations and 1 perforation. Seventy-five percent of patients were dead by the time of
data collection, with a median interval between stenting and death of 105 days.
CONCLUSION: Colonic obstruction may be treated using endoscopic techniques. The placement of SEMS seems to be a safe and effective treatment.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


SURGERY I POSTER EXHIBITION HALL XL_____________________

9:0017:00

P0242 WHAT SWEDISH SURGEONS DO WHEN DETECTING


COMMON BILE DUCT STONES DURING CHOLECYSTECTOMY
F. Swahn1,*, L. Enochsson1, U. Arnelo2, M. Lohr2, R. Noel2
1
CLINTEC, Division of surgery, 2KAROLINSKA INSTITUTET, Stockholm,
Sweden
Contact E-mail Address: fredrik.swahn@ki.se
INTRODUCTION: About 11,000 cholecystectomies are done annually in
Sweden, most of which are completed laparoscopically (about 90%).
Management strategies for common bile duct stones (CBDS) have been discussed
in to an extreme extent and new options are rapidly emerging.
AIMS & METHODS: The aim of the study was to describe the current strategies
applied in routine clinical practice in Sweden. A survey questionnaire was mailed
to all hospitals (70) offering cholecystectomies and we obtained responses from
all of them (100%). The questionnaire captured information on the details of
clinical management strategies in a variety of different clinical manifestations of
CBDS.
RESULTS: 35 (50%) of the hospitals reported a predefined policy regarding the
management of CBDS. 65 (93%) hospitals used intra-operative cholangiography
as a routine, 2 in selective cases and 2 did not. Management of a 3 mm large
CBDS received that; 38 (54.3%) left it untreated, 23 (32.8%) performed some
kind of intra-operative procedure, 3 (4.3%) preferred a post-operative ERCP; In
case of a 6 mm large CBDS, the corresponding figures were; 3 (4.3%), 38
(52.2%), 17 (24.2%) respectively; In case of a 17 mm large CBDS: 23 (32.9%)
preferred open CBD exploration and 4 (4.3%) a laparoscopic CBD-exploration,
6 (8.6%) post-operative ERCP. 40 (57.1%) of the hospitals used intra-operative
ERCP with some kind of rendezvous cannulation technique.
CONCLUSION: Half of Swedens surgical units do not follow a predefined
policy regarding the intra-operative management of CBDS. Intra-operative
ERCP with rendezvous cannulation technique is currently the strategy that is
gaining popularity.
Disclosure of Interest: None declared
P0243 INDEPENDENT PROGNOSTIC FACTORS AFTER RESECTION
OF PERIHILAR CHOLANGIOCARCINOMA: ANALYSIS OF 307
PATIENTS FROM TWO HPB CENTERS
J. Wiggers1,*, B. Groot Koerkamp2, P. Allen2, O. Busch1, M. DAngelica2,
R. Dematteo2, D.-J. Gouma1, P. Kingham2, W. Jarnagin2, T.van Gulik1
1
Surgery, Academic Medical Center, Amsterdam, Netherlands, 2Surgery,
Memorial Sloan Kettering Cancer Center, New York, United States
Contact E-mail Address: j.k.wiggers@amc.nl
INTRODUCTION: The purpose of this study was to determine survival and
independent prognostic factors after resection of perihilar cholangiocarcinoma
(PHC).
AIMS & METHODS: Patients with PHC resected between 1991 and 2012 were
identified from prospectively maintained databases from two institutions (in
Europe and USA). Patients with final pathology other than PHC or in-hospital
mortality were excluded. Prognostic factors were evaluated using univariate
Kaplan-Meier survival analysis with log-rank test and multivariable cox-proportional hazards modelling using backward selection with likelihood ratio test.
RESULTS: 307 patients underwent resection for PHC. The median overall survival was 38 months, and 5-year survival 37%. In multivariable analysis four
factors were independently associated with a poor prognosis: a positive resection
margin, HR 1.69 [95% CI: 1.25-2.28], p 0.001, one or more positive lymph

nodes, HR 2.31 [1.66-3.23], p50.001, perineural invasion, HR 1.59 [1.13-2.23],


p 0.008, and moderate or poor differentiation, HR 1.64 [1.15-2.33], p 0.006.
Other traditional factors were associated with a poor prognosis only in univariate
analysis, including lymphovascular invasion, non-papillary tumor, T-stage (7th
edition), and AJCC stage (7th edition). Patients with at least 3 out of 4 poor
prognostic factors (n 90) had a median survival of 19 months [95% CI: 16-22]
versus 52 months [95% CI: 40-64]. Analyzing R0 patients separately resulted in
the same independent prognostic factors.
CONCLUSION: A positive resection margin, one or more positive lymph nodes,
perineural invasion and moderate or poor differentiation are independent prognostic factors after resection of PHC. Based on these poor prognostic factors we
will derive and validate a prognostic nomogram for resected perihilar
cholangiocarcinoma.
Disclosure of Interest: None declared
P0244 SUCCESSFUL ENHANCED
MAJOR LIVER SURGERY

RECOVERY

PROGRAMME

IN

J. Savikko1,*, M. Ilmakunnas2, H. Makisalo1, A. Nordin1, H. Isoniemi1


Department of Transplantation and Liver Surgery, 2Department of
Anaesthesiology and Intensive Care Medicine, Helsinki University Central
Hospital, Helsinki, Finland
Contact E-mail Address: johanna.savikko@helsinki.fi
1

INTRODUCTION: Enhanced recovery protocols after surgery accelerate


patients recovery and shorten hospital stay as a result of the optimization of
perioperative care. In colorectal surgery these protocols show high-level evidence
on reducing primary and total hospital stay without compromising the patient
safety. This increased knowledge of perioperative pathophysiology and care has
also been slowly implemented into liver surgery. However, in liver surgery the
experience of optimized protocols is still limited.
AIMS & METHODS: Here we studied in a prospective way the implementation
of multimodal rehabilitation protocol in a tertiary liver surgery unit within a one
year period. This study involves the first 134 consecutive patients who were
treated according to the enhanced recovery principles in open or laparoscopic
liver surgery. An opioid-sparing pain treatment regimen was chosen for these
patients together with early mobilization and oral feeding as well as avoidance or
quick removal of drains and catheters shortly after surgery. Primary pain control
was achieved either with epidural or locally inserted wound catheter analgesia.
Peroral combination of pregabalin, ibuprofen and slow-release tramadol was also
routinely administered shortly after the operation for pain relief.
RESULTS: All investigated liver resections were performed between April 1st,
2013 and March 31st, 2014. Most of the resections (72%) were major liver
surgery involving 2 or more liver segments. Operations were done due to colorectal livers metastases (55% of cases), other liver metastases (9%), hepatocellular
carcinoma (13%), gall bladder carcinoma (7%), peripheral cholangiocarcinoma
(6%), and the rest 10% were done for benign liver tumors. Operations requiring
hepatobiliary reconstructions were excluded from this study. 125 of the operations were open and 9 laparoscopic surgery.
56 of the operated patients were female, 78 male. Age median was 63 years (range
26-86 years). Only 2 patients were admitted to intensive care unit postoperatively;
1 planned admission, 1 due to perioperative pulmonary embolism. Median postoperative hospital stay was 4 days (range 2-11 days). 80% of all patients were
discharged by the 5th postoperative day: 35% at the 3rd, 29% at the 4th and
15% at the 5th postoperative day. Two of the laparoscopically-operated patients
were discharged at the 2nd, 6 at the 3rd and 1 patient at the 5th postoperative
day. 5% of all patients were discharged via their own district hospitals.
Only 3 patients were readmitted back to the liver surgery ward; 1 patient (discharged at the 3rd day) because of pain problems and 2 patients (both discharged
at the 5th day) because of elevated liver enzymes seen at the scheduled control
visit few days after discharge.
CONCLUSION: Enhanced recovery protocol for perioperative care was introduced safely and effectively after major liver surgery. Routine discharge 2-3 days
after laparoscopic resection and even 3-4 days after open resection is realistic and
achievable.
Disclosure of Interest: None declared
P0245 HEPATOBILIARY
SCINTIGRAPHY
USING
99MTCMEBROFENIN FOR THE ASSESSMENT OF LIVER FUNCTION
AND BILIARY DECOMPRESSION IN PATIENTS WITH
RESECTABLE HILAR CHOLANGIOCARCINOMA
K.P. Cieslak1,*, J.K. Wiggers1, R.J. Bennink2, O.R. C. Busch1, D.J. Gouma1,
T.M. van Gulik1
1
Surgery, 2Nuclear Medicine, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: k.p.cieslak@amc.nl
INTRODUCTION: Assessment of future remnant liver (FRL) function is crucial
in resectable hilar cholangiocarcinoma (HCCA) while complete biliary drainage
of the FRL is considered essential for postoperative function and regeneration in
extended resections. 99mTc-mebrofenin-hepatobiliary-scintigraphy (HBS) provides segmental, quantitative information on parenchymal function in the
uptake phase, while the excretion of 99mTc-mebrofenin depends on drainage of
the biliary system.
AIMS & METHODS: The aim of this study was to evaluate the value of HBS in
the preoperative work-up of patients undergoing resection for HCCA.
From 2008 to 2013, 67 patients suspected of HCCA underwent resection (7/67
(10.4%) hilar resection and 60/67 (89.6%) hilar resection in combination with
liver resection). Preoperative HBS was used to generate time-activity curves from
regions-of-interest (total liver and FRL). The excretion rate was calculated as
decrease in mebrofenin activity in time (%/min) in the FRL.

A197

United European Gastroenterology Journal 2(1S)

P0246 IATROGENIC
BILIARY
INJURIES:MULTIDISCIPLINARY
MANAGEMENT IN A MAJOR TERTIARY REFERRAL CENTER

resections for suspected pHCCA between 1998 and 2013. Sarcopenia was
assessed in patients in whom an adequate preoperative CT scan was available,
by measuring total skeletal muscle mass at the level of the third lumbar vertebra.
Sex-specific cut-off values for sarcopenia were determined by optimum stratification. Clinicopathological data, postoperative morbidity (Clavien-Dindo grade
3), mortality and long-term survival were analysed.
RESULTS: Sarcopenia was present in 41 (42%) of 97 patients with pHCCA and
was correlated with lower body mass index. Sarcopenia was associated with 30day/in-hospital mortality (24% vs. 9%, p 0.037). Overall postoperative complication rate (Clavien-Dindo grade 3) was higher in sarcopenic patients (66%
vs. 46%), though this was not statistically significant (p 0.058). However, sarcopenia was predictive for sepsis (OR 6.77, 1.67 to 27.43, p 0.007). Estimated
five-year overall survival rate was lower for sarcopenic patients (18 vs. 36%,
p 0.024). After correction for lymph node status, resection margin status,
tumour differentiation grade and postoperative complications in multivariable
analysis, sarcopenia was revealed as an independent predictor for worse overall
survival (HR 1.93, 1.08 to 3.43; p 0.026).
CONCLUSION: Sarcopenia has a negative effect on postoperative outcome and
overall survival following resection of pHCCA and should therefore be considered in preoperative risk assessment.
Disclosure of Interest: None declared

O.H. Abdulsalam1,*, I.A. Salama1, H. Shoreem1, S. Saleh1, K. Aboella1,


M. Hoyseni2, M. Abbasy2, G. Badra3,4, M.S. Hashim4
1
Hepato-pancreatico-biliary surgery, 2DEPARTMENT OF RADIOLOGY,
3
DEPARTMENT OF HEPATOLOGY, 4HEPATOLOGY, National Liver
Institute, sheben elkom, Egypt
Contact E-mail Address: OSHEGAZY2002@YAHOO. COM

P0248 RESECTION AND RECONSTRUCTION OF THE HEPATIC


ARTERY FOR ADVANCED CHOLANGIOCARCINOMA: COULD
ARTERIOPORTAL SHUNTING ALTER MICROVASCULAR
RECONSTRUCTION?

RESULTS: HBS was performed in 51 of 67 patients. Preoperative biliary drainage had been performed in 44/51 patients. HBS showed sufficient function in
30/44 patients (group A), whereas 14/44 patients required additional procedures
(group B), consisting of revision of biliary drainage (n 8; 18.2%), portal vein
embolization (n 2; 4.5%) or a modified (parenchyma sparing) technique (n 8;
18.2%). Overall excretion rate in group A was 2.17%/min (IQR25-IQR75 1.032.36) vs. 1.15%/min (IQR25-IQR75 0.81-1.50) in group B (p 0.03).
Overall mortality in 67 patients was 7.5%. Morbidity was 50.0% and 42.9% in
group A and B, respectively (p 0.75). Two patients died due to postoperative
liver failure: 1/30 (3.3%) in group A with sufficient FRL-function but low excretion rate and 1/14 (7.1%) in group B despite revision of biliary drainage
(p 0.54).
CONCLUSION: HBS provides combined quantitative assessment of parenchymal function (uptake phase) and biliary decompression (excretion phase) of the
FRL enabling identification of patients who require additional or modified procedures prior to resection of HCCA.
Disclosure of Interest: None declared

INTRODUCTION: Iatrogenic biliary injuries are considered as the most serious


complications during cholecystectomy. Better outcomes have been shown in
cases managed in a specialized center.
AIMS & METHODS: To evaluate the management and outcome of biliary
injuries by multidisciplinary team in major referral hepatobiliary center. From
January 2002 to January 2012,472 patients (302 females & 170 males) with postcholecystectomy biliary injuries were managed with multidisciplinary team at
National Liver Institute using endoscopy in 232 patients, in addition to percutaneous techniques in 42 patients and surgery in 198 patients.
RESULTS: Endoscopy was very successful initial treatment of 232 patients
(49%) being less invasive in comparison to surgery in treatment of mild/moderate
biliary leakage (68%) and biliary stricture (47%) with increased success by addition of percutaneous (Rendezvous technique) in 18 patients (3.8%). Surgery was
needed in 198 (42%) for major duct transection, ligation, major leakage and
massive stricture. Surgery was urgently in 62 patients and electively in 156
patients. Hepaticojejunostomy was done in most of cases (96) patients with
transanastomatic stents. There was only one mortality after surgery due to biliary
sepsis, and postoperative stricture was in 3 cases (1.5%) treated with percutaneous dilation and stenting.
CONCLUSION: Management outcome of biliary injuries becomes better with a
multidisciplinary care team, with initial minimal invasive technique to major
surgery in major complex injury encouraging for early referral to highly specialized hepatobiliary centers.
REFERENCES
1-Flum DR, Cheadle A, Prela C, et al. Bile duct injuries during cholecystectomy
and survival in medicare beneficiaries. JAMAA 2003; 290: 2168-2173.
2-Tamqvist B, Zheng Z, Ye W, et al. Long-term effects of iatrogenic bile duct
injury during cholecystectomy. Clin Gastroenterology Hepatol 2009; 7: 10131018.
3-Sicklick JK, Camp MS, Lillemoe KD, et al. Surgical management of bile duct
injuries sustained during laparoscopic cholecystectomy. Ann Surg 2005; 241: 786795.
4-Wange A and Nilsson M. Iatrogenic bile duct injury: a population-bases study
of 152776 cholecystectomies in the Swedish inpatient registry. Arch Surg 2006;
141: 1207-1213.
5-Khan MH, Howard TJ, Fogel EL, et al. Frequency of biliary complications
after laparoscopic cholecystectomy detected by ERCP: Experience at a large
tertiary referral center. Gatrointest Endosc 2007; 65: 247-252.
6-Ludwing K, Bernhardt J, Steffen H, et al. Contribution of intraoperative cholangiography to incidence and outcome of common bile duct injuries during
laparoscopic cholecystectomy. Surg Endosc 2002; 16: 1098-1104.
7-Caroll BJ, Birth M and Phillips EH. Common bile duct injuries during laparoscopic cholecystectomy that result in litigation. Surg Endosc 1998; 12: 310-313.
8-Singh V, Narasimhan KL, VermaGR, et al. Endoscopic management of traumatic hepatobiliary injuries. J Gastro-enterol Hepatol 2007; 22: 1205-1209.
Disclosure of Interest: None declared
P0247 IMPACT OF SARCOPENIA ON OUTCOMES FOLLOWING
RESECTION OF PERIHILAR CHOLANGIOCARCINOMA
R.J. S. Coelen1,*, J.K. Wiggers1, C.Y. Nio2, S.van Dieren3, M.G. H. Besselink1,
O.R. C. Busch1, T.M. van Gulik1
1
Surgery, 2Radiology, 3Epidemiology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: r.j.coelen@amc.nl
INTRODUCTION: Loss of skeletal muscle mass, sarcopenia, reflects the frailty
status of patients and has recently been associated with worse outcomes following surgery for malignancies of gastrointestinal origin. The aim of this study was
to investigate the impact of sarcopenia on postoperative morbidity and survival
following resection of perihilar cholangiocarcinoma (pHCCA).
AIMS & METHODS: Data were retrospectively collected from a prospectively
maintained database including all patients in our institute undergoing major liver

T. Noji1,*, T. Tsuchikawa1, T. Nakamura1, E. Tamoto1, K. Okamura1,


T. Shichinohe1, S. Hirano1
1
Gastroenterological Surgery II, Hokkaido University, Graduate School of
Medicine, Sapporo city, Japan
Contact E-mail Address: drnoji@med.hokudai.ac.jp
INTRODUCTION: The anatomic features of the hepatic hilum facilitate invasion of the hepatic arteries by cholangiocarcinoma. To accomplish curative resection, hepatic artery resection and reconstruction is sometimes required for such
advanced cases. One small study suggested that arterioportal shunting (APS)
might be useful in these patients. Surgical results with more cases and the survival
impact of APS for cholangiocarcinoma have not yet been investigated.
AIMS & METHODS: The aim of this case controlled study was to evaluate the
safety of APS and whether APS could be an alternative to microvascular
reconstruction.
Patients and Methods: Thirty nine patients with intra- or extra-hepatic cholangiocarcinoma who underwent hepatic arterial resection were evaluated. There
were 18 patients with APS (APS group) and 21 patients with microvascular
arterial reconstruction (MVR group).
RESULTS: Preoperative statuses of the patients from both groups were similar,
except for a number of patients with preoperative portal embolization. There
were no significant differences in incidences of postoperative complications
(Clavien-Dindo  IIIa) between the two groups. However, the incidence of
liver abscess formation was significantly higher in the APS group (38.9% vs
4.8% p 0.02). Treatments for these liver abscesses were complicated.
Mortality (hospital death) was 6% in APS group, 0% in MVR group, respectively (p 0.46). Cumulative 3- and 5-year survival rates were 53.1% and 22.1%,
respectively, in the MVR group, and22.2% and 11.1%, respectively, in the APS
group (p 0.11).
CONCLUSION: Microvasucular arterial reconstruction should be used as the
first-line strategy for patients with intra/extra-hepatic cholangiocarcinoma. APS
is indicated when the artery cannot be microscopically anastomosed.
REFERENCES
1. Kondo S, Hirano S, et al. Arterioportal shunting as an alternative to microvascular reconstruction after hepatic artery resection. Br J Surg 2004; 91: 248251.
Disclosure of Interest: None declared
P0249 SURGICAL OUTCOME OF HILAR PLATE RESECTION:
EXTENDED HILAR BILE DUCT RESECTION WITHOUT
HEPATECTOMY
T. Noji1,*, T. Tsuchikawa1, T. Nakamura1, E. Tamoto1, K. Okamura1,
T. Shichinohe1, S. Hirano1
1
Gastroenterological Surgery II, Hokkaido University, Graduate School of
Medicine, Sapporo city, Japan
Contact E-mail Address: drnoji@med.hokudai.ac.jp
INTRODUCTION: In the treatment of hilar cholangiocarcinoma, several studies
have advocated en bloc major hepatectomy to achieve negative histologic margins and improved survival. However, we know that there are some patients with
distal cholangiocarcinoma with longitudinal spread remaining in the hilar portion, without infiltration beyond the bile duct wall. We also know that there are a
few patients with Bismuth type I hilar cholangiocarcinoma without infiltration
beyond the bile duct wall. These tumors are likely to have superficial spreading,
which would be difficult to accurately diagnose preoperatively. It remains
unknown whether, for patients with such a non-invasive tumor, extended hepatectomy would be appropriate. We have done extended extrahepatic bile duct
resection at the level of the hilar plate with curative or palliative intention for
selected patients with or without hilar malignant tumors, calling this procedure
hilar plate resection (HPR).
AIMS & METHODS: The results of a retrospective study evaluating the clinical
benefits in patients who underwent HPR for biliary malignancies are reported.

A198
Surgical procedure of HPR: Nodal clearance around the pancreatic head and
skeletonization of the portal vein and the hepatic artery were performed first. The
portal vein and the hepatic artery were then separated from the surrounding
tissue upward to the hilar plate, where the duct cannot be further separated
from the vasculature. This was considered the limit of ductal transection without hepatectomy, which is at the right edge of the posterior portion of the right
portal vein and the right edge of the umbilical portion of the left portal vein.
Then, the gallbladder with the cystic plate was resected toward the hepatic
hilum. Finally, the extrahepatic duct at the hilar plate was resected.
Patients: Fifty-two patients with cholangiocarcinoma underwent HPR. The procedure was performed in 28 patients with curative resection (cHPR group) and in
24 patients with palliative intention (pHPR group). In the same period, one
hundred twenty-eight patients with cholangiocarcinoma underwent major hepatectomy with intrahepatic cholangiojejunostomy (Hx group). We compared with
these groups in term of post operative complications and survival.
RESULTS: There were no significant differences in the number of patients with
postoperative complications and in postoperative hospital stay. The overall
cumulative survival rates of each procedure (Hx group, cHPR group, and
pHPR group) were 40%, 38%, and 11% at 5 years, respectively. There was no
significant difference between Hx and cHPR group in survival rates (p 0.87).
But the survival rate of the pHPR group was significantly lower than that of the
Hx group (p 0.03). The survival rate of the pHPR group was lower, but not
significantly, than that of the cHPR group (p 0.08).
CONCLUSION: HPR appears to be safe and feasible for selected patients with
cholangiocarcinoma. However, the indications for HPR should be restricted.
Disclosure of Interest: None declared
P0250 LAPAROSCOPIC GASTRECTOMY FOR GASTRIC CANCER:
RESULTS OF IMPLEMENTATION OF A NEW TECHNIQUE
E.J. Jongerius1, M. I.van Berge Henegouwen1, S.M. Lagarde1, S.S. Gisbertz1,*
surgery, AMC, Amsterdam, Netherlands
Contact E-mail Address: s.s.gisbertz@amc.nl
1

INTRODUCTION: Although different (neo)adjuvant strategies are being developed, surgical treatment remains the cornerstone of curative treatment for gastric
cancer. Standard operative procedure has traditionally been an open (sub)total
gastrectomy with a modified D2-lymphadenectomy. In an attempt to lower perioperative morbidity, we designed and standardized a laparoscopic technique to
perform a (sub)total gastrectomy for the treatment of patients with potentially
curable gastric cancer.
AIMS & METHODS: Aim of this study was to describe the short-term results of
the first series of laparoscopic gastrectomies in patients with potentially curable
gastric cancer.
In this prospective cohort trial we evaluated the first series of consecutive patients
with potentially curable gastric cancer who underwent a laparoscopic (sub)total
gastrectomy with a modified D2-lymphadenectomy the first year following introduction of the laparoscopic technique. Primary endpoint was perioperative morbidity and mortality. Secondary endpoints were hospital length of stay, number
of harvested lymph nodes and radicality of surgery (R0 resection rate).
RESULTS: From February 2013 until April 2014 28 patients out of a total of 38
patients underwent a laparoscopic gastrectomy (73.7% of all gastrectomies).
Eighteen patients (64.3%) underwent a total gastrectomy and 10 patients
(35.7%) a subtotal gastrectomy. In 5 patients (17.9%) at least 6 cm of esophagus
was co-resected. 18 patients (64.3%) received neo-adjuvant chemotherapy. There
were 3 conversions (10.7%). Reasons for conversion were tumor involvement of
the duodenum with a narrow relation to the pancreatic head in 2 cases and tumor
ingrowth in the left hemidiafragm necessitating partial diaphragm resection in 1
case. The median operation time was 320 min (SD 66.8), median blood loss 200
cc (SD 269.6) and median hospital stay 8 days (SD 6.3). The overall complication
rate was 21.4% (6 patients). There were 2 complications requiring re-intervention
(7.1%). Both patients had an anastomotic dehiscence for which surgical drainage
was performed. One of these patients eventually died of the septic consequences
(total hospital mortality 3.6%). In 1 patient peri-operatively peritoneal metastases were detected and a palliative resection was performed. In 26 patients the
tumor was radically removed (R0 resection rate 96.3%). Median lymph node
count was 25 (SD 8.5).
CONCLUSION: Laparoscopic surgery for gastric cancer is feasible with good
oncologic results and acceptable peri-operative morbidity and mortality.
Implementation of this technique was evaluated as successful and therefore it
is now standard surgical strategy at our center.
Disclosure of Interest: None declared
P0251 SUBMUCOSAL
TUNNEL
FOR
PERITONEAL
ACCESS
ASSOCIATED WITH AN OVER-THE-SCOPE CLIPS (OTSC)
CLOSURE: COMPARISON WITH TWO OTHER METHODS OF
GASTROTOMY CLOSURE AFTER NOTES PROCEDURES
J.-M. Gonzalez1,2,*, K. Saito1, C. Kang1, M. Gromski1, M. Sawnhey1,
R. Chuttani1, K. Matthes1
1
Gastroenterology, Beth Israel Medical Center, Harvard Medical School, Boston,
MA, United States, 2Gastroenterology, Aix-Marseille University, North Hospital,
Marseille, France
INTRODUCTION: Safe transgastric NOTES procedures require a reliable closure of the gastrotomy. Recently a novel peritoneal access method via a submucosal tunnel has been described with encouraging preliminary results.
AIMS & METHODS: The aim was to compare a submucosal tunnel access plus
over-the-scope clips (OTSC) for closure with two other closure modalities. It was
a prospective ex-vivo study on forty-two specimens equally randomized in three
groups and carried out in an Academic medical center. Fourteen procedures were

United European Gastroenterology Journal 2(1S)


performed in each group including: 1.) Tunnel (6 cm) endoclips; 2.) Knife
balloon dilation access OTSC; 3.) Tunnel OTSC. The main outcome measurements were: pressurized air-leak test was realized to evaluate the strength of
the closure. Stomach volumes, procedure times, number of clips, and incision
sizes were also registered.
RESULTS: The mean air leak pressure was statistically higher in group 3 than in
groups 1 and 2: 95.2  19.3 mmHg vs. 72.5  35.2 and 79  24.5 mmHg
(p50.05). The gastrotomy creation times for groups 1, 2 and 3 were 28.0 
10.1, 4.3  1.4 and 20.1  10.6 minutes, respectively, with significantly lower
time in the group 2 (p50.001). The closure times were 16.1  6.1, 6.5  1.2 and
5.3  3.0 minutes, respectively, and significantly longer in the endoclip group
(p50.001). There was no difference in the volumes and the incision sizes between
the three groups.
CONCLUSION: The combination of a submucosal tunnel access and OTSC
offers a stronger closure than the other methods studied.
Disclosure of Interest: None declared
P0252 NEW
MULTICOLORED
MULTIMATERIAL
BIOELASTIC
ORGAN REPLICATION USING HYBRID MDCT AND 3D PRINTING
TECHNOLOGY FOR TANGIBLE DIGESTIVE SURGERY
SIMULATION
M. Sugimoto1,*
Gastroenterology, Kobe University, KOBE HYOGO, Japan
Contact E-mail Address: sgmt@med.kobe-u.ac.jp
1

INTRODUCTION: Our new technology of Bio-Texture Modeling by hybrid


MDCT and 3D printing system enabled manufacturing patient-specific 3D
organ replicas. We developed the latest generation of 3D printer by simultaneous
jetting of different types of model materials.
AIMS & METHODS: The objective was to develop and evaluate patient-specific, anatomically accurate, bioelastic 3D replica for simulation, navigation and
training of digestive surgery in 40 clinical cases. Based on DICOM data from
MDCT, after generating its surface polygons using OsiriX application, the inkjet
3D printer created life-size copies of the 3D organs, blood vessels, and abdominal
cavity. We programmed a printer to create clear models made from acrylic resins
that allowed us to visualize and understand the gastrointestinal and hepatobiliary
pancreatic complex internal structures and blood vessels or the exact tumor
locations. We printed liver models compounding the polyvinyl alcohol (PVA)
to make the model a realistic stand-in for ultrasonic diagnosis, hepatic intervention and surgical simulation.
RESULTS: The patient individual multicolored 3D printed models were useful
for visible and tangible surgical simulation and navigation to plan and guide the
successful gastrectomy, colectomy, hapatobiliary pancreatic surgeries in total of
40 patients including 20 laparoscopic surgeries. The 3D objects using a combination of transparent and soft materials allowed creation of translucent medical
models that show visceral organs and other details that can be handled, overcoming the limitation of the conventional image-guided navigation. The gel-like
support material, which is specially designed to support complicated geometries,
is easily removed by hand. This provided realistic simulation of suturing and
dissection to provide specific values of bio-texture in gastrointestinal hepatobiliary pancreatic organs for tensile strength and elongation to break. The PVA was
available for wet tissue simulation in ultrasonography and intervention in hepatic
surgery.
CONCLUSION: New 3D printing techniques delivered tangible and safe surgery
training and could help younger, less experienced surgeons practice with accurate
copies for digestive surgery. Its combines the advantages of conventional 3D
modeling and precise virtual 3D planning and can be applied advantageously
in personalized surgical simulation and navigation.
Disclosure of Interest: M. Sugimoto Financial support for research from: Fasotec
Inc.
P0253 TRANSRECTAL NOTES VERSUS LAPAROSCOPIC AND OPEN
CHOLECYSTECTOMY IN AN ANIMAL MODEL OF CALCULOSE
CHOLECYSTITIS
O. Ryska1,*, Z. Serclova1, J. Martinek2, R. Dolezel3, J. Kalvach3, T. Henlin4,
E. Laszikova4, S. Juhas5, J. Juhasova6, M. Ryska3
1
Department of Surgery, Horovice Hospital, Horovice, 2Hepatogastroenterology
department, Institute for Clinical and Experimental Medicine, 3Department of
Surgery, 4Department of Anesthesiology, Central Military Hospital, Prague,
5
Institute of Animal Physiology and Genetics, Libechov, 6Institute of Animal
Physiology and Genetics, Prague, Czech Republic
INTRODUCTION: Natural-orifice transluminal endoscopic surgery (NOTES)
as an evolving concept has been studied in several experimental trials. However,
randomized experimental study evaluating NOTES in the area of calculose cholecystitis is missing. Transrectal compared to more frequently used transvaginal
access offers good manipulation in the upper abdomen and is not limited to the
female population. Also the physiologic impact during NOTES may differ from
laparoscopy and open procedures because of presumed longer operation and
need of extensive body positioning.
AIMS & METHODS: The aim of the study was to compare transrectal NOTES,
laparoscopic and open approach to cholecystectomy in animal with calculose
cholecystitis.
Laparoscopy (3-ports) was performed, bile was aspirated from the bladder and 4
gallstones obtained by human cholecystectomy were inserted via cholecystotomy
in all 42 animals four week prior planned intervention. Animals were than randomized into NOTES (N 14), open (N 11), laparoscopic (N 11), and sham
groups (N 6). In NOTES cholecystectomy a double channel endoscope was
used to enter the abdominal cavity via rectotomy performed by needle knife

A199

United European Gastroenterology Journal 2(1S)


and balloon dilatation. A standard laparoscopic grasper was advanced to grip the
fundus. Cystic duct and cystic artery were clipped and the preparation finished
with a hook knife. The access site incision was endosutured by OVESCO clip.
Small (5-6cm) subcostal incision and 3-ports laparoscopy were performed in
open and laparoscopic groups. For hemodynamic monitoring using LiDCO,
central venous and arterial catheter were introduced. After a follow-up period
of 30 days, the animals were euthanized and necropsies were performed.
RESULTS: The procedure time was significantly longer in NOTES than in open
and laparoscopic groups 145 (90-240) vs. 40 (25-65) vs. 63 (40-90) minutes, p
50.001. In 3 animals from NOTES group the bladder dissection was complicated by severe bleeding, which was not treatable endoscopically. NOTES technique was indicated as unfeasible and these animals could not be evaluated
afterwards. Perforation of the gall bladder occurred in 9/11 in NOTES versus
1/11 (RR: 9.0; 1.36-59; p 0.02) and 4/11 (RR: 2.3; 1.1-5.2; p 0.04) in open and
laparoscopy groups. All followed hemodynamic parameters including heart rate,
mean arterial pressure, cardiac index, central venous pressure and systemic vascular resistance did not differ from sham animals in all groups. Gallstones with
wall inflammation confirmed histologically were present in all extracted bladders.
All rectotomies were healed, however intraabdominal infection occurred more
frequently in NOTES (4/11) than in open (2/11) and laparoscopic (1/11) groups.
CONCLUSION: Despite the technical difficulties and longer operational times,
NOTES did not affect hemodynamic parameters. However, the feasibility rate of
NOTES in the area of calculose cholecystitis did not reach conventional
approaches. There were more intraoperative and postoperative complications
in NOTES group. Transrectal access can be used universally and closed safely
but risk of intraabdominal contamination during the procedure remains an issue.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


IBD I POSTER EXHIBITION HALL XL_____________________

9:0017:00

P0254 HCMV AND EBV VIRAL LOAD IN MUCOSA OF PATIENTS WITH


CHRONIC INFLAMMATORY BOWEL DISEASE
R. Ciccocioppo1, A. Gallia1,*, G.A. Petazzi1, E. Betti1, V. Imbesi1,
G.C. Cangemi1, F. Racca1, F. Broglia2, F. Baldanti3, G.R. Corazza1
1
Clinica Medica I, 2Servizio di Endoscopia Digestiva, 3Unita` di Virologia,
Fondazione IRCCS Policlinico San Matteo, Universita` di Pavia, Pavia, Italy
Contact E-mail Address: rachele.ciccocioppo@unipv.it
INTRODUCTION: Immunosuppressants and biologicals are considered the
mainstay of therapy for inflammatory bowel disease (IBD) thanks to the possibility of inducing remission and preventing disease progression. However, the
growing and earlier use of these medications predisposes the patients to an
increased risk of opportunistic infections, which represent an important cause
of morbidity and mortality. Human Cytomegalovirus (HCMV) and Epstein-Barr
virus (EBV) play a prominent role in the development of acute colitis in immunecompromised patients. In a previous study, our group has defined the spectrum
of conditions associated with infection by HCMV and EBV, associating their
presence with the refractory to conventional therapies and identifying the main
risk factors for reactivation, as well as to detect in quantitative real-time PCR
(RT-PCR), performed on fresh intestinal biopsies, the most sensitive method for
diagnosis.
AIMS & METHODS: We investigated the role of these viruses in IBD pathogenesis by evaluating the presence of viral DNA within the cells of the intestinal
mucosa, in particular in enterocytes and lamina propria mononuclear cells
(LPMCs). We enrolled 7 IBD patients (5/2 M/F, mean age 47), 1 patient with
profound combined immunodeficiency (M, 28 years) and 8 healthy controls
(HC). All patients underwent lower endoscopy with multiple biopsies.
Enterocytes were separated on a Percoll density gradient and LPMCs obtained
by enzymatic digestion. The viral load was assessed by quantitative RT-PCR on
mucosal specimens, enterocytes and LPMCs. Wilcoxon and Mann-Whitney tests
were applied for statistical analysis.
RESULTS: Viral DNA was found in the mucosa of all the patients and in 2
control subjects, with double positivity for HCMV and EBV DNA in 6 patients,
while EBV DNA alone in the remaining 2 patients and HC. In different colonic
locations, 6 patients showed peak values for EBV DNA above 103 copies/105
cells in at least one location, while only 2 patients had similarly high values for
HCMV DNA. No HC showed peak values exceeding 102 copies/105 cells. Viral
DNA was found within enterocytes in 5 patients and in none of the HC, while
inside of LPMCs was evidenced in all patients and 3 HC. HCMV DNA was
found in enterocytes of only 2 patients, while 6 patients had detectable DNA in
LPMCs; instead 5 patients had EBV DNA in enterocytes and in all cases in
LPMCs. EBV DNA median values in healthy and injured mucosa, both in the
enterocytes (223.5 copies/105 cells) and in LPMCs (3348.5 copies/105 cells), were
significantly higher when compared to the levels of HCMV DNA (0 copies/105
cells; 6.5 copies/105 cells in enterocytes and LPMCs respectively) of both patients
and HC. Finally, in inflamed areas EBV DNA median values were higher than in
healthy mucosa.
CONCLUSION: Our data demonstrated the presence of EBV DNA in colonic
LPMCs and enterocytes of patients with IBD, with higher loads observed in the
first population. We also observed high levels of EBV DNA in enterocytes and
LPMCs in the presence of mucosal inflammation. This shows a preponderant
role of EBV compared with HCMV, with further studies needed to improve the
knowledge of the relationship between this virus and clinical manifestations.
Disclosure of Interest: None declared

P0255 AIEC-RECEPTOR CEACAM6 ABNORMAL EXPRESSION IN


CROHNS DISEASE DEPENDS ON HYPOXIA RESPONSIVE
ELEMENTS METHYLATION STATUS AND CHROMATIN
REMODELLING
J. Denizot1, A. Agus1,*, A. Desrichard2, N. Uhrhammer 2, A. DarfeuilleMichaud1, N. Barnich1
1
UMR1071 INSERM, Universite dAuvergne, 2Department of Oncogenetics,
Department of Breast Oncology, Centre Jean Perrin, Clermont-Ferrand, France
Contact E-mail Address: allison.agus1@udamail.fr
INTRODUCTION: Abnormal expression of CEACAM6 is observed at the
apical surface of the ileal epithelium in Crohns disease (CD) patients. This
allows Adherent-Invasive Escherichia coli (AIEC) to colonize gut mucosa, leading to development of inflammation. Our aims were to understand the regulation
of CEACAM6 expression in ileal mucosa of CD patients at the baseline and to
investigate molecular mechanisms involved in AIEC infection-dependent
CEACAM6 overexpression. Since changes in DNA methylation patterns were
reported in CD patients, we analyzed whether epigenetic mechanisms are
involved in the up-regulation of CEACAM6 expression in intestinal epithelial
cells.
AIMS & METHODS: Protein expression and localization were analyzed before
and after AIEC infection using immunofluorescence staining and Western-blot
analysis. HIF-1 and histone H3 Serine 10 phosphorylation (H3S10p) levels were
measured in CEACAM6 promoter region by chromatin immunoprecipitation
(ChIP) in intestinal epithelial cells (IEC). Transgenic CEABAC10 mice expressing human CEACAM6 were orally challenged with 109 AIEC LF82 bacteria. At
3 days post-infection, ileum-associated AIEC were quantified, and mRNA levels
were measured in isolated enterocytes.
RESULTS: Higher expression of CEACAM6 was observed in T84 cells compared to Caco-2 cells. This was associated to high binding of HIF-1 on the
CEACAM6 gene promoter in an open chromatin state region characterized by
increased in H3S10 phosphorylation level. In contrast, Caco-2 cells expressed low
levels of CEACAM6 due to a compact chromatin state in CEACAM6 promoter
(low level of H3S10p). AIEC infection led to increased CEACAM6 expression
related to enhance HIF-1 binding to CEACAM6 promoter. Abnormal H3S10
phosphorylation in CEACAM6 promoter following AIEC infection in IEC
enhanced HIF-1 binding, and subsequent CEACAM6 expression. In vivo,
increased levels of CEACAM6 and HIF-1 proteins were measured in ileal
enterocytes of AIEC-infected CEABAC10 mice, which could be due to high
H3S10 phosphorylation enabling HIF-1 binding to CEACAM6 promoter.
CONCLUSION: AIEC bacteria increased CEACAM6 expression in ileal enterocytes of CEABAC10 mice by stabilizing HIF-1 transcription factor and by
opening chromatin in CEACAM6 promoter. This allowed HIF-1 binding and
subsequent gene transactivation, indicating that abnormal CEACAM6 expression in ileal mucosa of CD patients could be related to AIEC colonizationinduced epigenetic regulation.
Disclosure of Interest: None declared
P0256 WESTERN DIET IN CEACAM6 EXPRESSING MICE: IMPACT ON
SHORT-CHAIN FATTY ACIDS PRODUCTION AND HOST
SUSCEPTIBILITY TO INTESTINAL INFLAMMATION
A. Agus1,*, J. Denizot1, J. Thevenot1, S. Massier1, E. Billard1, S. Denis1,
A. Darfeuille-Michaud1, N. Barnich1
1
UMR1071 INSERM, Universite dAuvergne, Clermont-Ferrand, France
Contact E-mail Address: allison.agus1@udamail.fr
INTRODUCTION: Recent advances have shown that abnormal inflammatory
response observed in Crohns disease (CD) involves interplay between intestinal
microbiota, host genetic and environmental factors. The escalating consumption
of fat and sugar in Western diets parallels an increased incidence of CD during
the latter 20th century. Western lifestyle could explain the increasing prevalence
of new diseases such as CD.
AIMS & METHODS: We aimed at understanding the multifactorial etiology of
CD by evaluating the modulation of host physiology in response to nutrition. We
analyzed the impact of a High-Fat/High-Sugar (HF/HS) diet in mice on gut
micro-inflammation, selection of E. coli population, concentration of shortchain fatty acids (SCFA) and expression of their free fatty acid-receptors such
as G-protein-coupled receptor 43 (GPR43). Mouse sensitivity to DSS-induced
colitis was assessed to evaluate the impact of nutrition in the sensibility to chemically-induced colitis. Mice fed a conventional or a HF/HS diet during 18 weekperiod, fecal lipocalin-2 (Lcn-2) was measured by ELISA to detect low-grade
inflammation during the course of treatment, E. coli populations associated to
colonic and ileal mucosa were quantified, production of SCFA by microbiota
were measured by gas chromatography in fecal samples. GPR43 receptor was
visualized by confocal microscopy after immunostaining of colonic mucosa tissues. The severity of DSS-induced colitis (1% of DSS in drinking water, 10 days)
was evaluated by disease activity index (DAI) measurement, histological score
and cytokine release.
RESULTS: HF/HS diet increased Lcn-2 level in stools from 5 weeks until 18
weeks of treatment, showing that HF/HS diet creates a specific inflammatory
environment in the gut. Interestingly, abnormal proportions of E. coli bacteria
were recovered from colonic and ileal mucosa of mice under HF/HS diet, compared to mice under conventional diet. SCFA concentrations (acetate, propionate, butyrate) were significantly decreased in fecal samples from mice under HF/
HS diet compared to mice fed a conventional diet. Combination of HF/HS diet
led to dysbiosis with an overgrowth of pro-inflammatory E. coli bacteria and a
decrease in protective SCFA producing bacteria. GPR43 receptor expression was
reduced in mice treated with an HF/HS diet compared to mice under a conventional diet. In addition, HF/HS diet led to an exacerbation of gut inflammation

A200
following DSS-induced colitis, with an increase of DAI, histological score and
release of pro-inflammatory cytokines.
CONCLUSION: Western diet creates a low-grade inflammation in the gut with a
decrease of protective SCFA producing bacteria, leading to overcolonization by
E. coli opportunistic pathogen bacteria which could aggravate the inflammatory
process resulting in chronic inflammation. Together, these findings support the
multifactorial etiology of CD and highlight the importance of nutrition factors in
CD pathogenesis.
Disclosure of Interest: None declared
P0257 VITAMIN D REGULATES THE TIGHT-JUNCTION PROTEINS
EXPRESSION IN ACTIVE ULCERATIVE COLITIS
A.G. Bonanomi1,*, V. Annese1, L. Retico1, M. Martinesi2, M. Stio2
1
Gastroenterology Unit 2, Azienda Ospedaliero-Universitaria Careggi Firenze,
2
Biochemical Sciences, University of Florence, Firenze, Italy
Contact E-mail Address: maria.stio@unifi.it
INTRODUCTION: Epithelial barrier function is primarily regulated by the
tight-junction proteins (TJ). Ulcerative colitis (UC) is characterized by Th2
immune response with inflammation and epithelial barrier dysfunction, including
an elevation of claudin-2 protein function (1).
In UC, epithelial leaks appear early due to micro-erosions resulting from upregulated epithelial apoptosis and from a significant IL-13-dependent arrest in
epithelial restitution (2).
Vitamin D is traditionally associated with bone metabolism. Importantly,
recently studies support an important role of vitamin D in the pathogenesis as
well as potential therapy of IBD. Vitamin D deficiency is in fact common in
patients with IBD (3).
AIMS & METHODS: Our aim was to determine whether vitamin D could affect
IL-13 and IL-6 levels, and regulate the activity of tight-junction proteins Claudin1, -2, -4 and -7 in the inflamed and non-inflamed colonic mucosa of UC patients.
Methods: Biopsies from the colon (rectum, sigma) of patients with active UC
were studied. Non-inflamed (NI) and inflamed (I) intestine tissues, obtained from
the same patient, were cultured with 10 nM 1,25(OH)2D3. After 24 h incubation
the medium was removed and used for the determination of IL-13 and IL-6 levels
by ELISA test. The lysates of biopsies were used to determine the levels of TJ
protein by Western blot analysis.
RESULTS: Claudin-1 and Claudin-2 proteins were up-regulated in active UC.
The treatment with 1,25(OH)2D3 increases the Claudin-1 levels in the NI tract
and decreases their level in the I tract, while the treatment with 1,25(OH)2D3
remarkably decreases the Claudin-2 protein level in both I and NI tract. Claudin4 and Claudin-7 proteins were down-regulated with Western Blot Analysis and
their levels increase when both NI and I tract were cultured in the presence of the
1,25(OH)2D3. IL-13 and IL-6 levels decrease incubating the biopsies with
1,25(OH)2D3.
CONCLUSION: Our study reports a down-regulation of claudin-4 and claudin7, and an up-regulation of claudin-2, that might lead to altered TJ structure and
be related to the impaired epithelial function in active UC.
Our results, indicating the inhibition of cytokine levels and the regulation of
Claudin-2, Claudin-4 and claudin-7 by 1,25(OH)2D3, suggest that vitamin D
may represent a potential target for the treatment of IBD.
REFERENCES
1) Hering NA and Schulzke JD. Therapeutic options to modulate barrier defects
in inflammatory bowel disease. Dig Dis 2009; 27: 450-454.
2) Schulzke JD, Ploeger S, Amasheh M, et al. Epithelial tight junctions in intestinal inflammation. Ann N Y Acad Sci 2009; 1165: 294-300.
3) Mouli VP and Ananthakrishnan AN. Review article: Vitamin D and inflammatory bowel disease. Aliment Pharmacol Ther 2014; 39: 125-136.
Disclosure of Interest: None declared
P0258 SMOKING IS ASSOCIATED WITH WATERY DIARRHEA AND
DECREASED LIKELIHOOD TO ACHIEVE CLINICAL REMISSION
IN COLLAGENOUS COLITIS
A. Munch1,*, J. Bohr2, A. Madisch3, O. Bonderup4, C. Tysk2, M. Strom1,
R. Mohrbacher5, R. Muller5, R. Greinwald5, S. Miehlke6 on behalf of European
Microscopic Colitis Group (EMCG)
1
University hospital, Linkoping, 2University hospital, Orebro, Sweden, 3Siloah
hospital, Hannover, Germany, 4Regional hospital, Silkeborg, Denmark, 5DrFalk
Pharma, Freiburg, 6Center for Digestive Diseases, Hamburg, Germany
Contact E-mail Address: andreas.munch@lio.se
INTRODUCTION: Smoking seems to be a risk factor for microscopic colitis and
smokers develop the disease more than 10 years earlier than non-smokers.
However, the impact of smoking on clinical activity and outcome has not been
elucidated.
AIMS & METHODS: In a post-hoc analysis from pooled data of two randomized controlled trials (BUC-60/COC and BUC-63/COC) we assessed the association of demographical (gender, age, smoking habits, previous and/or
concomitant medication, family history of inflammatory bowel disease) and clinical variables (duration of symptoms, mean number of stools/watery stools per
day, abdominal pain, clinical remission). Moreover, we analyzed the predictive
value of baseline parameters on clinical outcome in a logistic regression model.
RESULTS: Pooled data from 202 patients with active collagenous colitis (CC)
were available thereof 36% current smokers, 29% former smokers and 35% nonsmokers. Current smokers had an increased number of watery stools at baseline
compared to non-smokers (p 0.05). 20/137 (15%) patients treated with budesonide did not achieve clinical remission. The majority of these (85%) were either
smokers or former smokers. An association was found between smoking status
(current smokers vs. non smokers: OR 0.37, 95% CI: 0.14-0.96, p 0.041; former

United European Gastroenterology Journal 2(1S)


smokers vs. non smokers: OR 0.21, 95% CI: 0.07-0.60, p 0.004), mean number
of watery stools per day (OR 0.77, 95% CI: 0.66-0.90, p 0.001) and decreased
likelihood to obtain clinical remission. All other variables showed no significant
association.
CONCLUSION: Smoking is associated with increased number of watery stools
and decreased likelihood to achieve clinical remission in collagenous colitis.
Smoking seems to have an impact on disease activity and treatment outcome
in patients with CC.
Disclosure of Interest: A. Munch Financial support for research from: Abbvie,
Lecture fee(s) from: MEDA, Dr Falk Pharma, MSD, J. Bohr: None declared, A.
Madisch: None declared, O. Bonderup Lecture fee(s) from: Dr Falk Pharma, C.
Tysk Lecture fee(s) from: Tillotts Pharma, Falk Pharma, Ferring, MSD, and
AstraZeneca., M. Strom: None declared, R. Mohrbacher Other: employee of
DrFalk Pharma, R. Muller Other: employee of DrFalk Pharma, R. Greinwald
Other: employee of DrFalk Pharma, S. Miehlke Lecture fee(s) from: Dr Falk
Pharma
P0259 REDUCED MUCOSAL EXPRESSION OF INSOLUBLE KERATINS
8, 18 AND 19 IN ACTIVE COLITIS RELATIVE TO PROXIMAL
INACTIVE COLONIC MUCOSA: VALIDATION OF MASS
SPECTROMETRY DATA
A. Assad-Sangabi1,2,*, C. Evans3, D. Majumdar1, B. Corfe2, A. Lobo1
Gastroenterology Department, Royal Hallamshire Hospital, 2Oncology
Department, 3Department of Chemical and Biological Engineering, University of
Sheffield, Sheffield, United Kingdom
Contact E-mail Address: arash.sangabi@gmail.com
1

INTRODUCTION: Intermediate filaments (IF) are one of the main components


of the human cell cytoskeleton, which mainly consist of keratins (K). K8, K18
and K19 constitute the main keratins in the intestinal epithelial cells. Keratin
alteration may play a role in the pathophysiology of ulcerative colitis (UC). K8
-/- mice develop chronic colitis (1). Heritable predispositions to UC were mapped
to the K8/18 loci in human (2). K8 and K18 play a role in TNF- inducedapoptosis (3). We have previously shown reduced expression of insoluble K8,
K18 and K19 in active UC (ACT) relative to un-inflamed proximal colonic
mucosa (INACT) using mass spectrometry (MS) analysis in the IF fraction of
pooled patient samples from these two groups. The aim of this study was to use
antibody-based relative quantification of K8, K18 and K19 in individual patient
samples to validate MS results and describe variation in expression across the
cohort.
AIMS & METHODS: IF proteins were extracted from rectal biopsies in patients
with active colitis (n 9) as well as endoscopically and histologically un-inflamed
proximal colonic mucosa in each individual. IF proteins extracted from the
sigmoid colon of a normal individual was used as an internal control. Each
sample was dot-blotted on a membrane followed by immunoblotting for identification and quantification of keratins (8, 18 &19) sequentially. A control MCF-7
sample was included in all immunoblots to allow normalisation between sample
groups. Relative keratins concentration for each dot- blotted sample was inferred
by determining its signal intensity relative to the MCF-7 keratins signal intensity
measured in turn by densitometry. Statistical analysis to compare the two groups
was made separately for K8, K18 and K19 using Mann-Whitney U test.
RESULTS: Median relative IF protein levels from the active mucosa were 0.18,
0.28 and 1.48 for K8, K18 and K19, respectively were significantly lower than
those from the un-inflamed inactive mucosa: 1.21, 1.16 and 3.59 for K8
(p 0.02), K18 (p 0.03) and K19 (p 0.02), respectively. Median Barons endoscopy score in ACT and INACT biopsy samples were 2 (range 2-3) and 0 (range
0-1), respectively. Median histological activity index in ACT and INACT were 2
(range 1-3) and 0 (range 0). Median disease duration was 5 years in the cohort.
CONCLUSION: This study confirms reduced expression of insoluble keratins in
the active colonic epithelial cells relative to the un-inflamed proximal colonic
mucosa and validates our previous MS observations. Insoluble keratin expression may be used as a tissue marker of disease activity.
REFERENCES
1. Baribault H, Penner J, Iozzo RV, et al. Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev 1994; 8: 2964-2973.
2. Owens DW, Wilson NJ, Hill AJ, et al. Human keratin 8 mutations that disturb
filament assembly observed in inflammatory bowel disease patients. J Cell Sci
2004; 117(Pt 10): 1989-1999.
3. Caulin C, Ware CF, Magin TM, et al. Keratin-dependent, epithelial resistance
to tumor necrosis factor-induced apoptosis. J Cell Biol 2000; 149: 17-22.
Disclosure of Interest: None declared
P0260 PANCREATIC EXOCRINE INSUFFICIENCY IS NOT
CLINICALLY SIGNIFICANT PROBLEM IN PATIENTS WITH
ULCERATIVE COLITIS

B. Lindkvist1,*, B. Jonefall1, H. Strid2, M. Simren1


1
Medicine, 2Sahlgrenska University Hospital, Goteborg, Sweden
Contact E-mail Address: bjorn.lindkvist@vgregion.se
INTRODUCTION: It is not uncommon that patients with ulcerative colitis
report symptoms such as diarrhea, bloating and abdominal discomfort despite
a complete absence of biochemical and endoscopic signs of disease activity. One
possible explanation to this phenomenon is that these patients may suffer from
pancreatic exocrine insufficiency (PEI). One previous study has indicated that the
prevalence of PEI may be as high as 17% in patients with inflammatory bowel
disease (IBD) (1). However, most studies on PEI in IBD including the aforementioned have used fecal elastase (Fel-1) as the only method to investigate pancreatic exocrine function. Concerns have been raised about the diagnostic accuracy of
Fel-1 to diagnose PEI in IBD due to dilution effects and increased degradation.

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United European Gastroenterology Journal 2(1S)


Hence, studies on the prevalence of PEI in IBD patients using more specific tests
of exocrine pancreatic function are warranted. The 13C-mixed triglycerides
(MTG) breath test is a non-invasive pancreatic function test that can be used
to confirm the diagnosis of PEI with high sensitivity and specificity.
AIMS & METHODS: The aim of the present study was to investigate the prevalence of PEI and clinical factors associated with PEI in patients with ulcerative
colitis. Cases with ulcerative colitis seen at the out patient clinic of Sahlgrenska
University Hospital were included in the study. Ulcerative colitis disease activity
was evaluated by the Mayo scoring system for assessment of ulcerative colitis
activity, fecal calprotectin, and sigmoidoscopy. Patients were screened for PEI
using the Fel-1 test. Subjects with low Fel-1 were further examined using the 13CMTG breath test. Computed tomography (CT) was used to evaluate pancreatic
morphology in cases where the 13C-MTG breath test could confirm the PEI
diagnosis.
RESULTS: In total 192 patients with ulcerative colitis were included in the study
(mean age 44 years, 110 (57%) male, 93 (48%) with active disease). Fel-1 below
the lower limit of normal (200 g/g stool) was observed in 15 (7.8%) patients.
There was no difference in age, ulcerative colitis disease activity, stool frequency
or azathioprine use between patients with low and normal Fel-1 (Table 1).
Further examination of patients with low Fel-1 with the 13C-MTG breath test
revealed normal pancreatic exocrine function in all but one patient. This patient
had signs of atrophy of the pancreas on CT.
Table 1

Age, median (inter quartile


range)
UC, active disease (Mayo
score 40)
Self-reported increased
stool frequency
Calprotectin, median (inter
quartile range)
Azathioprine use

Fecal elastase
5200 g/g

Fecal elastase
4200 g/g

p-value

43 (39-61)

43 (33-54)

0.21

8/15 (53%)

85/177 (48%)

0.79

6/15 (40%)

59/177 (33%)

0.58

120 (52 to 390)

64 (18 to 260)

0.30

1/15 (7%)

27/177 (15%)

0.70

CONCLUSION: Fel-1 values below normal can be found in a minority of


patients with ulcerative colitis but the vast majority of these patients have no
signs of PEI when further tested with the 13C-MTG breath test. Our diagnostic
strategy using Fel-1 as a screening test followed by the 13C-MTG test as a
confirmatory test indicated that clinically significant PEI is rare in patients
with ulcerative colitis.
REFERENCES
1. Maconi G, et al. Dig Dis Sci 2008; 53: 262-270.
Disclosure of Interest: B. Lindkvist Financial support for research from: Abbott,
Consultancy for: Astra Zeneca, B. Jonefall: None declared, H. Strid: None
declared, M. Simren: None declared
P0261 ENTERIC GLIAL CELLS PRODUCE 15-HETE TO REGULATE
INTESTINAL EPITHELIAL PROPERTIES: DYSREGULATION IN
CROHNS DISEASE
S. Coquenlorge1, C. Pochard1,*, J. Jaulin1, T. Durand1, N. Cenac2,
N. Vergnolle2, M. Neunlist1, M. Rolli-Derkinderen1
1
inserm UMR913, nantes, 2Inserm, U1043, CNRS, U5282, toulouse, France
Contact E-mail Address: malvyne.derkinderen@univ-nantes.fr
INTRODUCTION: Accumulating data demonstrate that under physiological
conditions, enteric glial cells (EGC) positively regulate the intestinal epithelial
barrier (IEB). EGC are necessary for IEB homeostasis, increase IEB healing and
decrease IEB permeability, identifying EGC as a source for soluble factors able
to reinforce the IEB. The most recently discovered prostaglandin 15dPGJ2 is
produced by EGC to regulate intestinal epithelial cell (IEC) proliferation and
differentiation. However nothing is known considering other polyunsaturated
fatty acid (PUFA) metabolites that could also be produced by EGC.
AIMS & METHODS: The PUFA signature of the JUG embryonic cell line as
well as rat adult primary cultures of EGC were established using high sensitivity
liquid chromatography tandem mass spectrometry. Immunohistochemistry was
used to detect the 15-LOX producing enzyme of 15-HETE on rat and human
EGC cultures and on human sub-mucosal plexus. Pharmacological approach
was used to determine 15-HETE impact on Caco-2 monolayer cultivated or
not in presence of EGC. Direct injection of 15-HETE into the colon wall was
used to measure its impact on IEB permeability in vivo.
RESULTS: Among the 24 PUFA metabolite measured, rat EGC mostly produced 5- and 15-HETE. They also expressed the 15-lipoxygenase 2 (15-LOX2),
whereas the 15-lipoxygenase 1 was undetectable. 15-HETE increased IEC spreading, IEB resistance and decreased IEB permeability without affecting IEC proliferation. In addition, 15-LOX2 was expressed in human EGC in culture but also
in situ in EGC from submucosal ganglia. Interestingly, 15-HETE production by
EGC from CD patients was significantly reduced compared to EGC from control
patients. At the same time, CD EGC were unable to decrease IEB permeability,
but addition of 15-HETE backed up the permeability to control conditions.
In vivo, 15-HETE also reduced the IEB permeability, showing the potential of
15-HETE to reinforce IEB.

CONCLUSION: This study not only presents the first evidence for EGC functional abnormalities in CD, but also reveals that 15-HETE can reduce IEB
permeability
Disclosure of Interest: None declared
P0262 INFLUENCE OF ANTI-TNF THERAPY ON THE BONE
METABOLISM IN PATIENTS WITH INFLAMMATORY BOWEL
DISEASE
C.S. Beatriz1,*, V. Carmen1,2, G.M.Jose1, L. Susana1, F.-G. Pedro1,
G.-U. Mayte3, R. Monserrat1, R.J.Antonio2, C. Javier1
1
Gastroenterology, 2internal medicine, 3Bioquimical, H. U. MARQUES DE
VALDECILLA, SANTANDER, Spain
Contact E-mail Address: digcsb@humv.es
INTRODUCTION: Several studies have concluded that patients with inflammatory bowel disease (IBD) are at increased risk of osteoporosis. The increase of
proinflammatory cytokines, as TNF- and interleukins (IL) appear to mediate,
as a pathogenic mechanism, in the loss of bone mass density (BMD) in these
patients. However, the influence of anti-TNF drugs on the bone metabolism of
patients with IBD is not well known. Our aim is to evaluate the influence of antiTNF drugs on bone mineral density and markers of bone remodeling in IBD
patients.
AIMS & METHODS: Prospectively we have enrolled 8 patients (2 men and 6
women) with active IBD, 2 ulcerative colitis and 6 Crohns disease, all with
indication for treatment with anti-TNF drugs. Clinical data were collected on
standardized data forms. BMD values were measured by dual-energy X-ray
absortiometry (Hologic QDR 4500) at the lumbar spine (L1-L4) and femoral
neck (FN) baseline visit and after a year of treatment. We determined serum 25hydroxyvitamin D3 (25OHD ng/ml) and intact parathyroid hormone (PTH pg/
ml). Bone turnover markers were measured by fully automated electrochemiliminescence system (Elecsys 2010, Roche Diagnostic, Germany): aminoterminal
propeptide of type collagen (P1NP) and C-terminal telopeptide of type I collagen
(CTX) at baseline visit, 8 week, 6 month and a year after treatment.
RESULTS: In our study, mean age was 42 years (age range 24-54). Two patients
were treated with infliximab and 6 with adalidumab. All of them had been treated
previously with 5-ASA, Azathioprine in 50% and corticoids in 20%. Mean basal
weight (61 kg) did not change over treatment. The BMD in lumbar spine was
1.031 (0.112) g/cm2 at baseline and 1.037 (0.127) g/cm2 a year after. The BMD in
FN was 0.755 (0.131) g/cm2 and 0.774 (0.120) g/cm2 respectively. The percentage
of change in lumbar spine was 1% (p 0.77) and in FN 2.5% (p 0.15). Data
table show biochemical parameters and different percentages over basal state.

25OHD ng/ml
iPTH pg/ml
P1NPmg/L
-CTX ng/ml

Baseline

8 week

6 month

Year

21 (9)
27 (11)
49 (26)
0.421
(0.210)

21 (9) [0%]
37 (13) [37%]*
66 (26) [34%]*
0.380 (0.328)
[-9%]

24 (12)[14%]
30 (11) [11%]
61 (17) [24%]
0.488(0.326)
[15%]

23 (12) [9%]
38 (19) [40%]
43 (23) [-13%]
0.419(0.332)
[-2%]

CONCLUSION: 1. Bone mass in IBD patients with TNF-  inhibitors treatment


were similar at baseline and after a year of treatment.
2. P1NP was increased 8 week after the beginning of treatment but P1NP
returned to basal level after a year. Parathyroid hormone levels seem to increase
early after the beginning of treatment and remains above basal levels over time.
-CTX and vitamin D, bone resorption markers, were stable during treatment.
3. Further studies are required to analyze the relationship between this therapeutic agents and bone metabolism in IBD.
Disclosure of Interest: None declared
P0263 EDUCATION OF PATIENTS WITH CROHNS DISEASE ON THE
RISKS OF SMOKING REMAINS CHALLENGING
C. De Bie1,*, V. Ballet1, G.Van Assche1, S. Vermeire1, M. Ferrante1
Department of Gastroenterology, UNIVERSITY HOSPITALS LEUVEN,
Leuven, Belgium
1

INTRODUCTION: The detrimental effect of smoking on development and progression of Crohns disease (CD) is generally accepted. Although health care
professionals undoubtedly spend a lot of time in education of patients, the
actual awareness of smoking risks in CD patients is unclear.
AIMS & METHODS: We assessed several smoking behaviour parameters and
patients awareness on different consequences of smoking, through a simple
questionnaire in a single referral centre. During the outpatient clinic of gastroenterology, 625 consecutive patients with CD, 238 patients with ulcerative colitis
(UC) and 289 patients without an inflammatory bowel disease (non-IBD controls, NC) were requested to participate. Questionnaires included questions on
former and actual smoking behaviour, cessation attempts, nicotine dependence
(Fagerstrom score), and willingness to quit smoking. Patients were questioned on
their awareness of smoking-related risks on several aspects of health, including
detrimental effects on CD (Table 1).
RESULTS: Participation rates were 92% for CD (n 575, 46% male, 44 years,
44% never smoked), 93% for UC (n 238, 57% male, 45 years, 50% never
smoked) and 76% for NC (n 221, 48% male, 48 years, 55% never smoked).
At diagnosis, more CD patients were active smokers compared to UC patients
(40% vs. 17%, p50.001). Previous attempts to stop smoking and nicotine dependence were similar in all groups. Remarkably, smoking cessation rates after

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United European Gastroenterology Journal 2(1S)

diagnosis were not higher in CD compared to UC (both 56%, p 0.997). In


contrast, more CD than UC patients started smoking after diagnosis (12% vs.
6%, p 0.050). As shown in Table 1, the majority of patients recognized dangers
of smoking on general health (98-99%), lung cancer (95-97%), myocardial
infarction (89-92%), and stroke (78-87%). Although CD patients more frequently acknowledged risks of smoking on their disease, only 37% were aware
of the link with CD development, 30% of increased surgical rates, and 27% of
increased postoperative recurrence rates. Of note, within the CD population,
awareness was unrelated to actual smoking behaviour. Increased surgery rates
were acknowledged by 30% of active, 32% of former and 29% of non-smokers
(p 0.783). Active smokers not willing to quit smoking, most often denied a
potential bad influence of smoking on their disease. Previous surgery, level of
education and employment did not influence awareness. Finally, UC patients
were more frequently aware of an inverse relationship between smoking and
UC development (39% UC, 16% CD, 4% NC, p50.001).
Smoking increases
the risk of
bad general health
CD
UC
NC
lung cancer
CD
UC
NC
myocardial infarction
CD
UC
NC
stroke
CD
UC
NC
CD
CD
UC
NC
CD surgery
CD
UC
NC
postoperative CD recurrence
CD
UC
NC
UC
CD
UC
NC

Certainly I dont I dont I think


not
think so know
so
Certainly

0%
1%
0%

0%
0%
0%

2%
0%
0%

13%
12%
6%

85%
87%
94%

0%
0%
0%

1%
1%
0%

4%
4%
3%

18%
16%
12%

77%
79%
85%

0%
0%
0%

1%
1%
0%

10%
9%
8%

28%
31%
25%

61%
59%
67%

0%
0%
0%

2%
2%
0%

17%
20%
12%

30%
29%
27%

51%
49%
61%

4%
2%
0%

14%
19%
5%

45%
61%
71%

19%
10%
14%

18%
8%
10%

1%
1%
0%

10%
10%
4%

59%
72%
77%

20%
12%
11%

10%
5%
8%

2%
0%
0%

9%
12%
3%

62%
74%
81%

18%
10%
9%

9%
4%
7%

4%
10%
1%

12%
29%
3%

67%
48%
76%

13%
8%
13%

4%
5%
7%

CONCLUSION: Although CD patients were better informed on the detrimental


effects of smoking, the awareness rate was still low. These data may also suggest
more denial for the adverse consequences of smoking in active smokers. More
efforts need to be done on informing and educating patients regarding the risks
of smoking.
Disclosure of Interest: C. De Bie: None declared, V. Ballet: None declared, G.
Van Assche Financial support for research from: Abbvie, Ferring, Lecture fee(s)
from: Abbvie, MSD, Janssen Biologics, Consultancy for: PDL BioPharma, UCB
Pharma, Sanofi-Aventis, Abbvie, Ferring, Novartis, Biogen Idec, Janssen
Biologics, NovoNordisk, Zealand Pharma, Takeda, Shire, Novartis, BMS, S.
Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie,
Lecture fee(s) from: Abbvie, MSD, Ferring, UCB Pharma, Janssen Biologics,
Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Shire,
Pfizer, M. Ferrante Financial support for research from: Abbvie, Janssen
Biologics, MSD, Lecture fee(s) from: Abbvie, Janssen Biologics, MSD,
Tillotts, Ferring
P0264 HIF-1 MEDIATES THE HYPOXIC UP-REGULATION OF DLL4
AND JAG1 IN MACROPHAGES: RELEVANCE IN IBD
D. Ortiz-Masia1,*, D.C. Macias-Ceja1, J. Cosin-Roger1, S. Calatayud1,
C. Hernandez2, D. Barrachina1
1
PHARMACOLOGY, CIBEREHD-UNIVERSIDAD DE VALENCIA,
2
PHARMACOLOGY, FISABIO, VALENCIA, Spain
Contact E-mail Address: mdorma@uv.es
INTRODUCTION: Mucosal healing, which has been established as a target goal
in inflammatory bowel disease, involved the coordinated regulation of several
signaling pathways, including Notch signaling which plays an essential role in

differentiation. Macrophages constitute one of the central components of the


inflamed mucosa, and have the ability to modulate epithelial cell function. We
have previously reported1 HIF-1 stabilization in macrophages from the mucosa
of IBD patients and we aim to analyse here the expression of Notch ligands by
macrophages and the role of HIF-1.
AIMS & METHODS: U937 cells were subjected to hypoxia (3% O2) or normoxia (21% O2) and protein levels of HIF-1 were analysed by Western blotting
and the mRNA expression of Dll4 and Jag1 ligands by real time PCR (n 5). In
some cases, cells were subjected to transient transfection of HIF-1 with miRNA
or with an empty vector (mock, n 5). Analysis of the Jag1 gene promoter was
performed using a ChIP assay (n 3). Colonic surgical resections from both
damaged and non-damaged mucosa were obtained from IBD patients (n 11).
In both cases, macrophages were isolated from the mucosa and the expression of
Dll4 and Jag1 ligands was determined by real time PCR. HIF1, CD68 and Jag1
immunofluorescence experiments were performed in the mucosa of IBD patients.
RESULTS: In mock U937 cells, hypoxia induced HIF-1 stabilization and a
time-dependent increase in Dll4 and Jag1 mRNA expression, which starts to
be significantly different from normoxia 5 h later (4.1  0.4 and 18.5  2.1
fold induction vs macrophages in normoxia, respectively). The increase induced
by hypoxia was significantly decreased when macrophages had been treated with
miHIF-1 (0.94  0.34 and 4.3  2.4 fold induction vs macrophages in normoxia,
respectively). ChIP assay showed HIF-1 binding to the proximal promoter
region of Jag1 gene in hypoxia through the HREs sequences located between
positions -106 and -638. Immunofluorescence experiments revealed that CD68positive cells were co-localized with HIF-1 and Jag1 in the damaged mucosa of
IBD patients. The mRNA expression of Dll4 and Jag1 was significantly higher in
macrophages isolated from damaged mucosa than from non-damaged (1.5  0.2
and 3.2  0.7 fold induction vs macrophages from non-damaged mucosa,
respectively).
CONCLUSION: HIF-1 mediates the increase in the expression of Dll4 and
Jag1 induced by hypoxia in macrophages. Jag1 expression co-localizes with
HIF1 in macrophages of the mucosa of CD patients and it is higher in macrophages from damaged than from non-damaged mucosa.
REFERENCES
1. Ortiz-Masia`, D. et al. Hypoxic macrophages impair autophagy in epithelial
cells through Wnt1: relevance in IBD. Mucosal Immunol 2013 Dec 4.
Disclosure of Interest: None declared
P0265 THE
MACROPHAGE
PHENOTYPE
DIFFERENTIALLY
MODULATES NOTCH SIGNALING PATHWAY IN EPITHELIAL
CELLS: RELEVANCE IN DISEASE CROHNS
D. Ortiz-Masia1,*, J. Cosin-Roger1, S. Calatayud1, C. Hernandez2,
D. Barrachina1
1
PHARMACOLOGY, CIBEREHD-UNIVERSIDAD DE VALENCIA,
2
PHARMACOLOGY, FISABIO, VALENCIA, Spain
Contact E-mail Address: mdorma@uv.es
INTRODUCTION: Crohns disease (CD) is associated with impaired epithelial
barrier function. Restoration of mucosal integrity involves proliferation and
differentiation of intestinal epithelial cells and Notch signaling has been shown
to be central in the regulation of these processes. Macrophages are present in the
microenvironment surrounding the crypts in the intestine and may modulate the
behavior of epithelial cells. We have previously reported presence of both M1
and M2 macrophage phenotypes in the mucosa of ulcerative colitis patients1. We
aim to determine the role of different macrophage phenotypes on epithelial
Notch signaling and the relevance of this pathway in CD.
AIMS & METHODS: U937 cells were polarized towards a M1 phenotype with
IFN and LPS (24h) or M2 phenotype with IL-4 (72h) and these cells were cocultured with HT29 cells for 24h. Next we determined in epithelial cells, the
expression of HES1 by static cytometry and alkaline phosphatase activity.
Damaged mucosa of patients with CD was obtained. Protein levels of HES1
and the expression of CD86 (M1 marker) or CD206 (M2 marker), were quantified in the mucosa.
RESULTS: Immunofluorescence experiments show that M1 macrophages cocultured with HT29 cells did not significantly modify the expression of HES1
(87.4  5.4% vs the basal expression in HT29 cells) but induce a significant
(P50.05) increase in AP activity in epithelial cells (125.4  3.0% vs the basal
activity in HT29 cells). In contrast, M2-macrophages significantly (P50.05)
reduced in HT29 cells both, HES1 expression (62.1  11.1% vs the expression
in HT29 cells) and AP activity (62.5  4.1% vs the activity in HT29 cells). A
quantitative analysis of the number of CD86-and CD206-positive cells in the
damaged mucosa of CD patients as well as protein levels of HES1, reveal a
negative and significant correlation between the ratio of M2/M1 macrophages
and HES1 protein levels (Pearson r -0.6775, P value 0.031, n 10).
CONCLUSION: M2 macrophages induced a profound reduction in epithelial
Notch signaling and impair enterocyte differentiation while M1 macrophages
failed to do that. In the damaged mucosa of CD patients, the prevalence of
M2 macrophages, through diminution of both epithelial Notch signaling and
enterocyte differentiation, may impair epithelial regeneration.
REFERENCES
1. Cosin-Roger J, et al. M2 macrophages activate WNT signaling pathway in
epithelial cells: relevance in ulcerative colitis. PLoS One 2013; 8.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)


P0266 A DIMINISHED NOTCH SIGNALLING AND IMPAIRED
ENTEROCYTE DIFFERENTIATION IS OBSERVED IN EPITHELIAL
CELLS FROM DAMAGED MUCOSA OF CROHNS DISEASE
PATIENTS
1,*

D. Ortiz-Masia , J. Cosin-Roger , S. Calatayud , C. Hernandez ,


D. Barrachina1
1
PHARMACOLOGY, CIBEREHD-UNIVERSIDAD DE VALENCIA,
2
PHARMACOLOGY, FISABIO, VALENCIA, Spain
Contact E-mail Address: mdorma@uv.es
INTRODUCTION: Mucosal healing has been established as a key treatment
goal in Crohns disease (CD) that predicts sustained clinical remission and resection-free survival of patients. This process depends on the proper reconstruction
of the intestinal epithelium that depends on proliferation and differentiation of
progenitor cells, a process that is tightly regulated by activation of the Notch
signalling. We aim to determine the regulation of the Notch pathway and epithelial differentiation in the mucosa of CD patients.
AIMS & METHODS: Colonic surgical resections from both damaged and nondamaged mucosa were obtained from CD patients (n 11). Human intestinal
crypts were isolated from mucosa by using a non-enzymatic dissociation technique based on short-term EDTA treatment. Protein levels of IAP (marker of
enterocyte differentiation) and HES1 (a specific Notch target gene) were analyzed by Western blotting and immunohistochemistry (HES1). The expression of
MUC2 (a marker of goblet cell differentiation), CDX2 (a transcriptional activator of intestine specific genes involved in differentiation) and Math1 (a gene that
is repressed by HES1) was analyzed in epithelial cells by real time PCR. The
quantitative analysis of goblet cells was performed in the mucosa stained with
PAS.
RESULTS: A comparative study (fold induction vs crypts from non-damaged
mucosa) revealed a significant (P50.05) diminution in protein levels of HES1
(0.28  0.07) and IAP (0.20  0.10) and a significant increase in mRNA levels of
MUC2 (11.8  2.3), CDX2 (2.1  0.8) and Math1 (3.4  0.8) in crypts from
damaged mucosa. Immunostaining for HES1 revealed lack of this protein in
epithelial cells of the damaged mucosa. The percentage of goblet cells vs. total
nuclei in the crypt was significantly (P50.05) higher in the damaged (47.8 
4.4%) than in the non-damaged mucosa (29.2  2.4%).
CONCLUSION: The diminished Notch signaling and impaired enterocyte differentiation detected in epithelial cells from damaged mucosa of CD patients may
mediate the weakened mucosal healing observed in these patients.
Disclosure of Interest: None declared
P0267 HUMAN INTESTINAL FIBROBLASTS ARE NOVEL TARGET
CELLS FOR ALPHA-MELANOCYTE-STIMULATING HORMONE
POSSIBLE IMPLICATIONS FOR THE TREATMENT OF
STRICTURING CROHNS DISEASE WITH MELANOCORTIN
PEPTIDES AND DERIVATIVES
D. Bettenworth1,*, A. Stegemann2, P.R. Tepasse1, E. Rijcken3, M. Apel2,
M. Bohm2
1
Department of Medinice B, 2Department of Dermatology, 3Department of General
and Visceral Surgery, University Hospital Munster, Munster, Germany
Contact E-mail Address: dominik.bettenworth@ukmuenster.de
INTRODUCTION: Efficient treatment against fibrotic complications like intestinal strictures is still an unmet need in patients with Crohns disease. In dermal
fibroblasts, melanocortin peptides such as a-melanocyte-stimulating hormone (aMSH) were shown to modulate collagen synthesis. Moreover, in the bleomycin
scleroderma mouse model this peptide had anti-fibrotic effects. Thus, we wondered if human intestinal fibroblasts are also target cells for melanocortins in the
context of extracellular matrix synthesis.
AIMS & METHODS: Human intestinal fibroblasts were isolated from macroscopically normal colonic specimens of patients undergoing scheduled colonic
surgery (n 5) and were characterized by immunohistochemistry with antidesmin, anti-vimentin and anti-alpha-smooth muscle actin antibodies.
Melanocortin receptor (MC) expression was determined by RT-PCR.
Intracellular Ca2 mobilization indicating functional coupling of the detected
MC was assessed by FURA-2AM loading and fluorescence analysis. Collagen
type I expression was determined by RT-PCR and secretion of procollagen type I
C-terminal peptide by ELISA.
RESULTS: Immunocytochemistry with anti-desmin, anti-vimentin and antialpha-smooth muscle actin antibodies confirmed a myofibroblast phenotype of
isolated cells. MC expression profiling proved that these cells exclusively express
MC1. Truncated transcripts for proopiomelanocortin (POMC), the precursor of
a-MSH, were also detected but no functional full-length POMC mRNA. In
accordance, cells lacked POMC protein expression ruling out an autocrine
loop for alpha-MSH. No Ca2 mobilization was detected by FURA-2AM loading, after stimulation with a-MSH and fluorescence analysis. However, a-MSH at
doses between 10-6 and 10-10 M significantly suppressed procollagen type I Cterminal peptide secretion induced by TGF-b1. This effect was not paralleled by
reduction in corresponding COL(I) mRNAs indicating a posttranscriptional
mechanism of the regulatory effect of a-MSH on collagen synthesis.
CONCLUSION: These findings demonstrate that human intestinal fibroblasts
are novel targets for alpha-MSH. It will be intriguing to assess the effect of other
melanocortins and derivatives in these cells on collagen synthesis as well as the
impact of them in animal models of intestinal fibrosis.

Disclosure of Interest: None declared


P0268 HEARING LOSS IN PATIENTS WITH INFLAMMATORY BOWEL
DISEASE (IBD)
D. Wengrower1,*, C. Shaul2, U. Peleg2, L. Cohen3, M. Gross3, B. Koslowsky1
Digestive Disease Institute, 2ENT Dept, Shaare Zedek Medical Center, 3ENT
Dept, Hadassah University Hospital, Jerusalem, Israel
Contact E-mail Address: dovwen@szmc.org.il
1

INTRODUCTION: IBD has many characteristics of autoimmune diseases.


Sensorineural hearing loss has been reported in many autoimmune diseases.
Little is known about hearing loss in patients with IBD.
AIMS & METHODS: A prospective blinded comparative study was conducted
over a 3 year period. IBD patients and controls underwent a complete otorhinolaryngeal examination and eudiometry test.
RESULTS: Altogether 105 participants (76 patients and 29 controls) took part in
this study. 59(77%) had Crohns disease (CD) and 17(23%) had ulcerative colitis
(UC). Mean age was 36, 51% were males and 40% of the patients were presently
hospitalized due to IBD exacerbation. 16/76(21%) of the IBD patients complained of hearing loss since first IBD diagnosis and 13% had current hearing
disabilities. Audiometric examination revealed that any hearing loss (mild to
severe) was found in 23(30%) of the IBD population, compared to 3 (10%) of
the control group (p50.05). Sensironeural was the hearing deficiency type in
93% of them. Out of 46 patients, whose extraintestinal manifestation (EIM)
status was clearly documented, 43% (n 20) had EIMs. Hearing loss was present
in 5/20 (25%) of these patients, compared to 0/23 who did not have EIMs
(p50.01). IBD phenotype (inflammatory vs. obstructive/fistulary), current hospitalization and disease type (CD vs. UC) was not different between these groups.
CONCLUSION: Sensironeural hearing loss may be another EIM of IBD. It is
found in 30% of IBD patients, and in up to 43% of patients with other EIMs.
Early hearing evaluation should be recommended to IBD patients who have
other EIMs
Disclosure of Interest: None declared
P0269 ANTI-TNF-A INDUCTION REGIMEN MODULATES GUT
MICROBIOTA MOLECULAR COMPOSITION WHILE INDUCING
CLINICAL REMISSIONS: RESULTS FROM A PRELIMINARY
EVALUATION ON CROHNS DISEASE PATIENTS
F. Scaldaferri1,*, L. Lopetuso1, V. Petito1,1, D. Zambrano1, E. Schiavoni1,
R. landi1, M.T. pistone1, D. dambrosio1, O. Ricca1, G. Cammarota1, F. Paroni
Sterbini2, F. franceschi1, E. Gaetani1, M. Sanguinetti2, L. Masucci2,
A. Gasbarrini1,2
1
Internal Medicine Department, Gastroenterology division, 2Institute of
Microbiology, Catholic University of Sacred Heart of Rome, Rome, Italy
Contact E-mail Address: francoscaldaferri@gmail.com
INTRODUCTION: IBD, and in particular Crohns disease, is chronic inflammatory condition characterized by an abnormal immune response towards self
microbiota and by an abnormal gut microbiota composition, as determined by
new molecular techniques. Anti-TNF-a is one of the strongest therapeutical
options available, able to induce mucosal healing and restore mucosal immune
homeostasis. Little information exists on the ability of antiTNF-a to modulate
gut microbiota composition.
AIMS & METHODS: Aim of our study was to evaluate gut microbiota composition in Crohns disease patients before and after 6 weeks after anti-TNF-a
therapy.
Fecal samples were collected in 3 consecutive CD patients, the first day of the
first dose of anti-TNF-a therapy (infliximab) and following 6 weeks: 2 patients
displayed colonic CD and 1 ileo-ciecal CD (2 males of 23 and 33 years, and 1
female of 53 years), no-one took any antibiotic 2 weeks before starting anti-TNFa therapy or during the active treatment. Harvey Bradshaw scores at baseline and
after 6 weeks were respectively 4 and 3, 7 and 3 and 4 and 1.
Microbiota composition was assessed by Metagenomic, a technique assessing 16S
rRNA (Roche 454 GS Junior), following DNA isolation from stool samples
stored in 80 C. Data obtained were analyzed by suite Qiime.
RESULTS: Bacteria amplicons were detected in all samples. Prevalent classes of
bacteria were: Bacteroidia (min 18% - max 95%), Firmicutes (min 2% - max
58%%) and Proteobacteria (min 2% - max 22%). Following anti-TNF-a therapy, bacteroidetes reduced in all patients (min from 3% max from 67%).
Firmicutes, on the contrary, increased in levels. In 2 patients also proteobacteria
increased. Species Faecalibacterium was not present in 2 out of 3, but in one
patient, Fecalibacterium increased from 17% before therapy to 23% after
therapy.
CONCLUSION: Anti TNF-a treatment is associated with active modulation of
intestinal microbiota, including decrease in bacteroidetes and increase in firmicutes. Metagenomics seems a promising technique whose real application in clinic
is still under development.
REFERENCES
Arumugam M. 2011; 473.
Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience
of the human gut microbiota. Nature 2012; 489: 220-230.
Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience
of the human gut microbiota. Nature 2012; 489: 220-230.
Disclosure of Interest: None declared

A204
P0270 CHANGING TRENDS IN IBD HOSPITAL ADMISSIONS AND
MANAGEMENT IN ENGLAND, 2001-02 TO 2010-11
A. Ahmad1,*, T. Cowling1, A. Laverty1, J.-Y. Kang2, A. Majeed1, R. Pollok2
1
Department of Primary Care and Public Health, Imperial College, 2St Georges
Healthcare NHS Trust, London, United Kingdom
Contact E-mail Address: ahmir.ahmad@nhs.net
INTRODUCTION: Inflammatory bowel disease is a chronic disorder, affecting
240,000 people in the UK. The long-term impact of recent advances in IBD
management on hospital admissions and surgery is uncertain.
AIMS & METHODS: Our aim was to investigate trends in hospital admission,
fatality rates, surgery, endoscopy and cytokine inhibitor infusions for CD and
UC in England between 2001-02 and 2010-11.
We used admissions data from Hospital Episode Statistics, a national administrative database of all National Health Service hospital admissions and population data from the Office for National Statistics, England.
RESULTS: From 2001-02 to 2010-11, age-sex standardised day-case admission
rates increased by 460.4% (p50.001) and 127.0% (p50.001) for CD and UC
respectively. There was no significant change in inpatient admission rates for
CD and UC. Both inpatient and day-case rates of surgery and endoscopy fell
for both CD and UC [inpatient: CD surgery -8.9% (p50.001) CD endoscopy 14.4% (p50.001) UC surgery -6.8% (p50.001) UC endoscopy -10.5% (p50.01);
day-case: CD surgery -75.3% (p50.001) CD endoscopy -55.9% (p50.001) UC
surgery -66.7% (p50.001) UC endoscopy -17.2% (p50.001)]. Day-case infusions,
including cytokine inhibitor treatment, rose in both CD and UC, by 308.9%
(14.8% to 60.6%, p50.001) and 3475.0% (0.4% to 15.4%, p50.001) respectively.
CONCLUSION: Over the past decade inpatient admission rates for IBD have
remained static, but day-case admission rates have risen whilst the requirement
for surgery and endoscopy has fallen. The reduction in surgical and endoscopic
activity and the switch towards day-case activity may reflect recent advances in
IBD management, notably, the substantial increase in anti-TNF therapy.
Disclosure of Interest: None declared
P0271 EPIDEMIOLOGY AND TEMPORAL TRENDS (2000-2012) OF
INFLAMMATORY BOWEL DISEASE IN ADULT PATIENTS IN A
CENTRAL REGION OF SPAIN
A.J. Lucendo1,*, D. Herv as Cruz2, O. Roncero3, R. Lorente4, A. Bouhmidi5,
T. Angueira1, C. Verdejo4, I. Saluena5, S. Gonzalez-Castillo1, A. Arias6 on behalf
of The Ciudad Real province IBD working group
1
Gastroenterology, Hospital General de Tomelloso, Tomelloso, 2Gastroenterology,
Hospital Virgen de Altagracia, Manzanares, 3Gastroenterology, Hospital General
Mancha Centro, Alcazar de San Juan, 4Gastroenterology, Hospital General
Universitario de Ciudad Real, Ciudad Real, 5Gastroenterology, Hospital Santa
Barbara, Puertollano, 6Research Support Unit, Hospital General Mancha Centro,
Alcazar de San Juan, Spain
INTRODUCTION: A growing incidence of IBD in southern Europe has been
recently reported, with records of pediatric cases confirming these tendencies in
Spain. Data on adult population however, has not been provided for over 10
years and needs to be updated.
AIMS & METHODS: This study has two main objectives: (1) to estimate the
current prevalence of IBD in central Spain, and (2) to examine recent trends in
disease prevalence. A further goal was to characterize changes in disease presentation over time.
A multicenter retrospective registry of all adult patients with a diagnosis of IBD,
including both Crohns disease (CD) and ulcerative colitis (UC), attended in 5
public hospitals covering a population of 514,368 inhabitants was carried out.
RESULTS: In 2012, the prevalence of CD and UC in adults was 137.17/100,000
inhabitants [95% confidence interval (CI): 114 160] and 99.84/100,000 inhabitants (95% CI: 79 119), respectively. The mean incidence rate during 2000-1012
period of CD and UC was 8.9 and 5.6/100,000 inhabitants per year, respectively.
Most of our patients (75.55%) were diagnosed during the last 13 years. CD
affected equally both genders; a trend to progressive increase in the age at diagnosis, ileal location and inflammatory behavior was documented for CD patients.
In contrast, UC affected with a higher frequency to male subjects (57.8%,
p 0.015), specifically at an age over 40 years old. Age at UC onset trended to
progressively increase from 2000 to 2012 (p50.001), but the extension on the
disease remained unchanged.
CONCLUSION: A significant increase in the prevalence of IBD, especially for
CD, was documented in our region regarding previous estimation in Spain. CD
incidence reached similar figures to those provided for Northern Europe, increasing the burden of IBD over the health system.
Disclosure of Interest: None declared
P0272 HEPATOBILIARY DISEASES IN A PROSPECTIVE POPULATION
BASED COHORT WITH INFLAMMATORY BOWEL DISEASES
(ICURE)
A. Ronnblom1,*, T. Holmstrom1, H. Tanghoj1, F. Rorsman1, D. Sjoberg1
1
Dpt of Medical Sciences, Uppsala, Sweden
Contact E-mail Address: anders.ronnblom@akademiska.se
INTRODUCTION: The relation between hepatobiliary diseases and IBD has
been the focus for scientific research for many years. There are, however, few
prospective population based cohort studies in this area. Between 2005 and 2009
all newly diagnosed cases of IBD in all age groups in the Uppsala Health Care
Region were registered. The cohort consists of 790 individuals corresponding to
an average incidence of 20.0 new cases of UC/100 000/year and 9.9 new cases of
Crohns disease/100 000/year (REFERENCES

United European Gastroenterology Journal 2(1S)


JCC. 2013 Oct 1;7(9):e351-7. and JCC. 2014 Mar 1;8(3):215-22.)
AIMS & METHODS: During the winter 2013/14 all medical records were scrutinized and the results were collected. Liver function tests and investigation of
hepatobiliary diseases were collected. Liver function tests had been checked at
least once in 97.1% of the cohort. The main method for the diagnosis of PSC was
magnetic resonance cholangiopancreaticography (MRCP), or endoscopic retrograde cholangiopancreatography (ERCP) when the results were ambiguous.
Parenchyma diseases were investigated with liver biopsy and biochemical tests.
IBD was classified according to the Montreal classification.
RESULTS: Seventeen patients with PSC were diagnosed corresponding to an
overall prevalence of 2.15% (for UC 1.90% and for Crohns disease 2.65%). The
average age of these was 25,0 years. Among the 92 paediatric patients (517 years
old) three patients had autoimmune hepatitis, but none PSC. Three patients have
undergone liver transplantation and one has died of colonic carcinoma. Eleven
patients have demonstrated persistent elevation of ALP but have had a normal
MRCP or refused further investigation.
CONCLUSION: In this prospective population based cohort consisting of 526
patients with UC and 264 with Crohns disease, 17 cases of PSC was found,
among whom so far have been liver transplanted or have died because of
carcinoma. The average age of those affected by PSC is considerably lower than
usually is reported. Forthcoming study of ICURE will reveal if more patients will
be affected by liver disease.
Disclosure of Interest: None declared
P0273 CELIAC DISEASE IN IBD. OBSERVATIONS
POPULATION BASED COHORT OF IBD (ICURE)

FROM

A. Ronnblom1,*, T. Holmstrom1, H. Tanghoj1, A. Wanders1, D. Sjoberg1


1
Dpt of Medical Sciences, Uppsala, Sweden
Contact E-mail Address: anders.ronnblom@akademiska.se
INTRODUCTION: IBD and celiac disease are diseases with worldwide distribution and an increased incidence of them have been reported from many areas.
There is a shortage of studies investigating the possible concomitant appearance
of these diseases in the same individual and whether those affected by both
diseases demonstrate any particular phenotype. ICURE (IBD Cohort Uppsala
health Region) is a population based cohort of individuals with ulcerative colitis
(n 526, JCC. 2013 Oct 1;7(9):e351-7) Crohns disease (n 264, JCC. 2014 Mar
1;8(3):215-22) and microscopic colitis (n 272). We have previously reported the
occurrence of celiac disease among patients with microscopic colitis (Scand J
Gast 2013;48:825-830) and we now aimed to study the patients with UC and
Crohns disease in the same respect.
AIMS & METHODS: In 790 individuals diagnosed with ulcerative colitis or
Crohns disease between 2005 and 2009, the possible concomitant occurrence
of celiac disease was investigated. Medical notes were scrutinized and pathological specimens were re-examined.
RESULTS: Three hundred and ninety-nine of the 790 patients had been examined for the possibility of celiac disease, corresponding to an investigation of
49.4% of the total cohort. Sixteen patients with celiac disease were found, representing 2.05% of the cohort. Two patients with IBD and celiac disease developed
collagenous colitis 5 and 7 years later and one PSC after 3 years. A young man
with UC developed collagenous sprue. Compared with the non-celiacs the
patients with both IBD and celiac disease were younger (22.5 vs. 34.5 years,
p 0.0015) and those with colitis more often had an extensive disease (9/3 vs.
163/328, p 0.0026) and 76% were women.
CONCLUSION: Celiac disease is sufficiently common among patients with IBD
to motivate screening for this condition in the regular workup of patients with
ulcerative colitis and Crohns disease. Those affected by both diseases are predominantly young women with extensive colitis.
Disclosure of Interest: None declared
P0274 WORK DISABILITY AND PRODUCTIVITY LOSS IN PATIENTS
WITH INFLAMMATORY BOWEL DISEASES IN HUNGARY IN THE
ERA OF BIOLOGICS
B.D. Lovasz1,*, A. Balint2, M. Mandel1, P.A. Golovics1, L. Gulacsi3, B. Strbak3,
K. Farkas2, Z. Kurti1, B. Szilagyi1, A. Mohas1, T. Molnar2, P.L. Lakatos1
1
1st Department of Medicine, Semmelweis University, Budapest, 21st Department
of Medicine, University of Szeged, Szeged, 3Department of Health Economics,
Corvinus University of Budapest, Budapest, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: The IBD is a chronic and potentially debilitating disease
course can represent a heavy burden for patients, impacting every aspect of the
affected individuals life.
AIMS & METHODS: To assess work disability (WD) rates in an inflammatory
bowel disease (IBD) cohort involving patients with Crohns disease (CD) or
ulcerative colitis (UC) cohort and to identify possible clinical or demographic
factors associated with WD. Data from 443 (M/F: 202/241, CD/UC: 260/183,
mean age: 35.5 (CD) and 40.5 (UC) years, biological drug exposure 31.2% /
11.5%) consecutive patients were included. WD data were collected by questionnaire and the Work Productivity and Activity Impairment (WPAI) instrument.
Disability pension (DP) rates in the general population were retrieved from
public databases.
RESULTS: The overall DP rate in this IBD population was 32.3%, with partial
disability in 24.2%. Of all DP events, 88.8% were directly related to IBD.
Overall, full DP was more prevalent in IBD (RR:1.51, p50.001) and CD
(RR:1.74, p50.001) but not in UC compared to the general population and
also in CD compared to UC (OR: 1.57, p 0.03). RR for full DP was increased
only in young CD patients (RR535 year olds: 9.4; RR36-40 year olds: 9.4 and 5.6,
p50.01 for both). In CD, age group, previous surgery, disease duration, frequent

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United European Gastroenterology Journal 2(1S)


relapses, and the presence of arthritis/arthralgia were associated with an
increased risk for DP. Among employed patients, absenteeism and presenteeism
was reported in of 25.9% and 60.3% patients, respectively, leading to a 28% loss
of work productivity and a 32% activity loss, and was associated with disease
activity and age group. Average cost of productivity loss due to disability and
sick leave with human capital approach was 1450 and 430 E/patient/year, respectively (total productivity loss 1880 E/patient/year).
CONCLUSION: Risk of DP was highly increased in young CD patients (six to
nine fold). Previous surgery and presence of arthritis/arthralgia was identified as
risk factor for DP. Work productivity is significantly impaired in IBD and is
associated with high productivity loss.
Disclosure of Interest: None declared
P0275 INCREASED INTESTINAL PERMEABILITY AMONG FIRSTDEGREE RELATIVES OF CROHNS PATIENTS IS NOT
ASSOCIATED WITH INCREASED MUCOSAL ULCERATIONS ON
SMALL BOWEL VIDEO CAPSULE ENDOSCOPY
C. Teshima1,*, M. El Kalla2, S. Turk3, W. El Matary4, R. Valcheva1,
R. Danchak2, M. Gordon2, P. Ho1, A. Mullins2, D. Wong1, J. Meddings5,
H. Huynh2, L. Dieleman1
1
Medicine, 2Pediatrics, University of Alberta, Edmonton, Canada, 3Medicine, Free
University Amsterdam, Amsterdam, Netherlands, 4Pediatrics, University of
Manitoba, Winnipeg, 5Medicine, University of Calgary, Calgary, Canada
INTRODUCTION: First-degree relatives (FDR) of Crohns disease (CD)
patients have the highest risk for developing CD. CD patients and a substantial
portion of FDR have increased intestinal permeability. It is unclear whether
FDR have abnormal permeability because of early, asymptomatic CD or
whether this occurs without mucosal inflammation. Video capsule endoscopy
(VCE) is the most sensitive means of imaging the small intestine and can identify
mucosal lesions suggestive of subclinical CD. The purpose of our study was to
determine if abnormal small intestinal permeability in healthy FDR is associated
with small bowel mucosal abnormalities detected by VCE.
AIMS & METHODS: 342 CD patients consented to have their FDR between 1045 years of age contacted regarding study participation. Eligible FDR underwent
small bowel permeability testing as measured using the lactulose/mannitol (L/M)
test that is based on the fractional urinary excretion of these sugars. FDR with
abnormal permeability (defined as  0.030) were compared to FDR with normal
small permeability (50.025) by VCE to assess for small bowel inflammatory
changes. The primary outcome was the number of mucosal ulcerations seen on
VCE in each permeability group.
RESULTS: 223 FDR consented to participate and completed the intestinal permeability test. 40 (17.5%) had abnormally increased permeability. Subsequently,
59 subjects with normal and 29 subjects with abnormal permeability underwent
VCE. On VCE, there was no difference in small bowel mucosal abnormalities
with a mean of 2.27 (range 0-16) ulcers in the normal and 2.52 (range 0-15) ulcers
in the abnormal permeability groups respectively (NS). Surprisingly, 23.5% of
asymptomatic FDR had more than 3 small bowel lesions as shown by VCE,
irrespective of their intestinal permeability. These lesions were significantly associated with fecal calprotectin of 4 50 mg/g stool.
CONCLUSION: There is no association between small bowel ulcerations seen
on VCE between asymptomatic FDR of Crohns patients with abnormally
increased intestinal permeability and FDR with normal permeability. Thus, the
increased small bowel permeability in FDR does not seem to be caused by subclinical CD, but is likely an intrinsic gut barrier defect. Surprisingly, over 23% of
these FDR had 3 or more small bowel ulcers, associated with increased fecal
calprotectin levels.
Disclosure of Interest: None declared
P0276 PRE-POUCH ILEITIS: A MORE TREATMENT REFRACTORY
SUB-GROUP OF POUCHITIS
D.C. de Jong1,*, M.A. Samaan1, S. Sahami2, G.van den Brink1, M. Lowenberg1,
C. Ponsioen1, W.A. Bemelman2, G.R. DHaens1
1
Inflammatory Bowel Disease Unit, Academic Medical Centre, Amsterdam,
2
Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands
Contact E-mail Address: markasamaan@gmail.com
INTRODUCTION: Following restorative proctocolectomy (RPC) with ileal
pouch-anal anastomosis (IPAA) for ulcerative colitis, (UC) up to 50% of patients
will develop pouchitis. Moreover, a subgroup will also develop inflammation in
the pre-pouch ileum (pre-pouch ileitis, PI). Endoscopically, PI can mimic Crohns
disease (CD) but evidence suggests that PI may be a distinct disease entity. PI has
been reported more frequently in UC patients with primary sclerosing cholangitis
(PSC) undergoing IPAA. This group is also known to have higher rates of backwash ileitis and certain similarities have also been described between this and PI1.
AIMS & METHODS: Our aim was to assess the incidence, predictive factors and
response to treatment in a single centre cohort of pouch patients. We retrospectively collected data on 246 consecutive UC patients who underwent RPC and
IPAA over the last 15 years. Endoscopic and histological records were used to
identify individuals with PI, defined as ulceration seen in the afferent limb at
endoscopy and evidence of active inflammation in biopsy samples.
RESULTS: Seventy-nine (32%) of the 246 patients were found to have had
pouchitis. Twelve patients were found to have concurrent PI, representing 5%
of the total cohort. No patients had PI in the absence of pouchitis. Of those with
PI, 6 patients (50%) had antibiotic-refractory, chronic pouchitis (as previously
defined1): four of whom required steroids/immunomodulators and two required
treatment with anti-TNF agents. One had antibiotic-dependent pouchitis. The
remaining 5 were antibiotic responsive and did not require long-term treatment
for their symptoms. A higher proportion of patients in the PI group had PSC (2

of 12, 17%) compared to the non-PI group (11 of 234, 5%) though this difference
did not reach statistical significance (p 0.07).
Table 1: Showing demographic data for patients with and without pre-pouch
ileitis (PI)

Gender (female:male)
Smoker
Pouchitis
PSC
EIM

PI (n 12)

Non-PI (n 234)

4:8 (33%:66%)
1 (8%)
12 (100%)
2 (17%)
1 (8%)

109:125 (47%:53%)
26 (14%, n 185)
67 (30%, n 227)
11 (5%, n 234)
21 (10%, n 219)

CONCLUSION: Compared with pouchitis, PI is a rarer and less well-defined


condition. Its recognition is relevant to clinicians as the inflammation involved is
more extensive and can be more treatment refractory than isolated pouchitis. Our
study demonstrates high rates of antibiotic-refractory, chronic pouchitis among
those with concurrent PI when compared with published pouchitis cohorts2. An
alternative possibility is that PI is a distinct clinical entity with different pathophysiology to isolated pouchitis. The diagnosis of PI should be considered in all
patients with ulceration of the afferent limb rather than making the assumption
that Crohns disease is the underlying condition.
REFERENCES
1. Shen B, et al. Primary sclerosing cholangitis is associated with endoscopic and
histologic inflammation of the distal afferent limb in patients with ileal pouchanal anastomosis. Inflamm Bowel Dis 2011; 17: 1890-900.
2. Madiba TE and Bartolo DC. Pouchitis following restorative proctocolectomy
for ulcerative colitis: incidence and therapeutic outcome. J R Coll Surg Edinb
2001; 46: 334-337.
Disclosure of Interest: D. de Jong: None declared, M. Samaan: None declared, S.
Sahami: None declared, G. van den Brink: None declared, M. Lowenberg: None
declared, C. Ponsioen Financial support for research from: Abbott Laboratories,
Schering-Plough Corp., Falk Pharma, Tramedico, Consultancy for: Abbott
Laboratories, Glaxo Smith Kline, W. Bemelman: None declared, G. DHaens
Financial support for research from: Falk Pharma, MSD, Lecture fee(s) from:
MSD, UCB Inc., Abbott, Ferring Pharmaceuticals Inc., Consultancy for:
Abbott, Jansen Biologics,TEVA, Glaxo Smith Kline, Shire Pharmaceuticals
Inc., Nova Nordisk A/S, Pfizer Inc, MSD, UCB Inc.
P0277 UPTAKE OF INFLUENZA VACCINE IN ULCERATIVE COLITISA LONGITUDINAL, POPULATION BASED STUDY
D. Boltin1,2,*, R. Gingold-Belfer3, N.A. Kimchi2, O. Ben-Bassat1, J. Langiewicz4,
Y. Niv1, S. Birkenfeld4
1
Gastroenterology, Rabin Medical Center, Petah Tikva, 2Gastroenterology, Bat
Yamon Medical Center, Bat Yam, 3Rabin Medical Center, Petah Tikva, 4Clalit
Health Services, Tel Aviv, Israel
Contact E-mail Address: dboltin@gmail.com
INTRODUCTION: The incidence of vaccine-preventable disease is increasing.
Current practice guidelines recommend annual influenza vaccination for all
inflammatory bowel disease (IBD) patients.
AIMS & METHODS: We aimed to determine the annual uptake of influenza
vaccine in UC patients. Using the Business Objects database of Clalit Health
Services in the Tel Aviv district we identified all patients over 18 years old with a
diagnosis of Ulcerative colitis (UC) on 31.12.2005. This cohort was followed until
31.12.2012. Subjects over age 50 without IBD who are also targeted for influenza
vaccination served as controls. The uptake of annual influenza vaccination was
recorded.
RESULTS: 470 UC patients were included (241 (51.3%) males, age 50.418.4
years, disease duration 158.986.5 months), and 2960 controls. During the years
2006, 2007, 2008, 2009, 2010, 2011 and 2012 the uptake of influenza vaccination
was 101 (21.5%), 122 (26.0%), 147 (31.3%), 181 (38.5%), 177 (37.7%), 170
(36.2%) and 178 (37.9%) amongst UC patients, and 993 (33.5%), 1360
(45.9%), 1524 (51.5%), 1611 (54.4%), 1446 (48.9%), 1576 (53.2%) and 1557
(52.6%) amongst controls (p50.0001 for every year). Independent predictors
of vaccination included age (OR, 1.05; 95% CI, 1.03-1.06; p50.001) and cardiovascular risk (OR, 1.81; 95% CI, 1.31-2.49; p50.01).
CONCLUSION: Although uptake influenza vaccination is consistently lower in
UC compared to controls, an upward trend was observed over the study period.
Public health initiatives should target this high-risk population to promote
immunization.
REFERENCES
1. Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based
Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009; 3: 4791.
2. Longuet R, Willot S, Ginie`s J, et al. Immunization status in children with
inflammatory bowel disease. Eur J Pediatr 2013.
3. Wilckens V, Kannengiesser K, Hoxhold K, et al. The immunization status of
patients with IBD is alarmingly poor before the introduction of specific guidelines. Scand J Gastroenterol 2011; 46: 855861.
4. Benchimol EI, Hawken S, Kwong JC, et al. Safety and utilization of influenza
immunization in children with inflammatory bowel disease. Pediatrics 2013; 131:
e1811-e1820.
5. Fields SW, Baiocco PJ and Korelitz BI. Influenza Vaccinations: Should They
Really be Encouraged for IBD Patients Being Treated with
Immunosuppressives? Inflammatory Bowel Diseases 2009; 15: 649651.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)

P0278 UK IBD TWIN AND MULTIPLEX REGISTRY: CONCORDANCE


AND ENVIRONMENTAL RISK FACTORS OF TWINS WITH IBD
H. Gordon1,*, T. Orchard2, A. Steel1, M. Harbord1
Gastroenterology, Chelsea and Westminster Hospital, 2Gastroenterology, St
Marys Hospital, London, United Kingdom
1

INTRODUCTION: Twins offer insight into the relative importance of genetic


and environmental factors in disease development. Twin studies to date show
concordance in monozygotic twins with CD and UC to be 20-55% and 6.3-17%
respectively. Dizygotic concordance rates are 0-3.6% (CD) and 0-6.3% (UC) (1).
The UK IBD Twin and Mutliplex Registry is a research database established in
October 2013; this study reviews disease patterns and environmental risk factors
of twin pairs recruited.
AIMS & METHODS: Data subjects were recruited via clinician referral, IBD
charities and retracing members of a database dormant since 1996. Adult twin
pairs discordant and concordant for IBD were recruited. Data subjects completed a questionnaire regarding demographics, disease history and environmental exposure. Medical records were reviewed when available.
RESULTS: Demographics, Concordance and Zygosity: 100 twin pairs were
recruited. Mean age 57 years 5 months, range 21-83 years. 31 monozygotic:69
dizygotic. Ratio CD:UC 48:52. Concordance of twin pairs classified by zygosity and disease type is as follows:

Monozygotic
Dizygotic

Crohns Disease

Ulcerative Colitis

53.3%
10%

25%
19.4%

Early Environment: Higher rates of exclusive breastfeeding were reported in


concordant compared with discordant pairs (27.3% n 22 pairs vs 16.7%
n 78 pairs). Self reports of perceived childhood illness did not show any difference between IBD and healthy twins of discordant pairs (16.7%, 13/78 vs 19.2%,
15/78). However, the IBD twin more often recalled frequent gastrointestinal
infection prior to IBD onset in comparison with their healthy twin (10.3%, 8/
78 vs 3.8%, 3/78).
Diet: IBD twins from discordant pairs reported higher rates of consuming "ready
made" meals at least weekly before disease incidence (12.8%, 10/78 vs 5.1%, 4/
78).
Smoking: On review of discordant twin pairs (n 72), there was no significant
difference in numbers of current, ex and non smokers between subjects with UC
(n 41), CD (n 32) and their healthy twin at time of symptom onset.
Medication and Stress: On review of all IBD sufferers, 7.1% (8/112) and 13.4%
(15/112) used NSAIDS and antibiotics within 3 months preceding onset. 48.2%
(54/112) reported significant stress within the year preceding onset.
Time of onset in concordant pairs: The mean lag between diagnosis of concordant pairs was 7 years 5 months.
CONCLUSION: Concordance of twin pairs with CD is in keeping with previous
studies. However UC concordance is greater than expected; in particular 19.4%
dizygotic twin pairs with UC are concordant. This is 4 fold expected rates of nontwin sibling concordance(2), suggesting early environment to be important in
pathogenesis. This study supports an associaton between diet, stress and gastrointestinal infection with IBD onset. The lack of associatoin with smoking at
incidence may reflect sample size.
REFERENCES
1. Brant S. Update on the heritability of inflammatory bowel disease: The importance of Twin Studies. Inflamm Bowel Dis 2012.
2. Bodger, et al. Concordance for IBD among twins compared to ordinary siblings a Nowegian population based study. J Crohns Colitis 2010.
Disclosure of Interest: None declared
P0279 TEMPORAL
TRENDS
IN
NON-STRICTURING,
PENETRATING BEHAVIOUR AT DIAGNOSIS OF CROHNS

DISEASE IN OREBRO, SWEDEN: A POPULATION-BASED


RETROSPECTIVE STUDY UPDATED FOR 1988-2010

NON-

Y. Zhulina1, R. Udumyan2, I. Henriksson3, C. Tysk1,3, S. Montgomery2,


J. Halfvarson1,3,*
1
School of Health and Medical Sciences, Orebro University, 2Clinical
Epidemiology and Biostatistics Unit, Orebro University Hospital, 3Dep of Internal
Medicine, Div of Gastroenterology, Orebro University Hospital, Orebro, Sweden
Contact E-mail Address: jonas.halfvarson@orebroll.se

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INTRODUCTION: The incidence of Crohns disease is continuing to rise in


several countries and in others it appears to have already levelled off. We updated
our previous population based study,1 by re-extraction of all information on
patients diagnosed with Crohns disease between 1963 and 1987, and included
patients diagnosed with Crohns disease up to 2010.
AIMS & METHODS: Our aim was to assess temporal trends in incidence, prevalence and disease phenotype at diagnosis. Patients of all ages with a potential
diagnosis of Crohns disease were identified retrospectively by evaluation of
medical notes of all current and previous patients at the Colitis clinic, Orebro
University Hospital amended by computerised search in the inpatient, outpatients, primary care and histopatological records. The medical notes were reviewed
and patients were included if they lived within the catchment area at any time
during their disease course, were diagnosed between 1963-2010 and fulfilled the
Lennard-Jones criteria for Crohns disease. Disease phenotype was defined
according to the Montreal classification.

RESULTS: The mean incidence for the period 1988-2010 was 7.6/105 (95% CI:
6.7-8.4/105). A comparison with the earlier period 1963-1987 showed increased
age and sex standardised incidence rates of Crohns disease, with an incidence
rate ratio of 1.32 (1.11-1.57). The median (range) age at diagnosis increased from
28 (379) years to 37 (587) years (p 0.0002). Similarly, the point prevalence
increased from 178/105 (157-199) on 31 December 1987 to 267/105 (244 291) on
31 December 2010. Non-stricturing, non-penetrating disease at diagnosis
increased from 12.5% in 1963-1965 to 82.3% in 2005-2010.
CONCLUSION: The incidence of Crohns disease during the last two decades
increased. A striking increase in non-stricturing, non-penetrating disease at diagnosis was observed, suggesting earlier diagnosis or phenotypic change. The
observed point prevalence in 2010 is among the highest reported.
REFERENCES
1. Lindberg E and Jarnerot G. The incidence of Crohns disease is not decreasing
in Sweden. Scand J Gastroenterol 1991; 26: 495-500.
Disclosure of Interest: None declared

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P0280 INTERLEUKIN 6 GEN POLYMORPHISM IN PATIENTS WITH


INFLAMMATORY BOWEL DISEASES
D. Cibor1,*, D. Owczarek1, M. Glowacki1, K. Jablonski2, A. Jurczyszyn3,
A. Ciesla1, T. Mach1
1
Gastroenterology, Hepatology & Infectious Diseases, 2Medical Education,
3
Hematology, JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE,
Krakow, Poland
Contact E-mail Address: dorota.cibor@gmail.com
INTRODUCTION: Interleukin 6 (Il-6) plays an important role in the development of inflammatory process in IBD patients. The 174 G/C IL-6 promoter
polymorphism affects IL-6 transcription. The GG genotype seems to induce
higher IL-6 levels while the C allele (GC or CC) seems to be associated with
decreased transcription and secretion of IL-6.
AIMS & METHODS: Our study aimed to evaluate the effect of single nucleotide
polymorphism of IL-6 (174 G/C) on the disease course in patients with UC and
CD.
Material and methods: 105 patients (aged 18-75 years) with diagnosed IBD: 50
with CD and 55 with UC were involved in the study. The controls consisted of
124 healthy individuals. In all patients were evaluated following parameters:
disease duration, disease location, presence of complications, present pharmacotherapy, past surgical procedures, BMI, cigarette smoking. In all subjects
morphology, biochemical parameters, CRP, fibrinogen, IL-6 level and IL-6 polymorphism were assessed.
RESULTS: No statistically significant differences in IL-6 polymorphism were
observed between patients with UC, CD and controls. Patients with GG genotype were significantly younger at the disease onset. In IBD patients with GG
genotype higher mean IL-6 level was noticed as compared to other genotypes
(4.685 /- 5.9 vs 2.715 /- 5.1 in GC and 3.186 /- 3.6 in CC). In both UC and
CD patients with GG and GC genotype a positive correlation between IL-6 and
fibrinogen level as well CRP was found. In IBD patients with CC genotype no
correlation between IL-6 and fibrinogen was found (p 0.48).
CONCLUSION: The risk of developing IBD is not connected with IL-6 polymorphism. However, IL-6 variation might have an influence on the course of the
disease in IBD patients.
Disclosure of Interest: None declared
P0281 THE TPMT AND ABCB1 POLYMORPHISMS IN IBD PATIENTS
IN CRETE: IMPACT ON DISEASE AND RESPONSE TO TREATMENT
C. Coucoutsi1, A. Voumvouraki1, O. Sfakianaki1, G. Emmanuel1, E. Digenakis1,
I. Koutroubakis1, E. Kouroumalis1,*
1
Gastroenterology, University of Crete Medical School, Heraklion Crete,
Heraklion, Greece
Contact E-mail Address: kouroum@med.uoc.gr
INTRODUCTION: It is well known that polymorphisms of the TPMT gene
(coding for thiopourine methyl-transferase), influence response to treatment
with azathioprine. Polymorphisms of the ABCB1 gene (coding for p-glycoprotein
170) has been associated with IBD and resistance to treatment but results are
conflicting.
AIMS & METHODS: The aim of this study was to determine the frequencies of
TPMT and ABCB1 gene polymorphisms in IBD patients from Crete, a population genetically homogeneous, and how these polymorphisms might influence
response to treatment and disease behaviour. A total of 222 IBD patients, records
were reviewed for intake of azathioprine, possible adverse reactions, response to
treatment and need for colectomy. All patients were genotyped for TPMT gene
polymorphisms, that have been related to intolerance to azathioprine (G238C,
G460A and A719C) as well as ABCB1 gene polymorphisms (G2677T/A and
C3435T), using a PCR-RFLP method. The same polymorphisms were also determined in 119 age and sex healthy controls.
RESULTS: Allele frequencies of TPMT gene in our study population were found
to be in concordance with those reported in other Caucasian populations. 76 IBD
patients were identified receiving azathioprine, of whom 16 were discontinued (10
CD, 6 UC) due to adverse reaction. 2 of them were found to carry the G460A and
A719G alleles (TPMT 3A genotype) (12.5%). For the ABCB1 gene, G2677T/A
allele frequencies were found to be similar to those reported in the literature. There
was no association of G2677T/A or C3435T with clinical phenotype, or resistance
to treatment. However, 77.3% of 22/222 patients who did not respond to therapy
and required surgery, were found to carry both the C3434T and the G2677T
mutation
CONCLUSION: Our study was conducted in a genetically homogenous population in the island of Crete. No correlation of any single SNP was found with

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United European Gastroenterology Journal 2(1S)


either clinical activity or response to treatment. However, most patients who
carried both the G2677T and C3435T mutations were refractory to treatment,
a finding which implies that resistance to treatment in IBD patients is a more
complex issue, which requires the presence of a genetic locus rather than a single
SNP.
Disclosure of Interest: None declared
P0282 FC RECEPTOR TYPE IIIA POLYMORPHISMS AND THEIR
CORRELATION WITH CLINICAL OUTCOME IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE DURING A LONG TERM
FOLLOW UP

P0284 RARE VARIANTS IN XIAP IN MALE PEDIATRIC-ONSET


CROHNS DISEASE

G. Bodini1,*, V. savarino1, P. dulbecco1, I. baldissarro1, E. Savarino1


1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: A total of 20-30% of patients with active Crohns disease
(CD) do not respond to anti-TNF- treatments and up to 40% of patients in
chronic therapy experience a loss of response. Furthermore about 50% of
patients with ulcerative colitis (UC) experience a loss of response to antiTNF therapy after one year. The cause of this limited efficacy is unclear, but
past studies hypothesized that the individual variation of drug metabolism may
play an important role. Thus, given the limited data available, the role of Fc
IIIa receptor (i.e. one of the four receptors involved in the catabolic pathway of
anti-TNF- drugs) polymorphisms should be further explored.
AIMS & METHODS: The aim of this prospective, long-term follow up study
was to evaluate the correlation between Fc IIIa receptor polymorphisms and
clinical outcome in IBD patients undergoing biologic therapy.
We enrolled consecutive IBD patients who achieved clinical remission by antiTNF- therapy. Blood samples were collected at the beginning of biological
therapy. The assessment of IBD activity was based on the Harvey-Bradshaw
Index score (HBI, remission 55, mild disease 5-7, moderate disease 8-16,
severe disease 416) for CD patients and on the Mayo score (Mayo52 remission,
mild disease 2-5, moderate/severe disease 6-12) for UC patients. Biochemical
evaluation and clinical score were assessed every 8 weeks. For the genotyping
analysis we used a Light Snips (Tib-Molbiol, Genova, Italy) and the Real-Time
PCR Technique developed by Light Cycler 480 Instrument (Roche, Mannheim,
Germany).
RESULTS: We prospectively included 39 patients (12UC/27 CD, 16F/23M) with
a median follow-up of 66.8 weeks (10-112). A total of 25 (64.1%) (10UC/15CD)
patients kept in remission during the whole follow up period, while 14 (35.9%)
(2UC/12CD) experienced disease relapse. As shown in the Table, four out of 14
(28.6%) (1UC/3CD) patients who experienced disease relapse, had FcIIIa-158
V/V receptor polymorphism, while the remaining 10 (71.4%) (9CD/1UC) had
FcIIIa-158 F/V or F/F receptor polymorphisms. Out of 25 patients who kept in
remission, 3 (12%) (1CD/2UC) had FcIIIa-158 V/V receptor polymorphism,
whereas the remaining 22 (88%) (14CD/8UC) showed FcIIIa-158 F/V or F/F
receptor polymorphisms. Patients in remission tended to have more often
FcIIIa-158 V/V receptor polymorphism compared to patients who relapsed,
but statistical significance was not reached.

Polymorphism V/V
Polymorphism V/F F/F

Patients in Remission
(n 25)

Relapsers
(n 14)

3 (12%)
22 (88%)

4 (28.6%)
10 (71.4%)

p value
0.2251

CONCLUSION: The evaluation of Fc IIIa-158 V/V receptor polymorphism


does not seem useful in identifying patients who are more likely to lose anti TNF response during long term period. However, further larger studies are necessary
to investigate the role of Fc IIIa receptor polymorphisms.
Disclosure of Interest: None declared
P0283 GENOME-WIDE STUDY OF
INFLAMMATORY BOWEL DISEASES

ANTI-TNF

risk factors for CD or UC could be shown to be significantly associated with


differences in anti-TNF response in CD (full vs. non-response) and UC (full vs.
non-response), respectively.
CONCLUSION: This is the first GWAS of anti-TNF treatment response in IBD.
Power for detecting associated markers was limited. Collaboration between
owners of anti-TNF treated cohorts e.g. in the regi of the International
Inflammatory Bowel Disease Genetic Consortium (IIBDGC) may increase the
power for identifying SNPs associated with treatment response.
Disclosure of Interest: M. Hubenthal: None declared, A. Franke: None declared,
V. Andersen Consultancy for: MSD & Janssen

RESPONSE

IN

M. Hubenthal1,*, A. Franke1, V. Andersen2,3 on behalf of The Danish anti-TNF


study group
1
Christian-Albrechts-University of Kiel, Kiel, Germany, 2South Danish University,
Odense, 3South Jutland Hospital, Aabenraa, Denmark
Contact E-mail Address: vandersen@health.sdu.dk
INTRODUCTION: Biomarkers predictive of treatment response will help select
the optimal treatment for the individual patients. Genome-wide association studies (GWAS) on anti-TNF response in patients with Crohns Disease (CD) and
ulcerative colitis (UC) are limited.
AIMS & METHODS: We performed a GWAS using ImmunoChip on a clinically-based cohort of anti-TNF treated patients with CD and UC. Data on the
first treatment of anti-TNF was sampled retrospective from 18 medical departments in Denmark by young medical doctors from the patient records. Efficacy
was evaluated using a simple 3-step scale (full/partial/non-responds) based on the
information in the patient records. Efficacy reflected the maximum response
within 26 weeks after anti-TNF treatment initiation. In total, 130061 autosomal
single nucleotide polymorphisms (SNPs) pass quality control QC) (62341 failed
QC) in 592 unrelated individuals ( 34 failing QC). SNPs were assessed for full
versus non-responders (partial responders were omitted).
RESULTS: In total, 364 cases had CD (270 full, 41 partial, and 53 non-responders) and 197 cases had UC (124 full, 23 partial, and 50 non-responders) and 31
cases had undetermined disease and/or response. Loci previously published to be

Y. Zeissig1,2,*, B. Petersen3, S. Milutinovic4, J. Hartwig1, G. Mayr3, E. Bosse1,


K. Peuker1, M. Kohl2, M. Laass5, S. Billmann-Born3, C. Rocken6, M. Schrappe2,
P. Rosenstiel3, J.C. Reed4, S. Schreiber1, A. Franke3, S. Zeissig1
1
Internal Medicine I, 2Department of Pediatrics, 3Institute of Clinical Molecular
Biology, Kiel University, Kiel, Germany, 4Sanford-Burnham Medical Research
Institute, La Jolla, United States, 5Childrens Hospital, Medical Faculty Carl
Gustav Carus, Technische Universitat Dresden, Dresden, 6Institute of Pathology,
Kiel University, Kiel, Germany
Contact E-mail Address: szeissig@1med.uni-kiel.de
INTRODUCTION: The genetic basis of inflammatory bowel disease (IBD) is
incompletely understood and it has been suggested that rare genetic variants
contribute to the heritability of IBD.
AIMS & METHODS: Here, we aimed to study rare variants involved in the
pathogenesis of IBD. We performed exome sequencing and detailed immunological profiling in a patient with early onset Crohns disease (CD). The coding
region of the gene encoding X-linked inhibitor of apoptosis protein (XIAP) was
sequenced in samples of 275 paediatric IBD patients and 1047 adult-onset CD
patients. XIAP genotyping was performed in samples of 2680 IBD patients and
2864 healthy controls. Functional effects of the identified variants were investigated in primary peripheral blood mononuclear cells (PBMCs) and cultured cell
lines.
RESULTS: A novel, de novo, nonsense mutation in the gene encoding XIAP, a
gene previously linked to primary immunodeficiency, was identified in a male
patient with early-onset CD. Sanger sequencing of XIAP in large cohorts of
paediatric IBD and adult-onset CD revealed several additional XIAP variants.
XIAP variants were detected in four percent of male patients with paediatriconset CD and were confined to this subset of IBD patients without detection of
XIAP variants in either UC or adult-onset CD. CD in patients harbouring XIAP
variants was characterized by small and large intestinal involvement, perianal
disease, and stricturing behaviour. Functional studies in primary PBMCs and
cultured cell lines revealed that the majority of identified XIAP variants were
associated with selective defects in NOD1 and NOD2 signalling. NOD1/2 defects
occurred as a consequence of impaired association of mutant XIAP with RIPK2
and/or altered XIAP-dependent ubiquitylation of RIPK2 thus uncoupling
NOD1/2 from its downstream mediator NF-B.
CONCLUSION: Our studies reveal the frequent occurrence of XIAP variants in
male, pediatric onset CD. Moreover, our data provide a mechanistic basis to the
previously unexplained observation of functional NOD2 defects in the absence of
genetic variants in NOD2. Finally, given the known association of XIAP mutations with primary immunodeficiency and the observed defect in NOD1/2 signaling, our data lend further support to the concept of primary immunodeficiency in
a subset of CD patients.
Disclosure of Interest: None declared
P0285 MALNUTRITION SCREENING IN INFLAMMATORY BOWEL
DISEASE PATIENTS
A.A. Csontos1,*, A. Molnar2, I. Kovacs3, D. Kocsis4, M. Juhasz4, L. Herszenyi4,
P. Miheller4
1
2nd Departement, 2School of PhD. Studies of Semmelweis University,
Pathological Sciences, Health science research, Semmelweis University,
3
Hungarian Dietetic Association, 4Semmelweis University, 2nd Department of
Medicine, Budapest, Hungary
Contact E-mail Address: csontosagnesanna@gmail.com
INTRODUCTION: According to current guidelines, all IBD patients should be
screened regularly for malnutrition with a validated tool (focusing on BMI,
weight loss and food intake). In a previous screening study conducted in hospitalized patients (n 1252) malnutrition was as observed up to 20% using the
body mass index (BMI) calculation, while it was high as 40% according to the
validated malnutrition universal screening tool (MUST). We hypothesized that
even MUST is not the sufficient method to evaluate the risk of malnutrition of an
IBD patient.
AIMS & METHODS: 173 consecutive IBD (126 with Crohns disease CD and
47 with ulcerative colitis UC) patients were enrolled into the study. Body
composition was measured by InBody 720 body analyser device, using the bioelectrical impedance method. BMI and MUST were also calculated and compared
to main results of BIA (skeletal muscle mass SMM, body fat mass BFM fat
free mass-FFM).
RESULTS: Rate of malnutrition in IBD patients was detected in 16%, 32% and
44% in patients using BMI, MUST and BIA, respectively. Almost half of the CD
patients have a high risk of malnutrition based on the BIA parameters (48%),
while it was lower using the MUST criteria (34%) or the simple BMI calculation
(17%).
We compared patients body composition regarding their ranking on MUST
scale. We found that UC patients SMM and FFM altered significantly in the

A208
MUST cathegories (SMM p 0.032, FMM p 0.034 S, BFM p 0.083 NS),
while we found no significant changes among CD patients. (SMM p 0.823,
FMM p 0.815, BFM p 0.660 NS).
Although the differences werent significant, highest risk of malnutrition was
detected in stenosing CD patients (57%, 43% and 29% with BIA, MUST and
BMI, respectively). High portion of CD and UC patients was underweighted
(48% vs. 34%). Fat tissue deficiency was more pronounced in CD than in UC
(52% vs. 23%), even in patients with stenosing disease phenotype (57%).
CONCLUSION: BMI calculation is not the appropriate method to estimate the
risk of malnutrition in IBD patients. MUST score calculation is able to detect a
higher portion of endangered subjects. Although the availability is not as wide as
it should be, the BIA method is the most accurate test to evaluate the risk of
malnutrition. According to our findings it is a useful tool to plan the dietary
therapy of the patients, and it can be a recommended method especially in UC
patient care.
Disclosure of Interest: None declared
P0286 CORRELATION BETWEEN THE CLINICAL, ENDOSCOPIC AND
HISTOLOGICAL ACTIVITIES OF ULCERATIVE COLITIS
00
A. Milassin1,*, K. Farkas1, Z. Szepes1, M. Szu cs2, T. Nyari2, F. Nagy1,
A. Balint1, R. Bor1, T. Wittmann1, T. Molnar1
1
First Department of Medicine, 2Department of Medical Physics and Informatics,
University of Szeged, Szeged, Hungary
Contact E-mail Address: milagn422@gmail.com
INTRODUCTION: The assessment of ulcerative colitis (UC) activity is based on
a combination of symptoms, clinical examination and endoscopic finding. The
most important goals of the recent therapies of UC are to induce and maintain
clinical remission and to achieve mucosal healing. Mucosal healing is defined as
Mayo endoscopy subscore of 0 or 1 in the majority of the studies. Interestingly,
rate of endoscopic remission has been shown to be higher than that of clinical
remission in some trials.
AIMS & METHODS: The aim of our study was to evaluate the correlation
between clinical and endoscopic disease activities of UC defined by activity
scores. Clinical activities were defined by two activity indices: the
Rachmilewitz Activity Index (CAI) and the partial Mayo score. Every patient
underwent colonoscopy performed by 3 experienced gastroenterologists and
endoscopists. They graded the findings both according to the endoscopic part
of the Rachmilewitz Activity Index (EI) and the Mayo endoscopic subscore.
Mucosal healing was defined as Mayo endoscopic subscore and EI of 0.
Histological activity was scored by Riley score.
RESULTS: 100 UC patients were enrolled in the study (49 males, 51 females;
mean age at diagnosis: 32.5 years). They were diagnosed on the basis of standard
clinical, endoscopic and histologic criteria. Clinical and endoscopic activities
showed strong correlations using both scoring systems (p 0.0029 and
p 0.0001). Endoscopic disease activity also correlated with the histological
activity (p0.001). Significant correlation was shown between the clinical activity
and mucosal healing (p 0.0012 and p0.001). No association was showed with
the extension of the disease and clinical or endoscopic activity.
CONCLUSION: Assessment of mucosal healing is very important for guiding
therapy and for evaluation of remission in patients with UC. Our result showed
that the correlation between the clinical, endoscopic and histological activities is
very good in UC. Mucosal healing highly associated with clinical remission.
Disclosure of Interest: None declared
P0287 DIAGNOSTIC DELAY IN PEDIATRIC CROHNS DISEASE
PATIENTS IS LONGER THAN IN PEDIATRIC ULCERATIVE
COLITIS PATIENTS
A. Schoepfer1,*, E. Safroneeva2, N. Fournier1, G. Rogler3, J. Ezri1, A. Nydegger1,
S. Vavricka4, C. Braegger3 on behalf of Swiss IBD Cohort Study Group
1
University Hospital Lausanne / CHUV, Lausanne, 2University of Bern, Bern,
3
University Hospital of Zurich, 4University Hospital Zurich, Zurich, Switzerland
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: We have recently shown that the median diagnostic delay
(time from first IBD symptoms until IBD diagnosis is established) was 9 months
in adult Crohns disease (CD) patients and 4 months in adult ulcerative colitis
(UC) patients in Switzerland. Of note, 25% of CD patients had a diagnostic
delay 424 months. We also showed that the length of diagnostic delay in CD
patients represents a risk factor for complicated disease course and intestinal
surgery. There is a lack of data regarding diagnostic delay in pediatric IBD
patients.
AIMS & METHODS: We aimed to assess the diagnostic delay in pediatric CD
and UC patients and to identify risk factors for long diagnostic delay. Data from
the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (80%), regional hospitals (19%), and private practices (1%). Data on
diagnostic delay was provided by parents and physician questionnaires.
Diagnostic delay was further divided into the time interval from first symptoms
to the first consultation with the physician (patient-related interval) and the
interval from first physician consultation until IBD diagnosis was established
(physician-related interval). Long diagnostic delay was defined as delay lying
avove the 75th percentile. Non-normal data are presented as median, interquartile
range [IQR] and range.
RESULTS: A total of 100 pediatric CD (37% females) patients and 75 pediatric
UC patients (56% females) were included. Age at disease onset was 12 [10-14]
years in CD and 11 [7-13] years in UC patients. Diagnostic delay in CD was 4 [28] (range 0-82) months with the interval form first symptoms to physician visit of
1 [0-3] (range 0-24) months and from physician visit to diagnosis of 3 [1-9] (range
0-82) months. In UC patients the median diagnostic delay was 2 [1-7] (range 0-52)

United European Gastroenterology Journal 2(1S)


months with an interval from first symptom onset to physician visit of 0 [0-3]
(range 0-36 months) and from physician visit to diagnosis of 2 [1-4] (range 0-20)
months. Diagnostic delay in CD patients was significantly longer than in UC
patients (median 4 vs. 2 months, p 0.011). Long diagnostic delay was defined as
period of 48 months in CD and 47 months in UC patients. Neither gender, age
at diagnosis, disease location, positive IBD family history, nor provenience (rural
vs. non-rural) were associated with long diagnostic delay.
CONCLUSION: the median diagnostic delay in pediatric CD and UC patients in
Switzerland is 4 and 2 months, respectively. However, one fourth of pediatric CD
patients needs 48 monhts and one fourth of pediatric UC patients needs 47
months from first symptom onset to IBD diagnosis.
Disclosure of Interest: None declared
P0288 BEHAVIOR OF P-GLYCOPROTEIN 170 (P-GP) FUNCTIONAL
ACTIVITY IN PERIPHERAL BLOOD LYMPHOCYTES (PBL) OF
IBD PATIENTS DURING TREATMENT WITH ANTI-TNFS
A.M. Sambuelli1,*, C. Cortada2, A. Gil1, S. Negreira1, S. Huernos1,
S. Goncalves1, B. Maricel1, T. Pablo1
1
Medicine (IBD Section), HOSPITAL UDAONDO, 2Centro de Diagnostico
Molecular (CDM), Ciudad de Buenos Aires, Argentina
Contact E-mail Address: asambu@fibertel.com.ar
INTRODUCTION: Pgp, encoded by the MDR1 gene is a transmembrane, ATPdependent, efflux pump, expressed in cells with barrier function and PBL, removing drugs, toxins, xenobiotics. IBD share drugs Pgp influenced with other diseases (as steroids, 6-MP in leukemia cells). Pgp overexpression was implicated in
highly active resistant RA (Tsujimura, Ann Rheum Dis 2008) induced by IL2 and
TNF, influencing steroid efflux from lymphocytes, reporting that a single infliximab (IFX) infusion overcame refractoriness with elimination of Pgp high expressing CD4lymph and recovery of dexametasone in PBL with Ppg marked
decrease. Pgp measure in PBL could be an early marker of AntiTNFs efficacy
and Pgp activity could modify the efflux of concurrent Pgp substrates drugs.
AIMS & METHODS: We aimed to study Pgp activity in PBL of IBD pts. treated
with antiTNFs, investigating a potential role in IBD management. Pgp functionality was evaluated in PBL of IBD and healthy controls (HC: n30), studied in 5
groups of IBD pts. (n123 recruited) with at least 10 CD/10 UC each: - Before and
after 20 days of AntiTNF (IFX or ADA) in steroid refractory (group 1) or
thiopurine refractory (group 2), - Before and after 3 mo of 6-MP in steroid
refractory (group 3), - In Thiopurine sensitive (group 4) and Steroid sensitive
(group 5). Response criteria: at 45 days of AntiTNFs or 3 mo. of 6-MP (CDAI: a
70 points drop, Mayo score 3 points30% drop) categorized in: remission
(CDAI150, Mayo Sc.2) and partial response. Rhodamine123 (fluorescent
Pgp substrate) efflux was studied by flow cytometry, expressed by the behaviour
of 2 markers defined by % of cells with different fluoresc. levels: M1 (high
fluoresc./low Pgp pump activity), M2 (low fluoresc./Pgp high activity, used for
the results).
RESULTS: Basal Pgp values (meanSD) in total PBL (M2) were: Group 1: 41.4
18.5, Group 2: 32.1 13.6, Group 3: 44.119.8, Group 4: 36.116.9, Group 5:
37.516.4 and HC 39.012.3. Major finding was a significant decrease of Pgp
after AntiTNFs in IBD in most of responder pts. ( -difference- in refractory vs
remission p: 0.030018, and 0.0023 for groups 1 and 2, and vs. partial response
p 0.014 in group 2, Mann Whitney). Initial Pgp values of pts. with available
Pgp post AntiTNFs measures according response were: Group 1 (n 20)
38.017.7, 44.68.4, 38.621.0, Group 2 (n 23) 35.916.0, 34.89.9, 23.17.1
for remission, partial response and refractory. Post AntiTNFs: 26.216.0,
29.012.1, 47.019.3 (Group 1) and 21.011.6, 22.311.5, 36.011.7 (Group
2). Pts. with 6-MP monotherapy (n23) did not show signif. changes in Pgp. A
signif. decrease of Pgp in CD3 lymph. (only group 2 p50.003) after AntiTNFs
was observed in remission vs refractory pts. In B lymph. lower values post
AntiTNFs (group 1) were shown in responders as a trend. Values of post-treat.
IBD were lower than HC (p50.04).
CONCLUSION: 1) We found that AntiTNFs decreased Pgp activity in PBL of
IBD pts., significantly associated with treatment response; 2) AntiTNFs could
modify the transport of concurrent Pgp substrates. MDR1 polymorphism typing
is ongoing. Longer follow-up and larger size sample are needed to verify the value
of Pgp activity measurement in IBD management.
Disclosure of Interest: A. Sambuelli Financial support for research from: Invest.
iniciate study Abbvie, C. Cortada: None declared, A. Gil: None declared, S.
Negreira: None declared, S. Huernos: None declared, S. Goncalves: None
declared, B. Maricel: None declared, T. Pablo: None declared
P0289 PREDICTIVE FACTORS FOR CHRONIC INFLAMMATORY
BOWEL DISEASES IN PATIENTS PRESENTING WITH NEW
ONSET DIARRHEA
A.-M. Singeap1,*, A. Trifan1, I. Girleanu1, O.C. Stoica2, C. Stanciu2
1
INSTITUTE OF GASTROENTEROLOGY AND HEPATOLOGY IASI, GR T
POPA UNIVERSITY OF MEDICINE AND PHARMACY, 2INSTITUTE OF
GASTROENTEROLOGY AND HEPATOLOGY IASI, Iasi, Romania
Contact E-mail Address: anamaria.singeap@yahoo.com
INTRODUCTION: The diagnosis of chronic inflammatory bowel diseases (IBD)
requires chronic changes over time (colonoscopic inflammatory changes lasting
at least 6 months and chronic histological inflammation). The onset of chronic
IBD may mimic acute diarrhea (defined as having sudden onset and lasting less
than four weeks); on the other hand, acute diarrhea may be mistaken with a new
case of chronic IBD. Our aim was to find clinical or biological predictive factors
for the diagnosis of chronic IBD.
AIMS & METHODS: A prospective study was conducted on all cases of new
onset diarrhea which presented in our Gastroenterology Unit during 2012. Their

United European Gastroenterology Journal 2(1S)


initial evaluation included clinical exam, complete biological picture and colonoscopy. All cases of new onset diarrhea with uncertain etiology were followed and
the final diagnosis was established at least 6 months after the onset, by repeating
colonoscopy with biopsy. The final diagnosis was correlated with clinical and
biological parameters evaluated at the first presentation.
RESULTS: A total of 120 patients with new onset diarrhea presented to our unit
in 2012. After the initial work-up, 82 patients had a positive diagnosis (infectious
colitis, colorectal cancer, radiation colitis, ischemic colitis). The remaining 38
patients, including both patients with inflammatory changes at colonoscopy
and patients with normal colonoscopy were reevaluated by colonoscopy and
biopsies after 6 months. For 11 patients, results were conclusive for chronic
IBD, 5 patients had collagenous or lymphocytic colitis, and 22 patients were
diagnosed with acute self-limiting colitis or irritable bowel syndrome (IBS).
Among the parameters we analysed, anemia and hypoalbuminemia in the
onset of the symptomatology were significantly correlated with the subsequent
diagnosis of chronic IBD; elevated levels of inflammatory parameters like Creactive protein and erythrocyte sedimentation were present in similar proportions in the different types of final diagnosis except IBS; other biological parameters were not contributive; non-significant correlation was found with respect
to age, weight loss and clinical history or associated symptoms.
CONCLUSION: Anemia and hypoalbuminemia are predictive factors for
chronic inflammatory bowel diseases in patients presenting with new onset diarrhea; a more extensive initial work-up applied in these patients could bring an
early diagnosis for IBD.
Disclosure of Interest: None declared
P0290 INCIDENCE AND RISK FACTORS OF C. DIFFICILE INFECTION
IN ULCERATIVE COLITIS
O.C. Stoica1, A. Trifan1,*, I. Girleanu1, A.-M. Singeap1, C. Cojocariu1,
C. Stanciu2
1
University of Medicine and Pharmacy "Gr. T. Popa", 2Gastroenterology, Institute
of Gastroenterology and Hepatology, Iasi, Romania
Contact E-mail Address: stoica_oanacristina@yahoo.com
INTRODUCTION: Recent epidemiologic studies have shown that patients with
inflammatory bowel disease (IBD), in particular those with ulcerative colitis
(UC) are at increased susceptibility for Clostridium difficile infection (CDI) compared with the general population.
AIMS & METHODS: The objectives of this study were to assess the incidence
and risk factors for CDI in UC patients in a tertiary center from North-Eastern
Romania.
Data of all UC patients admitted at the Institute of Gastroenterology and
Hepathology, Iasi, Romania, between January 2012 and October 2013 were
analyzed. In patients with concomitant CDI, risk factors for CDI were identified.
RESULTS: A total of 70 UC patients were included in this prospective study,
amongst which eight (11.5%) were identified as having a concomitant CDI. On
univariate analysis, age 4 65 years (OR 1.53, CI 0.93-16.27; p 0.048), male
gender (OR 1.38, CI 0.30-14.91; p 0.032), hemoglobin 59 g/dL
(OR 1.93, CI 0.19-18.52; p 0.043), severe UC disease (OR 1.22,
CI 0.14-10.5; p 0.037), and serum albumin 53 g/dL (OR 1.86, CI 1.1210.14; p 0.012) were associated with CDI. However, on multivariate analysis,
only severe disease and serum albumin retained statistical significance.
CONCLUSION: CDI was detected in one of eight patients admitted with a UC
flare; severe UC disease and low serum albumin were independent risk factors for
CDI.
Disclosure of Interest: None declared
P0291 ASSESSMENT OF WALL INFLAMMATION AND FIBROSIS IN
CROHNS DISEASE AND ITS CORRELATION WITH BOWEL
SONOGRAPHY AND MRI-ENTEROGRAPHY
A. Rispo1,*, P.P. Mainenti2, G.D. De Palma3, D. Musto1, L. Bucci4,
F.P. DArmiento5, A. Testa1, M. Rea1, F. Sasso1, N. Caporaso1, F. Castiglione1
1
Gastroenterology, 2Radiology, 3General Surgery, 4Colorectal Surgery,
5
Pathology, AOU Policlinico Federico II of Naples, Naples, Italy
INTRODUCTION: Crohns disease (CD) is a chronic inflammatory bowel disorder which is relapsing and remitting in nature and is characterised by transmural inflammation. About the therapeutical management of CD, it is believed
to be particularly important to differentiate between active inflammation and
fibrotic lesions in CD patients. Bowel sonography (BS) and MRI-enterography
(MRI) are procedures widely used for diagnosing CD and its complications.
AIMS & METHODS: to define the features of the CD strictures, also correlating
BS and MRI with histopathology.
We performed an observational prospective study including all CD patients
undergoing surgery for strictures. Pre-operative assessment was performed by
BS and MRI. BS investigated for: bowel wall thickness (BWT), bowel wall
stratification, power-Doppler vascular pattern of the bowel wall, mesentery
hypertrophy and enlarged lymphnodes. MRI study included: BWT, T1-weighted
gadolinium-based contrast uptake, enhancement pattern, mural and lymph node/
cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated
images, mesenteric signal intensity on T2-weighted fat-saturated images.
Histopathological inflammation was graded by the acute inflammatory score
(AIS); the semi-quantitative degree of fibrosis was performed according to the
literature. Statistical analysis was performed using chi-square, MannWhitney U
test and Cohens k measure.
RESULTS: The study included 20 CD patients. The indications to surgery were:
obstructive symptoms in 13 patients, penetrating complications in 7 patients. All
but 3 strictures (87%) showed acute inflammation coexisting with fibrosis while
only 3 strictures were predominantly fibrotic On BS, the presence of a layered

A209
bowel wall stratification was the only variable associated with the presence of
fibrosis (k 0.72; p 5 0.03). About MRI, AIS correlated with mural thickness
and mural/CSF signal intensity ratio on T2 sequences (p 0.04, p 0.02) but not
with mural enhancement on T1 images (p 0.62).
CONCLUSION: The majority of strictures in CD patients treated by surgery are
consistent with a mixed type inflammation (acute inflammation plus fibrosis).
The presence of stratified BS pattern shows a significantly higher degree of
fibrosis while the evidence of high mural signal intensity on T2-weighted fatsaturated images on MRI reflects histological features of acute inflammation.
Even if the ideal definition of the type of the strictures in CD still remains
significantly out of reach, the combined use of BS and MRI can offer useful
information in a sub-group of patients needing surgery for complicating CD.
Disclosure of Interest: None declared
P0292 NEUTROPHIL VOLUME DISTRIBUTION WIDTH AS A NEW
MARKER IN MONITORING INFLAMMATORY BOWEL DISEASE
ACTIVITY
Y. Aydemir1, A. Yuce1,*, A. Pnar2, G. Hizal1, B. Berberoglu Ates1,
H. Hzarcoglu Gulsen1, H. Demir1, I.N. Saltik Temizel1, F. Akbiyik2, H. Ozen1
1
Pediatric gastroenterology, 2Department of Biochemistry, Hacettepe university
school of medicine, Ankara, Turkey
Contact E-mail Address: dryusufaydemir@yahoo.com
INTRODUCTION: Inflammatory bowel diseases (IBD) are immune-mediated
disorders resulting in chronic, relapsing inflammation of the gastrointestinal
tract. A prominent feature of inflammation in IBD is the involvement of effector
cells such as neutrophils, eosinophils and mast cells. Neutrophil volume distribution width (NVDW) generated by VCS technology is a new marker which reflects
neutrophil activation.
AIMS & METHODS: We sought to investigate the value of NVDW parameter
in monitoring disease activation in IBD patients. Neutrophil VCS parameters
were measured in IBD patients admitted to our outpatient clinic. Age and sex
matched healthy subjects were taken as the control group. Patients with acute or
chronic infection and accompanying inflammatory disease were excluded.
Pediatric Crohn Disease Activity Index (PCDAI) and Pediatric Ulcerative
Colitis Activity Index (PUCAI) were used to define disease activation.
Complete blood count, albumin, eritrocyte sedimentation rate, C-reactive protein
ve fecal calprotectin were studied routinely at each visit.
RESULTS: A total of 34 pediatric patients with IBD and 29 controls were
enrolled in the study. NVDW was significantly higher in patients with IBD
compared to healthy controls (p50.001). An increased NVDW level was
observed in IBD patients with activation (22.422.13) compared to those in
remission (19.221.63) (p50.001). There was no statistically significant difference between IBD patients in remission and healthy controls (p 0.115). A significantly increased NVDW was observed in CD patients with activation
compared to CD patients in remission (22.872.19 vs 19.681.85, p 0.002).
NVDW was significantly higher UC patients with activation compared to UC
patients in remission (22.072.08 vs 18.530.93, p50.001). NVDW was correlated with WBC count (r:0.712), platelet count (r:0.347), ESR (r:0.471), CRP
(r:0.699), fecal calprotectin (r:0.812), PUCAI (r:0.852) ve PCDAI (r:0.670). The
best cut-off of NVDW for prediction of disease activation in CD and UC in this
series was 20.39 with a sensitivity of % 90.9 and a specificity of %75 (AUC:0.852
CI 0.698-1.000 p 0.002) and 19.74 with a sensitivity of % 92.9 and a specificity
of % 90.9 (AUC:0.961, CI:0.889-1.000, p50.001) respectively.
CONCLUSION: As a quantitative, objective, and sensitive parameter, NVDW
has a potential to be an additional predictor for disease activation in IBD.
Disclosure of Interest: None declared
P0293 IBS-LIKE SYMPTOMS ARE COMMON IN PATIENTS WITH
ULCERATIVE COLITIS IN DEEP REMISSION BUT THEY DO NOT
SEEM TO BE CAUSED BY LOW GRADE INFLAMMATORY
ACTIVITY
B. Jonefjall1,*, L. Ohman1,2, M. Simren1,3, H. Strid1
1
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine,
Sahlgrenska Acadamy, University of Gothenburg, 2Department of Microbiology
and Immunology, Sahlgrenska Acadamy, University of Gothenburg, Institute of
Biomedicine, 3University of Gothenburg Centre for Person-Centred Care (GPCC),
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: borje.jonefjall@vgregion.se
INTRODUCTION: Gastrointestinal (GI) symptoms compatible with Irritable
Bowel Syndrome (IBS) are common in patients with ulcerative colitis (UC). It
has been suggested that these symptoms are a reflection of occult inflammation
rather than coexisting IBS.
AIMS & METHODS: The aim was to investigate possible factors correlating
with IBS-like symptoms in UC patients in deep remission by assessing inflammatory markers, other GI symptoms, psychological symptoms and quality of life
(QOL). In total, 297 patients with UC were included at a regular outpatient clinic
visit. The patients completed self-administrated questionnaires to assess diagnostic criteria for IBS (Rome III), severity of GI symptoms (Gastrointestinal
Symptom Rating Scale (GSRS)), QOL (IBDQ), psychological symptoms
(Hospital Anxiety and Depression scale (HAD)), stress (QPS Nordic) and nonGI somatic symptoms (PHQ-12). Fecal calprotectin was used as inflammatory
marker. Patients with a normal rigid sigmoidoscopy and calprotectin 4200 g/g
were further investigated with flexible sigmoidoscopy. Deep remission was
defined as a total Mayo-score 2 (endoscopic findings, rectal bleeding and physician global assesment subscores 0), with no relapse during the three-month
period prior to visit. Comparisons where made between patients in deep remission with (UCRIBS) and without (UCR-IBS) IBS-like symptoms and patients

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United European Gastroenterology Journal 2(1S)

with active disease (UCA). Comparisons between the three groups were performed with Kruskal-Wallis test and thereafter post-hoc tests with Mann
Whitney U test and Bonferroni correction, with p-value 50.017 considered
significant.
RESULTS: Among the patients, 46% (n 138) met the criteria for deep remission and 18% (n 25) of these patients experienced IBS-like symptoms. There
was no difference in fecal calprotectin levels between the UCRIBS and the
UCR-IBS patients. The UCRIBS patients reported significantly more severe
GI symptoms in general, lower QOL scores, higher levels of anxiety, stress and
non-GI somatic symptoms than the UCR-IBS patients (see table). The level of
somatic and psychological symptoms did not differ between the UCRIBS
patients and the UC patients with active disease (see table).
Median (IQR)
Level of sign
p50.017

UCRIBS
(n 113)

UCA
(n 159)

UCR
UCR
IBS
UCA vs
IBS
vs UCR-IBSvs UCA UCR-IBS

32 (13-64)
1.5 (1.2-1.9)
2.0 (1.0-5.0)
1.0 (0.0-3.0)
1.0 (0.0-2.0)
3.0 (1.0-5.0)

280 (80-715)
2.5 (1.8-3.1)
4.5 (2.0-8.0)
3.0 (1.0-6.0)
2.0 (1.0-3.0)
4.0 (2.0-7.0)

p 0.044
p50.001
p 0.001
p 0.048
p 0.003
p50.001

p50.001 p50.001
p 0.701p50.001
p 0.291p50.001
p 0.941p50.001
p 0.281p 0.001
p 0.132p50.001

183 (163-198)205 (192-213)167 (144-195)p50.001

p 0.142p50.001

UCR
IBS
(n 25)

Calprotectin (g/g) 18 (7-30)


GSRS Total
2.5 (2.1-3.1)
Anxiety (HAD)
5.0 (3.5-8.0)
Depression (HAD)
2.0 (1.0-7.5)
Stress (QPS Nordic) 2.0 (1.0-3.0)
Non-GI Sympt (PHQ)6.0 (3.5-8.5)
QOL (IBDQ)

CONCLUSION: IBS-like symptoms in UC patients in deep remission are


common. Psychological factors rather than low grade inflammatory activity
seem to be of importance for symptom generation. Interestingly, UC patients
in deep remission with IBS-like symptoms experience GI symptoms, reduced
psychological well-being and QOL compatible with UC patients with active
disease.
Disclosure of Interest: None declared
P0294 THE SEVERITY OF ABDOMINAL PAIN AT ONSET OF
ULCERATIVE COLITIS IS ASSOCIATED WITH IBS-LIKE
SYMPTOMS DURING CLINICAL REMISSION
B. Jonefjall1,*, H. Strid1, L. Ohman1,2, J. Svedlund3, A. Bergstedt3, M. Simren1,4
1
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine,
Sahlgrenska Acadamy, University of Gothenburg, 2Department of Microbiology
and Immunology, Institute of Biomedicine, Sahlgrenska Acadamy, University of
Gothenburg, 3Department of Psychiatry, Institute of Neuroscience and Physiology,
Sahlgrenska Acadamy, University of Gothenburg, 4University of Gothenburg
Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, University of
Gothenburg, Gothenburg, Sweden
INTRODUCTION: Symptoms compatible with Irritable Bowel Syndrome (IBS)
are common in patients with ulcerative colitis (UC) in clinical remission. It has
been suggested that these symptoms might arise due to postinflammatory
changes comparable with postinfectious IBS. Factors that increase the risk for
developing IBS-like symptoms in patients with new onset of ulcerative colitis are
not known.
AIMS & METHODS: The aim was to study factors in patients with new onset of
UC that predicts development of IBS-like symptoms during clinical remission. In
total, 98 patients with new onset of UC were followed prospectively during three
years with yearly follow up visits. The patients completed self-administrated
questionnaires at each visit to assess diagnostic criteria for IBS (Rome II), severity of gastrointestinal (GI) symptoms (GI Symptom Rating Scale (GSRS)) and
psychological symptoms (Hospital Anxiety and Depression scale (HAD)). Fecal
calprotectin, ESR and CRP were used as inflammatory markers. The Mayo score
was used to evaluate clinical disease activity. Remission was defined as a total
Mayo score 2 and an endoscopic subscore 1, with no relapse during the threemonth period prior to visit. Data from the first visit at the onset of UC were
compared between the group of patients that fulfilled the criteria for IBS while in
remission (UCRIBS) during follow-up and the group that did not (UCR).
RESULTS: Among the UC patients, 87 met the criteria for clinical remission,
and 25 (29%) of these reported IBS-like symptoms in remission, on at least at one
of the three follow-up visits. The UCRIBS patients suffered from more severe
GI symptoms including abdominal pain (see table) during their primary flare
than the UCR patients. The patients that experienced mild to severe abdominal
pain had an increased risk for developing IBS-like symptoms during follow-up
(OR 3.1 (95% CI 1.1-8.4) p 0.03), this occurred in 39% (n 17) of these
patients compared to 20% (n 8) of the patients that reported none or minor
abdominal pain. Female gender (p 0.10), being unmarried/single (p 0.05) and
higher depression scores (HAD p 0.09) tended to be more common among
UCRIBS patients. There was no difference in clinical disease activity
(Mayoscore p 0.42), inflammatory markers (Calprotectin p 0.29, CRP
p 0.36, ESR p 0.58) or disease extension (p 0.57) between the two groups.

Table to abstract P0294


GSRS - Median (IQR)

UCRIBS

UCR

p - value

Total
Diarrhea
Constipation
Abdominal Pain
Indigestion
Reflux

3.5
5.0
2.3
2.7
3.8
1.0

2.7
5.3
2.0
2.0
3.3
1.0

50.05
0.56
0.30
50.05
0.09
0.07

(2.2-4.0)
(3.3-6.3)
(1.7-2.8)
(1.8-2.8)
(2.8-4.6)
(1.0-2.0)

(2.1-3.3)
(3.8-6.7)
(1.7-2.7)
(1.7-3.0)
(2.4-4.1)
(1.0-1.5)

CONCLUSION: Patients with ulcerative colitis that develop IBS-like symptoms


during follow-up experience more severe GI symptoms, including abdominal
pain, at disease onset, despite no difference in inflammatory disease activity.
This might indicate a more sensitive GI tract in this category of patients.
Disclosure of Interest: None declared
P0295 NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AS A
POTENTIAL BIOMARKER FOR AXIAL INVOLVEMENT IN
INFLAMMATORY BOWEL DISEASE PATIENTS
C. Gonen1,*, D. Kurtulus2, K. Kochan1, A. Yesil1
1
Gastroenterology, Istanbul Haydarpasa Numune Training and Research Hospital,
2
Physical Therapy and Rehabilitation, Umraniye Training and Research Hospital,
Istanbul, Turkey
Contact E-mail Address: drcgnn@yahoo.com
INTRODUCTION: Axial arthropathy associated with inflammatory bowel diseases (IBD) includes isolated sacroiliitis, inflammatory back pain and ankylosing
spondylitis. There is no reliable laboratory test that can be used as a diagnostic
tool in the management or diagnosis of axial arthropathy in IBD. Neutrophil
gelatinase associated lipocalin (NGAL) is a recently identified molecule, which
has tissue destructive effects by protecting matrix metalloproteinase-9 from autodegradation. This represents an important mechanism by which NGAL may
contribute to the degradation and remodelling of the extracellular matrix, leading
to rheumatologic manifestations of IBD. Previously, we showed that serum
NGAL levels in IBD patients were significantly higher than healthy controls.
AIMS & METHODS: To investigate serum NGAL levels in IBD patients with
or without axial arthropathy. A total of 83 patients (64 with IBD, 19 with IBD
and axial arthropathy), and 40 age- and sex-matched healthy controls (HC) were
included in this study. Patients with peripheral joint involvement were excluded.
Serum NGAL levels were measured using ELISA.
RESULTS: The patients were aged between 16 and 74 years, and their mean age
was 39.1  11.5 years. Age, gender, and disease-year distributions were not
statistically significantly different among the groups. Serum NGAL levels were
elevated significantly in IBD patients with axial artropathy [median 234 U/L,
range (122-312) ng/ml] compared to IBD patients without axial involvement [168
U/L (57-310 ng/ml] (p:0.001) and HC group [122 (45-234) ng/ml] (p:0.004).
NGAL levels of the IBD group were significantly higher than those of the control
group (p:0.001). There was no significant difference between the IBD group and
IBD with axial involvement group in Hgb, WBC, CRP, and ESR values.
CONCLUSION: Serum NGAL levels were found to be elevated in IBD patients
with axial involvement when compared to IBD patients without involvement,
suggesting a partial pathophysiologic role in this particular extraintestinal manifestation. NGAL seems to be a promising biomarker for the diagnosis and
management of axial arthropathy in IBD.
REFERENCES
1. Yesil A, Gonen C, Senates E, et al. Relationship between neutrophil gelatinase-associated lipocalin (NGAL) levels and inflammatory bowel disease type
and activity. Dig Dis Sci 2013; 58: 2587-2593.
2. Gupta K, Shukla M, Cowland JB, et al. Neutrophil gelatinase-associated
lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9. Arthritis Rheum 2007; 56: 3326-3335.
3. Mattey DL, Packham JC, Nixon NB, et al. Association of cytokine and matrix
metalloproteinase profiles with disease activity and function in ankylosing spondylitis. Arthritis Res Ther 2012; 14: R127.
Disclosure of Interest: None declared
P0296 ANORECTAL STRICTURE IN CROHNS DISEASE: NATURAL
FATE OR CHALLENGING TARGET TO TREAT?
C. Brochard1,*, L. Siproudhis1, T. Wallenhorst1, P.N. DHalluin1, J.F. Bretagne1,
G. Bouguen1
1
Service des maladies de lappareil digestif, Rennes, France
Contact E-mail Address: charlene.brochard@chu-rennes.fr
INTRODUCTION: The natural history of non-fistulising perianal Crohns disease (PCD) remains unknown.
AIMS & METHODS: This study aimed to assess the long-term outcome of
anorectal strictures. Between January 2005 and October 2013, a tertiary referral
centre prospectively recorded each clinic of patients with PCD with detailed data
about the phenotype and disease activity of luminal and anal CD, medical treatment and surgery. At each visit, CD and PCD were assessed using the HarveyBradshaw Score, the Cardiff-Hughes classification and with the Perianal Disease
Activity Index. Follow-up was determined by the duration between the diagnosis
of anorectal stricture and the last visit. Cumulative incidence of stricture healing
(disappearance of the anal stricture) was estimated using a Kaplan-Meier method

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United European Gastroenterology Journal 2(1S)


and factor associated with an unfavourable course (persistent stricture S2, persistent stoma or proctectomy) with non-parametric test.
RESULTS: A total of 102 patients (M/F: 37/65) were included. The duration of
CD at diagnosis was 8.9 years. After a median follow-up period of 2.8 years, 52
of the 88 followed patients (59%) achieved anorectal stricture healing. Two
patients (2%) developed anal adenocarcinoma. Female gender (HR 2.05 [1.14.03], p 0.0221), disease duration of CD of less than 10 years (HR 1.94 [1.013.63], p 0.0271), and anal fistula at stricture diagnosis (HR 2.36 [1.21-5.05],
p 0.0106) were significantly associated with anorectal stricture healing in a
multivariate analysis model. Twenty-eight patients (32%) had an unfavourable
course at the end of follow-up. Gender and introduction or optimisation of
TNF antagonist treatment decreased the risk of unfavourable course in multivariate analysis. Conversely, the Luminal B2 phenotype at CD diagnosis was the
only factor associated with unfavourable course.
CONCLUSION: Anorectal stricture does not imply a non-reversible and complicated condition related to severe perianal Crohns disease. However, both
diagnosis of cancer and sepsis drainage remain challenging in this situation.
Disclosure of Interest: None declared
P0297 REDUCING UNNECESSARY COLONOSCOPY A COST
MINIMIZATION ANALYSIS OF NEW DIAGNOSTIC STRATEGIES
FOR EXCLUDING ORGANIC BOWEL DISEASE IN PRIMARY CARE
PATIENTS
C. Helsper1,*, L. Kok1, S.G. Elias1, H.E. Koffijberg1, K.G. Moons1, N.J. de Wit1
1
Julius Center for Health Sciences and Primary Care, UNIVERSITY MEDICAL
CENTER UTRECHT, Utrecht, Netherlands
Contact E-mail Address: c.helsper@gmail.com
INTRODUCTION: In general practice, complaints of the lower digestive tract
are frequently presented. Of those affected, only an estimated 7% suffers from
organic bowel disease (OBD), such as inflammatory bowel disease, diverticulitis
and cancer. [1] These patients should be referred for colonoscopy without delay.
Unfortunately, OBD is found in only one third of referred patients, indicating a
considerable number of unnecessary referrals in primary care.[2] Our research
group developed several diagnostic strategies to optimize colonoscopy referral
policy.
AIMS & METHODS: We aim to assess the benefits and costs of the diagnostic
strategies developed to reduce unnecessary colonoscopy referrals in primary care.
The diagnostic strategies combine patient history and physical examination with
two point of care tests (POCT); calprotectine and/or iFOBT. We evaluated the
benefits and costs of three diagnostic strategies, each at three cut-off points.
Strategies are: 1. iFOBT added to history and physical examination (iFOBT),
2. calprotectine added (Calpro), and 3. both POCT added (CiF). The three
different cut-off points are based on OBD risk for referral. Benefits are prevented
costs and prevented unnecessary referrals for colonoscopy. Costs are additional
costs and missed diagnoses.
RESULTS: A reduction of 0.5% (iFOBT), 5.4% (Calpro) and 5.9% (CiF) in the
number of colonoscopies cover the additional testing costs. The largest costsavings are achieved by iFOBT and CiF. At the 2.5% cut-off, these strategies
provide a modest cost reduction (1.3 and 0.2mln Euros, respectively) with 84
(2%) and 0 (0%) patients incorrectly not referred for colonoscopy annually in the
Netherlands. At a referral threshold of 5% OBD probability, a cost reduction of
E5.8 (iFOBT), E2.3 million (Calpro) and E4.7(CiF), Euros would be achieved at
an annual cost of 720 (4%), 720 (4%) and 306 (3%) incorrectly averted referrals
in the Netherlands, respectively. Cost reduction for all strategies even increased
at 7.5% OBD risk, but this threshold yielded much higher incorrectly referred
patients for all three strategies, above 1000 patients annually in the Netherlands.
CONCLUSION: Implementation of the diagnostic strategies as developed in the
CEDAR study are likely to reduce the colonoscopy related costs at a burden of
incorrectly averted referrals for colonoscopy. Implementation of the CiF and
iFOBT strategies at the lowest threshold value for referral, is likely to be safe
and modestly cost-saving. The CiF and iFOBT strategy at the 5% OBD probability threshold, might also be a valuable alternative in current practice given the
substantial costs savings and relative safety. The most appropriate threshold and
the resulting cost savings needs to be determined for the health care setting in
which it will be used.
REFERENCES
[1]. Muris J, et al. One-year prognosis of abdominal complaints in general practice: a prospective study of patients in whom no organic cause is found. Br J Gen
Pract 1996; 46: 715719.
[2]. Morini S, et al. Diagnostic yield of open access colonoscopy according to
appropriateness. Gastrointest Endosc 2001; 54: 175179.
Disclosure of Interest: None declared
P0298 DIFFERENTIATING CROHNS DISEASE FROM INTESTINAL
TUBERCULOSIS IN A TUBERCULOSIS ENDEMIC AREA
C. Panackel1,*, P.K.R.1, R. Thomas1, B. Sebastian1, R.M. Thomas2, S. Mathai1
1
Department of Gastroenterology and Hepatology, 2Pathology, Medical trust
Hospital, Kochi, kerala, India, Kochi, India
Contact E-mail Address: charlespanackel@hotmail.com
INTRODUCTION: Crohns disease (CD) and Ileocolonic Tuberculosis (ITB)
mimic each other in clinical, endoscopic and histologic features. In an ITB endemic country like India differentiating one from the other remains a challenge.
AIMS & METHODS: The aim of our study was to revalidate the existing clinical, laboratory and histological parameters that aid in differentiating Ileocolonic
Tuberculosis from Crohns disease.
Methods: We prospectively included patients with Ileocolonic ulcers. Patients
were diagnosed as either ITB or CD based on established criteria. All patients

were evaluated for Extra Intestinal Tuberculosis. Patients were followed up and a
repeat colonoscopy was performed at 3 months and at of 6 months of treatment;
diagnosis was revised if the patient did not demonstrate mucosal healing when
compared to the previous colonoscopy. Patients who completed follow up were
included in final analysis.
RESULTS: Sixty patients were included in the study of which fifty-five patients
completed follow up and were included in the analysis. A final diagnosis of CD
was made in 37 patients (67%), ITB in 18 patients (33%). Differentiating features
of ITB and Crohns are summarised in table -1. Quantiferon TB Gold in Tube
test was positive in 94.4% of ITB patients versus 19.3% of Crohns disease
patients (P- 50.001). The Sensitivity, Specificity, Positive predictive value,
Negative predictive value for Quantiferon TB Gold in tube test was 94.44%,
83.78%, 73.91% and 96.88% respectively.
Variables

CD (n 37)

TB (n 18)

P value

Mean Age (in years)


Male/ Female
Mean Duration of illness (Months)
Bleeding PR
Fever
TB QuantiferonGold in Tube
Positive
Negative
Granuloma Characteristics
Caseation
Large
Confluent
More than 5 granulomas/hpf
Band of epitheloid Histiocytes
Lymphoid cuff
Pericryptal
Microgranulomas
Focally enhanced colitis
Histology abnormal in
endoscopically normal sites

32.5
20/17
13.6
7 (18.9%)
4 (10.8%)

45
8/10
8
0 (0)
8 (44.4%)

0.1
0.7
0.026
0.04
0.004
50.001

6
31

17
1

0 (0)
5(13%)
7 (19%)
8 (21%)
71(19%)
19 (51%)
21(56.7%)
30 (81.1%)
15 (40.5%)
23 (60.5%)

5 (28%)
12 (66.6%)
13(72.2%)
10 (55.5)
8 (44.4%)
11 (61%)
3 (16.7%)
3 (16.7%)
2 (11.1%)
1(5%)

CONCLUSION: Longer duration of illness, bleeding per rectum, pericryptal


granulomas, microgranulomas, focally enhanced Colitis, histological changes
in antrum and histological abnormality in endoscopically normal sites favored
Crohns disease. Presence of fever, large granulomas, caseating granulomas, confluent granulomas, favored ITB. Quantiferon TB Gold in Tube test had good
sensitivity but poor specificity in differentiating ITB from Crohns disease.
REFERENCES
Kim BJ, Choi YS, Jang BI, et al. Prospective evaluation of the clinical utility of
interferon-c. Assay in the differential diagnosis of intestinal tuberculosis and
Crohns disease. Inflamm Bowel Dis 2011; 17: 13081313.
Disclosure of Interest: None declared
P0299 REPRODUCIBILITY OF SEROLOGIC ANTIBODY ACTIVITY AT
DIAGNOSIS AND AFTER TREATMENT IN PEDIATRIC
ULCERATIVE COLITIS AND CROHNS DISEASE
C. Olbjrn1,*, G. Perminow2, M.C. Smastuen3, B. Nakstad1, M.H. Vatn4
Department of Pediatrics and Adolescent Medicine, Akershus University Hospital,
Lrenskog, 2Department of Pediatrics, Oslo University Hospital, Ulleval,
3
Department of Biostatistics, University of Oslo, 4Epigen, Faculty Division
Akershus University Hospital, Oslo University Hospital, Oslo, Norway
Contact E-mail Address: chrisolb@gmail.com
1

INTRODUCTION: Serologic nuclear and anti microbial antibodies have been


recognized as predictive markers of disease course and complications in ulcerative colitis (UC) and Crohns disease (CD). The stability of serologic titers over
time of these markers has been questioned.
AIMS & METHODS: The aim of the present study was to compare antibody
titers before and after treatment in newly diagnosed treatment naive pediatric
patients with inflammatory bowel disease (IBD). Patients aged 518 years,
(N 57) diagnosed with IBD were included between 2005-2007 and followed
prospectively. Blood specimens were analyzed for antibodies (Prometheus labs,
San Diego) at diagnosis, and repeatedly after 1-2 years of treatment.
RESULTS: Among the 19 UC patients 68% were ANCA-positive versus 32% of
the 38 CD patients (p 0.02). In CD and UC patients respectively, the median
titers in EU/ml at baseline against I2, 249 and 257, Anti-Omp C, 3.1 and 3.6,
ASCA IgA, 8.4 and 3.1, ASCA IgG, 11.9 and 3.1 and CBir, 27 and 16, were not
significantly different at follow- up. The titers against ASCA IgA and IgG were
significantly higher in the CD patients versus UC patients both at diagnosis and
at follow-up (p 0.01 and p50.01, respectively) with post-treatment ASCA IgA
7.5 and ASCA IgG 12.8 in CD versus 3.1 and 6 in UC respectively (p50.01 and
0.03). There were no statistically significant differences for gender, or between the
different treatments of CD patients, in whom 18 of 38 patients had received
infliximab.
CONCLUSION: UC patients were significantly more frequently ANCA positive, whereas the CD patients had significantly higher titers against ASCA IgA
and IgG both at diagnosis and at follow-up. The present study demonstrates a
general reproducibility of the presence and titers of serologic antibodies from the

A212
time of diagnosis until 1-2 years of follow- up for IBD, indicating that serologic
markers measured at diagnosis may be applied as prognostic markers even after
years of treatment.
Disclosure of Interest: None declared
P0300 ULTRASOUND
BASED
REAL
TIME
ELASTOGRAPHY
RELIABLY IDENTIFIES FIBROTIC GUT TISSUE IN PATIENTS
WITH STRICTURING CROHNS DISEASE (GUT-RTE)
D.C. Baumgart1,*, H.-P. Muller1, U. Grittner2, D. Metzke1, A. Fischer1,
O. Guckelberger3, A. Pascher3, I. Sack4, M. Vieth5, B. Rudolph6
1
Department of Medicine, Division of Gastroenterology and Hepatology,
2
Department of Biostatistics and Clinical Epidemiology, 3Department of Surgery,
4
Department of Experimental Radiology, Charite Medical Center - Medical School
of the Humboldt-University of Berlin, Berlin, 5Department of Pathology,
University of Bayreuth, Bayreuth, 6Department of Pathology, Charite Medical
Center - Medical School of the Humboldt-University of Berlin, Berlin, Germany
Contact E-mail Address: daniel.baumgart@charite.de
INTRODUCTION: Crohns disease (CD) is a relapsing inflammatory disease.
Many patients experience intestinal strictures that require surgery if non amenable to medical therapy. Moreover, there is an unmet need to objectively assess
new treatment endpoints such as disease modification, structural damage and
restitution. Real time ultrasound elasticity imaging has not been systematically
developed yet to evaluate the viscoelastic properties of the human gut in vivo.
AIMS & METHODS: In this prospective, controlled and partially blinded study
unaffected and affected gut segments of 10 CD patients (male 6, median
age 49, median Harvey Bradshaw index 6) were examined pre-, intra- and
postoperatively with ultrasound including real time elastography (RTE) to assess
strain. Following surgical resection strain of full gut wall segments was analyzed
by direct tensiometry. Histopathological scoring of fibrosis with two independent, specific stains, molecular quantification of collagen content as well as morphometrics were performed. Data were aggregated at patient level and nonaggregated at segment level prior to statistical analysis including a non-linear
model where appropriate.
RESULTS: RTE strain was significantly different between unaffected and
affected segments (mean  SD 169.0  27.9 vs. 43.0  25.9; p50.001).
Moreover, mean RTE strain per patient was completely different in unaffected
(all 4 132) compared with affected (all 5 87) segments. An RTE strain cut point
of 110 reliably distinguished segments. Tensiometry strain in segments with an
RTE strain of 4110 was significantly greater than in those with 5 110 (mean 
SD 77.1  21.4 vs. 12.9  9.5; p50.001). These findings were further corroborated by morphometrics, collagen content and fibrosis score.
CONCLUSION: RTE allows bedside assessment of gut tissue mechanical properties in CD.
REFERENCES
Baumgart DC et al. Lancet 2012; 380: 1590-605.
Disclosure of Interest: D. Baumgart Other: The ultrasound unit was provided free
of charge for the duration of the study., H.-P. Muller: None declared, U.
Grittner: None declared, D. Metzke: None declared, A. Fischer: None declared,
O. Guckelberger: None declared, A. Pascher: None declared, I. Sack: None
declared, M. Vieth: None declared, B. Rudolph: None declared
P0301 CORRELATION
BETWEEN
MAGNETIC
RESONANCE
ENTEROGRAPHY, CAPSULE ENDOSCOPY, FECAL
CALPROTECTIN AND CRP IN PATIENTS IN CLINICAL REMISSION
WITH KNOWN SMALL BOWEL CROHNS DISEASE PRELIMINARY
RESULTS FROM THE PROSPECTIVE ISRAELI IBD RESEARCH
NETWORK (IIRN) STUDY
D. Yablecovitch1,*, S. Ben-Horin1, M. Amitai2, A. Lahat1, S. Neuman1,
B. Avidan1, O. Har-Noy1, N. Levhar1, R. Eliakim1
1
Departmet of Gastroenterology, 2Departmet of Radiology, Chaim Sheba Medical
Center, Tel Aviv University, Tel Hashomer, Tel Aviv, Israel
Contact E-mail Address: doronyab@gmail.com
INTRODUCTION: The correlation between clinical activity and intestinal
inflammation in Crohns Disease (CD) is modest. Biomarkers and imaging techniques are objective tools able to assess the biological activity.
AIMS & METHODS: Our aim was to objectively evaluate disease activity in
patients in clinical remission (CR) with small bowel CD (SBCD) by using capsule
endoscopy (CE), magnetic resonance enterography (MRE) and correlate the
findings with laboratory parameters of inflammation.
Thirty-five consecutive patients with known SBCD in CR were prospectively
recruited and underwent MRE, followed by Agile patency capsule (PC), and if
patency was proven, a video capsule. The Lewis score was calculated for each
tertile. C-reactive protein (CRP) and fecal calprotectin (FC) were evaluated for
their association with clinical activity, MRE and CE findings.
RESULTS: Eight of 35 cases with abnormal passage of PC were excluded, all of
which were predicted by MRE (NPV 100%). All video capsules reached the
cecum, including 9 additional cases predicted to be retained by MRE which
proved to be false positives (53%) by the PC. CE detected active disease in the
proximal-mid SB in 44% of the patients and in the distal SB in 48%. MRE
detected proximal-mid SB disease in only 18% and distal disease in 67% of
patients. Most (81%) of patients with SB lesions detected by CE had elevated
FC (cutoff, 30mg/g) while CRP (cutoff, 5mg/l) was increased in 19% of these
patients. FC modestly correlated with Lewis score (r 0.4). There was no correlation between CRP and Lewis score. Similarly, 78% of patients with active
disease on MRE had increased FC, while CRP was elevated in 22% of the
patients.

United European Gastroenterology Journal 2(1S)


CONCLUSION: 1. A PC prior to the CE procedure diminished the likelihood of
CE retention, and was superior to MRE in prediction of capsule retention. 2.
Despite CR active inflammation was detected in 4 50% of patients by CE. 3.
Proximal SB disease was better detected by CE than MRE. 4. FC associated
better than CRP with disease activity found by CE or MRE. 5. When used
properly, CE is a safe procedure in patients with SBCD.
# with the support of a grant from the Helmsley charitable trust.
Disclosure of Interest: None declared
P0302 SYSTEMATIC ANALYSIS OF FACTORS ASSOCIATED WITH
PROGRESSION AND REGRESSION OF ULCERATIVE COLITIS IN
THE SWISS IBD COHORT STUDY
E. Safroneeva 1,*, S. Vavricka2, N. Fournier3, F. Seibold4, C. Mottet3,
A. Straumann5, G. Rogler2, A. Schoepfer3 on behalf of Swiss IBD Cohort Study
Group
1
University Hospital Bern, Bern, 2University Hospital Zurich, Zurich, 3University
Hospital Lausanne / CHUV, Lausanne, 4Tiefenaustpital Bern, Bern, 5University
Hospital Basel, Basel, Switzerland
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: There is a lack of studies having systematically assessed in a
large cohort of patients with ulcerative colitis (UC) the disease location over time
as well as risk factors associated with progression or regression of disease extent.
AIMS & METHODS: We aimed to assess disease location over time and to
evaluate associated risk factors. Data from the Swiss IBD cohort study were
analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). Disease locations over time were analyzed and risk factor analysis for a change in disease location was performed
using logistic regression modeling. Non parametric data are illustrated as median
and interquartile range [IQR].
RESULTS: A total of 1,016 UC patients (45.6% females, median age at diagnosis 31 [23.3-40.5] years) were included. At diagnosis, UC patients presented
with the following disease locations: 199 (19.6%) proctitis, 338 (33.3%) left sided
colitis, 381 (37.5%) extensive colitis/pancolitis, and 98 (9.6%) unknown. During
a median of 9 [5-16] years disease duration, a disease progression was documented in 145/1016 (14.3%) of patients, a regression in 176/1016 (17.3%) of patients,
whereas 624/1016 (61.4%) of patients had a stable disease location (7% of
patients with unknown evolution of disease location over time). Logistic regression modeling identified the following factors associated with disease progression
in UC patients presenting with proctitis or left-sided UC at diagnosis: treatment
with systemic steroids (OR 2.077, 95%4CI 1.359-3.174, p 0.001), treatment
with immunomodulators (azathioprine, 6-MP, methotrexate) (OR 1.647,
95%4CI 1.119-2.424, p 0.011), treatment with TNF-antagonist(s) (OR
1.668, 95%4CI 1.077-2.581, p 0.022), and treatment with calcineurin-inhibitors (OR 3.159, 95%4CI 1.679-5.943, p 5 0.001). Neither gender, age at UC
diagnosis, body mass index, presence of extraintestinal manifestations, smoking
status at diagnosis, positive UC family history, nor 5-ASA treatment were associated with disease progression. No specific factors were found to be associated
with regression in UC patients with extensive colitis/pancolitis or left-sided colitis
at diagnosis.
CONCLUSION: Over a median of 9 years disease duration about two-thirds of
UC patients maintained the initial disease location whereas one-third either had a
progression or a regression of the initial disease location. Treatment with systemic steroids, immunomodulators, TNF-antagonists, or calcineurin-inhibitors
was significantly associated with disease progression.
Disclosure of Interest: None declared
P0303 PSORIASIS PHENOTYPE IN INFLAMMATORY
DISEASE: A CASE-CONTROL PROSPECTIVE STUDY

BOWEL

E. Lolli1,*, R. Saraceno2, A. Ventura2, G. Condino1, S. Onali1, P. Scarozza1,


A. Capanna1, C. Petruzziello1, E. Calabrese1, S. Chimenti2, F. Pallone1,
L. Biancone1
1
Gastroenterology Unit, University of Rome Tor Vergata, 2Dermatology Unit,
University of Rome Tor Vergata, Rome, Italy
Contact E-mail Address: elisabetta.lolli@uniroma2.it
INTRODUCTION: Psoriasis has been associated with Inflammatory Bowel
Disease (IBD). However, whether IBD is associated with specific phenotypes
of psoriasis is unknown.
AIMS & METHODS: In a case-control prospective study, we aimed to assess
psoriasis phenotype in IBD patients (pts), when using a non-IBD patients population as controls (non-IBD C). From January 2011 to November 2013, dermatological assessment was performed in 251 IBD pts under follow up.
Dermatological assessment was focused in detecting the presence of psoriasis
(present/absent) and in defining its characteristics (localization, phenotype),
including severity (mild/moderate/severe). In order to define psoriasis phenotype
in IBD, each IBD pt with psoriasis was matched for gender, ethnicity and age
(5 years) with one non-IBD pt with psoriasis, referring to the same centre. Data
were expressed as median (range) and differences between groups assessed by the
T test or the chi-squared test, as appropriate.
RESULTS: Dermatological assessment was performed in 251 IBD pts (115 F,
age 46 yrs, range 16-85; IBD duration 9 yrs, range 1-46): 93 UC (42 M, age 50,
range 22-85; UC duration 7 yrs, range 1-41; UC extent: proctitis 33, left 13,
extensive 42, ileal pouch 3, ileostomy 1, ileo-rectal anastomosis 1) and 158 CD
(91 M, age 43, range 16-80; CD duration 10 yrs, range 1-46; CD colitis 13, ileocolitis 32, ileitis 51, neo-terminal ileum 56, ileostomy 2, distal ileum jejunum 4).
Non-IBD C included 62 pts (35 M, age 47, range 18-75). Among the 251 IBD pts,
psoriasis was detected in 62 (25%; 36 CD, 26 UC). In the IBD group, the median
age and IBD duration were comparable in pts with or without psoriasis (years:

A213

United European Gastroenterology Journal 2(1S)


age 50 range 23-72 vs 47 range 16-85; IBD duration 9.5, range 1-46 vs 9, range 141; p ns for both). Mild plaque type psoriasis was detected in a higher proportion of IBD pts (52/62; 84%) than non-IBD C (33/62; 53%; p50.001). Scalp
psoriasis and sebopsoriasis were the more common psoriasis phenotype in IBD
(21/62; 84%), followed by palmo-plantar psoriasis (9/62; 14%) and by inverse
psoriasis (8/62; 13%). Psoriatic arthritis was detected in 10/62 (16%) non-IBD-C
and in 6/62(10%) IBD patients (p n.s.). Among the 62 IBD pts with psoriasis,
psoriasis developed after anti-TNFs in 6 (10%), including palmo-plantar (n 4),
sebopsoriasis (n 1), inverse psoriasis (n 1).
CONCLUSION: Results from a cohort of IBD patients matched with non-IBD
control patients suggest that specific phenotypes of psoriasis may be associated
with IBD.
Disclosure of Interest: None declared
P0304 CONTRAST ENHANCED ULTRASOUND AS A POINT-OF-CARE
TECHNIQUE IN COMPLICATED CROHNS DISEASE PATIENTS
E. Calabrese1,*, F. Zorzi1, E. Stasi1, E. Lolli1, S. Onali1, P. Scarozza1,
G. Condino1, C. Petruzziello1, L. Biancone1, F. Pallone1
1
Department of Systems Medicine, Gastroenterology Unit, University of Rome Tor
Vergata, Rome, Italy
Contact E-mail Address: emma.calabrese@uniroma2.it
INTRODUCTION: Crohns disease (CD) is associated with penetrating complications such as phlegmons and intra-abdominal abscesses. As the management of
the patients is influenced by the presence of such complications, a readily available tool for the diagnosis of extramural complications in CD is needed.
Preliminary findings suggest that the assessment of vascularity within intraabdominal masses may distinguish between phlegmons and abscesses.
AIMS & METHODS: Aim of our study was to evaluate the use of contrast
enhanced ultrasound (CEUS) to distinguish between phlegmons and intraabdominal abscesses in CD patients as a point-of-care technique. From
November 2011, consecutive patients with complicated CD were enrolled.
Indications of patient assessments by CEUS were symptoms, signs and biochemical exams indicating penetrating behavior (abdominal pain, mass, fever, elevated
CRP and leukocytosis). A total of 22 CD pts (14 M; median age 27 yrs, range 1875; disease duration: median 54 mos, range 1-564; CD site: ileal in 13 pts, ileocolonic in 9 pts; CD behavior: penetrating in 20 pts, stricturing in 2 pts; previous
ileocolonic resection in 9 pts) were included. Clinical evaluation by an IBD expert
and other cross sectional imaging techniques (MR and CT) were considered as
the standard.
RESULTS: CEUS detected abscesses in 9 and phlegmons in 12 pts. One patient
had an unspecified lesion that was diagnosed as metastasis by PET. Six out of 9
abscesses were confirmed by CT-Enteroclysis and these pts underwent surgery
during the follow up. The remaining 3 pts with abscesses were treated with
antibiotics and are still in follow up (17.5 mos). In the phlegmon group, 4 out
of 12 patients were evaluated by CT or MRI that confirmed CEUS findings in 3
cases but in one patient a deep abscess was identified and surgery was scheduled.
Eight out of 12 pts were clinically followed up (median: 16 mos). Two of these
patients developed an abscess after one week from CEUS despite medical treatment. Overall CEUS correctly identified 19 out of 22 lesions (86%) on the basis
of cross sectional imaging modalities and clinical follow up used as final
diagnosis.
CONCLUSION: CEUS is a non-invasive, radiation-free and point-of-care technique able to differentiate phlegmons from abscesses driving a prompt clinical
management in complicated CD patients.
Disclosure of Interest: None declared
P0305 ACCURACY
OF
SMALL
INTESTINE
CONTRAST
ULTRASONOGRAPHY COMPARED TO MAGNETIC RESONANCE
ENTEROGRAPHY IN CHARACTERIZING LESIONS IN PATIENTS
WITH CROHNS DISEASE
E. Calabrese1,*, E. Stasi1, F. Zorzi1, E. Lolli1, G. Condino1, S. Onali1,
C. Petruzziello1, M.C. Fantini1, P. Cerro1, P. Scarozza1, L. Biancone1,
F. Pallone1
1
Department of Systems Medicine, Gastroenterology Unit, University of Rome Tor
Vergata, Rome, Italy
Contact E-mail Address: emma.calabrese@uniroma2.it
INTRODUCTION: Small intestine contrast ultrasonography (SICUS) can detect
intestinal damage in patients with Crohns disease (CD).
AIMS & METHODS: We evaluated the diagnostic accuracy of SICUS in determining the site, extent, and complications of CD, compared with magnetic resonance (MR)-enterography as the standard. We performed a retrospective
analysis of 59 patients with CD [(M 34; median age: 46, CD site: ileal 36
(61%), ileocolonic 18 (30%), jejuno-ileal, 3 (5%), colonic 1 (2%); behaviour:
non-stricturing non-penetrating 10 (17%), structuring 31 (53%), penetrating 18
(30%); previous surgery 25 (42%)] evaluated by SICUS and MR-enterography 3
months apart, between January 2011 and March 2014. We evaluated disease site
(based on bowel wall thickness), extent of lesions, presence of complications
(stenosis, prestenotic dilation, abscess, or fistulas) using MR-Enterography as
the standard. Sensitivity, specificity, and diagnostic accuracy were calculated.
We determined the correlations in maximum wall thickness and disease extent
in the small bowel between results from SICUS and MR-Enterography.
RESULTS: SICUS identified the site of small bowel CD with 96% sensitivity,
71% specificity, and 93% diagnostic accuracy; it identified the site of colon CD
with 73% sensitivity, 93% specificity, and 88% diagnostic accuracy. Results from
SICUS and MR-enterography correlated in determination of bowel wall thickness (rho 0.51) and disease extent (rho 0.75; P5.0001 for both). SICUS
detected ileal stenosis with 90% sensitivity, 94% specificity, and 91.5%

diagnostic accuracy, and pre-stenotic dilation with 66% sensitivity, 83% specificity, and 73% diagnostic accuracy. SICUS detected abscesses with 75% sensitivity, 100% specificity, 98% diagnostic accuracy, and fistulas with 82% sensitivity,
81% specificity, and 81% diagnostic accuracy.
CONCLUSION: SICUS identified lesions and complications in CD patients
with high levels of sensitivity, specificity, and accuracy compared to MR-enterography. SICUS might be used as an imaging tool as part of a focused diagnostic
and follow up examination of patients with CD.
Disclosure of Interest: None declared
P0306 ASSOCIATION BETWEEN HIGH ADALIMUMAB DRUG LEVEL
AND MUCOSAL HEALING IN PATIENTS WITH CROHNS DISEASE
E. Zittan1,2,*, B. Kabakchiev2,3, J. Stempak2,3, G. Nguyen1,2, K. Croitoru1,2,
G.Van Assche1,2, A. Steinhart1,2, M. Silverberg1,2
1
University of Toronto, 2Zane Cohen Center Mount Sinai, 3lunenfeld-tanenbaum
research institute, Mount Sinai Hospital, Toronto, Canada
Contact E-mail Address: EZittan@mtsinai.on.ca
INTRODUCTION: The current approach to managing loss of response to anti-TNF
agents is based on clinical symptoms and empirically increasing the dose or shortening
the treatment interval as opposed to tailoring the drug concentrations in individual
patients. The primary objective of this study was to evaluate adalimumab drug levels
(ADL) and antibodies to adalimumab (ATA) in relation to disease activity.
AIMS & METHODS: A cohort of 61 patients with Crohns disease (CD) treated
with adalimumab between 2005-2013 were recruited to the study. Demographic
and clinical information was obtained from chart reviews and patient interview.
Disease activity was determined by Harvey-Bradshaw Index (HBI), ileocolonoscopy reports, and CRP levels. Clinical remission was defined by HBI4.
Mucosal healing was defined by the disappearance of all ulceration in all ileocolonic segments. ADL and ATA were tested using a liquid phase assay. ATA  1
U/mL were considered low titer.
RESULTS: 61 CD patients were included in the analysis. 39 of the patients were
previously on infliximab. 37 were on doses of adalimumab greater than 40mg
every other week. 18 of the patients were on concomitant immunosuppressant
therapy (methotrexate or azathioprine). 40 of the patients were in clinical remission. 11 (18%) subjects exhibited elevated ATA titers (41 U/mL). 14 had any
detectable ATA (4 0 U/mL). ADL levels were significantly higher in patients
with low ATA compared to those with elevated ATA titers (p 0.001). ADL
levels were not associated with CRP levels or with clinical remission (p 0.07 and
p 0.93, respectively. However, high median ADL drug level (5.8 mg/mL) was
associated with complete mucosal healing (p 0.017).
CONCLUSION: Adalimumab levels are not significantly associated with clinical
remission or CRP levels in Crohns disease patients. However, high adalimumab
drug levels were associated with complete mucosal healing. Further evaluation with
larger, prospective studies is required to further assess the important of drug level
monitoring in this setting, however, this study suggests that achieving adequate
adalimumab levels may be important toward realizing the goal of mucosal healing.
Our results also demonstrate the importance of using endoscopic assessment rather
than clinical or laboratory assessments to assess therapy response.
Disclosure of Interest: None declared
P0307 USEFULNESS OF A FAECAL CALPROTECTIN
SEMIQUANTITATIVE TEST IN PREDICTING RELAPSE IN
PATIENTS WITH ULCERATIVE COLITIS IN REMISSION

RAPID

E. Domenech1,2,*, E. Garcia-Planella3, M. Manyosa1,4, M. Chaparro5,


M. Barreiro-De-Acosta6, B. Beltran7, E. Ricart1,8, V. Garcia-Sanchez9,
M. Esteve1,10, M. Piqueras11, F. Bermejo12, A. Lopez-Sanroman13,
C. Taxonera14, J. Llao15, J. P5,16, E. Cabre1,4 on Behalf of the precucal Study
of Geteccu
1
Ciberehd, Barcelona, 2Gastroenterology, Hospital Universitari Germans Trias I
Pujol, Badalona, 3Hospital Santa Creu I Sant Pau, Barcelona, 4Hospital
Universitari Germans Trias I Pujol, Badalona, 5Hospital La Princesa, Madrid,
6
Chu Santiago, Santiago De Compostela, 7Hospital La Fe, Vale`ncia, 8Hospital
Clinic, Barcelona, 9Hospital Reina Sofa, Cordoba, 10Hospital MuTua De
Terrassa, 11Consorci Sanitari De Terrassa, Terrassa, 12Gastroenterology, Hospital
De Fuenlabrada, 13Hospital Ramon y Cajal, 14Hospital Clinico San Carlos,
Madrid, 15Xarxa Hospitalaria Althaia, Manresa, 16Ciberehd, Madrid, Spain
Contact E-mail Address: eugenidomenech@gmail.com
INTRODUCTION: Faecal calprotectin (CALf) is fairly correlated with clinical
and endoscopic activity in ulcerative colitis (UC), and it has also been demonstrated to be a good predictor of relapse. However, the routine use of CALf
measurement is constrained by the need for the patient to carry stool samples,
as well as handling and processing them in the laboratory. The availability of
hand held, single-use devices for CALf measurement that could be performed by
the patient himself, might spread the use of CALf in clinical practice.
AIMS & METHODS: Aim: To evaluate the usefulness of a rapid semi-quantitative test of CALf in predicting relapse in patients with UC in remission.
Patients and Methods: A prospective, multicentre study that included patients
with left-sided or extensive UC in clinical remission for 6 months on maintenance treatment with mesalazine. At baseline and every 3 months, patients were
evaluated clinically and semi-quantitative CALf was measured using a monoclonal
immunochromatography
rapid
test
(PreventID
CaldetectTM,
Immunodiagnostic AG, Germany) without manipulation of stools or laboratory
analysis, until relapse or 12 months of follow-up.
RESULTS: At least one determination of CALf with clinical follow-up was
available in 192 out 206 patients initially included in the study. 55% with extensive UC, 62% required corticosteroids in the past, and 88% were non-smokers.
From a total of 695 measurements of CALf, 81 (12%) were above the upper

A214
threshold of normality of the test (460 g/g) and 57 (8%) had limiting values
(15-60 g/g). During follow-up, 32 relapses (17% of patients) occurred. Having a
CALf 460 g/g was significantly associated with relapse at follow-up (35% vs.
12%, p50.0001), with a PPV of 35% and a NPV of 88%. 644 CALf determinations with a three-month follow-up were available; undetectable CALf was significantly associated with absence of recurrence, with a PPV of 100% and a NPV
of 93% (0% vs. 6%, p 0.002).
CONCLUSION: Rapid semi-quantitative measurement of CALf, with no need
for laboratory analysis and faecal samples handling, may be useful for monitoring patients with UC in remission.
Disclosure of Interest: None declared
P0308 MICRORNA-320 AS A BIOMARKER TO MONITOR THE COURSE
OF DISEASE ACTIVITY IN EXPERIMENTAL COLITIS AS WELL AS
IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
F. Pott1,2,*, C. Cichon3, M. Bruckner1, A. Schmidt3, D. Foll2, D. Bettenworth1
1
Department of Medicine B, 2Department of Pediatric Rheumatology and
Immunology, 3Infectiology, Centre for Molecular Biology of Inflammation,
University of Munster, Munster, Germany
Contact E-mail Address: AnnaFriederike. Pott@ukmuenster.de
INTRODUCTION: The pathogenesis of inflammatory bowel disease (IBD) is
still incompletely understood and patient-tailored therapy is an unmet need.
Thus, biomarkers are needed to follow the course of disease; however, sensitive
non-invasive markers to monitor the disease activity are still missing. Previously,
we could demonstrate a significant increase of microRNA-320 (miR-320) expression in murine DSS-induced colitis. Aim of this study was to evaluate the potential of miR-320 to monitor the course of inflammation in immunological and
bacterial driven experimental colitis as well as in IBD patients.
AIMS & METHODS: MiR-320 expression was assessed by qRT-PCR in murine
colonic tissue after induction of T cell transfer colitis as well as Salmonella and
Citrobacter (C.) rodentium-induced colitis. Additionally, miR-320 level was measured in human blood and stool samples from patients with Crohns disease (CD;
n 8) or Ulcerative colitis (UC, n 4) in remission or during acute flare and in
healthy controls (n 11). Disease activity was assessed by Crohns disease activity index (CDAI; active disease: CDAI4220; inactive disease: CDAI5150) in
CD patients and the clinical activity index (CAI; active disease: CAI44; inactive
disease: CAI53) in UC patients.
RESULTS: MiR-320 level in tissue samples from the transfercolitis was significantly increased in animals with severe colitis (410% loss of body weight) as
compared to controls (0.180.01 (colitis) vs. 0.110.03 (control);P 0.05)
whereas there was no significant increase of miR-320 in samples from C. rodentium-induced colitis (0.60.3 (control) vs. 1.10.7 (colitis);P 0.2) and
Salmonella-induced colitis (0.60.4 (control) vs. 0.060.02 (colitis);P 0.3).
MiR-320 expression in blood of CD patients was significantly increased in
acute flare (mean CDAI 2317.2) as compared to remission (mean
CDAI 9733.9) and healthy controls (x-fold increase:435.4152.7 (flare) vs.
70.128.7 (remission);P 0.05; vs. 24.68.8 (control);P50.001). Moreover,
miR-320 level of controls was significantly lower as compared to CD patients
in remission (P 0.01). Furthermore, miR-320 expression in blood as well as
stool from CD patients revealed a strong correlation with the CDAI (r2 0.78
(blood);r2 0.81 (stool)). In UC patients, miR-320 expression in blood obtained
during acute flare (mean CAI 6) or quiescent disease (mean CAI 1.5) also
revealed a significant increase of miR-320 expression as compared to healthy
controls (182.15111.4 vs. 24.68.8;P 0.03). As opposed to CD, miR-320
level in blood from UC patients was not significantly increased in acute flare
as compared to quiescent disease. However, miR-320 expression in stool from
UC patients was significantly enhanced in acute flare as compared to quiescent
disease (225.3535.4 (flare) vs. 68.540.6 (remission);P 0.02) showing a strong
correlation with the CAI (r2 0.68).
CONCLUSION: Our preliminary results indicate that miR-320 expression is
increased in classical IBD models but not significantly altered in bacterialinduced colitis. Furthermore, miR-320 expression in human blood and stool
samples follows the course of disease activity in IBD patients. Future studies
are needed to elucidate the potential of miR-320 to predict relapse and disabling
courses of disease.
Disclosure of Interest: None declared
P0309 THE APPROPRIATENESS OF TESTING AND INTERPRETATION
OF ANTI-TNF DRUG AND ANTIBODY CONCENTRATIONS: WHEN
SHOULD THEY BE ORDERED, AND WHAT TO DO WITH THE
RESULTS?
G.Y. Melmed1,2, P.M. Irving1,*, G.G. Kaplan1, B. Bressler1, J. Jones1,
P.L. Kozuch1, M.P. Sparrow1, F.S. Velayos1, L. Baidoo1, A.S. Cheifetz1,
S.M. Devlin1, L.E. Raffals1, N. Vande Casteele3, D.R. Mould4, M.C. Dubinsky2,
J.-F. Colombel5, W.J. Sandborn3, C.A. Siegel1 on behalf of BRIDGe (Building
Research in IBD Globally)
1
The BRIDGe Group, Hanover, 2Cedars-Sinai, Los Angeles, 3University of
California, San Diego, 4ProjectionsResearch Inc, Phoenixville, 5Mt Sinai Hospital,
New York, United States
Contact E-mail Address: melmedg@cshs.org
INTRODUCTION: The availability of drug concentration and antibody testing
for anti-TNF therapy promises optimized drug dosing and informed decisionmaking for patients with inflammatory bowel disease (IBD) treated with these
agents. However, there is no consensus on when to test and how to interpret the
results for various clinical scenarios. We applied the RAND/UCLA
Appropriateness Method toward establishing the appropriateness of when
these tests should be obtained, and how to act upon their results.

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: A comprehensive literature review was conducted on the
topic of drug concentration and anti-drug antibodies in patients with IBD for all
approved anti-TNF therapies. This review was presented to an expert panel
including clinician and pharmacokinetic experts who have published on the
topic, and the Building Research in Inflammatory Bowel Disease Globally
group, a globally diverse panel of 13 gastroenterologists clinically experienced
in IBD treatment and therapeutic drug monitoring. A total of 35 scenarios
assessed the appropriateness of obtaining these tests, and 143 additional scenarios addressed the appropriateness of various clinical strategies in response to test
results. Panelists used a modified Delphi method to rate each scenario through a
web-based survey, and then met in-person to discuss and anonymously re-rate
appropriateness on a 1-9 scale (1-3 inappropriate, 4-6 uncertain, 7-9 appropriate).
Disagreement was assessed using a validated index.
RESULTS: Assessment of anti-TNF drug and antibody concentrations was
rated appropriate at the end of induction therapy in primary nonresponders, in
secondary nonresponders, at least once during the first year of therapy, in
patients experiencing immune-related side effects, and when restarting a drug
following a drug holiday (before 2nd infusion). Routine assessment in responders
at the end of induction was rated uncertain. Panelists rated the appropriateness
of various clinical management options including changing therapy within-class,
switching out of class, adjusting drug dose/interval, adding/adjusting concomitant immunomodulators, and doing nothing for each of 6 permutations of
high/low drug concentration and high/low/undetectable antibody concentrations. These ratings were highly dependent on the specific clinical scenario for
which the test was obtained. For example, switching out of class when drug and
high antibody concentrations were detected was appropriate at the end of
induction in nonresponders, uncertain at the end of induction in responders,
and inappropriate during maintenance in responders.
CONCLUSION: The appropriate timing and how to respond to anti-TNF drug
and antibody testing for IBD was determined through a modified Delphi panel
based on expert interpretation of the literature. The time to test and clinical
action on the results is dependent on the specific clinical scenario. These recommendations can help guide clinicians to best optimize anti-TNF therapy.
Disclosure of Interest: G. Melmed Financial support for research from:
Prometheus Labs, Consultancy for: Abbvie, Jannsen, UCB, P. Irving Financial
support for research from: Therediag, Consultancy for: Abbvie, MSD, G.
Kaplan Financial support for research from: Merck, Abbvie, and Shire,
Lecture fee(s) from: Jansen, Merck, Schering-Plough, Abbvie, and UCB
Pharma, Consultancy for: Jansen, Abbvie, Merck, Schering-Plough, Shire, and
UCB Pharma, B. Bressler: None declared, J. Jones: None declared, P. Kozuch:
None declared, M. Sparrow Lecture fee(s) from: jannsen, abbvie, Consultancy
for: jannsen, F. Velayos: None declared, L. Baidoo: None declared, A. Cheifetz
Lecture fee(s) from: jannsen, abbvie, S. Devlin Financial support for research
from: Merck, Lecture fee(s) from: Abbvie, Janssen, Merck, Consultancy for:
Abbvie, Janssen, Merck, L. Raffals: None declared, N. Vande Casteele Lecture
fee(s) from: Abbvie, Consultancy for: Janssen Biologics BV, D. Mould
Consultancy for: Abbvie, Jannsen, Prometheus Lab, M. Dubinsky Financial
support for research from: Janssen, Prometheus Labs, Consultancy for:
Abbvie, Jannsen, Prometheus Labs, UCB, J.-F. Colombel Financial support
for research from: Abbvie, Jannsen, UCB, Consultancy for: Jansen, Merck,
Schering-Plough, Abbvie, and UCB Pharma, W. Sandborn Financial support
for research from: Janssen, Prometheus Labs, Consultancy for: Abbvie,
Jannsen, Merck, Prometheus Labs, UCB, C. Siegel Financial support for
research from: Abbvie, Jannsen, UCB, Consultancy for: Abbvie, Jannsen,
Prometheus Labs, UCB
P0310 IBD RECURRENCE AFTER STOPPING ANTI-TNF-ALPHA
THERAPY: A PROSPECTIVE RANDOMIZED CONTROLLED
STUDY COMPARING MESALAMINE AND AZATHIOPRINE AD
INTERIM RESULTS
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: The advent of tumor necrosis factor (TNF) antagonists has
dramatically changed the management of patients with inflammatory bowel diseases (IBD). However, despite more than a decade of clinical experience, there is
still debate about the optimal exit strategies from biologic therapies. Indeed, an
important issue concerns how to manage patients with long-standing remission
after stopping anti-TNF- drugs. Data on different maintenance strategies are
lacking.
AIMS & METHODS: We aimed to assess the efficacy of mesalamine (MESA)
vs. azathioprine (AZA) as maintenance therapy in IBD patients who withdrew
biological therapy after obtaining deep remission (i.e. clinical remission, biomarker remission and mucosal healing). Consecutive IBD patients who achieved
deep remission due to anti-TNF- therapies withdrew them and were prospectively randomized to two different maintenance treatments: MESA 2.4 gr/die in
ulcerative colitis (UC) and 3 gr/die in Crohns Disease (CD) patients or AZA 2.5
mg/kg/die. Then, patients were followed up every two months or before in case of
relapse, by means of routine biochemistry, clinical examination and endoscopy at
1-year or before in case of relapse. The Harvey-Bradshaw Index (HBI; remission
55) and Mayo score (remission 53) was used to evaluate clinical activity for CD
and UC, respectively, whereas endoscopy activity was assessed by means of
Mayo endoscopic score (endoscopic remission 52) or CD endoscopic index
(CDEIS; endoscopic remission 53).
RESULTS: We prospectively enrolled 16 patients with IBD [6UC/10CD; 8F/8M;
median age 44 (25-57)] who were followed-up for a median period of 48 (20-78)
weeks after achieving deep remission due to anti-TNF- therapy. Ten patients
[2UC/8CD; 5F/5M; median age 37.5 (25-53)] were randomized to MESA 2.4 gr/
die or 3gr/die and 6 patients [1UC/5CD; 3F/3M; median age 41.2 (21-47)] to

A215

United European Gastroenterology Journal 2(1S)


AZA 2.5 mg/kg/die. All AZA-treated patients (100%) kept in remission during
the entire follow up period [median period of 55.5 weeks (20-76)], whereas 3/10
(30%) MESA-treated patients [1UC/2CD; 0F/3M; median age 42 (29-52)] experienced clinical relapse after a median period of 14 weeks (8-26). The latter three
patients were shifted to AZA and clinical remission was restored.
CONCLUSION: Our preliminary data showed that AZA is more effective than
MESA in maintaining clinical remission in IBD patients who stopped biological
therapy after obtaining deep remission. Moreover, we observed that disease
recurrence due to mesalamine failure occurs a few weeks after biologic withdrawal and can be successfully treated with AZA.
Disclosure of Interest: None declared
P0311 MRI AND CLINICAL ASSESSMENTS FOR PERIANAL CROHNS
DISEASE: GAIN AND LIMITS
A. GARROS1, L. SIPROUDHIS1, B. TCHOUNDJEU1, T. ROHOU2,
C. BROCHARD1, T. WALLENHORST1, G. BOUGUEN1,3,*
1
Service des Maladies de lAppareil Digestif, 2Service de radiologie et imagerie
medicale, CHU Pontchaillou, 3INSERM U991, Universite de Rennes 1, Rennes,
France
INTRODUCTION: Assessment of perianal Crohns disease (PCD) remains challenging. ECCO guidelines recommended Magnetic resonance imaging (MRI) as a
gold standard but both accuracy and advantage of MRI remain scarce as compared to systematic clinical assessment. The aim of the study was to define
diagnosis values of both assessments.
AIMS & METHODS: Between January 2006 and April 2012, consecutive
patients with PCD assessed by MRI and clinical exam were prospectively
recorded. At each visit, perianal activity (Perianal Disease Activity Index) and
perianal phenotype (Cardiff-Hughes classification) were notified. MRI analyses
were independently reviewed and interpreted according to Cardiff-Hughes and
Van Assche classifications.
RESULTS: Overall, 122 combined evaluations were assessed in 70 different
patients. MRI failed to show superficial ulcerations in 20 of 21 patients as well
as severe ulcerations in 13 of 15 patients. MRI constantly failed to diagnose anal
stenosis (n 21). According to fistulizing lesions, the global agreement between
clinic and MRI was 60% to assess complex fistula. Clinical assessment underestimated 52% of multiple or ramified fistula tracts. Clinical exam (including
induration) failed to diagnose half abscesses described on MRI.
Table. Overall value of clinical or MRI assessment for each items

Items

test

G-S

Se

Ulceration
MRI Clinic 0.08
Stenosis
0
Fistula Cardiff*
Clinic MRI 0.94
Induration
0.4
Abscess
0.14

Sp

Youden
Index** Pos LR Neg LR C

0.94
1
0.15
0.86
1

0.02
0
0.09
0.26
0.14

1.33
1.12
2.86
-

0.98
1
0.40
0.70
0.86

0.68
0.83
0.58
0.28
0.70

CONCLUSION: ECCO guidelines for assessment of PCD should be applied


with some caution because of the low sensitivity of MRI for the diagnosis of
non-fistulizing PCD. Concomitant clinical and MRI assessments should be
recommended.
Disclosure of Interest: None declared
P0312 STEM CELL THERAPY IN EXPERIMENTAL ULCERATIVE
COLITIS: LOCAL VERSUS SYSTEMIC APPROACH
A. Sultan1,*, M. Maher1, S. Elgamal1, A. Elhawary2, Y. Zakaria1
Gastroenterology & Hepatology Unit, 2Pathology, Faculty of Medicine Mansoura
University, Mansoura, Egypt
Contact E-mail Address: ahmed_hasan_sultan@hotmail.com

showed less DAI, macroscopic & microscopic score than control diseased group
(p 50.05). Local enema group and systemic iv groups had no statistically significant difference in DAI, macroscopic nor microscopic scores.
CONCLUSION: Stem cell therapy via enema is a potential future therapy with
expected low side effects than systemic route for treating UC.
REFERENCES
1- Ko IK, Kim BG, Awadallah A, et al. Targeting improves MSC treatment of
inflammatory bowel disease. Am Soc Gene Cell Ther 2010.
2- Lanzoni G, Roda G, Belluzzi A, et al. Inflammatory bowel disease: moving
toward a stem cell-based therapy. World J Gastroenterol 2008; 14: 4616-4626.
3- Toruner M, Loftus EV Jr, Harmsen WS, et al. Risk factors for opportunistic
infections in patients with inflammatory bowel disease. Gastroenterology 2008;
134: 929936.
4- Singh Udai P, Singh Narendra P, Singh Balwan, et al. Stem cells as potential
therapeutic targets for inflammatory bowel disease. Front Biosci (Schol Ed) 2011;
2: 993908.
5- De Ugarte DA, Morizono K, Elbarbary AS, et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs
2004; 174: 101109.
6- Jackson Wesley M, Nesti Leon J and Tuan Rockey S. Concise review: Clinical
translation of wound healing therapies based on mesenchymal stem cells. Stem
Cells Transl Med 2012; 1: 4450.
Disclosure of Interest: None declared
P0313 SUSTAINED CLINICAL BENEFIT AND IMPROVED QUALITY OF
LIFE FROM MAINTENANCE INFLIXIMAB TREATMENT IN
INFLAMMATORY BOWEL DISEASE
A. Hossain1,*, M. Lordal1, A. Olsson1, A. Storlahls1, R. Befrits1
Gastroenterology and Hepatology, Karolinska university Hospital, Stockholm,
Sweden
Contact E-mail Address: akter.hossain@karolinska.se
1

INTRODUCTION: Infliximab is effective in inducing remission in inflammatory


bowel disease and many patients are treated for several years with sustained
clinical remission.
AIMS & METHODS: To evaluate the long-term outcome of maintenance infliximab (IFX) treatment in inflammatory bowel disease (IBD), regarding inflammatory activity, concomitant medication, quality of life (QoL) and whether
reduced intestinal surgery could be observed after initiation of treatment.
Patients with Crohns disease or ulcerative colitis, responding to IFX treatment
during one year and thereafter on continuous maintenance treatment, were eligible. Two hundred patients with Crohns disease (CD; n: 164), or ulcerative
colitis (UC; n: 36), were involved. Median age at diagnoses was 22 (3-64)
years. Five mg /kg body weight IFX was usually administered every eight
week. Inflammatory activity was assessed by Harvey Bradshaw index (HBI) in
Crohns disease. Concomitant medications were followed during the study
period, and Short Health Scale (SHS), a validated short questionnaire, was
used for measuring QoL. Hb, LPK, Albumin, CRP and calprotectin were monitored. Side effects and reasons for discontinuation were recorded. In this retrospective study the observation period ended in March 2014. Parameters and
treatment duration were estimated by last observation carried forward.
RESULTS: Median disease duration at start of treatment was 5.0 (0.2 - 44) years.
Median duration of IFX treatment was 3.4 (1.0-13.9) years. Table 1: Parameters
of inflammatory activity before and after start of IFX treatment

Before
After
P-value

HBI
(n:164)

CRP
(n: 196)

Alb
(n:199)

WBC
(n:198)

Calprotectin
(n:50)

8.04
2.76
50.0001

29.23
8.45
50.0001

34.98
37.28
50.0001

8.70
7.54
50.0291

3135 (1872-6200)
158 (30-1503)
50.0012

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel


disease of unknown etiology(1), affecting patients quality of life, and increases
cancer colon. Its incidence and prevalence are growing all over the world (2). Its
conventional therapy commonly fails to give satisfactory results and may cause
serious side effects(3). So, new treatment is needed. In UC, both damaged intestinal tissue and the immune system need to be repaired. Only stem cells (SCs) can
do this(4). Among adult SCs, adipose derived SCs can be easily obtained with less
heterogeneity in their immunophenotype and multilineage differentiation ability
than do bone marrow derived MSCs(5). Several papers had reported the efficacy
of systemically infused MSCs in treating experimental UC, but some trapped in
liver and lung, decreasing their effect in local injury site (colon) and increasing
required dose(4). Meanwhile, some papers reported the use of MSCs on experimental external wounds and reported some efficacy(6).
AIMS & METHODS: Evaluate effectiveness of stem cell therapy through local
enema & intravenous approaches. Induction of UC in sprague dawley (SD) rats
by 5% dextran sulphate sodium (DSS). Isolation of MSCs from adipose tissue
was done under sterile conditions. Cells were characterized using cell surface
markers by fluorescence-activated cell sorting analyses. First group was control
healthy group. Second group received 5% DSS for 7 days with no therapy. Third
group received local 1x106 ADMSCs enema. Fourth group received systemic iv
1x106 ADMSCs. Disease activity index (DAI) was assessed daily. On day 7 colon
was examined macroscopically & microscopically.
RESULTS: All groups received DSS had DAI higher than healthy control group
with statistically significant difference (p 50.05). Both groups receiving stem cells

SHS (n:60) was significantly improved in all QoL dimensions. Steroid treatment
and immunosuppression at start of IFX treatment were 51% and 62%, respectively. Corresponding figures at latest infusion were 10% and 43%. No opportunistic infection has been diagnosed. Ten infusion related moderate to severe
side effects were observed, leading to treatment discontinuation. Loss of response
occurred in 42 patients. Of those, 20 needed intestinal surgery. Twelve changed
anti-TNF therapy, one patient received alternative biological treatment and 9
continued without biological treatment. Surgery before initiation of IFX therapy
was necessary in 27% compared to 11% after treatment. Sixteen patients in
remission decided to stop treatment and 13 of those are still in remission with
only 4 on immunosuppression. One patient died several years after stopping
treatment from lung cancer and the remaining 2 were restarted on anti-TNF.
Twenty-four patients moved, while on therapy. Three patients were lost to follow
up and two stopped treatment because of malignancies.
CONCLUSION: Almost three-quarters of the patients demonstrated clinical
benefit from IFX treatment. Use of steroids was dramatically reduced with less
influence on the use of immunosuppression. SHS showed significant improvement of QoL. During the studied time period, surgery was less frequent after
initiation IFX treatment.
Disclosure of Interest: None declared

A216
P0314 MEAN
PLATELET
VOLUME
AND
NEUTROPHIL-TOLYMPHOCYTE RATIO AS NEW BIOMARKERS OF SUSTAINED
RESPONSE TO INFLIXIMAB THERAPY IN CROHNS DISEASE
PATIENTS
A. Sobolewska1,*, M. Wlodarczyk1, K. Stec-Michalska1, J. Fichna2,
M. Wis niewska-Jarosinska1
1
Department of Gastroenterology, 2Department of Biochemistry, Medical
Univeristy of Lodz, Lodz, Poland
Contact E-mail Address: dr.mwlodarczyk@gmail.com
INTRODUCTION: The loss of response to infliximab (IFX) in Crohns disease
(CD) patients is currently an important clinical problem. Therefore, searching for
predictors of maintenance or loss of response to anti-tumor necrosis factor-
(anti-TNF-) agents has become the aim of current studies in the field.
Recently, the neutrophil-lymphocyte ratio (NLR) and mean platelet volume
(MPV) have been proposed as new biomarkers of subclinical inflammatory process. Here we hypothesized that NLR or MPV may be used as cost-effective
biomarkers of subclinical inflammation during 52-week IFX therapy in CD
patients responding to induction treatment.
AIMS & METHODS: The study aimed at establishing whether NLR or MPV at
baseline and pre-infusion at week 14 are good predictors of sustained response
after week 14 in CD patients undergoing 52-week IFX therapy. 30 adult patients
with CD (11 women and 19 men; mean ageSD 32.08.6 years), who underwent
a 52-week course of treatment with IFX and achieved response to induction
treatment evaluated at week 14 were enrolled to the study. The control group
consisted of 12 healthy subjects. The association between NLR or MPV, baseline
disease parameters and maintained clinical response or remission during IFX
therapy was assessed.
RESULTS: Fifteen of CD patients (50%) have not reached full one year maintenance IFX treatment without loss of response. The analysis showed a statistically significant higher NLR (4.622.43 vs. 1.490.76; p5.001) and lower MPV
(10.250.99 vs. 11.291.08 fL; p .003) in CD patients compared to controls.
Higher NLR at baseline (5.852.71 vs. 3.391.28; p .003) and at week 14
(4.792.61 vs. 2.581.23; p .006) were observed in CD patients with loss of
response to IFX maintenance treatment than in those with sustained response.
NLR lower than 4.068 at baseline predicts sustained response with 80% sensitivity and 87% specificity. NLR lower than 3.667 at week 14 predicts sustained
response with 67% sensitivity and 80% specificity. MPV at week 14 in CD
patients with loss of response was significantly higher (11.311.16 fL vs.
10.190.52 fL; p .001) than in CD patients with sustained response. In patients
with sustained response to maintenance IFX treatment higher MPV between
baseline and week 14 was calculated (0.780.34 fL vs. 0.230.39 fL; p5.001).
MPV higher than 10.3 fL at week 14 predicts sustained response with 67%
sensitivity and 80% specificity. MPV between baseline and week 14 higher
than 0.4 fL predicts sustained response with 87% sensitivity and 93% specificity.
CONCLUSION: In CD patients with loss of response to IFX therapy higher
NLR and lower MPV were observed. It can be suggested that NLR and MPV
may serve as good predictors of sustained response to IFX maintenance treatment in CD patients as well as may allow selection of the most appropriate
therapy based on the individual approach. Further studies are warranted to
confirm our observations and to establish the cut-off points in a larger cohort.
Disclosure of Interest: None declared
P0315 ANTI-DRUG ANTIBODIES INHIBIT NEUTRALIZATION OF TNFALPHA IN INFLIXIMAB TREATED PATIENTS WITH
INFLAMMATORY BOWEL DISEASE (IBD)
A. Eser1,*, H. Vogelsang1, S. Reinisch1,2, G. Novacek1, C. Dejaco1, L. KazemiShirazi1, C. Primas1, C. Lichtenberger1, S. Brehovsky1, X. Liu3, A. Jain3,
S. Singh3, W. Reinisch1,2
1
Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria,
2
Department of Internal Medicine, McMaster University, Hamilton, Canada,
3
Prometheus Therapeutics & diagnostics, Prometheus Therapeutics & diagnostics,
San Diego, United States
Contact E-mail Address: walter.reinisch@meduniwien.ac.at
INTRODUCTION: Infliximab (IFX) trough levels (TL) as well as c-max levels
have been positively associated with its efficacy and negatively with IFX immunogenicity in patients with IBD. Clearance of IFX is increased in the presence of
anti-drug antibodies (ADA). However, to what extent ADAs impact the binding
and neutralization of soluble TNF-alpha in vivo remains largely unknown. In this
study we assessed the relationship between IFX-, ADA- and TNF-alpha levels at
a mid-infusion visit and at trough in patients with IBD on maintenance therapy.
AIMS & METHODS: Serum samples from 90 consecutive patients with IBD
(Crohns disease: n 66, ulcerative colitis: n 24) on IFX maintenance therapy
were obtained at mid-infusion visits and at trough. IFX and ADA were measured
by a homogeneous mobility shift assay from Prometheus, which allows detection
of ADA in the presence of IFX. Serum TNF- was measured by a Collaborative
Enzyme Enhanced immuno-Reactive (CEER) Assay.
RESULTS: Patients had received a median number of 11 IFX infusions (range 3
- 71) with a median dose of 5.5 mg/kg (4.1- 10.9 mg/kg) before study entry.
ADAs were detected in 18 pts at mid-infusion and in 21 pts at trough. In
ADA positive pts median serum concentration of IFX was significantly lower
than in ADA negative pts both at mid-infusion and at trough. Inversely, significantly higher serum concentrations of TNF- were detectable in ADA positive
pts at both visits (see Table). At trough the TNF-/IFX ratio was significantly
higher in ADA positive patients than in those without ADA (p50.0001). No
difference was seen in TNF- levels when segregated by IFX serum levels alone.

United European Gastroenterology Journal 2(1S)

Mid-infusion
ADA neg.
n 69
IFX (mg/ml)
13.59
median (range) (3.2-35.2)
TNF- (pg/ml)
5.5 (range)
median (range)

Trough
ADA pos.
n 21

p-value

ADA neg. ADA pos.


n 69
n 21
p-value

0.75
50.0001 6.36
(0.08-16.37)
(range)
10.2
0.04
7.5
(range)
(range)

0.42
(range)
25.6
(range)

50.0001
50.0001

Interestingly, 3/10 (30%) ADA negative pts at mid-infusion with an IFX concentration below 8 mg/ml turned ADA positive at trough versus 1/36(3%) pts
with an IFX concentration 8 mg/ml.
CONCLUSION: ADA detected in patients with IBD on IFX maintenance therapy impairs neutralization of soluble TNF- and is associated with lower serum
concentrations of IFX and higher levels of TNF- both at mid-infusion and at
trough. Our finding favours a strategy of a pre-emptive dose optimization in
ADA positive patients due to insufficient control of inflammation.
Disclosure of Interest: A. Eser Lecture fee(s) from: MSD, Abbvie, Consultancy
for: MSD, H. Vogelsang: None declared, S. Reinisch: None declared, G.
Novacek: None declared, C. Dejaco: None declared, L. Kazemi-Shirazi: None
declared, C. Primas: None declared, C. Lichtenberger: None declared, S.
Brehovsky: None declared, X. Liu: None declared, A. Jain: None declared, S.
Singh: None declared, W. Reinisch Lecture fee(s) from: MSD, Abbvie,
Consultancy for: MSD, Abbvie, Prometheus Labs
P0316 INFORMATION NECESSARY TO PREDICT INDIVIDUAL
INFLIXIMAB (IFX) PHARMACOKINETICS (PK) IN PATIENTS
WITH IBD
A. Eser1,*, H. Vogelsang1, G. Novacek1, S. Reinisch1, C. Primas1,
C. Lichtenberger1, S. Brehovsky1, D. Mould2, W. Reinisch1
1
Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria,
2
Projections Research Inc., Projections Research Inc., Phoenixville, United States
Contact E-mail Address: walter.reinisch@meduniwien.ac.at
INTRODUCTION: The increasing interest in monitoring serum IFX concentrations for purposes of therapeutic dose adjustment (TDA) has led to the availability of various assays whose validity remains to be determined. Only
population-based approaches to determine individual IFX PK are used so far.
AIMS & METHODS: Objectives: 1) Evaluate the performance of 3 different
IFX assays and 2) Determine how many samples are needed in order to estimate
individual PK accurately and precisely.
Serum samples were collected after the 3rdIFX infusion for measurement of IFX
and anti-drug antibodies (ADA) in 117 patients with IBD (87 CD, 30 UC).
The mean IFX dose was 5.84 mg/kg for patients with a mean weight of 68.37 kg
(ADA positive n 19, ADA negative n 98). For each patient, at least 2 samples
from within the same infusion interval were available. 41 patients had 42 IFX
concentrations. IFX serum concentrations were measured with ELISA assays
provided by Theradiag (France) (TD) and Immundiagnostik (ID, Bensheim,
Germany). IFX and ADA were also determined by a homogeneous mobility
shift assay from Prometheus. Assay performance was evaluated by running a
population PK model using Nonmem (version 7.2 Icon Dublin Ireland).
Estimated clearance, between subject variability (BSV) and residual error were
compared with literature values. Bayesian updating and forecasting was conducted using individual patient data and forecasting with different subsets of
information for each subject. Initially, only subject demographics (age, weight,
gender, albumin, ADA status and planned dose) were used. Forecast concentrations based only on this information were compared with the first observed
concentration value. Subsequent evaluations included progressively more PK
observations. Agreement between observed and forecast concentrations was evaluated graphically and via root mean square error (RMSE) and concordance.
RESULTS: Ability of assays to estimate clearance was variable with Prometheus
and ID performing better than TD, but all provided reasonable estimates. The
number of observations needed to accurately and precisely estimate individual
PK was similar for all 3 assays. If no serum concentrations are available the
precision of the prediction of subsequent IFX concentrations is poor
(RMSE 0.46, concordance 0.43) which is reflective of high BSV in IFX
PK. With more serum IFX concentration per patient, precision of forecast concentrations increased. With 3 observations (RMSE 0.15, concordance 0.86),
PK estimates were markedly improved. With 4 observations the predicted concentration was within the assay error (RMSE and concordance). Two vs. one
observation within a dose interval does not substantially impact precision, but
does impact time required to collect enough observations to obtain precise estimates of future IFX PK.
CONCLUSION: Assay quality is important for precisely estimated IFX clearance in IBD patients. TDA according to patient demographics and patient factors is imprecise. At best 3 to 4 measurements of IFX would be taken early on.
Based on this information it becomes feasible to dose to a target concentration
and to determine the dose necessary. It further provides tools to prospectively
determine which concentrations are leading to most favourable responses.
Disclosure of Interest: A. Eser Lecture fee(s) from: MSD, Abbvie, Consultancy
for: MSD, H. Vogelsang: None declared, G. Novacek: None declared, S.
Reinisch: None declared, C. Primas: None declared, C. Lichtenberger: None
declared, S. Brehovsky: None declared, D. Mould: None declared, W.
Reinisch: None declared

A217

United European Gastroenterology Journal 2(1S)


P0317 PROSPECTIVE, RANDOMIZED CLINICAL TRIAL COMPARING
THE EFFICACY OF TWO VACCINES AGAINST HEPATITIS B VIRUS
(HBV) IN INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS
M. Chaparro1,2, J. Gordillo3, E. Dome`nech2,4, M. Esteve2,5, M. Barreiro deAcosta6, A. Villoria7, E. Iglesias-Flores8, E. Alvarado3, J. Naves2,9, O. Ben tez2,5,
L. Nieto6, X. Calvet2,7, V. Garc a-Sanchez8, J.R. Villagrasa10, A.C. Mar n1,2,
M. Ramas1,2, I. Moreno11, J. Mate1,2, J.P. Gisbert1,2,*
1
Gastroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid,
3
Gastroenterology Unit, Hospital Santa Creu i Sant Pau, Barcelona,
4
Gastroenterology Unit, Hospital Universitario Germans Trias i Pujol, Badalona,
5
Gastroenterology Unit, Hospital Universitario Mutua de Terrassa, Terrassa,
6
Gastroenterology Unit, Complejo Hospitalario Universitario de Santiago,
Santiago de Compostela, 7Gastroenterology Unit, Hospital de Sabadell, Sabadell,
8
Gastroenterology Unit, Hospital Universitario Reina Sofa, Cordoba,
9
Gastroenterology Unit, Hospital Universitario Germans Trias i Pujol, Barcelona,
10
Preventive Medicine Unit, Hospital de La Princesa, 11Fundacion de Investigacion
Biomedica, Hospital de La Princesa and IP, Madrid, Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: Around 50% of IBD patients do not respond to the HBV
vaccine. To increase the success rate, different vaccination protocols have been
proposed although no study has been able to establish the optimal strategy for
IBD patients.
AIMS & METHODS: Aims: To compare the success rate between two HBV
vaccines in IBD patients: traditional (Engerix) and a new vaccine with adjuvant
(Fendrix). Secondary aim was to identify predictor factors of response to the
vaccine.
Methods: IBD patients with negative HBV serology and without previous vaccination against HBV were randomized to receive Fendrix or double doses of
Engerix at months 0, 1, 2 and 6. Anti-HBs concentration was measured 2
months after the 3rd and 4th doses (EUDRA CT number:2010-023947-14).
RESULTS: 170 patients had been included: 55% male, 52% with Crohns disease, 30% under immunosuppressants and 37% under anti-TNF treatment. 54%
of patients received Engerix and 46% Fendrix; the main characteristics of
patients (age, gender, type of IBD and treatment) were similar between the 2
groups. Overall, 44% of patients had response (anti-HBs3 100 IU/l) after the first
3 doses (161 patients have already received 3 doses), and 71% after the completion of the vaccination (134 have completed the vaccination). The response rate
after the 4 doses was 67% with Engerix vs. 76% with Fendrix (p 0.2); considering anti-HBs310 IU/l (the standard threshold), the response rate was higher
with Fendrix than with Engerix (87 vs. 73.6%, p 0.04). In patients under
immunosuppressants or anti-TNF drugs, the response (anti-HBs3100 IU/l) after
the 4 doses was 55% with Engerix vs. 69% with Fendrix (p 0.12). In the
multivariate analysis, older age (odds ratio [OR] 0.9, p50.0001) and immunosuppressants or anti-TNF concomitant treatment (OR 0.04, p50.0001), but
not the type of vaccine (OR 1.9, p 0.1), were associated with the response
rate to the vaccination. 7.7% of patients flared up during the study period, and
13% suffered adverse events (only 41% related with the vaccine, and all of them
mild). The frequencies of flaring up and adverse events were similar between the 2
groups.
CONCLUSION: A statistically significant different response rate to Fendrix
(single dose) or Engerix (double dose) has not been demonstrated in IBD
patients yet (although the trial is still ongoing). A 4-dose schedule increases the
response rate around 30% compared with a 3-dose regimen. The older age and
the immunosuppressive and anti-TNF treatment decrease the success rate of the
vaccine. Both vaccines seem to be safe in IBD patients.
Disclosure of Interest: M. Chaparro Other: Dra. M Chaparro has served as a
speaker and has received research funding from MSD and Abbvie, J. Gordillo:
None declared, E. Dome`nech: None declared, M. Esteve: None declared, M.
Barreiro de-Acosta: None declared, A. Villoria: None declared, E. IglesiasFlores: None declared, E. Alvarado: None declared, J. Naves: None declared,
O. Ben tez: None declared, L. Nieto: None declared, X. Calvet: None declared,
V. Garc a-Sanchez: None declared, J. R. Villagrasa: None declared, A. Mar n:
None declared, M. Ramas: None declared, I. Moreno: None declared, J. Mate:
None declared, J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker, a
consultant and advisory member for, and has received research funding from
MSD and Abbvie.
P0318 EFFICACY OF A SECOND ANTI-TNF IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE WHOSE PREVIOUS ANTITNF TREATMENT HAS FAILED: A META-ANALYSIS
1,2,*

1,2

1,2

1,2

J.P. Gisbert
, A.C. Mar n , A.G. McNicholl , M. Chaparro
Gasttroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid,
Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
1

INTRODUCTION: One-third of patients with Crohns disease (CD) or ulcerative colitis (UC) receiving anti-TNF therapy do not respond to treatment (primary failure), and a relevant proportion experience a loss of response (secondary
failure) or intolerance.
AIMS & METHODS: To investigate the efficacy of a second anti-TNF agent
after failure or intolerance to a first drug.
METHODS: Inclusion criteria: Studies evaluating the efficacy of infliximab
(IFX), adalimumab (ADA), and certolizumab pegol (CZP) as the second antiTNF drug in CD or UC. Search strategy: Bibliographical searches in PubMed.
Data synthesis: Percentage of response/remission; the meta-analysis was performed using the inverse variance method.
RESULTS: We included 42 studies (35 CD, 6 UC, 1 pouchitis). The CD studies
comprised 30 switching IFX!ADA, 4 IFX!CZP, and 1 ADA!IFX. Overall,

the second anti-TNF in CD induced remission in 43% (95%CI 38-48%;


I2 75%; 27 studies; 2,345 patients) and a response in 65% (95%CI 57-73%;
I2 92%; 26 studies; 1,922 patients) of patients. The remission rate was higher
when the reason to withdraw the first anti-TNF was intolerance (61%;
95%CI 40-82%; I2 89%) than after secondary (45%; 95%CI 34-57%;
I2 79%) or primary failure (30%; 95%CI 22-37%; I2 8%); response rates
were, respectively, 72%, 66%, and 60%. Six UC studies were identified, all of
them switching IFX!ADA, and only 4 of them reporting remission rates (151
patients), with figures ranging from 0% to 50%
CONCLUSION: The efficacy of a second anti-TNF in CD patients largely
depends on the cause for switching. The remission rate was higher when the
reason to withdraw the first anti-TNF was intolerance (61%), compared with
secondary failure (45%) and primary failure (30%).
Disclosure of Interest: J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker,
a consultant and advisory member for, and has received research funding from
MSD and Abbvie., A. Mar n: None declared, A. McNicholl: None declared, M.
Chaparro Other: Dra. M Chaparro has served as a speaker and has received
research funding from MSD and Abbvie
P0319 THE ONE-YEAR EFFICACY OF INFLIXIMAB DOES NOT
DEPEND ON THE TIMING OF BIOLOGICAL THERAPY IN
ULCERATIVE COLITIS
A. Balint1,*, T. Nyari2, Z. Szepes1, F. Nagy1, P. Miheller3, G. Horvath4,
P.L. Lakatos5, K. Palatka6, K. Farkas1, R. Bor1, T. Wittmann1, T. Molnar1
1
First Department of Medicine, 2Department of Medical Physics and Informatics,
University of Szeged, Szeged, 32nd Department of Medicine, Semmelweis
University, Budapest, 4Department of Gastroenterology, Semmelweis Health
Center, Miskolc, 51st Department of Medicine, Semmelweis University, Budapest,
6
2nd Department of Medicine, University of Debrecen, Debrecen, Hungary
Contact E-mail Address: molnar.tamas@med.u-szeged.hu
INTRODUCTION: Infliximab is an effective therapeutic option in patients with
refractory ulcerative colitis (UC). The optimal timing of infliximab therapy is still
one of the outstanding questions in the therapy of UC.
AIMS & METHODS: The aim of our study was to assess whether there is an
association between the one-year remission rates and the elapsed time between
the diagnosis and the start of infliximab therapy. 116 UC patients treated with
infliximab were enrolled in this retrospective study. The time elapsed between the
diagnosis and the first biological therapy was assessed in every patient, who was
then categorized to groups according to the elapsed time (45 years and 55
years; 0-2 years, 2-5 years, 5-10 years etc).
RESULTS: The mean elapsed time between the diagnosis and the start of biological therapy was 7 years (0-38 years). 50.4% of patients started infliximab
therapy within 5 years after diagnosis. After induction with infliximab 65.6%
of the enrolled patients achieved remission and 34.4% achieved response. After
one-year treatment period, the remission and response rates remained 67.7% and
21.8%. 10.6% of patients showed loss of efficacy at one year infliximab therapy.
Complete mucosal healing was detected in 31.2% and deep remission in 13.9% of
the patients at week 52. Response rates to infliximab therapy at one year were
significantly lower compared to rates at week 14 (p 0.029). The rate of remission and loss of efficacy did not depend on the elapsed time between the diagnosis
and the start of biological therapy. However, response rates were higher in longer
elapsed time (p 0.036).
CONCLUSION: Infliximab is effective for drug-refractory UC to induce and
maintain clinical remission. Our results did not reveal an association between the
remission rates and the elapsed time between the diagnosis and the first biological
therapy in UC.
Disclosure of Interest: None declared
P0320 HEAD-TO-HEAD COMPARISON OF 5 FECAL MARKERS TO
PREDICT RESPONSE TO INDUCTION AND MAINTENANCE
THERAPY WITH INFLIXIMAB IN ULCERATIVE COLITIS
PATIENTS; A PROSPECTIVE STUDY
A.C. Frin1,*, S. Nancey2, J. Filippi1, G. Boschetti2, B. Flourie2, J. Drai3,
P. Ferrari4, X. Hebuterne1
1
Gastro enterology, CHU Archet 2, Nice cedex 3, 2Gastro enterology,
3
Biochemistry, CHU Lyon sud, Hospices civils de Lyon, Pierre Benite, Lyon,
4
Biochemistry, CHU Pasteur, Nice cedex 3, France
INTRODUCTION: The role of faecal markers in monitoring anti TNF alpha
therapies has been insufficiently explored. This study aimed to determine the
usefulness of five faecal proteins in the prediction of clinical response to
Infliximab (IFX) in Ulcerative Colitis (UC): calprotectin (fCal), Lactoferrin
(fLac), M2PK (fM2PK), neopterin (fNeo), and zonulin (fZo).
AIMS & METHODS: Thirty-one consecutive patients with an active UC, requiring IFX [5 mg/kg at week 0 (W0), 2, 6 and every 8 W] were prospectively studied.
At W0, W2, W6 and W14, clinical activity was recorded and a stool sample
collected. Clinical response to induction therapy was defined at W14 as a reduction of at least 3 points and 30% of the Mayo score. In 25 patients, endoscopies
were performed at W0 and W12; an endoscopic Mayo subscore of 0 or 1 defined
endoscopic remission. Clinical response to maintenance therapy was evaluated at
W52 and optimization or discontinuation of IFX were considered as a failure.
RESULTS: At W0 the median partial Mayo Score, the endoscopic Mayo and the
UCEIS scores were 7/9 (2-9), 3/3 (2-3) and 8/11 (6-11) respectively. At W14, 19
patients (61%) were clinical responders and 13 (52%) experienced an endoscopic
response. The median levels of fCal drop dramatically from W0 to W14 in
responders [from 4260 mg/g (96-25051) to 128 mg/g (11-3782); p 0.0001]. In
contrast, it did not differ significantly in non-responders [from 9077 mg/g (21550000) to 2781 mg/g (203-14149); p 0.287]. Same trends were observed for fLac

A218
and fM2PK levels. At W2, fLac and fM2PK predicted accurately clinical
response to IFX induction (area under the curve (AUC) 0.82, 0.84 and 0.88
respectively): cuts-offs of 800 mg/g for fCal, 20000 ng/g for fLac and 50 UI/mL
for fM2PK determined by ROC curves allowed to discriminate clinical responders from non responders to induction therapy, with good sensitivities (Se) (82%,
81% and 88%, respectively), and specificities (Sp) (69%, 70% and 80%, respectively). FLac measured at W2 were the more valuable marker to predict endoscopic remission at W12 [(AUC 0.80, Se and Sp 72% with a cut-off of 32891
ng/g). At W14, the three previous markers were also reliable to predict clinical
response at W52 (AUC 0.82, 0.86 and 0.75 respectively) with best cut-offs of
146 mg/g for fCal, 3457 ng/g for fLac and 2.25 UI/mL for fM2-PK. FCal, fLac
and fM2PK were well correlated with both the endoscopic Mayo subscore and
the UCEIS. FNeo and fZo did not show any relevant result.
CONCLUSION: FCal, flac and fM2-PK predicted with a good accuracy the
clinical response to induction and maintenance IFX therapy in UC. The measurement of one of these markers at W0 and at the end of induction might
distinguish responders from non responders to IFX maintenance therapy
within one year.
Disclosure of Interest: None declared
P0321 ALTERATIONS OF FECAL MICROBIOTA AND METABOLIC
LANDSCAPE IN RESPONSE TO ORAL OR INTRAVENOUS IRON
REPLACEMENT THERAPY IN PATIENTS WITH INFLAMMATORY
BOWEL DISEASES
T. Lee1, A. Schmidt2,*, I. Lagkouvardos2, T. Clavel2, A. Walter3, M. Lucio3,
K. Smirnov3, P. Schmitt-Kopplin3, R. Fedorak1, D. Haller2
1
University of Alberta, Edmonton, Canada, 2Technical University of Munich,
Freising, 3Helmholtzzentrum Munchen, Munchen, Germany
Contact E-mail Address: annemarie.schmidt@tum.de
INTRODUCTION: Iron deficiency is a common complication in patients with
inflammatory bowel diseases (IBD) and oral iron replacement therapy is suggested to exacerbate IBD symptoms. We hypothesized that oral iron may impact
the composition of the gut microbiota and thereby affect the disease status.
AIMS & METHODS: An open-labelled clinical trial including patients with
Crohns disease (CD; N 29) or ulcerative colitis (UC; N 19) as well as control
patients with iron deficiency (iron saturation 5 16% and ferritin 5 100)
(N 20) was performed to compare the effects of oral (PO; ferrous sulfate) vs.
intravenous (IV; iron sucrose) iron replacement therapy over a period of three
months. The health status was assed via quality of life (EQ 5D and SIBDQ) and
disease activity (HBI and PMS) questionnaires. Stool and sigmoid mucosal biopsies were collected before and after treatment. Gut bacterial diversity and composition were assessed by high-throughput sequencing of 16S rRNA genes (V4
region). Fecal metabolites were analyzed by ESI-FT-ICR-MS.
RESULTS: PO and IV treatments were comparable regarding amelioration of
iron deficiency, with superior but not significant levels of ferritin and iron saturation in the IV group. Worsening or improvement of disease activity and quality
of life were independent of iron treatments (no difference between PO and IV).
Fecal bacterial diversity was significantly different between control, UC and CD
patients before and after iron treatment. Samples from IBD patients were characterized by marked inter-individual differences as well as lower phylotype richness and proportions of unknown Clostridiales. We identified the presence of 18
CD-specific molecular species (OTUs), many of which matched sequences of
facultative anaerobic bacteria. Major shifts in bacterial diversity occurred in
approximately half of the participants after treatment, independently of disease.
In those samples where bacterial profiles shifted, changes in diversity were significantly higher in IBD patients. However, no consistent changes in the occurrence of specific OTUs relative to iron treatment could be identified, suggesting
individual-specific responses to treatment. Metabolite analysis using OSC-PLC
classification showed a clear separation of both UC and CD from control
patients before the iron treatment. After therapy, metabolite profiles were only
different in UC patients indicating a possible convergence of CD patients with
control subjects in response to the iron treatment. Separation into IV- and POspecific metabolite profiles appeared in the control and CD group but not in the
UC group.
CONCLUSION: Shifts in bacterial diversity associated with iron treatment are
independent of the route of administration and are more pronounced in IBD
patients. Efficiency and clinical outcome of both iron therapies are comparable in
both IBD patient cohorts.
Disclosure of Interest: None declared
P0322 DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING
PARAMETERS AS PREDICTORS OF REMISSION IN CROHNS
DISEASE PATIENTS TREATED WITH ANTI-TNF THERAPY
A. Buisson1,2,*, C. Hordonneau3, J. Scanzi1, F. Goutorbe1, M. Goutte1,
B. Pereira4, G. Bommelaer1,2
1
Gastroenterology department, CHU Estaing Clermont-ferrand, 2Microbes,
Intestine, Inflammation and susceptibility of the host UMR 1071, Inserm/
Universite dAuvergne; USC-INRA 2018, 3Radiology department, CHU Estaing
Clermont-ferrand, 4Biostatistics unit, DRCI, CHU Clermont-ferrand, Clermontferrand, France
INTRODUCTION: Anti-TNF agents are the most effective therapy in Crohns
disease (CD). However, almost one-third of the patients experience primary failure to anti-TNF therapy. Diffusion-Weighted Magnetic Resonance EnteroColonography (DW-MREC) has shown good accuracy to detect and assess
inflammatory activity in CD1,2.
AIMS & METHODS: We aimed to study the DW-MREC parameters as predictors of advanced remission (clinical remission defined as CDAI 5150 AND

United European Gastroenterology Journal 2(1S)


CRP 55 mg/L), surgery, clinical remission (CDAI 5150) or clinical response
(CDAI70) after induction regimen of anti-TNF (week 12).
Overall, 28 consecutive CD patients were prospectively included during 1 year.
All the patients underwent a DW-MREC1,2 within 4 weeks before starting antiTNF. Adalimumab (ADA) was administered as 160mg at W0, 80mg at W2 and
40mg e.o.w. Infliximab (IFX) was administered as 5mg/kg at W0, W2 and W6.
The collected MRI parameters were: Clermont score1,2, apparent diffusion coefficient (ADC), Magnetic Resonance Index of Activity (MaRIA), presence of
stenosis, fistula, abscess, sclerolipomatosis or mesenteric lymph nodes.
RESULTS: Median age and disease duration at inclusion were 37 years (17-71)
and 34 months (0-456) respectively. Overall, 14 (50%) were smokers, 7 (25%)
underwent previous intestinal resection and 7 (25%) had ano-perineal lesions. 13
patients (46.4%) had ileal CD (L1), 3 (10.7%) colonic CD (L2), 12 (42.8%)
ileocolonic CD (L3). CD phenotypes were non-stricturing non-fistulizing (B1),
stricturing (B2) and fistulizing (B3) in 9 (32.1%),12 (42.9%), and 7 (25.0%)
patients, respectively. While 13 patients were treated with IFX (44.4%), 15
were treated with ADA (55.6%). Among them, 10 (35.7%) patients received
concomitant thiopurines. At inclusion, median CDAI was 225 (170-393) and
median C-reactive protein value was 17.1 mg/L (2.9-148). 13 patients (46.4%)
experienced advanced remission at W12.
Mean ADC seemed lower (1.912 vs 2.162, p 0.07) and mean MaRIA seemed
higher (47.0 vs 41.9, p 0.13) in the patients treated with anti-TNF therapy
which experienced advanced remission at W12.
Presence of mesenteric lymph nodes was predictive of no need for surgery at W12
in the patients treated with anti-TNF therapy (p 0.01). Sclerolipomatosis
seemed also predictive of no requirement for surgery at W12 in the patients
treated with anti-TNF therapy (p 0.13). Presence of mesenteric lymph nodes
was predictive of response to anti-TNF therapy at W12 (p 0.05).
CONCLUSION: MRI parameters reflecting inflammatory activity (presence of
mesenteric lymph nodes, sclerolipomatosis, low ADC) seemed predictors of
advanced remission or response to anti-TNF agents in CD. Despite the lack
of power due to small sample size, the intermediary results of our study show that
DW-MREC could be a useful and promising tool to predict effectiveness of antiTNF therapy in CD.
REFERENCES
Buisson A et al. Aliment Pharmacol Ther 2013; 37: 537-545.
Buisson A, Hordonneau C, et al. Am J Gastroenterol 2014; 109: 89-98.
Disclosure of Interest: A. Buisson Lecture fee(s) from: Abbvie, MSD, C.
Hordonneau: None declared, J. Scanzi: None declared, F. Goutorbe: None
declared, M. Goutte: None declared, B. Pereira: None declared, G.
Bommelaer: None declared
P0323 PREDICTIVE FACTORS OF EARLY INFLIXIMAB INFUSION
REACTIONS IN INFLAMMATORY BOWEL DISEASE
C. Duron1, A. Buisson1,2,*, M. Goutte1, B. Pereira3, G. Bommelaer1
1
Gastroenterology department, CHU Estaing Clermont-ferrand, 2 Microbes,
Intestine, Inflammation and susceptibility of the host UMR 1071, Inserm/
Universite dAuvergne; USC-INRA 2018, 3Biostatistics unit, DRCI, CHU
Clermont-ferrand, Clermont-ferrand, France
INTRODUCTION: Anti-TNF agents including infliximab (IFX), a chimeric
antibody, are the most effective therapies in inflammatory bowel diseases
(IBD). Early IFX Infusion Reaction (EIIR) is rare, but is a serious complication
in IBD patients, and could lead to drug withdrawal and consequently impact the
therapeutic strategy. The role of premedication remains uncertain.
AIMS & METHODS: We aimed to establish predictors of EIIR in IBD patients
and to assess the impact of premedication.
Patients, disease and infusions characteristics, collected for all IFX infusions
performed in our IBD Unit, were retrieved from electronic charts from 2008 to
2013. The EIIR were defined as events related to IFX infusions occurring within
two hours of the infusion. Univariate and multivariate analysis were performed
taking into account the inter-patients and intra-patients variability and interaction test.
RESULTS: Among the 80 included IBD patients, 51 (63.8%) had Crohns disease (CD). The mean age and disease duration were 38.8 years (14.1) and 7.4
years (7.0) respectively.
Overall, 23 IBD patients (28.8%) experienced EIIR. Age, prior history of intestinal resection, atopy or allergy, familial history of IBD, type of IBD, disease
location, disease extent or disease duration were not predictive of EIIR. In univariate analysis, non-stricturing non fistulising CD was predictive of EIIR
(26.4% vs 52.2%, p 0.03). This result was confirmed by multivariate analysis.
Of 1107 infusions, we observed 38 EIIR (3.4%). In univariate analysis, the first
four infusions (26.4% vs 52.6%, p 0.002) and the resumption of IFX after drug
holiday (17.2% vs 29.0%, p 0.001) were predictive of EIIR. Multivariate analysis confirmed that the resumption of IFX after drug holiday was a major risk
factor of EIIR (OR 24, p50.001) but not the first four infusions. Surprisingly,
a premedication (anti-histaminic or hydrocortisone) seemed to be a risk factor
for EIIR in univariate and multivariate analysis while concomitant therapies did
not prevent EIIR. As resumption of IFX after drug holiday was a major risk
factor for EIIR, interaction test was performed and showed that the increased
risk induced by the premedication was related to resumption of IFX after drug
holiday.
The patients who experienced EIIR and those who did not experience EIIR have
had to discontinue IFX therapy in 69.6% (16/23) and 50.9% (29/57) of cases,
respectively (NS).
CONCLUSION: EIIR is a major event in the history of IBD patients treated by
IFX as it leads to drug discontinuation and thus limits considerably the available
therapeutic armamentarium. The resumption of IFX after drug holiday is the
major risk of EIIR and could be predicted in part by the measurement of antidrug antibodies. Non stricturing non penetrating CD could be also a risk factor.

United European Gastroenterology Journal 2(1S)


The efficacy of premedication remains questionable and could be limited to the
high risk patients.
Disclosure of Interest: C. Duron: None declared, A. Buisson Lecture fee(s) from:
Abbvie, MSD, M. Goutte: None declared, B. Pereira: None declared, G.
Bommelaer: None declared
P0324 COMPARISON BETWEEN INFLIXIMAB AND ADALIMUMAB
FOR THE TREATMENT OF PERIANAL FISTULISING CROHNS
DISEASE
A. Tursi1, W. Elisei2, M. Picchio3, R. Faggiani4, C. Zampaletta4, G. Pelecca4,
G. Brandimarte5,*
1
Gastroenterology Service, ASL BAT, Andria, 2Division of Gastroenterology, ASL
Roma H, Albano Laziale (Roma), 3Division of Surgery, "P. colombo" Hospital,
ASL Roma H, Velletri (Roma), 4Division of Gastroenterology, "Belcolle"
Hospital, Viterbo, 5Division of Internal Medicine and Gastroenterology, "Cristo
Re" Hospital, Rome, Italy
INTRODUCTION: Infliximab (IFX) and Adalimumab (ADA) have improved
the management of perianal Crohns disease (CD). However, comparative studies
have not been reported previously.
AIMS & METHODS: Our aim was to compare the outcomes of CD patients
with perianal fistulising disease treated with IFX or ADA.
A retrospective medical record review of CD patients, who received IFX or ADA
for perianal fistulising disease, was conducted. Fistulas were assessed using
Magnetic Resonance Imaging (MRI), and seton placement was performed
when appropriate. A 36-month follow-up was performed.
RESULTS: Twenty CD patients (9 males and 11 females; median age 31.5 years,
range 18-39) were treated (9 with IFX and 11 with ADA). Seton placement was
performed in 18 patients (8 in IFX and 10 in ADA group).
The baseline Harvey-Bradshaw index (HBI) and perianal disease activity index
(PDAI) significantly decreased after 6 weeks and remained at similar levels for
the entire follow-up in both groups.
The complete response rate of fistulas was 75% of patients at 36 months (78% in
IFX and 73% in ADA group), with no significant difference between the two
study groups.
Setons were withdrawn from twelve patients (5 in IFX and 7 in ADA group),
who experienced complete response and showed no radiological evidence of disease at 12-month follow-up.
Two patients with complex fistulas failed to obtain fistula closure under antiTNF (one in each groups). Changing the anti-TNF was useless and both
patients underwent to permanent colostomy.
CONCLUSION: Efficacy of IFX and ADA was similar in treating perianal
fistulising CD patients.
Disclosure of Interest: None declared
P0325 EFFICACY AND SAFETY OF GRANULOCYTE, MONOCYTE/
MACROPHAGE ADSORPTIVE APHERESIS IN STEROIDDEPENDENT ACTIVE UC WITH INSUFFICIENT RESPONSE OR
INTOLERANCE TO IMMUNOSUPPRESSANTS AND/OR
BIOLOGICAL THERAPIES (THE ART TRIAL): SAFETY RESULTS AT
12 WEEKS
A. Dignass1,*, B. Bonaz2, A. Akbar3, R. Gruber4 on behalf of The ART trial
working group
1
Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany, 2CHU
Grenoble, Grenoble, France, 3St. Marks Hospital, London, United Kingdom,
4
Otsuka Pharmaceutical Europe Ltd., Frankfurt, Germany
Contact E-mail Address: axel.dignass@fdk.info
INTRODUCTION: Current medical treatment options for patients with steroiddependent, active ulcerative colitis (UC) with insufficient response or intolerance
to immunosuppressants (IS) and/or biologicals are limited and not evidencebased. In addition, the recognised related safety profiles are considerable. The
clinical use of Granulocyte, Monocyte/Macrophage Adsorptive (GMA) apheresis with Adacolumn has previously demonstrated a safe and efficacious use in
this subgroup of UC patients.
AIMS & METHODS: This study was an uncontrolled, open-label, multicenter
trial conducted in the UK, France and Germany (ART, NCT01481142).
Consecutive eligible patients (18-75 years, steroid-dependent active UC with a
Rachmilewitz (CAI) index 6 and an Endoscopic Activity Index (EAI) 4, and
insufficient response or intolerance to IS and/or biologicals) were included.
Patients received at least 5 weekly GMA apheresis. Evaluation visits were
planned at Week 12, 24 and 48. The primary endpoint was the remission rate
(CAI 4) at Week 12 in the Intention-to-treat (ITT) population. We report safety
results observed along with the earlier communicated 12 weeks interim efficacy
results of 55.9% response and 39.3% remission.
RESULTS: The safety population comprised 85 subjects having received at least
one apheresis treatment. 14 out of 85 patients (16.5%) discontinued up to Week
12. 61/85 patients (71.8%) experienced any AE; in 54 patients (63.5%) these were
of mild or moderate intensity, all transient, mainly consisting of headaches and
problems related to venous access difficulties. Six (7.1%) patients experienced
serious adverse events (SAEs), all unrelated to the study treatment. SAEs or AEs
that led to discontinuation or withdrawal from the study were either related to
the indication being studied (ulcerative colitis), or to poor venous access/ vascular
access. There were no clinically significant changes in vital signs. There were few
shifts from baseline to week 12 among clinically significant values in safetyrelevant laboratory parameters.
CONCLUSION: GMA apheresis with Adacolumn has shown benefit in more
than 50% of patients with moderate to severe, active, steroid-dependent UC and
insufficient response or intolerance to IS and/or biological agents. No new safety

A219
signals were observed, confirming the safety profile of GMA apheresis even in a
difficult-to-treat UC patients group.
REFERENCES
Habermalz B and Sauerland S. Clinical effectiveness of selective granulocyte,
monocyte adsorptive apheresis with the Adacolumn device in ulcerative colitis.
Dig Dis Sci 2010; 55: 14211428.
Disclosure of Interest: A. Dignass Financial support for research from: ART trial:
Investigator, Lecture fee(s) from: Otsuka, Consultancy for: Otsuka, B. Bonaz
Financial support for research from: ART trial: Investigator, Lecture fee(s) from:
Otsuka, Consultancy for: Otsuka, A. Akbar Financial support for research from:
ART trial: Investigator, Lecture fee(s) from: Otsuka, Consultancy for: Otsuka,
R. Gruber Other: Employee of Otsuka Pharmaceutical Europe Ltd.
P0326 MID-AND LONG-TERM OUTCOMES AND REMISSION
MAINTENANCE RATE BY PROLONGED TREATMENT WITH
TACROLIMUS FOR REFRACTORY ULCERATIVE COLITIS
A. Ito1,*, K. Shiratori1, O. Teppei1, M. Tanishima1, K. Tomoko1, I. Bunnei1
1
Departoment of Medicine, Institute of Gastroenterology, Tokyo Womens Medical
Unvercity, Tokyo, Japan
Contact E-mail Address: itoayumi@ige.twmu.ac.jp
INTRODUCTION: Efficacy of tacrolimus (TAC) as remission induction therapy
for refractory ulcerative colitis (UC) has been reported. However, hitherto midand long-term outcomes and remission maintenance rates following a prolonged
treatment with TAC have not been evaluated.
AIMS & METHODS: In this study, we were interested to evaluate the clinical
remission maintenance rate for TAC in patients with UC. For this study, we
included 29 patients (15 male and 14 female) who had received a TAC-based
induction therapy between April 2009 and December 2013 (mean observation
period 728  311 days). In 10 patients, TAC was administered for 90 days
including the period of remission induction, followed by switch to an immunomodulator (azathioprine) to maintain remission (group 1). In 19 patients, TAC
was continued beyond the period of remission induction to maintain remission
(group 2). The patients in groups 1 and 2 were matched with respect to gender,
disease duration, pre-TAC haemoglobin (Hb), C-reactive protein (CRP), clinical
activity index (CAI, according to Lichtiger), and endoscopic index (EI) at one
month after TAC administration. The total dose of prednisolone administered up
to the time when clinical remission was achieved, duration of hospital stay, and
the time to recurrence between the two groups were factored into analyses.
Remission was defined as a CAI score of 4 or less at week 4 or later after
TAC administration. Likewise, recurrence was defined as a case in whom the
blood trough level was increased (10 ng/dl or above) by means of intense intravenous regimen of prednisolone, switch to a biological preparation, repeat or
dose-escalating TAC administration required to induce remission.
RESULTS: There was no significant difference in gender, disease duration, preTAC Hb, CRP, CAI, total dose of prednisolone administered until remission,
duration of hospital stay, and the time to recurrence between the two groups. The
mean TAC administration period in group 2 was 235  122 days vs 86  13 days
for group 1. Further, the EI scores at one month after TAC administration were
5.8  1.6 and 7.8  2.1 for group 1 and group 2, respectively; the difference was
significant (P 5 0.012). Regarding the treatment safety, finger tremor was
observed in 2 patients in group 1 and 5 patients in group 2, renal dysfunction
was observed in none of the group 1 patients, but in 3 of group 2 patients.
CONCLUSION: In this study, although no significant difference was found in
the time to recurrence, the EI score at one month after TAC treatment was
significantly higher in group 2 compared with group 1. This finding suggests
that a maintenance dose of TAC is likely to maintain remission even in patients
with delayed mucosal healing. However, longer TAC therapy may carry higher
risk of adverse side effects.
Disclosure of Interest: None declared
P0327 STRESS AND NONSTEROIDAL-ANTIINFLAMMATORY DRUGS
(NSAID)-INDUCED EXACERBATION OF EXPERIMENTAL COLITIS
IS ATTENUATED BY ANTIBIOTIC RIFAXIMIN AND PROBIOTIC
SACCHAROMYCES BOULARDII
B. Brzozowski 1,*, M. Zwolinska-Wcislo 1, E. Karczewska 2, A. Ptak-Belowska3,
K. Urbanczyk 4, G. Krzysiek-Maczka3, M. Strzalka3, T. Brzozowski 3
1
Gastroenterology, Hepatology and Infectious Diseases Clinic, 2Department of
Microbiology, Faculty of Pharmacy, 3Department of Physiology, 4Department of
Pathomorphology, Jagiellonian University Medical College, Cracow, Poland
INTRODUCTION: Clinical and experimental studies have indicated that stress
plays an important role in the initiation and perpetuation of inflammatory bowel
disease (IBD), however, the mechanism of stress-induced alterations in the severity of the inflammatory process of colonic mucosa remains unclear. Colonic
microbiota is important component of IBD pathogenesis but its influence on
the colonic mucosal barrier under stress conditions as well as the efficacy of
treatment with antibiotics or probiotics on experimental colitis have not been
fully explained.
AIMS & METHODS: We studied the effect of cold stress on healing of experimental colitis induced in rats by intrarectal administration of 2,4,6- trinitrobenzenosulfonic acid (TNBS) and we assessed the involvement of colonic microflora
in healing of TNBS colitis in rats exposed to stress and stress combined with
aspirin (ASA) treatment. The efficacy of antimicrobial therapy by antibiotic
rifaximin or probiotic Saccharomyces boulardii on stress-induced impairment of
the healing of experimental colitis in the absence or presence of ASA treatment
was investigated. Animals with TNBS-induced colitis and exposed to cold stress
for 20 min every second day were treated i.g. daily with 1) vehicle (saline), 2)
Saccharomyces boulardii (108CFU/rat), 3) rifaximin (100 mg/kg), 4) ASA (20mg/

A220
kg) alone or 5) ASA (20 mg/kg) combined with Saccharomyces boulardii (108CF/
rat) or rifaximin (100 mg/kg). At day 10 upon colitis induction, the colonic blood
flow (CBF) was determined by H2-gas clearance technique, the blood was withdrawn for measurement of plasma MPO, IL-1 and TNF- levels and the expression of proinflammatory markers IL-1, TNF-, iNOS, COX-2 and HIF- were
analyzed in colonic mucosa of stressed rats.
RESULTS: Exposure to stress significantly increased the area of TNBS damage
and the concomitant administration of ASA further augmented the area of these
lesions. This delay in mucosal healing caused by cold stress was accompanied by
a significant fall in the CBF, the significant rise in tissue weight, a 4-fold increase
in MPO activity and the mucosal overexpression of IL-1, TNF-, iNOS, COX-2
and HIF1. In stressed animals, the significant increase of E. coli counts in feces
and the spleen were observed and this effect was significantly attenuated by both
rifaximin and Saccharomyces boulardii. Treatment with rifaximin and to lesser
extent with probiotic Saccharomyces boulardii significantly decreased the area of
colonic lesions while increasing CBF and significantly reducing the plasma IL-1
and TNF- levels and the colonic expression of proinflammatory markers.
CONCLUSION: 1/ Stress exacerbates experimental colitis due to increase of
intestinal pathogenic E. coli and this pathogenic bacteria translocation to the
extra-intestinal organs such as spleen, and 2/ Modifying of the intestinal microbiota through probiotics or selected antibiotics could be of clinical importance in
the limitation of the consequences of environmental factors such as stress and
adverse effects of NSAID therapy in patients with lower GI-tract disorders.
Disclosure of Interest: None declared
P0328 TNF-ALPHA AS INDUCTION AND MAINTENANCE THERAPY
FOR CROHNS DISEASE: A PROSPECTIVE OBSERVATIONAL
STUDY IN GERMANY
B. Bokemeyer1,2,*, U. Helwig3, N. Teich4, C. Schmidt5, T. Krummenerl6, A.K. Rupf7, H. Hartmann8, M. Blaker9, A. Krummenerl10, M. Duffelmeyer11,
R. Hinrichs12, P. Hartmann2, S. Nikolaus1, D. Huppe8, S. Schreiber1
1
Clinic of General Medicine I, University Hospital Schleswig-Holstein, Campus
Kiel, Kiel, 2Gastroenterology Practice Minden, Minden, 3Gastroenterology
Practice Oldenburg, Oldenburg, 4Gastroenterology Practice Leipzig, Leipzig,
5
Gastroenterology Clinic IV, University Hospital Jena, Jena, 6Gastroenterology
Practice, Munster, 7Medical Department, Clinic of Friedrichshafen,
Friedrichshafen, 8Gastroenterology Practice Herne, Herne, 9Gastroenterology
Practice Eppendorfer Baum, Hamburg, 10Department of Internal Medicine I,
Martha-Maria Hospital Halle Dolau, Halle (Saale), 11IOMTech GmbH, Berlin,
12
Competence Network IBD, Kiel, Germany
Contact E-mail Address: bernd.bokemeyer@t-online.de
INTRODUCTION: The nationwide BioCrohn Registry (Biological Registry with
Crohns Disease Patients in Germany) of the German Competence-Network IBD
is a five-year prospective registry of about 1,500 patients with Crohns disease
(CD) in Germany. This is a sub-study of the BioCrohn Registry reporting the
anti TNF-alpha antibody (TNF) steroid-free remission rates of induction and
maintenance therapy in 391 anti-TNF-na ve CD-patients with adalimumab
(ADA) or infliximab (IFX) up to 12-months follow-up.
AIMS & METHODS: Within the framework of this non-interventional prospective online documentation, data in respect to the course of disease, psychosocial
burden of disease, health economics and the genetic profile were examined. End
of 2012 the recruitment was stopped having 1,525 CD-patients included by 59
different gastroenterology practices and hospitals with IBD experience. All
patients have a 5 year follow-up period. The databank for baseline and 12months data has been closed in 03/2013 and after databank cleansing now we
have the finalized data including the 6- and 12-months visits.
RESULTS: 391 TNF-naive CD-patients (ADA: n 264; IFX: n 127) have
been analysed (average age: 36 years; female: 52%; smokers 34%; disease duration: 9.3 years; bowel resection: 33%; prior immunosuppressive therapy: 75%).
Baseline characteristics were similar in the two groups. The IBD-therapy followed an accelerated step-up management. Immunosuppressants were used in
19% at 6 and in 21% after 12 months. Accordingly to the TNF therapy, the use
of systemic glucocorticoids dropped over time (baseline until 6 and 12 months)
from 22.0% to 6.3% and 8.3%, respectively (p50.001). The remission rate
(PGA) at 6 months was 70.9% and 72.1% after 12 months. In spite of the
TNF-induced clinical remission (4 70%) the psychosocial impairments with
anxiety/depression (EQ-5D) showed only minor improvement and remained on
a relatively high level (baseline: 37%, 6 months: 31%, 12 months: 28%). In the
induction therapy with TNF we found a steroid-free remission (HBI5 5) in
67.1% at 6 months and in 68.9% at 12 months in the maintenance therapy.
Evaluating the efficacy of ADA vs. IFX we did not find any difference in steroid-free remission rates as an induction therapy at month 6 (ADA: 68.2%; IFX:
64.6%; p n.s.) or as a maintenance therapy at month 12 (ADA: 68.1%; IFX:
70.6%; p n.s.). In the per protocol TNF-group with regular visits at 6 and 12
months (n 264) 91.7% of these patients were still on TNF after 12 months.
Additionally 5.7% of the ADA-patients switched to IFX and 9.2% of the IFXpatients switched to ADA. This means that 76.8% of the patients starting with
TNF were on the same TNF therapy after 12 months.
CONCLUSION: In this real life setting anti-TNF therapy could induce steroidfree remission in about 70% with the relatively early escalation of therapy in
IBD-experienced centres. In comparison there is no difference in steroid-free
remission rates between ADA vs. IFX.
Disclosure of Interest: B. Bokemeyer Financial support for research from:
Abbvie, Ferring; UCB, Lecture fee(s) from: Abbvie, MSD, Ferring, Falk,
Takeda, Consultancy for: Abbvie, MSD, Ferring, Takeda, U. Helwig: None
declared, N. Teich: None declared, C. Schmidt: None declared, T.
Krummenerl: None declared, A.-K. Rupf: None declared, H. Hartmann: None
declared, M. Blaker: None declared, A. Krummenerl: None declared, M.
Duffelmeyer: None declared, R. Hinrichs: None declared, P. Hartmann: None

United European Gastroenterology Journal 2(1S)


declared, S. Nikolaus: None declared, D. Huppe: None declared, S. Schreiber:
None declared
P0329 PREDICTORS OF HOSPITALIZATION IN PATIENTS WITH
MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
FROM ULTRA 1 AND ULTRA 2
B. Feagan1,*, W.J. Sandborn2, W. Reinisch3, S. Ghosh4, A.M. Robinson5,
A. Lazar6, Q. Zhou5, M. Skup5, R.B. Thakkar5
1
Robarts Research Institute and University of Western Ontario, London, Canada,
2
UCSD, La Jolla, United States, 3McMaster University, Hamilton, 4University of
Calgary, Calgary, Canada, 5AbbVie Inc, North Chicago, United States, 6AbbVie
Deutschland GmbH & Co. KG, Ludwigshafen, Germany
INTRODUCTION: Patients with moderately to severely active ulcerative colitis
(UC) are frequently hospitalized due to disease deterioration. The factors associated with hospitalization risk in patients treated with non-biologic therapy for
UC are analyzed in patients randomized to placebo (PBO) in ULTRA 11 and
ULTRA 22.
AIMS & METHODS: ULTRA 1 had an 8 to 12 week double-blind (DB) phase
followed by an open-label (OL) all adalimumab (ADA) phase to week 52.
ULTRA 2 was a 52-week DB trial in which patients with inadequate response
could receive OL ADA 40 mg beginning at week 12. Patients with loss of
response or intolerance to prior anti-TNF use could enrol in ULTRA 2.
Logistic regression was used to determine predictors of all-cause and UC-related
hospitalization in PBO randomized patients from ULTRA 1 and ULTRA 2.
Baseline variables assessed were age, sex, disease duration, pancolitis, prior
anti-TNF use, CRP, albumin, Mayo score, aminosalicylate use, immunomodulator use, corticosteroid use, alcohol use, smoking status, and weight. Model 1
also included baseline endoscopy subscore (2 vs 3) and Model 2 also included
stool frequency (SFS, 0-1 vs 2-3), rectal bleeding (RBS, 0-1 vs 2-3), and PGA (0-2
vs 3) subscores. Patients were censored 70 days after moving to OL ADA.
RESULTS: Selected odds ratios for the association of baseline variables with
hospitalization for PBO randomized patients from ULTRA 1 and 2 are shown in
the table. In both regression models, male sex was a significant predictor for
lower risk of all-cause and UC-related hospitalization, whereas lower baseline
albumin and higher baseline CRP concentration were significant predictors for
higher risk of all-cause and UC-related hospitalization. Alcohol use was associated with UC-related hospitalization in both models. Disease activity at baseline, as measured by Mayo score or individual subscores, disease duration, prior
anti-TNF use, pancolitis, or use of aminosalicylates, immunomodulators, or
corticosteroids were not associated with hospitalization risk in either model.
Table. Logistic regression odds ratios for hospitalization in PBO-randomized
patients from ULTRA 1 and 2
Model 1

Sex (male)
Baseline CRP (mg/L)
Albumin (540 g/L)
Current alcohol use

Model 2

All-cause

UC-related

All-cause

UC-related

0.37**
1.01*
2.39*
1.82

0.41*
1.02**
2.82**
2.11*

0.35**
1.01*
2.50*
1.82

0.38*
1.02**
3.00**
2.12*

CONCLUSION: In this analysis, factors associated with hospitalization in


patients receiving non-biologic therapy for UC were sex, increased inflammation
(as measured by CRP) and low baseline albumin. These factors may be useful
when evaluating future therapeutic interventions in patients with UC failing
conventional therapy.
REFERENCES
1. Reinisch, et al. Gut 2011; 60: 780.
2. Sandborn, et al. Gastroenterol 2012; 142: 257.
Disclosure of Interest: B. Feagan Financial support for research from:
Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis,
Centocor, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech,
ActoGenix, Wyeth, Lecture fee(s) from: AbbVie, UCB, and Janssen,
Consultancy for: Millennium, Merck, Centocor, Elan/Biogen, Janssen-Ortho,
Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie,
Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals,
Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novonordisk, GSK,
Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan,
Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc,
Sigmoid Pharma, W. Sandborn Financial support for research from: AbbVie,
Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Millennium,
Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals,
and UCB Pharma., Lecture fee(s) from: AbbVie, Bristol-Myers Squibb, and
Janssen, Consultancy for: AbbVie, ActoGeniX NV, AGI Therapeutics, Inc.,
Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AMPharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic Healthcare Limited,
Aptalis, BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol-Myers
Squibb,
Celgene,
Celek
Pharmaceuticals,
Cellerix
SL,
Cerimon
Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado
Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical
Research Inc, Elan Pharmaceuticals, EnGene, Inc., Eli Lilly, Enteromedics,
Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc.,
Funxional Therapeutics Limited, Genzyme Corporation, Genentech, Gilead
Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences,
Ironwood Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc., Lexicon

United European Gastroenterology Journal 2(1S)


Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research
Laboratories, MerckSerono, Merck & Co., Millennium, Nisshin Kyorin
Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer
Pharmaceuticals, Orexigen Therapeutics, Inc., PDL Biopharma, Pfizer, Procter
and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis
Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix
Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, Sigmoid Pharma
Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L. A. Pharma
(UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma
AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics
Limited (VBL), Warner Chilcott UK Limited, W. Reinisch Consultancy for:
AbbVie, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers
Squibb, Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan,
Ferring, Genentech, Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin
Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma
Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer,
Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough,
Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult,
Zyngenia, Austria and 4SC, S. Ghosh Financial support for research from:
AbbVie, Consultancy for: AbbVie, Shire, Pfizer, Bristol-Myers Squibb, Janssen
and Merck & Co, Other: advisory committee or review panel for AbbVie and
Merck & Co., A. Robinson Shareholder of: AbbVie, Other: Employee: AbbVie,
A. Lazar Shareholder of: AbbVie, Other: Employee: AbbVie, Q. Zhou
Shareholder of: AbbVie, Other: Employee: AbbVie, M. Skup Shareholder of:
AbbVie, Other: Employee: AbbVie, R. Thakkar Shareholder of: AbbVie,
Other: Employee: AbbVie
P0330 DEEP REMISSION IMPROVES CLINICAL OUTCOMES AFTER
INFLIXIMAB DISCONTINUATION IN INFLAMMATORY BOWEL
DISEASES
C. Felice1,*, D. Pugliese1, M. Marzo1, G. Andrisani1, O.M. Nardone1, A. Papa1,
I. De Vitis1, G.L. Rapaccini1, L. Guidi1, A. Armuzzi1
1
IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato
Columbus, Catholic University, Rome, Italy
Contact E-mail Address: carla.felice@virgilio.it
INTRODUCTION: Recent studies underlined the importance to treat inflammatory bowel diseases (IBD) looking beyond symptoms and considering also
tangible indicators of disease remission, such as mucosal healing and normalization of biomarkers. A clear definition of deep remission has not been validated
yet. However, the achievement of clinical remission associated to mucosal healing
has been demonstrated to improve clinical outcomes during biological treatments. Some studies also showed that high C-reactive protein (CRP) levels at
the time of infliximab (IFX) discontinuation may represent a risk factor for
clinical relapse. No data are available so far about clinical outcomes of IBD
patients who discontinue IFX being in deep remission defined as the combination
of clinical remission, mucosal healing and normal CRP.
AIMS & METHODS: This single-centre study included IBD patients who discontinued maintenance treatment with IFX because of sustained steroid-free
clinical remission (HBI4 for Crohns disease -CD- and partial Mayo score2
for ulcerative colitis UC-, with no intake of systemic steroids during the last 12
months before discontinuation). Deep remission was defined as sustained steroidfree clinical remission associated to normal CRP (5 mg/l) and mucosal healing
(defined as absence of ulcers in CD, or endoscopic Mayo score of 0-1 in UC).
Primary endpoint was the comparison of clinical relapse between two groups of
patients who were in deep remission (group 1) or not (group 2) at the time of IFX
discontinuation. Secondary endpoints were endoscopic recurrence, hospitalizations, surgeries and retreatment with anti-TNF between the two groups.
RESULTS: Sixty-one patients (40 CD, 21 UC) were included in the study (group
1 n 34, group 2 n 27). Median follow-up after IFX discontinuation was 36
months (IQR 23-60). No significant differences were found among baseline characteristics. The rate of clinical relapse resulted significantly different between
groups: 14/34 (41%) in group 1 relapsed in comparison with 21/27 (78%) in
group 2 (p 0.009). Mucosal healing was the only other variable associated to
a lower incidence of clinical relapse (p 0.03). Median values of CRP at the time
of IFX discontinuation were not associated to a different clinical outcome. Time
to clinical relapse was significantly shorter in group 2: patients not in deep
remission at the time of IFX discontinuation relapsed after a median of 12
months (IQR 8,25-19.5) in comparison with 36 months (IQR 23-57) of group 1
(p50.001). No differences were found considering rates of endoscopic recurrence, hospitalization, surgery and need for anti-TNF retreatment. However,
patients in group 2 required hospitalization and retreatment with anti-TNF
significantly earlier in comparison with group 1 (p 0.02 and p 0.03,
respectively).
CONCLUSION: IBD patients who discontinue IFX because of sustained steroid-free clinical remission may relapse over time. However, the presence of deep
remission (clinical remission associated to mucosal healing and normal CRP) at
the time of IFX discontinuation seems to guarantee better clinical outcomes.
Disclosure of Interest: C. Felice: None declared, D. Pugliese: None declared, M.
Marzo: None declared, G. Andrisani: None declared, O. Nardone: None
declared, A. Papa: None declared, I. De Vitis: None declared, G. L.
Rapaccini: None declared, L. Guidi Other: MSD, AbbVie, A. Armuzzi
Financial support for research from: MSD, Lecture fee(s) from: MSD,
AbbVie, Chiesi, Ferring, Nycomed, Otsuka, Consultancy for: AbbVie, MSD,
Other: MSD, AbbVie, Ferring, Nycomed

A221
P0331 PHARMACOLOGY OF ETROLIZUMAB IN A PHASE 2 STUDY IN
MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
C. Looney1, F. Fuh1, M.T. Tang1, X. Wei1, M.E. Keir1, G.W. Tew1, J. EasthamAnderson1, L. Diehl1, A. Salas2, G. De Hertogh3, S. Francom1, H. Gilbert1,
D. Luca1, J.G. Egan1, S. Vermeire3, J.C. Mansfield4, C. Lamb4, B. Feagan5,
J. Panes2, D. Baumgart6, S. Schreiber7, I. Dotan8, W. Sandborn9, P. Rutgeerts3,
T.T. Lu1,*, S. OByrne1, M. Williams1
1
Genentech, Inc., South San Francisco, United States, 2Hospital Clinic de
Barcelona, Barcelona, Spain, 3University of Leuven, Leuven, Belgium, 4University
of Newcastle, Newcastle upon Tyne, United Kingdom, 5University of Western
Ontario, London, Canada, 6Humboldt-University of Berlin, Berlin, 7Christian
Albrechts University, Kiel, Germany, 8Tel Aviv University, Tel Aviv, Israel,
9
University of California San Diego, La Jolla, United States
Contact E-mail Address: bishop.caroline@gene.com
INTRODUCTION: Etrolizumab, a humanized antibody to the integrin 7,
blocks 47:MAdCAM-1 and E7:E-cadherin interactions, and has been
shown in a Phase 2 study to be effective at inducing clinical remission in patients
with moderate-to-severely active ulcerative colitis (UC).1 Maximal occupancy of
7 receptors was observed on lymphocyte subsets in peripheral blood and colonic
tissue in both dose cohorts (monthly subcutaneous doses of 100mg [low] or
300mgloading dose [high]), with a corresponding increase in B and T intestinal
homing lymphocytes in peripheral blood.2 Here we present the pharmacodynamic (PD) effects of etrolizumab in colonic tissue and the serum pharmacokinetics (PK) from the Phase 2 study.
AIMS & METHODS: Changes from baseline were assessed in colonic tissue gene
expression at weeks 6 and 10 (qPCR, n 96) and in E cells at week 10 (immunohistochemistry [IHC], n 55 & 73 in epithelium and lamina propria, respectively). Serum drug levels were measured at multiple time points following
etrolizumab administration.
RESULTS: Etrolizumab displayed linear kinetics, with 4.4 fold exposure
separation between the two dose cohorts. The average serum concentration of
etrolizumab at week 10 was 8.5mg/mL and 37.8mg/mL for the low and high dose
cohorts, respectively. There were no differences in 7 gene expression in colonic
tissue between the etrolizumab and placebo treated groups. E cells were
decreased in the intestinal crypt epithelium, but not in the lamina propria, in
etrolizumab-treated patients compared with placebo. Reduction in multiple markers associated with proinflammatory infiltration and active disease was
observed in etrolizumab-treated patients who achieved clinical remission compared to those who did not, including decreases in expression of proinflammatory cytokines, lymphocyte subset markers (CD3, CD19), MAdCAM-1, and
epithelial cell-associated E cells. Although maximal occupancy of 7 receptors
was observed in both low and high dose groups, there were no apparent differences in PD effects between the two etrolizumab-treated cohorts. Furthermore,
within the etrolizumab-treated cohorts, there were no observed drug exposure/
clinical remission relationships.
CONCLUSION: In this Phase 2 study, we confirmed etrolizumab target engagement and subsequent biological effects, both in peripheral blood and at the site of
disease pathobiology. PD effects were consistent with decreased inflammation in
the colonic mucosa, particularly in patients who attained clinical remission.
These findings contribute to the understanding of the mechanism of action of
etrolizumab: blockade of leukocyte homing to, and decreased inflammation in,
the colon.
REFERENCES
Vermeire S, et al. DDW, oral presentation, 18 May 2013.
Williams M, et al. UEGW, poster presentation, 15 October 2013.
Disclosure of Interest: C. Looney Other: Genentech, employee, F. Fuh Other:
Genentech, employee, M. Tang Other: Genentech, employee, X. Wei Other:
Genentech, employee, M. Keir Other: Genentech, employee, G. Tew Other:
Genentech, employee, J. Eastham-Anderson Other: Genentech, employee, L.
Diehl Other: Genentech, employee, A. Salas Financial support for research
from: Palau Pharma, Roche Pharma AG, Boehringer Ingelheim, Lecture fee(s)
from: Pfizer, G. De Hertogh Consultancy for: Genentech, Inc, Centocor, Inc.,
Shire Pharmaceuticals, Inc., Novartis Pharmaceuticals, Inc, Galapagos NV, S.
Francom Other: Genentech, employee, H. Gilbert Other: Genentech, employee,
D. Luca Other: Genentech, employee, J. Egan Other: Genentech/Roche,
employee, S. Vermeire Financial support for research from: Merck, Abbvie,
UCB, Consultancy for: Pfizer, Abbvie, Merck, Takeda, UCB, Shire, Ferring,
J. Mansfield Financial support for research from: Genentech, Inc.,
Consultancy for: Genentech, Inc., Tillotts Pharmaceuticals, C. Lamb Financial
support for research from: Genentech, Immundiagnostik, Roche Diagnostics
UK, B. Feagan Consultancy for: Abbott/AbbVie, ActoGenix, Amgen, Astra
Zeneca, Avaxia Biologics, Axcan, Baxter Healthcare Corp, BoehringerIngelheim, Bristol-Myers Squibb, Celgene, Elan/Biogen, EnGene, Ferring,
Roche/Genentech, GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood
Pharma, Janssen Biotech, Kyowa Hakko Kirin Co, Lexicon, Lilly, Merck,
Millennium Pharma, J. Panes Consultancy for: Abbvie, BMS, Genentech,
MSD, Roche, Tygenics, Boehringer Ingelheim, Pfizer, Nutrition Science
Partners, Topivert, Novo Nordisk, D. Baumgart Financial support for research
from: Abbott, Shire, Hitachi, Lecture fee(s) from: medac, Shire, Ferring
Pharmaceuticals, MSD, Falk Foundation, Consultancy for: Abbott, MSD,
Roche, Genentech, Pfizer, S. Schreiber Financial support for research from:
AstraZeneca Pharmaceuticals, UCB Pharma, Shire Pharmaceuticals Group,
Lecture fee(s) from: Falk Foundation, Consultancy for: Abbott, AstraZeneca
Pharmaceuticals, Bayer AG, Berlex Laboratories, Bristol-Myers Squibb,
Centocor, Chemocentryx, Ferring Pharmaceuticals, Otsuka Pharma.,
Progenika Biopharma, Genentech, Schering-Plough, Shire Pharmaceuticals
Group, UCB Pharma, Novartis Pharmaceuticals, Pfizer Inc, NovoNordisk, hospira, Takeda, I. Dotan Lecture fee(s) from: Abbott Laboratories, Falk Pharma,
Ferring Pharmaceuticals, J. C. healthcare, Consultancy for: Centocor, Inc.,

A222
Genentech, Atlantic Healthcare Ltd, Pfizer, Bioline Rx, W. Sandborn
Consultancy for: ActoGeniX NV, Amgen, AM-Pharma BV, BoehringerIngelheim Inc, Bristol Meyers Squibb, Celgene, Cosmo Technologies,
Coronado Biosciences, Eisai Medical Research Inc., Elan Pharmaceuticals, Eli
Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Glaxo Smith Kline,
Ironwood Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Millennium
Pharmaceuticals, Nisshin Kyorin Pharmaceuticals Co., Ltd, Novo Nordisk A/
S, Orexigen Therapeutics, Inc., Pfizer, Prometheus Laboratories, Receptos, P.
Rutgeerts Financial support for research from: UCB Pharma, Abbott, J&J,
Merck & Co, Lecture fee(s) from: Abbott, Merck & Co, Consultancy for:
UCB Pharma, Merck, Bristol-Myers Squibb, Genentech Inc., Abbott,
Centocor - J&J, Millenium/ Takeda, Neovacs, Actogenics, Robarts, Amgen,
Pfizer, Falk Pharma, Tillotts, T. Lu Other: Genentech, employee, S. OByrne
Other: Genentech, employee, M. Williams Other: Gilead Sciences, employee
P0332 CLINICAL OUTCOME OF PERIANAL CROHNS DIESEASE AND
IMPACT OF TREATMENT STRATEGIES OVER THE TIME
C. Reenaers1,*, A. Natalis1, E. Louis2
1
CHU Sart Tilman, Liege, Belgium, Liege, Belgium, 2Hepato-Gastroenterology,
CHU Sart Tilman, Liege, Belgium, Liege, Belgium
Contact E-mail Address: catherinereenaers@hotmail.com
INTRODUCTION: Perianal Crohns disease (pCD) is associated with complications leading to recurrent surgery and tissue damage. Immunosuppressive drugs
(IS) including anti-TNF have changed the management of pCD.
AIMS & METHODS: Our aim was to describe the management and the natural
history of a cohort of patients with active pCD and to identify predictive factors
of poor evolution.
Methods: A retrospective study of pCD patients registred in the database of the
university hospital of Lie`ge, Belgium. Perianal lesions included abscess, fistulae,
anal fissure, anal strictures. pCD treatments included antibiotics, surgical drainage (with or without seton), stoma. Medical treatments including IS and antiTNF were recorded at pCD diagnosis and over follow-up. pCD relapse was
defined as antibiotherapy for recurrent abscess, the need for surgical drainage
or stoma. The subroups of patients followed before (old cohort) and after (young
cohort) the year 2000 were compared in a subanalysis.
RESULTS: 181 patients with pCD were included. Mean follow-up was 7.9 years
Mean time between CD and pCD diagnosis was 6.3 years. Lesions at pCD
diagnosis were abscess in 93/181 (51%), fistula in 91/181 (50%; 77/93 of complex
fistulae), anal fissure in 28/181 (15%), anal stricture in 18/181 (10%). At diagnosis abscess drainage was performed in 31/181 (17%), drainage seton in 44/
181 (24%), stoma in 18/181 (10%). 132/181 (74%) and 83/181 (47%) had IS and
anti-TNF respectively at pCD diagnosis. Relapse rate was 51% within a mean
time of 33 months. During follow-up 15% required a stoma. Predictive factors of
relapse were perianal abscess (p50.0001, HR 4.4), fistula (p50.0001,
HR 4.5) or surgical drainage at diagnosis (p50.0001, HR 4.5), young age
at pCD diagnosis (28 versus 31 yo, p 0.02), short time between CD and pCD
diagnosis (5.7 versus 7 years, p 0.01), IS (p 0.04, HR 1.8) and anti-TNF
(p 0.01, HR 1.5) at pCD diagnosis. Anti-TNF during follow-up, time to
introduce them and duration of anti-TNF treatment were not predictive of
relapse. The young and old cohort had the same characteristics at pCD diagnosis
except a higher use of IS (87% vs 48%, p50.0001) and anti-TNF (3% vs 68%,
p50.0001) in the young cohort. Clinical outcome including the time to relapse,
type of relapse, need for surgery and stoma was similar in both cohorts.
CONCLUSION: In our cohort of pCD patients half of them had a perianal
relapse over the time requiring surgery in more than 2/3 of them. At pCD
diagnosis perianal abscess, fistula, surgical drainage, young age, treatment with
IS or anti-TNF were associated with a higher risk of relapse. Although higher
prescription of anti-TNF and IS in the last years new treatment strategies have
not impacted the outcome of pCD.
Disclosure of Interest: None declared
P0333 BIOMARKER ANALYSES FROM A PHASE 2 STUDY
EVALUATING THE ANTI-INTERLEUKIN-13 ANTIBODY
TRALOKINUMAB IN PATIENTS WITH ULCERATIVE COLITIS
C. Balendran1,*, J. Kilhamn1, S. Pierrou1, E. Rehnstrom1, N. Henderson1,
K. Randall2, G. Hughes2, M. Knutsson1, F. Erlandsson1, M.B. Hansen1,
S. Danese3
1
AstraZeneca, Molndal, Sweden, 2AstraZeneca, Alderley Park, United Kingdom,
3
Istituto Clinico Humanitas, Milan, Italy
INTRODUCTION: Interleukin-13 (IL-13) is a central cytokine effector in the Thelper 2 immune response that has been proposed to be a key driver of ulcerative
colitis (UC) pathogenesis. Tralokinumab (CAT-354) is a human immunoglobulin
G4 antibody that inhibits binding of IL-13 both to IL-13 receptor (IL-13R) alpha
1 and IL-13R alpha 2.
AIMS & METHODS: The aim of these analyses was to gain insight into the
mechanistic action of tralokinumab in a phase 2 study in patients with UC.
Overall, 111 patients with moderate-to-severe UC were randomised in a 1:1
ratio to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks
during a 12-week treatment phase. Serum samples were obtained at baseline and
at 2-week intervals throughout the treatment phase. Biopsies were taken during
colonoscopy at baseline and after 8 weeks of treatment from mucosal areas
judged by the endoscopist to represent inflamed and normal colonic mucosa.
IL-13 levels were assessed in serum and biopsy homogenates at baseline and
following treatment. Changes from baseline to week 8 in colonic mRNA expression were assessed by in situ hybridisation for the tight junction protein claudin-2
and by quantitative PCR for selected IL-13-regulated genes. Data were analysed
by treatment and treatment response, with clinical response defined as a decrease

United European Gastroenterology Journal 2(1S)


in total Mayo score of  3 points and  30%, and a decrease in rectal bleeding
subscore of  1 point or an absolute subscore of 0 or 1.
RESULTS: A time-dependent increase in total IL-13 serum levels was observed
with tralokinumab but not with placebo. Free IL-13 was detectable in homogenates of inflamed colonic mucosa; however, there was no consistent trend regarding changes from baseline after 8 weeks treatment with tralokinumab. At
baseline, in situ claudin-2 mRNA expression was higher in inflamed versus
normal colonic mucosa. Claudin-2 mRNA expression decreased from baseline
in clinical responders. There were numerical increases from baseline in colonic
mucosal mRNA levels for IL-6, IL-8 and S100 calcium binding protein A8 (a
subunit of calprotectin) in clinical responders in the tralokinumab group compared with clinical responders in the placebo group. A numerical decrease from
baseline in mRNA for tumour necrosis factor receptor superfamily member 12A
was seen in the tralokinumab group compared with placebo. However, gene
expression changes were small and would not remain significant after correcting
for multiple statistical comparisons.
CONCLUSION: Claudin-2 may be a useful prognostic biomarker for UC. Total
IL-13 in serum increased with tralokinumab treatment, supporting systemic
target engagement. In colonic mucosa, small expression changes in IL-13-regulated genes were associated with tralokinumab treatment, though measurement
of free IL-13 could not confirm target engagement by tralokinumab in colonic
mucosa.
Disclosure of Interest: C. Balendran Other: Employee of AstraZeneca, Molndal,
Sweden, J. Kilhamn Other: Employee of AstraZeneca, Molndal, Sweden, S.
Pierrou Other: Employee of AstraZeneca, Molndal, Sweden, E. Rehnstrom
Other: Employee of AstraZeneca, Molndal, Sweden, N. Henderson Other:
Employee of AstraZeneca, Molndal, Sweden, K. Randall Other: Employee of
AstraZeneca, Alderley Park, United Kingdom, G. Hughes Other: Employee of
AstraZeneca, Alderley Park, United Kingdom, M. Knutsson Other: Employee of
AstraZeneca, Molndal, Sweden, F. Erlandsson Other: Employee of AstraZeneca,
Molndal, Sweden, M. Hansen Other: Employee of AstraZeneca, Molndal,
Sweden, S. Danese Lecture fee(s) from: Schering-Plough, Abbott Laboratories,
Merck & Co, UCB Pharma, Ferring, Cellerix, Celtrion, Millenium, Takeda,
Nycomed, Pharmacosmos, Actelion, Alpha Wasserman, Genentech,
Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals,
TiGenix, Vifor and Johnson & Johnson, Consultancy for: Schering-Plough,
Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Celtrion,
Millenium, Takeda, Nycomed, Pharmacosmos, Actelion, Alpha Wasserman,
Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo
Pharmaceuticals, TiGenix, Vifor and Johnson & Johnson, Other: Advisory
board member for Schering-Plough, Abbott Laboratories, Merck & Co, UCB
Pharma, Ferring, Cellerix, Celtrion, Millenium, Takeda, Nycomed,
Pharmacosmos, Actelion, Alpha Wasserman, Genentech, Grunenthal, Pfizer,
AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, TiGenix, Vifor and
Johnson & Johnson
P0334 THREE-YEAR STEROID FREE REMISSION AND SAFETY OF
AZATHIOPRINE TREATMENT IN INFLAMMATORY BOWEL
DISEASE PATIENTS
C. Cassieri1,*, R. Pica1, E. V. Avallone1, M. Zippi1, C. Corrado1, P. Vernia1,
P. Paoluzi1, E.S. Corazziari1
1
Internal Medicine and Medical Specialties, Sapienza "University", Rome, Italy
Contact E-mail Address: claudio.cassieri@libero.it
INTRODUCTION: Purine analogue azathioprine (AZA) is widely used for
induction and maintenance of remission in steroid dependent patients with
inflammatory bowel disease (IBD).
AIMS & METHODS: We investigated its efficacy and safety in maintaining
steroid-free remission in steroid dependent IBD patients three years after the
institution of treatment. Data from consecutive IBD outpatients referred in
our Institution, between 1985-2012, were reviewed and all patients treated with
AZA were included in this retrospective study. AZA was administered at the
recommended dose of 22.5 mg/kg. Blood chemistry was analysed before administration of the drug, every 10-15 days for the first 3 months and then every 1-2
months following the institution of treatment.
RESULTS: Out of 2472 consecutive IBD outpatients visited in the index period,
AZA was prescribed to 360 patients, 189 (52.5%) were affected by Crohns
disease (CD) and 171 (47.5%) by ulcerative colitis (UC). Seventy-eight patients
with a follow-up 536 months were excluded from the study. Two hundred and
eighty-two patients were evaluated, 152 (53.9%) with CD and 130 (46.1%) with
UC. One hundred and fifty-four (54.6%) were male and 128 (45.4%) female
(average age of 33.7513.82 SD years, range 14-76 y.). Three years after the
institution of treatment, 170 (60.3%) patients still were in steroid-free remission
(101 CD vs 69 UC, 66.4% and 53.1%, respectively, p 0.0279), 62 (22%) had a
relapse requiring retreatment with steroids (38 UC vs 24 CD, 29.2% and 15.8%,
respectively, p 0.0091), 50 (17.7%) discontinued the treatment due to side
effects (27 CD vs 23 UC, 17.8% and 17.7%, respectively). Loss of response
from 1st to 3rd year of follow-up was low, about 12%.
CONCLUSION: Three years after the onset of treatment 60% of patients did
not require further steroid courses. After the first year loss of response was low in
two subsequent years. In the present series the maintenance of steroid-free remission was significantly higher in CD than in UC patients. The occurrence of side
effects leading to the withdrawal of AZA treatment has been low.
Disclosure of Interest: None declared

A223

United European Gastroenterology Journal 2(1S)


P0335 EFFICACY OF AN MMP9-SPECIFIC MONOCLONAL ANTIBODY
IN A DSS-INDUCED COLITIS MODEL OF ULCERATIVE COLITIS

P0337 BODY MASS INDEX VARIATION IN INFLIXIMAB-TREATED IBD


PATIENTS

D. Marshall1, R. Spangler1, C. OSullivan1, J. Adamkewicz1, V. Smith1,*


1
Gilead Sciences, Inc., Foster City, United States

D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1


1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com

INTRODUCTION: Ulcerative colitis (UC) remains a high unmet medical need


with no current curative therapies; the majority of patients with UC require lifelong treatment to prevent disease progression. UC is characterized by diseasespecific upregulation of matrix metalloproteinase 9 (MMP9). MMP9 can exert
pathogenic effects both by degrading extracellular matrix (ECM) proteins and
participating in tissue destruction and by activating or releasing growth factors
and cytokines from the ECM or cell surface. Previous attempts to target MMPs
with broad-spectrum or semi-selective inhibitors in oncology and inflammatory
diseases have been unsuccessful, partly due to their lack of specificity.
AIMS & METHODS: Here we used immunohistochemistry to confirm MMP9
induction at colitic foci in both human and DSS-exposed mice and evaluated
efficacy of a therapeutically-dosed MMP9-specific monoclonal antibody
(AB0046) in a DSS-induced colitis model of UC.
RESULTS: MMP9 immunoreactivity was limited in the healthy colon, but was
strongly induced and had a similar pattern of expression at active disease sites in
human UC and mouse DSS-colitis tissue. In disease, MMP9 was expressed in
abscessed and necrotic crypts and regions of cryptitis containing neutrophilic
infiltrates as well as by macrophages within the lamina propria. Extracellular
MMP9 staining colocalized with regions of destruction in the epithelial crypt
basement membrane. Inhibiting MMP9 in established DSS-induced colitis with
AB0046 resulted in a significant protection (50%) against body weight loss and
endoscopically assessed disease, and a 45% reduction in the incidence of diarrhea. Colons from AB0046-treated animals exhibited less crypt destruction, less
inflammatory cell infiltration, and a reduction in MMP9 expression. In concordance with the IHC analysis, AB0046 treatment resulted in a decrease in histopathologic disease scores. Interestingly, AB0046 treatment resulted in reduction
of serum markers of inflammation including IL-6, CXCL2, KC/GRO, MPO,
LIF, MCP-1/2/5, MIP-3, and TIMP-1.
CONCLUSION: MMP9 is highly expressed in human UC and in mouse DSSexposed colons. The ability of MMP9 to degrade basement membrane and to
activate or release pro-inflammatory factors from the ECM make this protein a
compelling therapeutic target in colitis. Treatment of established DSS-induced
colitis with an MMP9-specific monoclonal antibody resulted in improvement in
clinical measures of disease, histopathology, as well as in systemic markers of
inflammation. These data suggest that an MMP9 specific monoclonal antibody is
a promising therapeutic strategy for treatment of UC. Gilead Sciences has developed a humanized MMP9-specific monoclonal antibody that is currently in a
Phase 1b clinical trial in UC.
Disclosure of Interest: D. Marshall Other: Is an employee of Gilead Sciences, Inc.,
R. Spangler Other: Is an employee of Gilead Sciences, Inc., C. OSullivan Other:
Is an employee of Gilead Sciences, Inc., J. Adamkewicz Other: Is an employee of
Gilead Sciences, Inc., V. Smith Other: Is an employee of Gilead Sciences, Inc.
P0336 INFLIXIMAB ONE HOUR INFUSIONS A GOOD CHOICE FOR
IBD PATIENTS?
D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1
1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com
INTRODUCTION: The use of anti-TNF agents as maintenance therapy in IBD
patients is well documented. However, administration of Infliximab (IFX)
implies long hours at the hospital, with significant costs and inconvenience. A
shorter infusion protocol would minimize such drawbacks, maintaining the same
safety and efficacy.
AIMS & METHODS: To evaluate the safety and efficacy profile of one hour
IFX infusion.
Between November 2012 and December 2013, the occurrence of acute adverse
reactions to IFX was prospectively documented. Patients under maintenance
therapy, with at least 4 infusions with no history of reactions, received one
hour infusions. This was followed by 1-hour surveillance in the next 5 infusions,
and 30 minutes from then on.
RESULTS: From a total of 95 patients under IFX therapy (Average age: 38.8 
14.2 years old; Female - 58%; Crohns Disease 66, Ulcerative Colitis 25,
Unclassified IBD 4), about 68% (65/95) started receiving one hour infusions
(average of 6 per patient, total of 390 infusions), while 31.6% (30/95) were kept
under the usual two hour protocol, with two hour infusions followed by one or
two hours of surveillance.
In the one hour infusion group, 38.4% were under combined therapy with immunosuppressive agents and 23% received hydrocortisone and/or clemastine as
prophylactic medication. There was no adverse reaction noted in this group. In
92.3% of the patients, the therapeutic regimen remained the same, but in the
remaining 7.7%, an increase in dosage or interval shortening was needed. One
patient had to change to Adalimumab (ADA) due to poor response to IFX.
In the 2-hour infusion group, 56.7% were under combined therapy with immunosuppressants and 43.3% received prophylactic medication. A total of 5 reactions were described (2.46%), 2 of which were severe (0.98%), leading to IFX
definitive suspension. Initial regimen was maintained in 93.3% (28/30) of these
patients, while 6.7% (2/30) had to increase IFX dosage or shorter intervals
between infusions.
CONCLUSION: During maintenance therapy, 1 hour infusions are safe and
effective, minimizing costs associated with IFX therapy, and allowing shorter
hospital stays and better quality of life to IBD patients.
Disclosure of Interest: None declared

INTRODUCTION: A significant number of patients with IBD present with


nutritional deficiencies and malnutrition is relatively common. There are several
ways of describing response to Infliximab (IFX). However, nutritional status is
rarely used as a tool to evaluate the efficacy of this anti-TNF agent.
AIMS & METHODS: To establish a relation between BMI changes and clinical
response in patients treated with IFX.
Patients with IBD treated with IFX for at least a year were included. Their BMI
was measured before starting IFX, after remission induction therapy, and then
after 1 and 3 years of maintenance therapy. Response to IFX was evaluated
through clinical and laboratorial data.
RESULTS: A total of 62 patients were included (average age 37.3  13.8 years
old; 71% females; Crohns Disease 45, Ulcerative Colitis 19). Their initial
average BMI was 21.43.07 (10 patients with BMI518.5 16.1%; 8 patients
with BMI425 12.9%). After induction, no significant change was noted in
BMI, but one year later, a meaningful increase was noted (21.4 to 22.7;
p 0.049). After three years of therapy, this tendency was more evident (21.4
to 22.8; p 0.026), as only 2 patients still had BMI518,5, whilst 16 had weight
excess (26%).
There was a significant increase in BMI in patients who responded to therapy, in
contrast to those who maintained clinical activity. The average BMI actually
decreased in the latter group (1,81 vs. -0,96; p 0.012). This increase was
noted particularly in patients who had initial BMI518.5 (p 0.032), as well as
in male patients and with small bowel involvement. Factors such as age, disease
duration, smoking or other medication did not show significant association with
BMI.
CONCLUSION: Nutritional deficits are common clinical issues in IBD patients.
Therapy with Infliximab is clearly associated with improved nutritional status in
patients who are responders, unlike those who mantained disease activity. This
association is more clearly noted in the group with lower initial BMI.
Disclosure of Interest: None declared
P0338 MONITORING VITAL SIGNS DURING INFLIXIMAB INFUSION
IS IT REALLY USEFUL?
D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com
1

INTRODUCTION: Monitoring vital signs is part of the surveillance protocol


during Infliximab infusions in most IBD reference centers. Despite being innocuous, it is a time consuming task, representing another burden to already strained
healthcare professionals. In this era of increasing medical care costs, and with the
growing number of IBD patients treated with biological agents, it becomes essential to analyze if this practice is able to predict or identify adverse reactions to
Infliximab.
AIMS & METHODS: To evalute the usefulness of monitoring vital signs during
Infliximab infusions.
From January 2013 to December 2013, each patients pulse (HR), systolic blood
pressure (SBP), temperature (Temp) and pulse oximetry (SpO2) were registered
during Infliximab infusions. Acute adverse reactions were also recorded.
RESULTS: A total of 593 Infliximab infusions were administered to 95 patients
(average of 6.2  1.3 infusions per patient; median age: 38.8  14.2 years old;
59% females; Crohns Disease 66, Ulcerative Colitis 29). The overall incidence of acute infusion reaction was 2.2% (13 of 593 infusions), affecting 6
patients (6.3%). Two of them were serious, with bronchospasm and angioedema.
Comparing baseline vital signs between groups with and without acute reactions,
no relevant differences were noted (HR: 78 vs. 81/min, p 0.23; SBP: 106 vs. 109
mmHg, p 0.12; Temp: 35.9 vs. 36.1 C, p 0.68; SpO2: 98% vs. 99%, p 0.42).
Vital signs measured immediately before and during acute reactions were also
compared. No significant change was noted in most cases, except during the two
serious reactions, in which there was an increase in heart rate (67 to 110 beats/
min and 86 to 112/min) and a fall in one of the patients SpO2 (97 to 85%),
maintaining stable blood pressure and temperature.
CONCLUSION: Scheduled monitoring of vital signs during Infliximab infusions
was unable to predict acute reactions or to identify patients with increased risk of
such reactions, though it can help to assess its severity. Such conclusions do not
suggest a more distant surveillance, but emphasize that clinical symptoms should
be the main focus.
Disclosure of Interest: None declared

A224
P0339 HISTOLOGICAL AND ENDOSCOPIC REMISSION INDUCED BY
INFLIXIMAB IN MODERATE TO SEVERELY ACTIVE ULCERATIVE
COLITIS PATIENTS HERICA STUDY
F. Magro1,*, S. Lopes2, J. Lopes2, E. Rodrigues-Pinto2, F. Portela3, M. Silva3,
J. Cotter4, M. Joao Moreira4, P. Lago5, C. Lopes5, C. Caetano5, P. Peixe6,
C. Chagas6, L. Carvalho6, S. Lopes3, B. Rosa4, A. Albuquerque7, C. CamilaDias8, J. Afonso9, K. Geboes10, F. Carneiro7 on behalf of Working group
1
Gastroenterology, 2Centro Hospitalar Sao Joao, Porto, 3Centro Hospitalar de
Coimbra, Coimbra, 4Centro Hospitalar do Alto Ave, Guimaraes, 5Centro
Hospitalar do Porto, Porto, 6Centro Hospitalar de Lisboa Ocidental, Lisboa,
7
Centro Hospitalar de Sao Joao, 8CINTESIS - Center for research in health
technologies and information systems, 9Department of Pharmacology and
Therapeutics, Porto, Portugal, 10University Hospital KU, Leuven, Belgium
Contact E-mail Address: fm@med.up.pt
INTRODUCTION: Correlation between histological activity, endoscopic findings, levels of calprotectin and lactoferrin in ulcerative colitis (UC) are not well
established. Infliximab can induce remission. Residual microscopic active inflammation may predict relapse. Non-invasive methods such as calprotectin may be
appropriate for this purpose.
AIMS & METHODS: The primary aim was to evaluate the histological remission induced by infliximab at week 8 (Geboes 53.0); secondary aims were to
evaluate the association between histological remission, mucosal healing, faecal
calprotectin and faecal lactoferrin. 20 patients with moderate to severe UC
(Mayo score 6-12) with inadequate response to corticosteroids or corticosteroid
dependence, all of them anti-TNF na ve, started infliximab in a prospective,
open-label, multi-centre study, with 1 year of follow-up, 4 visits assessments
(baseline, week 8, week 30, and week 52). Topical treatment was not allowed.
In each visit, Mayo score, faecal calprotectin and lactoferrin were evaluated, and
sigmoidoscopy with biopsies was performed. The worst sample was used for
histological score (Geboes index GI) and the patients were considered in
deep remission when in clinical remission (Mayo score 52) and GI 3 and
calprotectin levels 5100mg/L and lactoferrin 7.25mg/L and mucosal healing
at endoscopy (0 or 1).
RESULTS: Out of the 20 patients, 13 had left-sided colitis (E2) and 7 had
pancolitis (E3). At weeks 8, 30 and 52, 15%, 30% and 35% of the patients,
respectively, were on histological remission. At the same intervals, 10%, 20%
and 10% of the patients, respectively, were in deep remission. Sixty-six percent of
those on histological remission at week 8 had persistent remission at week 30 and
52, and 100% of those on histological remission at 30 week persisted thereafter.
Calprotectin 4100mg/L at week 8 predicted histological activity (sensitivity:
76%; specificity: 100%), with a positive predictive value (PPV) of 100% and a
negative predictive value (NPV) of 42%. Lactoferrin levels higher than 7.25 mg/L
at week 8 predicted histological activity (sensitivity: 94%; specificity: 66%), with
a PPV of 94% and a NPV of 66%. The probability of being in histological
remission once achieving mucosal healing (PPV) was 55% (weeks 30 and 52)
and the probability of endoscopic mucosal healing with calprotectin 100mg/L
was 100% and 75%, respectively, at weeks 30 and 52.
CONCLUSION: Infliximab is able to induce and maintain histological remission
in ulcerative colitis patients. High levels of calprotectin and lactoferrin predict
persistent histological activity.
Disclosure of Interest: None declared
P0340 ANTI-TNF HAS A FAVORABLE EFFECT ON INSULIN
SENSITIVITY IN NON-DIABETIC, NON-OBESE PATIENTS WITH
INFLAMMATORY BOWEL DISEASE
F. Kothonas1,*, S.A. Paschou2, A. Myroforidis1, V. Loi2, T. Terzi 2,
O. Karagianni2, A. Poulou1, A. Vryonidou2, K. Goumas1
1
Gastroenterology Department, 2Endocrinology Department, Hellenic Red Cross
Hospital, Athens, Greece
Contact E-mail Address: fotiskothonas@gmail.com
INTRODUCTION: Insulin resistance is very common in autoimmune systemic
diseases and recently it was also found in children and adults with inflammatory
bowel disease (IBD). Inflammation and insulin resistance are closely linked, and
inflammatory cytokines such as tumor necrosis factor alpha (TNFa) may inhibit
insulin signaling and promote insulin resistance. The aim of this study was to
investigate the effect of anti-TNF therapy on glucose and lipid metabolism in
non-diabetic, non-obese patients with IBD.
AIMS & METHODS: We studied 41 patients with IBD (25M/16F, 36.4  11
(19-64) years old, 28 with Crohns disease and 13 with ulcerative colitis), without
known history of diabetes. Eighteen patients (9M/9F, 33.6  8.8 years) were on
anti-TNF therapy for more than 1 year, while the other 23 patients (16M/7F,
38.7  12.5 years) were treated with azathioprine and mesalazine (Aza/Mes).
Nine of the patients from the second group were then treated with anti-TNF
and studied again 6 months after. Fasting glucose, insulin, c-peptide, HbA1c,
lipids, and CRP levels were determined and HOMA-IR index was calculated, in
all patients. Statistical analysis of the data was performed using SPSS 16.00.
RESULTS: Three of the patients were diagnosed with overt diabetes and were
excluded from the analysis. Patients from the two therapy groups were matched
for age (anti-TNF: 33.6  8.8 years vs Aza/Mes: 38.7  12.5 years, p40.05) and
BMI (anti-TNF: 23.3  3.4 vs Aza/Mes: 23.1  1.7, p40.05), and were not
obese. We did not find any statistical differences between the patients from the
two therapy groups in the levels of fasting glucose (anti-TNF: 88  10.7 vs Aza/
Mes: 93.4  14.9 mg/dl, p40.05), insulin (anti-TNF: 10.9  7.9 vs Aza/Mes: 12.1
 6.6 mIU/ml, p40.05), c-peptide (anti-TNF: 1.9  0.9 vs Aza/Mes: 2.2  1.4
ng/ml, p40.05), HbA1c (anti-TNF: 5.2  0.3 vs Aza/Mes: 5.3  0.4%, p40.05),
total cholesterol (anti-TNF: 168.6  32.7 vs Aza/Mes: 162.8  34.3 mg/dl,
p40.05), HDL (anti-TNF: 57.5  15.7 vs Aza/Mes: 53.8  20.3 mg/dl,

United European Gastroenterology Journal 2(1S)


p40.05), LDL (anti-TNF: 95.8  28.7 vs Aza/Mes: 90.7  24.4 mg/dl,
p40.05), triglycerides (anti-TNF: 75.8  37.6 vs Aza/Mes: 90.8  61.3 mg/dl,
p40.05), CRP (anti-TNF: 3  5.4 vs Aza/Mes: 4.9  6.1, p40.05) and in the
HOMA-IR index (anti-TNF: 2.77  2 vs Aza/Mes: 3.1  1.9, p40.05). In
patients who were treated for 6 months with anti-TNF, a statistically significant
decrease in insulin (before: 15.4  5.8 vs after: 10.2  2.7 mIU/ml, p 0.049) and
c-peptide (before: 2.4  1.2 vs after: 1.4  0.4 ng/ml, p 0.038) levels as well as
the HOMA-IR index (before: 4.1  2.1 vs after: 2.3  0.7, p 0.047) was
observed, without any statistically significant changes in weight, BMI, glucose,
HbA1c, lipids and CRP levels (in all comparisons p40.05).
CONCLUSION: These preliminary data indicate that anti-TNF therapy may
have a favorable effect on insulin sensitivity in non-diabetic, non-obese patients
with inflammatory bowel disease.
Disclosure of Interest: None declared
P0341 HUMAN
SAFETY,
PHARMACOKINETICS
AND
PHARMACODYNAMICS OF THE GPR84 ANTAGONIST GLPG1205,
A POTENTIAL NEW APPROACH TO TREAT IBD
F. Vanhoutte1,*, S. Dupont2, T.Van Kaem1, M.-H. Gouy2, L. Gheyle3,
R. Blanque2, R. Brys1, N. Vandeghinste1, W. Haazen3, G.van t Klooster1,
J. Beetens1
1
GALAPAGOS NV, Mechelen, Belgium, 2GALAPAGOS SASU, Romainville,
France, 3SGS Life Science Services, CPU, Antwerp, Belgium
Contact E-mail Address: johan.beetens@glpg.com
INTRODUCTION: Free fatty acids (FFAs) are nutritional components and
metabolic intermediates that play important roles in a wide range of cellular
functions (energy source, membrane structure, signalling). Recently, FFAs
have been reported to activate a family of G protein-coupled receptors, which
are involved in the pathophysiology of a variety of diseases, including metabolic
and inflammatory disorders. GPR84 is activated by medium chain FFA (carbon
length C9-C14). The receptor is primarily expressed on white blood cells (PMN,
monocyte/macrophage) consistent with a reported role for GPR84 in
inflammation.
We identified GLPG1205 as a potent and selective antagonist of GPR84, inhibiting GPR84 activation in HEK cells, as well as GPR84-induced neutrophil migration. In a mouse IBD model (DSS), GLPG1205 dose-dependently decreased the
disease activity index, to a similar level as sulphasalazine and cyclosporine. The
histological score for colon lesions, neutrophil influx as well as colonic MPO
content was substantially reduced.
AIMS & METHODS: To evaluate the safety, tolerability, pharmacokinetics
(PK) and pharmacodynamics (PD) of GLPG1205 in healthy volunteers, and
identify a dose for subsequent Proof of Concept studies in inflammatory bowel
disease.
GLPG1205 was administered as a liquid suspension, providing maximal dose
flexibility, as single doses (10 up to 800 mg) or multiple doses (50, 100 and 200
mg once daily (QD) for 14 days). Each dose level was evaluated in panels of 8
male healthy volunteers, with 6 receiving GLPG1205 and 2 placebo. In order to
evaluate target engagement, PD was assessed by a competitive radiolabeled binding assay in whole blood, using a tritiated GPR84 antagonist chemically closely
related to GLPG1205.
RESULTS: In healthy volunteers, GLPG1205 was generally safe and well tolerated up to 100 mg QD for 14 days, with no adverse effects on ECG, vital signs or
laboratory parameters. The most relevant adverse event was headache. The PK
of the compound showed a good oral bioavailability with a long half-life (4 one
day) and a dose-proportional increase in exposure. Steady state was reached after
8 to 10 days. GLPG1205 showed concentration-dependent target engagement in
whole blood (ex vivo), showing similar potency as in in vitro assays. The singledose PK/PD data demonstrated a clear relationship between drug exposure and
PD effect. Complete target occupancy for 24 hours after once daily dosing in
volunteers was observed at doses of 100 and 200 mg QD.
CONCLUSION: GLPG1205, a potent and selective inhibitor of GPR84, is safe
and generally well tolerated in healthy volunteers. It shows a favorable PK/PD
profile, clearly demonstrating the ability of the compound to antagonize GPR84,
a target which might be implicated in several neutrophil- and macrophage-driven
inflammatory conditions. At 100 mg once-daily, full 24-hour inhibition was
obtained. This dose will be studied in Proof of Concept studies to evaluate the
efficacy and safety of GLPG1205 in patients with Crohns disease and ulcerative
colitis.
Disclosure of Interest: F. Vanhoutte Other: employee, S. Dupont Other:
employee, T. Van Kaem Other: employee, M.-H. Gouy Other: employee, L.
Gheyle: None declared, R. Blanque Other: employee, R. Brys Other: employee,
N. Vandeghinste Other: employee, W. Haazen: None declared, G. van t
Klooster Other: employee, J. Beetens Other: employee
P0342 EFFECTS OF A FODMAP- RESTRICTED DIET ON IRRITABLE
BOWEL SYMPTOMS IN PATIENTS WITH INFLAMMATORY
BOWEL DISEASE
F.van Megen1,*, G.E. Kahrs1, J.G. Hatlebakk1
1
1Department of Clinical Nutrition and Section of Gastroenterology, Department
of Medicine, Clinical Institute 1, BERGEN, Norway
Contact E-mail Address: frida_van_megen@hotmail.com
INTRODUCTION: The FODMAP (fermentable oligo- di- and monosaccharides, and polyols) -restricted diet has previously been proven effective to improve
symptoms in patients with irritable bowel syndrome (IBS). FODMAPs are small
osmotic active and poorly absorbed short-chain carbohydrates, and include fructose (found in fruit), lactose (found in milk products), fructans (found in grain
and vegetables), galacto-oligosaccharides (found in legumes) and polyols (found

United European Gastroenterology Journal 2(1S)


in sweetened products). FODMAPs are rapidly fermented by bacteria in the
colon and can cause bloating, increased gas production, abdominal pain and
altered bowel movements. FODMAPs do not cause IBS, but a FODMAPrestricted diet may improve the symptoms. Patients with inflammatory bowel
disease (IBD) often suffer from persistent symptoms even though the inflammatory activity is in remission. This study aimed to investigate the FODMAPrestricted diet in patients with IBD in remission with persistent symptoms consistent with IBS.
AIMS & METHODS: A 6 week intervention was undertaken in 12 IBD-patients
(10 ulcerative colitis and 2 Crohns disease, 3M/9W, age 23-57 years) in remission
with CRP55mg/L and faecal calprotectin 5100mg/kg, and fulfilling the
ROME-III criteria for IBS. FODMAP intake was determined by 4 days prospective dietary registrations at 0 and 6 weeks. Instructions and follow-up were
given by a clinical dietician. IBS-symptoms and quality of life (QoL) were
assessed with questionnaires (IBS-SSS and SF-36). Compliance was assessed by
VAS-scales. Colonic fermentation was measured by breath tests with sampling
for 180min after intake of 10g lactulose. Statistics: T-tests and ANOVA
(p50.05).
RESULTS: FODMAP intake was significantly reduced from median 6.3g/d to
1.5g/d (p 0.0005). IBS symptoms were significantly reduced from median IBSSSS score 265.0 to 67.6 (p50.0001), and resolved in 58% of patients (remission
classified as score 575). Symptoms were reduced in the first 3 weeks and
remained stable from 3 to 6 weeks. Mental-related QoL significantly improved
from median score 43.8 to 53.3 (p 0.039). There was a positive trend for physical-related QoL with mean score 41.0 vs. 47.1 (p 0.05). QoL improved over
the whole 6 weeks of the intervention. The scores for the SF-36 health domains
bodily pain (53.3) and vitality (52.1) improved most, with p-values 0.004
and 0.017, respectively. Gas production did not change (AUC 3488 vs. 3390 ppm
x min, p 0.8). Mean compliance with the diet was 93%, and 73% continued the
diet one month after the intervention.
CONCLUSION: The FODMAP-restricted diet resolved or improved IBS symptoms and QoL, and should be considered an effective treatment for patients
experiencing symptoms in spite of remission from IBD.
Disclosure of Interest: None declared
P0343 INCREASED EXPRESSION OF T-CELL-ASSOCIATED GENES IN
BASELINE BIOPSIES FROM TNF ANTAGONIST NAIVE PATIENTS
WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE
COLITIS WHO UNDERGO REMISSION IN RESPONSE TO
ETROLIZUMAB IN A PHASE II TRIAL
G.W. Tew1, J. Hackney2, D. Gibbons3, C. Lamb4, D. Luca1, J. Egen1,
S. Vermeire5, J. Mansfield4, B. Feagan6, J. Panes7, D. Baumgart8, S. Schreiber9,
I. Dotan10, W. Sandborn11, J. Kirby4, P. Irving3, G. De Hertogh5,
G.Van Assche5, P. Rutgeerts5, S. OByrne1,*, A. Hayday3, M. Keir1
1
Genentech Research and Early Development, South San Francisco, 2Genentech
Research and Early Development, San Francisco, CA, United States, 3Kings
College London, London, 4University of Newcastle, Newcastle upon Tyne, United
Kingdom, 5University of Leuven, Leuven, Belgium, 6University of Western Ontario,
Ontario, Canada, 7Hospital Clinic Barcelona, Barcelona, Spain, 8HumboldtUniversity of Berlin, Berlin, 9Christian Albrechts University, Kiel, Germany, 10Tel
Aviv University, Tel Aviv, Israel, 11University of California, San Diego, United
States
Contact E-mail Address: keir.mary@gene.com
INTRODUCTION: Etrolizumab is a humanized antibody to the integrin 7
subunit that blocks 47 and E7 binding to MAdCAM-1 and E-cadherin,
respectively. In a recent phase II randomized double-blind placebo-controlled
trial (EUCALYPTUS), induction therapy with etrolizumab showed clinically
meaningful efficacy compared to placebo at week 10 in patients with moderate
to severely active ulcerative colitis.
AIMS & METHODS: RNA sequencing of inflamed colonic biopsies from TNF
antagonist na ve etrolizumab-treated patients who took part in EUCALYPTUS
was used as a hypothesis-free approach to identify gene expression patterns
associated with clinical remission in response to etrolizumab. Gene set enrichment analysis of pre-defined immune cell gene sets was performed. Following
this, differentially expressed genes of interest were evaluated in sorted CD4 or
CD8 E7-positive and -negative T cells from colonic biopsies of nonEUCALYPTUS UC patients and control subjects.
RESULTS: TNF antagonist na ve patients that underwent remission in response
to etrolizumab had higher baseline expression of T cell-associated genes in mucosal biopsies, while high baseline expression of neutrophil-associated genes was
associated with etrolizumab non-response. Patients with higher than median gene
expression levels of the T cell associated genes ITGAE (E integrin), granzyme A
and TMEM200A were enriched for remission in response to etrolizumab. As
increased E gene expression was associated with remission, sort purified
E7-positive T cells from biopsies of UC patients were used to test for increased
expression of other remission-associated T cell genes. Gene expression of granzyme A in CD4 and CD8 T cells (p50.01) and TMEM200A in CD8 T cells
(p50.05), along with other effector molecules such as granzyme B and perforin
in CD4 T cells (p50.05), were found to be increased in E7-positive T cells
relative to E7-negative T cells from UC patients but not healthy subjects.
Finally, gene expression of the effector molecules granzyme A and B were
decreased following etrolizumab treatment in patients achieving remission.
CONCLUSION: Enrichment of T cell associated genes, including E and granzyme A, was observed in baseline colonic biopsies from TNF antagonist na ve
patients that achieved clinical remission in response to etrolizumab. These candidate biomarkers may identify patients whose disease pathobiology is predominantly T cell-mediated and may benefit from etrolizumab treatment.
Disclosure of Interest: G. Tew Other: Genentech, employee, J. Hackney Other:
Genentech, employee, D. Gibbons Financial support for research from:

A225
Genentech, Cerimon Pharmaceuticals, C. Lamb Financial support for research
from: Genentech, Immundiagnostik, Roche Diagnostics UK, D. Luca Other:
Genentech, employee, J. Egen Shareholder of: Genentech/Roche, Other:
Genentech/Roche, S. Vermeire Financial support for research from: Merck,
Abbvie, UCB, Consultancy for: Pfizer, Abbvie, Merck, Takeda, UCB, Shire,
Ferring, J. Mansfield Financial support for research from: Genentech Inc.,
Consultancy for: Genentech Inc.; Tillotts Pharmaceuticals, B. Feagan
Consultancy for: Abbott/AbbVie, ActoGenix, Amgen, Astra Zeneca, Avaxia
Biologics, Axcan, Baxter Healthcare Corp, Boehringer-Ingelheim, BristolMyers Squibb, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genentech,
GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharma, Janssen
Biotech, Kyowa Kakko Kirin Co, Lexicon, Lilly, Merck, Millennium Pharma,
J. Panes Consultancy for: Abbvie, BMS, Genentech, MSD, Roche, Tygenics,
Boehringer Ingelheim, Pfizer, Nutrition Science Partners, Topivert, Novo
Nordisk, D. Baumgart Financial support for research from: Abbott, Shire,
Hitachi; Speaking and Teaching: medac, Shire, Ferring Pharmaceuticals, MSD,
Falk Foundation, Consultancy for: Abbott, MSD, Roche, Genentech, Pfizer, S.
Schreiber Financial support for research from: AstraZeneca Pharmaceuticals,
UCB Pharma, Shire Pharmaceuticals Group, Lecture fee(s) from: Falk
Foundation, Consultancy for: Abbott, AstraZeneca Pharmaceuticals, Bayer
AG, Berlex Laboratories, Bristol-Myers Squibb, Centocor, Chemocentryx,
Ferring Pharmaceuticals, Otsuka Pharma., Progenika Biopharma, Genentech,
Schering-Plough, Shire Pharmaceuticals Group, UCB Pharma, Novartis
Pharmaceuticals, Pfizer Inc, NovoNordisk, Hospira, Takeda, I. Dotan Lecture
fee(s) from: Ferring Pharmaceuticals Inc, Abbott Laboratories, J. C. healthcare,
Falk Pharma, Consultancy for: Centocor, Inc., Genentech, Atlantic Healthcare
Ltd, Pfizer; Bioline Rx, W. Sandborn Consultancy for: ActoGeniX NV, Amgen,
AM-Pharma BV, Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celgene,
Cosmo Technologies, Coronado Biosciences, Eisai Medical Research Inc., Elan
Pharmaceuticals, Eli Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences,
Glaxo Smith Kline, Ironwood Pharmaceuticals, Janssen, Lexicon
Pharmaceuticals,
Millennium
Pharmaceuticals,
Nisshin
Kyorin
Pharmaceuticals Co., Ltd, Novo Nordisk A/S, Orexigen Therapeutics, Inc.,
Pfizer, Prometheus Laboratories, Receptos, J. Kirby: None declared, P. Irving:
None declared, G. De Hertogh Consultancy for: Genentech, Inc, Centocor, Inc.,
Shire Pharmaceuticals, Inc., Novartis Pharmaceuticals, Inc, Galapagos NV, G.
Van Assche Financial support for research from: Abbvie, MSD, Lecture fee(s)
from: Abbvie, Janssen, Aptalis, Ferring, Warner Chillcott, Consultancy for:
Abbvie, Takeda, MSD, Janssen, BMS, Robarts Clinical Trials, P. Rutgeerts
Financial support for research from: UCB Pharma, Abbott, J&J, Merck & Co,
Lecture fee(s) from: Abbott, Merck & Co, Consultancy for: UCB Pharma,
Merck, Bristol-Myers Squibb, Genentech Inc., Abbott, Centocor - J&J,
Millenium/ Takeda, Neovacs, Actogenics, Robarts, Amgen, Pfizer, Falk
Pharma, Tillotts, S. OByrne Other: Genentech, employee, A. Hayday
Financial support for research from: Genentech, ImmunoQure, Lecture fee(s)
from: MedImmune., Consultancy for: HS-Lifesciences, ImmunoQure, M. Keir
Other: Genentech, employee
P0344 QAX576, AN ANTIINTERLEUKIN (IL)-13 MONOCLONAL
ANTIBODY, FOR THE TREATMENT OF PATIENTS WITH
FISTULISING CROHNS DISEASE (CD): RESULTS OF A PROOF-OFCONCEPT STUDY
G. Rogler1,*, A. Stallmach2, S. Fichtner-Feigl3, S. Schreiber4, A. Sturm5,
E. Ramsden6, P. Moulin6, D. Lee6, A. Christ6
1
Division of Gastroenterology and Hepatology, University Hospital, Zurich,
Switzerland, 2Department of Internal Medicine IV, Jena University Hospital, Jena,
3
Department of Surgery, University Medical Center Regensburg, Regensburg,
4
Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel,
5
Charite Campus Virchow Klinikum, Medical Department, Berlin, Germany,
6
Novartis Institutes for BioMedical Research, Basel, Switzerland
INTRODUCTION: Recent studies have identified IL-13 as a key cytokine driving the tissue remodelling that accompanies fistula formation in CD. This study
assessed the effect of QAX576, an antiIL-13 monoclonal antibody on fistula
healing in patients with fistulising CD.
AIMS & METHODS: In this 52 weeks (6 weeks treatment, 46 weeks observation), multi-centre, parallel group, double-blind, active controlled study, 23
patients (18 years) were planned to be included. Enrolment was stopped after
10 patients due to slow recruitment. Eligible patients (CD  6 months,  1
perianal fistula,  1 ineffective fistula treatment but no previous anti-TNF 
treatment failure) were randomized to receive intravenously either QAX576 10
mg/kg (at baseline, Weeks 3 and 6; placebo at Week 2; n 6) or infliximab (IFX)
5 mg/kg (at baseline, Weeks 2 and 6; placebo at Week 3; n 4). The primary
variable was the number of patients (responders) achieving complete closure of
all perianal fistulas for  4 weeks (compared to historical placebo rate of 13%).
Secondary variables included clinical assessments of the fistulas and MRI-based
activity scores of the fistula tracts.
RESULTS: Nine patients were included in the pharmacodynamic analysis set
(QAX576 6; IFX 3 [one patient excluded due to protocol deviation]). The
primary endpoint was achieved by two patients (33.3%; 90% CI: 0.114, 0.656)
in the QAX576 group. One patient stopped treatment due to abscess formation
(Week 3), one due to lack of efficacy (Week 14). In the QAX576 group, patients
had 1-4 secreting fistulas at baseline. Both responders had complete closure with
absence of any secretion within 3 weeks, although the MRI activity score
remained stable or even increased in these two patients. Fistula secretion
remained stable in three patients and fluctuated in one. All patients in the IFX
group were responders.
Immunohistochemistry of fistula tissue at baseline confirmed epithelial expression of IL-13R2 (but not IL-13R1) and de-differentiation of distorted,
entrapped crypts; SNAIL expression as marker of invasiveness was not found.

A226
Overall, 35 AEs were reported in four patients (66.7%) in the QAX576 group; 24
AEs were reported in four patients (100%) in the IFX group. Majority of AEs
were mild or moderate in severity. No death was reported in this study. One SAE
(procedural pain) was reported in the IFX group.
CONCLUSION: In this study, QAX576 was well tolerated. As expected IFX was
a powerful agent to induce fistula closure. Blockade of IL-13 may be effective,
too, as compared to historical placebo rates, although the very low patient
number does not allow a formal assessment.
Disclosure of Interest: G. Rogler Financial support for research from: Abbot,
Abbvie, Ardeypharm, Essex/MSD, FALK, Flamentera, Novartis, Roche,
Tillots, UCB, Zeller, Lecture fee(s) from: Astra Zeneca, Abbott, Abbvie,
FALK, MSD, Phadia, Tillots, UCB, Vifor, Consultancy for: Abbot, Abbvie,
Boehringer, Calypso, FALK, Genentech, Essex/MSD, MSD, Novartis, Pfizer,
Roche, UCB, Takeda, Tillots, Vifor, A. Stallmach Financial support for research
from: Abbvie, Pentax, Lecture fee(s) from: Abbott, Boehringer Ingelheim, Dr.
Falk Pharma, MSD, Recordati Pharma, Schering Plough, Shield Holding, Shire,
UCB, Vifor, Consultancy for: 4SC, Abbvie, Astellas, Boehringer Ingelheim,
MSD, S. Fichtner-Feigl: None declared, S. Schreiber Lecture fee(s) from:
MSD, Other: Paid advisor for MSD, A. Sturm: None declared, E. Ramsden
Other: Employed by Novartis, P. Moulin Shareholder of: Novartis, Other:
Novartis employee, D. Lee Shareholder of: Novartis, Other: Novartis employee,
A. Christ Shareholder of: Novartis, Roche, Other: Novartis employee
P0345 THE INFLUENCE OF ANTI-ADALIMUMAB ANTIBODIES ON
ADALIMUMAB TROUGH LEVELS, TNF-A LEVELS AND CLINICAL
OUTCOME
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: There is increasing evidence on the role of low trough levels
and the development of anti-TNF- antibodies for the occurrence of lack/loss of
response to Infliximab (IFX) therapy in patients with Crohns Disease (CD).
Therefore, several recent papers and guidelines suggested the need for dosing
IFX concentrations and anti-IFX antibodies in order to treat better CD patients.
To date, there are limited data on the role of Adalimumab (ADA) trough levels
and anti-ADA antibodies (AAA) for the management of CD patients.
AIMS & METHODS: We assessed the role of AAA on ADA trough levels,
TNF- concentrations, clinical biomarker (i.e. C-reactive protein) and clinical
outcome. In this prospective observational cohort study, performed at a single
tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66)] infliximab-na ve
patients with CD achieving disease remission and in maintenance treatment with
ADA were included and followed-up. Blood samples were drawn at standardized
time points (i.e. every 6 months or in case of CD relapse) just before ADA
injection. Trough ADA serum concentration and AAA were measured using
an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego,
United States). Blood samples were considered positive for AAA presence if
AAA were  1.7 U/mL and for ADA trough levels if ADA levels were  5
mg/ml. Disease activity was assessed at the same points by means of routine
biochemistry and the Harvey-Bradshaw Index (HBI, remission 55, mild disease
5-7, moderate disease 8-16, severe disease 416).
RESULTS: We have data from 189 blood samples. AAA were observed in 42/
189 (22.2%) samples, out of whom 16/42 (38.1%) had levels of AAA 1.7 U/mL.
ADA trough levels were found in 183/189 (96.8%) samples, out of whom 168/183
(91.8%) had a value of drug levels 5 mg/ml. Overall, 5/23 (21.7%) patients had
AAA and 22/23 (95.6%) were positive for ADA levels. Blood samples with AAA
had lower ADA trough levels [7.54 (0-26.49) vs. 9.45 (0.14-23.62); p 0.002] and
higher TNF- concentrations [5.9 (4.1-11.5) vs. 3.6 (0-27.2); p 0.0007] than
blood samples without evidence of AAA. Moreover, patients with blood samples
positive for AAA reported HBI values higher compared to patients without
evidence of AAA [10 (3-17) vs. 5 (2-17); p 50.0001]. Finally, no difference was
found in terms of mean PCR values between patients with AAA and those without [8.1 (3-76.4) vs. 5.2 (2.6-56); p 0.39].
CONCLUSION: Development and presence of AAA decreases ADA trough
levels and increases TNF- concentrations in blood samples from CD patients
on maintenance treatment with ADA, thus favoring clinical relapse in them as
demonstrated by the increased values of HBI scores recorded at the time of blood
sampling.
Disclosure of Interest: None declared
P0346 TNF-A LEVELS STRONGLY CORRELATED WITH DISEASE
ACTIVITY BASED ON HBI AND CDEIS IN PATIENTS WITH
CROHNS DISEASE IN MAINTENANCE TREATMENT WITH
ADALIMUMAB
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: In the last two decades the therapeutic paradigm of Crohns
disease (CD) has changed dramatically thanks to the use of biological drugs. In
this scenario, we must consider the pivotal role of tumor necrosis factor-alpha
(TNF-), a pro-inflammatory cytokine, in the pathogenesis and relapse of CD.
High levels of TNF- have been associated with the development of intestinal
inflammation in CD and blocking this cytokine with anti-TNF- molecules may
result in mucosal healing. In addition several studies have shown increased TNF levels in the serum and in the intestinal mucosa of patients with CD. However,
little is known about the course of TNF- levels and their relationship with
disease recurrence in CD patients during maintenance treatment with
Adalimumab.

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: We assessed TNF- levels in patients with CD who were
in maintenance treatment with ADA and correlated them with clinical and endoscopic disease activity. In this prospective observational cohort study, performed
at a single tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66) infliximab-na ve patients with CD in maintenance treatment with ADA were included
and followed-up. Blood samples were drawn at standardized time points (i.e.
every 6 months and in case of CD relapse) just before ADA injection.
Antibodies against ADA (AAA) were measured using an homogenous mobility
shift assay (HMSA; Prometheus Lab, San Diego, United States). Blood samples
were considered positive for AAA presence if 1.7 U/mL. Disease activity was
assessed at the same points by means of the Harvey-Bradshaw Index (HBI,
remission 55). Moreover, endoscopic activity was assessed at baseline and at
the time of relapse by means of CD endoscopic index (CDEIS; endoscopic remission 59).
RESULTS: We have data from 133 blood samples. AAA were observed in 26/
1339 (19.5%) samples, and 10/26 (38.5%) had a value of AAA 1.7 U/mL.
TNF- levels were present in all samples assessed [mean 4.4, range (0-27.2)].
Patients in clinical remission based on HBI had lower TNF- levels compared
to patients who relapsed [3.7 (0.2-20.2) vs. 5.6 (1.3-27.2); p 0.0002]. Similarly,
patients in endoscopic remission based on CDEIS had lower TNF- levels compared to patients who relapsed [3.1 (0.2-20.2) vs. 4.3 (1.3-27.2); p 0.0034]. Perpatient median TNF- levels were strongly correlated with median HBI scores
(r2 0.702, p50.0001). Moreover, TNF levels were also correlated with CDEIS
(r2 0.350, p 0.001).
CONCLUSION: TNF- levels strongly correlated with disease activity based on
HBI and CDEIS indices in patients with CD in maintenance treatment with
ADA. Indeed, moderate to severe patients often have high sustained TNF-
levels.
Disclosure of Interest: None declared
P0347 LONG-TERM OUTCOMES OF PATIENTS WITH ULCERATIVE
COLITIS TREATED WITH INFLIXIMAB
F.L. Roy1, L. Siproudhis1, C. Brochard1, V. Desfourneaux2, P.-N. DHalluin1,
M. Pagenault1, J.-F. Bretagne1, G. Bouguen1,3,*
1
Service des Maladies de lAppareil Digestif, 2Service de Chirurgie Viscerale, CHU
Pontchaillou, 3INSERM U991, Universite de Rennes 1, Rennes, France
INTRODUCTION: Data on the long-term efficacy of infliximab for the treatment of ulcerative colitis are scarce. Sustained remission, recurrence and outcomes after infliximab withdrawal beyond one year as well as predictors of longterm outcomes are unknown.
AIMS & METHODS: The medical records of all patients with ulcerative colitis
and treated with infliximab in a referral center between 2001 and 2012 were
reviewed through September 2013. The cumulative incidence of surgery, remission and recurrence with or without infliximab withdrawal were estimated using
the Kaplan-Meier method. Independent predictors of all outcomes were identified using a Cox proportional hazards model.
RESULTS: A total of 100 patients (63 males) with ulcerative colitis and treated
with at least one infliximab infusion were included. At infliximab initiation, 17%
of patients had severe acute colitis defined by the absence of response following
intravenous steroid and 56% of patients had pancolitis. Concomitant treatment
at infliximab initiation included steroids and immunosuppressants for 62% and
52% of patients, respectively. After a median follow-up of 55.1 months, the
cumulative probabilities of surgery were 27%, 33% and 36% at 1, 3 and 5
years, respectively. A CRP 4 6mg/L at week 6 was associated with colectomy
(HR 3.43, 95% CI, 1.17-10.9; p .023). Clinical remission was obtained in
64% of patients but almost half of the patients relapsed (28/64; 44%). Overall
the cumulative probabilities for sustained clinical remission were 19%, 31% and
38% at 1, 3 and 5 years, respectively. The absence of infliximab withdrawal was
the only factor independently associated with sustained clinical remission
(HR 4.6, 95% IC, 1.66-13.85; p 0.0029). Infliximab was withdrawn in 38 of
the 64 patients in clinical remission. After a median follow up of 54 months
following infliximab withdrawal, 10% (4/38) underwent colectomy, 63.2% (24/
38) patients relapsed, and 36.8% (14/38) remained in clinical remission. The
cumulative probabilities of relapse after IFX withdrawal at 1, 3 and 5 years
were 24%, 61% and 81%, respectively. A young age 5 21 years at UC diagnosis
(HR 12, 95% IC, 2.77-58.24; p 0.001) and platelets rate 4 400000/mm3 at
IFX withdrawal (HR 6.68, 95% IC 1.55-30.82; p 0.011) were associated with
relapse.
CONCLUSION: After a follow-up of almost 5 years, about one-third of patients
experienced sustained clinical remission and one-third of patients underwent
surgery. Most of the patients relapsed after infliximab withdrawal. These results
suggest early optimization of infliximab treatment to avoid dreaded outcomes
and to continue infliximab among responders to sustain remission.
Disclosure of Interest: None declared

A227

United European Gastroenterology Journal 2(1S)

MONDAY, OCTOBER 20, 2014


9:0017:00
PAEDIATRIC: LOWER GI POSTER EXHIBITION HALL XL_____________________
P0348 CORRELATION OF PROBE-BASED CONFOCAL LASER
ENDOMICROSCOPY FINDINGS IN THE DUODENUM AND
TERMINAL ILEUM OF PEDIATRIC INFLAMMATORY BOWEL
DISEASE PATIENTS, A PILOT STUDY
A.A. Shavrov1,*, A.Y. Kharitonova1, B. Claggett2, D.K. Brown3,
D.A. Morozov4, A.A. Shavrov1, J.J. Liu3
1
Endoscopy Department, The Scientific Center of Childrens Health Russian
Academy of Medical Sciences, Moscow, Russian Federation, 2Department of
Medicine, Brigham and Womens Hospital Harvard Medical School, Boston,
3
Division of Gastroenterology, University of Arkansas for Medical Sciences, Little
Rock, United States, 4Institute of Pediatric Surgery, The Scientific Center of
Childrens Health Russian Academy of Medical Sciences, Moscow, Russian
Federation
Contact E-mail Address: shavrovnczd@yandex.ru
INTRODUCTION: Studies over the past two decades have convincingly demonstrated the role of barrier dysfunction in the pathogenesis of inflammatory bowel
disease (IBD). We have previously found that optical biopsy with probe-based
confocal laser endomicroscopy (pCLE) could be used to assess mucosal barrier
function and predict disease relapse in pediatric IBD patients. The purpose of
this pilot study is to evaluate the correlation of pCLE findings between duodenal
and terminal ileum in pediatric IBD patients.
AIMS & METHODS: This is a prospective study of pediatric IBD (Crohns
disease - CD and ulcerative colitis-UC) patients undergoing pCLE during both
EGD and colonoscopy in a tertiary referral center. The barrier function was
assessed with the density of epithelial gaps on pCLE of the duodenum and
terminal ileum. Adequate imaging of the duodenum and terminal ileum were
defined as at least 3 normal, non-diseased areas sampled; a minimum of 3 villi
with the highest number of epithelial gaps were analyzed. The epithelial gap
density was calculated based on the total number of epithelial gaps observed
normalized per 1000 epithelial cells counted on adequately imaged villi.
RESULTS: A total of 13 IBD patients (9 CD, 4 UC) underwent EGD and
colonoscopy with adequate pCLE imaging of the duodenum and terminal
ileum in the study. There were 8 F (62%) and 5 M (38%) with a median age
of 15 yr (range 10 to 20). The median duration of disease at the time of pCLE was
3 yr (range 0 to 9); for therapy, 4 patients (31%) were on anti-TNF agents, 6
(46%) were on 5-ASA and/or immunomodulators, 1 (7%) were on steroids, 2
(15%) were on no therapy. The disease distributions for CD were: ileo-colitis in 7
patients (78%), ileitis in 1 (11%) and colitis 1 patients (11%). For UC: 1 patients
(25%) had pan-colitis, distal colitis in 2 (50%) and proximal colitis in 1 (25%).
The gap density (mean  SE) in the terminal ileum was 5.6  1.7 gaps/1000 cells,
while in the duodenum was 1.7  0.5 gaps/1000 cells. There were modest correlation between the gap density in the terminal ileum and duodenum with a spearman correlation coefficient of 0.42 (p 0.15)
CONCLUSION: In this pilot study of pediatric IBD patients, we found pCLE
findings of barrier function as measured by epithelial gap density in the terminal
ileum and duodenum had modest correlation. Future larger studies are warranted to further investigate the correlation of barrier function in the proximal
and distal intestine.
Disclosure of Interest: None declared
P0349 INCIDENCE OF PEDIATRIC INFLAMMATORY
DISEASE IN MINHO-PORTUGAL IS INCREASING

BOWEL

C.A. Machado1,*, I. Martinho2, C. Laranjeira3, M. Figueiredo4, C. Carvalho5,


A. Reis6, F. Pereira7, E. Trindade8, H. Antunes9,10
1
School of Health Sciences, University of Minho, Braga, 2Paediatrics Department,
Unidade Local de Saude do Alto Minho, Viana do Castelo, 3Paediatrics
Department, Centro Hospitalar do Alto Ave, Guimaraes, 4Paediatrics Department,
Centro Hospitalar do Medio Ave, Vila Nova de Famalicao, 5Paediatrics
Department, Hospital de Santa Maria Maior, Barcelos, 6Paediatrics, Centro
Hospital do Tamega e Sousa, Amarante, 7Paediatric Gastroenterology
Department, Centro Hospitalar do Porto, 8Paediatrics, Centro Hospitalar de Sao
Joao, Porto, 9Life and Health Sciences Research Institute (ICVS), School of
Health Sciences, ICVS/3Bs - PT Government Associate Laboratory, University of
Minho, Braga/Guimaraes, 10Gastroenterology, Hepatology and Nutrition Unit,
Paediatrics Department, Hospital de Braga, Braga, Portugal
Contact E-mail Address: caamachado@sapo.pt
INTRODUCTION: INTRODUCTION: Inflammatory bowel disease (IBD)
includes Crohns disease (CD), ulcerative colitis (UC) and indeterminate IBD
(IIBD). Although it primarily affects adults, the diagnosis in patients under 18
is about 25% to 30%, being CD the most frequent. Studies report an increase in
the incidence of CD, but a stable incidence of UC. A 2010 study in Minho reports
an incidence of 6.4/100000 (CD:66%; UC:34%).
AIMS & METHODS: Our aim was to characterize patients diagnosed with IBD
from 2002 to 2013, between the ages of 0 to 17 years and 365 days, residents in
Minho (districts of Braga and Viana do Castelo), calculate the incidence and
evaluate the health-related quality of life. We conducted a retrospective study, by
collecting information from the patients personal clinical chart. Also performed
was a cross-sectional study applying the IMPACT-III questionnaire that
assesses the quality of life of pediatric patients with IBD above 9 years old.
RESULTS: 137 subjects were found. The incidence in 2002-2013 was 5.0/100000
children-years (CD:66%, UC:32%, IIBD:2%), increasing from 2.4/100000
(CD:65%, UC:35%) in the first three years to 8.8/100000 (CD:75%, UC:23%,
IIBD:2%) in the last three (p 50.0001). Abdominal pain was the most frequent
symptom in CD and hematochezia in UC. In the IMPACT-III, the average
score was 136.5  19.2 (n 32), with a Cronbachs alpha 0.91.

CONCLUSION: There was a significant increase in the incidence of IBD, mainly


due to CD. The symptoms usually indicate the type of IBD, and again in pediatric cases, abdominal pain is more prevalent than diarrhea in the presentation of
CD. The quality of life seems to be similar to that found in other studies, still
showing good internal consistency of the IMPACT-III.
Disclosure of Interest: None declared
P0350 CUMULATIVE INCIDENCE AND ASSOCIATED FACTORS OF
MUCO-CUTANEOUS MANIFESTATIONS IN PAEDIATRIC-ONSET
CROHNS DISEASE: A POPULATION-BASED STUDY
C. Templier1,*, H. Sarter2, D. Turck3, M. Fumery4, G. Savoye5, B. Catteau1,
C. Spyckerelle6, E. Laberenne7, O. Mouterde8, D. Djeddi9, S. Buche1, L. PeyrinBiroulet10, E. Delaporte1, C. Gower-Rousseau2 on behalf of Epimad Group
1
Dermatology, 2Epidemiology, 3Paediatric Clinic, UNIVERSITY AND
HOSPITAL LILLE, Lille, 4Gastroenterology, University and Hopsital, Amiens,
5
Gastroenterology, University and Hopsital, Rouen, 6Paediatric Clinic, Catholic
University, Lille, 7Gastroenterology, General Hospital, Seclin, 8Paediatric Clinic,
University and Hopsital, Rouen, 9Paediatric Clinic, University and Hopsital,
Amiens, 10Gastroenterology, University and Hopsital, Nancy, France
Contact E-mail Address: corinne.gower@gmail.com
INTRODUCTION: Muco-cutaneous manifestations (MCM) are common in
adult patients with Crohns disease (CD), but their frequency in paediatriconset CD is unknown.
AIMS & METHODS: The aims of our study were in a population-based paediatric-onset CD cohort: i) to determine the cumulative incidence of MCM, including aphtous stomatis (AS), erythema nodosum (EN) and pyoderma gangrenosum
(PG); and ii) to identify the socio demographic and clinical factors at CD diagnosis associated with a higher risk of developing MCM during the CD course.
Patients and Methods: Clinical data at diagnosis and at maximal follow-up were
recorded in a population-based paediatric-onset CD cohort (n 537, 517 years
at CD diagnosis) diagnosed from 1988 to 2004. Data on MCM were reviewed by
a dermatologist. Risks of developing MCM were estimated by survival analysis
and Cox models.
RESULTS: Median age at CD diagnosis was 14.6 years (Q1 12.2; Q3 16.1)
and 53.6% of patients were males. At CD diagnosis, 87 patients (16.2%) had
MCM including 26 of them (30%) with at least 2 MCM. After a median followup of 11 years (Q1 7; Q3 15), 148 patients (28%) developed a total of 175
MCM, including 110 (63%) AS, 59 (34%) EN, and 6 (3%) PG. Cumulative
incidence of developing MCM was 21% [17.7 -24.6], 25% [21.6-29.0], 27%
[23.5-31.2] and 28% [24.3-32.3] at 1, 5, 10 and 15 years, respectively. In multivariate analysis, female gender (HR 2.6 [1.4-4.6]; p 0.002), patients 515 years
at diagnosis (HR 2.2 [1.3-3.8]; p 0.003) and L4 location at diagnosis
(HR 2.2 [1.3-3.6]; p 0.002) were significantly associated with a higher risk
of developing MCM during the CD course.
CONCLUSION: In this population-based paediatric-onset CD cohort, MCM
are frequent both at diagnosis and during CD course, and are associated to
female gender, young age and L4 location at CD diagnosis. These results reinforce the need of a close collaboration between dermatologists, paediatric gastroenterologists and gastroenterologists in paediatric-onset CD in order to optimize
the therapeutic management of these patients.
Disclosure of Interest: C. Templier: None declared, H. Sarter: None declared, D.
Turck: None declared, M. Fumery: None declared, G. Savoye: None declared, B.
Catteau: None declared, C. Spyckerelle: None declared, E. Laberenne: None
declared, O. Mouterde: None declared, D. Djeddi: None declared, S. Buche:
None declared, L. Peyrin-Biroulet: None declared, E. Delaporte: None declared,
C. Gower-Rousseau Lecture fee(s) from: Ferring, MSD
P0351 LONG-TERM EFFICACY OF ADALIMUMAB IN PAEDIATRIC
PATIENTS WITH CROHNS DISEASE
W.A. Faubion1, M. Dubinsky2, F. Ruemmele3,*, J. Escher4, J. Rosh5, A. Lazar6,
S. Eichner7, Y. Li7, N. Reilly7, R.B. Thakkar7
1
Mayo Clinic, Rochester, 2Cedars-Sinai Medical Center, Los Angeles, United
States, 3Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, Paris,
France, 4Erasmus MC-Sophia Childrens Hospital, Rotterdam, Netherlands,
5
Goryeb Childrens Hospital/Atlantic Health, Morristown, United States, 6AbbVie
Deutschland GmbH & Co. KG, Ludwigshafen, Germany, 7AbbVie Inc, North
Chicago, United States
INTRODUCTION: The efficacy of adalimumab (ADA) in children with moderately to severely active Crohns disease enrolled in the IMAgINE 1 trial has
been reported up to week (wk) 521. Long-term efficacy of ADA in patients (pts)
enrolled in the on-going open-label (OL) extension, IMAgINE 2, is presented.
AIMS & METHODS: Pts who completed IMAgINE 1 through wk 52 were
allowed to enroll in IMAgINE 2. Pts entering from blinded therapy received
OL ADA according to body weight (40 kg: 40 mg ADA every other wk
[EOW]; 540 kg, 20 mg ADA EOW). At or after wk 8, pts experiencing flares
(increase in PCDAI 15 points compared to PCDAI at previous visit) could
move to wkly (EW) dosing. Pts entering IMAgINE 2 from OL ADA (40 mg
ADA or 20 mg ADA EW) continued to receive the same dose. Remission
(PCDAI10) and response (PCDAI decrease 15 points from IMAgINE 1 baseline) over time were assessed in pts who entered IMAgINE 2. Missing data were
handled using non-responder imputation (NRI) and last observation carried
forward (LOCF). Endpoints are also reported as observed. A data cut-off of
Jun 30, 2013 was used for this analysis.
RESULTS: Of the 188 randomized pts in IMAgINE 1, a total of 100 pts enrolled
in IMAgINE 2. As of Jun 30, 2013, a total of 54 pts are ongoing in the study.
Approximately 2/3 of pts entered IMAgINE 2 in remission and almost all entered
with response (67% and 95%, respectively). Observed remission and response

A228

United European Gastroenterology Journal 2(1S)

rates remained stable over time during IMAgINE 2 (Table). Mean PCDAI scores
decreased from 40.1 at IMAgINE 1 baseline to 8.6 at wk 192 of IMAgINE 2
(Table). Adverse event rates from IMAgINE 1 baseline up to wk 260 have been
previously reported and no new safety signals were observed with prolonged
ADA use.2
Table. Rates of remission and response and observed mean PCDAI scores during
IMAgINE 2
Week
Remission (%)
NRI
LOCF
Observed
Response (%)
NRI
LOCF
Observed
Mean PCDAI

24

48

72

96

120

144

168

192

67.0
67.0
67.0

59.0
62.2
62.8

55.0
61.2
66.3

50.0
57.1
64.1

54.0
61.2
70.1

51.0
62.2
73.9

51.0
63.3
79.7

42.0
62.2
79.2

26.0
61.2
81.3

95.0
95.0
95.0
10.2

88.0
91.8
93.6
10.3

75.0
85.7
90.4
9.2

74.0
87.8
94.9
8.9

72.0
85.7
93.5
9.4

66.0
85.7
95.7
7.9

64.0
87.8
100
6.1

48.0
82.7
90.6
7.5

29.0
81.6
90.6
8.6

The number of pts declined over time due to discontinuations and not all pts had
reached later time points. Results after wk 192 are not shown as few pts had
reached longer study durations.
CONCLUSION: Results of the on-going OL study support clinically meaningful
efficacy with long-term ADA therapy beyond four years of exposure in children
with moderately to severely active CD.
REFERENCES
1. Hyams et al. Gastroenterol 2012; 143: 365-374.
2. Rosh et al. J Crohns Colitis 2014; 8: S243.
Disclosure of Interest: W. Faubion Consultancy for: Genentech, Connecticut
Childrens Medical Center - Safety officer on subcontracted award through
NIH for clinical trial, Other: Board membership (no personal compensation):
Shire Development, Inc - Pediatric UC Advisory Board, Janssen Services LLC DEVELOP Registry Scientific Advisory Committee, UCB Biosciences Advisory
board, M. Dubinsky Financial support for research from: Janssen, Consultancy
for: AbbVie, Janssen, Takeda, Pfizer, Prometheus labs, Santarus, UCB, F.
Ruemmele Lecture fee(s) from: Shering-Plough, Nestle, MeadJohnson, Ferring,
MSD, Johnson & Johnson, Centocor, Other: Board membership:
SAC:DEVELOP (Johnson & Johnson), invited to MSD France, Nestle
Nutrition Institute, invited to Nestle Health Science, invited to Danone, invited
to MeadJohnson, Biocodex, J. Escher Financial support for research from:
MSD, Lecture fee(s) from: MSD, Consultancy for: Janssen Biologics, Other:
Board membership: scientific advisory committee of DEVELOP study (Janssen
Biologics), J. Rosh Financial support for research from: AstraZeneca, AbbVie,
Janssen, UCB, Lecture fee(s) from: Abbott Nutrition, Prometheus, Consultancy
for: AbbVie, Janssen, Soligenex, Other: Board membership: GI Health
Foundation, A. Lazar Shareholder of: AbbVie, Other: Employee: AbbVie, S.
Eichner Shareholder of: AbbVie, Other: Employee: AbbVie, Y. Li Shareholder
of: AbbVie, Other: Employee: AbbVie, N. Reilly Shareholder of: AbbVie, Other:
Employee: AbbVie, R. Thakkar Shareholder of: AbbVie, Other: Employee:
AbbVie
P0352 LONG-TERM SUSTAINED RESPONSE AND DURABILITY OF
INFLIXIMAB FOR THE PEDIATRIC INFLAMMATORY BOWEL
DISEASE IN KOREA
H.-J. JANG1,*, J.S. MOON1, J. YOO1, P. CHUN1, J.S. KO1, H.R. YANG2,
J.Y. JANG3, J.K. SEO1
1
Department of Pediatrics, Seoul National University College of Medicine,
2
Department of Pediatrics, Seoul National University Bundang Hospital,
3
Department of Pediatrics, SMG-SNU Boramae Medical Center, SEOUL, Korea,
Republic Of
Contact E-mail Address: bearinspring@hotmail.com, mjschj@snu.ac.kr
INTRODUCTION: Inflammatory bowel disease (IBD) is increasing in Korea,
especially in the pediatric population. Along with the classical treatment of 5ASA, steroid, and immunomodulators, biologic agents such as infliximab (IFX),
adalimumab are used increasingly. However, the safety and efficacy of IFX has
not been evaluated much for long-term follow-up.
AIMS & METHODS: This is a single-center retrospective cohort study of 100
pediatric IBD (Crohn disease 90, Ulcerative colitis 10) who used infliximab from
2004 to 2014. The total duration of IFX administration, the dose intensification
(DI), the sustainability and efficacy of DI, and immunomodulator use with or
without IFX were analyzed. We also analyzed 3 groups to assess the efficacy and
durability of IFX into sustained remission, recaptured response, and treatment
failure group. Recaptured response meant the patients who recaptured remission
by dose intensification.
RESULTS: The total duration of follow-up for patients was 61.746.6 months.
The mean duration of IFX administration was 31.028.0 months. Average age
of IFX initiation was 14.13.3 years. The interval between IFX initiation and
dose intensification was 23.423.3 months. Dose intensification was in 53
patients out of 100 for the study period. Sustained remission was in 44 patients
out of total and recaptured response was in 42, respectively. Treatment failure
was 16 out of 100, who discontinued IFX eventually. We checked for sustained
remission rate annually and the rate was declining over time with 46% at 12-24
months, 41% at 24-36 months, and 40% at 36-48 months, respectively.
CONCLUSION: This study shows that almost half of the patients with IFX
maintained sustained remission until 2-year follow-up. And recapture rate was

75% for DI, which means high response of treatment efficacy for IFX dose-up.
Further study about DI will be needed for the risk factors, for optimal timing of
application in clinical course, and for any possible adverse events in long-term
follow-up.
Disclosure of Interest: None declared
P0353 FOCUSED EDUCATION AND VACCINE ACCESS IN CLINIC
IMPROVE INFLUENZA VACCINATION RATES IN CHILDREN
WITH INFLAMMATORY BOWEL DISEASE
K. Huth1,*, E. Benchimol2, D. Mack2
Pediatrics, University of Ottawa, 2Gastroenterology, Hepatology & Nutrition,
Childrens Hospital of Eastern Ontario, Ottawa, Canada
Contact E-mail Address: khuth@cheo.on.ca

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at


increased risk of experiencing complications of influenza infection, thus international guidelines recommend annual influenza vaccination for this population.
The vaccine is available at no cost in primary care physician offices, walk-in
clinics and pharmacies in Ontario, Canada, yet vaccine uptake remains low.
AIMS & METHODS: We sought to understand barriers to obtaining influenza
vaccination in a pediatric IBD cohort, and to determine the impact of educational intervention and vaccine provision in IBD clinic on vaccine uptake. The
study was completed over two successive influenza seasons. During the 20122013 season (Year 1), we surveyed parents and IBD patients aged 14 years
regarding influenza vaccination attitudes and practices. The following year
(Year 2), an educational module was developed to address concerns about vaccination identified in Year 1. Parents and patients presenting to IBD clinic in the
ten weeks prior to the 2013-2014 influenza season were provided with the educational module (Phase 1). When the trivalent inactivated influenza vaccine (TIIV)
became available, patients were offered both the educational module and the
opportunity for vaccination during their IBD clinic visits (Phase 2). Chi-squared
analysis was used to identify significant differences in vaccination rates in each
intervention group. Demographic factors were associated with survey responses
and vaccination status.
RESULTS: During Year 1, 180 of 183 parents (98%) completed the survey along
with all 108 adolescents. Median patient age at time of study was 11 years, 63%
were males, and 67% had Crohns disease. Most patients (74%) were on immunomodulator or biologic medications. In Year 1, 47% of patients obtained the
TIIV, and 34% of patients reported obtaining the vaccine annually. Reasons for
non-vaccination included a perceived lack of benefit (29%) and concerns about
adverse events (20%). Most families (91%) reported they would obtain influenza
vaccination if their physician provided evidence of its benefit. Year 2 patients
(n 228) did not differ significantly in age, IBD subtype, disease severity or
medications from Year 1 patients. 95% of patients and parents who reviewed
the educational module reported that it was useful. 71% reported that the
module informed their decision to obtain the TIIV, including 19% who had
not planned to obtain the TIIV prior to reviewing the module. In Year 2, the
vaccination rate in Phase 1 patients who received the educational module alone
was 75%, compared to 89% of Phase 2 patients who received both the educational module and the option of obtaining the TIIV in IBD clinic (p 0.0043).
Amongst the patients who took part in both Year 1 and Year 2 (n 129), serial
determinations of influenza vaccination rates demonstrated an increase from
45% to 82% (P50.0001).
CONCLUSION: Despite widespread access to the TIIV at no cost, traditional
methods of promoting vaccination have yielded low uptake in IBD patients.
Providing a focused educational module on efficacy and safety addressed barriers
faced by vaccine-hesitant families and improved influenza vaccination rates.
Additional vaccine uptake can be achieved by combining educational intervention with provision of influenza vaccination during IBD clinic visits.
Disclosure of Interest: None declared
P0354 ACCUMULATION OF INTRA-ABDOMINAL ADIPOSE TISSUE IN
PEDIATRIC CROHNS DISEASE
K. Frivolt1,2,*, H. Hetterich3, T. Schwerd1, M.S. Hajji1, P. Bufler1,
E. Coppenrath3, S. Koletzko1
1
Dr. v. Hauner Childrens Hospital, University Munich Medical Center, Munich,
Germany, 22nd Department of Pediatrics, Comenius University Medical School,
Bratislava, Slovakia, 3Institute of Clinical Radiology, University Munich Medical
Center, Munich, Germany
Contact E-mail Address: klarato@gmail.com
INTRODUCTION: Increased visceral adipose tissue (VAT) inflammation is a
characteristic hallmark of surgical resections from Crohns disease (CD) patients.
Recent evidence points towards an active immunological role of VAT in CD
pathogenesis in addition of VAT being a defense mechanism for bacterial translocation during intestinal inflammation. Magnetic resonance imaging (MRI)
studies showed accumulation of intra-abdominal VAT in adults, especially in
patients with fistulas and strictures.
AIMS & METHODS: We aimed to quantify the abdominal adipose tissue compartments using MRI (Achieva, Philips Healthcare, Hamburg, Germany) in 29
pediatric CD patients compared with 14 control children (CC) undergoing MRI
examination of abdomen for other reason. Total abdominal (TA) adipose tissue,
consisting of subcutaneous (SC) and intra-abdominal (IA) adipose tissues were
retrospectively measured by a radiologist blinded to the clinical data in transverse
slices centered on the umbilicus and expressed as mean  standard deviation in
cm2. IA/TA and IA/height ratios were assessed and analyzed for association
markers. We recorded the mathematically weighted Pediatric Crohns Disease
Activity Index (wPCDAI), disease phenotype, laboratory and anthropometric
data at the time of MRI. Mann-Whitney test was applied to analyze differences

United European Gastroenterology Journal 2(1S)


between patients and CC. The correlation significance was determined by means
of Spearman correlation analysis. P50.05 was considered statistically significant.
RESULTS: CD patients included 20 males and 9 females (mean age 14.8  3.6
years, range 7.7-18.3) with a mean BMI of 18.3  2.7, range 14.0-23.2. Median
disease duration from diagnosis to MRI was 21 months (range 0-136). Noncomplicated disease behavior (B1) was present in 25/29, 4/29 had stricturing
(B2) and 6/29 perianal disease. CC included 4 males and 10 females (mean age
12.8  4.5 years, range 3.0-18.0), BMI (mean 17.6  3.2, range 13.4-23.6). CD
patients had higher IA adipose tissue (41.720.3 vs. 28.711.6, p50.05) but
similar SC and TA adipose tissues compared to CC (104.4  70.9 vs. 96.54 
50.8 and 146.1  84.7 vs. 125.3  61.5, NS). The IA/TA and IA/height ratios
were significantly higher in CD patients compared to CC, respectively (0.310.10
vs. 0.240.04 and 25.912.7 vs. 18.47.8, p50.05). Patients with disease duration under 2 years (n 14) had lower IA/TA ratio (0.280.08 vs. 0.350.10,
p50.05) compared to longer disease. The IA/TA ratio correlated with disease
duration (p50.05, r 0.425). No association was found between IA/TA and IA/
height ratios and disease phenotype or therapy.
CONCLUSION: Intra-abdominal adipose tissue is increased and accumulates
with disease duration in pediatric-onset CD.
Disclosure of Interest: None declared
P0355 PHARMACOKINETICS AND SAFETY OF MULTIMATRIX
MESALAZINE IN CHILDREN AND ADOLESCENTS WITH
ULCERATIVE COLITIS
C. Cuffari1, D. Pierce2, B. Korczowski3, K. Fyderek4,*, H.Van Heusen5,
S. Hossack6, P. Martin5
1
The Johns Hopkins University School of Medicine, Division of Pediatric
Gastroenterology and Nutrition, Baltimore, MD, United States, 2Shire,
Basingstoke, United Kingdom, 3Medical College, University of Rzeszow, Rzeszow,
4
University Childrens Hospital of Cracow, Cracow, Poland, 5Shire, Wayne, PA,
United States, 6Covance Clinical Research Unit Limited, Leeds, United Kingdom
Contact E-mail Address: pmartin@shire.com
INTRODUCTION: Oral formulations of mesalazine (5-aminosalicylic acid; 5ASA) are recommended first-line therapy for adults with active mild-to-moderate
ulcerative colitis (UC). However, little data are available on the use of mesalazine
in paediatric UC. This phase 1, multicenter, randomized, open-label study
(NCT01130844) evaluated the pharmacokinetic and safety characteristics of 5ASA and its associated metabolite, acetyl-5-ASA (Ac-5-ASA), after once-daily
administration of multimatrix mesalazine to children and adolescents with UC.
AIMS & METHODS: Patients aged 5-17 years with a UC diagnosis of 3
months were eligible to enrol. Study participants (stratified by body weight)
were administered 30, 60, or 100 mg/kg/day multimatrix mesalazine once-daily
for 7 days. In order to attain these doses in children, smaller-sized 300 mg and
600 mg multimatrix mesalazine tablets were developed to supplement the existing
approved 1200 mg tablet. Mesalazine was administered to patients at home on
Days 1-4 and on-site on Days 5-7, during which pharmacokinetic blood and
urine samples were collected and safety evaluations performed. Plasma and
urine concentrations of 5-ASA and Ac-5-ASA were determined using a validated
LC/MS/MS assay. Derived pharmacokinetic parameters for assessment included
maximum concentration (Cmax, ss), time of Cmax, ss (tmax), area under the curve
for one dose interval (AUCss), renal clearance (CL5SUB4R5/SUB4), and
percent of dose absorbed.
RESULTS: A total of 52 patients (21 at 30 mg/kg; 22 at 60 mg/kg; and 9 at 100
mg/kg) were treated. Mean (standard deviation) age was 13.3 (3.06) years, and
median (range) time since UC diagnosis was of 1.83 (0.2- 9.6) years. By Day 5,
steady state plasma concentrations for 5-ASA and Ac-5-ASA were attained for
all dose groups. On Day 7, dose-proportional increases in mean AUCss and Cmax,
ss for both 5-ASA and Ac-5-ASA were observed between 30 and 60 mg/kg/day
cohorts. For 30, 60, and 100 mg/kg/day doses, the mean percentages of 5-ASA
absorbed from multimatrix mesalazine were 29.4%, 27.0%, and 22.1%, respectively. The mean CLR ranges for 5-ASA and Ac-5-ASA, respectively, were 5.06.5 L/h and 10.0-16.2 L/h. Treatment-emergent adverse events were reported by
19.2% of all patients; events were similar among different dose and age groups
and no new safety signals were identified.
CONCLUSION: Across all dose groups, children/adolescents with UC receiving
multimatrix mesalazine demonstrated pharmacokinetic profiles for 5-ASA and
Ac-5-ASA similar to those observed in historical adult data. Multimatrix mesalazine was well tolerated across all dose and age groups, and no novel safety
signals were reported.
Disclosure of Interest: C. Cuffari Consultancy for: Shire, Prometheus and Abbott
Nutritionals, D. Pierce Shareholder of: Shire, Other: Former employee of Shire,
B. Korczowski: None declared, K. Fyderek Financial support for research from:
Received a grant from Shire for the study research conducted, H. Van Heusen
Shareholder of: Shire, Other: Employee of Shire, S. Hossack Other: Employee of
Covance, which received funding from Shire for assistance with the pharmacokinetic analysis, P. Martin Shareholder of: Shire, Other: Employee of Shire
P0356 DEVELOPMENT OF THE DAILY ULCERATIVE COLITIS SCALE
FOR CHILDREN AND CAREGIVERS: FINDINGS FROM COGNITIVE
DEBRIEFING INTERVIEWS
E. Flood1, D.G. Silberg2, B. Romero1, K. Beusterien3, M.H. Erder2,*
1
ICON Commercialisation and Outcomes, Bethesda, MD, 2Shire, Wayne, PA,
3
ORS Health, Washington, DC, United States
Contact E-mail Address: herder@shire.com
INTRODUCTION: To test and refine the Daily Ulcerative Colitis Scale
(DUCS), an electronic daily sign and symptom diary with a patient-reported

A229
outcomes (PRO) version for children 8-17 years and an observer-reported outcomes (ObsRO) version for caregivers of children aged 5-10 years.
AIMS & METHODS: This was a twovisit cognitive debriefing interview study
involving children with mild to moderate ulcerative colitis (UC) aged 8-17 years
and caregivers of children aged 5-10 years. Mild to Moderate UC was
defined based on the Pediatric Ulcerative Colitis Activity Index (PUCAI) score
at the time of the interview. The interviews involved an initial set of open-ended
questions on the signs, symptoms and impacts of UC to confirm findings from a
previous concept elicitation study, followed by cognitive debriefing of the DUCS
along with items to assess global health, and items to examine device usability
and characteristics of the sample. The visit 1 interview was held in person and
lasted approximately 1 hour. Visit 2 took place by telephone 3 days after visit 1
and lasted about 25 minutes and was used to explore feasibility. Sample characteristics were analysed using descriptive statistics (mean, SD, median, range for
continuous variables and N, % for categorical variables). Interview transcripts
were analysed using qualitative analysis software, MAXqda, in which codes were
applied to allow focussed review of responses across the sample. Findings were
used to refine the DUCS to ensure clarity, relevance and comprehensiveness.
RESULTS: The PRO sample consisted of 38 participants (22 females and 16
males), with 2 participants completing interviews for 2 different diary versions for
a total of 40 completed interviews. Age at study enrollment ranged from 8 to 17
years (mean of 12.8; SD 2.4; median of 13). The average PUCAI score, administered at visit 1, was 12.3 (SD 14.2), range 0 to 45. The caregivers of 7 children
participated in the cognitive debriefing interviews of the ObsRO version. One
caregiver tested two different versions of the eDiary for a total of 8 completed
ObsRO interviews. The average age of the 7 caregiver participants was 41.5 years
(SD 6.4; median of 42). The caregivers children were an average age of 8.5 years
(SD 1.7; median of 9). Findings from the visit 1 concept elicitation questions were
consistent with those of the initial concept elicitation study. Four rounds of
revisions were made to the PRO and ObsRO DUCS based on patient/caregiver
interview feedback, as well as feedback from the FDA. The FDA suggested
changes such as changing response scales, as well as the addition of questions
to capture certain symptoms overnight. Patient input influenced changes such as
clarification of text and graphics, and the selection of the optimal pain scale. The
eDiarys usability was also assessed. Both child and adult participants found the
device easy to use and navigate.
CONCLUSION: The DUCS eDiaries are content valid instruments capturing
signs and symptoms of pediatric UC and are appropriate for measuring treatment benefit in pediatric UC clinical trials.
Disclosure of Interest: E. Flood Other: Employee of ICON, which was contracted
by Shire to perform the research for the creation of the DUCS, D. Silberg
Shareholder of: Shire, Other: Employee of Shire, B. Romero Other: Employee
of ICON, which was contracted by Shire to perform the research for the creation
of the DUCS, K. Beusterien Other: Performed this work when she worked at
Oxford Outcomes, which provides consulting services to Shire, M. H. Erder
Shareholder of: Shire, Other: Employee of Shire
P0357 AORTIC INTIMA-MEDIA THICKNESS AS AN EARLY MARKER
OF ATHEROSCLEROSIS IN CHILDREN WITH INFLAMMATORY
BOWEL DISEASE
M. Aloi1,*, L. Tromba2, V. Rizzo1, G. DArcangelo1, A. Dilillo1, S. Blasi2,
F. Civitelli1, F. Viola1, A. Redled2, S. Cucchiara1
1
Pediatric Gastroenterology And Liver Unit, 2Department of Surgical Sciences,
SAPIENZA UNIVERSITY OF ROME, Rome, Italy
Contact E-mail Address: marina.aloi@uniroma1.it
INTRODUCTION: Aims of this study were to determine the presence of
endothelial dysfunction by measuring aortic intima-media thickness (aIMT)
and carotid intima-media thickness (cIMT) and to evaluate the role of traditional
risk factors for premature atherosclerosis in children with inflammatory bowel
disease (IBD).
AIMS & METHODS: Thirty-four children with IBD [25 Crohns disease (CD)
and 9 ulcerative colitis (UC); mean age 11.1 years] and 27 healthy subjects
matched for sex and age were enrolled. In all patients, demographic characteristics and risk factors for atherosclerosis (age, sex, body mass index, blood pressure, dyslipidemia, active and passive smoking, family history for cardiovascular
diseases), CD and UC clinical activity scores and inflammatory markers, were
evaluated. Aortic IMT and cIMT were measured by high resolution B-mode
ultrasound.
RESULTS: Aortic IMT was significantly higher in patients than controls
(p50.001). No significant differences were found for cIMT, although the carotid
thickness was higher in IBD patients than healthy subjects. At a univariate
analysis, inflammatory markers levels and tobacco smoking exposure were significantly related to higher aIMT values, while at a multivariate analysis the
inflammatory status was the only independent variable correlated with high
aIMT.
CONCLUSION: Aortic IMT is an earlier marker of preclinical atherosclerosis in
young children with active IBD, than cIMT. The inflammatory status and the
smoking exposure are significantly correlated with the premature endothelial
dysfunction. These data emphasize the importance of controlling the chronic
intestinal inflammation and endorsing smoke-free environments for children
and adolescents with IBD
Disclosure of Interest: None declared

A230

United European Gastroenterology Journal 2(1S)

P0358 GROWTH IMPROVEMENT IN ADALIMUMAB-TREATED


PAEDIATRIC PATIENTS WITH CROHNS DISEASE: DATA FROM
IMAGINE 1
T. Walters1,*, W.A. Faubion2, A. Griffiths1, R. Baldassano3, J. Escher4,
F. Ruemmele5, J.S. Hyams6, A. Lazar7, S. Eichner8, Y. Li8, B. Pappalardo8,
R.B. Thakkar8
1
The Hospital for Sick Children, Toronto, Canada, 2Mayo Clinic, Rochester,
3
Childrens Hospital of Philadelphia, Philadelphia, United States, 4Erasmus MCSophia Childrens Hospital, Rotterdam, Netherlands, 5Universite Sorbonne ParisCite, Hospital Necker-Enfants Malades, Paris, France, 6Connecticut Childrens
Medical Center, Hartford, United States, 7AbbVie Deutschland GmbH & Co. KG,
Ludwigshafen, Germany, 8AbbVie Inc, North Chicago, United States
INTRODUCTION: Children with Crohns disease (CD) often have impaired
growth. The IMAgINE 1 trial demonstrated the safety and effectiveness of adalimumab (ADA) on inducing and maintaining remission in children with moderately to severely active CD1. The impact of ADA therapy on growth in patients
with delayed growth at trial entry is analyzed.
AIMS & METHODS: In IMAGINE 1, patients aged 6-17 years with baseline
(BL) PCDAI 430 received open-label induction of ADA at weeks 0/2 according
to body weight (40kg, 160/80mg; 540kg, 80/40mg). At week 4, patients were
randomized to double-blind higher-dose (HD) ADA (40kg, 40mg every other
week [EOW]; 540kg, 20mg EOW) or lower-dose (LD) ADA (40kg, 20mg
EOW; 540kg, 10mg EOW) to week 52. Patients were allowed to escalate to
blinded weekly therapy for flare or non-response, followed by open-label HD
ADA weekly for continued flare or non-response. Change from BL in height
velocity z-score was measured at weeks 26 and 52 in patients with and without
growth delay at BL (defined as height velocity z-score  -1.0) in all ADA patients
regardless of treatment group. Subgroup analyses by BL corticosteroid use, disease severity (based on median BL PCDAI of study population (PCDAI 5 40,
moderate CD; PCDAI  40, severe CD), and prior infliximab (IFX) use were
performed.
RESULTS: Overall, statistically significant improvement in growth was observed
at weeks 26 and 52 with ADA maintenance therapy in patients with growth delay
(median height velocity z-score at BL -2.9 and median change from BL at weeks
26 and 52; 2.4 and 3.3, respectively, each p50.001), but not in patients with
normal growth (BL median 0.2; median change from BL 0 at weeks 26 and
52). No statistically significant differences between LD and HD ADA were
observed. Growth improvement trended to be larger in patients with BL corticosteroid use, with severe CD, and in IFX na ve patients (Table).
Table. Median BL height velocity z-score values and change from BL at weeks 26
and 52 in patients with growth delay (height velocity z-score  -1.0 at BL)
BL
LD
HD
IFX na ve
IFX experienced
Corticosteroid use at BL
No corticosteroid use at BL
Moderate CD
Severe CD

-3.0
-2.8
-3.1
-2.3
-2.8
-2.9
-3.2
-2.7

(N 47)
(N 42)
(N 54)
(N 35)
(N 38)
(N 51)
(N 26)
(N 63)

Week 26

Week 52

2.5*
2.3*
2.7*
1.7*
2.5*
2.3*
2.7*
2.3*

3.4*
3.3*
3.8*
1.4*
4.3*
2.3*
3.0*
3.8*

(N 47)
(N 42)
(N 54)
(N 35)
(N 38)
(N 51)
(N 26)
(N 63)

(N 30)
(N 29)
(N 41)
(N 18)
(N 23)
(N 36)
(N 22)
(N 37)

CONCLUSION: ADA treatment significantly improved growth in children with


moderately to severely active CD and growth delay. The pronounced effect of
ADA on growth in children with concomitant corticosteroid use or severe disease
by PCDAI requires confirmatory studies.
REFERENCES
1. Hyams et al. Gastroenterol 2012; 143: 365-374.
Disclosure of Interest: T. Walters Financial support for research from: AbbVie,
Janssen, Merck, Lecture fee(s) from: AbbVie, Janssen, Merck, W. Faubion
Consultancy for: Genentech, Connecticut Childrens Medical Center - Safety
officer on subcontracted award through NIH for clinical trial, Other: Board
membership (no personal compensation): Shire Development, Inc - Pediatric
UC Advisory Board, Janssen Services LLC - DEVELOP Registry Scientific
Advisory Committee, UCB Biosciences Advisory board, A. Griffiths Financial
support for research from: Johnson and Johnson, Abbvie, Lecture fee(s) from:
AbbVie, Consultancy for: Abbvie, Nutricia, Janssen Canada, MSD, Ferring,
Shire, Other: Educational program support: Abbvie; Janssen Canada, R.
Baldassano Consultancy for: AbbVie, Janssen Ortho Biotech, Takeda, J.
Escher Financial support for research from: MSD, Lecture fee(s) from: MSD,
Consultancy for: Janssen Biologics, Other: Board membership: scientific advisory committee of DEVELOP study (Janssen Biologics), F. Ruemmele Lecture
fee(s) from: Shering-Plough, Nestle, MeadJohnson, Ferring, MSD, Johnson &
Johnson, Centocor, Other: Board membership: SAC:DEVELOP (Johnson &
Johnson), invited to MSD France, Nestle Nutrition Institute, invited to Nestle
Health Science, invited to Danone, invited to MeadJohnson, Biocodex, J. Hyams
Lecture fee(s) from: Janssen Orthobiotech, Consultancy for: Janssen
Orthobiotech, AbbVie, TNI Biotech, EnteraHealth, Pfizer, Soligenix, Takeda,
Other: Expert testimony and payment for development of educational presentations: Janssen Orthobiotech, A. Lazar Shareholder of: AbbVie, Other: Employee:
AbbVie, S. Eichner Shareholder of: AbbVie, Other: Employee: AbbVie, Y. Li
Shareholder of: AbbVie, Other: Employee: AbbVie, B. Pappalardo Shareholder
of: AbbVie, Other: Employee: AbbVie, R. Thakkar Shareholder of: AbbVie,
Other: Employee: AbbVie

P0359 TREATMENT OF CORTICOSTEROID NAIVE PAEDIATRIC AND


ADOLESCENT PATIENTS WITH ULCERATIVE COLITIS BY
THERAPEUTIC DEPLETION OF MYELOID LINEAGE
LEUCOCYTES AS MONOTHERAPY OR IN COMBINATION WITH
LOW DOSE PREDNISOLONE AFTER FAILURE OF FIRST-LINE
MEDICATIONS
T. Tanaka1,*, S. Sugiyama1, H. Goishi 1, T. Kajihara1, M. Akagi 1, T. Miura1
Department of Gastroenterology, Akitsu Prefectural Hospital, Hiroshima, Japan
Contact E-mail Address: tomotaka@c.do-up.com
1

INTRODUCTION: Given that patients with active ulcerative colitis (UC) have
elevated and activated myeloid lineage leucocytes including the CD14CD16
monocyte phenotype known to be a major source of tumour necrosis factor-,
selective depletion of these leucocytes by granulocyte and monocyte adsorption
(GMA) should be an effective intervention in UC patients. This thinking is most
relevant in paediatric and adolescent patients in whom long-term drug therapy
may adversely affect their growth and development.
AIMS & METHODS: This study was to evaluate the efficacy of GMA as a
remission induction therapy in children and adolescents with UC in whom
first-line medications had failed. In a single centre setting, a total of 27 consecutive children and adolescents, age 11-19 years, bodyweight 31.5-56.5kg were given
mesalazine or sulphasalazine as a first-line medication. Twenty patients relapsed
while under first-line medication or did not respond to first-line medication and
received GMA with the Adacolumn, 2 sessions in the first week, and then weekly,
up to 11 sessions. Patients who achieved a decrease of 5 in the clinical activity
index (CAI) were to continue with GMA, while non-responders were to receive
0.5 to 1.0 mg/kg bodyweight/day prednisolone (PSL) plus additional GMA sessions. However, PSL was to be tapered immediately after CAI started to fall. At
entry and week 12, patients UC severity was clinically and endoscopically evaluated, allowing each patient to serve as her/his own control.
RESULTS: At entry, all 27 patients were corticosteroid na ve and none had
extensive loss of the mucosal tissue at the affected sites. Seven patients achieved
sustained remission with the first-line medications and did not receive GMA.
Eight patients did not respond well to the first 5 GMA sessions and received
PSL plus GMA, and in 2 of these with severe UC, the PSL dose was temporarily
increased to 2mg/kg bodyweight while 12 patients responded to the first 5 GMA
sessions and received additional sessions. At entry, the average CAI was
13.02.4, range 8-17, and the average endoscopic index was 8.81.6, range 711. The corresponding values at week 12 were 2.10.2, range 1-4 (P50.001) and
2.40.2, range 1-4 (P50.001). PSL was tapered to 0mg within 3 months in the 8
PSL treated patients. Therefore, at week 12, all 27 patients had achieved clinical
remission, majority with mucosal healing (complete remission). Except difficulties in achieving blood access causing needle pain in a few cases, no serious GMA
related adverse event was observed, and compliance was good, no refusal to
receive GMA and no withdrawal from the GMA treatment.
CONCLUSION: In this study, GMA in paediatric and adolescent corticosteroid
na ve patients with active UC refractory to first-line medication was associated
with clinical remission and mucosal healing, while in non-responders to GMA
monotherapy, addition of PSL enhanced the efficacy of GMA and tapering of
the PSL dose immediately after the fall in CAI score was not associated with UC
relapse. Therefore, with its favourable safety profile, the majority of young steroid na ve patients with active UC refractory to first-line medication should
respond well to GMA and be spared from pharmacological interventions.
Disclosure of Interest: None declared
P0360 PAEDIATRIC IBS IS ASSOCIATED WITH INCREASED SERUM
LEVELS OF PROINFLAMMATORY CYTOKINES
L. Ohman1,2,*, S. Isaksson1,2, E. Melen3,4, I. Kull3,4, M. Wickman3,4,
A. Bergstrom3, M. Simren1, O. Olen4,5
1
Dept. Internal Medicine and Clinical Nutrition, 2Dept. Microbiology and
Immunology, Sahlgrenska Academy at University of Gothenburg, Gothenburg,
3
Institute of Environmental Medicine, Karolinska Institutet, 4Sachs Children and
Youth Hospital, Stockholm South General Hospital, 5Dept.of Medicine, Clinical
Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
Contact E-mail Address: lena.ohman@microbio.gu.se
INTRODUCTION: The pathogenesis of irritable bowel syndrome (IBS) in children is not completely understood, but in adults IBS has been associated with
low-grade inflammation. The aim of this study was therefore to evaluate the
serum levels of cytokines to determine whether paediatric IBS is associated
with increased immune activity.
AIMS & METHODS: In the population based birth cohort BAMSE (n 4089)
adolescents were invited to participate in the 16-year follow up, of which 2547
(62%) agreed to undergo blood testing and clinical examination. Serum samples
were obtained from 41 IBS patients (33 (80%) females) and 97 controls with no
gastrointestinal (GI) symptoms (63 (65%) females). IBS patients fullfilled the
Rome III criteria and were symptomatic at the time of blood sampling.
MesoScale Discovery (MSD) multiplex immunoassay analysis was used for the
measurement of the following serum cytokines; IL-2, IL-4, IL-5, IL-6, IL-8, IL10, IL-12p70, IL-13, IL-17A, IFN-, IL-1, and TNF. Data shown as median
(pg/ml), range 25-75 percentile.
RESULTS: IBS patients had increased serum levels of IL-6 as compared to
controls with no GI symptoms (0.39 pg/ml (0.3-0.7) vs. 0.30 pg/ml (0.2-0.4);
p 0.006). Also levels of TNF (1.65 pg/ml (1.2-2.0) vs. 1.3 pg/ml (1.0-1.8);
p 0.06) and IL-8 (4.51 pg/ml (3.5-5.6) vs. 3.77 pg/ml (2.9-5.3); p 0.1) tended
to be increased in serum of IBS patients relative to controls. The levels of IL-6,
TNF or IL-8 did not differ between patients with or without constipation or
atopic symptoms (asthma, eczema and/or rhinitis). The levels of IL-1 were
under the detection limit in more than 80% of the samples and were therefore

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United European Gastroenterology Journal 2(1S)


not statistically analysed. Remaining serum cytokines, IL-2, IL-4, IL-5, IL-10,
IL-12p70, IL-13, IL-17A and INF- were similarly expressed in IBS patients and
controls.
CONCLUSION: Children with IBS have increased serum levels of proinflammatory cytokines, which mimics previously presented data from adults with IBS.
Thus, paediatric IBS, similar to IBS in adults, is associated with increased
immune activity.
Disclosure of Interest: None declared
P0361 3D HIGH-DEFINITION ANORECTAL MANOMETRY
CHILDREN WITH FUNCTIONAL ANORECTAL DISORDERS

IN

M. Banasiuk1,*, A. Banaszkiewicz1, P. Albrecht1


1
Pediatric Gastroenterology and Nutrition, Medical University of Warsaw,
Warsaw, Poland
Contact E-mail Address: mbanasiu@tlen.pl
INTRODUCTION: 3D high-definition anorectal manometry (3D HDARM) is
the most precise tool to assess function and 3D topographic picture of pressures
along the anal canal. Until now, it has been used only in adult population. The
feasibility in paediatric population has not been evaluated so far.
AIMS & METHODS: The aim of the study was 3D manometric evaluation of
anorectal function in children with functional anorectal disorders.
Children with functional anorectal disorders diagnosed according to III Rome
Criteria were prospectively enrolled in the study. Manometry procedures were
performed with ManoScan A300 (Given Imaging Ltd) without premedication.
Pressures within the anal canal and 3D picture of sphincters were obtained. If
possible, defecation dynamics and thresholds of sensation were evaluated.
RESULTS: 40 children (24 male; age: 9 weeks-15 years, median: 80 months) were
studied. All children suffered from functional constipation. 13 out of 40 children
presented with fecal incontinence and constipation. Mean resting and squeeze
sphincter pressures were 78.98 mmHg and 190.27 mmHg, respectively. The
length of the anal canal was 0.9-4.3 cm. Dyssynergic defecation type I was the
most common type of abnormal defecation dynamics (9 out of 24 children).
Sensation of urge was absent in 6 out of 18 children with the maximum
volume of balloon equalled 140 cc. Recto-anal inhibitory reflex was present in
all children. There were no lesions of sphincters according to 3D topographic
picture of the anal canal.
CONCLUSION: 3D HDARM is a feasible method that can be used in paediatric
population.
Disclosure of Interest: M. Banasiuk Financial support for research from: Given
Imaging GmbH, A. Banaszkiewicz: None declared, P. Albrecht: None declared
P0362 RECURRENT
ABDOMINAL
PAIN
IN
ADOLESCENTS:
COMORBIDITY WITH RECURRENT HEADACHE, BACK PAIN,
DIZZINESS, PRESYNCOPE/SYNCOPE, CHRONIC FATIGUE AND
ASSOCIATION WITH FERRITIN, SOLUBLE TRANSFERRIN
RECEPTOR AND C-REACTIVE PROTEIN LEVELS
M. Shubina1,*, S. Tereshchenko1, N. Gorbacheva1, I. Olkhovskiy1, M. Stolyar1,
V. Babushkin1
1
Scientific research institute of medical problems of the North, Krasnoyarsk,
Russian Federation
Contact E-mail Address: legise@mail.ru
INTRODUCTION: Many of common complains in routine adolescents medicine
practice such as recurrent abdominal pain (RAP) and other recurrent pain syndromes, dizziness, presyncope/syncope and chronic fatigue are significantly associated with anxiety disorders and depression. Data about association of these
conditions are limited. Some cases of RAP may be associated with iron deficiency
and inflammatory diseases, but association iron deficiency and inflammatory
markers with RAP frequency is not studied well.
AIMS & METHODS: 459 adolescents aged 12-18 were screened for RAP (criteria
were as follow: (1) More than two episodes of RAP per month in the last 2 months
OR (2) Abdominal pain intensity according 7-items Likert-type pain scale  4).
Criteria for recurrent headache were as follow: (1) Headache episodes in the last
year 4 10 OR (2) Headache episodes 4 1 per month in the last three months OR
(3) Headache intensity according 7-items Likert-type pain scale  4. Criteria for
recurrent back pain and dizziness were as follow: (1) More than two episodes per
month in the last 2 months OR (2) Intensity according 7-items Likert-type scale 
4. Adolescents were asked about history of presence of symptoms presyncope/
syncope. Chronic fatigue was estimated with original 10-items questionnaire
with assessment of as difficulty or inability initiating activity; reduced capacity
maintaining activity; and difficulty with concentration, memory, and emotional
stability. Plasma concentrations of ferritin, soluble transferrin receptor (sTfR) and
C-reactive Protein (CRP) were estimated with ELISA kits.
RESULTS: We have found positive association between RAP and recurrent
headache (p 0.002), recurrent back pain (p 0.002), recurrent dizziness
(p 0.002), and chronic fatigue (p 0.002). Results are shown in Table 1.
Table to abstract P0362
Comorbidity symptoms
positive adolescents

RAP absence RAP presence P (two-tailed exact


(n 384)
(n 75)
Fisher test)

Recurrent headache (n 193)


Recurrent back pain (n 80)
Recurrent dizness (n 42)
Presyncope/syncope (n 88)
Chronic fatigue (n 28)

38.8%
15.1%
6.8%
17.1%
3.9%

58.7%
29.3%
21.3%
26.7%
17.3%

0.002
0.005
0.003
0.079
50.001

We have found lower ferritin level (p 0.024), higher sTfR level (p 0.043), and
higher sTfR/log ferritin index (p 0.037) in adolescents subgroup with frequent
episodes of RAP (4 2 times per month). No differences have been found in CRP
levels according assigned RAP criteria and RAP frequency. We have also found
no distinctions in ferritin, sTfR, and CPR levels in accordance of presence/
absence of headache, back pain, dizziness, presyncope/syncope, and chronic
fatigue.
CONCLUSION: RAP in adolescents has comorbidity with broad spectrum of
other symptoms (recurrent headache, back pain, dizziness and chronic fatigue).
Because of most of these conditions have psychosomatic pathogenic components,
we suggest that RAP diagnostics and treatment in adolescents should require
estimation and correction their mental health status. We also suggest that adolescents with frequent episodes of RAP should be tested for iron deficiency.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
OTHER LOWER GI DISORDERS I POSTER EXHIBITION HALL
XL_____________________
P0363 PSYCHOLOGICAL EFFECTS OF COLORECTAL
SCREENING INVITATIONS: A RANDOMIZED TRIAL

CANCER

B. Kirken1,*, P. Berstad1,2, T.de Lange1, G. Hoff1,2, T. Bernklev2


1
Cancer Registry of Norway, Oslo, 2Telemark Hospital, Skien, Norway
Contact E-mail Address: benedicte.kirkoen@kreftregisteret.no
INTRODUCTION: A cancer screening programme with the ability to reduce
mortality might be seen as a health service for many with objective benefit for
only a few. Screening might cause worries, and has a potential negative influence
on the mental health of the population that could outweigh the benefits. The
present study therefore aimed to investigate the psychological reactions towards
invitations to screening for colorectal cancer, as part of an evaluation of a pilot
for a national screening programme in Norway.
AIMS & METHODS: In a prospective, randomized trial participants were
invited to either flexible sigmoidoscopy (FS) screening, Faecal
Immunochemical test (FIT), or no screening (the control arm). With the invitation, the participants received a Health-related Quality of Life (HRQoL) questionnaire (The ShortForm-12) and an anxiety and depression questionnaire
(Hospital Anxiety and Depression Scale), which they were asked to complete
and return. Number of invited individuals and questionnaire response rates in
the randomization arms were 3804 and 47% in the FS arm, 6780 and 51% in the
FIT arm, and 6433 and 33% in the control arm, respectively. Among the responders, mean ages in the trial arms were 63.5, 62.4 and 62.9 years, and 55%, 56%
and 57% were women, respectively.
RESULTS: A one-way Analysis of Variance revealed no significant difference
between the three arms in four out of the eight HRQoL dimensions (table 1).
However, contrast analysis revealed that the FIT arm showed significantly lower
physical functioning compared to the control arm. The FS arm showed significantly better social functioning and mental health, compared to both the FIT
arm and the control arm, and better role of emotions compared to the control
arm. Further, there was a significant difference between the three arms in the
anxiety subscale of HADS (table 1). The FS arm had lower anxiety levels compared to the control arm and to the FIT arm. The minimal important difference
was operationalized as a difference of at least half a s.d. Thus none of the
statistical differences were considered clinically relevant, indicating little effect
of being invited for screening on HRQoL and anxiety.
Mean

Physical functioning
Role physical
Bodily pain
General health
Vitality
Social functioning
Role emotional
Mental health
Anxiety

FS

FIT Control p*

85.5
82.5
82.4
67.0
60.3
89.5
87.6
81.5
3.4

84.1
80.0
81.1
67.3
58.7
87.3
85.6
79.7
3.8

86.3
80.6
81.8
67.9
59.3
87.0
84.2
80.1
3.9

.02
.11
.26
.63
.19
5.01
.02
.03
5.01

p FS vs p FIT vs p FS vs
control control
FIT
.37

.01

.10

5.01
.01
.03
5.01

.64
.19
.97
.81

5.01
.06
.01
5.01

Table 1. *One-way ANOVA of differences between the three arms, p5.05.


Higher scores indicate better HRQoL, and higher levels of anxiety.
CONCLUSION: Our findings indicate no negative psychological reactions to
receiving an invitation for colorectal cancer screening with either of the two
screening modalities FS or FIT. Thus the burden of participating in a screening
programme seems limited at invitation.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)

P0364 THE
COST-EFFECTIVENESS
OF
FULL
SPECTRUM
ENDOSCOPY (FUSE) COLONOSCOPY FOR COLORECTAL
CANCER SCREENING
C. Hassan1,*, I. Gralnek2
ONRM Hospital, Rome, Italy, 2Department of Gastroenterology, Rambam
Health Care Campus, Haifa, Israel
Contact E-mail Address: cesareh@hotmail.com
1

INTRODUCTION: As compared with Standard Forward Viewing (SFV) colonoscopy, Full Spectrum Endoscopy (Fuse) colonoscopy increases the adenoma
detection rate and thereby impacts the recommended post-polypectomy surveillance intervals per current US and European guidelines [1].
AIMS & METHODS: As compared to SFV colonoscopy, we aimed to assess the
cost effectiveness of FUSE colonoscopy in a CRC screening and surveillance
program. We constructed a Markov model to simulate the occurrence of colorectal neoplasia in a cohort of 100,000 subjects ages 50 to 100 years of age. The
cost-effectiveness of FUSE was compared with that of SFV colonoscopy, with
each test being assumed to be repeated every 10 years for those 50 to 80 years of
age. Sensitivity for adenomatous and hyperplastic polyps 5 mm, 6-9 mm, and
high-risk polyps (10 mm; 510 mm with unfavourable histology or multiplicity)
were derived from the recent RCT tandem Fuse colonoscopy study [1]. Postpolypectomy surveillance was modeled according to polyp histology. Medicare
costs were adopted and used in the analysis.
RESULTS: For the modeled cohort, the significantly higher sensitivity of FUSE
colonoscopy in detecting additional colonic adenomas resulted in an increase in
CRC prevention from 58% to 74%, corresponding to a gain of 9 days per person
(2,413 life-years for the entire cohort). This 16% increase led to an absolute
reduction in the cost of CRC care from $90 million to $57 million. This $33
million cost savings was only minimally impacted by the higher cost of more
frequent post-polypectomy colonoscopy surveillance rates, so that FUSE was
associated with a savings of $146 per person. Thus, SFV colonoscopy appeared
to be dominated by the FUSE colonoscopy strategy, with FUSE colonoscopy
being both more effective and less costly. By assuming 68 million of American
subjects between 50 and 80 years of age and an annual incidence of 107,483 CRC
cases without screening for a discounted annual CRC care cost of $3.7 billion, the
additional efficacy of FUSE over SFV would result into the annual prevention of
10,318 CRC and the annual saving of $0.3 billion for CRC related costs.
CONCLUSION: As compared to SFV colonoscopy, FUSE colonoscopy appears
to be more cost-effective for CRC screening and surveillance. In particular, the
higher associated costs of more frequent post-polypectomy colonoscopy surveillance were compensated by the significant overall reduction in CRC treatment
costs.
REFERENCES
[1] Gralnek IM, Siersema PD, Halpern Z, et al. Standard forward-viewing colonoscopy versus full-spectrum endoscopy: an international, multicentre, randomised, tandem colonoscopy trial. Lancet Oncol 2014; 15: 353-360.
Disclosure of Interest: None declared
P0365 SESSILE SERRATED VERSUS CONVENTIONAL ADENOMAS.
DIFFERENT POLYPS IN DIFFERENT POPULATIONS
G. Michalopoulos1, S. Vrakas1, S. Charalampopoulos1, V. Ntouli1,
S. Lamprinakos1, K. Makris1, C. Tzathas1,*
1
Gastroenterology, Tzaneion, General Hospital of Piraeus, Piraeus, Greece
Contact E-mail Address: gmicha78@hotmail.com
INTRODUCTION: There are emerging data indicating that Sessile Serrated
Adenomas may have different epidemiological characteristics than conventional
adenomas.
AIMS & METHODS: This prospective study was aimed to identify any differences in the characteristics of patients with Sessile Serrated Adenomas with and
without dysplasia (SSA/Ds) in comparison to patients with conventional
Adenomatous Polyps (APs). 85 patients with APs and SSA/Ds were included
and data regarding age, sex, smoking, BMI, waist-hip-ratio and medical history
(arterial hypertension and diabetes mellitus) were collected. A univariate and a
multivariate regression analysis were performed using z test.
RESULTS: 156 APs and 53 SSA/Ds of 85 patients (mean age 66.19.8 and
63.19.4 years, respectively) with their characteristics and the results from univariate and multivariate regression analysis are presented in the following table.
SSA/D vs AP (univariate)

OR

P-value

95% C. I.

Sex (women/men)
BMI
Waist-hip-ratio
Diabetes Mellitus
Hypertension
SSA/D vs AP (multivariate)
Diabetes mellitus
Hypertension

2
0.92
0.01
0.09
0.24
OR
0.1
0.3

0.034
0.031
0.06
50.001
50.001
P-value
50.001
0.001

1.05-3.84
0.85-0.99
0.0002- 1.30
0.02-0.33
0.12- 0.47
95% C. I.
0.03-0.36
0.14-0.63

There was no statistical significant difference regarding sex, BMI and waist-hipratio (p40.05) in the multivariate regression analysis. A peak incidence of SSA/
Ds was observed in the ages of 51-60 years compared to a peak incidence in the
ages of 61-70 years of APs (p 0.001). No significant difference between groups
regarding smoking was observed (p40.05).

CONCLUSION: SSA/Ds compared to APs are more common in women, they


have a peak incidence 10 years earlier and tend to occur in patients with lower
BMI. Waist-hip-ratio, although not statistically significant, had a trend for lower
values in patients with SSA/D. The results from both analyses show that SSA/Ds
are less common in patients with diabetes mellitus and hypertension in comparison to APs.
Disclosure of Interest: None declared
P0366 SESSILE SERRATED ADENOMAS, ARE THERE ANY RISK
FACTORS?
G. Michalopoulos1, S. Vrakas1, S. Charalampopoulos1, V. Ntouli1,
S. Lamprinakos1, K. Makris1, C. Tzathas1,*
1
Gastroenterology, Tzaneion, General Hospital of Piraeus, Piraeus, Greece
Contact E-mail Address: gmicha78@hotmail.com
INTRODUCTION: Evidence is conflicting regarding the risk factors for development of Sessile Serrated Adenomas.
AIMS & METHODS: This prospective study was performed in order to identify
differences in the characteristics of patients with Sessile Serrated Adenomas with
and without dysplasia (SSA/D) in comparison to patients with normal colonoscopies. Data from127 patients (100 with normal colonoscopies and 27 with SSA/
Ds) regarding age, sex, smoking habits, BMI, waist-hip ratio and medical history
(arterial hypertension, diabetes mellitus, past history of polyps) was collected and
analyzed by multivariate logistic regression analysis. Four age subgroups: 41-50,
51-60, 61-70 and 71-80 were analyzed with univariate logistic regression analysis.
Analyses was performed using Stata 9.0
RESULTS:
SSA/D vs Normal (multivariate)

OR

P-value

95% C. I.

Age
Current smokers
Personal medical history of polyps
Age
SSA/Ds vs Normal (univariate)
41-50
51-60
61-70
71-80

1.04
4.35
3.34
OR

0.008
0.003
0.004
P-Value

1.01-1.08
1.63-11.59
1.48-7.58
95% CI

1.33
9.88
8.72
26.18

0.84
0.032
0.047
0.003

0.07-23.5
1.21-80.07
1.02-74.11
3.03-225.9

No statistical significant difference was observed regarding diabetes mellitus,


hypertension, BMI and waist-hip-ratio.
CONCLUSION: Smoking and personal past history of polyps increase the risk
for SSA/Ds in comparison to normal population. Increasing age also increases
the risk for SSA/Ds, especially after the age of 50.
Disclosure of Interest: None declared
P0367 DRUG ALLERGY AND RISK OF LYMPH NODE METASTASIS IN
RECTAL CANCER
C. Gao1,*, J.-T. Li1, L. Fang1, H.-C. Zhao1
1
Department of Gastroenterology, China-Japan Friendship Hospital, Ministry of
Health, Beijing, China
Contact E-mail Address: gaochun@bjmu.edu.cn
INTRODUCTION: Previous epidemiologic studies have reported that a history
of allergy is associated with reduced risk of colorectal cancer and other malignancies. However, no information is available for the association between allergy
and risk of lymph node metastasis.
AIMS & METHODS: Our study was designed to determine this association in
rectal cancer.
Patients who were treated at our hospital in the period from January 2003 to
June 2011, and with a pathological hospital discharge diagnosis of rectal adencarcinoma, were included. The clinical, laboratory and pathologic parameters
were analyzed. Multivariate logistic regression model was used to determine
the association. Moreover, for type of allergic drug, sub-group analysis was
performed.
RESULTS: 469 patients were included, including 231 with pathological lymph
node metastasis (pLNM) (49.3%) and 238 without pLNM. Univariate analysis
showed, compared with patients without pLNM, patients with pLNM had a
younger age (60.612.8 yr vs. 63.612.2 yr, p 0.012), a lower percentage of
drug allergy (8.7% vs. 16.0%, p 0.016), an increased CEA (median/interquartile-range 5.40/2.40-13.95 vs. 3.50/2.08-8.67, p 0.009), and a lower serum
sodium (1413.1mmol/L vs. 1422.9 mmol/L, p 0.028). Multivariate analysis
showed that drug allergy was associated with a reduced risk of pLNM
(OR 0.553; 95% CI, 0.308-0.994; p 0.048). In addition, our results showed
that: (1) for tumor classification, patients with drug allergy had a higher percentage of group patients with pT1/ pT2; and (2) for type of allergic drug, this
inverse association was found for penicillins, not for other allergic drugs.
CONCLUSION: Drug allergy is associated with a reduced risk of pLNM in
rectal cancer.
Disclosure of Interest: None declared

A233

United European Gastroenterology Journal 2(1S)


P0368 PROGNOSTIC VALUE OF HUMAN PAPILLOMAVIRUS IN ANAL
SQUAMOUS CELL CARCINOMA
P.S. Ravenda1, E. Magni1, E. Botteri1, M. Manzotti1, M. Barberis1,
C. Trovato2,*, V. Dellacqua1, M.C. Leonardi1, M. Sideri1, N. Fazio1,
M.G. Zampino1
1
EUROPEAN INSTITUTE OF ONCOLOGY, Milan, Italy, 2Endoscopy
Division, EUROPEAN INSTITUTE OF ONCOLOGY, Milan, Italy
Contact E-mail Address: cristina.trovato@ieo.it
INTRODUCTION: Anal cancer is an uncommon malignancy but its incidence is
increasing worldwide. Chemoradiation is the standard primary treatment for
patients with loco-regional limited disease. However, once patients develop metastatic spread, the prognosis is very poor. Human papillomavirus (HPV) is present
in around 80% of anal cancers but its prognostic/predictive value is essentially
unknown.
AIMS & METHODS: We retrospectively evaluated 50 patients with anal squamous cell carcinoma treated at our Institution with chemoradiotherapy for locoregional disease. HPV status was evaluated from paraffin-embedded tumor tissues collected at the time of diagnosis by a polymerase chain reaction analysis.
RESULTS: Among 50 patients 42 (84%) were HPV-positive. Thirty-two (64%)
patients were positive to genotype 16, two (4%) to genotype 18 and three (6%) to
both 16 and 18. Lymph nodal involvement and clinical stage at diagnosis were
more advanced for HPV-positive patients. After a median follow-up of 4 years
(range 0.4-13.8) 46 (92%) patients were alive. Overall, 8 patients relapsed: 1 locoregional, 1 regional and 6 distant recurrences were observed. Four patients died
from metastatic disease. Five-year disease-free survival (DFS) in HPV-positive
and HPV-negative patients was 92.5% and 50.0%, respectively (p 5 0.01). In
multivariate analysis, HPV-positivity was associated with a statistically significant better 5-year DFS. Five-year overall survival in HPV-positive and HPVnegative patients was 93.3% and 66.7%, respectively (p 0.12).
CONCLUSION: In our study HPV-positive anal cancers had a statistically significant improved DFS compared to HPV-negative group.
Disclosure of Interest: None declared

rounds for an optimal preventative effect. The diagnostic yield of advanced


neoplasia may increase with the use of two FITs per round. Therefore, in this
study we assessed the diagnostic yield and participation rate of two-sample FIT
screening during three successive rounds in a population-based screening pilot in
the Netherlands.
AIMS & METHODS: A representative sample of the Dutch population
(n 3197) aged 50-75 years was randomly selected and invited by mail for
three rounds of two-sample FIT screening with a 2-year interval. Participants
received two identical FIT tests per round to sample on two consecutive bowel
movements. Tests were analyzed using the OC Sensor Micro (Eiken Japan) with
a positivity cut-off level of 50ng Hb/ml ( 10 mg Hb/g feces). Participants with at
least one positive test were offered colonoscopy. For each round, we excluded
individuals who met exclusion criteria (history of CRC, IBD, colon imaging  3
years, life expectancy 55 years, inability to give informed consent) died, moved
away or were positive at previous rounds.
RESULTS: The participation rate was 64.4% (95% Confidence Interval (CI)
62.566.4%) at the third round, compared to 62.1% (1647/2652; 95% CI:
60.2-63.9%) in the second and 61.3% (1875/3061; 95% CI: 59.663.1%) in the
first round. One test was positive in 145 (9.8%; 95% CI 8.411.4) individuals and
in 41 (2.8%; 95% CI 2.03.7) both FITs tested positive. Of the 134 (92%)
patients who proceeded to colonoscopy, 5 had CRC and 13 had an advanced
adenoma (defined as an adenoma 10mm, with 25% villous component or
high-grade dysplasia). The positive predictive value (PPV) for advanced neoplasia was 13.4% (95% CI 8.6-20.3) for at least one positive test and 18.4% (95% CI
9.0-33.9) when both tests were positive. The two-sample methodology detected
61.1% additional participants with advanced neoplasia (p 0.28) who would
have been missed with a single FIT test per round; 4 (80%) participants who
had CRC and 7 (53.9%) who had an advanced adenoma had only 1 positive test.
Table, 2-sample FIT screening (1positive) in multiple rounds
Eligible
invitees Participation PR

n
P0369 ASSOCIATION BETWEEN COLORECTAL NEOPLASMS AND
METABOLIC SYNDROME IN A PORTUGUESE POPULATION
1,*

D. Trabulo , S. Ribeiro , C. Martins , C. Teixeira , C. Cardoso ,


J. Mangualde1, R. Freire1, E. Gamito1, A.L. Alves1, F. Augusto1, I. Cremers1,
A.P. Oliveira1
1
Gastroenterology, Hospital de Sao Bernardo - Centro Hospitalar de Setubal,
Setubal, Portugal
Contact E-mail Address: danieltrabulo@yahoo.com
INTRODUCTION: There has been a growing recognition of metabolic syndrome (MS) as an important risk factor for cardiovascular disease and malignancies. Several investigators from Eastern countries have considered MS as a
possible risk factor for colorectal neoplasms.
AIMS & METHODS: The aim of this study was to evaluate the association of
MS and colorectal cancer and adenomas in a Western country, where the incidence of MS is over 27%.
Methods: Prospective study between March 2013 and March 2014. MS was
diagnosed according to National Cholesterol Education Program-ATP III.
Demographic characteristics, anthropometric measurements, metabolic risk factors and colonoscopy pathologic findings were assessed in patients with MS
(group 1) who underwent routine colonoscopy at our department. This data
was compared with consecutive patients without metabolic syndrome (group
2), with no differences regarding sex and age. Informed consent was obtained
and the ethics committee approved this study. Statistical analysis was performed
with T-student and 2 tests; p-value0,05 was considered statistically significant.
RESULTS: We evaluated a total of 258 patients, 129 with MS; 50% males;
mean-age 67,1 years (50-87). Among the MS group, 94% had high blood pressure, 91% had increased waist circumference, 60% had diabetes, 55% had low
HDL cholesterol level, 50% had increased triglyceride level and 54% had obesity
(BMI30kg/m2). 51% presented 4 criteria of MS. MS was associated with
increased presence of adenomas (43% vs 25%, p 0.004) and colorectal cancer
(13% vs 5%; p 0.027), compared with patients without MS. MS was also
positively associated with multiple (3) adenomas (35% vs 9%, p 0.024) and
sessile adenomas (69% vs 53%; p 0.05). No differences existed between location (p 0.086), grade of dysplasia (p 0.196) or size of adenomas (p 0.841).
Increased waist circumference was an independent risk factor for the presence of
adenomas (85% vs 15%, p 0.05).
CONCLUSION: In our population, MS was associated with colorectal cancer
and adenomas. Central obesity was also associated with an increased risk.
Recommendations for colorectal cancer screening in patients with MS may
need to be different from the average risk population. To our knowledge, no
previous study evaluated this association in Portuguese patients.
Disclosure of Interest: None declared
P0370 THIRD ROUND OF TWO-SAMPLE IMMUNOCHEMICAL FECAL
OCCULT BLOOD TEST SCREENING IN THE NETHERLANDS
E.H. Schreuders1,*, S. Nieuwenburg1, A. Kapidzic1, E.J. Grobbee1, A.J.
van Vuuren1, W. Spijker2, M.J. Bruno1, E.J. Kuipers1, M.C. Spaander1
1
Gastroenterology and Hepatology, Erasmus MC, 2Stichting Bevolkingsonderzoek
Zuid-West Nederland, Rotterdam, Netherlands
Contact E-mail Address: e.schreuders@erasmusmc.nl
INTRODUCTION: Screening for colorectal cancer (CRC) by means of immunochemical fecal occult blood test (abbr. iFOBT or FIT) requires successive

Round 1 3061
Round 2 2654
Round 3 2297

DR
Advanced
neoplasia CRC
n (%)
n (%)

n (%)

n (%)

1876 (61.3)
1647 (61.2)
1480 (64.4)

239 (12.8) 76 (4.1)


141 (8.6) 26 (1.6)
145 (9.8) 18 (0.8)

PPV
Advanced
neoplasia %
(95% CI)

12 (0.6) 34% (28.3 40.7)


4 (0.2) 19.0% (13.3 - 26.4)
5 (0.2) 13.4% (8.6 - 20.3)

CONCLUSION: Two-sample FIT screening is associated with a stable and high


participation rate of more than 60% after three rounds. Positivity rates and
detection rates with two-sample FIT screening, are higher compared to historical
data of screening with one-sample FIT per round (van Roon Gut 2012). This
implies that FIT screening with two samples has an added benefit to detect a
maximum number of individuals with advanced neoplasia.
Disclosure of Interest: None declared
P0371 LIFESTYLE, ENVIRONMENT OR GENDER WHAT HAS
BIGGER IMPACT ON THE INCIDENCE OF COLORECTAL
NEOPLASIA?
E. Waldmann1,2,*, G. Heinze3, M. Britto-Arias1,2, D. Sallinger1,2, I. Gessl1,2,
A. Ferlitsch1,2, M. Trauner1,2, M. Ferlitsch1,2
1
Quality Assurance Working Group of the Austrian Society of Gastroenterology
and Hepatology, 2Div. of Gastroenterology and Hepatology, Dept. of Internal
Medicine III, 3Department for Medical Statistics, Division of Clinical Biometrics,
Medical University of Vienna, Austria, Vienna, Austria
Contact E-mail Address: monika.ferlitsch@meduniwien.ac.at
INTRODUCTION: Recommendations for colorectal cancer (CRC) screening
are based on patients age and family history of cancer, although men are at
higher risk for adenomas and CRC and develop the lesions earlier than women.
Several risk factors such as BMI, gamma GT levels, presence of diabetes and
physical activity are known to increase the incidence of adenomas and CRC but
less is known about the impact of those risk factors on prevalence of colorectal
neoplasia in men and women.
AIMS & METHODS: To investigate the impact of risk factors on sex specific
adenoma detection rates (ADR) and advanced adenoma detection rates
(AADR). We included patients who attended preventive health check up examinations and screening colonoscopy at the same time point (within six months) in
Austria between November 2007 and December 2012.
RESULTS: The investigated risk factors had greater impact on male patients
than on female patients. High BMI influenced ADR (p50.0001) and AADR
(p50.0001) in male patients and ADR (p 0.0229), but not AADR (p 0.2720)
in female patients. High gamma GT levels also increased ADR (p50.0001,
OR 1.11, CI 1.05-1.16) and AADR (p 0.0045, OR 1.12, CI 1.04-1.21)
in male, but not in in female patients (p 0.5237, OR 1.02, CI 0.96-1.09 for
ADR and p 0.3804, OR 0.95, CI 0.85-1.07 for AADR). Presence of diabetes
has an impact on ADR (p 0.0049, OR 1.2) and AADR (p50.0001, OR 1.6)
in male, but not in female patients (p 0.276, OR 1.1 and p 0.234, OR 1.3).
Physical activity impacts ADR (p 0.0018, OR 0.8) and AADR (p50.001,
OR 0.6) in male as well as AADR in female patients (p 0.0150, OR 0.7)
but not the ADR in female patients (0.0792, OR 0.8).
CONCLUSION: Our results show that acknowledged risk factors for colorectal
neoplasias seem to affect particularly male patients which raises the need of
implementation of gender specific prevention recommendations for CRC, especially for men with risk factors.
Disclosure of Interest: None declared

A234
P0372 ANTI-HER2/NEU PEPTIDE WAS LABELED WITH TC-99M TO
DETECT HER2-POSITIVE TUMORS IN COLORECTAL HCT-15
DERIVED XENOGRAFTS
A.-S. Ho1,*, C.-C. Cheng2, C.-C. Chang3, H.-C. Lin1, T.-Y. Luo2, J. Chang4
Cheng Hsin General Hospital, Taipei, 2Institute of Nuclear Energy Research,
Taoyuan, 3Taipei Medical University Hospital, 4Taipei Medical University, Taipei,
Taiwan, Province of China
Contact E-mail Address: js.chang@tmu.edu.tw
1

INTRODUCTION: HER2/neu is reported as an overexpressed target on the cell


surface in variety of solid cancers such as gastric cancer and breast cancer. Here,
we (1) validated that HER2 is a tumor-treated target in colorectal cancer, and (2)
designed an anti-HER2/neu peptide (AHNP)-labeled Tc-99m to detect the
expression of HER2 in HER2-postive HCT-15-induced tumors.
AIMS & METHODS: The aim of this study was to create a HER2-binding
peptide, AHNP, labeled with Tc-99m to detect HER2-positive tumors. First,
the colorectal cancer cells, HCT-15, were used to investigate the binding specificity of AHNP. The AHNP was conjugated with HYNIC and PEG at N and Cterminus, respectively. The designed AHNP was chelated with Tc-99m through
HYNIC and the isotope-labeled rate was analyzed by iTLC. Then, a
nanoSPECT/CT was used for tumor detection.
RESULTS: We found that HER2 was overexpressed in colorectal HCT-15
tumor cells and the tumors of HCT-15-induced xenograft mice using Western
blots. AHNP labeled with fluorescent FITC was performed to detect the binding
efficacy of AHNP to HCT-15 in vitro using flow cytometry. The results revealed
that AHNP specifically bound to HER2-positive HCT-15 cells compared to
HER2-negative gastric MKN45 tumor cells, indicating that AHNP can be
applied to diagnose HER2-positive tumors. Therefore, we labeled nuclear isotope, Tc-99m, with AHNP coupled with PEG to prolong the half-life of peptide
in animals. The labeled rate of Tc-99m with AHNP through HYNIC chelating
was measured 4 90% using iTLC analysis. However we did not observe apparent difference in nuclear imaging for detecting tumors in HCT-15-induced xenografts, suggesting that peptide was unstable or rapidly metabolized in animals.
CONCLUSION: Our results showed that HER2 overexpressed in colorectal
HCT-15 cells as a tumor target. HER2 specific binding peptide, AHNP, can be
used to detect HER2-positive tumors as a good candidate tool in vitro, however,
it was rapidly metabolized in animals.
Disclosure of Interest: None declared
P0373 BISULFITE-BASED DNA METHYLATION ASSESSMENT FROM
RECENT AND ARCHIVAL FORMALIN-FIXED, PARAFFIN
EMBEDDED (FFPE) COLORECTAL SAMPLES
A. Kalmar1,2,*, B. Peterfia2, P. Hollosi3,4, B. Wichmann1,2, V.A. Patai1,
A. Scholler1, I. Furi1, Z. Tulassay1,2, B. Molnar1,2
1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular
Medicine Research Unit, Hungarian Academy of Sciences, 31st Department of
Pathology and Experimental Cancer Research, Semmelweis University, 4Tumor
Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary
Contact E-mail Address: alexandra.kalmar@gmail.com
INTRODUCTION: Surgically removed formalin-fixed, paraffin-embedded
(FFPE) specimens are routinely used for morphological and molecular diagnostics, although application of these samples in molecular biology analyses can be
challenging. Methylation-sensitive high-resolution melting analysis (MS-HRM)
is a cost-effective tool for the assessment of DNA methylation level alterations
during several types of tumor formation including colorectal cancer (CRC).
AIMS & METHODS: We aimed to compare the applicability of recent and
archive FFPE tissue samples for gene-specific MS-HRM using two different commercially available DNA isolation kits. Genomic DNA isolation was performed
from two groups of FFPE blocks; archive samples older than 5 years (n 10; 5
CRC, 5 normal adjacent tissue (NAT)), recent samples younger than 6 months
(n 10; 5 CRC, 5 NAT) using FFPE DNA Isolation Kits from Roche and Qiagen.
The yield and purity of DNA samples were evaluated by spectrophotometry and
by fluorometry. The integrity and applicability of DNA for PCR was examined by
qPCR and a multiplex PCR experiment that contains primers producing four
amplicons with different lengths. DNA samples were bisulfite converted and
gene-specific DNA methylation analyses were performed for MAL, SFRP1 and
SFRP2 genes by using MS-HRM analysis and GS Junior sequencing
RESULTS: Based on OD260 measurements the Qiagen method resulted in a
slightly higher recovery in archive and a significantly higher recovery in fresh
FFPE samples compared to the Roche method. More selective detection of RNA
and DNA by fluorometric dyes revealed that Qiagen samples contain high
amounts of RNA, more than the Roche isolated samples, which was also supported by the higher OD260/280 and OD260/230 ratios of Qiagen samples. The
two isolation methods did not differ significantly in their DNA yield in case of
archive samples, but Qiagen yielded about two times more DNA in average from
fresh FFPE samples. The DNA integrity and amplificability of fresh FFPE
samples were higher than the archive ones. Despite the equal DNA yield of
Qiagen and Roche samples in the archive sample group, the integrity of Roche
samples was higher, and their qPCR amplification was also significantly more
effective. Identical DNA methylation pattern was detected by MS-HRM for
Qiagen and Roche samples in the fresh FFPE group. However, in case of archive
samples, more reproducible methylation results were obtained from Roche samples. The differences in the methylation level of selected tumor samples could be
confirmed also by sequencing the PCR products of MS-HRM examinations.
CONCLUSION: Sufficiently reproducible MS-HRM results can be obtained
from recently fixed, fresh FFPE samples, but less reliable results can be expected
for archive ones. In case of archive samples more parallel reactions, and usage of
highly effective primer assays is recommended.

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: None declared
P0374 COMPARISON OF AUTOMATED AND MANUAL
ISOLATION FOR DNA METHYLATION ANALYSIS OF BIOPSY,
FRESH FROZEN AND FFPE COLORECTAL CANCER SAMPLES

DNA

A. Kalmar1,2,*, B. Peterfia1,2, B. Wichmann1,2, A. V. Patai1, B.K. Bartak1,


Z.B. Nagy1, I. Furi1, M. Juhasz1, L. Herszenyi1, Z. Tulassay1,2, B. Molnar1,2
1
2nd Department of Internal Medicine, SEMMELWEIS UNIVERSITY,
2
Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest,
Hungary
Contact E-mail Address: alexandra.kalmar@gmail.com
INTRODUCTION: A broad range of biological samples are being analysed with
increasing number in the routine pathology; automated DNA isolation can be a
promising solution to decrease the hands-on time.
AIMS & METHODS: Our aim was to analyse the performance of MagNA Pure
96 nucleic acid isolation system in DNA isolation from fresh frozen, biopsy and
formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Furthermore, we
aimed to test the applicability of the isolated DNA in downstream DNA methylation analyses, and to compare results after automated and manual isolation.
Fresh frozen (n 20; 10 CRC, 10 normal adjacent tissue (NAT)) tissue specimens, biopsies (n 20; CRC 10, healthy colonic tissue 10), FFPE blocks
(n 20; 10 CRC, 10 NAT) were collected. DNA isolation was performed from
the fresh frozen and biopsy samples with QIAamp DNA Mini Kit (Qiagen) and
with automated method with MagNA Pure DNA and Viral NA Small Volume
kit (Roche Applied Science) on the MagNA Pure 96 system Kit in parallel, the
FFPE samples were isolated with manual QIAamp DNA FFPET kit (Qiagen)
and with automated MagNA Pure DNA and Viral NA Small Volume kit (Roche
Applied Science). After DNA quantity and quality measurements, DNA methylation levels for MAL, SFRP1 and SFRP2 were analysed with methylation-specific high resolution melting analysis (HRM).
RESULTS: Yield of manually isolated samples were found to be equal in fresh
frozen tissue samples and significantly higher compared to the automated
method in the case of biopsy and FFPE samples. OD260/280 ratio was found
to be similar in fresh frozen and biopsy samples, while manual isolation resulted
in higher purity in FFPE samples. OD260/230 ratio was similar in fresh frozen
tissue samples after both isolation methods, the automated method was superior
in biopsy samples and the manual protocol in FFPE samples. DNA integrity was
found to be the highest in fresh frozen samples, and half of the analyzed FFPE
samples showed higher integrity after manual extraction, while the rest of samples had similar integrity after both methods. In biopsy and fresh frozen samples
DNA methylation estimations were found to be highly similar after two isolation
methods. In the FFPE samples the linearity of the assays lower even in FFPE
samples SFRP1 and SFRP2 assays showed good correlation in the methylation
percent data after the two different isolation methods.
CONCLUSION: Similar DNA methylation results were found after automated
and manual DNA isolation, thus automation can be a suitable alternative in
CRC diagnosis workflow beside manual protocols especially for laboratories
with high sample throughput.
Disclosure of Interest: None declared
P0375 CORRELATION BETWEEN THE LOCATION OF THE INITIAL
AND RECURRENT COLONIC POLYPS
A.T. Oliveira1,*, P. Freire1, S. Campos1, S. Giestas2, S. Mendes1, P. Amaro2,
F. Portela1, C. Sofia1
1
Gastroenterology, 2Centro Hospitalar e Universitario de Coimbra, Coimbra,
Portugal
Contact E-mail Address: torresoliveiraana@gmail.com
INTRODUCTION: The post-polypectomy surveillance colonoscopy is recommended because of the risk of synchronous and recurrent lesions. There are
several factors used to stratify the probability of polyp recurrence. However,
there are no studies correlating the location of the initial polyp and that of the
recurrent one.
AIMS & METHODS: The aim of this study is to verify if the polyp location at
the surveillance colonoscopy is correlated with the location of the previously
excised polyps at the baseline colonoscopy.
We included all patients submitted to two total colonoscopies, with at least oneyear interval and complete excision of the polyps detected in the baseline colonoscopy. We evaluated 346 patients, of whom 78 were excluded for not having
polyps at the surveillance colonoscopy. We divided the intestine into cecum,
ascending, transverse, descending, sigmoid and rectum and also evaluated the
characteristics of polyps. We used the Kolmogorov-Smirnov test to determine the
normality, Kappa for agreement and Chi-square, t-Test or Mann-Whitney as
necessary.
RESULTS: We found a male predominance (64.9%) and a mean age of 6410
years. The number and size of the polyps at the initial and surveillance colonoscopy was 31 vs 21 polyps and 119 vs 75mm, respectively. The mean
interval between the two colonoscopies was 3720 months. The overall agreement rate of polyp location between colonoscopies was 44%. Probability of
recurrence in the several segments: cecum 50.0% [OR 6.4-62.4], ascending
57.0% [OR 2.3-7.2], transverse 46.4% [OR 1.9-6.9], descending 34.6% [OR
1.3-4.4], sigmoid 57.6% [OR 2.3-6.9], rectum 40.4% [OR 1.6-5.1], p50.001.
No statistically significant difference was found between the rates of recurrence
at the same location, taking into consideration: polyp morphology (sessile
59.8%; pedunculated 51.6%), size (11mm), polypectomy technique (biopsy forceps 64.3%; snare 54.0%; mucosectomy 70.4%), histology (low-grade dysplasia
54.7%, high-grade dysplasia 41.7%; hyperplastic 64.9%), resection (complete
48.6%; fragmented 58.3%). There was also no difference after stratification in

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United European Gastroenterology Journal 2(1S)


advanced adenoma (50.5%), non-advanced adenoma (56.8%) and hyperplastic
(64.9%).
CONCLUSION: There seems to be a significant correlation between the initial
location of polyps and the recurrence site in the surveillance colonoscopy. This
may have future implications in terms of technical execution and accuracy of the
procedure, including alerting for better scrutiny of the segment with previous
polypectomy.
Disclosure of Interest: None declared
P0376 COMPARISON THE EFFICIENCY OF HIGH RESOLUTION
MELTING ANALYSIS AND PYROSEQUENCING IN COLON
CANCER DNA METHYLATION STUDIES
B. Peterfia1,*, P. Hollosi2, B. Wichmann1, Z. Tulassay1, B. Molnar1
2nd Deptartment of Internal Medicine, 21st Department of Pathology and
Experimental Cancer Research, Semmelweis University, Budapest, Hungary
Contact E-mail Address: peterfiab@yahoo.co.uk
1

INTRODUCTION: Identification of differentially methylated regions (DMRs)


in the genome of cancer samples by comparing them with normal samples is a
basic process in the course of epigenetic investigations. Methylation-sensitive
high-resolution melting analysis (MS-HRM) and pyrosequencing of bisulphite
modified DNA are two of the most popular technologies among single locus
DNA methylation studies. Both techniques involve PCR amplification of bisulphite converted DNA, although they differ in their cost, hands-on time and in the
output information they provide.
AIMS & METHODS: In order to test MS-HRM and pyrosequencing on colon
cancer samples, fresh frozen tissue specimens were collected (20 CRC, 15 adenoma and 20 normal adjacent tissue (NAT)). After DNA isolation and bisulphite
conversion, 12 different CpG rich regions of 9 genes were amplified by PCR
(COL1A2, ENTPD5, PRIMA1, PTGDR, SFRP2, SOCS3, SULF1, SULT1A1
and THBS2). PCR amplification was carried out with primers designed to
amplify both methylated and unmethylated templates. After amplification MSHRM was carried out, and PCR amplicons were subsequently pyrosequenced.
RESULTS: In general, MS-HRM provided less accurate estimation, thus it is not
suitable to detect very slight methylation level alterations. However, results of
MS-HRM and pyrosequencing were in harmony with each other in 89% of cases.
The number of hypermethylated tumours found by MS-HRM versus pyrosequencing was as follows: COL1A2: 5 vs. 7; PRIMA1: 5 vs. 7; PTGDR: 3 vs. 0;
SFRP2: 13 vs. 13; SOCS3: 10 vs. 12; THBS2: 4 vs. 5, respectively. A promoter of
an alternative variant of THBS2 was found to be hypomethylated in 4 vs. 5
tumour samples. The total number of DMRs found in the 20 CRC samples
investigated was 44 by MS-HRM and 49 by pyrosequencing, which means that
the efficiency of MS-HRM is 82% of the pyrosequencing. In contrast to pyrosequencing, MS-HRM was able to detect sample heterogeneity, especially in case
of adenomas and tumour samples. Further experiments with laser captured
microdissected cells from these samples revealed that epithelial cells were hypermethylated in tumours, while no DNA methylation level alteration could be
detected in stromal cells.
CONCLUSION: Taken together, MS-HRM is cost-effective and needs less
manual work than pyrosequencing, which makes it a suitable tool for DNA
methylation screening study. The efficiency of MS-HRM is close to that of the
pyrosequencing in DMR detection. Moreover, it gives information about sample
heterogeneity. The major advantage of pyrosequencing is its higher sensitivity
and the single CpG site information it provides.
Disclosure of Interest: None declared
P0377 TARGETED, NEXT GENERATION 454 SEQUENCING OF COLON
CANCER BIOPSIES YIELDS THERAPEUTICAL AND DIAGNOSTIC
DATA
B. Peterfia1,*, B. Wichmann2, A. Kalmar1, A. V. Patai1, Z. Tulassay1, B. Molnar1
1
2nd Deptartment of Internal Medicine, 2Molecular Medicine Research Unit,
Semmelweis University, Budapest, Hungary
Contact E-mail Address: peterfiab@yahoo.co.uk
INTRODUCTION: Mutation analysis of certain genes is an essential procedure
for an individualized therapy. The number of important target genes is gradually
rising, pressing a requirement for continuous expansion of analytic methods.
Fulfilling this goal in a time-efficient manner is a big challenge for diagnostic
laboratories, using conventional sequencing procedures.
AIMS & METHODS: Creating a mutation sequencing panel helped us to reach
the aim to investigate the potential of Next Generation Sequencing (NGS) in
colon cancer genotyping. A multiplex PCR panel was designed to amplify mutation hot spots of 12 selected genes. Those genes were selected that are frequently
mutated in colon cancer or that are investigated in routine oncodiagnostics
(APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, MSH6, NRAS, PIK3CA,
SMAD2, SMAD4, TP53). Amplicons were sequenced by a GS Junior
Instrument (Roche) using ligated and barcoded adaptors. Eight samples could
be sequenced in one single run. Altogether, control cell lines with known mutation profiles and 60 DNA samples were investigated by the panel (8 normal colon
mucose; 33 adenomas and 17 adenocarcinomas).
RESULTS: In control cell lines (HT29 and Caco-2), 4 mutations were anticipated to be found by our panel; and three of them were successfully detected.
Only one adenine insertion, which was located in an adenine homopolymer
region, was not detected. We found one mutated normal of eight investigated
samples (12.5%). This rate was much higher in adenomas and carcinomas (78%
and 76%, respectively), indicating high sensitivity. The average number of mutations found in mutated samples was 1 in low grade adenomas; 1.8 in high grade
adenomas; 1.9 in carcinomas and 2.3 in serrated adenomas. The only mutation
found in normal samples was a germ line APC mutation. This typical gatekeeper

suppressor gene was mutated in adenomas more frequently than in carcinomas


(36% vs. 24%), in contrast with other caretaker or proto-oncogenes. The most
frequently mutated genes were APC, TP53 and KRAS with 36%, 18% and 26%
frequencies in adenomas and 24%, 47% and 45% frequencies in carcinomas,
respectively. Interestingly, there was no sample found having APC and TP53
mutations together.
CONCLUSION: Our NGS based screening panel can be a useful and affordable
tool to study the mutation profile of colon cancer. Additionally, not only can it
detect sporadic, but many of frequent germ line mutations as well. Its application
in diagnostic practice to predict therapeutic response is worth to consider.
Disclosure of Interest: None declared
P0378 REPORTED DELAY IN THE DIAGNOSIS OF COLORECTAL
CANCER: ANALYSIS OF GP REPORTS OF AVOIDABLE DELAY
FROM THE RCGP NATIONAL AUDIT OF CANCER
C.M. Dobson1, E. Titova2, G. Rubin1,*
1
School of Medicine, Pharmacy & Health, Durham University, Durham,
2
Lincolnshire Partnership NHS Foundation Trust, UK, Lincolnshire, United
Kingdom
Contact E-mail Address: c.m.dobson@durham.ac.uk
INTRODUCTION: The UK has significantly poorer cancer survival rates than
comparable countries(1) and diagnostic delay is perceived to be a significant
contributory factor to this (2). In 2009/10 The RCGP undertook a National
Audit of Cancer Diagnosis in Primary Care, obtaining data on 18,889 cancer
patients, from 1120 practices (3). GPs also provided free text comments on any
perceived avoidable delays within the patients diagnostic pathway.
AIMS & METHODS: The aim of this study was to analyse the principal causes
of delay, as reported by GPs.
The audit contained data on 2737 patients with colorectal cancer and avoidable
delay was reported for 36%. Free text reports of the nature of the delay were
available for 753 (28%) patients. These were transformed into quantitative data,
utilising an extended version of The Model of Pathways to Treatment (4) as an
analytical framework. Comments were independently categorised by CD and
GR, with disagreements in categorisation reconciled through discussion. A proportion (10%) of cases were also coded by ET, as a data quality measure. In
order to validate GP perceptions of diagnostic delay we compared categorised
primary care and referral intervals for patients with and without perceived delay,
using a chi-squared test.
RESULTS: GP reports of avoidable diagnostic delay were significantly associated with longer primary care and referral intervals (p 50.0001). The commonest reasons for delay were GP (mis)appraisal (29%), referral delays (e.g.
routine rather than urgent) (13%) and investigation delays (28%). For colorectal
cancer patients, help seeking delay was also a prominent factor (8%). Because
these causes of delay were reported by GPs there was a potential reporting bias,
with delays occurring prior to first consultation or in secondary care possibly
being under-reported.
CONCLUSION: The causes of diagnostic delay for patients with colorectal
cancer are complex. GP appraisal and type of referral appeared to be substantial
contributors to cases of avoidable diagnostic delay. Interventions aimed at reducing the time to diagnosis should consider the specific causes of delay for colorectal cancer patients.
REFERENCES
1. Coleman MP, Forman D, Bryant H, et al. Cancer survival in Australia,
Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the
International Cancer Benchmarking Partnership): an analysis of populationbased cancer registry data. Lancet 2011; 377: 127138.
2. Trring ML, Frydenberg M, Hansen RP, et al. Time to diagnosis and mortality in colorectal cancer: a cohort study in primary care. Br J Cancer 2011; 104:
934940.
3. Rubin G, McPhail S and Elliott K. Royal college of general practitioners:
national audit of cancer diagnosis in primary care, 2011.
4. Walter F, Webster A, Scott S, et al. The Andersen Model of Total Patient
Delay: a systematic review of its application in cancer diagnosis. J Health Serv
Res Policy 2012; 17: 110118.
Disclosure of Interest: None declared
P0379 CONFOCAL LASER ENDOMICROSCOPY FOR THE DETECTION
OF EARLY MUCOSAL CHANGES IN RECTAL STUMPS OF
PATIENTS WITH FAMILIAR ADENOMATOUS POLYPOSIS
C. Bucci1,2,*, V. DAngelo1, G.B. Rossi1, V. Passananti3, M. De Bellis1,
A. Tempesta1
1
Istituto Nazionale Tumori, Fondazione G. Pascale, Naples, 2University of Salerno,
Salerno, 3University Federico II, Naples, Italy
INTRODUCTION: Familial adenomatous polyposis (FAP) is an inherited,
autosomal-dominant disease caused by a germline mutation of the adenomatous
polyposis coli gene (APC). This condition inevitably leads to colorectal cancer.
Prophylactic colectomy, or proctocolectomy with ileal pouch-anal anastomosis
(IPAA) is recommended. Since any remaining rectal mucosa might still be at risk
for malignancy, endoscopic surveillance of both the residual rectal stump and the
ileal pouch is mandatory. Confocal laser endomicroscopy (CLE) is a novel technique that performs virtual histology of gastrointestinal mucosa with high accuracy, detecting in vivo early mucosal changes.
AIMS & METHODS: Aims: To assess the appropriateness of CLE for in vivo
diagnosis of abnormal mucosal changes in rectal stumps of patients with FAP.
Methods: Both white light endoscopy (WLE) and CLE were utilized in the examination of rectal stumps in 12 patients who had undergone proctocolectomy with
IPAA. During WLE normal mucosa and polyps were classified according to both

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United European Gastroenterology Journal 2(1S)

Paris and Kudo classifications. CLE images were scored according to the
MIAMI classification. Targeted biopsies were taken from normal mucosa and
polyps were removed with biopsy forceps or polypectomy snares. CLE and histological findings of both background mucosa and polyps were compared.
RESULTS: WLE revealed that all but one patient had diminutive polyps (table
1) and the background mucosa always appeared normal. CLE confirmed that
background mucosa was normal in all cases, whereas the diminutive polyps were
classified adenomas in 9/11 patients and hyperplastic in 2/11 cases. After pathological examination, biopsies of the background mucosa always revealed normal
colonic mucosa, while the diminutive polyps resulted to be 6/11 adenomas with
low grade dysplasia (LGD), 3/11 adenomas with high grade dysplasia and 2/11
LGD adenomas with serrated features.
White
light
Polyp
Patient size (mm) Endoscopy

Paris/Kudo
MIAMI
Classification Classification Histology

1
2
3
4
5
6

3
4
4
6
4
7

adenoma
adenoma
adenoma
adenoma
adenoma
adenoma

Is-IIIL
Is-IIIL
Is-IIIL
Is-IIIL
Is-IIIL
IIa-IIIL

adenoma
adenoma
adenoma
adenoma
adenoma
adenoma

Low grade adenoma


Low grade adenoma
High grade adenoma
High grade adenoma
Low grade adenoma
Low grade adenoma with
serrated features

adenoma

Is-IIIL

adenoma

8
9
10
11

3
5
3
3

adenoma
hyperplastic
hyperplastic
hyperplastic

Is-II
Is-IIIL
Is-II
Is-II

hyperplastic
adenoma
adenoma
hyperplastic

Low grade adenoma with


serrated features
High grade adenoma
Low grade adenoma
Low grade adenoma
Low grade adenoma

Table 1. Summary of findings in operated FAP patients undergoing surveillance


with WLE and CLE
CONCLUSION: CLE showed good correlation with pathology in diagnosing
diminutive polyps of rectal stumps in patients with FAP. Possibly, CLE could be
useful for tailoring the surveillance in these patients. However, further studies are
needed to confirm this hypothesis.
Disclosure of Interest: None declared
P0380 MICROMETASTASES IN THE SENTINEL NODE OF PATIENTS
WITH STAGE I AND II COLON CANCER
D.A. M. Sloothaak1,2,*, R.van der Linde3, M.S. Reimers4, C.J. van de Velde4,
W.A. Bemelman1, D. Lips3, J.C. van der Linden5, H. Doornewaard6, P.J. Tanis7,
E.S. van der Zaag2, K. Bosscha3, C.J. Buskens7
1
Surgery, Academic Medical Center, Amsterdam, 2Surgery, Gelre Hospital,
Apeldoorn, 3Surgery, Jeroen Bosch Hospital, s Hertogenbosch, 4Surgery, Leiden
University Medical Center, Leiden, 5Pathology, Jeroen Bosch Hospital, s
Hertogenbosch, 6Pathology, Gelre Hospital, Apeldoorn, 7Surgery, Academic
Medical Centre, Amsterdam, Netherlands
Contact E-mail Address: d.a.sloothaak@amc.nl
INTRODUCTION: According to the guidelines for TNM staging of colorectal
cancer, occult nodal tumour cells are categorised as micrometastasis (MMs) and
isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs,
but not ITCs, are prognostic for disease recurrence in patients with stage I/II
colon cancer.
AIMS & METHODS: The objective of this retrospective multicentre study was to
analyse the incidence of MMs in the sentinel node of patients with stage I/II colon
cancer, to analyse the correlation between MMs, tumour differentiation and vasoinvasive growth, and to analyse the prognostic value of MMs for disease recurrence. Patients with elective surgery for stage I/II colon cancer were identified from
databases about ex vivo sentinel lymph node mapping and ultrastaging, from three
Dutch hospitals (2005-2012 Gelre Hospital (GH), 2011-2013 Leiden University
Medical Center (LUMC) and 2010-2012 Jeroen Bosch Hospital (JBH)).
Immunohistochemical staining was performed with antibody against pan-cytokeratin (LUMC, JBH) or cytokeratin-18 (GH) and findings were classified according
to the 6th AJCC staging manual. Univariable analysis was applied for the correlation between MMs, tumour differentiation and vaso-invasive growth. Two year
disease-free-survival (2yDFS) of patients with MMs, ITCs and patients without
occult nodal tumour cells was compared with a Kaplan-Meier analysis.
RESULTS: A total of 214 patients were pooled in a multicentre database (GH
n 128; LUMC n 19; JBH n 67). MMs were found in twelve patients (5.6%),
ITCs in 39 patients (18.2%) and occult tumour cells were absent in 163 patients
(76.2%). Between these three groups, there were no significant differences in
baseline characteristics or type of surgery. Tumour differentiation and vasoinvasive growth were comparable as well. Four patients with MMs received
adjuvant therapy (33.3%) which was significantly more than patients with
ITCs (n 1; 2.6%) or patients without occult tumour cells (n 7;
4.3%)(p 0.004). After a median follow up of 20 months (IQR 20-47) recurrence
of cancer was diagnosed in 12 patients (5.1%). Three recurrences were diagnosed
in patients with MMs; one locoregional recurrence despite adjuvant treatment,
and two distant metastases in patients who did not receive adjuvant treatment.
Survival analysis showed a significantly reduced 2yDFS in patients with MMs
compared to patients with ITCs or patients without occult tumour cells
(p 0.013).
CONCLUSION: In this study, the incidence of MMs in patients with stage I/II
colon cancer was 5.6%, and was not correlated to tumour differentiation or vaso-

invasive growth. Despite a relative large proportion of patients with adjuvant


treatment, MMs were prognostic for disease recurrence.
Disclosure of Interest: None declared
P0381 PLASMA MICRORNAS AS SCREENING BIOMARKERS FOR
COLORECTAL ADENOMAS
A.M. Verma1,2, M. Patel1,2,*, M. I. Aslam1,2, P. Wurm2, J. Jameson2,
J.H. Pringle1, B. Singh2
1
Cancer Studies and Molecular Medicine, University of Leicester, 2University
Hospitals Leicester, Leicester, United Kingdom
Contact E-mail Address: ajaymarkverma@gmail.com
INTRODUCTION: The identification and resection of colorectal adenomas
during screening colonoscopy is the cornerstone of colorectal cancer prevention
within bowel cancer screening programmes (BCSP).
Biennial faecal occult blood testing (FOBt) of patients aged 60-75 is the screening
tool within the United Kingdom BCSP with a positive test identifying patients
requiring colonoscopy. At screening colonoscopy, the yield for adenomas is
46.5% and for adenocarcinomas in 6%. 1 Whilst effective, FOBt lacks high
sensitivity, specificity and accuracy. As a result, half of screening colonoscopies
are normal or reveal other gastrointestinal disorders such as haemorrhoids and
diverticular disease (that have lead to false positive FOBt results). This is a
concern as colonoscopy is an invasive test which can cause patient harm.
Another concern is the uptake of FOBt within screened populations is less
than 60%. 1
A biomarker screening test based on blood sampling may increase uptake
especially for individuals not keen to undertake faecal testing. If a biomarker
had a high sensitivity, specificity and accuracy, the proportion of patients undergoing screening colonoscopy and having a non adenoma/ adenocarcinoma diagnosis would fall.
AIMS & METHODS: We plan to investigate microRNAs (miRs short (18-24
nucleotides) evolutionary conserved non-coding RNA molecules) as potential
biomarkers. 220 FOBt positive patients undergoing BCSP colonoscopy were
recruited and samples of whole blood were taken (100 patients with adenomas,
90 controls normal or non adenoma/ adenocarcinoma diagnosis). RNA was
extracted from plasma and converted to complementary DNA. Pooled groups of
patients with adenomas and controls were analysed using array cards. MiRs 19a,
98, 146b, 186, 331-5p, 452 and 625 were identified as candidate biomarkers. All
cases were analysed for these candidates using quantative polymerase chain
reaction.
RESULTS: All 7 candidate MiRs showed significant differences in expression in
patients with colorectal adenomas when compared to controls.
MiRs 19a, 331-5p, 452 p 50.05, miRs 98, 146b p 50.01, miRs 186, 625
p 50.001.
When ROC curve analysis was performed area under the curve was higher in
patients with diverticular disease/ haemorrhoids than those without (0.866 vs
0.788).
CONCLUSION: This study suggest plasma miRs are potential screening biomarkers for patients with colorectal adenomas and also may help to identify
patients with adenomas in the cohort of patients with background diverticular
disease/ haemorrhoids. Further study and analysis is needed to validate these
exciting findings.
REFERENCES
1. Lee TJW, Rutter MD, Blanks RG, et al. Colonoscopy quality measures:
experience from the NHS Bowel Cancer Screening Programme. Gut 2012; 61:
1050-1057.
Disclosure of Interest: None declared
P0383 ACUTE TREATMENT OF MALIGNANT COLORECTAL
OCCLUSION: SELF-EXPANDABLE METALLIC STENTS AS
BRIDGE-TO-SURGERY OR PALLIATIVE TREATMENT VERSUS
EMERGENCY SURGERY
D. Fernandes1,*, S. Domingues1, B.M. Goncalves1, J.-B. Soares1, P. Bastos1,
A. Ferreira1, R. Goncalves1, A. Mesquita Rodrigues2, L. Lopes3, C. Rolanda1
1
Gastroenterology, 2Surgery, Hospital de Braga, Braga, 3Gastroenterology,
Unidade Local de Saude do Alto Minho, Viana do Castelo, Portugal
Contact E-mail Address: daliafernandes09@gmail.com
INTRODUCTION: Colorectal cancer presents as acute bowel occlusion in 1040% of the patients. There are two main therapeutic approaches for decompression: emergency surgery and the endoluminal placement of self-expandable
metallic stents (SEMS). Due to high mortality and morbidity rates associated
to emergency surgery, SEMS placement as bridge-to-surgery or as palliation is
being increasingly used with controversial results.
AIMS & METHODS: This study aimed to clarify the risk/benefit of the mentioned approaches. We conducted a retrospective longitudinal multicenter study,
including 189 patients with acute malignant colorectal occlusion, diagnosed
between January 2005 and March 2013. Demographic, clinical characteristics
of the patients, tumor features and procedure details were analyzed.
RESULTS: Globally (85 patients 35 bridge-to-surgery and 50 palliative)
SEMSs technical success was 94.4%. Palliative SEMS had a limited clinical
success (60.0%) and were associated to 40.0% of complications. SEMS occlusion
(18.8%) was the more frequent, followed by migration (9.4%) and bowel perforation (7.1%). Elective surgery after stenting was associated to a higher frequency of primary anastomosis (93.8% vs 76.4%; p 0.038), and a lower of
colostomy (25.7% vs 54.9%; p 0.004) and overall mortality (31.3% vs 56.7%;
p 0.020). However, no significant differences were identified concerning to
postoperative complications. In palliative treatment, there was no difference in
complications rate and overall mortality between SEMS and decompressive

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United European Gastroenterology Journal 2(1S)


colostomy. In this SEMS subgroup, we found a higher rate of reinterventions
(40.4% vs 5.0%; p 0.004) and a longer hospital stay (14,9 vs 7,3 days;
p 0.004).
CONCLUSION: SEMS placement as bridge-to-surgery should be considered in
acute treatment of colorectal malignant occlusion, since it has advantages regarding to primary anastomosis, colostomy rate and overall mortality. However, the
longer the SEMS stayed in place the higher the risk for complications. Therefore
in palliative SEMS, despite the possible psychological effect of not having a
colostomy, it does not seem to present significant advantages comparing to the
decompressive colostomy.
Disclosure of Interest: None declared
P0384 THE EVALUATION OF NEW COLORECTAL CANCER
TREATMENTS ON CHEMICALLY INDUCED COLON CANCER
MODEL
H. Kuznietsova1,*, H. Svitina2, O. Lynchak1, O. Babuta1, V. Kyryk3,
I. Skrypkina4, M. Kuchma2, Y. Shablii2, O. Dzhus1, E. Denis1, L. Garmanchuk1,
G. Lobintseva2, V. Shablii2, V. Rybalchenko1
1
Institute of biology, Taras Shevchenko National University of Kyiv, 2Institute of
Cell Therapy, 3State institute of genetics and regenerative medicine Academy of
Medicine of Ukraine, 4Institute of molecular biology and genetics of National
Academy of Science of Ukraine, Kyiv, Ukraine
Contact E-mail Address: biophyz@gmail.com
INTRODUCTION: Today new approaches for colorectal cancer treatment
appear through traditional chemotherapy failure. The specificity of potential
therapeutics, impact on malignant cells and/or their restraint within the tumor
nodes, as well as the mininization of therapy and carcinogenesis side effects, are
at the top of interests. Proteine kinase inhibitors are the most specific anticancer
agents due to malignant cell peculiarities, whereas stem cells are the most specific
anticancer drug vehicles due to tumor node metabolism. But the effects of the
first and the last often are evaluated on xenograft models characterized by the
immune deficient status of the host. So it is impossible to assess the state of the
organism experiencing cancer adequately.
AIMS & METHODS: The investigation of the effects of new protein kinase
inhibitors pyrrol derivates (PD) 5-amyno-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H- pyrrol-3-one and 1-(4-Cl-benzyl)-3-Cl-4-(CF3- fenylamino)-1H-pyrrol-2,5-dione compared with therapeutic 5-fluorouracil (5FU) and
the effect of allogenic trophoblast stem cells (TSC) on the tumor formation and
growth and on the state of apparently healthy colon mucosa was undertaken.
The 1,2-dimethylhydrazine (DMH) induced rat colon cancer model, which has
histopathological and biochemical features similar to human colorectal cancer,
was used. Carcinogenesis was initiated by 20 weekly injections of DMH (20 mg/
kg) (up to tumor formation equal R1-2N0-1M0 stage of human colorectal cancer)
and followed by PD daily or 5FU weekly treatments for 7 weeks, or with TSC
intravenous transplantation at 22nd week with no treatment for further 5 weeks.
At 27th week of experiment the animals were euthanized, the colorectal tumors
were counted and measured, the samples of colon walls with and without tumors
were processed and examined under the light microscopy.
RESULTS: PD reduces the tumor number (Nt) and total tumor lesions area (St)
at 27th week by preventing of new tumor formation and by regress of existing
ones, as well as 5FU does (Nt and St at 27th week are less than these ones at 20th
week). PD also diminishes the DMH-induced inflammation of the apparently
healthy colon mucosa, whereas 5FU escalates this process. The data obtained
suggest cell death predominantly by necrosis was caused by 5FU and by apoptosis one caused by PD. TSC transplanted at 22nd week at high dose (1.5*106
cells/kg) stops tumor growth compared to nontreated rats, as well as reduces
mucosa inflammation, but does not cause regression of existing tumors (Nt and
St at 27th week are the same at 22nd week). TSC transplanted at the same time at
low dose (0.5*106 cells/kg) attenuates the inflammation features but doesnt
affect tumor growth. We suppose TSC signals dominate the cancer stem cells
ones and therefore contribute to normalization of cancer stem cells microenvironment and thus prevent further carcinogenesis.
CONCLUSION: Targeted therapy is suitable for non-metastatic stage of colorectal cancer, whereas the administration of stem cells could stop further carcinogenesis only but couldnt reduce the existing tumor nodes.
Disclosure of Interest: None declared
P0385 THE INDICATION FOR ADDITIONAL SURGICAL COLECTOMY
WITH NODAL DISSECTION IN T1 COLORECTAL CARCINOMAS
H. Miyachi1,*, S.-E. Kudo1, K. Ichimasa1, Y. Kouyama1, T. Hisayuki1,
H. Oikawa1, Y. Mori1, M. Misawa1, T. Kudo1, K. Kodama1, T. Hayashi1,
K. Wakamura1, A. Katagiri 1, M. Kaga1, E. Hidaka1, F. Ishida1, S. Hamatani1
1
Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
HOSPITAL, Yokohama, Japan
INTRODUCTION: With the introduction of screening programs for colorectal
cancer and the recent advancement in EMR and ESD technology, a lot of T1
colorectal carcinomas are resected endoscopically with negative margins, and the
percentage of early carcinomas amenable to endoscopic resection has increased.
But, around 10% of the patients of T1 colorectal carcinoma have lymph node
metastasis (LNM). Then, additional surgical colectomy with nodal dissection
should be considered after endoscopic treatment. Therefore, it is critical to determine the criteria for curative endoscopic resection.
AIMS & METHODS: The aim is to clarify clinicopathological risk factors for
LNM of T1 colorectal carcinomas and to establish the indication for additional
surgical colectomy with nodal dissection.
A total of 19882 colorectal neoplasms excluding advanced cancers have been
resected endoscopically or surgically at our unit from April 2001 to October

2013. Of these, 907 T1 carcinomas were included. Initial or additional surgical


colectomy with nodal dissection was performed in 568 cases, and of which LNM
was found in 55 cases (9.7%). We analyzed the clinicopathological risk factors as
follows: age, gender, size, location, morphology, vessel permeation, tumor budding, poorly-differentiated or mucinous carcinoma (POR/MUC) component,
desmoplastic reaction (DR) on the superficial layer, degree of SM invasion,
and state of muscularis mucosae (MM grade). MM grade was evaluated into
two conditions using the desmin immunostaining: MM grade 1 (complete or
almost maintenance) and MM grade 2 (fragmentation or disappearance).
Finally, based on significant factors, we stratified these T1 cancers into 3
groups at ultralow, low and high risk of LNM.
RESULTS: The existence of vessel permeation, tumor budding, POR/MUC
component, MM grade 2 or the gender of female was significant. In contrast
with MM grade 2, no lesions corresponding to MM grade 1 had LNM. Among
T1 carcinomas with MM grade 2, male patients without vessel permeation,
tumor budding or POR/MUC component showed low incidence (1/93: 1.1%)
of LNM, while 54 (12.7%) of 433 patients with at least one factor had LNM.
CONCLUSION: The indication for additional surgical colectomy after endoscopic resection has been more clarified and simplified: MM grade 1 was suggested to be an anti-risk factor for nodal metastasis (Ultralow-risk group). T1
carcinomas with MM grade 2 and without female gender, vessel permeation,
tumor budding or POR/MUC component may be acceptable for only monitoring (Low-risk group). For T1 carcinomas with MM grade 2 and with at least one
factor, additional surgical colectomy with lymph node dissection should be
recommended (High-risk group).
Disclosure of Interest: None declared
P0386 DOES THE TYPE OF COLECTOMY MODIFY THE RISK OF
DESMOID TUMOR DEVELOPMENT IN FAMILIAL
ADENOMATOUS POLYPOSIS PATIENTS?
Z. Wang1, T. Walter2, O. Guillaud2, A. Pasquier3, E. Cotte3, O. Vinet2,
G. Poncet4, T. Ponchon5, J.-C. Saurin5,*
1
Hospices Civils de Lyon, Lyon, France, 2Gastroenterology, 3surgery, Hospices
Civils de Lyon, 4surgery, 5Gastroenterology, E. Herriot Hospital, Hospices Civils
de Lyon, Lyon, France
Contact E-mail Address: jean-christophe.saurin@chu-lyon.fr
INTRODUCTION: Desmoid tumors represent one major complication of the
disease in patients with familial adenomatous polyposis (FAP). Our aim was i) to
study factors associated with the development of desmoid tumors in a large
cohort of FAP patients and ii) to review the different treatment proposed with
corresponding results.
AIMS & METHODS: We reviewed retrospectively 190 cases of patients with
FAP, with complete medical records, followed at our institution between 1965
and 2013. There were 10 patients with biallelic MUTYH mutation (mean age
56,5 years) and 180 patients with either identified APC gene mutation, either a
personal and family history suggesting APC-related polyposis (mean age 44,1
years, 22-85).
Treatment of desmoid tumor was proposed in those patients with progressive
disease at radiological evaluation on a 4 to 6 month observational period. The
response was evaluated retrospectively from the reports, according to RECIST
criteria.
RESULTS: The median follow-up since the diagnosis of FAP was of 25 years.
No patients (0/10) with MUTYH mutation ever developed desmoid tumor. In
contrast, 31/180 (17.2%) patients with a mutation/phenotype of APC related
polyposis (11 H, 20 F) developed 58 DT, at a mean age of 44,1 yrs (range 2278 yrs). The localization of DT was: mesenteric 25, abdominal wall 25, extraabdominal 3 (breast 2, gluteal muscle 1). From these 180 patients, a colectomy
with ileo-rectal anastomosis had been performed in 104 (12 with DT, 11%) and
proctocolectomy in 76 (19 with DT, 25%, p 0.027). There was no other factor
associated with the development of DT, including the modality of surgery (laparotomy versus laparoscopy). As regards the treatment of DT: no treatment was
proposed in 3 patients (mean FU 7,17 years); 12 patients (with 28 DT) had 29
medical therapeutic sessions with a mean duration of 12,8 months (range 3-24
months). Following RECIST criteria, a response was observed in 3 tumors
(10.3%), a stabilisation in 17 cases (58.7%) and a progressive disease in 9
cases (31%). Medical treatment was: celecoxib (6 sessions), sulindac (9), tamoxifen (4), imatinib (8), sorafenib (1), bevacizumab (2). Surgical treatment of the
DT was attempted for 32 tumors from 16 patients: 12 mesenteric (5 recurrences,
41.6%) et 21 extra mesenteric (6 recurrences, 28.5%).
CONCLUSION: This study suggests that the type of colorectal surgery
(colectomy versus proctocolectomy) is a major determinant of the risk of developping desmoid tumors in APC type FAP patients. If confirmed, this may impact
profoundly our surgical choices in these patients. On the other hand, we confirm
the low efficacy of available medical treatments for desmoid tumors of FAP
patients, and the high prevalence of post-surgical recurrences.
Disclosure of Interest: None declared
P0387 RADIATION PROCTOCOLITIS RESPONSE TO ARGON PLASMA
COAGULATION
J.S. Mcgrath1,*, D. Pace2, J. Mercer1, M. Borgaonkar1
Medicine, 2Memorial University, St. Johns, Canada
Contact E-mail Address: jmcgrath@mun.ca

INTRODUCTION: A mainstay in the treatment of prostate and some gynecological cancers is the use of external beam radiation therapy. Radiation proctitis
is a well-recognized complication of pelvic radiation and Argon Plasma
Coagulation (APC) is a very effective means of treatment. The literature supporting the use of APC is small.

A238
AIMS & METHODS: The current study is a prospective analysis of patients with
radiation proctitis referred from the Newfoundland and Labrador Bliss Murphy
Cancer Centre. There were 81 patients referred to one gastroenterologist and 55
were treated with APC (Jan. 2010 to Dec. 2013). We studied the complete resolution of symptoms which was defined as the absence of rectal bleeding. A partial
resolution was defined as a reduction in rectal bleeding.
RESULTS: This prospective cohort study was performed on all adults who
underwent colonoscopy for radiation proctitis. In total, 81 patients were seen,
90.1% men and mean age 68.4 (range: 48-87 years). The average time between
the last dose of radiation and the development of symptoms of proctocolitis was
21.8 months (range: 0-132 months). Complete resolution of symptoms was
reported in 75.9% of cases, partial resolution in 22.2% and only one patient
(1.85%) showed no improvement. The mean sessions of treatment with APC
was 1.86, (range 1-4). Furthermore, 61.5% of those with incomplete response
had other potential sources of rectal bleeding identified such as hemorrhoids or
an anal fissure. The rate of complications was 3.6% with 2 patients developing a
rectal ulcer. Colonic adenomas were detected in 60.5% of individuals and colorectal cancer is 6.2%. Hemoglobin values before and after APC were available in
ten patients and the mean increase was 9.6 g/L (range: -3 to 25 g/L).
CONCLUSION: APC is a safe and effective therapeutic modality for the treatment of radiation-induced proctitis. Pelvic radiation exposure can be associated
with the development of symptoms of radiation proctitis. It is also associated
with the development of adenomas and colorectal cancer. This is the largest
reported case series to date regarding the utilization and efficacy of APC.
Disclosure of Interest: None declared
P0388 INHIBITION OF HUMAN AND MOUSE INTESTINAL AFFERENT
MECHANOSENSITIVITY BY ACTIVATION OF GUANYLATE
CYCLASE C
A. Broadhead1,*, C. McGuire1, D. Reed1, M. Peiris1, C. Knowles1, C. Kurtz2,
A. Silos-Santiago2, D. Bulmer1, L.A. Blackshaw1
1
Queen Mary University of London, London, United Kingdom, 2Ironwood
Pharmaceuticals Inc., Cambridge, United States
Contact E-mail Address: a.broadhead@qmul.ac.uk
INTRODUCTION: The guanylate cyclase C (GCC) agonist linaclotide reduces
abdominal pain in constipation-predominant IBS (IBS-C). Its mechanism of
action is via production and release of cyclic guanosine monophosphate
(cGMP) by intestinal epithelial cells, which subsequently acts on high-threshold
colonic afferent endings to reduce generation of pain signals in response to
mechanical stimuli[1].
AIMS & METHODS: To determine 1. if inhibition of afferents by GCC agonism
and by cGMP is seen also in a tubular preparation of mouse colon; 2. if this
translates to inhibition of responses to the same stimulus in human appendix.
Electrophysiological responses were recorded from human extrinsic nerve bundles innervating tubular preparations of appendix[2]. A similar preparation was
used in mice to record responses of lumbar splanchnic afferents innervating the
distal colon.
RESULTS: Distension of mouse colon caused reproducible, stimulus-dependent
excitation of splanchnic afferents up to 60mmHg. Administration of cGMP
(500uM) or GCC agonist (linaclotide 1uM) significantly reduced the response
to medium-level (40mmHg; N 7, p 0.01) and high-level distension (60mmHg;
N 7, p 0.02). No effect was seen on response to low-level distension
(20mmHg; N 7, p 0.9). In recordings of human appendix afferent responses
to ramp distension (0-60mmHg), we attempted to release endogenous cGMP by
activating GCC maximally with intraluminal enterotoxin ST (100nM). This had
a similar pattern of effect as activation of GCC on mice on responses to distension, inhibiting only at high levels of distension (25% reduction, N 5,
p 0.008).
CONCLUSION: GCC agonists inhibit mechanosensory responses to distension
in intact in vitro preparations of both human and mice large intestine, but only at
high intensities that correspond to those that would evoke pain in vivo. This
provides important validation of the mechanism of action of linaclotide in relieving pain in IBS-C via peripheral inhibition of nociceptors in human intestine.
REFERENCES
1. Castro J et al. Gastroenterology 2013; 145: 1334-1346.
2. Peiris M et al. Gut 2011; 60: 204-208.
Support: Ironwood Pharmaceuticals Inc., Forest Laboratories.
Disclosure of Interest: A. Broadhead Financial support for research from:
Ironwood Pharmaceuticals Inc., Bowel and Cancer Research, C. McGuire:
None declared, D. Reed: None declared, M. Peiris: None declared, C.
Knowles: None declared, C. Kurtz Financial support for research from:
Ironwood Pharmaceuticals Inc., Shareholder of: Ironwood Pharmaceuticals
Inc., A. Silos-Santiago Financial support for research from: Ironwood
Pharmaceuticals Inc., Shareholder of: Ironwood Pharmaceuticals Inc., D.
Bulmer Financial support for research from: Pfizer, Shareholder of: GSK, L.
A. Blackshaw Financial support for research from: Ironwood Pharmaceuticals
Inc., Grunenthal, Lecture fee(s) from: Almirall
P0389 PATHOPHYSIOLOGICAL
CHARACTERIZATION
OF
SYMPTOM-BASED CLUSTERS OF PATIENTS WITH IRRITABLE
BOWEL SYNDROME FOLLOWING A COMBINED NUTRIENT AND
LACTULOSE CHALLENGE TEST
B.L. Neve1,*, R. Brazeilles1, M. Derrien1, J. Tap2, D. Guyonnet1, H. Tornblom3,
L. Ohman3, M. Simren3
1
Life Science, Danone Research, Palaiseau, 2INRA, Jouy en Josas, France,
3
Department of Internal Medicine & Clinical Nutrition, Institute of Medicine,

United European Gastroenterology Journal 2(1S)


Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: boris.le-neve@danone.com
INTRODUCTION: We recently demonstrated that a combined nutrient and
lactulose challenge test allows symptom-based clustering of patients with irritable
bowel syndrome (IBS) unrelated to exhaled gas and Rome III subtype (Le Neve
et al Am J Gastro 2013; oral communication UEGW 2013).
AIMS & METHODS: The aim was to further characterize the two IBS clusters
previously identified. We included 100 patients with IBS (Rome III) and 38
healthy controls. The fasted subjects were served a test meal consisting of a
400ml liquid breakfast (Nutridrink, 1.5 kcal/ml) containing 25g lactulose.
The severity of gastrointestinal (GI) symptoms, fatigue, somatization, anxiety
and depression were evaluated by questionnaires before the test (IBS-SSS,
GSRS, VSI, FIS, PHQ-15, HAD), as well as visceral sensitivity (barostat) and
fecal microbiota composition (16S rRNA pyrosequencing). The intensity of eight
GI symptoms, the overall level of digestive comfort and the amount of exhaled
H2/CH4 were assessed every 15min during 4h after meal intake. A mapping of the
eight GI symptoms was done using a Principal Components Analysis (4h mean
score). Independently, a hierarchical cluster analysis was performed on the same
parameters to identify GI symptom-based IBS clusters.
RESULTS: The combined nutrient and lactulose challenge test discriminated
IBS from healthy controls. The challenge also allowed clustering of IBS patients
in two subgroups i.e High GI symptom (HGS) and Low GI symptom (LGS)
based on intensity of GI symptoms, in line with our previous study. Patients in
the HGS group (n 39; mean 4h pain 9.3, bloating 10.3, distension 11.2,
discomfort 11.8) displayed higher IBS-SSS score (353.7 vs. 236.8; p50.0001)
and higher levels of anxiety (9.0 vs. 7.0; p50.05), fatigue (71.3 vs. 42.2; p50.001)
and somatization (14.7 vs. 11.8; p50.01) as well as lower overall digestive comfort (8.0 vs. 12.8; p50.001) than patients in the LGS group (n 61; mean 4h
pain 2.4, bloating 3.0, distension 3.4, discomfort 4.8; p50.001). Patients
in the HGS group displayed significantly higher rectal sensitivity compared to
both LGS patients and healthy controls (p50.001 for pain intensity at 12 and
24mm Hg). No significant difference was seen between IBS clusters for fecal
microbiota composition.
CONCLUSION: A test meal containing 25 g of lactulose allows clustering of IBS
patients according to their GI symptom response, which reflects visceral sensitivity, IBS severity and psychological co-morbidity. This clustering cannot be
predicted by fecal microbiota composition. The lactulose challenge test appears
to be a promising tool to better define postprandial symptoms and the pathophysiology of IBS, and to non-invasively assess visceral sensitivity.
Disclosure of Interest: B. Le Neve Other: Danone Research employee, R.
Brazeilles Other: Danone Research employee, M. Derrien Other: Danone
Research employee, J. Tap Financial support for research from: Danone
Research, D. Guyonnet Other: Danone Research employee, H. Tornblom:
None declared, L. Ohman: None declared, M. Simren Financial support for
research from: Danone Research, Consultancy for: Danone Research
P0390 NORMAL SIGMOID PENETRABILITY TO FLUORESCENT
BEADS THE SIZE OF BACTERIA IN PATIENTS WITH IRRITABLE
BOWEL SYNDROME
C. Wising1,*, E. Almqvist2, L. Eklund2, H. Tornblom2, M. Simren2,
M.E. Johansson1, G.C. Hansson1, H. Sjovall2
1
Institute of Biomedicine, 2Institute of Medicine, Sahlgrens Academy, University of
Goteborg, Goteborg, Sweden
Contact E-mail Address: henrik.sjovall@medfak.gu.se
INTRODUCTION: Altered intestinal barrier function has been suggested to play
an important role in the pathophysiology of IBS, but the properties of one of the
most important components of the intestinal barrier, the intestinal mucus layer,
have not been studied in IBS. The colonic mucosa is covered by a thick mucus
layer consisting of an inner adherent layer and an outer loose layer. The inner
layer is normally devoid of bacteria. We tested the hypothesis that the penetrability of colonic mucus in situ to fluorescent beads the size of bacteria is
increased in patients with irritable bowel syndrome (IBS).
AIMS & METHODS: Sigmoid biopsies were taken from unprepared colon in 12
healthy controls (mean age 28 years, 5 males and 7 females) and 14 IBS patients
(2 males and 12 females), 2 IBS-C, 2 IBS-D and 10 IBS-M). 21 patients who
underwent colonoscopy for other reasons (e.g. bleeding of unknown origin), with
prepared colon, and 27 patients with ulcerative colitis (UC) in remission served as
positive controls. The biopsies were mounted horizontally in an oxygenized perfusion chamber. After 20 minutes, a standardized amount of fluorescent beads
with a size similar to that of bacteria (2 and 1 and 0.5 um) were added on the
mucosal side. 40 minutes later, bead distribution was assessed by confocal laser
microscopy at three laser frequencies, 488, 555 and 639 nm. The confocal images
were transferred into Matlab and were processed by customized software. Mean
bead intensity per 10 mm slice was calculated as a function of distance from end
of crypt openings and the distance of this slice from end of tissue was used as a
marker for bead penetrability. Mucus thickness was also measured repeatedly
over time in a horizontal perfusion chamber using a micropipette after addition
of charcoal particles to the apical side of the biopsy.
RESULTS: When measured repeatedly over time using carbon powder and a
micropipette ruler, mucus thickness after 60 min was 54065 mm in the controls
and 61050 in the IBS patients (p 0.19). When studied with fluorescent
microbeads, the distance of the slice with maximal bead intensity from the
mucosa at 60 minutes was 40060 mm in the controls and 47080 mm in the
IBS patients (p 0.50). In the control patients, with prepared colon, the corresponding value was 50060 mm (n.s.). In contrast, in prepared colon from UC
patients in remission the distance was 28060 mm (p50.01 versus other groups).
Three different bead sizes were used to test the occurrence of size-dependent

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United European Gastroenterology Journal 2(1S)


permeability. However, no significant differences in impermeable layer thickness
were found between the three bead sizes in any of the groups.
CONCLUSION: The values for mucus thickness in unprepared colon obtained
with the micropipette ruler carbon powder and the data obtained with the
fluorescent microbeads agree closely, with slightly lower values obtained with the
microbeads. In this small sample, sigmoid mucus from patients with IBS symptoms tended to have a mucus layer slightly thicker than in healthy controls (n.s.
with both techniques), while the UC patients in remission had a markedly
reduced thickness of the bead-impenetrable mucus layer.
REFERENCES
Johansson ME, Sjovall H and Hansson GC. The gastrointestinal mucus system
in health and disease. Nat Rev Gastroenterol Hepatol 2013; 10: 352-361.
Disclosure of Interest: None declared
P0391 A
PILOT
RANDOMIZED
PLACEBO-CONTROLLED
MULTICENTER STUDY ON THE EFFECT OF PALMITOYLETHANOLAMIDE AND POLYDATIN IN PATIENTS WITH
IRRITABLE BOWEL SYNDROME
C. Cremon1,*, G. Barbara1, L. Bellacosa1, M.R. Barbaro1, J. Santos2,
M. Vicario2, M. Pigrau2, C. Alonso2, S. Bruley des Varannes3, M. Neunlist3,
D. De Filippis4, T. Iuvone4, V. Di Marzo5, R. De Giorgio1, R. Corinaldesi1,
V. Stanghellini1
1
Department of Medical and Surgical Sciences, University of Bologna, Bologna,
Italy, 2Institut de Recerca de lHospital, Vall dHebron, Barcelona, Spain, 3Institut
des Maladies de lAppareil Digestif, Hotel Dieu, Nantes, France, 4Department of
Pharmacy, University of Naples Federico II, Naples, 5Institute of Biomolecular
Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Naples), Italy
Contact E-mail Address: cesare.cremon@aosp.bo.it
INTRODUCTION: Intestinal immune activation and mast cell intestinal infiltration play a pathophysiological role in the irritable bowel syndrome (IBS).
Palmithoylethanolamide (PEA), the saturated fatty acid ethanolamide of palmitic acid, structurally related to the endocannabinoid anandamide, exerts antiinflammatory and anti-nociceptive actions and inhibits mast cell activation.
Polydatin (PD) acts synergistically with PEA in reducing mast cell release of
cytokines and related T cell activation.
AIMS & METHODS: We designed a pilot, phase 2, randomized, double-blind,
placebo-controlled, multicenter study evaluating the efficacy and safety of PEA/
PD in patients with IBS. Patients with Rome III confirmed IBS and healthy ageand gender-matched subjects (HC) were recruited from 5 European study centers
(Bologna, Nantes, Barcelona, Tuzla, and Zagreb). After a 2-week run-in, the
patients were randomly assigned to oral tablets micronized PEA/PD 200 mg/
20 mg or placebo, b.i.d for 12 weeks. The efficacy evaluation included the assessment of: 1) mast cell infiltration and endocannabinoid system in patients with
IBS vs. HC. 2) the effect of active treatment vs. placebo on mast cell infiltration,
endocannabinoid system, and symptoms in patients with IBS. Colonic mucosal
biopsies were obtained during at screening visit and at the end of the study.
Biopsies were processed for quantitative immunohistochemistry for mast cells,
and for biomolecular analysis of the endocannabinoid system (by liquid chromatography and western blot).
RESULTS: A total of 54 patients with IBS (29 allocated to PEA/PD and 25 to
placebo) and 12 HC were recruited in the study. Mast cell counts were significantly
increased in patients with IBS in comparison with HC (5.3%2.7% vs. 3.21.3;
p 0.013). Compared to HC, expression of the peripheral cannabinoid receptor
CB2 in the tissue was higher in IBS (p 0.012) while the fatty acid amide oleoylethanolamide was significantly reduced (p 0.007). The logistic model for repeated
measures did not reveal statistically significant effects of PEA/PD on mast cells and
endocannabinoid system. Nonetheless, compared with placebo, PEA/PD improved
abdominal pain severity (repeated measure ANOVA test; P50.05).
CONCLUSION: Our study suggests that PEA/PD is a promising effective treatment in the management of pain in patients with IBS. Whether the PEA/PD
effect is secondary to mast cell stabilising or to modulation of the endocannabinoid system remains to be further investigated. ClinicalTrials.gov Identifier:
NCT01370720.
Disclosure of Interest: None declared
P0392 ASSOCIATION BETWEEN CHANGES
OF INTESTINAL
MICROBIOTA, CHARACTERISTICS OF ANORECTAL MOTILITY
AND RECTAL SENSITIVITY DISTURBANCES USING HIGHRESOLUTION ANORECTAL MANOMETRY (HRAM) IN PATIENTS
WITH DIARRHEA-PREDOMINANT IRRITABLE BOWEL
SYNDROME
E. Polouektova1,*, S. Kuchumova1, V. Ivashkin1, E. Kostryukova 2,
O. Storonova1, O. Liashenko1, A. Troukhmanov 1, V. Govorun2, O. Shifrin1,
A. Sheptulin1
1
I. M. Sechenov First State Moscow Medical University, 2Scientific Research
Institute of Physical-Chemical Medicine, Moscow, Russian Federation
Contact E-mail Address: polouektova@rambler.ru
INTRODUCTION: At present the role of changes of the intestinal microbiota in
pathogenesis of irritable bowel syndrome (IBS) is widely discussed. Impact of
microbiome on the gastrointestinal motility and visceral hypersensitivity is
assumed. However the relevant data have been investigated insufficiently.
AIMS & METHODS: To estimate correlation between changes of the composition of intestinal microbiota, anorectal motility disorders and visceral hypersensitivity in patients with diarrhea-predominant IBS (IBS-D).
31 patients with IBS-D (clinical type was determined according to the ROME III
criteria) and 15 healthy volunteers were studied. All subjects were analysed by
examining sequencing data of the 16s rRNA from fecal samples, the hydrogen

breath test with lactulose to determine small intestinal bacterial overgrowth


(SIBO), high-resolution anorectal manometry (HRAM) using 20 channel
water-perfused catheter with a polyethylene balloon (Solar GI, MMS, the
Netherlands).
RESULTS: By sequencing of the 16s rRNA differences were found in the composition of intestinal microbiota between the IBS-D patients and healthy volunteers. In patients with IBS Bacteroides (18.9%), Coprococcus (7.2%) and Blautia
(5.4%) were detected more often, the control group showed prevalence of Blautia
(17.1%), Prevotella (8.3%) and Faecalibacterium (6.9%) (p50.05). A positive
result of breath test (the presence of SIBO) was found in 20 patients with IBSD (62.5%) and was not detected in the control group. A negative correlation was
revealed between positive result of the breath test and the following parameters
of rectal sensitivity and function of the anal sphincter: average pressure of the
anal sphincter, average maximum compression pressure of the anal sphincter, the
threshold for strong urge to defecate and maximum tolerable volume (p50.05).
CONCLUSION: Disruptions in the qualitative and quantitative composition of
intestinal microbiota are found in patients with IBS-D; these changes are correlated with the parameters of anorectal motility and rectal sensitivity.
Disclosure of Interest: None declared
P0393 INSULAR HTR1A-NR2B PATHWAY MEDIATE THE VISCERAL
HYPERSENSITIVITY INDUCED BY CHRONIC STRESS IN RATS
H. Sun1,*, L. Yi1, L. Zhou1, Y. Chen1, Y. Jiang1, P. Wu2, S. Xu1
Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji
Hospital, Tongji University School of Medicine, 2Clinical Nutrition, Tongji
Hospital, Tongji University School of Medicine, shanghai, China
Contact E-mail Address: s-haijie@163.com
1

INTRODUCTION: In many clinical studies, 5-HT1A receptor (HTR1A) of the


central nervous system (CNS) was thought to be important in the pathogenesis of
chronic stress related functional gastrointestinal disorders (FGIDs), but its
potential mechanism is still not clear. Some studies thought the abnormality of
HTR1A in CNS, through changing neuron activities of visceral sensory area such
as insular cortex, mediated visceral hypersensitivity which was an important
pathophysiological mechanism of stress-related FGIDs. NR2B was perhaps
one key downstream signaling molecule of HTR1A. Insular HTR1A-NR2B
pathway is inferred to be important in modulating the visceral hypersensitivity
induced by chronic stress.
AIMS & METHODS: This study aimed to determine if insular HTR1A-NR2B
pathway influences the activity of insula and mediates the visceral hypersensitivity induced by chronic stress in rats. Chronic water avoidance stress (WAS) was
used to establish visceral hypersensitivity rat models. Visceral sensitivity was
determined by measuring the visceromotor response (VMR) amplitude to
60mmHg colorectal distention (CRD). The HTR1A agonist 8-OH-DPAT and
the HTR1A antagonist WAY100635 were microinjected into the left or right
insular cortex. The expression levels of 5-HT, HTR1A, NR2B and c-fos were
observed by RT-PCR, Western Blot or immunohistochemical staining.
RESULTS: Compared with sham WAS and normal rats, the expression levels of
5-HT and HTR1A in the bilateral insular cortex of WAS rats were significantly
lower (p50.05), but the expression levels of c-fos and NR2B were significantly
higher in the bilateral insular cortex of WAS rats (p50.05). After 8-OH-DPAT
intervention of left or right insular cortex, the VMR amplitudes to 60mmHg
CRD could be significantly reduced in WAS rats (p50.01). After WAY100635
intervention of left or right insular cortex, the VMR amplitudes have no significant changes in WAS rats (p40.05). The expression levels of bilateral insular
NR2B and c-fos in 8-OH-DPAT intervention group were significantly lower than
that in WAY100635 intervention group (p50.05).
CONCLUSION: Through regulating the activity of insular neuron, HTR1ANR2B pathway has a critical role in mediating the visceral hypersensitivity
induced by chronic stress in rats.
Disclosure of Interest: None declared
P0394 HIGHER FREQUENCY OF NEGATIVE SELF-ESTEEM AND
INFERIOR COPING STRATEGIES FOUND AMONG IBS PATIENTS
A. Faresjo1,*, L. Viktorsson2, V. Tegelstrom3, T. Faresjo1, M.P. Jones4,
S. Walter5, E. Grodzinsky3
1
Medicine and Health, linkopings University, Community medicine, 2Medicine and
Health, Linkopings universitet, 3Unit of Research and development, County
Council of Ostergotland, Linkoping, Sweden, 4Psychology Department, Macquarie
University, Sydney, Australia, 54Institution of Clinical and Experimental Medicine,
Division of Gastroenterology, Linkoping, Sweden
Contact E-mail Address: ashild.olsen.faresjo@liu.se
INTRODUCTION: A positive self-image is one of the key components for good
health and wellbeing. Irritable Bowel Syndrome has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances somatization, catastrophizing or altered visceral interoception by
negative emotions and stress (1,2).
AIMS & METHODS: Aims to investigate the psychosocial constructs of selfesteem and sense of coherence among IBS patients compared to non-IBS
patients. A case-control study in primary care setting among IBS patients meeting the ROME III criteria (n 140) compared to controls i.e non-IBS patients
(n 213) in primary care without any present or previous gastrointestinal complaints. The data were collected through self-reported questionnaires of psychosocial factors.
RESULTS: IBS patients reported significantly higher frequency of more negative
self-esteem than controls (p50.0001), had lower scores on the positive selfesteem measurement (p50.0001), and lower sense of coherence (p50.0001)
than the controls. The IBS cases were also less likely to report good health

A240
status (p50.0001) and less likely to report a positive belief in the future
(p50.0001). After controlling for relevant confounding factors in multiple
regressions, the more negative self-esteem for IBS patients remained statistically
significant (p 0.02), as were the lower scores for sense of coherence for IBS
cases (p 0.04).
CONCLUSION: The more frequently reported negative self-esteem and inferior
coping strategies among IBS patients found in this study suggest the possibility
that psychological therapies such as cognitive behavior therapy might be helpful
for these patients. However these data do not indicate the causal direction of the
observed associations. More research is therefore warranted to determine whether
these psychosocial constructs are more frequent personality traits in IBS patients
or if the disease itself lowers self-esteem and leads to inferior coping strategies.
REFERENCES
1. Bengtsson M, Sjoberg K, Candamio M, et al. Anxiety in close relationships is
higher and self-esteem lower in patients with irritable bowel syndrome compared
to patients with inflammatory bowel disease. Eur J Intern Med 2013; 24: 266-272.
2. Lackner JM, Gudleski GD, Firth R, et al. Negative aspects of close relationships are more strongly associated than supportive personal relationships with
illness burden of irritable bowel syndrome. J Psychosom Res 2013; 74: 493-500.
Disclosure of Interest: None declared
P0395 LABOUR PRODUCTIVITY LOSS BECAUSE OF IRRITABLE
BOWEL SYNDROME COMPLAINTS
C. Flik1,*, W. Laan1, A. Smout2, N.de Wit1
1
Julius Center, Health Sciences and Primary Care, University Medical Centre,
Utrecht, 2Gastroenterology and Hepatology, Academic Medical Centre,
Amsterdam, Netherlands
Contact E-mail Address: c.e.flik@umcutrecht.nl
INTRODUCTION: Irritable Bowel Syndrome (IBS) is the most prevalent
chronic functional bowel disease. IBS often results in a substantial disease
burden for the patient and leads to considerable medical costs. Systematic
reviews reporting economic consequences of IBS focus on direct medical costs
and indirect societal costs, such as loss of productivity. When calculating indirect
costs for IBS most researchers only take the costs for loss of labour days into
account. In our view disease-related loss of labour productivity should also consider the IBS-related impact on work productivity on the days that the IBS
patient is present at work.
AIMS & METHODS: We report the overall impact of IBS on labour productivity, i.e. the combined number of sick leave days and the loss of efficiency
during the days IBS patients did work with active IBS complaints.
207 adult patients (18-65 years of age) with IBS, meeting Rome III criteria, who
were recruited for a randomized controlled trial on hypnotherapy were selected.
The impact of IBS on work was measured with four questions of the Trimbos/
iMTA questionnaire for Costs associated with Psychiatric Illness (Tic-P): question 1 is about absenteeism from work because of IBS in the past two weeks (yes/
no), Q2 about absenteeism for more than two weeks (yes/no),Q3 assessed if one
was hindered by IBS complaints when working in the past two weeks (no, not at
all; yes, somewhat; yes considerably) and Q4 assessed how efficient one has
worked with the IBS complaints (from zero, indicating maximally inefficient
up to 10: as efficiently as normal).
RESULTS: Of the 140 patients who had a job, 104 (74.3%) were women and 36
(25.7%) men. Of these female IBS patients 19 (18.2%) were absent from work
because of IBS complaints, 10 (9.6%) less than two weeks, 9 (8.7%) more than
two weeks. Eleven of these patients had moderate and 8 patients had severe IBS.
Five of the male IBS patients (13.9%) were absent from work because of IBS complaints, 3 (8.3%) less than two weeks, 2 (5.6%) more than two weeks; one had
moderate and four severe IBS. IBS subtype was known of 131 working IBS patients,
21 (16%) had IBS-Constipation, 33 (25.2%) had IBS-Diarrhea and 77 (58.8%) had
IBS-Mixed type. Of the patients with IBS-C 2 (9.5%) were absent less than two
weeks, 0% more than two weeks; of the patients with IBS-D 3 (9.1%) were absent
less than two weeks and 2 (6.1%) more than two weeks; of the patients with IBS-M 8
(10.4%) were absent for less than two weeks and 8 (10.4%) for more than two weeks.
In 20% of the female and 7% of the male working IBS patients IBS complaints
had no impact on their labour productivity, 64% of women and 23% of men
were hindered to some extent and 16% of women and 23% of men were hindered
very much by their IBS complaints in performing their job; 33.3% of women and
52.8% of men indicated that they worked less efficiently than normal (score  6)
because of their IBS complaints.
CONCLUSION: IBS complaints do not only result in substantial absenteeism
from work, but also in severe loss of efficiency among those IBS patients who do
not report sick, but continue working. When quantifying disease-related loss of
labour productivity both aspects should be taken into account.
Disclosure of Interest: None declared
P0396 EXTENSIVE OVERLAP AMONG PATIENTS WITH IRRITABLE
BOWEL SYNDROME WITH CONSTIPATION, CHRONIC
IDIOPATHIC CONSTIPATION, FUNCTIONAL DYSPEPSIA, AND
GASTROESOPHAGEAL REFLUX DISEASE: A CROSS-SECTIONAL,
POPULATION-BASED SURVEY
N. Vakil1, J.M. Johnston2,*, M. Stelwagon2, E. Shea2, S. Miller3
1
University of Wisconsin School of Medicine and Public Health, Madison,
2
Ironwood Pharmaceuticals, Cambridge, 3Lieberman Inc., Great Neck, United
States
INTRODUCTION: Individuals with functional gastrointestinal disorders
(FGIDs) may report symptoms of more than one FGID as well as symptoms of
gastroesophageal reflux disease (GERD). This US cross-sectional Internet-based
survey assessed overlap of these disorders and sufferers symptom experience.

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: A random sample of 10,030 US citizens completed an
online screening questionnaire to identify those meeting Rome III criteria for
irritable bowel syndrome with constipation (IBS-C), chronic idiopathic constipation (CIC), and/or functional dyspepsia (FD), and/or who reported GERD
(defined as heartburn or regurgitation twice/week in the absence of treatment).
Survey responses were weighted for age and gender to be representative of the US
census. Respondents who met criteria for 1 condition completed a detailed
questionnaire including a symptom checklist and questions about bothersomeness, severity and frequency of symptoms and healthcare-seeking behaviour.
Respondents reported symptoms experienced in the past 12 months, rating
them on a scale from less than 5 days a year to everyday. Overall and
individual gastrointestinal (GI) symptom bothersomeness was reported on a 5point scale from not at all to extremely bothersome.
RESULTS: A total of 2641 respondents met criteria for 1 condition. Including
those with overlapping conditions, 328 met criteria for IBS-C, 552 for CIC, 1690
for FD and 1337 for GERD; 56.5%, 39.9%, 44.7% and 44.2%, respectively,
reported very/extremely bothersome GI symptoms. Overall, 1592 (60.3%) met
criteria for a single condition, 832 (31.5%) met criteria for 2 conditions and 217
(8.2%) met criteria for 3. Of the 4 conditions, respondents with IBS-C were the
most likely to have overlapping conditions. Overall bothersomeness of symptoms
increased with condition overlap: 22.5-30.4% of respondents with 1 condition
had very/extremely bothersome symptoms, compared to 37.1-65.7% of those
with 2 conditions, and 65.1-73.5% of those with 3 conditions. With the exception
of heartburn/acid reflux, the frequency and bothersomeness of individual symptomsincluding abdominal pain, bloating, diarrhea, and constipationalso
increased with condition overlap.
TABLE 1. Condition Overlap

N (total 2641)
One Condition Only
and IBS-C1
and CIC1
and FD1
and GERD1
3 conditions

IBS-C
(n 328)

CIC
(n 552)

FD
(n 1690)

GERD
(n 1337)

57 (17%)

207 (38%)

721 (43%)
247 (15%)
289 (17%)

247 (75%)
137 (42%)
113 (34%)

289 (52%)
160 (29%)
104 (19%)

607
137
160
650

650 (38%)
217 (13%)

(45%)
(10%)
(12%)
(49%)

217 (16%)

CONCLUSION: Functional GI disorders frequently overlap with each other and


with GERD. Patients with overlapping FGIDs have more frequent and bothersome symptoms and greater symptom burden. Results of clinical trials in FGIDs
may be modified by overlapping FGIDs; baseline symptom severity may be
affected by FGID overlap and global response measures may mask therapeutic
response in one or the other FGID. (Study sponsored by Forest Laboratories, Inc.,
and Ironwood Pharmaceuticals, Inc.)
Disclosure of Interest: N. Vakil Financial support for research from: Pfizer,
Consultancy for: Astra Zeneca, Ironwood, Otsuka, Takeda, Shareholder of:
Meridian (stock ownership), J. Johnston Shareholder of: Ironwood
Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals, M. Stelwagon
Shareholder of: Ironwood Pharmaceuticals, Other: Employee Ironwood
Pharmaceuticals, E. Shea Shareholder of: Ironwood Pharmaceuticals, Other:
Employee Ironwood Pharmaceuticals, S. Miller Consultancy for: Astra Zeneca,
Ironwood, Otsuka, Takeda, Pfizer
P0397 THE PATH FROM GI SYMPTOMS TO DEPRESSED MOOD AND
ELEVATED STRESS: IS IT SPECIFIC TO IBS?
M. Jones1,*, S. Walter2, E. Grodzinsky3, L. Viktorsson3, N.J. Talley4, A. Faresjo5
1
Psychology Department, Macquarie University, North Ryde, Australia,
2
Institution of Clinical and Experimental Medicine, 3Department of Medical and
Health Sciences, Linkoping University, Linkoping, Sweden, 4Faculty of Health &
Medicine, University of Newcastle, Callaghan, Australia, 5Dept of Medicine and
Health Sciences, Linkoping University, Linkoping, Sweden
Contact E-mail Address: mike.jones@mq.edu.au
INTRODUCTION: The irritable bowel syndrome (IBS) has been associated with
depressed mood1 and elevated levels of perceived life stress2, presumably via the
adverse effects of the gastrointestinal (GI) symptoms associated with the disorder. However some degree of GI symptoms are also present in non-IBS individuals, including healthy community members.
AIMS & METHODS: We aimed to determine whether the path from GI symptoms to disordered mood leading to elevated perceived stress was different in IBS
and non-IBS or undifferentiated between these groups.
Subjects (n 192, 16% IBS, 84% controls) were all patients at primary health
care clinics in one of three Swedish cities as part of the Twin Cities study based
at Linkoping University. Rome II criteria were assessed by the standard Rome
Foundation questionnaire. GI symptom burden was assessed by 14 day diary and
measures included percent of days with record of nausea, bloating, any abdominal pain (AP), moderate AP and intense AP. Maximum recorded pain intensity
was also noted. Mood was assessed via questions addressing depression symptoms and the EuroQol 5 questionnaire. Stress was measured via the Perceived
Stress Scale (PSS). A Structural equation model (SEM) was used to model latent
variables for GI symptom burden predicting mood, which then predicted stress.
Standardized path coefficients are reported along with measures of model fit.
RESULTS: In the combined sample GI symptom burden was found to predict
mood (b 0.184, SE 0.076) and mood was found to predict stress (b 0.591,
SE 0.080). When stratified, the model path coefficients were not different in
any significant respect between IBS and non-IBS patients. GI symptoms

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United European Gastroenterology Journal 2(1S)


predicting mood yielded: IBS (b 0.163, SE 0.176) and control (b 0.219,
SE 0.090) while for mood predicting stress: IBS (b 0.708, SE 0.141) and
control (b 0.582, SE 0.089). Model fit did not differ significantly between
the combined and stratified models, indicating that the subtle observed differences in path coefficients were consistent with random chance. The latent variables representing GI symptoms and mood provided an adequate representation
of the GI and mood constructs (c2/df 1.73, CFI 0.99, RMSEA 0.06). This
was equally true in the IBS and control groups.
CONCLUSION: Our data support the general hypothesis that symptom experience is associated with elevated mood disturbance which is associated with elevated levels of psychological stress. However while it has been assumed that there
is something special about IBS symptomatology that induces mood disorder, our
data suggests that while IBS is associated with higher levels of symptoms, the
association between GI symptoms and mood, thence perceived stress exists
equally in IBS and non-IBS individuals.
REFERENCES
1. Blanchard, EB, et al. The role of anxiety and depression in the irritable bowel
syndrome. Behav Res Ther 1990; 28: 401-405.
2. Murray, CD, et al. Effect of acute physical and psychological stress on gut
autonomic innervation in irritable bowel syndrome. Gastroenterology 2004; 127:
1695-1703.
Disclosure of Interest: None declared
P0398 FUNCTIONAL SYMPTOMS IN THE GENERAL POPULATION
DIARY VERSUS QUESTIONNAIRE
M. Jones1,*, S. Walter2, N. Talley3, L. Agreus4, A. Andreasson4,5
Department of Psychology, Macquary University, North Ryde, Australia,
2
Institution of Clinical and Experimental Medicine (IKE), Linkoping University,
Linkoping, Sweden, 3Faculty of Medicine, University of Newcastle, Newcastle,
Australia, 4Karolinska Institutet, Centre for Family Medicine, Huddinge, 5Stress
Research Institute, Stockholm University, Stockholm, Sweden
Contact E-mail Address: anna.andreasson@ki.se
1

INTRODUCTION: Previous studies have found discrepancies between recall


and diary reports of symptoms[1]. While questionnaires are commonly used
and convenient they can also be prone to recall bias [2]. Since the standard
Rome criteria are symptom recall based, if the source of symptom information
tangibly changes the clinical picture it calls into question diagnostic criteria.
AIMS & METHODS: We investigated the concordance between the IBS-supportive criteria pain relieved by defecation and onset of stools associated with
a change in stool consistency between questionnaire recall and prospective diary
reports. The present study population consists of 272 participants of a random
population based colonoscopy study. Pain relieved by defecation (PRBD) was
identified in 7 day diary records by selecting all hours when defecation was
reported then checking whether pain was reported in a two-hour window prior
to the hour in which defecation was reported but was absent in the two hour
window after defecation was reported. The Rome II IBS criterion of stool consistency altered by pain was assessed by comparing the distribution of Bristol
stool scores (Bristol) on days when pain was reported to the distribution on days
when no pain was reported. Statistical contrasts, based on unconditional logistic
regression, are adjusted for repeated measurements on individuals using the
linearization method to yield correct standard errors and p-values.
RESULTS: Pain relieved by defecation: The PRBD pattern was ever identified in
3.4% of participants compared with the corresponding questionnaire item asking
whether pain was ever relieved by defecation in a 3-month recall period where the
prevalence was 55.3%. However concordance between diary and questionnaire
was only 66.1% and kappa was close to zero (0.07). The PRBD diary pattern was
seen significantly more often in persons who reported pain relieved by defecation
on the questionnaire (7.2%) than persons who did not (1.3%) indicating that
diary and questionnaire are not completely disconnected. Change in stool form
with pain: Among all participants, hard stools were more often reported on pain
days (OR: 4.06, 95% CI: 2.14-7.71, p50.001 for Bristol score 1 and OR: 2.67,
95% CI: 1.61-4.42, p50.001 for Bristol score 2). However this was true for all
participants, regardless of whether they reported onset of pain or discomfort
associated with hard stools on the questionnaire. No difference in the occurrence
of loose stools on pain versus non-pain days was observed, not even in participants who reported onset of pain associated with loose stools.
CONCLUSION: The poor concordance between prospective diary and retrospective questionnaire might be due to any of: 1) poor recall when completing
questionnaires, 2) symptoms fluctuate over short time scales or 3) a 7 day diary is
too short to accurately capture low prevalence conditions. Given the apparent
central importance of measurement methodology to prevalence of disease the
reasons for this poor concordance needs to be elucidated.
REFERENCES
1. Dinning PG, et al. The impact of laxative use upon symptoms in patients with
proven slow transit constipation. BMC Gastroenterol 2011; 11: 121.
2. Coughlin SS. Recall bias in epidemiologic studies. J Clin Epidemiol 1990; 43:
87-91.
Disclosure of Interest: None declared
P0399 EFFECT OF THE FODMAP-RESTRICTED DIET ON COLONIC
GAS PRODUCTION CAPACITY IN PATIENTS WITH FUNCTIONAL
GASTROINTESTINAL DISORDERS
M.L. Ones1,*, I. Thun1, F.Van Megen1, M.H. Morken1, G.E. Kahrs1,
G.M. Oldery1, T. Hausken1, J.G. Hatlebakk1
1
Department of Clinical Nutrition and Section of Gastroenterology, Department of
Medicine, Clinical Institute 1 (K1), University of Bergen, Haukeland University

Hospital, Bergen, Norway


Contact E-mail Address: mon083@student.uib.no
INTRODUCTION: The FODMAP-(fermentable oligo-, di-, and monosaccharides and polyols) restricted diet is used as a treatment for functional gastrointestinal disorders such as irritable bowel syndrome (IBS) [1], with the goal of
reducing fermentation and gas related symptoms. We wanted to investigate
whether the capacity for gas production changed over time when consuming a
FODMAP-restricted diet among patients with IBS or functional dyspepsia (FD).
AIMS & METHODS: 29 patients with IBS (n 19) or FD (n 10), were diagnosed according to ROME III criteria for IBS and FD (24F/5M, age 3411y).
Participants were instructed thoroughly about the diet from a clinical dietician
and followed closely for 6  1 weeks. Repeated 4 days prospective food records
(baseline and 6 weeks) were used to measure diet changes and adherence to the
diet. Lactulose breath test was performed before, and during the last week of the
diet. Participants were adviced to not drink/eat/smoke 10 hours before the test
(usually at 8:30). After baseline breath test they consumed 10 g of lactulose
dissolved in 120 ml water and breath samples were collected every 15 min for
180 min. Hydrogen and methane gas was analysed in a Model SC Quintron Gas
Chromatograph. The area under the curve (AUC) was used as a measurement for
gas production, and breath samples before lactulose intake were used to study
adherence with the diet. Statistical test used were paired t-test, Wilcoxon signed
rank and Spearman and Pearson correlation test.
RESULTS: The FODMAP intake significantly decreased from median 8 g/d to
0.25 g/d (p 5 0.0001), and good adherence was also verified by baseline breath
samples for hydrogen which decreased from median 6 to 2 ppm (p 0.0124), and
methane from median 25 to 18 ppm (n.s. p 0.6797). 28 (18 IBS/10 FD) had
hydrogen production and there was a significant reduction from median 4418 to
1710 ppmxmin (p 0.0035) during the diet intervention. 9 (7 IBS/2FD) participants had methane production, with a reduction from median 9495 to 6750
ppmxmin (n.s. p 0.5415). Correlation between the change in FODMAP
intake and the change in hydrogen (r -1609, p 0.4045) or methane production
was not significant (r -0.1019, p 0.7943).
CONCLUSION: The FODMAP-restricted diet was associated with a reduction
in the capacity for hydrogen gas production in patients with IBS or FD, which
might indicate a shift in colonic microbiome
REFERENCES
1. Halmos EP, et al. A diet low in FODMAPs reduces symptoms of irritable
bowel syndrome. Gastroenterology 2014; 146: 67-75 e5.
Disclosure of Interest: None declared
P0400 WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT IN IBS: A
MULTIFACETED PROBLEM
A. Frandemark1,*, G. Ringstrom1, H. Tornblom1, M. Simren1
1
Deparment of Internal Medicine & Clinical Nutrition, Institute of Medicine,
Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
Contact E-mail Address: asa.frandemark@gmail.com
INTRODUCTION: IBS is one of the most prevalent functional gastrointestinal
disorders. Earlier studies have shown that IBS patients are more likely to be
impaired at work and during daily activities compared to non-IBS patients.
However, factors of importance for this impairment have not yet been fully
examined.
AIMS & METHODS: Our aim was to investigate the relationship between work
impairment and other factors related to IBS. We included 533 patients with IBS
(median age 34 (17-80) years, 420 females). The patients completed the Work
Productivity and Activity Impairment Questionnaire:IBS (WPAI:IBS), as well as
questionnaires to assess IBS symptom severity (IBS-SSS), GI-specific anxiety
(VSI), somatic symptoms (PHQ-15), depression and anxiety (HAD), and fatigue
(MFI). Uni- and bivariate analyses were performed, as well as linear regression
analyses to determine factors independently associated with the work productivity and activity impairment measures.
RESULTS: The IBS patients reported 719% (meanSD) absenteeism (actual
work time missed), 3325% presenteeism (impairment while at work), 3627%
overall work productivity loss and 4627% activity impairment. Female IBS
patients reported greater activity impairment than males (4727 vs. 4127%;
p50.05), but no other gender differences were found. A weak, but statistically
significant negative association was noted between age and activity impairment
(rho -0.11; p50.05), but otherwise age was not associated with the work productivity and activity impairment. No differences between IBS-subtypes were
found. With increasing severity of IBS symptoms, somatic symptoms and GIspecific anxiety, higher degrees of absenteeism, presenteeism, overall work productivity loss and activity impairment were seen (p50.0001 for all). Among the
fatigue measures, physical fatigue, general fatigue and reduced activity demonstrated the strongest associations with the work productivity and activity impairment (rho 0.28-0.47; p50.01). Weaker, but still statistically significant
associations were seen between general anxiety and depression and presenteesim,
overall productivity loss and activity impairment (rho 0.19-0.30; p50.05).
Using linear regression analysis, IBS symptom severity, GI-specific anxiety and
general fatigue were independently associated with presenteeism (R2 0.36;
p50.05) and overall productivity loss (R2 0.42; p50.05), while activity impairment was independently associated with IBS symptom severity and general fatigue (R2 0.40; p50.05).
CONCLUSION: Work productivity and activity impairment is a substantial
problem in patients with IBS. A combination of IBS and somatic symptom
severity, fatigue and psychological factors seem to impact the IBS patients ability to be active and productive at work. Based on this, a multidimensional
treatment approach for IBS patients seems logical.
Disclosure of Interest: None declared

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P0401 THE SEVERITY OF SYMPTOMS RELATED TO IRRITABLE


BOWEL SYNDROME IS A RISK FACTOR FOR THE
MISCLASSIFICATION OF SIGNIFICANT ORGANIC DISEASE

P0403 VALIDATION OF THE USE OF THE ICD-10 DIAGNOSTIC CODE


FOR IRRITABLE BOWEL SYNDROME IN THE SWEDISH
NATIONAL PATIENT REGISTER

D. Carter1,2,*, E. Bardan1,2, E. Derazne 1, B. novis1,2, M. Beer-Gabel1,2


1
Sackler Faculty of Medicine, Tel Aviv, 2Gastroenterology, Chaim Sheba Medical
Center, Ramat Gan, Israel
Contact E-mail Address: dr.dancarter@gmail.com

N. Jossan1,*, A.-S. Backman2, M. Linder2, M. Altman2, M. Simren2, O. Ole`n2,


H. Tornblom1
1
Dept of Internal Medicine, Institute of Medicine, Sahlgrenska Academy,
University of Gothenburg, Gothenburg, Sweden, Gothenburg, 2Clinical epidemiology uniit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden
Contact E-mail Address: hans.tornblom@gu.se

INTRODUCTION: The diagnosis of Irritable Bowel Syndrome (IBS) is based


mainly of clinical evaluation. The reported incidence of misclassification of significant organic diseases in previously diagnosed IBS patients differs between
studies.
AIMS & METHODS: We examined the incidence and risk factors for the diagnosis of significant organic diseases (inflammatory bowel disease (IBD), Celiac
disease, gastrointestinal malignancy and thyroid dysfunction) in a cohort of
2645 IBS.
RESULTS: During follow-up, organic disease was diagnosed in 27 subjects
(1.03%): IBD in 23, Celiac disease in 2, IBD and Celiac disease in one and
hypothyroidism in one. The mean interval from the diagnosis of IBS to the
diagnosis of an organic disorder was 13.088.51 months. Increased symptom
severity was the only significant risk factor for the misclassification of an organic
disease (HR 2.26, 95%CI 1.01-5.05 p 0.047). The risk ratio for misclassification
of organic diseases in moderate to severe IBS was increased by 2.575 (95%CI
1.10-6.51, p 0.027) in relation to mild IBS.
CONCLUSION: The incidence of misclassification of major organic disease in
IBS patients was low. Increased symptoms severity was the only significant risk
factor for the misclassification of organic disorders. Further gastrointestinal evaluation should be considered when symptoms are moderate to severe.
Disclosure of Interest: None declared
P0402 BILE ACID DIARRHOEA MASQUERADES AS DIARRHOEAPREDOMINANT IRRITABLE BOWEL SYNDROME: RESULTS
FROM A DUAL CENTRE PROSPECTIVE STUDY
I. Aziz1,*, S. Mumtaz2, H. Bholah2, F.U. Chowdhury3, D.S. Sanders1,
A.C. Ford2
1
Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, 2Leeds
Gastroenterology Institute, 3Nuclear Medicine Department, St Jamess University
Hospital, Leeds, United Kingdom
INTRODUCTION: Several studies have suggested that bile acid diarrhoea
(BAD) can present with symptoms that are compatible with diarrhoea-predominant irritable bowel syndrome (IBS-D). However, uncertainty exists as these have
often been retrospective, have not defined IBS-D according to accepted diagnostic criteria, or have included patients with chronic diarrhoea in the analysis. We
have examined this issue in a well-characterised cohort of patients with rigorously defined IBS-D.
AIMS & METHODS: This was a prospective cross-sectional survey conducted
among consecutive patients with IBS-D attending Gastroenterology clinics in
two hospitals in Sheffield and Leeds, UK. All patients underwent 23-seleno 25homo-tauro-cholic acid (SeHCAT) scanning according to local protocol, with a
retention of 515% at day 7 used to confirm BAD. The degree of BAD was
classed as severe if retention 55%, moderate if 5.0%49.9%, and mild if
10.0%414.9%. Presence of IBS-D was defined according to the Rome III criteria. Patients with other known risk factors for BAD, including previous cholecystectomy, terminal ileal Crohns disease, terminal ileal resection, pelvic or
abdominal radiotherapy, coeliac disease, or microscopic colitis, were excluded.
Participants completed the patient health questionnaire-15, a validated somatisation score, and the hospital anxiety and depression score. Demographic data,
including age, gender, lifestyle, and body mass index (BMI) were collected. The
effect of all these factors on presence or absence of BAD was examined by
multivariate logistic regression analysis, with results expressed as odds ratios
(ORs) with 99% confidence intervals.
RESULTS: This is an interim analysis of an ongoing study. In total, 51 patients
with IBS-D according to the Rome III criteria have been recruited to date (37
(72.5%) female, mean age 47.0 years). In total, 14 (27.5%) were found to have
BAD following SeHCAT scanning. Of these, nine (17.6%) had severe BAD, four
moderate, and one mild. Mean age, BMI, anxiety, depression, and somatisation
scores were not significantly different among those with, compared with those
without, BAD. No predictors of presence of BAD were identified following
multivariate logistic regression.
CONCLUSION: Our data suggest that more than one-in-four IBS-D patients, if
investigated, have definite evidence of BAD. In the majority, this is severe.
Failure to investigate patients to exclude BAD as an underlying cause of symptoms compatible with IBS-D results in misdiagnosis and a failure to institute
effective therapy, in the form of bile acid sequestrants. This suggests that future
IBS management guidelines should advocate diagnostic testing to exclude BAD
before a diagnosis of IBS-D is made.
Disclosure of Interest: I. Aziz: None declared, S. Mumtaz: None declared, H.
Bholah: None declared, F. Chowdhury: None declared, D. Sanders: This study
was funded by investigator-initiated grant from GE healthcare, A. Ford: This
study was funded by investigator-initiated grant from GE healthcare.

INTRODUCTION: Irritable bowel syndrome (IBS) is a diagnosis based on


symptom criteria. In order to perform epidemiologic studies based on national
health-care registers there is a need to assess the accuracy of the diagnostic code
in clinical practice at different time points.
AIMS & METHODS: The aim of this study was to evaluate the positive predictive value of the ICD-10 (International Classification of Diseases, version 10)
code for IBS in Sweden in hospital based outpatient care during 2005 (using the
Rome II criteria) and 2010 (Rome III criteria). We identified all Swedish adults
that had received the ICD-10 code for IBS as the main diagnosis during hospitalbased outpatient care in 2005 and 2010 by use of the Swedish National Patient
Register. We excluded individuals from the IBS cohort if they had been diagnosed with predefined diagnoses, incompatible with IBS, during a time span of 6
months before or after the IBS diagnosis. The National Board of Health and
Welfare generated a random sample of 300 identities. Each medical record was
retrieved and read by two of the authors (N. J. and H. T.) who noted if symptoms
compatible with IBS according to Rome II criteria (2005 cohort) or Rome III
criteria (2010 cohort) could be identified.
RESULTS: We received a total of 248 medical records (2005, n 127; 2010,
n 121). In 173 patients (70%), the diagnosis fulfilled diagnostic criteria with
a high certainty and in 75 patients (30%) it did not. The proportions of valid
diagnoses were similar in 2005 (Rome II criteria, 68%) and 2010 (Rome III
criteria, 72%) (2 0.67, df 1, p .41). Out of the 75 cases that did not fulfill
diagnostic criteria, 24 were labeled probable IBS because of insufficient medical data. There was no difference when comparing tertiary (72% correct) and
secondary care (69% correct) (p .62), but a significant difference in accuracy
was noted comparing departments of internal medicine (155/210, 74%) and non
internal medicine departments (18/38, 47%) (p .001). The most common reasons for a diagnosis being judged as not valid were: insufficient patient data
available in 33 patients (13%), symptoms only including abdominal pain/discomfort or abnormal bowel habit in 19 patients (8%), an obvious misuse of the
diagnosis in 12 patients (5%) and too short duration of symptoms in 11 cases
(4%).
CONCLUSION: The use of the ICD-10 diagnostic code for IBS in Swedish
secondary and tertiary care has a high validity in departments of internal medicine but less so in other departments. This finding needs to be addressed when
planning and interpreting epidemiologic studies of IBS.
Disclosure of Interest: N. Jossan: None declared, A.-S. Backman: None declared,
M. Linder: None declared, M. Altman: None declared, M. Simren: None
declared, O. Ole`n: None declared, H. Tornblom Lecture fee(s) from: Almirall,
Shire, Consultancy for: Almirall, Danone, Shire
P0404 ALTERATIONS IN ENTERIC GLIA CELL PHENOTYPE AND
FUNCTIONS IN IRRITABLE BOWEL SYNDROME
N.L. Lilli1,*, Q. Lucille1, A. Philippe1, R.-D. Malvyne1, D. Tony1, K. Elise2,
B. Giovanni3, D.G. Roberto3, B.D. V. Stanislas2, C. Emmanuel2, N. Michel1
1
Inserm U913, 2IMAD, Nantes, France, 3Dimec, Bologna, Italy
Contact E-mail Address: libera.lilli@gmail.com
INTRODUCTION: Irritable bowel syndrome (IBS) is a complex disease characterized by symptoms including chronic abdominal pain or discomfort and
alteration of bowel habit. Increasing evidence demonstrates a central role of
intestinal epithelial barrier (IEB) dysfunction, and especially increased paracellular permeability, in the pathophysiology of IBS. The enteric nervous system
(ENS), and in particular enteric glial cells (EGC) play a pivotal role in the
maintenance of IEB.
AIMS & METHODS: The purpose of this study was to characterize the lesions
of the EGC in IBS patients and the putative causative role of soluble factors
produced by the colonic IEB microenvironment in these lesions. Methods:
Eighteen IBS patients (6 constipation-predominant IBS (IBS-C), 6 diarrhea-predominant IBS (IBS-D) and 6 mixed bowel habits IBS (IBS-M) patients) and 9
healthy controls (HC) were included. For each patient gastrointestinal symptoms
were assessed using the Rome III questionnaire and colonoscopy was performed
with 12 biopsies of left colon. Paracellular and transcellular permeability was
measured on 3 biopsies using the Ussing chambers. Supernatant was obtained
by incubation of 4 biopsies in Krebs-Hepes solution during 25 minutes at 37 C.
At the end of the incubation time, biopsies were processed for Western blot
analysis. Both total Glial fibrillary acidic protein (GFAP) expression and the
55-kDa band as well as S100b were analysed. The mRNA expression levels of
glial markers (Sox-10; S100b) and inflammatory cytokine TNF-a were measured
using real-time PCR. Intracellular calcium flux in response to adenosine triphosphate (ATP) stimulation was measured using Fluo-4 probe in culture of rat
EGC after 48h incubation with patients and HC supernatants or protease-activated receptor agonists (SLIGRL and Thrombin), serotonin or histamine.
RESULTS: Paracellular and transcellular permeability of biopsies from all subtypes of IBS patients was similar as compared to HC, except in the IBS-C subtype for which transcellular permeability was significantly increased. No
difference in S100b, total GFAP and the specific 55-kDa band expression was
observed for any subtype. Sox-10 and S100b mRNA expression was similar in
biopsies of all IBS subtypes as compared to HC. Interestingly, we observed a

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United European Gastroenterology Journal 2(1S)


significant increase in TNF-a mRNA expression in IBS-M but not C or D subtype as compared to control. Intracellular calcium responses (maximal amplitude
and half max duration) to ATP were significantly decreased in rat EGC cultures
incubated with supernatants of IBS-D and M but not C subtypes as compared to
control. No difference in calcic response to ATP was observed in EGC cultures
after incubation with different SLIGRL, thrombin, serotonin and histamine
concentrations.
CONCLUSION: Our study demonstrates that enteric glial phenotype and functions are altered in IBS in a subtype dependent fashion. The mediators responsible for these changes as well as the functional consequences of these changes
remain to be identified.
Disclosure of Interest: None declared
P0405 ABDOMINAL PAIN VERSUS ABDOMINAL DISCOMFORT:
IMPLICATIONS FOR DIAGNOSTIC ASSESSMENT OF IRRITABLE
BOWEL SYNDROME (IBS)
O. Palsson1,*, S. Heymen1, W.E. Whitehead1
1
Department of Medicine, Division of Gastroenterology and Hepatology,
University of North Carolina, Chapel Hill, United States
Contact E-mail Address: opalsson@med.unc.edu
INTRODUCTION: Diagnostic questions in the current Rome criteria for IBS
inquire about frequency of abdominal discomfort or pain, whereas the U. S.
Food and Drug Administration guidelines for IBS clinical trials only reference
abdominal pain frequency. It is unknown to what extent people perceive abdominal pain and discomfort differently or whether both are needed in GI diagnosis
questions.
AIMS & METHODS: We compared abdominal pain and discomfort ratings in a
U. S. nationwide internet community survey of 328 adults, containing the Rome
III diagnostic questions for IBS in the new response formats planned for Rome
IV diagnoses (Gastroenterology 2013;144(5) Suppl.1:S-916), including the standard in the past 3 months, how often did you have discomfort or pain anywhere
in your abdomen? and alternative forms of that question replacing abdominal
discomfort or pain with only pain or only discomfort. Also included was a
multiple-choice question about the extent to which abdominal pain and discomfort are experienced as separate sensations, and demographic questions. To avoid
over-estimating agreement between alternative question forms, responses from
people who reported having neither pain nor discomfort in the abdomen in the
past 3 months were excluded from analysis, as well as those inconsistent on either
of two repeated quality-check questions, leaving 218 for analysis. Analysis calculated percent agreement between alternate question forms, and also Cohens
Kappa (K-values) for diagnostic performance as this controls for rate of chance
agreement (K 4 0.8 excellent agreement).
RESULTS: The subjects (52.8% females; mean age 45.8, range 19-85 years)
varied widely in their perception of the relationship between abdominal pain and
discomfort: 33.9% stated they were entirely or mostly independent sensations,
27.1% that they were mostly or entirely the same sensation, and 39.0% that both
were equally true i.e., they could be either separate sensations or discomfort a
mild version of pain. Only about half of subjects rated frequency of pain alone
(52.8%) and discomfort alone (55.5%) as identical in intensity (i.e., same
response option chosen on the 9-point frequency scale) to ratings on the standard
pain or discomfort question. However, when the diagnostic frequency threshold for IBS (43 days a month in the past 3 months) was compared, the agreement with pain or discomfort on that threshold being met (when met by either
version) was 72.4% (K 0.63) for the pain alone and 76.8% (K 0.66) for
discomfort alone, and 81.3% between the latter two (K 0.74). When full IBS
criteria were examined using the 3 different question versions, the agreement with
the standard question version when at least one method qualified subjects as IBS
was 80.8% (K 0.85) for the pain-only version and 87.7% (K 0.90) for discomfort-only, with the latter two also showing 87.7% agreement (K 0.90). IBS
diagnosis with discomfort alone diagnosed a slightly higher rate of IBS (71 cases)
compared to the other 2 versions (66 cases each).
CONCLUSION: The use of abdominal discomfort or pain as a criterion for
IBS diagnosis is ambiguous because there is no agreement among U. S. adults
regarding whether these are qualitatively different sensations. However, in 4 out
of every 5 cases the same individuals would be diagnosed IBS regardless of which
descriptor is used. [Supported by a grant from Salix Pharmaceuticals]
Disclosure of Interest: O. Palsson Financial support for research from: Salix
Pharmaceuticals, S. Heymen Financial support for research from: Salix
Pharmaceuticals, W. Whitehead Financial support for research from: Salix
Pharmaceuticals
P0406 PREVALENCE OF ORGANIC GASTROINTESTINAL DISEASE IN
SUSPECTED IRRITABLE BOWEL SYNDROME (IBS) VARIES
ACCORDING TO SUBTYPE
P. Patel1,*, P. Moayyedi2, P. Bercik2, M.-I. Pintos-Sanchez2, C. Bolino2,
D. Morgan3, A. Ford4
1
School Of Medicine, University of Leeds, Leeds, United Kingdom, 2Farncombe
Family Digestive Health Research Institute, Gastroenterology Division, McMaster
University, Health Sciences Center, 3Gastroenterology Department, St. Josephs
Healthcare, Hamilton, Canada, 4Leeds Gastroenterology Institute, St. Jamess
University Hospital, Leeds, United Kingdom
Contact E-mail Address: um10pp@leeds.ac.uk
INTRODUCTION: In patients who report symptoms compatible with IBS in the
absence of alarm symptoms, guidelines suggest the diagnosis can be made without investigations. However, there are few validation studies of the current goldstandard, the Rome III criteria, and the prevalence of organic gastrointestinal
(GI) disease in people with suspected IBS is unclear.

AIMS & METHODS: We evaluated consecutive patients with Rome III-defined


IBS, and examined whether prevalence of organic GI disease varied according to
IBS subtype, or the presence or absence of alarm symptoms. Demographic and
symptom data were collected from 4224 patients with GI symptoms attending
outpatient clinics at two hospitals in Hamilton, Ontario. Participants completed
the Rome III diagnostic questionnaire for the functional GI disorders, which was
used to categorise IBS subtype. Individuals underwent colonoscopy, with assessors blinded to symptom status. Patients with normal colonoscopy and no evidence of coeliac disease were classed as having no organic GI disease. Prevalence
of organic GI disease was compared according to IBS subtype, and in patients
who did, compared with those who did not, report alarm symptoms (weight loss,
rectal bleeding, anaemia, or family history of colorectal cancer) using a 2 test.
RESULTS: 537 patients met Rome III criteria for IBS (mean age 42yrs, 404
(75.2%) females). Organic GI disease was present in 138 (25.7%), with the commonest finding Crohns disease (n 46 (8.6%)). 63 patients had IBS-C, 209 IBSD, and 265 IBS-M. Prevalence of organic GI disease was significantly lower in
IBS-C (n 8 (12.7%)) versus IBS-D (n 67 (32.1%)) or IBS-M (n 63 (23.8%))
(p 0.005) (Table). In the 410 patients who reported 1 alarm symptom, prevalence of organic GI disease was significantly higher (n 116 (28.3%)) compared with 127 patients who did not report any alarm symptom (n 22 (17.3%))
(p 0.013). In IBS-D, there was a significantly higher prevalence of organic GI
disease in those with alarm symptoms (36.0%) compared with those without
(17.85%) (p 0.02). However, IBS-C and IBS-M prevalence of organic GI disease in patients with alarm symptoms versus those without was not significantly
higher (IBS-C 11.6% versus 15.0%, p 0.708; IBS-M 25.6% versus 17.7%,
p 0.202

No organic GI disease (%)


Ulcerative colitis (%)
Crohns disease (%)
Colorectal cancer (%)
IBD unclassifiable (%)
Microscopic colitis (%)
Coeliac disease (%)

Total IBS
(n 537)

IBS-D
(n 209)

IBS-C
(n 63)

IBS-M
(n 265)

399 (74.3)
34 (6.3)
46 (8.6)
14 (2.6)
24 (4.5)
12 (2.2)
8 (1.5)

142 (67.9)
19 (9.1)
21 (10.0)
5 (2.4)
11 (5.3)
8 (3.8)
2 (1.0)

55 (87.3)
1 (1.6)
2 (3.2)
2 (3.2)
2 (3.2)
0 (0)
2 (3.2)

202 (76.2)
14 (5.3)
23 (8.7)
7 (2.6)
11 (4.2)
4 (1.5)
4 (1.5)

CONCLUSION: Patients with suspected IBS-C are unlikely to have underlying


organic GI disease, compared with IBS-D or IBS-M. Although the incorporation
of the absence of alarm symptoms into the diagnostic criteria for IBS reduced the
likelihood of organic GI disease, this was only for IBS-D and, because alarm
symptoms are so common, 60% of patients still have normal investigations.
Better ways of diagnosing IBS are needed.
Disclosure of Interest: None declared
P0407 SOMATISATION LEVEL VARIES ACCORDING TO IRRITABLE
BOWEL SYNDROME (IBS) SUBTYPE AND DRIVES BLOATING
SEVERITY
P. Patel1,*, P. Moayyedi2, P. Bercik2, M.-I. Pintos-Sanchez2, C. Bolino2,
D. Morgan3, A. Ford4
1
School Of Medicine, University of Leeds, Leeds, United Kingdom, 2Farncombe
Family Digestive Health Research Institute, Gastroenterology Division, McMaster
University, Health Sciences Center, 3Gastroenterology Department, St. Josephs
Healthcare, Hamilton, Canada, 4Leeds Gastroenterology Institute, St. Jamess
University Hospital, Leeds, United Kingdom
Contact E-mail Address: um10pp@leeds.ac.uk
INTRODUCTION: Literature suggests that somatisation is strongly associated
with IBS. However, it remains unclear whether the degree of somatisation varies
according to IBS subtype. Furthermore, whether there is an association between
higher levels of somatisation and more severe IBS symptoms is unknown.
AIMS & METHODS: Demographic and symptom data were collected from
4224 adult patients attending gastrointestinal (GI) outpatient clinics at two hospitals in Hamilton, Ontario. Participants completed the Rome III diagnostic
questionnaire for the functional GI disorders. Somatisation data were collected
via the Patient Health Questionnaire-15 (PHQ-15), comprising 15 somatic symptom items. To avoid overestimation of the severity of somatisation we excluded
the 3 GI items from the original PHQ-15 questionnaire to form the PHQ-12.
Somatisation severity was categorised according to total PHQ-12 (minimal 3,
low 4-7, medium 8-12 and high 13) with a maximum somatisation score of 24.
Mean somatisation score and total number of somatic symptoms reported were
compared between IBS subtypes (diarrhoea-predominant (IBS-D), constipationpredominant (IBS-C), and mixed stool pattern (IBS-M)) using analysis of variance. The effect of level of somatisation on the severity of individual IBS symptoms, including lower abdominal pain or discomfort, stool frequency, stool
consistency, bloating or abdominal distension, tenesmus, and urgency was compared according to IBS subtype using a 2 test with P values of 50.01 denoting
statistical significance.
RESULTS: 840 patients met the Rome III criteria for IBS and provided complete
somatisation data (mean age 38.3 years, 702 female (83.6%)). Of these, 289
patients had IBS-D, 138 IBS-C, and 413 had IBS-M. Mean PHQ-12 scores
were significantly higher in those with IBS-M (n 10.35), compared with IBSC (n 8.94) or IBS-D (n 9.24) respectively (P50.001). Mean number of PHQ12 symptoms reported was also significantly higher in IBS-M patients (7.2) compared with patients with IBS-C (n 6.2) or IBS-D (n 6.4) respectively
(P50.001). High level of somatisation was present in 222 patients (26.4%).

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The prevalence of a high level of somatisation was significantly greater in patients


with IBS-M (131 patients (31.7%)) compared with IBS-C (31 (22.5%)) or IBS-D
(60 (20.8%)) respectively (p 0.003). For all subtypes of IBS, high levels of
somatisation were associated with a greater severity of bloating or abdominal
distension (P50.001 for IBS-M and IBS-D, and p 0.004 for IBS-C respectively). For patients with IBS-M, high levels of somatisation were also associated
with a significantly greater prevalence of likelihood of reporting 53 stool per
week (p 0.001). No other significant associations between somatisation severity
and symptom severity were observed.
CONCLUSION: IBS-M is strongly associated with higher levels of somatisation.
The number of reported somatic symptoms reported is higher in IBS-M compared with other IBS subtypes. Severity of bloating or abdominal distension
reported by all patients with IBS is strongly associated with high levels of somatisation. This suggests psychological stress may drive the severity of this commonly reported symptom in IBS, and may partly explain why it can be difficult to
treat.
Disclosure of Interest: None declared
P0408 INTESTINAL AND SYSTEMIC IMMUNE
PATIENTS WITH IRRITABLE BOWEL SYNDROME

MARKERS

IN

Z. Mujagic1,2,*, E.F. Tigchelaar1,3, A. Smolinska1,4, A.A. Masclee2,


S. Zhernakova1,3, F.-J. van Schooten1,4, C. Wijmenga1,3, D.M. Jonkers1,2
1
Top Institute Food and Nutrition (TIFN), Wageningen, 2Division
Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School
for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center
(MUMC), Maastricht, 3Department of Genetics, University of Groningen,
Groningen, 4Department of Toxicology, NUTRIM School for Nutrition,
Toxicology and Metabolism, Maastricht University Medical Center (MUMC),
Maastricht, Netherlands
Contact E-mail Address: z.mujagic@maastrichtuniversity.nl
INTRODUCTION: Immune activation (low grade inflammation) and an altered
intestinal microbiota are postulated to be involved in the multi-factorial pathophysiology of Irritable Bowel Syndrome (IBS), especially in the diarrhea predominant subtype. Fecal calprotectin and plasma cytokines, as markers of intestinal
inflammation and systemic immune activation, respectively, and the antimicrobial protein human beta defesin-2 (HBD-2), have previously been assessed in IBS
patients, but results were inconsistent and numbers were too small for subtype
analyses.
AIMS & METHODS: The aim of our study was to compare fecal calprotectin,
HBD-2 and plasma cytokines levels of a large well characterized IBS cohort to
healthy controls (HC), and to assess differences between subtypes.
Fecal and blood samples were obtained from IBS patients (Rome III) and ageand gender-matched HC. Calprotectin and HBD-2 levels in fecal samples were
analyzed by ELISA, while non-stimulated levels of IL-1, IL-6, IL-8, IL-10, IL12P70 and TNF- were assessed by Luminex assay. Kruskal Wallis test was used
for multi-group comparison and Mann-Whitney U test for 2-group comparisons,
with post-hoc Bonferroni correction (for multiple testing).
RESULTS: We included 164 HC and 264 IBS patients (IBS5SUB4TOTAL5/
SUB4): 92 diarrhea predominant (IBS-D), 48 constipation predominant (IBSC), 105 with mixed stools (IBS-M) and 19 with undefined subtype (IBS-U). IBSU was not analyzed separately due to small numbers. Calprotectin was higher in
IBS5SUB4TOTAL5/SUB4 compared to HC (median [IQR]: 40.3 [19;81] vs.
20.4 [5-48] ug/g, p 50.001, resp), and in all IBS-subtypes compared to HC. HBD2 levels were lower in IBS5SUB4TOTAL5/SUB4 compared to HC (31.0
[18;48] vs. 37.5 [27;60] ng/g, p 50.01), which was also true for IBS-D vs. HC.
The cytokines IL-1 (0.11 [0.11;1.12] vs. 0.11 [0.11;1.46] ug/l, p 50.01) and IL-6
(0.19 [0.19;0.19] vs. 0.52 [0.19;3.13] ug/l, p 50.01) were lower in
IBS5SUB4TOTAL5/SUB4 vs. HC, while IL-12p70 (0.08 [0.08;3.52] vs.
0.08 [0.08;1.53] ug/l, p 50.01) and TNF- (0.45 [0.26;0.69] vs. 0.67 [0.38;8.32]
ug/l, p 50.01) were higher IBS5SUB4TOTAL5/SUB4 compared to HC.
The IL10/12 ratio was also lower in IBSTOTAL compared to HC (0.45
[0.26;0.69] vs. 0.67 [0.38;8.32], p 50.01). The findings were consistent for all
subtypes, apart for TNF- being only increased in IBS-D and no differences
found between all subtypes and HC for IL-1. No significant differences were
found for IL-8 and -10.
CONCLUSION: Calprotectin levels were significantly higher, but mildly elevated, in IBS patients and all subtypes compared to HC, pointing to low grade
mucosal inflammation in IBS. The overall cytokine levels were low, but combined systemic cytokine data point to a pro-inflammatory state in the total group
of IBS patients as well as in all subtypes. Interestingly, HBD-2 levels were lower
in IBS patients compared to HC, especially in IBS-D, suggesting an altered hostmicrobe interaction.
In conclusion, our data point to a low-grade mucosal and systemic inflammatory
state with reduced intestinal defensin levels in IBS patients when compared to
healthy controls. The findings did not depend on dominant bowel habits, indicating that immune activation may plays a role in the pathophysiology of all IBS
subtypes.
Disclosure of Interest: Z. Mujagic: None declared, E. Tigchelaar: None declared,
A. Smolinska: None declared, A. Masclee Consultancy for: Pentax medical,
Grunenthal GmbH, Ferring, S. Zhernakova: None declared, F.-J. van
Schooten: None declared, C. Wijmenga: None declared, D. Jonkers: None
declared

P0409 ENDOSCOPIC
FINDINGS
AND
CLINICOPATHOLOGIC
CHARACTERISTICS OF ISCHEMIC COLITIS: A PORTUGUESE
CENTER EXPERIENCE
C. Leitao1,*, A. Santos1, H. Ribeiro1, J. Pinto1, A. Caldeira1, R. Sousa1,
J. Tristan1, E. Pereira1, A. Banhudo1
1
Servico de Gastrenterologia, Hospital Amato Lusitano - Unidade Local de Saude
de Castelo Branco, Castelo Branco, Portugal
Contact E-mail Address: catia.f.leitao@gmail.com
INTRODUCTION: Ischemic colitis (IC) is the most common vascular disorder
of the intestinal tract and the second most common cause of lower digestive
bleeding. The clinical disease course of ischemic colitis may vary from self-limiting to life-threatening and has a wide spectrum of endoscopic findings.
AIMS & METHODS: In this study, we made a retrospective analysis of endoscopy Endings and clinicopathologic characteristics of IC in the endoscopy center
of our hospital during the last 10 years (2002 to 2012) and try to identify the
predictors of endoscopic severity of IC. The data collected included demographic
(age, gender), clinical (symptoms, comorbidities and medication), laboratory
(hemoglobin, leucocytes, C-reactive protein, lactate dehydrogenase), and endoscopic findings (localization, extension, severity of the lesions) and outcomes
(length of hospitalization stay, treatment and death).
RESULTS: The study included 194 patients (92 women; 62 men), with mean age
of 75 years. The most common comorbid disease was hypertension (56.5%),
followed by cardiovascular disease (21.5%), arrhythmias (14.8%) and cerebrovascular disease (6.6%). The majority of patients had a history of drug use
(89.6%), 23.4% of them nonsteroidal anti-inflammatory agents and 13.6% digitalis preparations. Hematochezias (79.2%) and abdominal pain (73.3%) were the
most common presentation symptoms. The average elapsed time between the
beginning of the symptoms and the diagnosis was 2,1 days. Ischemic lesions
were located mainly in the left colon (77.3%) and were found in more than 2
colonic segments in 42.9%. The endoscopic lesions were grade I in 57.1%, grade
II in 39.6% and grade III in 3.2% of patients. The involvement of more than 2
colonic segments (50.0001), the involvement of sigmoid and descendent colon
(50.0001), anemia (50.04), and mortality (50.0001) were significantly
higher in patients with severe endoscopic lesions. Death occurred in 4 patients
(2.6%) and surgery was performed in only 1 patient. The mean length of hospital
stay was 7.5 days. The involvement of more than 2 colonic segments (p40.0001),
longer elapsing time between the beginning of symptoms and the diagnosis
(p40.0001), antibiotics use (p40.009) and age higher than 80 years (p
50.001) were related to longer hospitalization.
CONCLUSION: In our study, the majority of patients were female, over 50
years of age and with several risk factors. The clinical disease course was selflimiting and was associated a low mortality. The involvement of more than 2
colonic segments, the involvement of sigmoid and descending colon and anemia
may be predictive factors of endoscopic severity in IC. An intimate knowledge of
endoscopic findings and pathologic characteristics of ischemic colitis plays a
pivotal role in decreasing the misdiagnosis rate of ischemic colitis.
Disclosure of Interest: None declared
P0410 THE CLINICAL CHARACTERISTICS OF PATIENTS WITH
PNEUMATOSIS CYSTOIDES INTESTINALIS IN JAPAN
M. Miura1,*, D. Saito1, M. Hayashida1, A. Sakuraba1, Y. Yamada1,
G. Koyama1, S. Takahashi1
1
The Third Department of Internal Medicine, Kyorin University School of
Medicine, Tokyo, Japan
INTRODUCTION: Pneumatosis cystoides intestinalis (PCI) is a relatively rare
disease, in which multilocular or linear pneumatic cysts developed under the
mucosa or serosa of the intestinal wall. In recent years, with the advances in
imaging technologies, the number of reported cases of PCI has been increasing.
Here, we investigated the clinical characteristics of patients with PCI.
AIMS & METHODS: 55 patients were diagnosed as PCI at Kyorin University
Hospital during the 6-year period from September 2007 to August 2013. We
conducted a retrospective analysis of the clinical characteristics of these patients,
including sex, age, the site of lesion, symptoms and treatments.
RESULTS: The male to female ratio was 29:26 and the median age was 64.7
years. The diagnosis was made by CT(47 cases), or colonoscopy (8 cases). In
regard to the site of lesion, the stomach was 2 patients, small intestine was 18
patients, ascending colon was 26 patients, transverse colon was 4 patients, descending colon was 2 patients and the sigmoid colon was 2 patients. 31 patients
complained of symptoms of abdominal pain (18), abdominal distension (9), fever
(2), diarrhea (2), and melena (1). There were 20 patients whose condition was
idiopathic and 35 patients whose condition was secondary to other underlying
diseases including diabetes (12), malignant tumors (9), intestinal tract necrosis
(9), collagenosis (7), constipation (1), chronic obstructive pulmonary disease (1)
and ileus (1). Eleven patients had a history of steroid use, and 12 patients had a
history of treatment with -glucosidase inhibitors. Thirty-four patients received
in hospital treatment including conservative treatments such as nil by mouth,
treatment with prokinetic agents, supplemental oxygen in 24 patients and
abdominal operation in 11 patients. Portal venous gas (HPVG) was observed
in 9 patients, and 8 of these had underlying intestinal tract necrosis.
CONCLUSION: In most patients, PCI is mild, asymptomatic and resolves spontaneously. The principally used treatment strategy for PCI is conservative treatment. Appropriate consideration of the indications for operation is important for
avoiding unnecessary invasive treatment. However, especially in cases of PCI
complicated by HPVG, underlying intestinal tract necrosis should be borne in
mind and it seems to be important to promptly determine whether emergency
surgery is needed. There are numerous unresolved issues in respect of the pathological characteristics of PCI, therefore, further accumulation and examination

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United European Gastroenterology Journal 2(1S)


of cases are necessary. Further elucidation of the pathological characteristics and
establishment of suitable treatments are expected.
Disclosure of Interest: None declared
P0411 PROFILE AND OUTCOME OF PATIENTS WITH ISCHEMIC
COLITIS
R. Oprita1,*, F. Musat1, A. Ragea1
1
Gastroenterology, Bucharest Clinical Emergency Hospital, bucharest, Romania
Contact E-mail Address: ruxandraa@netscape.net
INTRODUCTION: - Ischemic colitis incidence is most likely underestimated
because the mild form often is of transient nature and misdiagnosed when
patients suffer from other diseases such as inflammatory bowel disease or infectious colitis.
AIMS & METHODS: We prospectively studied patients referrd for colonoscopy
for lower gastro-intestinal bleeding from January 2013 until January 2014.
There were enrolled 74 patients (27 females and 47 males), aged between 20 to 75
years old, with a median age of 51 years old.
The findings at colonoscopy will depend on the stage and severity of ischemia. In
the early stages of ischemia, petechial hemorrhages are interspersed with areas of
pale, edematous mucosa. Later, segmental erythema, with or without ulcerations
and bleeding, may be observed. The colon single-stripe sign, a single longitudinal
ulcerated or inflamed colon strip, may characterize milder disease. With more
severe ischemia, the mucosa appears cyanotic, dusky, gray, or black.
Pseudopolyps and pseudomembranes may be appreciated, as well. A chronic
stage of ischemia characterized by stricture, decreased haustrations, and mucosal
granularity may occur several weeks or months later.
There are no endoscopic findings that are specific for ischemia, thus the clinical
setting must be considered.
RESULTS: Conditions mandating anticoagulation, such as atrial fibrillation or
dilated cardiomyopathy, were identified in 32% of case patients. Conditions
requiring antiarrhythmic therapy were identified in 25% of case patients; in 4
of the patients, cocaine was identified as the leading cause.
Of 74 patients, 5 required immediate surgery and 3 of them were positive for
clostridium difficile.
CONCLUSION: Ischemic colitis occurs as the result of a compromise in intestinal blood flow that can produce a spectrum of injury from transient self-limited
ischemia to fulminant ischemia or transmural infarction. Its diagnosis requires a
high index of suspicion, and the clinician should consider the diagnosis in
patients with acute abdominal pain and bloody stools.
REFERENCES
Reinus JF, Brandt LJ and Boley SJ. Ischemic diseases of the bowel. Gastroenterol
Clin North Am 1990; 19: 319.
Hourmand-Ollivier I, Bouin M, Saloux E, et al. Cardiac sources of embolism
should be routinely screened in ischemic colitis. Am J Gastroenterol 2003; 98:
1573.
Longstreth GF and Yao JF. Diseases and drugs that increase risk of acute large
bowel ischemia. Clin Gastroenterol Hepatol 2010; 8: 49.
Disclosure of Interest: None declared
P0412 CHRONIC KIDNEY DISEASE AND HIGH ECOG PERFORMANCE
STATUS ARE RISK FACTORS FOR SEVERE ISCHEMIC COLITIS
S.R. Jee1,*, S.R. Choi2, G.A. Song3, S.J. Park4, C.S. Song5, H.U. Park6
1
gastroenterology, INJE UNIVERSITY COLLEGE OF MEDICINE, 2Dong-A
University, 3gastroenterology, Busan national University, 4gastroenterology, Kosin
University, 5gastroenterology, Good Samsun hospital, 6gastroenterology,
Maryknoll Hospital, Busan, Korea, Republic Of
Contact E-mail Address: tokimom@nate.com
INTRODUCTION: Ischemic colitis is most frequent form of intestinal ischemic
disease. However, there have been debates about prognostic factors of ischemic
colitis
AIMS & METHODS: The aim of this study was to identify risk factors of severe
ischemic colitis. From January 2000 to December 2011, a retrospective study was
undertaken of patients with ischemic colitis hospitalized at 4 university hospitals
and 2 secondary hospitals at Busan, Korea. Patients with colon ischemia were
divided into two groups: those with mild disease and those with severe disease.
Data collected included age, sex, symptoms (abdominal pain, hematochezia and
abdominal angina), cormobidity (hypertension, diabetes mellitus, ischemic heart
disease, stroke, arrhythmia, congestive heart failure, peripheral vascular disease,
chronic obstructive lung disease, chronic kidney disease, hemodialysis, peritoneal
dialysis, hyperthyroidism, hypothyroidism and irritable bowel syndrome),
laboratory findings (total cholesterol, TG, LDL, HDL, total protein, albumin,
Hg, WBC count, Platelet count, ESR and CRP), endoscopic fidings (location of
lesions), and ECOG performance status.
RESULTS: A total of 292 patients were enrolled (mild group: 259, severe group:
33). In univariate analysis, location (involving Rt. Colon), chronic kidney disease
(stage V), ECOG, Platelet count, CRP were significant risk factors for severe
ischemic colitis. In multivariate analysis, chronic kidney disease (stage V) (OR,
5.289; 95% CI 1.308-21.378; p 0.019), ECOG (OR, 1.690; 95% CI 1.108-2.579;
p 0.015) were significant risk factors for severe ischemic colitis.
CONCLUSION: Chronic kidney disease (stage V) and high ECOG performance
status were independent risk factors for severe ischemic colitis. More caution
would be necessary when treatment of patients with ischemic colitis having
these factors.
Disclosure of Interest: None declared

P0413 RESECT AND DISCARD (RD) STRATEGY FOR COLONIC


POLYPS- AN ASIAN PERSPECTIVE, ARE WE READY?
C.T. W. Chia1, Y.M. Yun2,*, S. Thrumurthy3, S.K. K. Tsao1
1
Gastroenterology & Hepatology, Tan Tock Seng Hospital (TTSH), Singapore,
Singapore, 2Monash University, Victoria, Australia, 3University of Aberdeen,
Scotland, United Kingdom
Contact E-mail Address: christopher_tw_chia@ttsh.com.sg
INTRODUCTION: The current practice of routinely resecting all diminutive (15mm) and small (6-9mm) colonic polyps and submitting them for histopathologic
assessment has several disadvantage in terms of cost-effectiveness and risks from
repeated colonoscopies. The resect-and-discard (RD) strategy has been proposed
to reduce retrieval of diminutive polyps (1-5mm) for histology which has been
deemed not to have advanced histologic features. RD strategy for small polyps
(6-9mm) are still controversial. The prevalence of advanced histologic features in
the diminutive and small polyp category remains small but not clearly defined.
AIMS & METHODS: In this cross-sectional study, we aim to find the prevalence
of small & diminutive polyps resected that shows advanced histologic features
such as high grade dysplasia (HGD) or carcinoma to determine if RD policy is
feasible in the local Asian tertiary setting. Data was retrieved from Jan-Dec 2009
with assistance from the Pathology Department to identify all submitted colonic
polyp specimens. Each patient also had their colonoscopy report (s) and detailed
histology report reviewed by 2 separate colleagues within the team to ensure data
consistency. The variables captured include demographics, total polyp number,
polyp distribution in the colon, histology, polyp size and respective number in
each histology subtype and concurrent colorectal carcinoma (CRC).
RESULTS: There were a total 1482 polypectomy specimens retrieved for histology from 871 patients. The colonic distribution of the polyps was 45.4% right
sided, 46.1% left sided and 8.5% rectal.
Please refer to Table 1 for summary of polyp distribution and dysplasia.

Colonic polyp histology

Tubular
Adenoma
(TA)

Serrated
Tubulovillous Villous
Adenoma Adenoma
Adenoma
(SA)
Hyperplastic
(VA)
(TVA)

Low grade dysplasia (LGD)


High grade dysplasia (HGD)
No dysplasia
Total number (1482)

79.2%
20.8%
NA
1067(72%)

26.7%
73.3%
NA
150(10.1%)

0.0%
100.0%
NA
3(0.2%)

83.9%

NA

16.1%
100.0%
118(8.0%) 144(9.7%)

There were 844 diminutive polyps (1-5mm), 447 small polyps (6-9mm) and 191
large polyps (10mm). The proportion of HGD seen in each of these groups
were 18.7%, 37.6% and 56.5% respectively. The percentage of HGD present in
diminutive and small polyps was relatively high and significant. There were no
concurrent carcinomatous features seen in all the polyps.
CONCLUSION: These findings showed that a significant proportion of diminutive polyps (18.7%) and small polyps (37.6%) harboured features of HGD, which
is significantly higher than previous findings of 1% for diminutive polyps in some
literatures. Based on size alone without the aid of narrow band imaging (NBI) or
other forms of image enhanced endoscopy (IEE), we find that RD strategy for
diminutive or small polyps may miss a significant group of patients with
advanced neoplastic histology who needs earlier colonoscopic surveillance.
There may be merits in the RD approach but this would require incorporation
of other real-time endoscopic modalities such as IEE and more robust evaluation
REFERENCES
Rex DK. Risks and potential cost savings of not sending diminutive polyps for
histologic examination. Gastro Hepatol 2012; 8: 128130.
Zauber AG, et al. Colonoscopic polypectomy and long-term prevention of CRC
deaths. N Engl J Med 2012; 366: 687-696.
Disclosure of Interest: None declared
P0414 THE STRAY PATIENT DEMOGRAPHIC LABEL: IMPLICATIONS
FOR PATIENT SAFETY AND QUALITY IN THE ENDOSCOPY UNIT
D.C. Sadowski1,*, G. Lutzak1
1
Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Canada
INTRODUCTION: Over a 6-month period, 3 separate incidents occurred in our
unit where the wrong patient demographic labels were affixed to the endoscopy
biopsy requisition form (EBRF), the biopsy specimen container (BSC) or both.
This type of incident can have a significant impact on patient safety and is an
indicator of poor quality in the specimen control process.
AIMS & METHODS: The purpose of this study was to identify factors contributing to this medical error and to develop a process to prevent future occurrences. A Quality Assurance Review (QAR) was conducted to determine the
systems issues that contributed to these incidents. This review was carried out
at the Royal Alexandra Hospital, Edmonton, Canada. The endoscopy unit at this
hospital performs about 18,000 procedures per year. A QAR using Systems
Analysis Methodology (SAM) was conducted to identify issues that contributed
to the patient-specimen mismatches. SAM identified the following system issues:
a) variation in the set-up of nursing workspaces, b) variation in where and when
the EBRF was completed, and c) the occurrence of stray patient demographic
labels. The QAR identified several recommendations to prevent future mislabeling: a) standardize how nursing workspaces are set up, b) develop a checklist to
ensure proper patient identification prior to procedure initiation, proper labeling
of EBRF and BSC, completion of EBRF, and c) remove all patient demographic
labels from the theatre immediately after the conclusion of the procedure.

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United European Gastroenterology Journal 2(1S)

RESULTS: Since EBRF and BSC mislabeling incidents are rare events; we utilized indicators of EBRF information quality as surrogate markers for effectiveness of the QAR recommendations. We deemed the following factors as key
quality indicators of EBRF information: a) completion of clinical history by
physician, b) correct identification of specimen anatomic site, c) avoidance of
ambiguous terminology, and d) correct patient label on EBRF and BSC. We
tracked these indicators daily. We reported the data weekly to physician leaders
and other healthcare providers in order to engage them in this initiative. We used
the Reporting and Learning System (RLS) for patient safety to monitor reporting of similar incidents. Prior to implementation of the QAR recommendations,
the average number of EBRFs containing deficient information was 16.6/month.
Subsequent to the implementation of QAR recommendations, this number
decreased to 6.4/month (p 0.02). However, in the 7 months subsequent to the
QAR recommendation implementation, we had 4 further incident of mislabeling
with the wrong patient label and 3 episodes of unlabeled specimen containers.
CONCLUSION: Stray patient data labels are a significant contributing factor to
EBRF and BSC mislabeling. QARs can reduce the incidence of this medical error
and improve quality of EBRF completion; however, without health care provider
engagement, serious incidents may still occur.
Disclosure of Interest: None declared

n
w
a
r
ithd

P0415 A
NOVEL
SAMPLING
DEVICE
FOR
COLLECTING
MUCOCELLULAR MATERIAL FROM THE UNPREPARED RECTUM
J. Booth1,*, J. Lacy-Colson2, M. Norwood3, C. Murray1
1
Origin Sciences Ltd, Cambridge, 2Surgery, Royal Shrewsbury Hospital,
Shrewsbury, 3Surgery, Leicester Royal Infirmary, Leicester, United Kingdom
Contact E-mail Address: jodie.booth@originsciences.com
INTRODUCTION: Earlier detection of colorectal and other gastrointestinal
malignancies is an urgent objective. Currently much effort is directed at the
development of in vitro diagnostic tests that evaluate informative protein or
DNA biomarkers in blood or stool samples. Stool samples are relatively inconvenient to collect, require special handling facilities, and additionally suffer from
contamination that may interfere with molecular assays. Blood samples, while
more convenient, may not be as informative early in the disease process. Several
studies have shown that significant numbers of exfoliated cells and their products
are retained in a muco-cellular layer overlying the colonic mucosa but distinct
from the stool itself, and that this material flows toward the rectum, where it can
be captured for analysis
AIMS & METHODS: Origin Sciences has developed a novel sampling device,
which incorporates an inflatable nitrile membrane. Following insertion into the
unprepared rectum via a standard proctoscope, the membrane is inflated to make
contact with the rectal mucosa for 10 seconds. The membrane is then deflated
and retracted into the device prior to removal from the patient. Upon retraction
the material sampled from the rectal mucosa is retained on the inverted membrane, which acts as a receptacle for the addition of buffer to preserve the
material for subsequent analysis.
RESULTS: The sampler has now been tested in over 2000 patients and healthy
volunteers, and has shown excellent patient acceptability. Tests and in vitro
experiments with monolayers of cultured human cells indicate that the membrane
captures intact cells, which are easily washed off the membrane for further investigation. Detailed evaluation of the mucous-associated soluble material captured
by the device in both normal and diseased states, shows it to be rich in protein
and nucleic acids. Levels of soluble protein material present in the buffer vary
between 90 and 3000 g/mL, with a mean of 710 g/mL. As part of a programme to identify novel cancer biomarkers, Origin Sciences has evaluated the
presence of auto-antibodies in the proteinaceous component of the preparation,
and has detected informative auto-antibody isotypes IgA, IgG and IgM by
ELISA. The preparation is also rich in nucleic acids. DNA is found in amounts
ranging from 0.5 to 21.9 ug/mL. Laboratory experiments have shown that this
DNA retains a high degree of integrity and is suitable for PCR amplification, and
subsequent sequencing, since we have been able to detect a number of genes by
quantitative PCR.
CONCLUSION: The sampling device represents a novel and minimally invasive
means of capturing biomarker-rich material from the unprepared rectum. Since
there is minimal contamination by stool, the material collected is readily analysable, in principle lending itself to Point of Care tests for a wide range of indications, including infectious and inflammatory diseases of the GI tract in addition
to malignancy. The device can be used as a robust means of collecting material
for later analysis by a wide range of technologies.
Disclosure of Interest: None declared
P0416 SYMPTOM-SPECIFIC REFERRAL CONTENT: WHAT DOES THE
GASTROENTEROLOGIST NEED?
S.L. Eskeland1,*, L. Aabakken2, T.de Lange1
1
Department of Medical Research, Brum Hospital, Vestre Viken Hospital Trust,
2
Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo,
Norway
Contact E-mail Address: s.l.eskeland@medisin.uio.no
INTRODUCTION: Low quality referrals are a challenge for gastroenterologists
when assessing and prioritizing the patients. However, it is not known which
information the gastroenterologists rely on for this task. We wanted to identify
what gastroenterologists considered the most important variables to include in
the referral letters for 9 common indications.
AIMS & METHODS: 25 Norwegian gastroenterologists completed a web-based
survey where they were asked to select the 15 most important variables out of a
list of 29-36 potential variables.

RESULTS: For all 9 indications, information about duration, current medical


treatment and weight loss were selected. The remaining selected variables were
for:
Dyspepsia: Medical history, nausea/vomiting, reflux, hematemesis, dysphagia,
abdominal pain, effect of anti-acid treatment, general condition, abdominal palpation (AP), previous gastroscopies and lab-analyses for anaemia and faecal
occult blood (FOBT).
Dysphagia: Progression (intermittent, stable, progressive), texture provoking dysphagia, subjective localization of obstruction, hematemesis, regurgitation of
undigested foods, presence of reflux, stimulantia, ulcerogenic medication, general
condition, previous endoscopies and radiology and lab-analyses for anaemia.
Diarrhoea: Hematochezia, nocturnal diarrhoea, recent antibiotic treatment, general condition, digital rectal exploration (DRE), previous endoscopies and labanalyses for anaemia, FOBT, celiac disease, infection/inflammation, inflammatory bowel disease (IBD) and faecal bacteria/parasites.
Bowel changes: Type of change, hematochezia, abdominal pain, B symptoms
(fever, night sweat, weight loss), AP, DRE, general condition, previous endoscopies and lab-analyses for anaemia, celiac disease, IBD and FOBT.
Hematochezia: Blood colour, location of blood (on paper/on faeces/in faeces),
percentage of bowel movements with observed blood, bowel changes, symptoms
from upper or lower GI-tractus, hematemesis, AP, DRE, previous endoscopies
and lab-analyses for anaemia, IBD and FOBT.
Chronic abdominal pain: Medical history, characterization and location of pain,
nocturnal pain, relation to meals, presence of bowel changes, AP, general condition, previous radiology/endoscopies and lab-analyses for anaemia, liver/pancreatic function, IBD and FOBT.
Constipation: Main complaint (hard/ rare/slow etc), frequency and consistency of
bowel movements, hematochezia, abdominal pain, effect of treatment-attempts,
predisposing factors, AP, DRE, previous endoscopies and lab-analyses for anaemia, thyroid disease and FOBT.
Jaundice: Medical history, exposure liver-toxic substances, stimulantia, colour
changes urine/faeces, abdominal pain, AP, liver stigmata, previous radiology
and lab-analyses for liver/pancreatic function, hepatitis serology, specific liver
diseases and infection/inflammation.
Weight loss: Presence of any abdominal symptoms, B symptoms, abdominal
pain, appetite, food intake, general condition, AP, symptoms/findings from
other organ-systems, previous radiology and lab-analyses for anaemia, celiac
disease and FOBT.
CONCLUSION: We identified 15 variables considered essential by gastroenterologists for each of the 9 most common reasons for referrals. Validation of the
relation between the findings and the quality of referrals remains unknown, and
need further assessments.
Disclosure of Interest: None declared
P0417 PREVIOUS SCREENING EPISODE PREDICTORS OF REPEAT
PARTICIPATION IN THE NHS BOWEL CANCER SCREENING
PROGRAMME
S.H. Lo1, S.P. Halloran2,3,*, J. Snowball2, H.E. Seaman2,3, J. Wardle1,
C.von Wagner1
1
Department of Epidemiology and Public Health, Health Behaviour Research
Centre, University College London, London, 2NHS Bowel Cancer Screening
Southern Programme Hub, 3University of Surrey, Guildford, United Kingdom
Contact E-mail Address: s.halloran@nhs.net
INTRODUCTION: Effective colorectal cancer (CRC) screening using faecal
occult blood (FOB) tests requires adherence to a programme of repeat participation. This study investigated previous screening episode predictors of screening
uptake among previous responders.
AIMS & METHODS: The NHS Bowel Cancer Screening Programme (BCSP) in
England offers biennial screening using a guaiac FOB test. Uptake data for the
second (R2) and third (R3) biennial invitation round were studied among 62,099
individuals (aged 60-64) in the Southern Hub of the BCSP. R3 invitees comprised
three subgroups: Consistent Screeners (screened in R1 and R2), Dropouts
(screened in R1, not screened in R2) and Late Entrants (not screened in R1,
screened in R2). Predictors of uptake derived from previous screening episodes
included late return of the test kit (after more than 28 days), test results and
compliance with follow-up investigations (usually colonoscopy). Age, gender,
area-level socioeconomic deprivation and screening history were included in
multivariable logistic regression analyses.
RESULTS: Overall uptake among previous responders was 86.6% in R2 and
88.6% in R3. In R3, repeat uptake was 94.5% among Consistent Screeners,
59.8% among Dropouts and 78.0% among Late Entrants (differences between
groups, p50.001). Returning the test kit after more than 28 days in a previous
episode was associated with a reduced likelihood of repeat uptake in R2 (82.3%
vs. 88.7%, p50.001) and R3 (84.5% vs 90.5%, p50.001). Receiving an abnormal test result was also strongly associated with reduced repeat uptake in R2
(61.4% vs. 86.8%, p50.001) and R3 (65.7% vs. 88.8%, p50.001). Furthermore,
repeat uptake in R2 and R3 was particularly low among subjects who had not
attended their follow-up test (R2: 24.3% vs. 67.1%, p50.001; R3: 43.2% vs.
69.9%, p50.001).
CONCLUSION: Previous screening episode factors related to various stages of
the screening process have been implicated in subsequent uptake. These previous
screening episode predictors could be used to identify individuals at risk of
dropping out of screening and provide an opportunity to tailor invitation and
reminder letters to elicit increased uptake by selected sub-populations.
Disclosure of Interest: None declared

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P0418 CAN WE EXPLAIN THE APPARENT DECLINE IN UPTAKE OF
INVITATIONS FOR COLORECTAL CANCER SCREENING IN
ENGLAND?
J. Snowball1, H.E. Seaman1,2, S.P. Halloran1,2,*
1
NHS Bowel Cancer Screening Southern Programme Hub, 2University of Surrey,
Guildford, United Kingdom
Contact E-mail Address: s.halloran@nhs.net
INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) provides biennial guaiac-based faecal occult blood test (gFOBT) screening for colorectal cancer (CRC) to individuals aged 60-74 years (inclusive). Uptake of
screening invitations in England, which averages about 55%, is affected by individual factors that include screening history, sex and level of social deprivation.
Data for 2013 indicate a marked decline in uptake in England during the second
half of 2013. The BCSP in England is co-ordinated by five regional Hubs; each
works with local screening centres that provide follow-up investigations (usually
colonoscopy) for individuals with a positive gFOBT result. The Southern Hub
provides the screening service to about 26% of the population in England (14.6
million); it sends over one million invitations for screening and analyses about g
million test kits every year. Uptake in the Southern Hub averages 61% (2012/
2013) but demonstrates the decline since June 2013 reported across the rest of the
country, an observation investigated by the Southern Hub research team.
AIMS & METHODS: All BCSP screening activity is recorded on the Bowel
Cancer Screening System (BCSS). Data for the period 2009-2013 were analysed
to investigate patterns of uptake according to age, sex, screening episode, index
of multiple deprivation (IMD) and screening centre.
RESULTS: Amongst individuals aged 60-74 years, although subject to marked
fluctuations throughout each year, the overall trend was towards increased
uptake until June 2013, after which uptake declined sharply. Uptake amongst
first-time invitees aged 60 years was the most consistent (55%) between 2009 and
2012, although a marked fall in uptake was evident from mid-2013. The most
deprived showed the greatest fall in the first invitation episode (60-year-olds) and
there was no change in uptake by the least deprived individuals. Different patterns observed across screening centres may reflect different start dates resulting
in a different mix of episodes, with the population with the longest screening
history possibly subject to screening fatigue.
CONCLUSION: We have not explained the decline in uptake of CRC cancer
screening invitations during 2013. A decline in CRC screening uptake has been
observed by the other BCSP Hubs and by the NHS screening programmes for the
breast and cervix (personal communication), although the decline in uptake of
breast and cervix screening has been more gradual. It may be that the public is
reacting to adverse publicity about the benefits of screening surrounding breast
screening, in particular, although data from the Scottish programme do not
demonstrate the decline observed in England (personal communication). The
benefits of CRC screening are well-recognised and efforts to improve uptake
of screening invitations and close monitoring of uptake should continue.
Disclosure of Interest: None declared
P0419 PATIENT PREFERENCES FOR TERMINOLOGY USED TO
IDENTIFY FECAL INCONTINENCE
S. Heymen1,*, O. Palsson1, S.M. Kim1, S. Twist1, W.E. Whitehead1
Medicine, University of North Carolina, Chapel Hill, United States
Contact E-mail Address: steve_heymen@med.unc.edu

CONCLUSION: We recommend excluding the term Diarrhea as it is not specific


to leakage of diarrhea. The remaining top three terms were ranked identically for
participants with and without FI: 1) Bowel Incontinence, 2) Bowel Control
Issues, 3) Accidental Bowel leakage. All three terms scored below the median
on the Uncomfortableness domain. The term used most often by providers, fecal
incontinence, did not score in the top 10 on any of the 3 domains. Accidental
Bowel leakage, recently described as patients preferred term, ranked 3rd. This
information may help improve communication between patients and providers
and enable more patients to receive treatment. Supported by Salix
Pharmaceuticals.
Disclosure of Interest: None declared
P0420 SORD OVEREXPRESSION AND OTHER ASPECTS OF
DYSREGULATED PROTEIN EXPRESSION IN HUMAN
PRECANCEROUS COLORECTAL NEOPLASMS: A QUANTITATIVE
PROTEOMICS STUDY
T. Staiano1,*, A. Uzozie2, P. Nanni2, M. Giancarlo2
ENDOSCOPY AND GASTROENTEROLOGY UNIT, A. O. ISTITUTI
OSPITALIERI DI CREMONA, CREMONA, Italy, 2ENDOSCOPY AND
GASTROENTEROLOGY UNIT, University of Zurich, zurig, Switzerland
Contact E-mail Address: terrystaiano@libero.it
1

INTRODUCTION: Colorectal adenomas are cancer precursor lesions of the


large bowel. A multitude of genomic and epigenomic changes have been documented in these preinvasive lesions, but their impact on the protein effectors of
biological function has not been comprehensively explored.
AIMS & METHODS: Using shotgun quantitative MS, we exhaustively investigated the proteome of 30 colorectal adenomas and paired samples of normal
mucosa. Total protein extracts were prepared from these tissues (prospectively
collected during colonoscopy) and from normal (HCEC) and cancerous (SW480,
SW620, CACO2, HT29, CX1) colon epithelial cell lines. Peptides were labeled
with isobaric tags (iTRAQ 8-plex), separated by OFFGEL electrophoresis, and
analyzed by LC-coupled tandem MS. Non-redundant protein families (4325 in
tissues, 2017 in cell lines) were identified and quantified. Principal component
analysis of the results clearly distinguished adenomas from normal mucosal
samples, and cancer cell lines from HCEC cells.
RESULTS: Two hundred twelve proteins displayed significant adenoma-related
expression changes (q-value 5 0.02, mean fold change vs. normal mucosa /1.4), which correlated (r 0.74) with similar changes previously identified by our
group at the transcriptome level. Fifty-one (25%) proteins displayed directionally similar expression changes in colorectal cancer cells (vs. HCEC cells) and
were therefore attributed to the epithelial component of adenomas. Although
benign, adenomas already exhibited cancer-associated proteomic changes: 69
(91%) of the 76 protein upregulations identified in these lesions have already
been reported in cancers. One of the most striking changes involved sorbitol
dehydrogenase (SORD), a key enzyme in the polyol pathway.
CONCLUSION: Validation studies revealed dramatically increased SORD concentrations and activity in adenomas and cancer cell lines, along with important
changes in the expression of other enzymes in the same (AKR1B1) and related
(KHK) pathways. Dysregulated polyol metabolism may represent a novel facet
of the metabolome remodeling associated with tumorigenesis.
Disclosure of Interest: None declared

INTRODUCTION: Fecal incontinence (FI) affects 9% of non-institutionalized


U. S. adults, but fewer than 30% have discussed this problem with their physician. This is unfortunate because effective treatments are available. Two factors
that may contribute to low consulting rates are embarrassment about this taboo
topic and unfamiliarity with the terms used by physicians.
AIMS & METHODS: Our goal was to identify terms that are the most acceptable and understandable to FI patients to make it easier for clinicians to inquire
about and discuss FI with patients, and easier for patients to disclose the problem. Thirty patients with FI (29 women) recruited by advertisement participated
in internet chat rooms of 1-5 persons. They were asked: What words do you use
to describe your FI when you are talking to doctors, family members, or
friends? with requests to rate 3 domains on a 0-10 scale: 1) the understandability
of these terms, 2) their appropriateness for discussions with others, and 3) the
patients level of discomfort (embarrassment) in using the term. Based on focus
group input, 29 terms were selected for participants to evaluate for a national
survey. Thirty-one terms were not included because the investigators deemed
them to be offensive (e.g., squirts, shits, taco butt) or because they were adjectives
describing emotional reactions to FI or characteristics of FI (e.g. Embarrassing,
Disgusting). This sample was stratified by FI status, age, sex, and race/ethnicity.
RESULTS: The national survey recruited 560 participants (42% with FI). Sixtyfour participants were excluded for answering identical questions inconsistently.
The remaining 496 participants had a mean age of 47.5 (range 18-91) years, 48%
of participants were males, and race/ethnicity was 69.6% Caucasian, 15.7%
Hispanic, and 14.7% African American. Participants were also divided into
three age groups for analysis: 35 and younger (n 146), 36-64 (n 243) and 65
and older (n 106). Appropriateness ratings are reported here. When we compared the ratings from participants with FI and without FI, four of the top five
rated terms were the same for both groups (Bowel Incontinence, Bowel Control
Issues, Accidental Bowel Leakage, and Diarrhea). Women rated all of these
terms as significantly more Appropriate than men did. A consistent race/ethnicity
pattern showed highest Appropriateness ratings for Caucasians, then Hispanics,
and lowest by African Americans on all of these terms. Ratings also differed
significantly by age group, increasing with age across the three groups for all of
these terms. Ratings differed on only one of these terms due to Education level
(Bowel Control Issues) or Income (Bowel Incontinence).

P0421 KNOWLEDGE AND PERCEPTION OF DOCTORS ON RISK


FACTORS AND SCREENING OF COLORECTAL CANCER (CRC)
Y.J. Wong1,*, Z. Poh1, M.L. Ong1, K.L. Shum1, V. Namasivayam1, K.L. Ling1
1
Gastroenterology, Singapore General Hospital, Singapore, Singapore
Contact E-mail Address: eugene.wong@mohh.com.sg
INTRODUCTION: CRC has claimed 214,675 lives Europe and is expected to
rise by 12% by 20201. Knowledge and perception of doctors is important to
future success of CRC screening program as early detection of CRC improve
survival. However, little is known about doctors knowledge and perception
towards CRC. We aim to determine current knowledge and perception of colorectal cancer screening amongst junior doctors.
AIMS & METHODS: 169 junior doctors practicing across 7 specialties at a local
academic institution were recruited from July -September 2013. Standardized
questionnaires consisting of 44 questions were administered during structured
resident teaching sessions that were unrelated to CRC. Individual responses
were collected. Absent doctors were contacted via email. Standard statistical
techniques were employed.
RESULTS: 74% (125/169) of junior doctors responded. Respondents mean age
was 27.7 years (23-35). Mean duration of practice locally was 3.2 years (1-8).
Majority (97.6%) were aware that CRC is curable if treated early, and 85.6%
recognized that CRC screening reduces mortality. Only 78.4% recognized CRC
as the commonest cancer locally. Most CRC risk factors (CRC-RFs) such as age,
family history, smoking, inflammatory bowel disease and colonic polyps were
correctly identified (84.8-100%). However, knowledge of modifiable CRC-RFs
was poor. Few recognized diabetes mellitus (5.6%), sedentary lifestyle (39.2%)
and obesity (43.2%) as CRC-RFs. In addition, 10.4% wrongly identified traditional medicine as a CRC-RF, and only 45.7% correctly identified the recommended age for CRC screening according to local guidelines. More fresh
graduates (PGY1) correctly identified 80% of CRC-RFs compared to the
rest (40% vs 21.9%; p 0.044). Only 90.4% and 88% identified colonoscopy
and fecal occult blood test (FOBT) as acceptable CRC screening methods. 94.2%
felt FOBT had poor test performance. Physicians concerns for colonoscopy
included cost (76.9%), risk of perforation (61.5%), bleeding (46.2%), and inconvenient bowel preparation (66.7%). In spite of this, 80.8% will offer colonoscopy
while only 68% will offer FOBT for CRC screening to their patients. There was

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no difference in attitudes and practice patterns between doctors of different postgraduate years.
CONCLUSION: Majority of junior doctors correctly identified CRC as a significant healthcare burden, and that CRC screening and early detection reduces
mortality. However, knowledge on modifiable CRC-RFs is still lacking. Many
had concern about FOBT test performance, and more will offer screening colonoscopy. Continual medical education for junior doctors on modifiable CRC-RF
and importance of CRC screening should be emphasized for continual success of
CRC screening.
REFERENCES
1. GLOBOCAN. Estimated cancer incidence, mortality and prevalence worldwide
in 2012, 2012.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


NERVE GUT AND MOTILITY
XL_____________________

POSTER

EXHIBITION

9:0017:00
HALL

P0422 OSMOTIC LAXATIVES ARE ASSOCIATED WITH LOWER


RIGIDITY IN IDIOPATHIC PARKINSONISM
A. Augustin1,*, A. Charlett2, C. Weller1, S.M. Dobbs1,3, D. Taylor1, M. Ibrahim4,
I. Bjarnason3, R.J. Dobbs1,3
1
Pharmaceutical Science, Kings College London, 2Statistics Unit, Centre for
Infectious Disease Surveillance and Control, Public Health England,
3
Gastroenterology, Kings College Hospital, 4Diagnostic Immunology Laboratory,
Kings College and St Thomass Hospitals, London, United Kingdom
Contact E-mail Address: sylvia.dobbs@kcl.ac.uk
INTRODUCTION: In idiopathic parkinsonism (IP), flexor rigidity is greater the
higher the circulating natural-killer cell count, an effect modulated by CD4
count.1 These counts are higher with hydrogen-breath-test positivity for smallintestinal-bacterial-overgrowth. Two-thirds of IP-patients are positive at
presentation.
AIMS & METHODS: Improving intestinal transit with laxatives might reduce
rigidity by reducing overgrowth.
Relationships of interventions for constipation to rigidity and overgrowth were
explored using generalised linear mixed models. Surveillance yielded 1378 objective measures of arm rigidity in 74 IP-patients over 343 person years, with 437 2-h
lactulose-hydrogen-breath-tests in 48. Maintenance osmotic laxative (macrogols)
was exhibited in 50 (176 person years); bulk-forming laxative (ispaghula husk/
methylcellulose/sterculia) in 52 (196); enterokinetic agent (prucalopride) in 25
(45); and guanylate cylase-C receptor agonist (linaclotide) in 8 (12).
RESULTS: Osmotic laxative was the only intervention associated with a change in
rigidity. Flexor rigidity increased (by 6.8 (4.3, 9.4) % per year, p 0.001) where not
exhibited, stabilised where exhibited (1.4 (95% CI -0.9, 3.8) % per year, p 0.2).
Bulk-forming laxative had no additional effect on rigidity (p 0.5). Similarly, the
ratio, flexor to extensor rigidity, indicating tendency to simian posture, increased
(3.2 (0.7, 5.7) % per year, p 0.01) where osmotic laxative was not exhibited,
stabilised where exhibited (-1.6 (-3.9, 0.8) % per year, p 0.2). Bulk-forming laxative had no additional effect on the ratio (p 0.6).
Only bulk-forming laxative was associated with change in breath-hydrogen. Peak
hydrogen was lower by 11 (1. 20) ppm (p 0.03) where exhibited, with no differential effect of time (p 0.9). (Odds ratio for a positive breath-test where exhibited compared with where not: 0.55). Osmotic laxative had no additional effect
on peak hydrogen (p 0.3).
CONCLUSION: Osmotic laxative may reduce rigidity by reducing inflammation, directly, or by removing an inhibitory effect on anti-parkinsonian medication. Any effect of overgrowth on rigidity may relate to organisms not flagged by
hydrogen-breath-test.
REFERENCES
1. Dobbs RJ et al. Leukocyte-subset counts in idiopathic parkinsonism provide
clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A
surveillance study. Gut Pathogens 2012; 4: 12.
Disclosure of Interest: None declared
P0423 DOES BODY POSITION MODIFY ANORECTAL PRESSURE
VALUES RECORDED BY THREE-DIMENSIONAL HIGHRESOLUTION ANORECTAL MANOMETRY?
A. Benezech1,2,*, M. Bouvier1,2, J.-C. Grimaud1,2, N. Lesavre3, K. Baumstarck4,
V. Vitton1,2
1
Centre dExploration Fonctionnelle Digestive, Service de Gastroenterologie,
Hopital Nord, 2Interface de Recherche Translationnelle en Neurogastroenterologie,
CRN2M, UMR 7286, Aix-Marseille Universite, 3Centre dInvestigation Clinique
9502, Hopital Nord, 4Unite dAide Methodologique a` la Recherche Clinique,
EA3279, Laboratoire de Sante Publique, Aix-Marseille Universite, Marseille,
France
INTRODUCTION: Anorectal manometry is the gold standard in the physiological exploration of anorectal disorders. In recent years, three-dimensional highresolution anorectal manometry (3DHRAM) was developed. However, exams
(conventional manometry or 3DHRAM) are traditionally made in the left lateral
decubitus position while anorectal symptoms (dyschezia and anal incontinence)
occur in the standing or sitting position.
AIMS & METHODS: The aim of our prospective study was to compare the
pressure values obtained by 3DHRAM in the lying position (left lateral decubitus
position) and in the standing position.
All patients referred to our center to explore anal incontinence or dyschesia by
3DHRAM and EUS were eligible. Patients with a history of anorectal surgery or
suffering from anal pain were excluded. The 3DHRAM was performed by the

same operator successively in the left lateral decubitus position and in the standing position. The EUS was perfomed the same day. KESS and Wexner scores
were routinely rated, as well as size and weight of the patients. The calculated
number of patients required for this study was 40.
RESULTS: These are preliminary results (20 patients included in the 40 to be
included). 17 females and 3 males, with a median age of 41 years (20-73) and a
median body mass index of 23 kg/m2 (17-36) were included. The indication of
examinations was anal incontinence in 8 patients and constipation in 12 cases,
with a median KESS score of 20 (9-32) and a median Wexner score of 9 (7-20).
No manometric measured parameters was significantly different in the supine or
standing position, whatsoever in the subgroup of incontinent patients or in the
subgroup of constipated patients.
CONCLUSION: These preliminary results showed no significant difference
between the pressure values measured by 3DHRAM in the supine and standing
position. At this stage of study, two hypotheses can be advanced: 1) the lack of
power related to the low effective since we have included only half of the patients
required; 2) no difference whatever the position of the patient when the measurements are made with 3DHRAM. Analysis of the results when all patients will be
included will provide the answer to this question.
Disclosure of Interest: None declared
P0424 BUSERELIN INDUCES ENTERIC NEURONS TO EXPRESS
CORTICOTROPIN-RELEASING FACTOR
B. Ohlsson1,*, C. Karlsson2, U. Voss3, G. Molin2, S. Ahrne2, E. Ekblad3,
E. Sand3
1
Department of Clinical Sciences, Lund University, Division of Internal Medicine,
Malmo, 2Food Hygiene, Dept of Food Technology, Engineering and Nutrition,
Division of Applied Nutrition, Lund University, 3Department of Experimental
Medical Science, Neurogastroenterology Unit, Lund University, Lund, Sweden
Contact E-mail Address: bodil.ohlsson@med.lu.se
INTRODUCTION: Treatment with gonadotropin-releasing hormone (GnRH)
analogs have led to severe dysmotility, which implicates roles for the reproductive
peptide/hormones in the gastrointestinal tract. Administration of the GnRH
analog buserelin to rats leads to neurodegeneration and ganglioneuritis.
During these experiments, we have observed that the treated rats have exhibited
a more stressed behavior than controls. Stress has been shown to increase secretion of corticotropin-releasing factor (CRF) and to increase intestinal permeability in humans, and to increase locomotion, rearing, pellet excretion, and altered
colonic microbiota in rodents. CRF is highly expressed in the enteric nervous
system in humans and rodents, and has been shown to abolish the vasoactive
intestinal peptide (VIP)-induced neuronal survival.
AIMS & METHODS: The aim of the present study in rat was to evaluate the
effect of the GnRH analog buserelin on enteric neurons immunoreactive to CRF
and the intestinal microbiota.
Forty rats were given either buserelin (B) (20 g, 1 mg/ml) or saline (C) subcutaneously, once daily for five days, followed by three weeks of recovery, representing one session of treatment. Two weeks after the fourth session, the animals
were euthanized. Gastrointestinal tissue were collected and analyzed for neuronal
survival and CRF immunoreactivity. Microbial DNA (16S rRNA genes) was
extracted from the colonic mucosa and analyzed with molecular genetic methods.
The Terminal Restriction Fragment Length Polymorphism (T-RFLP) method
was used to analyze microbial diversity. Bacterial abundance of the bacterial
groups Clostridium leptum and Enterobacteriaceae was estimated using separate
quantitative PCR assays.
RESULTS: Body weight transiently increased by buserelin treatment at week 5
and 9 (p 5 0.001). Enteric neurons were reduced in number by approximately
40% in both submucous and myenteric ganglia of ileum and colon. Enteric
neurons in colon immunoreactive to CRF increased in submucous ganglia
(C 10 (6-16)%, B 21 (14-25)%, p 5 0.05) and in myenteric ganglia (C 7
(5-9)%, B 19 (18-23)%, p 5 0.01) due to buserelin treatment. In submucous
ganglia, the number of neurons immunoreactive to both nitric oxide synthase
(NOS) and CRF increased due to buserelin treatment (p 5 0.05). In the myenteric ganglia, the number of neurons immunoreactive to NOS or VIP, in addition
to CRF, tended to increase after buserelin treatment (p 5 0.14 and p 5 0.08,
respectively). The CRF fiber density was unaffected by buserelin treatment
throughout all the different layers of the bowel wall. The total amount of bacteria
and diversity in colon did not differ between groups. The number of bacteria in
the group of Enterobacteriaceae was significantly lower in buserelin-treated rats
compared to saline-treated rats (p 5 0.05), whereas the total amount of bacteria
in the groups of Clostridium leptum did not differ between broups.
CONCLUSION: The relative number of enteric neurons expressing CRF was
increased after induction of enteric neuropathy. The enteric nervous system
shows proof of plasticity, since NOS-immunoreactive neurons starts to express
CRF after buserelin treatment. Despite a marked enteric neuropathy, no signs of
bacterial overgrowth or diminished diversity are at hand in colon.
Disclosure of Interest: None declared
P0425 FUNCTIONAL CONSEQUENCES AFTER BUSERELIN-INDUCED
ENTERIC NEUROPATHY IN RAT
B. Ohlsson1,*, E. Ekblad2, B. Roth1, B. Westrom3, P. Bonn2, E. Sand2
Department of Clinical Sciences, Lund University, Division of Internal Medicine,
Malmo, 2Department of Experimental Medical Sciences, Neurogastroenterology
Unit, Lund University, 3Department of Biology, Functional Biology, Lund
University, Lund, Sweden
Contact E-mail Address: bodil.ohlsson@med.lu.se
1

INTRODUCTION: Women treated with gonadotropin-releasing hormone


(GnRH) analogs develop in some cases enteric neuropathy with ensuing severe

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United European Gastroenterology Journal 2(1S)


dysmotility. Administration of GnRH analog to rats leads to similar degenerative
changes and ganglioneuritis.
AIMS & METHODS: The aim of the present study in rat was to evaluate the
enteric neuropathy, in terms of affected neuronal subpopulations and gastrointestinal function, and to investigate levels of zonulin and titers of GnRH and
luteinizing hormone (LH) and their receptors in plasma.
Forty rats were given either the GnRH analog buserelin (B) (20 g, 1 mg/ml) or
saline (C) subcutaneously, once daily for five days, followed by three weeks of
recovery, representing one session of treatment. Two weeks after the fourth
session, the animals were euthanized. Prior to sacrifice, feces were analyzed for
weight and fat, and GI transit time and galactose absorption were studied.
Neuronal subpopulations and survival were analyzed in GI tissue. Blood samples
were analyzed for zonulin, GnRH and LH and their receptors.
RESULTS: Body weight transiently increased by buserelin treatment at week 5
and 9 (p 5 0.001). Buserelin increased estradiol in plasma and uterine muscle
layers were thickened, implicating high estrogen activity. Enteric neurons were
reduced in number by approximately 40% in both submucous and myenteric
ganglia of ileum and colon. Feces weight decreased in buserelin-treated rats
(C 4.3 (3.4- 5.9) g; B 3.2 (2.4-3.6) g, p 5 0.01) whereas fat content in feces
increased (C 2.8 (2.9-3.9)%; B 3.6 (2.6-3.2)%, p50.01), compared to salinetreated rats. Total GI transit time and galactose absorption were not affected by
buserelin treatment. Studies on the various neuronal subpopulations in colon
showed increased relative number of somatostatin immunoreactive neurons in
submucous, but not myenteric, ganglia while the numbers of cocaine-amphetamine-related transcript (CART), calcitonin gene-related peptide (CGRP), galanin, gastrin-releasing peptide (GRP), neuropeptide Y (NPY), nitric oxide
synthase (NOS), serotonin, substance P (SP) and vasoactive intestinal peptide
(VIP) were unchanged. The levels of zonulin in plasma and the titers of antibodies against GnRH, LH or their receptors were unaffected by buserelin
treatment.
CONCLUSION: A marked enteric neuropathy is at place with only modest
effects on gastrointestinal function after buserelin treatment. Altered feces
weight and fat content is suggested as early signs of dysfunction.
Disclosure of Interest: None declared
P0426 CHARACTERIZATION OF BIOMECHANICAL PROPERTY OF
INTESTINAL SMOOTH MUSCLE USING HILL-TYPE MUSCLE
MODEL; ANIMAL STUDY
S.-J. Nam1, H.J. Chun1, J.H. Hong2, J.J. Seo2, S.Z. Yoon3, S.H. Kim1, J.M. Lee1,
I.K. Yoo1, H.S. Choi1, E.S. Kim1, B. Keum1, Y.T. Jeen1, H.S. Lee1, C.D. Kim1,*,
S.W. Lee1, J.-J. Park1
1
Internal Medicine, Korea University College of Medicine, 2Control and
Instrumentation Engineering, Korea University, 3Anesthesiology, Korea University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: pinetrees@daum.net
INTRODUCTION: Various treatment modalities for GI motility disorders have
been developed so far including medications and electrical stimulation. But little
is known about biomechanical properties of gastrointestinal smooth muscle, in
contrast to vascular or respiratory smooth muscle. In this study, we made a novel
actuator model for characterization of biomechanical property of small intestinal
smooth muscle.
AIMS & METHODS: In the order to characterize active and passive properties
of intestinal smooth muscle, we performed tensile test and isometric, isotonic
experiments using viable small intestines of 3 month old pig. In the tensile testing,
we connected excised intestinal samples to the universal testing machine developed by our own group only for soft tissue measurement. In isometric and
isotonic experiments, porcine small intestine was bathed in HTK-solution for
preservation of energy source. After connection of the sample to sensor,
muscle contraction was induced by acetylcholine chloride. Contractile force
and velocity were measured by isometric force transducer and isotonic
transducer.
RESULTS: In tensile experiment, tensile stress was maximum at the 1.67 times
its original length and 0.702N at break point. In isometric experiment, maximum
contractile force was observed at the resting length which was 12.350.5 mN
after 50min of acetylcholine stimulation. Intestinal smooth muscle contraction
was sustained for 55min. In isotonic experiment, intestinal smooth muscle was 10
to 100 times slower than skeletal muscle contraction. We calculated contractile
velocity for various loads and acquired load free contractile velocity by curve
fitting method (0.4952 mm/min). Finally, we combined previously acquired passive and active parameters of intestinal smooth muscle to make a comprehensive
intestinal smooth muscle model.
CONCLUSION: In this study, we characterized active and passive parameters
and applied them to modified Hill type muscle model for making a novel actuator of intestinal smooth muscle. This study would provide basic tool for understanding biomechanical properties of intestinal smooth muscle, and we can utilize
this as basic data for development of a more efficient GI electrical stimulator.
Disclosure of Interest: None declared

P0427 5HT SELECTIVE RECEPTOR AGONISTS AND GALLBLADDER


MOTILITY IN PATIENTS WITH MIGRAINE
D. Georgescu1,*, C. Georgescu2, R. Buzas1
1
Internal medicine, University of Medicine, 2Neurology, County Hospital,
Timisoara, Romania
Contact E-mail Address: dgeorgescu@hotmail.com
INTRODUCTION: Some 5HT selective receptor agonists (triptans) are reported
to have gastric motor effects but less is known about their role on gallbladder
(GB) motility.
AIMS & METHODS: Assessment of GB motility in patients treated with orodispersable triptans .30 patients diagnosed with mild to moderate migraine: 15
with with aura (3 men, 12 women, mean age 43.1317.72 years) and 15 without
aura ((1 man, 14 women, mean age 47.7318.50 years), with an ejection fraction (EF) of GB 5 60%, previously measured by elipsoid ultrasound Dodds
method, without prokinetic treatments, collagen or thyroid disease, diabetes
mellitus, cardiac, liver or kidney failure, undertook this study. The same measurements were made while having a migraine attack, before and every 15 minutes till 90 minutes after receiving 5 mg of orodispersable zolmitriptan.
RESULTS: There was no statistical significant difference between initially EF of
the two groups (p 0.8190). Patients with migraine with aura showed before therapy a mean EF 42.534.31%; after therapy the mean EF improved significantly:
48.803.23% (p 0.0001). Patients with migraine without aura displayed an initially mean EF 42.533.27% and had a very statistically significant response to
therapy with increasing of EF to 61.477.07% (p50.0001). There was also a
statistically significant difference of respose to therapy in patients with migraine
without aura (61.477.07% vs 48.803.23%; p50.0001).
CONCLUSION: 5HT selective receptor agonists increased GB motility in
migraine attacks with a better response in patients without aura.
REFERENCES
1. Dodds WJ, Groh WJ, Darweesh RM, et al. Sonographic measurement of
gallbladder volume. Am J Roentgenol 1985; 145: 1009-1011.
2. Bigal ME, Ferrari M, Silberstein SD, et al. Migraine in the triptan era: lessons
from epidemiology, pathophysiology, and clinical science. Headache 2009;
49(Suppl. 1): S21-33.
3. Cipolla G, Sacco S, Crema F, et al. Gastric motor effects of triptans: open
questions and future perspectives. Pharmacol Res 2001; 43: 205-210.
4. Moroa E, Cremaa F, De Pontib F, et al. Triptans and gastric accommodation:
pharmacological and therapeutic aspects. Dig Liver Dis 2004; 36: 8592.
5. Deixler E and Helmke K. Extrahepatic cholestasis during therapy with zolmitriptan. Z Gastroenterol 2005; 43: 1045-1049.
Disclosure of Interest: None declared
P0428 NEUROPATHOLOGICAL ANALISYS AND CLINICAL FEATURES
OF CHRONIC CONSTIPATION IN PATIENTS WITH PARKINSON
DISEASE
F. Giancola1,*, C. Sorteni2, F. Torresan3, A. Ioannou3, M. Guarino4,
G. Barbara3, C. Cremon3, R. Latorre3, R. Chiocchetti2, C. Vallorani2,
P. Clavenzani2, P. Cortelli5, V. Stanghellini3, C. Sternini6, R. De Giorgio3
1
Dept Vet Med Sci and Dept Med Surg Sci, 2Dept Vet Med Sci, 3Dept Med Surg
Sci, University of Bologna, 4Neurology Unit, St. Orsola-Malpighi Hospital, 5Dept
Biom and Neuromot Sci, University of Bologna, Bologna, Italy, 6CURE/Dig Dis
Res Center, Div Dig Dis, Depts Med Neurobiol, David Geffen School of Medicine,
University of California at Los Angeles, Los Angeles, California, United States
Contact E-mail Address: fiorella.giancola2@unibo.it
INTRODUCTION: Chronic constipation (CC) represents one of the most
common gastrointestinal (GI) complaints in Parkinsons disease (PD), being
diagnosed in about 80% of patients. Furthermore, CC often precedes the somatic
motor impairment in PD. The enteric nervous system (ENS), controlling gut
functions, can be a target of the PD although the precise neurochemical ENS
abnormalities underlying CC/PD patients remain largely unknown.
AIMS & METHODS: In CC/PD patients we aimed to: 1) characterize constipation by assessing colonic transit time (TT) and anorectal manometry (AM); 2)
analyze colonic submucosal neurons of PD patients vs controls, particularly
assessing the secretomotor neuron component.
GI symptoms were evaluated by the Rome III questionnaire, while PD was established by a Unified Parkinsons Disease Rating Scale (part III). CC was studied in 25
PD patients (7F, 18M; age range: 64-85 yrs) by TT, AM and colonoscopy; 14 control
subjects (4F, 10M; age range: 33-77 yrs) undergoing screening colonoscopy were also
enrolled in the study. Using routine biopsies during colonoscopy, we obtained submucosal specimens with related neural network in 10 CC/PD patients and 10 controls.
The submucosal plexus was studied by immunohistochemistry on whole mount preparations using a mouse monoclonal anti-HuC/D as pan-neuronal marker
(Invitrogen, 1:50) and two rabbit polyclonal anti-VIP (vasoactive intestinal peptide7913; CURE/DDRC, UCLA, 1:2500) and anti-pChAT (peripheral choline acetyl
transferase, Justus-Liebig-University Giessen, Germany; 1:100) antibodies.
RESULTS: Four groups of CC/PD patients were characterized: a) 55% with a
delayed TT and altered AM; b) 15% with a delayed TT; c) 20% with an altered
AM; d) the remaining 10% with no evident functional impairment. There were
no significant differences in the number of HuC/D immunoreactive (-IR) neurons/ganglion between CC/PD (4.70.8) and controls (5.51.5); however, a
reduced number of HuC/D/VIP-IR neurons was found in CC/PD (73.317.1)
vs controls (86.010.9) (P50.05). No significant changes were detected for HuC/
D/ChAT neurons in both groups (85.611.1 vs. 91.210.1).
CONCLUSION: Most (90%) of CC/PD patients has a marked impairment of
colonic motor and rectal sensory functions. Neurochemical changes in a subset of
VIP containing secretomotor neurons suggest that altered secretory mechanisms
may accompany sensorymotor dysfunction in PD-related CC pathophysiology.

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Disclosure of Interest: None declared


P0429 EHLERS-DANLOS SYNDROME
SYMPTOMS, DIFFERENT DISEASES

P0431 RECIPROCAL MODULATION OF INTESTINAL SMOOTH


MUSCLE CELL CONTRACTILITY BY TH17 AND TH1 CYTOKINES
AND

IBS

SAME

GI

G. Mohammadian1,2,*, J. Lunding3, G. Lindberg2,3


1
Center of Digestive Diseases, Karolinska Universtity Hospital, 2Institution of
Medicine, Huddinge, KAROLINSKA INSTITUTET, 3Center of digestive diseases, Karolinska University Hospital, Stockholm, Sweden
Contact E-mail Address: ghazaleh.mohammadian.kermani@ki.se

H. Akiho1,*, K. Ohbuchi2, K. Tsuchiya2, E. Ihara3, K. Nakamura3,


M. Yamamoto2
1
Gastroenterology, Kitakyushu Municipal Medical Center, Kitakyushu, 2Tsumura
Research Laboratories, Tsumura & Co., Ibaraki, 3Medicine and Bioregulatory
Science, Kyushu University, Fukuoka, Japan

P0430 COMBINED EFFECT OF EARLY LIFE STRESS AND ACUTE


STRESS AS A NEW MODEL FOR FUNCTIONAL DYSPEPSIA

INTRODUCTION: Gastrointestinal motility disorders, such as infection, IBD,


ileus, achalasia and functional gastrointestinal disease, have been associated with
immune activation. We have previously reported that the hypercontractility of
small intestinal (SI) smooth muscle cells (SMC) is mediated by IL-17A-induced
NFkB/IkBz-RGS4 signaling resulting in down regulation of RGS4 activity.
RGS4 is known to suppress Gaq/11 signaling triggered by stimulation of the
acetylcholine (muscarinic 3) receptor. On the contrary, IL-1, which is known
to induce hypomotility of SMC, upregulates RGS4 expression and function.
However, these opposite effects by IL-17A and IL-1 both have been found to
be mediated by NFkB/IkBz activation. In the present study, we have investigated
the mechanism by which IL-17A- and IL-1-induced NFkB/IkBz activation produces the different outcomes.
AIMS & METHODS: Murine SMCs were isolated, cultured, and treated with
various chemical probes, IL-17A, IL-1, and IL-4 (1050 ng/ml). Contraction
was assessed using a cell imaging analyzer on a temperature-responsive UpCell
96-well plate. Activation of NFB was evaluated by the strength of the nuclear
NFB p65 immunosignal. Activation of RGS4, myosin light chain (MLC) and
MAPKs were determined by immunoblotting.
RESULTS: IL-17A significantly enhanced carbachol-induced contractile
responses, concomitant with increased phosphorylated MLC (p-MLC) and
decreased RGS4 activity. IL-1 significantly decreased p-MLC and increased
RGS4 activity. These effects of IL-17A and IL-1 were both abrogated by an
NFB inhibitor and IB siRNA. Screening of activated MAPK using a proteome profiler revealed that IL-1 activated p38MAPK and JNK but IL-17A
activated p38MAPK only. The effect of IL-17A was abrogated by p38MAPK
inhibitors but not by JNK inhibitors. The effect of IL-1 was abrogated by JNK
inhibitors but enhanced by p38MAPK inhibitors. Anisomycin, a p38MAPK
activator induced hypercontractility.
CONCLUSION: These data suggest that the balance of relative activity levels of
JNK and p38MAPK is critical for determining the direction of contractile
response and that NFB/ IB signaling fuels the movement of MAPK-triggered
molecular events toward/against hypercontractility of SI SMC. The relatively
stronger activation of p38MAPK may result in hypercontractility, induced by
IL-17A, and that of JNK may result in hypocontractility, induced by IL-1. Our
findings may lead to the development of new pharmacotherapeutic strategies for
gastrointestinal motor dysfunctions.
Disclosure of Interest: None declared

H. Abdel-Aziz1, W. Wadie2, H.F. Zaki2, J. Muller1, M.T. Khayyal3,*


1
Scientific Department, Steigerwald Arzneimittelwerk, Darmstadt, Germany,
2
Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, 3Pharmacology,
Faculty of Pharmacy, Cairo University, Darmstadt, Egypt
Contact E-mail Address: heba.abdelaziz@gmail.com

P0432 EXPECTATIONS OF PATIENTS WITH IRRITABLE BOWEL


SYNDROME (IBS): A PROSPECTIVE SURVEY OF THE FRENCH
ORGANIZATION OF IBS PATIENTS

INTRODUCTION: Ehlers-Danlos syndrome (EDS) is usually an autosomal


derived disease with defects in the collagen synthesis. It is divided into six subgroups according to the Brighton criteria. The most common subtype gives
hypermobility of the joints, frequent luxations and fractures. It is also connected
with gastrointestinal symptoms, most commonly abdominal pain and other
symptoms that are included in the functional symptom spectrum. Patients with
EDS fulfil the Rome III criteria for functional gastrointestinal disorders in 84%.
So far there are no systematic studies of GI physiology and treatment for GIdisorders in these patients.
AIMS & METHODS: To evaluate symptoms, gastrointestinal work up, opioid
therapy, treatment response to octreotide, and findings on 24h ambulatory small
bowel manometry in patients with EDS.
Information obtained from patient database and retrospectively acquired information from the medical record system in the out- and inpatient clinic in Center
of Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
RESULTS: The search found 24 patients from 2001 to 2014, all but one were
female. Abdominal pain was present in 100%, change of bowel habits in 19/24.
Ten had done small bowel manometry, 3 of them were classified as enteric
dysmotility and 5 patients had some changes of MMC phase III. Ten of the
patients had tried octreotide and seven of them had clinical response and continued the octreotide treatment. Eleven patients were unable to do small bowel
manometry due to use of opioids and three are on the waiting list for the
manometry.
CONCLUSION: We show that patients with EDS have a high frequency of
changes in small bowel manometry and high prevalence of enteric dysmotility.
Treatment with octreotide is effective, even without having enteric dysmotility.
Abdominal pain in patients with EDS should not be considered as IBS but EDS
should be considered in patients with joint hypermobility and abdominal pain.
Further studies are needed for evaluation of gastrointestinal physiology of
patients with EDS.
Disclosure of Interest: None declared

INTRODUCTION: Functional dyspepsia (FD) is one of the most common GI


disorders. Because of the chronic relapsing nature & lack of effective treatment
options, FD is associated with significantly impaired quality of life and considerable health care costs.
Based on the central role stress seems to be playing in functional GI diseases,
available animal models for FD rely on exposing animals to various types of
stress either in the neonatal period or in adulthood.
However, clinical studies have shown that adverse physiological or psychological
experiences in early life are associated with the development of FD symptoms, as
well as acute stressful conditions in adulthood. Hence, childhood traumatic
experiences followed by later exposure to acute stress may play key roles in the
development & in modulation/ maintenance of FD.
AIMS & METHODS: In the present study, we tried to mimic this situation by
combining early life stress (neonatal maternal separation, NMS) and acute stress
in adulthood (restraint stress, RS) in rats, in the hope of developing a multidimensional experimental model of FD with closer resemblance to the clinical
situation.
To explore the validity of this sequential stress model in trying to develop new
drugs for FD, we tested the effects of STW5, a multicomponent herbal preparation widely used to treat FD with strong clinical evidence, as a standard drug.
RESULTS: Fundus strips from rats subjected to the combined stress showed
significantly reduced responses to adrenaline, carbachol, KCl and 5HT as compared to those from normal rats or animals subjected to either stressor. Animals
treated with STW5 showed normalized response to adrenaline, carbachol and
5HT. Combined stress also markedly increased plasma levels of CRF to twice as
much as either stressor alone. The elevation of CRF was associated with a
corresponding increase in plasma corticosterone. Pretreatment with STW5 protected against the increase in both CRF and corticosterone. None of the treatments significantly affected active plasma Ghrellin.
CONCLUSION: These data indicate that combined early life stress and acute
stress effectively induce stomach motility disorders as well as hormonal derangements that might be more representative of the complex clinical situation and
might represent a model for the screening of new FD drugs.
Disclosure of Interest: H. Abdel-Aziz Other: Employee of Steigerwald
Arzneimittelwerk GmbH, W. Wadie: None declared, H. Zaki: None declared,
J. Muller Other: Employee of Steigerwald Arzneimittelwerk GmbH, M. Khayyal
Financial support for research from: Steigerwald Arzneimittelwerk GmbH

J.-M. Sabate1,*, P. Ducrotte2, T. Piche3, F. Zerbib4, M. Dapoigny5, S. Bruley


Des Varannes6, B. Bonaz7, F. Mion8, F. Iglicki1, D. Denhez1, D. Tchatat1,
S. Facon9, P. Jouet1
1
Hepatogastroenterology, Hopital Louis Mourier, Colombes,
2
Hepatogastroenterology, CHU de Rouen, Rouen, 3Hepatogastroenterology,
Hopital LArchet, Nice, 4Hepatogastroenterology, Hopital Saint Andre, Bordeaux,
5
Hepatogastroenterology, CHU de Clermont Ferrand, Clermont-Ferrand,
6
Hepatogastroenterology, CHU de Nantes, Nantes, 7Hepatogastroenterology,
CHU de Grenoble, Grenoble, 8Service des Explorations Fonctionnelles, Hopital
Edouard Herriot, Lyon, 9Association des Patients Souffrant du Syndrome de
lIntestin Irritable, Hopital Louis Mourier, Colombes, France
Contact E-mail Address: jean-marc.sabate@lmr.aphp.fr
INTRODUCTION: IBS may be responsible for an impaired quality of life (QoL)
and represents an economic burden for society. Efficacy of treatments is poor
and patients often feel isolated and dissatisfied with medical care1. This work
aims to describe the characteristics of IBS in members of the French organization
of IBS patients (APSSII, www.apssii.org) and to compare their expectations to
their past experiences with health care providers.
AIMS & METHODS: From January to June 2013 all members of APSSII were
asked (once, by mail or online) to answer a questionnaire with a description of:
IBS, treatments, impact on QoL, expectations and experiences in relation to the
disease and health care system.
RESULTS: 222 out of 330 members (67%) responded (women 68.5%, age
46.517.7 years, disease duration 8.80.7 years, IBS-D 33.6%, IBS-C 26.7%,
IBS-A 38.2%). A colonoscopy was performed in 87%, and diagnosis was made
by a physician in 88%. Patients were followed up by a doctor in 65% (specialist
57% or GP 38%), and 82% had consulted for IBS in the last 12 months. Past or
current treatments were antispasmodics (46%), laxatives (25%), antidepressants
(25%), probiotics (38%), homeopathy (34%), hypnosis (15%), relaxation (31%),
osteopathy (28%), acupuncture (25%) and 46% were on a diet. IBS was severe
(IBS-SSS 4 300) in 53% and major depression was present in 45% (HAD score
4 19). QoL was impaired (FDDQL score 4114), more frequently in women
(44.914 vs. 40.214.4 (p 0.039), with no difference according to IBS subtype,
and was correlated with disease severity and HAD score (r -0.707 and r 0.484, p50.001; respectively). Patients expectations about IBS were improved
health, information on the causes and treatments for 94%, and better disease recognition for 86%. Expectations vs. experiences (%) in relation to the
medical providers were: sufficient information (94% vs. 16%), listening with
empathy (97% vs. 36%), providing hope (85% vs. 9%), improved health

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United European Gastroenterology Journal 2(1S)


(95% vs 15%). Patients thought that their doctors had good knowledge on IBS
in 18%, believed in their symptoms in 47% and suggested to them that "it was
in their head" in 65%. Only 16% were satisfied with the health care system for
IBS management and 68% considered that an improvement in the management
of symptoms would have an impact on overall IBS cost. There was a discrepancy
between the desired information sources on IBS (more information via the
doctor) and the reality: internet 84%, specialist 47.9% and GP 32%.
CONCLUSION: These French data on expectations of IBS patients from a
survey conducted among members of a patients organization show 1) a severe
disease with frequent psychological impact and impaired QoL, 2) many unsatisfied expectations with respect to the disease and health care professionals, and 3)
a need for improving the quality of patient-physician relationship.
REFERENCES
1. Halpert et al. Dig Dis Sci 2010; 55: 375-383.
Disclosure of Interest: None declared
P0433 PROTECTIVE EFFECTS OF SACRAL NERVE STIMULATION
AGAINST TNBS-INDUCED ACUTE INTESTINAL INFLAMMATION
J. Bregeon1,*, A.C. Cordeiro1, P. Aubert1, J. Jaulin1, J. Chevalier1, J. Hervouet2,
D. Minault2, E. Coron1, M. Neunlist1, G. Meurette1
1
Inserm U913, Digestive Diseases Institute, Nantes University Hospital, 2Inserm
U1064, Laboratoire des grands animaux, Nantes University Hospital, NANTES,
France
INTRODUCTION: Inflammatory Bowel Diseases (IBD) dramatically alter the
quality of life for the young adult and have a high societal cost. Treatments of
IBD have made recent progress but their adverse side effects are numerous and
relapse prevention remains a problem. Enhancing intestinal epithelial barrier
(IEB) functions emerges as a promising new therapeutic approach. The enteric
nervous system (ENS), a key regulator of gut homoeostasis, exhibits major barrier protective effects. Sacral nerve stimulation (SNS), probably via activation of
the ENS, has been reported to enhance IEB resistance (1) but its putative protective effects in response to inflammatory challenge remain unknown.
AIMS & METHODS: Therefore, the aim of this study was to determine whether
SNS protects barrier dysfunction as well as modulates intestinal inflammation
induced by an acute inflammatory stress induced by TNBS. Twelve pigs were
implanted for percutaneous bilateral SNS (S3 stimulation) (Medtronic 041828004, Minneapolis, USA; 14 Hz, 210ms). Six pigs were stimulated 3 hours prior
and 3 hours after administration of rectal enemas of TNBS (15 mg/ml). Control
animals (CT) were implanted but not stimulated and also received TNBS enema.
Rectal panparietal biopsies were performed before (T0) and 1h, 3h, 24h after
enema. Intestinal para- and transcellular permeability was assessed in Ussing
chambers. In vivo, intestinal inflammation was evaluated by endoscopy and confocal endomicroscopy (CEM) scores. Impact of SNS upon the mucosal changes
induced by TNBS was evaluated by combining histological and transcriptomic
approaches.
RESULTS: In CT, a significant and transient increase in rectal para- and transcellular permeability was measured as early as 3h following TNBS enema. 24h
after enemas permeability was still increased in CT as compared to its T0 value.
In SNS pig, a significant and transient increase in para- and transcellular permeability occurred as early as 1h following TNBS enema. However, 24h after
enemas permeability was similar to its T0 value. At 24h, similar results were
observed at the rectosigmoidal hinge level. Consistently, the SNS pigs exhibited
a trend toward a lower UCEIS score (p 0.07, n 5) as compared to CT. At 24h,
CEM scores revealed that TNBS induced alterations in crypt circularity, tortuosity and brightness were significantly reduced by SNS as compared to control
(p 0.05, n 6; p 0.008, n 6, respectively). Furthermore, epithelial desquamation and edema formation was significantly larger in CT as compared to SNS
pigs (p 0.03, n 6, both measures). Finally, mRNA expression of key tight
junction proteins such as Claudin-1 (p 0.04, n 6) and ZO-1 (p 0.03, n 6)
were significantly increased in SNS (p 0.04, n 6; p 0.03, n 6, respectively)
as compared to CT pigs. Western blot analysis of ZO-1 also showed that ZO-1
protein expression was increased in SNS as compared to CT animals (p 0.018,
n 6).
CONCLUSION: Altogether these results show that SNS exhibit major reparative properties on mucosal lesions induced by acute inflammatory stress. These
identify SNS as a putative alternative or complementary therapy targeting diseases such as IBD.
REFERENCES
(1) Neurogastroenterol Motil 2012; 24: 267e110.
Disclosure of Interest: None declared
P0434 FAECAL INCONTINENCE IN TYPE 2 DIABETICS: COMPARISON
WITH NON DIABETIC HEALTHY INDIVIDUALS AND ANALYSIS
OF RELATED FACTORS
J.X. Jorge1,2,*, L.S. Fernandes3, C.C. Almeida2, F.J. Delgado4, E.A. Panao5,
M.A. Simoes2
1
Faculty of Medicine, Agostinho Neto University, Luanda, Angola, 2Faculty of
Medicine, University of Coimbra, Coimbra, 3Medicine Urgency, Hospital
Fernando Fonseca, Lisboa, 4Medicine, Hospital de Alcobaca, Alcobaca,
5
Gastroenterology, Hospital dos Covoes, Coimbra, Portugal
Contact E-mail Address: cambombo@hotmail.com
INTRODUCTION: Faecal incontinence is a complaint that some type 2 diabetic
patients frequently refer1. The factors involved with are not well known.
AIMS & METHODS: The aim of this study was to compare the frequency of
faecal incontinence between type 2 diabetic patients and non diabetic healthy
individuals and to analyse some factors involved in this perturbation in diabetics.

A questionnaire of Gastrointestinal Symptoms Rating Scale2 was completed by


to 140 type 2 diabetics and 132 non diabetic healthy individuals, matched by age
and gender.
RESULTS: The frequency of faecal incontinence in diabetics vs. non diabetics
was 14.3% vs. 3.1%, p 50.01. According to the severity, the frequency of faecal
incontinence between diabetics vs. non diabetics was as follows: minor symptoms, 3.6% vs. 2.3%; moderate symptoms, 7.9% vs. 0.8%; severe symptoms,
2.1% vs. 0.0%; very severe symptoms, 0.7% vs. 0.0%, p 0.03.
When analysing the frequency of faecal incontinence in diabetics according to the
disease duration, 5/ 10 years vs. 410 years the results was 9.5% vs. 24%, p
50.01. The symptoms for severity was also significantly higher in diabetics with
more than 10 years of disease, p 0.01. In diabetic patients, age, gender and
glycaemia control did not influence the frequency and severity of faecal
incontinence.
CONCLUSION: 1- Faecal Incontinence is more frequent and severe in type 2
diabetics than non diabetic healthy individuals. 2- Diabetes duration influences
the frequency and the severity of faecal incontinence. 3- Age, gender and glycaemia control did not influence the frequency and the severity of faecal incontinence in type 2 diabetic patients.
REFERENCES
1 Ditah I, et al. Clin Gastroenterol Hepatol 2014; 12: 636-643.
2 Strid H, et al. Nephrol Dial Transplant 2002; 17: 1434-1439.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS I POSTER EXHIBITION
HALL XL_____________________
P0435 PHENOTYPIC PLASTICITY OF ALVEOLAR MACROPHAGES IN
GASTROESOPHAGEAL REFLUX DISEASE WITH PULMONARY
MANIFESTATIONS AND ITS COMBINATION WITH ASTHMA
I.V. Maev1,*, S.V. Lyamina2, I.Y. Malyshev3
Propaedeutics of Internal Diseases and Gastroenterology, 2Pathophysiology,
Propaedeutics of Internal Diseases and Gastroenterology, 3Pathophysiology,
Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: svlvs@mail.ru
1

INTRODUCTION: To date it is known that in spite of different points of view


on etiology and variety of cellular and molecular pathogenetic components of
pulmonary manifestations in gastroesophageal reflux disease (GERD) and combination of GERD and asthma there is a key feature of inflammation and the
immune response disorder in the form of Th1/Th2 imbalance in the pathogenesis
of the disease. Th1 or Th2 direction of immune response is mainly predetermined
by innate and adaptive immune response cells - macrophages. Considering the
concept of M1/M2 programming in changing microenvironment, macrophages
can obtain either pro-inflammatory L1 phenotype, or alternatively anti-inflammatory M2 phenotype and change their phenotype in the disease formation. So
we can suppose that Th1/Th2 imbalance is mainly due to impairment ability of
macrophages to adequate change their phenotype, i.e. with impaired phenotypic
plasticity of macrophages.
AIMS & METHODS: Assessment of alveolar macrophages (AM) phenotypic
plasticity in GERD and its combination with asthma and healthy volunteers
under the influence of different serum (FBS) concentrations. Methods: In vitro
experiments were carried out on AM, isolated from BALF of patients with
GERD (n 15, 46.414.18 y.o.), combination of GERD and asthma (n 16,
49.303.64 y.o.) and healthy volunteers (HV) (n 10, 51.833.52 y.o.). AM
phenotype was assessed by flow cytometry (Beckman Coulter, FC500) by cytokine production of proinflammatory M1, anti-inflammatory L2 and bivalent
L1/L2 cytokines in culture medium (CM) of AM (BenderMedSystems,
BMS810FF). Phenotypic plasticity of AM was measured as percentage change
of markers during 36 hours of AM reprogramming in the presence of 0%, 10%,
40% standard fetal bovine serum, containing endogenous reprogramming factor
surfactant protein D.
RESULTS: Pooled analysis of M1 and M2 phenotypic plasticity in GERD and
its combination with asthma against HV showed maximum of M1 phenotypic
plasticity in GERD M1/M2 index of the macrophages ability to change their
phenotype towards M1 was 5.33 and this was 8.5 times increased vs combination
of GERD and asthma (p50.05). Maximum macrophage phenotypic plasticity
towards M2 phenotype was observed in combination of GERD and asthma and
M1/M2 index of phenotypic plasticity was 5.45 times higher than in GERD.
CONCLUSION: The ability of AM to change their phenotype under the influence of the microenvironment in GERD and its combination with asthma was
changed as compared to healthy volunteers. In GERD macrophages possess
more possibilities to obtain M1 phenotype than M2, but the in combination of
GERD and asthma macrophages are more predisposed to obtain M2 phenotype.
So the studied ability of macrophages to adapt their phenotype to the microenvironment and to reprogram the phenotype of the cells can be thought of as the
base for new therapy approach in personalized medicine influencing the initial
links of inflammatory response and Th1/Th2 imbalance even in initial stages of
pathological process.
Disclosure of Interest: None declared

A252
P0436 INCREASED
LEPTIN
SIGNALING
IN
ESOPHAGEAL
ADENOCARCINOMA CELL LINE TREATED WITH PERITUMORAL
ADIPOSE TISSUE-DERIVED CONDITIONED MEDIUM
E. Trevellin1, M. Scarpa2,*, A. Carraro3, L. Saadeh2, M. Cagol2, R. Alfieri2,
U. Tedeschi3, C. Castoro2, R. Vettor1
1
Dept. of Medicine DIMED, University of Padova (Italy), 2Oncological Surgery
Unit, Oncological Institute (IOV-IRCCS), Padova, 3Dept. of General Surgery and
Odontoiatrics, University of Verona, Verona, Italy
INTRODUCTION: Obesity is associated with an increased risk of cancer and it
has been hypothesized that the action of adipokines (e.g. leptin and adiponectin)
may influence tumor invasiveness.
AIMS & METHODS: Our aim is to investigate if peritumoral adipose tissue may
play a direct role by altering the expression of genes involved in migratory/
mesenchymal transition processes in human esophageal adenocarcinoma cells.
Human esophageal adenocarcinoma cells (OE33) were cultured with conditioned
medium (CM) derived from adipose tissue fragments of peritumoral and distal
(omental) depots of 15 patients with esophageal adenocarcinoma, undergoing
surgical resection. After 48h we measured mRNA levels of leptin receptor
(ObR), adiponectin receptor (AdipoqR), alpha-smooth muscle actin (-SMA)
and E-cadherin (CDH1) in OE33 cells using Real Time quantitative PCR.
RESULTS: Gene expression of ObR, AdipoqR, -SMA and CDH1 were dramatically increased in OE33 cells cultured with CM, compared to control cells.
Moreover, expression of ObR, AdipoqR -SMA and CDH1 was significantly
higher in OE33 cells cultured with CM of peritumoral depot, compared to cells
cultured with CM of omental depot. Interestingly, ObR and -SMA expression
was significantly increased in OE33 cells cultured with CM of peritumoral depot
derived from patients with lymph node involvement (N), compared to peritumoral CM of patients with no positive lymph node (N-).
CONCLUSION: Our results suggest that peritumoral adipose tissue may influence esophageal adenocarcinoma cells, through the action of secreted factors. In
particular, leptin signaling may be involved in the induction of -SMA expression in esophageal adenocarcinoma cells, possibly promoting a more aggressive
behaviour of tumor.
REFERENCES
Prieto-Hontoria PL, et al. Role of obesity-associated dysfunctional adipose tissue
in cancer: a molecular nutrition approach. Biochim Biophys Acta 2011; 1807: 664678.
Jeong YJ, et al. Expression of leptin, leptin receptor, adiponectin, and adiponectin receptor in ductal carcinoma in situ and invasive breast cancer. J Breast
Cancer 2011; 14: 96-103.
Zhao L, et al. Possible involvement of leptin and leptin receptor in developing
gastric adenocarcinoma. World J Gastroenterol 2005; 11: 7666-7670.
Howard JM, et al. Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma. Br J Surg 2010; 97: 1020-1027.
Disclosure of Interest: None declared
P0437 SURFACTANT PROTEIN D AND ALVEOLAR MACROPHAGES
PHENOTYPE AS ADDITIONAL MARKERS IN DIAGNOSTICS OF
GASTROESOPHAGEAL REFLUX DISEASE WITH PULMONARY
MANIFESTATIONS AND ITS COMBINATION WITH ASTHMA
S. V. Lyamina1,*, I.V. Maev2, I.Y. Malyshev3
pathophysiology, Propaedeutics of Internal Diseases and Gastroenterology, 2
Propaedeutics of Internal Diseases and Gastroenterology, 3pathophysiology,
Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: svlvs@mail.ru

INTRODUCTION: Actual pathogenesis studies of pulmonary manifestations in


gastroesophageal reflux disease (GERD) and its combination with asthma
showed that respiratory system inflammation and imbalance between Th1 and
Th2 immune responses are the main pathologic components of the process.
Considering the present-day concept of Th1/Th2 Paradigm and M1/M2 macrophages programming, immune response disorders depend largely on the balance
of functional phenotypes of alveolar macrophages (AM). One of significant
bivalent regulatory components of AM activity is surfactant protein D (SP-D).
So we suppose that pooled analysis of AM phenotype with quantitative and
qualitative analysis of SP-D composition in broncho-alveolar lavage fluid
(BALF) will add to research in pathogenesis of pulmonary manifestations in
GERD and can be used as additional biomarker in GERD and its combination
with asthma.
AIMS & METHODS: This study evaluated pooled data of AM phenotype and
quantitative/qualitative composition of SP-D in BALF in patients with pulmonary GERD manifestations and its combination with asthma in comparison with
healthy volunteers. Methods: Pooled analysis of AM phenotype in patients with
GERD (n 15, 46.414.18 y.o.), combination of GERD and asthma (n 16,
49.303.64 y.o.) and healthy volunteers (HV) (n 10, 51.833.52 y.o.) was performed by flow cytometry (Beckman Coulter FC500) by expression of M1 and
M2 AM phenotypes CD markers (CD25, CD80 and CD163, CD206, respectively) and cytokine production of proinflammatory M1, anti-inflammatory L2
and bivalent L1/L2 cytokines in culture medium (CM) of AM
(BenderMedSystems, BMS810FF). Quantitative analysis of SP-D in BALF
was performed by ELISA. Qualitative assessment of SP-D oligomeric forms in
BALF was performed by western blot analysis using tris-acetate gels (Invitrogen,
NuPAGE, # EA03752BOX).
RESULTS: Analysis of AM phenotype in patients with GERD, its combination
with asthma vs. HV showed that pooled M1/M2 ratio of AM CD markers and
cytokine production was 2.16 and 2.52, 0.91 and 0.84 vs. HV, respectively. The
results indicates shift of AM towards M1 phenotype vs HV in GERD and

United European Gastroenterology Journal 2(1S)


towards M2 phenotype vs HV in combination of GERD and asthma. SP-D
level in BALF in patients with GERD was 2.66 times decreased vs patients with
combination of GERD and asthma (155.8318.13 ng/ml vs 414.7250.22 ng/ml,
p50.05) and 3.42 times decreased vs. HV (155.8318.13 ng/ml vs 533.2021.12,
p50.05). Qualitative analysis of SP-D oligomeric forms in GERD and its combination with asthma showed predominance of monomeric forms vs HV with
monomeric and multimeric SP-D oligomers.
CONCLUSION: In GERD with pulmonary manifestations and combination of
GERD and asthma AM phenotype and quantitative and qualitative composition
of SP-D in BALF vary against healthy volunteers and each other. Shift of AM
phenotype towards M1 vs healthy and significant maximum decreased SP-D level
in BALF are typical for GERD with pulmonary manifestations, whereas shift of
AM phenotype towards M2 and less decreasing SP-D level in BALF are specific
for combination of GERD and asthma. There were no significant differences in
qualitative oligomeric composition of SP-D in BALF in GERD and its combination with asthma.
Disclosure of Interest: None declared
P0438 INITIAL
EXPERIENCE
WITH
HEMOSPRAY
IN
THE
TREATMENT OF ACUTE UPPER GASTROINTESTINAL BLEEDING
B. Disney1,*, A.K. Kurup1, S. Ishaq1, S. Shetty1, H. Muhammad1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom, Dudley,
United Kingdom
1

INTRODUCTION: Upper gastrointestinal bleeding remains a medical emergency. Endoscopic therapies such as adrenaline injection, heater probe and
clips are used to achieve haemostasis. However, accurate delivery of these
endotherapies can be challenging. Hemospray (Cook Medical, Winston-Salem,
North Carolina, USA), an inorganic haemostatic powder, is licensed for use in
non-variceal acute upper GI bleeding. The delivery system allows a wide area of
coverage, negating the need for accuracy, and has promising results.
AIMS & METHODS: Retrospective analysis of all upper GI bleeds utilising
Hemospray following its introduction to Russells Hall Hospital in July 2013.
Patients were identified using the Unisoft endoscopy database and endoscopy
unit logbooks. Data on the use of Hemospray, bleeding lesion identified and use
of other therapeutic modalities were collected. Outcomes including mortality,
primary haemostasis and rebleeding were obtained. The aim of this study was
to assess the effectiveness of Hemospray in the real-life setting.
RESULTS: Hemospray was used 17 times in 13 patients with acute upper GI
bleeding (mean age 69 years, range 37-96 years; 69% male). The patients had a
median Blatchford score of 10 (range 5-13) and Rockall score of 7 (range 3-8).
Three patients had Hemospray used on more than one occasion.
The cause of bleeding was peptic ulcer in 10/17 patients (58.8%), upper GI malignancy in 6/17 patients (35.3%) and unknown source in 1/17 patients (5.9%).
Hemospray was used as primary endotherapy in 11/17 patients (65%) achieving
initial haemostasis in 16/17 cases (94%). Technical failure occurred in one patient
with the cartridge failing to operate and deliver Hemospray. Rebleeding within 30
days occurred with 6/17 uses (35%); 5 of these in the context of peptic ulcer disease
and 1 in upper GI malignancy. When Hemospray was used as primary therapy
rebleeding occurred on 4 occasions compared to 2 when used as second line therapy
(p 0.57). Blatchford scores were higher in those patients suffering from rebleeding
(12 versus 10, p 0.21). No significant differences in rebleeding was noted between
malignant and non-malignant causes of acute upper GI bleeding. 30-day mortality in
this patient cohort was 2/13 (15.4%). There were no documented complications of
Hemospray therapy.
CONCLUSION: Hemospray is a safe, and easy to use, endoscopic therapy with
excellent initial haemostasis as both a primary or second line treatment. In the
context of bleeding as a result of upper GI malignancy Hemospray provided
good palliation. Although there appeared to be a higher rebleeding rate seen
when Hemospray was used as primary therapy this was not significant and
may reflect the low numbers in the study.
REFERENCES
1. Leblanc S, Vienne A, Dhooge M, et al. Early experience with a novel hemostatic powder used to treat upper GI bleeding related to malignancies or after
therapeutic interventions. Gastrointestinal Endoscopy 2013; 78.
2. Chen YI, Barkun AN, Soulellis C, et al. Use of the endoscopically applied
hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary
experience. Gastrointestinal Endoscopy 2012; 75.
Disclosure of Interest: None declared
P0439 CORRECT USE OF PROTON-PUMP INHIBITORS FOR STRESS
ULCER PROPHYLAXIS IN INTENSIVE CARE UNIT: NO GI
BLEEDING AND NO CL. DIFFICILE?
S. Segato1,1, L. Bardelli1, C.C. Cortelezzi1,*, M. Parravicini1, M. Montanari1,
S. Piana1, S. Bonecco1, S. Segato1, G. Bisso1, G. Minoja2
1
Gastroenterology, 2Intensive Care Unit, Azienda Ospedaliero Universitaria
Macchi Varese, Varese, Italy
Contact E-mail Address: sergio.segato@ospedale.varese.it
INTRODUCTION: Despite limited data about their use in critically ill patients,
proton pump inhibitors (PPIs) have become the first line therapy in stress ulcer
prophylaxis (SUP). PPIs may increase the risk of hospital-acquired pneumonia
and enteric infections, especially Clostridium difficile related diarrhoea. Many
studies showed an overuse of acid suppressive therapy in Intensive Care Unit
(ICU), with unintended consequences of therapy.
AIMS & METHODS: The aim of the study was to evaluate the current practice
of SUP, the correlation with the evidence-based American Society of HealthSystem Pharmacist (ASHP) guidelines and the occurrence of GI hemorrhage,
pneumonia, and CDI in critical care setting.

A253

United European Gastroenterology Journal 2(1S)


The study was made on 300 consecutive patients (186 men, 114 women, medium
age 63.9 yrs, range 23-99 yrs, median ICU stay 11.42 days range 3-45 days)
admitted to ICU of the teaching hospital Macchi Varese between January 1st
and June 30th 2012 and January 1st and June 30th 2013; patients admitted to
neurocritical care unit and children under 18 yrs were excluded. Data about
clinical indications, drug assumption and outcomes (gastrointestinal haemorrhage, pneumonia and enteric infections) were collected during ICU stay.
RESULTS: Mechanical ventilation for more than 48h was the reason for initiating prophylaxis in 294 patients (98%); 6 pts. had a platelet count under 50.000/
mm3.
281 pts (93.6%) used PPIs (omeprazole 40mg daily i.v.), 19 pts (6.3%) H2RAs
(ranitidine 150 mg every 8 hours i.v.), 296 pts (98.6%) antibiotics, 166 pts
(55.3%) vasoactive drugs.
32 patients (10.6%) developed nosocomial pneumonia; 26 of them had other risk
factors (1 asthma, 14 chronic obstructive lung disease, 1 AIDS, 10 were older
than 75 years). One pt had Clostridium difficile related dyarrhea. One pt with a
history of active duodenal ulcer had ulcer bleeding.
CONCLUSION: All SUP were classified as appropriate according to the ASPH
guidelines. PPIs represent the first line therapy. Bleeding from stress ulceration is
extremely uncommon; Clostridium difficile related dyarrhea is unexpectedly rare
too. Patients who developed hospital-acquired pneumonia during acid-suppressive therapy, usually had other risk factors linked to this kind of infection. In this
prospective observational study, the occurrence of GI bleeding and symptomatic
CDI in critically ill patients, treated following ASHP guidelines, is lower than
reported in other studies. More data from well-designed randomized clinical
trials are needed before any change in practice.
Disclosure of Interest: None declared
P0440 A COMPARISON OF THE GLASGOW-BLATCHFORD SCORE
AND AIMS65 SCORE IN PREDICTING NEED FOR CLINICAL
INTERVENTION AND MORTALITY IN ACUTE NON-VARICEAL
UPPER GI BLEEDS: A RETROSPECTIVE COHORT STUDY
A.J. Palmer1, F. Moroni1,*, S. McLeish1, G. Campbell1, J. Bardgett1, J. Round1,
C. McMullan1, M. Rashid1, R. Clark1, D. De Las Heras 2, C. Vincent2
1
Medicine, Raigmore, 2Medicine, Raigmore Hospital, Inverness, United Kingdom
Contact E-mail Address: andrew.palmer1@nhs.net
INTRODUCTION: The early use of risk stratification scores is recommended by
the International Consensus Upper Gastrointestinal (GI) Bleeding Group for
patients presenting with acute non-variceal upper GI bleeds (ANVUGIB) 1.
Such models permit identification of patients who are suitable for early hospital
discharge or even outpatient care. The most widely used is the GlasgowBlatchford Score (GBS) 2. The score ranges from 0 to 23 and the risk of requiring
clinical intervention and death has been shown to increase with increasing score 3.
More recently a simpler scoring system known as AIMS65 was devised, which is
based on serum Albumin (530g/dl), INR 41.5, altered Mental status
(GCS514), Systolic BP (590) and age 465. One point is scored for the presence
of each variable and it has been shown to accurately predict mortality, length of
stay, and be superior to the GBS in predicting mortality 4,5. However, its ability
predict the need for clinical intervention has yet to be established.
AIMS & METHODS: The aim of this study was to examine the ability of the
AIMS65 score in predicting the need for clinical intervention and mortality in
comparison to the GBS. To do this we performed a retrospective analysis of 150
adults who presented to a single district general hospital in Scotland with a
primary diagnosis of ANVUGIB and who underwent upper GI endoscopy
between March 2008 & April 2013. GBS and AIMS65 scores were calculated
and requirement for clinical intervention, defined as the need for endoscopic
treatment, blood transfusion and/ or surgery was recorded. The area under the
receiving-operator characteristic curve (AUROC) was calculated for each score.
RESULTS: Of the 150 patients 62% were male and 38% female. The mean age
was 68 years (SD 16), GBS 7.9 (SD 4.6) and AIMS65 score 1.0 (SD 1.0). The
overall mortality was 6%. The GBS had a high predictive accuracy and was
superior to AIMS65 in predicting requirement for any clinical intervention
(AROC 0.81 vs. 0.70), blood transfusion (AROC 0.85 vs. 0.67) and endoscopic
therapy (AROC 0.67 vs. 0.58). With respect to mortality, AIMS65 was superior
to the GBS (AROC 0.79 vs. 0.68). Patients with a GBS 54 experienced no
mortality, GBS 4 58 2.6% and for those with GBS 8 10.1%. For the GBS
these cut off values maximised the sensitivity and specificity for inpatient mortality. Patients with low risk AIMS65 scores (0 or 1) experienced mortality (4%)
questioning its use as a risk stratification tool for safe, early, hospital discharge.
CONCLUSION: In our population the GBS was superior to the AIMS65 score
in terms of predicting the need for any clinical intervention, blood transfusion or
endoscopic therapy. We identified potential cut off values for the GBS that allow
stratification of patients into low, medium and high risk groups on the basis of
predicted mortality. This warrants further investigation.
REFERENCES
(1) Barkun et al. Ann Intern Med 2010; 152: 101-113.
(2) Blatchford et al. Lancet 2000; 356: 1318.
(3) Srygley et al. JAMA 2012; 307: 1072.
(4) Saltzman et al. Gastrointest Endosc 2011; 74: 1215.
(5) Hyett et al. Gastrointest Endosc 2013; 77: 551.
Disclosure of Interest: None declared

P0441 OUTCOMES
AND
PREDICTIVE
FACTORS
TRANSCATHETER ARTERIAL EMBOLIZATION FOR NONVARICEAL UPPER GASTROINTESTINAL BLEEDING

OF

H.H. Lee1,*, J.M. Park1, C.-H. Lim1, J.S. Kim1, Y.K. Cho1, B. I. Lee1, I.S. Lee1,
S.W. Kim1, M.-G. Choi1
1
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea,
Republic Of
Contact E-mail Address: hanyee99@hanmail.net
INTRODUCTION: Transcatheter arterial embolization (TAE) has been considered a therapeutic option for upper gastrointestinal (GI) bleeding when endoscopic treatment fails.
AIMS & METHODS: We aimed to assess the efficacy and clinical outcomes of
TAE for acute nonvariceal upper GI bleeding and to identify predictors of
recurrent bleeding within 30 days.
Transcatheter angiography was performed in 66 patients (42 men, 24 women;
mean age, 60.3  12.7 years) who experienced acute nonvariceal upper GI bleeding during a 7-year period. Clinical information was reviewed retrospectively.
Outcomes included technical success rates, complications, and 30-day rebleeding
and mortality rates.
RESULTS: TAE was feasible in 59 patients. The technical success rate was
98.3%. Rebleeding within 30 days was observed in 46.6% and was managed
with reembolization in 8 patients, endoscopic intervention in 5, surgery in 2,
and conservative care in 12. The 30-day overall mortality rate was 42.4%. Of
the 34 patients whose initial endoscopic hemostasis failed, 31 (91.2%) underwent
angiographic embolization, which was successful in 30. Rebleeding occurred in
15 patients (50.0%), mainly because of malignancy. Two factors were independent predictors of rebleeding within 30 days by multivariate analysis: coagulopathy (OR, 4.37; CI, 1.2515.29; P 0.021) and embolization in 32 territories
(OR, 4.93; CI, 1.4317.04; P 0.012). Catheterization-related complications
included hepatic artery dissection and splenic embolization.
CONCLUSION: TAE controlled acute nonvariceal upper GI bleeding effectively. TAE may be considered when endoscopic therapy is unavailable or unsuccessful. Coagulopathy and embolization of 32 territories were significant
predictors of angiographic failure. Correction of coagulopathy before TAE is
recommended.
REFERENCES
1. Loffroy R, Guiu B, Cercueil JP, et al. Refractory bleeding from gastroduodenal ulcers: arterial embolization in high-operative-risk patients. J Clin
Gastroenterol 2008; 42: 361-367.
2. Rockall TA, Logan RF, Devlin HB, et al. Incidence of and mortality from
acute upper gastrointestinal haemorrhage in the United Kingdom. Steering
Committee and members of the National Audit of Acute Upper
Gastrointestinal Haemorrhage. BMJ 1995; 311: 222-226.
3. Hearnshaw SA, Logan RF, Lowe D, et al. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK
audit. Gut 2011; 60: 1327-1335.
Disclosure of Interest: None declared
P0442 DOES DISCHARGE HEMOGLOBIN AFFECT OUTCOME OF
PATIENTS WITH ACUTE NON-VARICEAL UPPER
GASTROINTESTINAL BLEEDING?
J.M. Lee1, H.J. Chun1,*, I.K. Yoo1, S.J. Nam1, S.H. Kim1, H.S. Choi1,
E.S. Kim1, B. Keum1, Y.T. Jeen1, H.S. Lee1, C.D. Kim1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Korea University College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: jmlee1202@gmail.com
INTRODUCTION: Many patients with gastrointestinal bleeding show anemia
and usually need red blood cell transfusion. Several studies suggested that restrictive transfusion strategy and low hemoglobin threshold for transfusion showed
acceptable outcomes in patients with acute upper gastrointestinal bleeding [1,2].
But clinicians are concerned about low hemoglobin affects prognosis and clinical
outcome after discharge. This study aimed to assess whether discharge hemoglobin influences on outcomes, or not, in patients with acute non-variceal gastrointestinal bleeding.
AIMS & METHODS: Retrospective analysis was carried out on patients who
had upper gastrointestinal bleeding between January 2011 and December 2012.
We analyzed the patients who had lowest hemoglobin below 10 g/dL during
admission. Patients with variceal bleeding, stroke, or cardiovascular disease
were excluded. We divided the patients into two groups by discharge hemoglobin
(Low discharge hemoglobin group; 8 g/dL  hemoglobin 510 g/dL, High discharge hemoglobin group; 10 g/dL  hemoglobin 512 g/dL) and compared
clinical outcomes and hemoglobin level changes.
RESULTS: A total of 212 patients with upper gastrointestinal bleeding had
undergone the endoscopic hemostasis during study periods. One hundred two
patients had satisfied the inclusion criteria. Fifty patients discharged with hemoglobin level under 10 g/dL and fifty two patients discharged with hemoglobin
level over 10 g/dL. There was no significant difference of endoscopic findings
between two groups. Patients in low discharge hemoglobin group showed a lower
consumption of pRBC(Low discharge Hb group; 3.2  1.4 pint, High discharge
Hb group; 4.1  1.8 pint, P Value 0.01) and shorter hospital days (Low discharge Hb group; 4.3  2.5 days, High discharge Hb group; 5.6  4.2 days).
Hemoglobin levels were not fully recovered at out-patient department until 7
days after discharge. But, most patients showed hemoglobin recovery at 45
days after discharge (Low discharge Hb group; Hb 12.2  2.0 g/dL at OPD
45, High discharge Hb group;; Hb 11.9  2.0 g/dL at OPD 45). Clinical symptoms after discharge were presented no significant difference between two groups.

A254
CONCLUSION: In patients with acute gastrointestinal bleeding, discharge
hemoglobin between 8 to 10 g/dL was showed favorable outcomes during outpatient department follow-up. It seems to be tolerable level without additional
pRBC transfusion. Despite of high hemoglobin over 10 g/dL at discharge, there
was no significant advantage in clinical outcome. Our result can increase the
evidence available to support restrictive transfusion strategies in patients with
acute non-variceal upper gastrointestinal bleeding.
REFERENCES
1. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper
gastrointestinal bleeding. New Eng J Med 2013; 368: 11-21.
2. Rockey DC. To transfuse or not to transfuse in upper gastrointestinal hemorrhage? That is the question. Hepatology 2014. doi: 10.1002/hep.26994.
Disclosure of Interest: None declared
P0443 EVALUATION OF THE PREDICTIVE VALUE OF REBLEEDING
RATE OF FORREST SIMPLIFIED CLASSIFICATION
J. Moleiro1,*, A. Ferreira2, J. Torres3, E. Barjas3, M. Cravo3
1
Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.
P. E., Lisboa, 2Gastroenterology, Centro Hospitalar do Algarve, Portimao,
3
Gastroenterology, Hospital Beatriz Angelo, Loures, Portugal
Contact E-mail Address: joana_moleiro@hotmail.com
INTRODUCTION: A simplification of the Forrest classification (FC) into three
levels (high risk: Ia; increased risk: Ib to IIc; low risk: III) has recently been
proposed (1).
AIMS & METHODS: Our aim was to evaluate the prognostic value of this new
simplified classification (SC) in predicting re-bleeding of peptic ulcer (PU) and to
compare it with the traditional FC. We retrospectively identified patients
admitted to our unit between 07/2012 to 02/2014 with upper gastrointestinal
bleeding due to PU. Demographic, clinical, laboratorial and endoscopic data
were collected. Therapeutic interventions and cases of re-bleeding and mortality
within a 30 days period were registered. The predictive value of the FC and SC
were compared using logistic regression and ROC curves.
RESULTS: 81 patients underwent upper gastrointestinal endoscopy due to
bleeding PU; the mean age was 70  16 years; 61 (75%) were men. Clinical
presentation of PU bleeding was melena in 33 cases (41%), hematemesis in 29
(36%), symptomatic anemia in 8 (10%), hematochezias in 7 (9%) and hemodynamic instability in 4 (5%). The mean hemoglobin at admission and heart rate
were 8.75 g/dL and 94 bpm, respectively. Forty-eight percent of the ulcers were
located in the stomach and 52% in the duodenum. Endoscopic therapy was
performed in 39 patients (49%), and was effective in 38. One patient (1.2%)
required surgery. At the 30th day, re-bleeding occurred in 15 patients (19%)
and the mortality rate was 6%. Re-bleeding occurred in 1 of 2 patients with
Forrest Ia ulcer (high risk) and 8 (38%) with Forrest IIa (increased risk). The
odds ratio for re-bleeding of high risk and increased risk ulcers was 33.00 and
14.30 (p 0.013), respectively. The AUROC (for re-bleeding) was 0.733 for SC
and 0.723 for FC.
CONCLUSION: FC maintains its predictive value in determining re-bleeding in
PU. The proposed SC maintains the prognostic value of the FC, and therefore is
an alternative to assess the risk of re-bleeding.
REFERENCES
Groot NL, Oijen MG, Kessels K, et al. Reassessment of the predictive value of
the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified? Endoscopy 2014; 46: 46-52.
Disclosure of Interest: None declared
P0444 SURVIVAL OUTCOMES AFTER IMPLEMENTATION OF THE UK
IMPROVING OUTCOMES GUIDANCE (IOG) FOR OESOPHAGEAL
AND GASTRIC CANCERS
R.K. Fofaria1,*, J. Deacon1, A.Z. Al-Bahrani2, A. Polychronis3, I.R. Sargeant1,
D. Morris1
1
Gastroenterology, Lister and QEII Hospitals, Stevenage, 2General Surgery,
Watford Hospital, Watford, 3Medical Oncology, Mount Vernon Cancer Centre,
Northwood, United Kingdom
Contact E-mail Address: rishi.fofaria@nhs.net
INTRODUCTION: Oesophago-gastric (OG) cancer is the 3rd most common
cause of cancer-related death in the UK. Historically, it has been suggested
that the UK may have lagged behind European OG survival outcomes because
of fragmentation of service provision, suboptimal access to leading specialist
centres and delayed presentation and referral of patients from primary care.
The Improving Outcomes Guidance (IOG) for Upper GI Cancers (2001) and
Manual for Cancer Services (2004, 2011) recommended centralising curative
therapies, reconfiguring access to diagnostic/staging services and formalising
the role of the Cancer Network and peer-reviewed Network Site Specific
Groups. Lister and QE2 District Hospitals (part of the Mount Vernon Cancer
Network) cover a catchment population of 600,000 people and reconfigured their
upper GI cancer services in mid-2009.
AIMS & METHODS: Aims: To assess survival outcomes in patients with OG
cancer over a 9-year period before and after the reconfiguration of a local upper
GI cancer network.
Methods: The medical, endoscopic and computerised notes of multi-disciplinary
team meetings of all patients diagnosed with OG cancer between 1 January 2004 31 March 2013 were retrospectively analysed. Age, sex, histology, tumour site,
treatment intent and number of patients surviving at 6, 12, 24 and 42 months and
at 1 April 2014 were noted. The 2 (Chi-Square) test was used to analyse the
significance of survival outcomes.
RESULTS: From January 2004 - December 2008 there were: 139 gastric cancers
(27% curative therapeutic intent) and 234 oesophageal cancers (23% therapeutic

United European Gastroenterology Journal 2(1S)


intent; 63.6% adenocarcinoma), with overall 12-month survival of 30% and 42%
and 42-month mortality of 12% and 15%, respectively. From January 2009
March 2013 there were: 111 gastric cancers (18% curative therapeutic intent;
68.5% male; average age 75) and 230 oesophageal cancers (26.5% therapeutic
curative intent; 65.2% male; average age 72; 69.1% adenocarcinoma) with overall 12-month survival of 40% and 36% and 42-month mortality of 16% and 8%,
respectively (p40.05 for all corresponding follow-up intervals). Sub-group analysis shows increased survival in the 2009-2013 gastric cancer cohort treated with
curative intent at 6 months (p50.05) and palliative therapy at 12 months
(p50.05). There was no significant decrease in survival outcome at any stage
of follow up in both cancer groups and cohorts.
CONCLUSION: These findings are in keeping with national outcomes and show
that the institution of recommendations from the IOG, including centralisation
of curative therapies and access to specialist services, show no significant decrease
in survival outcome for OG cancer. Indeed, there is a modest increase in shortterm gastric cancer survival. The lower percentage of patients treated with curative intent, compared to national data, may reflect the late presentation of OG
cancers and partially explain survival outcomes in this population.
REFERENCES
Improving outcomes in upper GI cancers: the manual NHS Executive, DoH,
UK, January 2001.
Manual for cancer services: upper GI measures National Cancer Action Team,
2004, 2011.
Cancer Research UK. http://www.cancerresearchuk.org (accessed 22 April 2014)
National Oesophago-Gastric Cancer Audit (NOGCA), UK The RCS, AUGIS,
BSG, RCR, HSCIC (2010, 2012, 2013)
Disclosure of Interest: None declared
P0445 THE FLAME MODEL: SUPPORTING ENDOSCOPY TRAINING
IN LOW RESOURCE SETTINGS
S. Goddard1,*, J. Ansell1, N. Hawkes2
School of Postgraduate Medical and Dental Education, Cardiff University,
2
Gastroenterology Department, Royal Glamorgan Hospital, Cardiff, United
Kingdom
Contact E-mail Address: goddardsg@cardiff.ac.uk
1

INTRODUCTION: Simulation permits selective breakdown of key motor skills


for a clinical procedure into basic steps, which is better for acquisition, teaching
and assessing. (1, 2) Environment doesnt significantly affect skills transfer,
implying endoscopy can be learnt outside the clinical setting. Basic endoscopic
competencies can be taught with ex-vivo animal models. (3) The British Society
of Gastroenterology supported an excursion to Kurdistan whose remit to trainthe-trainers required provision of a suitable model.
AIMS & METHODS: Develop and Validate: Flexible Lightweight Animal
Model for gi Endoscopy (FLAME), to support hands-on endoscopy training
in a low-resource setting, specifically, to facilitate training in GI haemostasis,
variceal banding and polypectomy. Pilot prototyping indicated use of a lightweight, mouldable, plastic frame with selected ports for the attachment of premade animal tissue patches with bespoke defects. Potential port sites were analysed to optimise access and offer different technical challenges. A foil plate and
cling film wrap-around supported use of diathermy and prevented fluid leakage.
The model was housed in foam and enclosed in a lightweight box. External
Velcro straps provided further anchorage. The model was validated during a
hands-on training course conducted in Erbil, Iraq in February 2014. Attendees
completed 11-point realism (visual, anatomical and mechanical) surveys based on
a 7 point Likert scale,(4) separately for GI haemostasis, variceal banding and
polypectomy. Analysis using Wlicoxon signed rank test (PASW Statistics 18) for
non-parametric data reported scores against a hypothetical mean of 4.0 for
statistical significance (n 17 gave 490% power to detect a difference of 1
point).
RESULTS: 20 delegates (6 consultants, 14 trainees) completed the surveys. For
polypectomy all scores were greater than 1 point above the 4.0 hypothethical
mean, range 5.26-5.76 (score of 7 indicates strong agreement with realism). Mean
overall score was 5.59 [p50.05; CI 4.96-6.22]. For both variceal banding and GI
haemostasis, all mean scores were above 4.0 though the overall reality scores did
not reach significant difference; variceal banding - range 4.62-5.31, overall score
4.62; GI haemostasis range 4.5-5.83, overall score 4.56. Separate evaluation of
the overall training course revealed high levels of delegate satisfaction, principally
the hands-on model training elements.
CONCLUSION: The FLAMEs initial evaluation in a course setting demonstrates face and content validity for polypectomy. Whilst banding and GI haemostasis values didnt achieve statistical significance ratings for all parameters,
all were higher than the hypothetical mean. The model is cost-effective, easy to
transport, robust in practice and was highly valued by delegates in course evaluation. We plan further adaptations with follow-up validation studies.
REFERENCES
1. Hamdorf J and Hall J. Acquiring surgical skills. Br J Surg 2000; 87: 28-37.
2. Kopta J. An approach to the evaluation of operative skills. Surgery 1971; 70:
297-303.
3. Parra-Blanco A, Gonzalez N, Gonzalez R, et al. Animal models for endoscopic training: do we really need them? Endoscopy 2013; 45: 478-484.
4. Sedlack R, Baron T, Downing S, et al. Validation of a colonoscopy simulation
model for skills assessment. Am J Gastroenterol 2007; 102: 64-74.
Disclosure of Interest: None declared

A255

United European Gastroenterology Journal 2(1S)


P0446 THE FIRST REPORT ON THE GASTROPROTECTIVE EFFECT
OF TRIPEPTIDE T-34 UNDER CONDITIONS OF WATERIMMOBILISATION STRESS IN RATS
C. Nasadyuk1,*, A. Sklyarov1
1
Biochemistry, DANYLO HALYTSKY LVIV NATIONAL MEDICAL
UNIVERSITY, Lviv, Ukraine
Contact E-mail Address: nasadyukch@gmail.com
INTRODUCTION: There is accumulating evidence that a number of short peptides are envolved in the regulation of the function of gut and may be considered
as new pharmacological drugs for the prevention and treatment of gastric
ulceration.
AIMS & METHODS: Objective of our research was to explore the effect of
tripeptide T-34 (H-Glu-Asp-Gly-OH) on the area of water-immobilisation
stress (WIS)-induced gastric lesions in rats and activities of NO-synthases
(NOS) and lipid peroxidation processes in gastric mucosa (GM).
The studies were conducted on white male rats. 30 min before the exposure to
WIS rats were pretreated with T-34 introduced intragastrically (IG) in dose 10mg
(n 5) or intraperitoneally (IP) - 2mg (n 5). Control rats were injected 0.5 ml of
saline (n 5). After 5 hours of WIS, rats were sacrificed, gross inspection of GM
was conducted and NOS activity, NO and MDA content in GM were determined. In blood plasma L-arginine concentration was measured.
RESULTS: WIS caused the formation of gastric lesions (181.9 mm), accompanied by acute rise of NO-synthase activity (p50.05), in particular its inducible
isoform iNOS (p50.01), increased production of NO and MDA (p50.05) in
GM compared to intact rats. The concentration of L-arginine, NO precursor, in
blood plasma decreased (p50.05). Pretreatment with T-34 IG caused 27%
(p50.05) decrease of ulceration area, at that NOS activity decreased for 45%
(p50.05), iNOS activity diminished for 60% (p50.01) in GM compared to
control rats. Decrease of NO (p50.05) and tendency to decrease of MDA content in GM were also noted, whereas L-arginine concentration in plasma
increased (p50.05). Pretreatment with T-34 IP also resulted in the decrease of
iNOS activity in GM (p50.05) but no statistically significant difference of the
area of GM damage was evaluated compared to saline-treated rats exposed to
WIS.
CONCLUSION: T-34 decreased the indices of nitrooxidative stress in GM under
the conditions of WIS-induced gastric lesions in rats. IG administration of T-34
was superior to IP injection of this compound towards reduction of gastric
mucosa damage. Deeper studies on the elucidation of the cytoprotective effect
of tripeptide T-34, optimization of dosage and route of application are required.
Disclosure of Interest: None declared
P0447 THE FREQUENCY AND TYPE OF HISTOLOGICAL GASTRIC
CHANGES IN PATIENTS WITH FUNCTIONAL DYSPEPSIA
I. Korendovych1,*, A. Svintsitskyy1, O. Kuryk2,3, G. Solovyova1,2
1
Internal Medicine #3, Bogomolets National Medical University, 2Oberig clinic,
3
Morbid Anatomy, Bogomolets National Medical University, Kyiv, Ukraine
Contact E-mail Address: ira-korendovych@yandex.ru
INTRODUCTION: Though the symptoms of functional dyspepsia (FD) are not
considered to correlate with mucosa changes the histopathological evaluation
seems to be fundamental not to miss the early onset of atrophic-metaplastic
transformation.
AIMS & METHODS: Our aim was to assess the frequency and type of histological changes in patients with functional dyspepsia. This work was a part of a
randomized superiority trial in which combined treatment using eradication therapy (ET) plus antidepressant by comparison with ET for patients with FD was
assessed. Adult patients (18 - 65 years) with confirmed diagnosis of FD by the
Rome III criteria (2006) were eligible to participate. Exclusion criteria: the presence of red flag signs and other comorbidities that could explain the symptoms. Biopsy specimens were taken from stomach following the Houstonupdated gastric biopsy sampling protocol for the next histological examination.
One expert gastrointestinal pathologist, blinded to all patient clinical but not
endoscopic information, assessed all tissue samples. The degree of inflammatory
changes was scored by the 4-grade Visual Analogue Scale, atrophy - following
Operative Link for Gastritis Assessment (OLGA) and metaplasia - following
Operative Link on Gastric Intestinal Metaplasia (OLGIM) staging systems. All
patients were tested for H. pylori using two methods (rapid urease test and by
morphological examination).
RESULTS: 75 patients fulfilled all criteria and were included into the study.
Mean age was 40.33.9; males 26 (34.7%). H. pylori was detected in all 75
patients. The main location of H. pylori infection was antral part. Patients had
mainly a mild degree of mucosal inflammation (84%) which in most cases was
limited to antral part. Atrophy was statistically significant more frequently diagnosed in antrum (64.0%) than in corpus (12.0%) (p50.0001) and in all cases
didnt exceed OLGA stage I. Metaplasia of intestinal type was found in 26
(34.7%) patients in antral part and was not detected in corpus (p50.0001). No
case of dysplasia was detected. We also tried to collate the degree of gastritis and
the stage according to OLGA (2008) in antrum and corpus with the presence of
such clinical syndromes of FD as postprandial distress and epigastric pain. No
statistically significant correlation was found (p40.05).
CONCLUSION: As in most studies, we also didnt find the correlation between
stage and degree of gastritis and clinical symptoms of FD. But we shouldnt
forget about possible microscopic changes of mucosa when dealing with functional patients, thus conducting a primary prophylaxis of gastric cancer.
Disclosure of Interest: None declared

P0448 THE IMPACT OF ERYTHROMYCIN


ACTIVITY IN EXPERIMENTAL PIGS

ON

MYOELECTRIC

T. Douda1,*, J. Kvetina2, I. Tacheci1, M. Pavlik3, M. Kunes4, M. Kopacova1,


S. Rejchrt2, J. Bures2
1
2nd Department of Medicine- Gastroenterology, 22nd Department of Medicine,
Charles University Faculty of Medicine & University Teaching Hospital, Hradec
Kralove, Czech Republic, 3Centre of Advanced Studies, University of Defence,
Faculty of Military Health Service, 4Biomedical Research Centre, University
Teaching Hospital, Hradec Kralove, Czech Republic
Contact E-mail Address: tomas.douda@fnhk.cz
INTRODUCTION: Surface electrogastrography (EGG) is a non-invasive
method for the assessment of gastric myoelectrical activity. Erythromycin, as a
potent prokinetic drug, increases the dominant frequency of EGG both in
humans and experimental pigs. The aim of this study was to evaluate the effect
of erythromycin on the porcine EGG power (assessed by areas of amplitudes)
and power ratio (simple fraction ratio of the areas of amplitudes after and before
erythromycin administration).
AIMS & METHODS: Six mature female pigs (3 months old, mean weight
23.22.1, median 23 kg) were included in the study. All EGG recordings were
performed under general anaesthesia in the morning after 24 hours of fasting (by
means of the MMS EGG System, Enschede, the Netherlands). The baseline EGG
recording lasted 15 min., erythromycin ethylsuccinate (1,500 mg) was subsequently administered by gastric tube into the stomach. The EGG trial recording
lasted 150 min. (ten 15-minute intervals: P1 to P10) after erythromycin administration. Running spectral analysis (based on Fourier transform) was used for
initial evaluation of the EGG. The gastric myoelectric activity was estimated
by EGG power analysis and by power ratio assessment.
RESULTS: Erythromycin increased the EGG power significantly after 15 to 30
min. from the baseline mean value 828633 (V^2) to 15834238 (at P1) and
11022077 (P2 interval), p 0.003. Afterwards, the EGG power decreased to its
minimum at P4 (237200), p50.001; and increased to 7091213 V^2 after 150
min. (at P10), p50.001. The EGG power ratio reached the highest values at P1
(1.643.98) and P2 (1.914.27), decreased significantly at P4 (0.290.27; p50.001)
and balanced out after 150 min. at P10 interval (1.152.48; NS: p 0.668).
CONCLUSION: A medium single dose of erythromycin caused a significant
increase in the EGG power and power ratio after 15 to 30 min. after intragastric
administration. Both myoelectrical markers decreased after 60 min. and returned
close to the initial values after 150 min.
Acknowledgement
The study was supported by research grant IGA NT/14270-3.
Disclosure of Interest: None declared
P0449 FUNCTIONAL
DIGESTIVE ORGANS

MOTOR-SECRETORY

LIGAMENTS

OF

Y. I. Reshetilov1,*, S.N. Dmitrieva1, H.Y. Vasilchenko1, N.N. Protsenko1


1
Family Medicine and Gastroenterology Department, State Institution
Zaporizhzhya Medical Academy of Postgraduate Education, Ukraine, Zaporozhye,
Ukraine
INTRODUCTION: Definition of motor stomach and duodenum disorders role
in gastroduodenal zone development process is interesting for peculiarities of
digestive system disorder clinical realization. Phase structure of interdigestive
motility reflects changes of digestive system activity and inactivity periods; influences interdigestive cycle duration and essentially changes during gastric and
duodenum diseases.
AIMS & METHODS: Patients with functional diseases (65), chronic gastritis/
gastroduodenitis (184) and duodenal peptic ulcer (55) took part in study of
stomach and duodenum motility (GDM). Also 30 healthy men took part in
this testing. GDM was studied by the special bougie. Electrodes were based in
duodenum, antrum and in body of stomach. External probe ends were connected
with polygraph strain gauge, which registered GDM and defined interdigestive
cycle periods of inactivity (I phase) and activity (II phase intermittent motility,
III phase rhythmic phase).
RESULTS: Correct alternation of GDM was diagnosed among healthy men: I
phase 22.42.0; II phase 42.62.6; III phase 5.61.7 min, in case of interdigestive cycle total time is 69.72.3 min. Amplitude and frequency characteristics of stomach and GDM were lowest during I phase (1-4 low-amplitude
contractions per min), but they became higher during II phase (3-8 contractions
of different height per min) and during III phase (9-15 rhythmic amplitude
signals per min). Phase research of intragastric pH in basal conditions showed,
that stomach pH decreases till 1.00.10 during II phase and it increases till
1.70.12 during the third one, as maximal realization of acidogenesis stomach
function at the beginning of working period. Patients were separated in 3 observation groups: with heightened, preserved and reduced acidogenesis stomach
function. The I group endurance period of inactivity (1 phase) lasted for
15.61.0 min, working period of II and III phase was increased till 50.61.0
and 6.20.9 min, properly (P50.05). Patients of the II group had phase indexes,
which essentially did not differ from control group results (20.61.6-42.32.35.21.3; P40.05). In the group motor indexes and interdigestive total time did
not statistically differ from check ones (P40.05). Patients from the III group had
these results: I phase lasted for 27.30.9 min, II phase 38.50.7 and III phase
was shortened to 4.11.1 min; the inactive period increase was determined by
means of working period, which was equivalent to gastroduodenodyskinesia.
CONCLUSION: In case of inflammatory gastroduodenum pathology, GDM
structure changes according to the picularities of stomach acidogenesis during
intagastral cycle. This fact can be explained by secretory and motor function of
digestive system functional correlation.
Disclosure of Interest: None declared

A256

United European Gastroenterology Journal 2(1S)

P0450 HIGH ONE-YEAR RESPONSE RATE TO PERMANENT GASTRIC


ELECTRICAL STIMULATION AND IMPROVED QUALITY OF LIFE
IN PATIENTS WITH NON-ESTABLISHED INDICATIONS FOR
TREATMENT SELECTED BY A TEMPORARY STIMULATION
PERIOD
B. Serrano Falcon1,2,*, S. Kilincalp3, M. Simren4, G. Ringstrom4,
H. Abrahamsson4, H. Tornblom4
1
Dept of Internal & Clinical Nutrition, Institute of Medicine, Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden, 2Servicio de Aparato
Digestivo, Hospital Clnico San Carlos, Madrid, Spain, 3Department of gastroenterology, Diskapi Yildirim Beyazit Education Hospital, Ankara, Turkey, 4Dept of
Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: hans.tornblom@gu.se
INTRODUCTION: Gastric electrical stimulation (GES) with the Enterra system
is a therapeutic alternative for patients with therapy refractory nausea and vomiting secondary to diabetic or idiopathic gastroparesis (GP). Some patients with
normal gastric emptying also benefit from GES (Andersson et al, 2011) after
selection with a temporary percutaneous stimulation (TPGES) test.
AIMS & METHODS: The aim of this study was to assess response rate and
quality of life after one year of treatment with GES in patients selected by a
TPGES test period. We used the TPGES technique described by us previously in
a randomized double blind crossover design with 2 weeks stimulation ON (5-7
mA range) followed by stimulation OFF, or the opposite order. Treatment
response was defined as a symptom reduction 50% during the ON period
compared to the OFF period for one or both of weekly nausea hours (WNH)
and weekly vomiting frequency (WVF). Non-responders to blinded TPGES were
offered an open treatment period with increased stimulation (5-10 mA as tolerated). The response to permanent GES was judged by the same response definition but comparing one-year data with baseline symptom registration. Quality of
life was evaluated by use of the SF36 questionnaire at baseline and after 12
months of GES therapy.
RESULTS: Twenty-eight patients (22 female (78.6%), median age 43.5 years
(range 20-70)) with therapy refractory nausea and vomiting were included.
Gastric emptying was normal in 17 patients (61%) and delayed in 11 (39%).
Ten patients (36%) were responders after blinded TPGES and 18 were not. Six
accepted an open stimulation period during which two more were responders and
two were judged as responders by patient preference, both of whom had diabetes
mellitus. Thus, a total of 14 patients (50%) were offered and accepted a permanent device (Table 1). After one year of GES treatment, 11 patients (79%) were
still responders. Response to treatment could not be predicted by gastric emptying status, neither after TPGES (p .70) nor after GES (p .61). Responders to
GES had a significant improvement in quality of life after one year comparing
with baseline in terms of bodily pain (p .017), vitality (p .035), social functioning (p .026), role emotional (p .038), mental health (p .024) and general
health (p .017).
Table 1. Clinical diagnosis, gastric emptying status, TPGES response and oneyear response number in patients selected for permanent GES.

Diagnosis (n)

Gastroparesis

Responders
TPGES
(open stim)

Diabetes mellitus (5)


Idiopathic gastroparesis (3)
Postsurgical nausea or vomiting (7)
Functional dyspepsia (9)
Enteric dysmotility (4)

0
3
5
0
3

3 (2)
1
3 (1)
5 (1)
2

Responders
1 year GES
3
1
2
3
2

CONCLUSION: TPGES is a good selection tool for patients with non-established indications for GES treatment and results in a high one-year response rate.
A significant improvement in quality of life after 1 year of GES therapy was also
shown in the responder group.
Disclosure of Interest: B. Serrano Falcon: None declared, S. Kilincalp: None
declared, M. Simren: None declared, G. Ringstrom: None declared, H.
Abrahamsson: None declared, H. Tornblom Lecture fee (s) from: Almirall,
Shire, Consultancy for: Almirall, Danone, Shire
P0451 EFFICACY OF PNEUMODILATION IN ACHALASIA AFTER
FAILED HELLER MYOTOMY
C. Saleh1,*, F. Ponds1, M. Schijven1, A. Smout1, A. Bredenoord1
gastroenterology and hepatology, academic medical center (AMC), Amsterdam,
Netherlands
Contact E-mail Address: c.m.saleh@amc.uva.nl
1

INTRODUCTION: Heller myotomy is an effective treatment for the majority of


achalasia patients. However, a small proportion of patients suffers from persistent or recurrent symptoms after surgery and they are usually subsequently treated with pneumodilation (PD).
AIMS & METHODS: The efficacy of PD as secondary treatment for achalasia
has scarcely been studied. This study therefore aimed to investigate the efficacy of
PD as treatment for achalasia patients suffering from persistent or recurrent
symptoms after Heller myotomy. 20 patients with recurrent or persistent symptoms (Eckardt score 43) after Heller myotomy were selected. Patients were
treated with PD, using a graded distension protocol with balloon sizes ranging

from 30 to 40 mm. After each dilation symptoms were assessed to evaluate


whether a subsequent dilation with a larger balloon size was required. Patients
with recurrent or persistent symptoms (Eckardt score 43) after treatment with a
40-mm balloon were identified as failures.
RESULTS: 12 patients presented with achalasia type I, 6 with achalasia type II
and 2 with achalasia type III (Chicago classification). Median relapse time was 4
years after Heller myotomy (IQR: 7 years and 9 months). 3 patients were not
suitable for PD; 1 patient was morbidly obese and 2 had a mega-oesophagus. 5
patients were successfully treated with one 30-mm balloon dilation (median
follow-up time: 2 years; IQR: 7 years). 8 patients required dilations with 30and 35-mm balloons (median follow-up time: 6 years; IQR: 6.5 years). 4 patients
underwent 3 dilations with balloon sizes up to 40 mm, and all failed on the 40mm balloon as well. Thus, PD was successful for 13 out of the 17 patients who
could be treated, resulting in a success rate of 76% for treatable patients or 65%
for all patients. Patients successfully treated with a 30-mm balloon all suffered
from achalasia type I. Baseline LOS pressure (before dilation) was not different
between successfully treated patients (Median: 15.0 mmHg; IQR: 11.5 mmHg)
and those that failed (median: 12.5 mmHg; IQR: 6.5 mmHg) treatment (p40.05).
Furthermore, baseline Eckardt scores were not predictors of successful treatment; there was no difference between successful (median: 6; IQR: 2) and
failed (median: 5.5; IQR: 3.25) treatment. Baseline symptom pattern was not a
predictor of successful treatment either.
CONCLUSION: Pneumodilation for recurrent symptoms after previous Heller
myotomy has a success rate of 76%, using 30- and 35-mm balloons. Patients with
recurrent symptoms after pneumodilation with 35-mm balloon are likely to also
fail after dilation with a 40-mm balloon.
Disclosure of Interest: None declared
P0452 IS DIFFERENTIATING BETWEEN HIATUS HERNIA IIIA AND
IIIB IN HIGH RESOLUTION MANOMETRY USEFUL IN CLINICAL
PRACTICE?
C. Ciriza De Los Rios1,*, F. Canga1, I. Castel1, G. Castellano1
1
gastroenterology, HOSPITAL UNIVERSITARIO DOCE DE OCTUBRE,
Madrid, Spain
Contact E-mail Address: constanzacarpa@gmail.com
INTRODUCTION: Oesophageal high resolution manometry (HRM) is a useful
tool for the detection of hiatus hernia (HH) as two high pressures zones, lower
oesophageal sphincter (LOS) and crural diaphragm (CD) can be clearly identified. Two types of HH have been described in HRM, type IIIa, associated with a
further decrease in LOS pressure during inspiration, and IIIb associated with an
increase in LOS pressure during inspiration.
AIMS & METHODS: The aim of this study is to determine if these HRM
classifications for hiatus hernia are useful in clinical practice.
39 consecutive patients with HH detected by HRM were included. HRM
(Manoscan; Given) was performed in supine and analyzed according to 2012
Chicago classification criteria. HH was defined as a separation 4 2 cm between
LOS and CD at inspiration. Upper endoscopy was performed on all patients and 24
hours pH-monitoring on 30 (76.9%) of them. Statistical analysis: U Mann Whitney;
Chi-Square.
RESULTS: Clinical data, HRM and pH-monitoring results are expressed in the
table. Hypotensive LOS (resting pressure 5 10 mmHg) was found in 42.8% HH
IIIa and in 27.8% HH IIIb; oesophagogastric junction (OGJ) obstruction (IRP-4
415 mmHg) at the level of the CD was found in 19.1% HH IIIa and in 16.7%
IIIb (p 0.591). There were no significant differences in oesophageal body motility (normal 76.2% in HH IIIa and 61.1% in HH IIIb; p 0.457). Multiple water
swallow test was normal in 47.4% in HH IIIa and in 75% in HH IIIb (p 0.055).

A257

United European Gastroenterology Journal 2(1S)

Clinical data
Age
Sex (F)
BMI (kg/m2)
Abdominal perimeter (cm)
Co-morbidity
No
Yes
Previous PPI treatment
Upper endoscopy
Normal
Peptic esophagitis
Barrett
Ring/Stenosis
Diverticulum
Other (gastritis, ulcer)
Resting pressure (mmHg)
IRP-4s
OGJ total length (cm)
Oesophageal length (cm)
Sac length
DCI (mmHg.cm.s)
VFC (cm/s)
IBP (mmHg)
Distal Latency (s)
Abnormal
Positive symptom index

HH IIIa (n 21)

HH III b (n 18)

p-value

63.8 [57.4-70.1]
13 (58.9%)
30.7 [27.9-33.5]
105.7 [100.8-110.6]
1 (4.8%)
20 (95.2%)
19 (90.5%)
10 (47.6)
2 (9.5%)
4 (19.1%)
2 (9.5%)
1 (4.8%)
2 (9.5%)

58.6 [51.8-65.3]
9 (50%)
27.2 [25.2-29.2]
97.4 [91.2-103.5]
2 (11.1)
16 (88.9%)
15 (83.3%)
12 (66.8%)
1(5.5%)
4 (22.2%)
1 (5.5%)

0.234
0.455
0.037
0.078
0.873
0.424
0.311

HRM parameters
12.6 [8.7-16.5]
8.9 [6.1-11.8]
7.3 [6.3-8.3]
20.5[19.4-21.7]
3.3 [2.5-4]
1474.4 [1027.5-1921.2]
3.8 [2.8-4.8]
18.6 [14.4-22.8]
5.4 [4.8-6.1]
pH-monitoring result
7 (43.8%)
3 (18.7%)

always associated with an abnormal last MRS swallow according to CC criteria


(premature swallow, n 4; rapid contraction, n 3; hypercontractile swallow,
n 1; failed, n 1). This was observed also in the only case with normal MRS.
CONCLUSION: MRS was a useful complementary test during HRM in order to
detect esophageal motility abnormalities in patients with either normal or abnormal standard manometry. Moreover, MRS was superior to standard assessment
in provoking esophageal symptoms in patients with NCCP or dysphagia and
permitted to correlate them to abnormal motor function.
Disclosure of Interest: None declared
P0454 VALIDATION OF THE CHICAGO CLASSIFICATION FOR THE
DIAGNOSES OF PRIMARY ESOPHAGEAL MOTILITY DISORDERS
BASED ON OUTCOME DATA
G. Capovilla1, R. Salvador1, M. Costantini1, L. Nicoletti1, G. Zaninotto2,
E. Savarino1,*
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, Italy, 2Imperial College, London, United Kingdom

12.5 [9-12,3]
6.7 [3.7-9.8]
7.7[6.3-9.1]
20.8[19-22.7]
3.1 [2.1-4.2]
2070 [868.7-3272.7]
4.2[2.9-5.4]
23.1[14.9-31.3]
5.9[5.6-6.3]

0.945
0.112
0.791
0.813
0.646
1
0.626
0.967
0.119

7 (50%)
3 (21.4%)

0.509
0.558

CONCLUSION: There were no significant differences between the two HH types


in the clinical data, in upper endoscopy, HRM and pH-monitoring results
although patients with HH IIIa are more obese and tend to have a more hypotensive LOS. The differentiation between both subtypes is therefore not useful for
routine clinical practice.
Disclosure of Interest: None declared
P0453 MULTIPLE
RAPID
SWALLOWING
IS
A
USEFUL
COMPLEMENTARY TEST TO CORRELATE SYMPTOMS TO
ESOPHAGEAL MOTILITY ABNORMALITIES
E. Savarino1,1,*, C.de Cassan1, F. Galeazzi1, R. Salvador1, E. Marabotto2,
M. Furnari2, P. Zentilin2, N.de Bortoli3, S. Marchi3, R. Bardini1,
G.C. Sturniolo1, V. Savarino2
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, 2Department of Internal Medicine, University of Genoa, Genoa,
3
Department of Internal Medicine, University of Pisa, Pisa, Italy
INTRODUCTION: Although esophageal motor disorders (EMD) are associated
with non-cardiac chest pain (NCCP) and dysphagia, minimal data support a
direct relationship between abnormal motor function and symptoms. Indeed, a
recent study failed to observe a correlation between high-resolution manometry
(HRM) metrics and symptoms during the manometric protocol. On the other
hand, multiple rapid swallowing (MRS) has been recently suggested as a complementary test during HRM in order to observe abnormalities in inhibitory or
excitatory esophageal mechanisms that could potentially underlie esophageal
symptoms. Limited data are available on the role of MRS in eliciting NCCP
or dysphagia during HRM testing.
AIMS & METHODS: We aimed to evaluate the yield of MRS to provoke
esophageal symptoms in patients with normal or abnormal standard manometry.
Consecutive patients with NCCP or dysphagia without previous surgery were
enrolled. All patients underwent HRM as follows: after a 5-min baseline recording to locate and assess the esophago-gastric junction, the subjects took 10 single
water swallows (5 mL) at 30-s intervals (standard assessment) and two MRS (one
swallow every 23s) while 10mL of water was injected steadily into their mouths
through a syringe. Symptoms reported were recorded and graded based on a 5point Likert scale (0-4) and a 10-cm visual analogue scale (VAS). The tracings
were analyzed based on Chicago Classification (CC) criteria for EMD and,
further, MRS were analyzed for completeness of esophageal body inhibition
and for augmentation of contraction after the last MRS swallow. Also the last
swallow during MRS was classified according to the CC criteria.
RESULTS: We enrolled 31 [18M/13F; mean age 55 (35-78)] patients complaining
of NCCP (n 14) and dysphagia (n 17) as major symptom. Fourteen (45%)
patients had incomplete esophageal body inhibition, whereas 13 (42%) patients
failed to increase wave amplitudes after MRS. Overall, 18 (58%) patients had
abnormal MRS, with 5 (16%) of them having normal peristalsis. No patient
complained of NCCP or dysphagia during standard assessment. In contrast, 9
(29%) patients reported either NCCP [n 5; mean Likert scale 3.0 (range 2.0-4.0)
and VAS scale of 7.7 (6.6-9.2)] or dysphagia [n 4; mean Likert scale 2.8 (range
2.0-3.0) and VAS scale of 7.6 (5.2-8.8)] during at least one MRS (p 0.0020).
Among them, at standard manometric assessment, we found normal peristalsis
(n 2), Jackhammer Esophagus (n 3), distal esophageal spam (n 2), outflow
obstruction (n 1), and absent peristalsis (n 1), whereas MRS resulted to be
abnormal in 8 cases. Interestingly, when symptoms were reported, they were

INTRODUCTION: Early comparisons between 8-channel water-perfused (WP)


conventional manometry and 36 pressure transducers solid-state (36-SS) highresolution manometry (HRM) showed that high spatial resolution increases the
diagnostic yield and accuracy for clinically relevant esophageal motility disorders
(EMD). Thus, a new classification of EMD based on HRM findings, the Chicago
Classification (CC), has been proposed. Limited data are available on the clinical
impact of this classification in terms of patients outcome.
AIMS & METHODS: We aimed to prospectively assess the clinical value of the
CC comparing the diagnoses of EMD obtained by using the 36-SS and the 24channel WP system in a group of patients with esophageal symptoms and evaluating their clinical outcome at 1-year after treating them based on 36-SS HRM
findings. Diagnoses of EMD have been collected from a prospective, randomized, double blind, crossover study aimed to measure and compare normal
values of conventional and high-resolution manometry metrics as well as to
assess the inter-rater and inter-device agreement for the diagnoses of EMD
between the 36-SS (Given Imaging, US) and the 24-WP system (EB Neuro,
Italy). Twenty patients [11M/9F; 48 (43-55)] underwent both procedures blinded
and in random order. Two expert reviewers (RS, ES) performed a blind analysis
of the patients plots. Diagnoses based on CC were obtained. Inter-rater and
inter-device agreement for each reviewer were evaluated. Then, according to
CC-based diagnoses at 36-SS HRM plus impedance-pH features in case of suspected reflux disease, patients were empirically treated and followed-up for 1
year. Outcome was evaluated as positive (50% of symptomatic relief) or negative (550%) based on validated disease-related questionnaires.
RESULTS: Diagnostic inter-device agreement was moderate for both reviewers
[k (RS) 0.5; k(ES) 0.4], whereas diagnostic inter-rater agreement was higher
for the 36-SS (k 1) than for the 24-WP (k 0.68) system. As to the outcome
evaluation at 1-year, we found that 17/20 (85%) patients had a positive outcome.
Among them, 7 patients had dysphagia with achalasia (type II, n 5; type III,
n 1; type I, n 1) and were surgically (n 4) or endoscopically (n 3) treated,
7 patients had reflux symptoms with normal peristalsis (NP; n 4) or frequent
failed peristalsis (FFP; n 2) or weak peristalsis (WP; n 1) and were surgically
(n 2, Nissen Fundoplication) or medically (n 5, PPI plus alginate) treated, 1
patient had chest-pain with WP and was treated with PPI plus prokinetic and,
finally, 2 patients had dysphagia with FFP and outflow obstruction (OO) and
were treated with prokinetic and endoscopic dilatation, respectively. Out of 3/20
(15%) patients with a negative outcome, 1 had dysphagia with NP (also at 24-WP
HRM) and was treated with PPI plus prokinetic, 1 had regurgitation with OO
(normal peristalsis at 24-WP HRM) and was treated with PPI plus prokinetic,
and 1 had chest-pain with distal esophageal spasm (FFP at 24-WP HRM) and
was treated with endoscopic dilatation.
CONCLUSION: The 36-SS HRM was more accurate and reproducible than the
24-WP system for diagnosing clinically relevant EMD based on the CC.
Moreover, the Chicago classification has been found greatly useful as diagnostic
tool in order to obtain good outcome in patients reporting esophageal symptoms.
Disclosure of Interest: None declared
P0455 CLINICAL AND ENDOSCOPIC CHARACTERISTICS CAN HELP
DISTINGUISH PSEUDOACHALASIA FROM ACHALASIA
F.A. Ponds1,*, I.M. van Raath1, A.J. Smout1, A.J. Bredenoord1
Department of Gastroenterology and Hepatology, Academic Medical Centre
Amsterdam, Amsterdam, Netherlands
Contact E-mail Address: f.a.ponds@amc.uva.nl
1

INTRODUCTION: Pseudoachalasia is a condition in which clinical and manometric signs of idiopathic achalasia are mimicked by another abnormality, most
often a malignancy. An underlying malignancy should be recognized early to
prevent inappropriate therapeutic intervention and delay in appropriate treatment. However, clinical identification of pseudoachalasia can be challenging.
AIMS & METHODS: The aim of our study was to identify characteristics that
suggest potential pseudoachalasia caused by malignancy. Patients diagnosed with
achalasia by manometry were retrospectively included between 2000 - March
2014 in a single centre. Manometric criteria for achalasia were defined as aperistalsis and dysrelaxation of the lower oesophageal sphincter (LOS).
Pseudoachalasia was diagnosed in patients with clinical and manometric signs
of achalasia that were found to have an underlying malignancy. Clinical (Eckardt
symptom score), manometric, endoscopic and radiological findings were
reviewed and compared between patients with pseudoachalasia versus achalasia.
RESULTS: In total 205 patients with achalasia were included (116 male, median
age 52 (39-64) (median (IQR)). Pseudoachalasia was diagnosed in 10 patients
(4.9%, 8 male) and caused by oesophageal adenocarcinoma (n 3), oesophageal

A258

United European Gastroenterology Journal 2(1S)

squamous cell carcinoma (n 3), adenocarcinoma of the cardia (n 3) or pancreatic adenocarcinoma (n 1). The underlying malignancy was found at EUS
(30%), at a second or third endoscopy with biopsies (20%) or during a treatment
session (30%; 2x Heller myotomy, 1x pneumodilation). In 20% of the patients a
CT-scan after achalasia treatment, performed because of quick recurrence of
symptoms, eventually showed the malignancy. Patients with pseudoachalasia
were older at time of diagnosis compared to achalasia patients (68 (50-72) vs
51 (38-63), p 5.05)), had a shorter clinical history (6 (5-12) months vs 24 (11-68)
months, p 5.01) and lost more weight (12 (10-20) kg vs 6 (0-10) kg, p 5.01). The
Eckardt symptom score was higher in the group with pseudoachalasia (9 (8-10) vs
7 (6-9), p 5.05). However when the score was corrected for weight loss no
difference was seen (6 (6-7) vs 5 (5-7), p 4.05). Manometries in both groups
showed aperistalsis and dysrelaxation of the LOS, with no difference in LOS
pressure (33 (19-35) mmHg vs 23 (18-32) mmHg, p 4.05). In 80% of patients
with pseudoachalasia a barium oesophagography was performed and in 75% it
was suggestive of achalasia showing an enlarged diameter, narrowing of the LOS
and stasis of contrast compared to 91% in idiopathic achalasia. All patients with
pseudoachalasia underwent 1 or more endoscopies and in 80% the LOS was
difficult or even impossible to pass. In achalasia patients the LOS was difficult
to pass during endoscopy in only 22%.
CONCLUSION: Advanced age, short clinical history, considerable weight loss
and difficulty in passing the LOS during endoscopy are characteristics that
should arouse a higher suspicion of pseudoachalasia and warrant additional
investigations. It is not possible to distinguish pseudoachalasia from achalasia
with the conventional diagnostics used for achalasia such as manometry and
barium oesophagography.
Disclosure of Interest: None declared
P0456 DEVELOPMENT OF AN ENDOSCOPY- AND HISTOLOGYBASED ACTIVITY INDEX FOR EOSINOPHILIC ESOPHAGITIS
A. Schoepfer1,*, A. Straumann2, R. Panczak3, C. Kuehni3, Y. Romero4,
J. Alexander4, I. Hirano5, N. Gonsalves5, G. Furuta 6, E. Dellon7, J. Leung8,
M. Collins9, C. Bussmann10, P. Netzer3, S. Gupta11, M. Chehade 12,
F. Moawad13, S. Aceves14, J. Wo15, M. Zwahlen3, E. Safroneeva3 on behalf of
International Eosinophilic Esophagitis Activity Index Study Group
1
University Hospital Lausanne / CHUV, Lausanne, 2University Hospital Basel,
Basel, 3University of Bern, Bern, Switzerland, 4Mayo Clinic Rochester, Rochester,
5
Northwestern University of Chicago, Chicago, 6University of Colorado, Aurora,
7
University of North Carolina, Chapel Hill, 8Tufts Medical Center, Boston,
9
Cincinnati Children Hospital, Cincinnati, United States, 10Viollier Pathology
Basel, Basel, Switzerland, 11Indiana University of Medicine, Indianapolis, 12Mount
Sinai Food Allergy Institute, New York, 13Walter Reed Army Hospital, Bethesda,
14
University of California, San Diego, 15Indiana University, Indianapolis, United
States
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: A validated instrument to assess severity of eosinophilic
esophagitis (EoE) in clinical trials and observational studies is urgently needed.
The international Eosinophilic Esophagitis Activity Index (EEsAI) study group
is currently developing an activity index for adult EoE patients. Three instruments have been developed to assess endoscopic, histologic, and clinical EoE
activity.
AIMS & METHODS: We aimed to develop instruments that assess endoscopic
and histologic findings and the corresponding score based on the items that best
explain the variability in the physician global assessment (PGA) of EoE severity.
To assess whether items of the patient-reported outcomes (PRO) instrument,
which is designed to assess symptom severity, also help to explain the variability
of the PGA. We sought input from the experts and patients to generate the item
list to be included into 3 different instruments. Physicians provided PGA that
took into account symptoms, endoscopy, and histology and was assessed on a
Likert scale from 0 to 10. Using the physician instrument, severity of EoE-associated endoscopic features including white exudates, rings, edema, furrows, and
strictures was graded. Severity of EoE-associated histologic findings including
peak eosinophil counts, eosinophil abscesses, basal layer enlargement, and subepithelial fibrosis was assessed by the means of histopathology instrument. The
dysphagia characteristics and behavioral adaptations associated with consumption of foods of different consistencies, among others, were assessed using the
PRO instrument. Linear regression and analysis of variance (ANOVA) was used
to evaluate the extent to which variations in the severity of EoE-associated
endoscopic and histologic features explain the variability in PGA. ANOVA
was used to examine the extent to which variations in symptom severity help
to explain the variability in PGA over and above variations in severity of endoscopic and histologic features.

RESULTS: The physician, histopathology, and PRO instruments were evaluated


in 153 adult EoE patients (72.5 % males, median age 38 years) recruited in
Switzerland and in the United States. Variations in severity of endoscopic features including white exudates, rings, edema, furrows, and strictures explained
52 % of the PGA variability. Variations in severity of histologic features including the peak esophageal eosinophil numbers and eosinophilic microabscesses
explained additional 9 % of the variability in PGA. Variations in symptom
severity (7 items of the PRO module recalled over the last 7 days) explained an
additional 10 % of the variability in PGA.
CONCLUSION: The variations in severity of EoE-associated endoscopic and
histologic features explained most variability in physician global assessment of
EoE severity (total of 61 %).
Disclosure of Interest: None declared
P0457 DIETARY TREATMENTS FOR INDUCING REMISSION OF
EOSINOPHILIC ESOPHAGITIS. A SYSTEMATIC REVIEW AND
META-ANALYSIS
A.J. Lucendo1,*, A. Arias2, J. Gonzalez-Cervera3, J.M. Tenias2
1
Gastroenterology, Hospital General de Tomelloso, Tomelloso, 2Research Support
Unit, Hospital General La Mancha Centro, Alcazar de San Juan, 3Allergy,
Hospital General de Tomelloso, Tomelloso, Spain
Contact E-mail Address: alucendo@vodafone.es
INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic esophageal
immune/allergy-mediated disorder, which represents a distinctive form of foodallergy. Various dietary interventions have been used to treat patients with EoE,
yielding varied results.
AIMS & METHODS: This systematic review assesses the efficacy of different
dietary therapies in inducing disease remission of EoE in adult and pediatric
patients with the disease.
A systematic search was performed in MEDLINE, EMBASE, and SCOPUS for
studies investigating the efficacy of various dietary interventions in inducing
remission (515 eosinophils/hpf) of inflammatory infiltration as observed in esophageal biopsies from both pediatric and adult EoE patients. Summary estimates, including 95% confidence intervals (95% CI), were calculated for
exclusive feeding with amino acid-based elemental formulas, allergy testing-directed food elimination diets, and six-food elimination diets (SFED). A fixed or
random effects model was used depending on heterogeneity (I2); publication bias
risks were assessed by means of funnel plot analysis.
RESULTS: The search yielded 578 references, of which 30 were included in the
quantitative summary. All told, the studies described 1,285 EoE patients (1,124
children and 161 adults) undergoing different dietary treatments. Elemental diets
were effective in 90.4% of cases (95% IC: 84.795.5%, I2: 2.3%), SFED in 73%
(66.678.9%; I2: 0%), and allergy testing-directed food elimination induced
remission in 46.3% of cases (35.657.1%; I2: 7 6.4%). Additional dietary therapy
strategies (elimination of cows milk and gluten-free diets) were also evaluated.
Overall, no significant differences in remission rates were documented between
children and adults (67.4% vs. 71.5%).
CONCLUSION: Dietary treatment is effective in achieving histological remission in patients with EoE. Elemental diets and SFEDs were the most consistent
alternatives, achieving 515 eosinophils/hpf in 90.4 and 73% of treated patients,
respectively.
Disclosure of Interest: None declared
P0458 IS EOSINOPHILIC
ALLERGIC RHINITIS?

ESOPHAGITIS

CORRELATED

WITH

A. Soylu1,*, H. Kaya2, S. Cakmak1, S. Poturoglu3, A. Altntas2, I. Sevindir1


1
Gastroenterology, 2Otorhinolaryngology, Bakirkoy Dr Sadi Konuk Research and
Training Hospital, 3Gastroenterology, Haseki Research and Training Hospital,
Istanbul, Turkey
Contact E-mail Address: aliyesoylu@superonline.com
INTRODUCTION: Eosinophilic esophagitis (EoE) is a rare disorder and is
reported to be associated with concurrent allergic disorders. In this study, we
aimed to evaluate the prevalance EoE in patients with allergic rhinitis and to
assess clinical features in those patients having EoE.
AIMS & METHODS: Patients with allergic rhinitis were questioned with respect
to esophageal and gastric symptoms (i.e., epigastric pain, gastroesophageal reflux
(GER), dysphagia), and underwent upper gastrointestinal (GI) endoscopy and
serum IgE level measurement. Multiple tissue samples were taken from the
upper, middle and lower esophagus, gastric corpus and antrum, and duodenum
during upper GI endoscopy. EoE was defined as the presence of eosinophilic

P0457
Dietary Treatment

Overall effect

Children

Adult

All
Elemental diets
Allergy testing-direct elimination diets
SFED
Gluten-free diet
Milk elimination diet
Subgroups according to quality
Medium/High - High
Low Medium/Low

67.9% (57.9% 77.1%)


90.8% (84.7% - 95.5%)
46.3% (35.6% - 57.1%)
73% (66.6% - 78.9%)
52.2% (15.3% - 87.8%)
68.2% (47.8% - 85.6%)
69.8% (58.4% - 80.1%)
60.6% (35.3% - 83.1%)

42
13
13
6
6
3
32
10

67.4%
90.4%
47.9%
72.8%
45.5%
66.6%
70.3%
58.5%

34
12
12
4
4
2
26
9

71.5% (53.3% - 86.7%)


94.4% (17/18)
26.6 (4/15)
73.1% (64.8% - 80.7%)
100% (1/1)
100% (1/1)
70.6% (51.1% - 86.8%)
100% (1/1)

6
1
1
2
1
1
5
1

(55.9% - 78%)
(83.5% - 95.5%)
(36.8% - 59.1%)
(62.5% - 82%)
(2.6% - 93.8%)
(44.7% - 84.8%)
(56.5% - 82.4%)
(32.2% - 82.3%)

United European Gastroenterology Journal 2(1S)


infiltration in the squamous epithelium of the esophagus (eosinophil number
15/HPF for patients using PPI and 20/HPF for patients not using PPI) and
the absence of eosinophilic infiltration in corpus, antrum and duodenum.
Reexamination with upper GI endoscopy was performed after a 2-month
proton pump inhibitor (PPI) therapy. Allergy test results were recorded.
Symptoms, serum IgE levels, allergy test positivity, Helicobacter pylori positivity,
endoscopic findings and histologic findings were compared between patients with
EoE and those without EoE.
RESULTS: Sixty seven patients were included in the study. Of them, 15 were
male. Mean age of male and female patients were similar (p 0.129).
Histopathological diagnosis of EoE was made in 7 patients (10.4%) and none
of them had a history of PPI usage prior to diagnosis. Symptoms of GER and
dysphagia were present in 71.4% and 28.57% of patients with EoE, while they
were present in 28.30% and 1.67% of those without EoE. In patients with
histologically proven EoE (n 7), 4 had endoscopic findings compatible with
EoE (57%), 2 had grade A reflux esophagitis (28.6%) and 1 had normal endoscopic findings. In patients without EoE (n 60), 1 had endoscopic findings
compatible with EoE and 3 had grade A reflux esophagitis. All patients with
EoE had eosinophil number 20/HPF in tissue samples from upper and middle
portion of the esophagus. Serum IgE levels were significantly higher in patients
with EoE than in those without EoE (281.59204.12 vs 105.75161.6)
(p 0.013). H. pylori positivity were similar (p 0.816). Allergy test positivity
was 85.7% in patients with EoE and 50% in those without EoE.
CONCLUSION: GER is the most common symptom in patients with EoE.
EoE may be present even in patients with normal endoscopic findings
Serum IgE levels are higher and allergy test positivity are more common in
patients with allergic rhinitis and EoE.
EoE is common in patients with allergic rhinitis.
It is important to question patients with respect to EoE symptoms in patients
with allergic rhinitis and high serum IgE levels, especially when corticosteroid
therapy is considered.
Disclosure of Interest: None declared
P0459 CLINICAL AND HIGH RESOLUTION MANOMETRY DATA
SUPPORT THE HYPOTHESIS THAT PROTON PUMP INHIBITORRESPONSIVE ESOPHAGEAL EOSINOPHILIA REPRESENT A
GERD-RELATED PHENOMENON
O. Bartolo1, C.de Cassan1, R. Caccaro1, F. Galeazzi1, T. Morbin1, S. Tolone1,
R. Salvador1, G.C. Sturniolo1, M. Costantini1, E. Savarino1,*
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, Italy
INTRODUCTION: Eosinophilic esophagitis (EoE) and Proton Pump Inhibitorresponse esophageal eosinophilia (PPI-REE) present similar phenotypic appearance, similar histopathology but different response to antisecretory therapy.
Thus, it is unclear if PPI-REE is a gastro-esophageal reflux disease (GERD)related phenomenon, a subtype of EoE, or a completely unique entity. High
resolution manometry (HRM) is a novel technique that has been recently
shown to provide new insights on GERD pathogenesis. In particular, esophago-gastric junction (EGJ) morphology different from type I and weak peristalsis have been strongly associated with GERD.
AIMS & METHODS: We aimed to compare HRM features of patients with EoE
and PPI-REE. Consecutive patients with symptoms suggestive of EoE underwent
upper endoscopy in order to assess the presence of at least 15 eos/hpf on oesophageal biopsies at mid/proximal esophagus and, then, were treated with twicedaily PPI for at least 8 weeks. Thereafter, patients repeated upper endoscopy and
were stratified into two groups: EoE, in case of persistence of at least 15 eos/hpf
on oesophageal biopsies, and PPI-REE, in case of less than 15 eos/hpf and a 50%
decrease from baseline. Patients underwent also HRM with a 5-min baseline
recording to assess the EGJ and 10 single water swallows (5 mL) at 30-s intervals
to evaluate the esophageal peristalsis. Tracings were analyzed based on Chicago
Classification and each EGJ was classified as: Type I, no separation between the
Lower Esophageal Sphincter and the Crural Diaphragm; Type II, minimal
separation (41 and 52 cm); Type III, 42 cm of separation.
RESULTS: Thirty-one patients were identified as having EoE [24M/7F; mean
age 28 (18-75)], whereas 10 patients were diagnosed with PPI-REE [9M/1F; mean
age 38 (20-64)]. The two cohorts had similar dysphagia for solids (EoE 71% vs.
PPI-REE 66%, p 0.6979), bolus impaction (65% vs. 60%, p 1.000) and chestpain (23% vs. 20%, p 1.000), but different heartburn (26% vs. 60%,
p 0.0485) and regurgitation (16% vs. 50%, p 0.0446). Endoscopic features
had the same frequency between EoE and PPI-REE: rings (45% vs. 50%,
p 1.000), furrows (26% vs. 10%, p 0.4101) and plaques (23% vs. 40%,
p 0.4132). Esophageal strictures tended to be more frequent in EoE (52% vs.
10%, p 0.0592). At HRM testing, EoE patients had higher mean integrated
relaxation pressure [9 (2-16) vs. 6 (2-16), p 0.0616] and LES basal pressure [26
(10-54) vs. 17 (1-34), p 0.0388], but similar mean distal contraction integral
[1094 (522-2653) vs. 1763 (483-5281), p 0.5613] compared to patients with
PPI-REE. Type II and III EGJs were less common in EoE than in PPI-REE
patients (9% vs. 50%, p 0.0129). Manometric diagnoses were similar between
EoE and PPI-REE: weak peristalsis including large or small breaks and frequent
failed peristalsis (16% vs. 40%, p 0.2221), absent peristalsis (3% vs. 10%,
p 1.0000) and distal esophageal spasm (3% vs. 0%, p 1.0000).
CONCLUSION: Typical reflux symptoms and HRM features GERD-related are
more common in patients with PPI-REE than in patients with EoE. These data
support the hypothesis that PPI-REE may represent a GERD-related phenomenon rather than a subtype of EoE or a separate entity. Further larger studies are
needed to confirm these findings.
Disclosure of Interest: None declared

A259
P0460 LONG-TERM EFFICACY OF PROTON-PUMP INHIBITOR
THERAPY IN ADULT PATIENTS WITH PPI-RESPONSIVE
ESOPHAGEAL EOSINOPHILIA
J. Molina- Infante1,*, J. Martinek2, M.D. Rivas3, J. Krajciova2, F.J. Moawad4,
C. Martinez-Alcala1, B.D. van Rhjin5, J. Barrio6, J. Zamorano3,
A.J. Bredenoord5, E.S. Dellon7
1
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain,
2
Gastroenterology, Institutu Klinicke a Experimentaln Medicny, Prague, Czech
Republic, 3Research Unit, Hospital San Pedro de Alcantara, Caceres, Spain,
4
Gastroenterology, Walter Reed National Military Medical Center, Bethesda,
United States, 5Gastroenterology, Academic Medical Center, Amsterdam,
Netherlands, 6Gastroenterology, Hospital Rio Hortega, Valladolid, Spain,
7
Gastroenterology, Center for Esophageal Diseases and Swallowing, University of
North Carolina School of Medicine, Chapel Hill, United States
Contact E-mail Address: xavi_molina@hotmail.com
INTRODUCTION: Proton pump inhibitor-responsive esophageal eosinophilia
(PPI-REE) is diagnosed in at least a third of patients with a phenotype suggestive
of eosinophilic esophagitis (EoE). However, neither long-term response to PPI
therapy in PPI-REE patients nor influencing factors have been evaluated yet.
AIMS & METHODS: We aimed to determine the long-term efficacy of PPI
therapy in PPI-REE and its association to CYP2C19 genotype status.
Retrospective multicenter study in PPI-REE adult patients, defined by consensus
guidelines. After a diagnosis of PPI-REE, PPI therapy was tapered and maintained at the lowest dose with the target endpoint of clinical remission.
Histological remission was defined by 5 15 eos/HPF. Follow-up endoscopy
was performed at 12 months or longer on PPI maintenance dose. CYP2C19*2
and CYP2C19*17 were determined from blood samples in Spanish patients.
RESULTS: 46 PPI-REE patients were included (mean follow-up time: 27 months
(12-79)). While on clinical remission on low-dose PPI therapy, 34/46 (74%) had
sustained histologic remission (19 double-dose PPI, 21 single-dose PPI). In 8/12
relapsers (66%) on maintenance PPIs, esophageal eosinophilia recurred exclusively at the distal esophagus. Compared to patients with sustained PPI-response
(n 13), this subset of distal relapsers showed borderline significant higher rates
of CYP2C19*2 rapid metabolizer genotype (100% vs. 53%, P 0.07) and reflux
esophagitis at baseline (50% vs. 0%, P 0.08). All distal relapsers re-achieved
histological remission after PPI-dose intensification (omeprazole 40 mg bid).
CONCLUSION: 74% of adult PPI-REE patients had persistent clinico-histological remission on low-dose maintenance PPI therapy. While on clinical remission, two thirds of relapsers showed eosinophilic inflammation limited to the
distal esophagus. Baseline reflux esophagitis and a CYP2C19 rapid metabolizer
genotype were associated to this relapsing pattern and histological remission was
re-achieved after PPI-dose intensification in all patients.
Disclosure of Interest: None declared
P0461 RESULTS OF LIQUID CYTOLOGY IN THE DIAGNOSIS AND
MONITORING EOSINOPHILIC OESOPHAGITIS
J. Rodr guez Sanchez1,*, B. Lopez Viedma1, E.de la Santa Belda1, P. Olivencia
Palomar1, J. Olmedo Camacho1, M. Garc a Rojo2
1
Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real,
2
Pathology, Hospital de Jerez de la Frontera, Jerez de la Frontera, Spain
Contact E-mail Address: joakinrodriguez@gmail.com
INTRODUCTION: Esophagoscopy with biopsy is considered the only method
for diagnosis and monitoring EoE. Therefore it is important to find out less
invasive diagnostic methods. Regarding this issue, obtaining oesophageal cytology is a way to explore to design in the future devices that allow to obtain
samples without endoscopy and biopsy. The aim of the study was to analyze
the accuracy of liquid-based cytology (LC) of the esophagus in the diagnosis and
monitoring EoE histological activity.
AIMS & METHODS: LC specimens were obtained in patients with active EoE
(AEoE) (15 eo/hpf) and EoE in remission (EoER) (515 eo/hpf) by oesophageal aspirate samples collected after instillation of 50 cc of saline solution suctioned by bronchioalveolar lavage system adapted to the gastroscope. The
samples were collected in Cytolyt solution (Hologic), obtaining Papanicolaou
and May-Grunwald/Giemsa that were assessed by two independent pathologists.
EoE specimens were compared with LC obtained from patients with GERD.
RESULTS: Specimens of 36 patients (69.4% male, mean age 30.88 years) were
included. AEoE (17, 47.2%), EoER (11, 30.5%) and GERD (8, 22.2%). Eo / hpf
proximal oesophageal biopsies (AEoE 28.58 vs EoER 2.09 vs GERD 1.25, p5
0.001) and distal (AEoE 23.33 vs EoER 2.36 vs GERD 2.50, p 0.002). LC Eo/
hpf (AEoE 9.23 vs EoER 1.54 vs GERD 2, p 0.01). Linear correlation between
Eo/hpf average biopsy and LC Eo/hpf: r 0.57, p 5 0.001. For diagnosis of
EoE,  3 Eo/hpf in LC obtained a Sensitivity 70%, specificity 81%, PPV 86%
and NPV 60% (AUC 0.81, p 0.01). For detection of AEoE,  3 Eo/hpf in LC
obtained a sensitivity 70%, specificity 82%, PPV 81% and NPV 66%
(AUC 0.87, p 0.001).
CONCLUSION: LC in oesophageal aspirate obtained by a cutoff in 3 eo/hpf
seems to be effective for the diagnosis and monitoring activity in EoE. These
results open the door to the development of non endoscopic devices that allow us
the diagnosis and monitoring of disease noninvasively.
Disclosure of Interest: None declared

A260

United European Gastroenterology Journal 2(1S)

P0462 CORRELATION BETWEEN CLINICAL, HISTOLOGIC AND


ENDOSCOPIC ACTIVITY IN EOSINOPHILIC OESOPHAGITIS.
PRELIMINARY RESULTS OF SENECA PROJECT (SPANISH STUDY
OF ENDOSCOPY AND EOSINOPHILS CORRELATION
ASSESSMENT)
J. Rodr guez Sanchez1,*, J. Molina Infante2, J. Barrio Andres3, I. Perez
Mart nez4, A. Bouhmidi Assakali5, J.A. Olmos Jerez6, B. Madrigal Rubiales7,
E.de la Santa Belda1, B. Lopez Viedma1, J. Olmedo Camacho1
1
Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real,
2
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, 3Gastroenterology,
Hospital del Rio Hortega, Valladolid, 4Gastroenterology, Hospital Universitario
Central de Asturias, Oviedo, 5Gastroenterology, Hospital Santa Barbara,
Puertollano, 6Gastroenterology, Hospital Rey Juan Carlos, Mostoles, 7Pathology,
Hospital del Rio Hortega, Valladolid, Spain
Contact E-mail Address: joakinrodriguez@gmail.com
INTRODUCTION: Esophagoscopy with biopsies is considered the gold standard for diagnosis and monitoring EoE. This is due to lack of correlation
between histology, endoscopy and clinical manifestations of the disease. A
novel endoscopic classification for assessment of eosinophilic esophagitis (EoE)
activity has been recently proposed (EREFs). We aimed to address the correlation of clinical and endoscopic EoE activity scores with histological response
after different therapeutic interventions.
AIMS & METHODS: Spanish multicenter prospective study in consecutive
patients with EoE, according to consensus guidelines. Clinical (Dysphagia
Symptom Score (DSS) Scale) and endoscopic (EREFS) disease activity, along
with eosinophil peak count, were assesed at baseline and after topical steroids or
elimination diet, including food reintroductions. Histological remission was
defined by 5 10 eos/HPF at both distal and proximal esophagus. Patients
were subclassified: Group A (Baseline), Group B (No histological remission
after therapy/food reintroduction) and Group C (Histological remission after
therapy/food reintroduction).
RESULTS: 79 patients undergoing 128 upper endoscopies have been included so
far (77.2% male, age 34.7 years-old, dysphagia 100%). Group A: 47 (36.7%),
Group B: 61 (47.7%) and Group C: 20 (15.6%). DSS score was significantly
higher in Group A (A 7.16, B 5.15, C 3.70; p 0.006), but no differences
were observed between groups B and C (p 0.12). Regarding endoscopic findings, inflammatory features were significantly decreased after histological remission (furrows: A 63.8%, B 72.1%, C 40%; p 0.034 / exudates (grade 2):
A 10.6%, B 18%, C 5%;p 0.002), but not fibrostenotic features (pseudorings: A 68.1%, B 55.4%, C 55%;p 0.44/stricture: A 10.6%, B 9.8%,
C 5%;p 0.75). Mucosal edema was common at baseline and persistent
regardless of histological remission (A 61.7%, B 78.7%, C 60%; p 0.09).
CONCLUSION: EoE clinical activity significantly decreased after different therapeutic interventions, with no differences between patients showing eosinophilia
remission or persistence after therapy. Histological remission was correlated with
significant decrease of inflammatory endoscopic features, but not of fibrostenotic
findings. Mucosal edema was mostly persistent regardless of histological remission, suggesting it might belong to the fibrotic remodelling spectrum.
REFERENCES
Disclosure of Interest: None declared
P0463 IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE,
GLOBUS IS ASSOCIATED WITH ABNORMAL OROPHARYNGEAL
ACID EXPOSURE
M. Di Stefano1, C. Mengoli1,*, M. Bergonzi1, E. Pagani1, E. Miceli1,
G.R. Corazza1
1
1st Department of Internal Medicine, IRCCC Policlinico S. Matteo, University of
Pavia, Pavia, Italy
Contact E-mail Address: m.distefano@unipv.it
INTRODUCTION: Globus, a persistent or intermittent non-painful sensation of
a lump or foreign body in the throat, is frequently associated with gastroesophageal reflux disease (GERD): it is estimated that up to 68% of GERD patients
suffer from globus. However, previous esophageal pH and pH-impedance studies
failed to define a causative role of acid or non-acid reflux in globus
pathophysiology.

AIMS & METHODS: The aim of this study was to investigate both distal and
proximal, oropharyngeal acid exposure, with a new device, in patients with nonerosive reflux disease (NERD) with and without globus.
A group of 37 patients affected by NERD was enrolled. The presence of reflux
symptoms was evaluated and severity was graduated by VAS. In eight patients,
globus was the main symptom; in the other 29, globus was not present and they
were thus considered the control group. Patients underwent standard stationary
esophageal manometry (6 channelssleeve) and 24-hr pH-impedance esophageal
monitoring (Sleuth, Sandhill Scientific) combined with 24-hr oropharyngeal pH
monitoring (Restech Dx-pH Measurement System).
RESULTS: Distal esophageal acid exposure (pH 54), number of acidic and
weakly acidic reflux episodes and proximal extension of refluxate were similar
between patients with and without globus. On the contrary, patients with globus
showed a significantly longer oropharyngeal exposure to pH55.5 (total duration
of acid exposure: 222 min  230 min vs 47 min  88 min, p50.05; and percent of
recording: 16.0716.2% vs 3.566.84%, p50.05), compared to patients without
globus; the longest episode of oropharyngeal acid exposure was significantly
longer in patients with globus than in patients without globus (110 min  115
min vs 15 min  25 min; p50.05). A higher score for heartburn was evident in
the group of patients without globus (3.453.31 vs 1.311.44, p50.05); no
difference was found in regurgitation, cough, sore throat, or thoracic pain
score. Finally, the prevalence of esophageal motor disorders was similar in the
two groups.
CONCLUSION: Oropharyngeal acid exposure could have an important pathophysiological role in globus onset. Oropharyngeal pH monitoring seems a more
accurate diagnostic tool than the standard 24-hr pH-impedance study to define
the role of acid exposure in this subgroup of patients.
REFERENCES
1. Selleslagh M, van Oudenhove L, Pauwels A, et al. Nat Rev Gastroenterol
Hepatol 2014; 11: 220-233.
2. Chevalier JM, Brossard E and Monnier P. 2003; 260: 273-276.
Disclosure of Interest: None declared
P0464 UNDERSTANDING THE CAUSE OF PERSISTENT GERD
SYMPTOMS DESPITE PROTON PUMP INHIBITOR THERAPY:
IMPEDANCE-PH MONITORING REVISITED
D. Ang1,*, I. Hussain1, F. Kwong Ming1
Gastroenterology, Changi General Hospital, Singapore, Singapore
Contact E-mail Address: ang_daphne@yahoo.com
1

INTRODUCTION: Non-response to proton pump inhibitor (PPI) therapy in


patients with reflux symptoms and a normal gastroscopy remains a challenge.
Impedance-pH (MII-pH) monitoring clarifies the symptom profile and evaluates
patients objectively for acid reflux (AR) and non-acid reflux (NAR).
AIMS & METHODS: To study MII-pH characteristics in patients referred for
GERD evaluation who remain symptomatic despite PPIs, and study mechanisms
related to persistent symptoms. Methods: Between January 2009-December 2013,
consecutive patients with typical symptoms (group 1); atypical symptoms (group
2) and non-cardiac chest pain (NCCP, group 3) underwent 24 hour MII-pH after
PPI washout. Prevalence of (i) oesophageal acid exposure time (AET)44.2%; (ii)
bolus exposure (BE41.4%), (iii) high reflux numbers (473) and/or (iv) positive
symptom marker based symptom index (SI 50%) and/or symptom association
probability (SAP 95%) for AR or NAR events was compared between groups
by chi-square and student t-testing.
RESULTS: 208 patients (80M, mean age 45.9  12.5) were studied (Table 1).
Elevated AET occurred in 24 (11.5%). 120 (57.7%) recorded a positive study on
MII-pH evaluation despite a normal overall AET. Group 1 and 3 patients had
significantly more symptomatic AR events (p50.05) compared to group 2.
Symptomatic NAR related events did not differ significantly different between
groups. Patients with a positive symptom association for AR events were more
likely to have abnormal BE (p 0.01) and abnormal reflux numbers (p50.05).
Table 1.
CONCLUSION: Use of MII-pH in PPI non-responders identifies AR and NAR
events and serves as an important diagnostic modality to evaluate the symptom
profile and guide appropriate therapy, which may extend beyond PPIs.
Disclosure of Interest: None declared

Table to P0464

Raised AET
No. of AR events (mean, SEM)
No. of NAR events (mean, SEM)
No of proximal reflux events (mean,SEM)
Total no. of reflux events
Total bolus exposure time (mean, SEM)
Positive symptom association for acid reflux
Positive symptom association for non-acid reflux

Group 1
Typical
(N39M,55F)

Group 2
Atypical
(N34M,50F)

9/94 (9.6%)
22.6  2.3
26.1  2.7
p50.05 compared to group 3
25.5 2.3
p50.05 compared to group 3
48.6  3.9
p50.005 compared to group 3
1.7  0.2
45/94(47.8%)
p50.05 compared to groups 2
43/94 (45.7%)

13/84(15.5%)
21.2  1.9
23.1  1.5
p50.05 compared to group 3
23.7  1.7
p50.05 compared to group 3
44.0  2.5

2/30(6.7%)
18.3  3.0
17.1  2.1

1.5  0.1
23/84 (27.4%)

1.2  0.2
19/30(63.3%)
p50.05 compared to groups 2
10/30(33.3%)

39/84(46.4%)

Group 3
Non cardiac chest pain (N7M,23F)

17.1  2.8
35.4 3.8

United European Gastroenterology Journal 2(1S)


P0465 ACID AND NON ACID REFLUXES MODIFY THE BASELINE
IMPEDANCE VALUES IN A LARGE SERIES OF NERD PATIENTS
F.P. Zito1,*, P. Andreozzi1, A. DAlessandro1, I. Arnone1, M. Pesce1, E. Efficie1,
G. Affinito1, D. Esposito1, G.D. De Palma1, G. Sarnelli1, R. Cuomo1
1
Clinical Medicina and Surgery, UNIVERSITY OF NAPLES " FEDERICO II",
Naples, Italy
Contact E-mail Address: francescozito1@hotmail.com
INTRODUCTION: Esophageal baseline impedance (BI) may be considered as
an indirect way to express macroscopic and/or microscopic mucosal integrity
since recent evidence has shown that patients with both erosive or non erosive
esophagitis have lower level of BI than healthy subjects.
AIMS & METHODS: The aim of our study was to evaluate how BI is transiently
influenced by the nature of reflux events.
We studied 60 patients (28 M - mean age 45.8  16.1) with typical GERDsymptoms (heartburn and regurgitation) and negative endoscopy, who performed a 24h-pH impedance monitoring from January to March 2014. Among
these, 33 exams were performed on therapy with proton pump inhibitor, while 27
were off-therapy. For each patient, 24 hours esophageal BI was calculated during
the first period of 60 seconds without an impedance event (swallow or reflux)
every four hours. Then, we calculated BI immediately before and 1 minute after
the end of the same reflux event. Pre and post-reflux BI for acid and non acid
were calculated in off and on-therapy patients, respectively. Moreover, for each
reflux episode, the minimum pH reached was also registered.
RESULTS: 24 hours BI and pre-reflux BI were similar for both acid and non
acid events (2422641 vs 2424758m and 2386497 vs 2384639 m, respectively, all p NS). On the contrary, a significant reduction between pre and postreflux BI for acid and a significant increase was registered for non acid reflux
(2424758 vs 2130721 m, p 0.001 and 2384640 vs 2767489 m,
p 0.004, respectively). The same results were observed in the subgroups of
subjects off and on therapy (Off-therapy: 2330766 vs 2083684 m, p50.01;
On therapy: 2187478 m vs 2713503 m, p50.01, respectively).
Most interestingly differences between pre and post-reflux BI of all patients were
positively correlated to the pH nadir of each reflux event (p50.0001, r2 0.42).
CONCLUSION: Baseline impedance may be transiently influenced by the nature
of reflux episodes, being acid and non-acid refluxes respectively associated with a
decrease and an increase of baseline impedance. Our data indicate that nature of
refluxes is able to differently affect BI, likely, if this phenomenon underlies
changes in mucosal integrity or it is associate with abnormal perception deserves
further investigation.
Disclosure of Interest: None declared
P0466 PATIENTS WITH ACTIVE CELIAC DISEASE HAVE ALTERED
INTERCELLULAR SPACES AND TIGHT JUNCTION STRUCTURE
OF THE LOWER ESOPHAGUS THAT MAY EXPLAIN THE HIGH
PREVALENCE OF REFLUX SYMPTOMS IN THESE PATIENTS
G. I. Longarini1,*, F. Nachman2, S. Salim1, H. Hwang1, A.F. Costa1, M.
I. Pinto3, X.X. Wang3, H. Vazquez1, C. Fuxman2, M.L. Moreno1, S. Niveloni1,
E. Smecuol1, R. Mazure1, E. Maurino1, E. Verdu3, J.C. Bai1
1
Medicine, Hospital Udaondo, 2Fundacion Favaloro, Buenos Aires, Argentina,
3
Farncombe Institute, McMaster University, Hamilton, Canada
Contact E-mail Address: fdnachman@intramed.net
INTRODUCTION: Patients with untreated celiac disease (CD) often complain
of reflux symptoms, which in 30% of cases are considered moderate to severe
(CGH 2011; 9: 214-9). The gluten-free diet leads to a rapid and persistent
improvement in reflux symptoms and most cases do not require the use of
proton pump inhibitors. The mechanisms involved in the expression of reflux
symptoms in CD patients are unknown.
AIMS & METHODS: Objective: We explored symptomatic and mucosal markers of permeability of the lower esophagus in patients with newly diagnosed CD
at the time of diagnostic endoscopy, patients with symptoms of GERD but no
CD (GERD controls) and healthy controls without symptoms (healthy controls:
HC).
Methods: A cohort of 23 consecutive patients with active CD at the time of
diagnosis, 5 GERD control patients, and 11 HC subjects, were enrolled in the
study. Nine out of 23 CD patients had GERD symptoms considered as moderate
or severe (42 points in the GSRS questionnaire). Endoscopic biopsies from the
distal esophagus were obtained 2 cm above the z-line. Samples were assessed for
histological damage, dilated intercellular space (DIS) scores by optical microscopy (OM) and electron microscopy (EM), and tight junction (TJ) mRNA
expression for zonnula occludens-1 (ZO-1) and claudin-2 and -3 (CL-2; CL-3)
using Real Time qRT-PCR.
RESULTS: Patients with active CD had increased DIS scores compared to HC
subjects (OM: 8.03.1 vs. 2.22.5; p50.003 and EM: 31.79.5 vs. 15.05.1;
p50.04) but similar to GERD controls. CD patients without GERD symptoms
also had higher DIS scores compared to HC (OM: p50.006; EM: p50.03) but
similar to those in CD patients with GERD symptoms. Overall CD patients had
lower expression of ZO-1 than HC (CD patients with and without GERD symptoms: p50.003 and p40.05; respectively). A non-statistical trend for higher CL-2
and CL-3 expression was observed in CD patients compared with GERD controls and no differences were detected between CD subgroups with or without
GERD symptoms. CD patients had similar expression of CL-2 and CL-3 compared to HC.
CONCLUSION: Our study suggests an impairment of mucosal permeability in
the distal esophagus of patients with active CD irrespective of the presence of
GERD symptoms. The altered expression of ZO-1, and CL-2 and CL-3 may
underlie loss of TJ integrity in the esophageal mucosa, an expression pattern
that is reminiscent of intestinal permeability abnormalities observed in CD,

A261
and that may contribute to reflux symptom expression and its reversion by the
gluten-free diet.
Disclosure of Interest: G. Longarini: None declared, F. Nachman: None declared,
S. Salim: None declared, H. Hwang: None declared, A. Costa: None declared,
M. Pinto: None declared, X. X. Wang: None declared, H. Vazquez: None
declared, C. Fuxman: None declared, M. Moreno: None declared, S. Niveloni:
None declared, E. Smecuol Financial support for research from: Astra Zeneca,
Lecture fee(s) from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, R.
Mazure: None declared, E. Maurino: None declared, E. Verdu: None declared, J.
Bai: None declared
P0467 RECEPTOR MODULATION AND MAP-KINASE SIGNALING
INDUCED BY STW5 AND BY THE PROTON-PUMP INHIBITOR
OMEPRAZOL IN A RAT MODEL FOR GASTROESOPHAGEAL
REFLUX DISEASE AND IN HET1A-CELLS
H. Abdel-Aziz1,*, O. Kelber 2, M.T. Khayyal 3, G. Ulrich-Merzenich4
1
University of Munster, Munster, 2Steigerwald Arzneimittelwerk GmbH,
Darmstadt, Germany, 3Cairo University, Cairo, Egypt, 4Medical Clinic III, UKB,
University of Bonn, Bonn, Germany
Contact E-mail Address: gudrun.ulrich-merzenich@ukb.uni-bonn.de
INTRODUCTION: We had earlier demonstrated that STW5 affects multiple
chemokine families on genome and proteome level reducing inflammation in
the esophageal tissue in our rat model for gastroesophageal reflux disease
(GERD)1.
AIMS & METHODS: Here we investigated selected receptors and which signaling cascades are activated during the anti-inflammatory processes by STW5 and
by the proton-pump inhibitor Omeprazole (O). Methods: Rats were pretreated
with either STW5 (0.5 or 2ml/kg) or O (30mg/kg). Esophagitis was induced
surgically followed by a further 10d treatment. On day 10 animals were sacrificed
and whole cell lysates of the esophagi were evaluated by Western Blot analysis for
the receptors GPR 84 and LOX-1 (lectin-like oxidized low density lipoprotein
receptor 1) and the stress induced mitogen activated kinase (MAPK) p38.
Further investigations were undertaken with the human esophageal squamous
cell line HET-1A. Inflammation was induced with Capsaicin (50mM, 18hrs) and
cells were treated with either STW5 (0.17; 0.5; 1.7; 5ml/ml) or O (10mg/ml; 30mg/
ml). MAPKs p38, ERK1 and 2 were determined. Data were normalized either
with the respected unphosphorylated protein or with -Actin.
RESULTS: The LOX-1 receptor was only detected in the esophagi of rats with
esophagitis, but not in the esophagi of sham operated or treated rats. The GPR
84 receptor was increased in the esophagitis group compared to the sham group
and down regulated by STW5 and O. In the sham group neither total p38 MAPK
nor the phosphorylation of p38 was increased. The treatment of STW5 inhibited
the phosphorylation of p38 MAPK in the tissue, but did not influence the
increase in the total amount of p38 of the esophagitis group. In HET1A cells
capsaicin slightly increased the expression of GPR84 which was reduced by the
high concentration of STW5. Capsaicin induced an increase in the phosphorylation of ERK1/2 compared to the control. This increase was inhibited in the
presence of STW5 as well as in the presence of O.
CONCLUSION: The LOX-1 and the GPR 84 receptor activation contribute to
experimental GERD. They are targeted like P38, which is known to be acid
sensitive in GERD2, by STW5. Data further substantiate differential
MAPKinase signaling in GERD. They support the classification of GPR84 as
proinflammatory receptor with a link to the immune response in oesophageal
tissue.
REFERENCES
1 Abdel-Aziz, et al. United Eur Gastroenterol J 2013; 1: A113OP380.
2 Rafiee, et al. Am J Physiol Cell Physiol 2006; 291: C931-C945.
Disclosure of Interest: H. Abdel-Aziz Other: employee of Steigerwald
Arzneimittelwerk GmbH, O. Kelber Other: employee of Steigerwald
Arzneimittel GmbH, M. T. Khayyal Financial support for research from:
Steigerwald Arzneimittelwerk GmbH, G. Ulrich-Merzenich Financial support
for research from: Steigerwald Arzneimittelwerk GmbH
P0468 EXPRESSION OF VEGF AND VEGFR IN EROSIVE AND
NONEROSIVE REFLUX DISEASE
J. Wasielica-Berger1,*, A. Pryczynicz2, J. Daniluk1, P. Rogalski1, A. Kemona2,
A. Dabrowski1
1
Department of Gastroenterology and Internal Medicine, 2Department of
Pathomorphology, Medical University of Bialystok, Bialystok, Poland
Contact E-mail Address: jwasielica@o2.pl
INTRODUCTION: Up to 70% of patients with gastro-esophageal reflux disease
do not have erosions visible in conventional endoscopy. They are classified as
non-erosive reflux disease (NERD). Studies on endoscopy with optical magnification described a variety of minimal changes in NERD patients, also concerning
vessels. Until now it is not clear why some patient develop erosions and others do
not. Differences in self-defense mechanisms may matter. Vascular endothelial
growth factor (VEGF) is a signal protein working through its receptor
(VEGFR) promoting angiogenesis and wound healing.
AIMS & METHODS: We evaluated squamous epithelium above Z line in magnification up to 105 times in 20 patients with NERD, 12 patients with erosive
esophagitis (EE) and 5 controls (patients without reflux disease). The magnified
images were analyzed with respect to: visibility of palisade blood vessels, appearance of intrapapillary capillary loops (IPCLs) and white points seen as whitish
pinpoint spots encirculating IPCLs or independent from IPCLs. Biopsy specimens for the histopathologic examination were taken 1-2 cm above Z line. In
histology presence of inflammation was evaluated in a scale from 0 (absent) to 3
(severe). Expression of VEGF and VEGFR in squamous epithelium was

A262

United European Gastroenterology Journal 2(1S)

evaluated by immunohistochemistry method. The reaction of VEGF and


VEGFR proteins was defined as low if positive in less than 33% of vessels,
moderate if positive in 33-66% of vessels and high if positive in over 66% of
vessels. Statistics was executed with Fisher exact test.
RESULTS: Expression of VEGF and VEGFR was significantly higher in EE
than NERD group (p50.05). Control group had comparatively low expression
of VEGF and VEGFR.
VEGF expression

VEGFR expression

Number of
patients

Low *

Moderate

High *

Low **

Moderate

High **

EE
NERD
Controls

0 (0%)
8 (40%)
2 (40%)

5 (42%)
8 (40%)
3 (60%)

7 (58%)
4 (20%)
0 (0%)

1(8.3%)
11 (55%)
3 (60%)

4 (33.3%)
5 (25%)
1 (20%)

7(58.3%)
4 (20%)
1 (20%)

Enlarged IPCLs, white points or diminished visibility of palisade vessels seen in


magnification endoscopy did not correlate with expression of VEGF and
VEGFR, neither did the grade of esophagitis evaluated in plain histology.
CONCLUSION: VEGF and VEGFR expression is higher in EE than NERD
patients. This phenomenon may be the part of esophageal mucosa healing in EE.
Disclosure of Interest: None declared
P0469 EXPRESSION OF EPIDERMAL GROWTH FACTOR RECEPTOR
IN PATIENTS WITH GASTRO-OESOPHAGEAL REFLUX DISEASE
AND IN THOSE WITH SYSTEMIC SCLEROSIS
P. Zentilin1,*, E. Marabotto1, L. Assandri1, F. Grillo2, L. Mastracci2,
M. Giuseppe3, A. Sulli4, E. Savarino5, V. Savarino1
1
Department of Internal Medicine, Gastroenterolgy Unit, 2Department of Surgical
Sciences and Integrated Diagnostics, Pathological Anatomy Unit, 3Department of
Internal Medicine, Internel Medicine Unit, 4Department of Internal Medicine,
Rheumatology Unit, Genova, 5Department of Surgery, Oncology and
Gastroenterology, Gastroenterolgy Unit, Padova, Italy
Contact E-mail Address: pzentilin@unige.it
INTRODUCTION: Epidermal growth factor (EGF) and its receptor (EGFR), a
tyrosine kinases receptors (TKs), are associated with epithelial proliferation and
restitution, the two key mechanisms involved in oesophageal epithelial defense
against reflux. It has been shown that EGFR expression increases with the progression from gastro-oesophageal reflux disease (GORD) to Barretts oesophagus/adenocarcinoma. Systemic sclerosis (SSc) is characterized by deposition of
collagen and other extracellular matrix proteins in the connective tissues, imbalance of the immune system, and microvasculature abnormalities. Besides TKs
physiological roles, they are key players in various diseases, including SSc.
Indeed, their pathological activation may drive carcinogenesis, vascular remodelling, and fibrogenesis. No studies investigated the EGFR expression on oesophageal mucosa of SSc patients.
AIMS & METHODS: We aimed to assess and compare the presence of EGFR
expression on oesophageal mucosa of GORD and SSc patients. We studied 24
SSc (22F, median age 56yrs) and 22 GORD (9F, median age 64yrs) patients.
They underwent upper endoscopy and multiple specimens (n 4) were taken
from the distal oesophagus (at the Z-line and 2 cm above it). Biopsies were
fixed in formalin and embedded in paraffin. After preparation, anti-human
EGFR monoclonal antibody, clone H11 (anti-EGFR) (Dako), was applied to
the slides and EGFR expression was considered positive when staining was
detected on the membrane. Patients were endoscopically classified as having
erosive oesophagitis (EO), non-erosive reflux disease (NERD, in case of no
mucosal breaks and GORD symptoms) or negative endoscopy (NE, in case of
no mucosal breaks and absence of GORD symptoms). Microscopic oesophagitis
(MO) was diagnosed by using a previously validated score.
RESULTS: At endoscopic evaluation, 3/24 (13%) SSc patients had EO, 11/24
(46%) had NERD and 10/24 (42%) had NE, whereas at microscopic evaluation 3
had evidence of erosive oesophagitis, 11 of MO and 10 of normal mucosa,
respectively. Among GORD patients, we found at endoscopic and microscopic
evaluation that 3/22 (14%) had EO with histological reply of 2 erosive oesophagitis and 1 MO, 12/22 (55%) had NERD with evidence of MO and 7/22 (31%)
had normal findings at both measurements. Overall comparison of EGFR
expression between SSc and GORD patients was not significant, whereas comparison of EGFR expression between the 10/24 SSc and 7/22 GORD patients
without endoscopic and histological alterations was statistically significant
(p 0.0068). EGFR expression between the 14/24 SSc patients with erosive
and microscopic oesophagitis was higher than in the 10/24 with normal
mucosa (p 0.0177) as well as in GORD patients with and without oesophagitis
(p 0.0004). In GORD patients EGFR expression decreases proximally, while in
SSc patients it seems overexpressed.
CONCLUSION: In GORD patients, EGFR expression correlates with histological findings and seems to play a major role in maintaining epithelial integrity.
In SSc patients, it is overexpressed and this can act as an inflammatory reactive
stimulus, even in the absence of microscopic lesions.
Disclosure of Interest: None declared
P0470 ACID INFUSION INTO THE STOMACH DOES NOT AFFECT THE
NUMBER OF MEAL-INDUCED TRANSIENT LOWER ESOPHAGEAL
SPHINCTER RELAXATIONS (TLESR)
P. Banovcin1,*, J. Halicka1, M. Halickova1, J. Androvic1, M. Duricek1,
R. Hyrdel1, M. Tatar1, M. Kollarik1,2

JESSENIUS FACULTY OF MEDICINE, COMENIUS UNIVERSITY,


Martin, Slovakia, 2JOHNS HOPKINS SCHOOL OF MEDICINE, Baltimore,
United States
Contact E-mail Address: pbanovcin@gmail.com
INTRODUCTION: TLESRs are considered to be the most important mechanism of gastroesophageal reflux (GER). However, the regulation of TLESRs by
acid is incompletely understood. We have recently reported that acid in the
esophagus enhanced TLESR (Abstract Tu1868, Digestive Diseases Week,
Gastroenterology Vol. 146[2014] suppl.). Specifically, we found that the acid
infusion into the esophagus increased the number of meal-induced TLESRs by
60% compared to control infusion.
AIMS & METHODS: In the present study we evaluated the effect of acid infusion into the stomach on the meal-induced TLESRs. The study was carried out in
healthy subjects (age 23  0.3 years) None of the subjects had any esophageal
motility abnormality as defined by Chicago criteria. TLESRs were evaluated by
using high resolution manometry (HRM). The study was performed in sitting
position. For infusions a tube (O. D. 1mm) was attached to the HRM catheter
with the opening positioned in the stomach at least 5 cm below the manometrically identified lower esophageal sphincter. Each subject was studied at two
occasions (control or acid infusion) separated by at least 7 days. Following a
standard meal (chicken sandwich and soda drink), acid (0.15 M HCl) or water
was infused into the stomach (8ml/min, 20 min) by using a perfusion pump.
TLESRs were counted during 2h following the completion of the infusion. In
some subjects TLESRs were also counted during 20 min of acid infusion. The
study conformed to Declaration of Helsinki. All subjects gave informed consent.
RESULTS: 10 subjects (7M/3F) completed the study. We found that acid infusion into the stomach did not affect the number of meal-induced TLESRs. The
number of TLESRs (median[interquartile range]) during 2h following the control
vs. acid infusion was 17[12-18.75] vs. 15.5[12.25-20.25], n 10, p NS, Wilcoxon
Signed-Rank Test). The average duration of TLESRs was not changed
(16.3s0.4s, n 153 vs. 17.2s0.7s, n 151, P40.2, unpaired T-test). The
number of TLESRs during the acid infusion was also not affected (quantified
in 6 subjects, 4M/2F). The number of TLESRs during the 20 min of control vs.
acid infusion was 5.5[2.75-6] vs. 4[3.25-4.75], n 6, p NS, Wilcoxon SignedRank Test).
CONCLUSION: We conclude that the acid infusion into the stomach does not
affect the meal-induced TLESR. These results are consistent with the notion that
the direct effects of acid in the stomach has limited role in the regulation of
TLESR. Our results also indicate that the substantial enhancement of TLESR
by acid infusion into the esophagus observed in our previous study was not due
to acid effect in the stomach.
Supported by BioMed Martin (ITMS: 26220220187) co-funded by EU.
Disclosure of Interest: None declared
P0471 EFFECT OF GHRELIN ON EXPERIMENTAL ESOPHAGITIS IN
RATS
P. Konturek1,*, K. Celinski2, G. Burnat1, S. Kwiecien3, M. Raithel4,
S. Konturek3, T. Brzozowski3
1
Department of Medicine II, Thuringia Clinic, Saalfeld, Germany, 2Department of
Gastroenterology, Medical Academy Lublin, Lublin, 3Institute of Physiology,
University School of Medicine, Cracow, Poland, 4Department of Medicine I,
University Erlangen-Nuremberg, Erlangen, Germany
INTRODUCTION: Both ghrelin and leptin are involved in the regulation of
food intake but their effect on the development of experimental reflux esophagitis
(RE) is unknown.
AIMS & METHODS: The present study was designed to assess; 1) the effects of
pre-treatment with ghrelin and leptin on lesion score and esophageal blood flow
in rats with RE; 2) the influence of ghrelin and leptin on mucosal gene expression
and release of proinflammatory cytokines (IL-1b, TNF-a and IL-6) and 3) the
influence of ghrelin and leptin on the expression of COX-2 and HSP70 in esophageal mucosa during development of RE. RE was induced in rats (n 6/
group) according to technique proposed by Nakamura et al (Jpn J Pharmacol
1982, 32:445) by two ligation of 1) the duodenum at the pyloric sphincter and 2)
at the region between the forestomach and gastric corpus. Following treatment
groups were used: A) intact rats; B) rats with RE pretreated 1h before with saline
(control); C) rats pretreated with ghrelin (40 mg/kg i.p.) and D) leptin (40 mg/kg
i.p.) 1 h before exposure to RE. The lesion score (scale 0-5) and esophageal blood
flow using H2 gas clearance was measured. In addition, gene expression of IL-1b,
TNF-a, IL-6 and release of these cytokines was analyzed by quantitative RTPCR and ELISA. Furthermore, gene expression of COX-2 and HSP70 was
measured by RT-PCR.
RESULTS: Both ghrelin and leptin significantly attenuated (by 50%) the lesion
score induced by RE and this effect was accompanied by a significant increase in
esophageal blood flow. The expression of mRNA for COX-2 TNF-a, IL-1b and
IL-6 was negligible in the intact esophageal mucosa but was upregulated in
esophageal mucosa of rats with RE. The pretreatment with ghrelin and leptin
decreased the expression of mRNA for COX-2, TNF-a, IL-1b and IL-6. In
contrast, HSP70 was significantly downregulated in esophageal mucosa of rats
with RE and this effect was reversed in rats pretreated with ghrelin or leptin.
Ghrelin receptor (GHS-R) was detected both in intact and RE-inflamed esophageal mucosa.
CONCLUSION: Appetite hormones, such as leptin and ghrelin, significantly
attenuate the inflammatory reaction in esophageal mucosa caused by pathologic
reflux of gastric acid. The anti-inflammatory effect of ghrelin and leptin is may be
attributed to their inhibitory effect on expression and release of proinflammatory
cytokines, COX-2 and the restoration of protective Hsp70 inhibited due to RE.
Disclosure of Interest: None declared

A263

United European Gastroenterology Journal 2(1S)


P0472 ROLE OF ACID AND NON-ACID REFLUX IN ESOPHAGEAL
MUCOSAL DAMAGE (EROSIVE ESOPHAGITIS AND BARRETTS
ESOPHAGUS)
V. Kaibysheva1,*, A. Trukhmanov1, A. Ponomarev1, O. Storonova1,
M. Konkov1, V. Ivashkin1
1
FIRST MOSCOW STATE MEDICAL UNIVERSITY, Moscow, Russian
Federation
INTRODUCTION: The effect of acid reflux is commonly accepted nowadays.
Substantial experimental and clinical evidence strongly supports the importance
of acid and pepsin in causing esophageal mucosal injury. The role of weakly-acid
and duodenogastroesophageal reflux as an etiological factor of esophageal mucosal injury is not clarified until recently. With introduction of combined esophageal pH-impedance monitoring, a precise diagnostic test for non-acid reflux is
now available.
AIMS & METHODS: The aim of this study was to assess the role of acid and
non-acid reflux in esophageal mucosal injury. 127 patients (75(59.1%) women
and 52(40.9%) men, averaging 48.6  14.9 years), off acid-suppressive therapy
underwent diagnostic work-up including upper-GI endoscopy with biopsy and
combined esophageal pH-impedance monitoring. According to data from pHimpedance study patients were subdivided into three groups by predominant
characteristic of reflux: GERD with acid reflux (n 65; AR); GERD with
weakly-acid reflux (n 36, WR), and GERD with duodenogastroesophageal
reflux (n 26, DGR).
RESULTS: Rhe absence of endoscopically visible lesions or catarrhal esophagitis
(NERD) was found during endoscopy in 55.4%, 86.1%, and 76.9% for AR, WR,
DGR, respectively (p (AR-WR) 50.05). Erosive esophagitis (ERD) was found in
40%, 13.9% and 23.1% for AR, WR, DGR, respectively (p (AR-WR) 50.05).
Esophageal ulcers were found only in AR group in 4.6%. Moreover, AR and
DGR patients had significantly higher activity and degree of mucosal inflammation than patients in WR group (o50.05). Endoscopic changes indicating
Barretts esophagus with histologic presence of esophageal intestinal metaplasia
was found in 16%, 5.8%, and 42.9% for AR, WR, DGR, respectively (oARDGR50.05; pWR-DGR50.05).
CONCLUSION: Higher frequency of esophageal mucosal injury in AR group in
comparison with patients in WR group suggests that acid is the key factor in
causing esophageal injury. While weakly acidic reflux does not contribute significantly to esophageal mucosal damage. Similarly, the DGR patients had significantly higher rate of intestinal metaplasia which indicates the important role
of duodenal content (bile or alkaline pancreatic secretions) in developing
Barretts esophagus.
Disclosure of Interest: None declared
P0473 IMPEDANCE-PH REFLUX PATTERNS IN PATIENTS WITH NONEROSIVE REFLUX DISEASE AND EROSIVE REFLUX DISEASE
V. Kaibysheva1,*, A. Trukhmanov1, V. Ivashkin1
1
FIRST MOSCOW STATE MEDICAL UNIVERSITY, Moscow, Russian
Federation

differences between acid and bolus clearances time may be caused by two different mechanisms of clearance. Volume clearance is achieved by peristalsis while
chemical clearance requires neutralization by saliva.
REFERENCES
1. Shay S, Tutuian R, Sifrim D, et al. Twenty-four hour ambulatory simultaneous impedance and pH monitoring: a multicenter report of normal values from
60 healthy volunteers. Am J Gastroenterol 2004; 99: 10371043.
Disclosure of Interest: None declared
P0474 CHARACTERISTICS OF NIGHTTIME REFLUX ASSESSED BY
USING MULTI-CHANNEL INTRALUMINAL IMPEDANCE PH
MONITORING AND A PORTABLE ELECTROENCEPHALOGRAPH
Y. Fujiwara1,*, Y. Kohata1, T. Tanigawa1, T. Watanabe1, K. Tominaga1,
T. Arakawa1
1
Osaka City University, Osaka, Japan
Contact E-mail Address: yasu@med.osaka-cu.ac.jp
INTRODUCTION: Nighttime reflux is strongly associated with sleep disturbances; however, the detailed characteristics of nighttime reflux occurring
during sleep have not been elucidated.
AIMS & METHODS: The present study aimed to analyze nighttime reflux by
using multi-channel intraluminal impedance pH (MII-pH) monitoring and a
portable electroencephalograph (EEG) in patients with gastroesophageal reflux
disease. Seventeen patients with heartburn and/or regurgitation were examined
by using MII-pH and a portable EEG simultaneously. Nighttime reflux was
divided based on reflux type, acidity, and extent. Phases of nighttime at bed
were divided as follows: (1) recumbent-awake before falling asleep; (2) nonrapid
eye movement (NREM); (3) rapid eye movement (REM); (4) awakening from
sleep; and (5) post-awakening in the morning.
RESULTS: A total of 184 nighttime refluxes were analyzed. Forty-three (23%)
refluxes occurred during recumbent-awake before falling asleep; 28 (15%) during
NREM; 14 (8%) during REM; 86 (46%) during awakening from sleep, with 50
(27%) during long awakening ( 5 min), and 13 (7%) during post-awakening in
the morning. Liquid reflux was common during awakening from sleep, NREM,
and REM. Prevalence of proximal migration was significantly lower in NREM
and REM than in the other phases. There was no difference in acidity and bolus
clearance time among the sleep phases. Nighttime reflux was highly prevalent
during long awakening (19/24, 79%). Among them, eight (42%) refluxes
occurred during the first epoch of long awakening.
CONCLUSION: Different reflux pattern at each phase during nighttime might
explain the pathogenesis of GERD and its related sleep disturbances.
Disclosure of Interest: None declared
P0475 THE CIRCULATING LEVEL OF CYTOKINES IN PATIENTS
WITH DIFFERENT FORMS OF GASTROESOPHAGEAL REFLUX
DISEASE: NON-EROSIVE REFLUX DISEASE, EROSIVE
ESOPHAGITIS AND BARRETTS ESOPHAGUS
Y. Evsyutina1,*, A. Truhmanov1, S. Lyamina2, I. Malyshev2, V. Ivashkin1
Sechenov First Moscow State Medical University., 2Moscow State University of
Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: uselina@mail.ru
1

INTRODUCTION: Non-erosive reflux disease (NERD) and erosive reflux disease (ERD) are the most common phenotypic presentations of gastroesophageal
reflux disease.
AIMS & METHODS: To assess acid and non-acid reflux patterns in patients
with NERD and ERD using combined esophageal pH-impedance monitoring.
133 patients (off acid-suppressive medication) complaining of reflux symptoms
were underwent diagnostic work-up including upper gastrointestinal endoscopy
and ambulatory 24-h esophageal pH-impedance monitoring. According to data
of endoscopy patients were graded to NERD (90 patients (67.6%)) and ERD (43
patients, (32.3%)).
RESULTS: When compared to NERD, ERD patients showed a higher incidence
of acid reflux episodes in 24 h (72 (43;103) vs. 47 (21; 68), p50.05) and higher
duration of total esophageal acid exposure (10.8% (6.6; 19.4) vs. 4.5% (1.4;7.1),
p50.05). Reflux-related acid exposure (pH drops associated with reflux detected
by impedance) in ERD patients was twofold higher than in NERD patients
(2.2% (1.6; 2.9) vs. 1.08% (0.5;1.9), p50.05). Similarly, reflux-related alkaline
exposure (pH elevation (pH47) [1] associated with reflux detected by impedance) was also higher in ERD patients (1.3% (0.8; 1.7) vs. 0.13% (0; 0.49),
p50.05). In contrast to ERD patients, NERD patients had significantly higher
(1.08% (0.46; 1.86) vs. 0.04% (0; 0.2), p50.05) reflux-related weakly acid
exposure (pH drops (pH57) [1] associated with reflux detected by impedance).
When compared with accepted normal values [1] NERD patients had significantly higher mean number of weakly-acid refluxes (41(28;55)). Episodes of
weakly-acid reflux in NERD patients happened mainly at postprandial period.
Median acid (chemical) clearance time was twice higher in ERD patients (120
(76; 166) s.) in comparison to NERDs (60 (49; 116) s.) group. Meanwhile, there
was no significant difference in median volume clearance time between ERD and
NERD patients (23.3 (20.3; 27.6) vs. 19.1 (16.2; 23.6) s, p40.05). In both GERD
groups median volume clearance was significantly faster than median chemical
clearance (p50.05). Meanwhile, esophageal mucosas exposure to reflux volume
during 24 hour period, as assessed by impedance monitoring, was similar in both
ERD and NERD patients (3.8% vs.3.1%, p40.05).
CONCLUSION: While ERD and NERD patients have similar total esophageal
bolus exposure, ERD patients have an increased level of esophageal acid exposure and reflux-related esophageal acid and alkaline exposure due to excessive
number of acid and alkaline reflux as well as long duration of chemical clearance.
Similarly, NERD patients have excessive number of postprandial weakly-acid
reflux and increased level of reflux-related esophageal weakly-acid exposure.
Consequently, this observation tends to support a notion that weakly-acid
reflux is less damaging to esophageal mucosa than acid reflux. Significant

INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the most


common diseases and, according to recent epidemiological studies, clinical and
endoscopic GERD symptoms can be detected in 8-25% of the population
depending on country, race and gender. In the Russian Federation, the prevalence of GERD reaches 11-15%. Despite improvements in diagnosis and treatment of GERD, there are still many unresolved issues. GERD is characterized by
disorders in immune response presented by misbalanced cellular (Th1) and
humoral (Th2) parts of immune response which depend on expression of
cytokines.
AIMS & METHODS: To determinate the circulating level of cytokines in
patients with different forms of gastroesophageal reflux disease (GERD): nonerosive reflux disease (NERD), erosive esophagitis and Barretts esophagus. In
prospective cohort study were included 55 patients and randomized in 4 groups:
group 1 - 20 patients with NERD (11 men, 9 women; average age 37.75 12.04),
group 2 20 patients with erosive esophagitis (13 men, 7 women; average age
38.3312.55), 3 group 5 patients with Barretts esophagus (5 men; average age
34.259.88) and group 4 (control group) 10 healthy volunteers (5 men, 5
women; average age 33.379.39). In all enrolled patients were performed the
upper gastrointestinal endoscopy and the determination of plasma cytokines
(IL-4, IL-8, IL-10, IFN-, TNF-) by flow cytometry. Statistical analyses were
performed using SPSS 17.0 statistical package.
RESULTS: In patients with erosive esophagitis the median rate of IL-8 was 17.54
pg/mL (95% CI, 15.83 to 19.24), IFN- 72.97 pg/mL (95% CI, 15.24 to 130.7),
TNF- 16.31 pg/mL (95% CI, 14.03 to 18.58). The expression of IL-8 in patients
with erosive esophagitis was 2,3 times higher than in patients with NERD
(o 0.02) and 5,04 times higher than in patients with Barretts esophagus
(o 0.02). The expression of IFN- in patients with erosive esophagitis was
2,58 times higher than in patients with NERD (o 0.03) and 27,03 times
higher than in patients with Barretts esophagus (o 0.03). The expression of
TNF- in patients with erosive esophagitis was 2,22 times higher than in patients
with NERD (o 0.04) and 2,26 times higher than in patients with Barretts
esophagus (o 0.05). In patients with Barretts esophagus the median rate of
IL-4 was 14.95 pg/mL (95% CI, 12.75 to 17.15), IL-10 9.2 pg/mL (95% CI,
8.75 to 9.68). The expression of IL-4 in patients with Barretts esophagus was
2.36 times higher than in patients with erosive esophagitis (o 0.03) and 3.33
times higher than in patients with NERD (o 0.05). The expression of IL-10 in
patients with Barretts esophagus was 1.59 times higher than in patients with

A264
erosive esophagitis (o 0.03) and 2.53 times higher than in patients with NERD
(o 0.03).
CONCLUSION: In patients with erosive esophagitis in comparison with NERD
and Barretts esophagus we found overexpression of pro-inflammatory cytokines
(IL-8, IFN-, TNF-), that reflects their role in the Th1 immune response. In
patients with Barretts esophagus in comparison with NERD and erosive esophagitis was the overexpression of anti-inflammatory cytokines (IL-4, IL-10),
that reflects their role in the Th2 immune response.
Disclosure of Interest: None declared
P0476 THE CIRCULATING LEVEL OF CYTOKINES IN PATIENTS
WITH REFRACTORY TO PROTON PUMP INHIBITORS
GASTROESOPHAGEAL REFLUX DISEASE
Y. Evsyutina1,*, A. Trukhmanov1, S. Lyamina2, I. Malyshev2, V. Ivashkin1
1
Sechenov First Moscow State Medical University, 2Moscow State University of
Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: uselina@mail.ru
INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the most
common diseases and, according to recent epidemiological studies, clinical and
endoscopic GERD symptoms can be detected in 8-25% of the population
depending on country, race and gender. In the Russian Federation, the prevalence of GERD reaches 11-15%. 50-60% of patients suffernig from refractory
GERD who despite the received therapy do not have improved clinical and
endoscopic picture, than can be explained with misbalance of Th1 and Th2
parts of immune response which depend on expression of cytokines.
AIMS & METHODS: To determinate the circulating level of cytokines in
patients with GERD depending on the response to standard proton pump inhibitors (PPI) therapy. In prospective cohort study were included 50 patients randomized in 3 groups: group 1 - 20 patients with non- refractory GERD (the
complete response to standard PPI therapy during 8 weeks which was defined
on disappearance of complaints) - 11 men, 9 women; average age 37.6610.02,
group 2 - 20 patients with refractory GERD (the partial response or absence of
response to standard PPI therapy during 8 weeks which was defined on maintenance of complaints) - 12 men, 8 women; average age 38.259.42, and group 3
(control group) 10 healthy volunteers (5 men, 5 women; average age
34.259.88). In all enrolled patients were performed the upper gastrointestinal
endoscopy and the determination of plasma cytokines (IL-4, IL-8, IL-10, IFN-,
TNF-) by flow cytometry. Statistical analyses were performed using SPSS 17.0
statistical package.
RESULTS: In patients with refractory to PPI gastroesophageal reflux disease in
comparison with patients with non- refractory GERD were higher levels of IL-8
(18.10 pg/mL vs. 6.66 pg/mL; o 0.02), IFN- (61.7 pg/mL vs. 24.10 pg/mL;
o 0.022), TNF- (14.77 pg/mL vs. 7.97 pg/mL; o 0.03). The high level of IL-8
is associated with relapse of erosive esophagitis within 2 years (p0.01).
CONCLUSION: In patients with refractory to PPI gastroesophageal reflux disease in comparison with non- refractory GERD was overexpressed IL-8, IFN-,
TNF-. Thus the high level of IL-8 was correlated with recurrent erosive esophagitis within 2 years, and this cytokine can be used as the marker defining the
prediction of a course of a disease.
Disclosure of Interest: None declared
P0477 IS THERE A REAL RISK OF THE LONG TERM MEDICAL
TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE?
R. Kroupa1,*, M. Jecmenova1, M. Dastych1, J. Dolina1, A. Hep1
1
Department of Gastroenterology and Internal medicine, University Hospital Brno
and Faculty of Medicine Masaryks University, Brno, Czech Republic
Contact E-mail Address: rkroupa@fnbrno.cz
INTRODUCTION: A prolonged acid inhibition may be associated with the
important consequences like nutritional defects, increased risk of fractures or
infections and development of gastric polyps. The majority of data originate
from retrospective epidemiological studies only.
AIMS & METHODS: The aim of the study was to prospectively evaluate the
incidence of the possible risk events among patients during the long term acid
suppressive treatment.
A prospective observational study in gastroesophageal reflux disease (GERD)
patients requiring a long term treatment with proton pump inhibitors (PPI) was
performed. The development of fractures, pulmonary and enteric infection and
gastric polyps were recorded. The results were compared with control group
recruited from endoscopy outpatients without any history of the proton pump
inhibitor intake.
RESULTS: The cohort of 230 patients on maintenance GERD treatment (44%
female, age 53.8 14.4) was followed-up for 7.1 years (1631 patient-years).
Results were matched with 209 controls. The users of PPI were equally likely
to develop fractures 3.5% (OR 0.53; 95% CI 0.21-1.32) and bronchopneumonia
0.4% (OR 0.29; 95% CI 0.03-2.87) as the controls. The development of infectious
diarrhea was less frequent in PPI users than in controls (OR 0.11; 95% CI 0.010.09). No case of hypomagnesemia was diagnosed in PPI users. Only a development of fundic gland polyps was associated with PPI use in 12.6% of exposed
patients (OR 2.7; 95% CI 1.07-6.63).
CONCLUSION: A long term acid suppressing treatment of gastroesophageal
reflux disease did not increase the likelihood of fractures, infectious diarrhea,
bronchopneumonia and hypomagnesemia. Our results could encourage the
importance of prospective evaluation of risk events in subgroups according to
the indication of PPI use.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0478 30 MAY BE MORE APPROPRIATE THAN 45 FOR THE
CRITICALLY ILL PATIENTS RECEIVING MECHANICAL
VENTILATION AND ENTERAL NUTRITION
Y. Leng1,*, Y. Liiu1
1
Intensive care unit, Peking University Third Hospital, Beijing, China, Beijing,
China
Contact E-mail Address: lengyuxin1980@126.com
INTRODUCTION: Semi-recumbent position plays a pivotal role in prophylaxis
for the development of ventilator-associated pneumonia in the critically ills. In
the present study, we aimed to find a more appropriate semi-recumbent position
between 30 and 45 for the critically ill patients receiving mechanical ventilation
and enteral nutrition on balancing their advantages in ventilator-associated
pneumonia (VAP) prophylaxis and disadvantages in organ protection.
AIMS & METHODS: A prospective, randomized clinical study to investigate the
effect of different HOB (30 or 45 ) on all extent gastroesophageal reflux, proximal gastroesophageal reflux and development of VAP; intra-abdominal pressure
(IAP), hemodynamic parameters [mean arterial pressure (MAP), abdominal perfusion pressure (APP), filtration gradient (FG)] and development of organ failure
was conducted on 86 consecutive patients admitted to a comprehensive intensive
care unit (ICU).
RESULTS: No significant differences in the incidence of VAP and number of all
extent reflux were found between 30 group and 45 group. However, the number
and percentage of proximal reflux in 45 group were unexpectedly higher than
30 group (Number: acid: p 0.022; weakly acidic: p 0.257; non acid:
p 0.168; Percentage: acid: p 0.000; weakly acidic: p 0.000; non acid:
p 0.000). Patients in 45 group had a trendency to develop new onset organ
failure more easily (45 vs. 30 : 11/42 vs. 5/44, p 0.077), accompanied with
higher IAPs measurement (17.645.32 mmHg vs.14.985.34 mmHg, p 0.023)
and lower MAP, APP, and FG (MAP, p 0.001; APP, p 0.000; FG, p 0.000).
CONCLUSION: For mechanically ventilated patients with enteral nutrition,
keeping the HOB at 45 doesnt show superiority over 30 . Elevating the HOB
from 30 to 45 cant reduce the incidence of VAP effectively but brings new
onset organ failure more easily.
REFERENCES
1. Leng YX, Zhang N, Zhu X, et al. Combined effects of elevated body position
on gastroesophageal reflux and intra-abdominal pressure in mechanical ventilated patients. Chin Crit Care Med 2011; 9: 534-537.
2. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the international conference of experts on intra-abdominal hypertension and abdominal
compartment syndrome: I. Definitions. Intensive Care Med 2006; 32: 1722-1732.
3. Cheatham ML, Malbrain ML, Kirkpatrick A, et al. Results from the international conference of experts on intra-abdominal hypertension and abdominal
compartment syndrome: II. Recommendations. Intensive Care Med 2007; 33:
951-962.
4. Sifrim D, Castell D, Dent J, et al. Gastro-oesophageal reflux monitoring:
review and consensus report on detection and definitions of acid, non-acid,
and gas reflux. Gut 2004; 53: 1024-1031.
Disclosure of Interest: None declared
P0479 DETECTION OF BURIED BARRETTS GLANDS
RADIOFREQUENCY ABLATION (RFA) WITH VOLUMETRIC
LASER ENDOMICROSCOPY (VLE)

AFTER

A.-F. Swager1,*, D.F. Boerwinkel1, D.M. de Bruin2, D.J. Faber2, T.G.


van Leeuwen2, B.L. Weusten1, S.L. Meijer3, J.J. Bergman1, W.L. Curvers1
1
Gastroenterology and hepatology, 2Biomedical Engineering, 3Pathology,
Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: a.swager@amc.uva.nl
INTRODUCTION: The prevalence and clinical relevance of Buried Barretts (BB)
epithelium after radiofrequency ablation (RFA) in Barretts oesophagus (BO) is
questioned. Recent studies using small optical coherence tomography (OCT)
catheters for scanning underneath the neosquamous epithelium demonstrated a
high prevalence of tissue structures that might correspond to BB. Histological
correlation, however, is lacking. Volumetric Laser Endomicroscopy (VLE) is a
novel balloon-based OCT imaging technique that provides a 6-cm long circumferential volumetric scan of the oesophageal wall layers to a depth of 3 mm with a
resolution comparable to low-power microscopy.
AIMS & METHODS: To evaluate if post-RFA subsquamous structures,
detected with VLE, actually correspond to BB and to pursue direct histological
correlation of VLE images.
In-vivo VLE was performed to detect subsquamous structures suspicious for BB
in patients with 100% endoscopic regression of dysplastic Barretts epithelium
after RFA. Areas with suspicious subsquamous VLE structures were marked
with electrocoagulation after which in-vivo VLE was repeated to confirm that
the correct area was demarcated. These areas were subsequently resected endoscopically, followed by immediate ex-vivo VLE scanning to reconfirm the presence of the subsquamous VLE structures. Extensive histological sectioning was
then performed and all histopathology slides were evaluated by an expert BO
pathologist (blinded for VLE images).
RESULTS: In 17 patients, 13 areas with suspicious subsquamous structures were
seen on in-vivo VLE and resected. Ex-vivo VLE of these 13 ER specimens
reconfirmed the presence of these subsquamous structures in 12 ER specimens.
Extensive histological sectioning of these areas showed BB in one area. The other
subsquamous VLE structures corresponded to dilated (ducts of) (sub)mucosal
glands or blood vessels.
CONCLUSION: VLE may potentially detect BB under endoscopically normal
appearing neosquamous epithelium. However, most post-RFA subsquamous
structures identified by in-vivo VLE did not correspond to BB. Further studies

A265

United European Gastroenterology Journal 2(1S)


are required to identify VLE features that allow for differentiation of BB from
normal subsquamous structures.
Disclosure of Interest: None declared
P0480 VOLUMETRIC LASER ENDOMICROSCOPY IN BARRETTS
OESOPHAGUS: A STUDY ON HISTOLOGICAL CORRELATION
A.-F. Swager1,*, D.F. Boerwinkel1, D.M. de Bruin2, G.J. Tearney3,
C.L. Leggett4, B.L. Weusten1, D.J. Faber2, T.G. van Leeuwen2, S.L. Meijer5,
W.L. Curvers1, J.J. Bergman1
1
Gastroenterology and hepatology, 2Biomedical Engineering, Academic Medical
Center, Amsterdam, Netherlands, 3Pathology and Wellman Centre for
Photomedicine, Massachusetts General Hospital, Boston, 4Division of
Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States,
5
Pathology, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: a.swager@amc.uva.nl
INTRODUCTION: Volumetric laser endomicroscopy (VLE) is a novel balloonbased optical coherence tomography (OCT) imaging technique. It provides a 6cm long circumferential volumetric scan of the oesophageal wall layers to a depth
of 3 mm with a resolution that is comparable to low-power microscopy. VLE has
the potential for detection and delineation of early neoplastic lesions in Barretts
oesophagus (BO). In order to investigate this, it is important that structures
identified on VLE can be correlated with histology and -vice versa- that of
areas containing early neoplasia on histology the corresponding VLE features
can be studied. Most previous OCT studies lack such a direct correlation between
histology and OCT images.
AIMS & METHODS: To investigate the optimal approach for one-to-one correlation of VLE images with histology.
BO patients with and without early neoplasia underwent endoscopic resection
(ER) of areas marked in-vivo with electrocoagulation markers (ECM).
Subsequently ER specimens underwent additional ex-vivo marking with several
different markers (ink, pin, ECM) followed by ex-vivo VLE scanning. Tissue
blocks were carefully sectioned guided by the placed markers. After further
histological processing a histopathology slide was sectioned from each block.
When necessary, extensive sectioning of tissue blocks was performed in order
to visualize all markers that were included in the tissue block on histology. All
histopathology and VLE slides were evaluated by 2 researchers and considered a
match if a)  2 markers were visible on both modalities and b) mucosal patterns
aside from these markers matched on both histology and VLE. All slides were
evaluated by an expert BO pathologist.
RESULTS: From 16 ER specimens (overall diagnosis: 7 non-dysplastic BO, 9
dysplastic BO (1 LGD, 4 HGD, 4 EAC)) 120 tissue blocks were sectioned of
which 57 contained multiple markers and thus could potentially be matched with
VLE. Based on several combinations of these markers in total 14 histology-VLE
matches could ultimately be constructed. Markers that achieved the best yield of
matches respectively were: in-vivo placed ECMs (8 matches with 12 markers),
pins (7 with 11), and ink (4 with 5). Histopathological evaluation was not hindered by marker use. In this pilot study the last 6 ER specimens yielded 9/14
matches demonstrating a clear learning curve due to methodological improvements in marker placement and tissue block sectioning.
CONCLUSION: One-to-one correlation of VLE and histology is complex but
feasible. The groundwork laid in this study will provide high-quality histologyVLE correlations that will allow further research on VLE structures and VLE
features of early neoplasia in BO.
Disclosure of Interest: A.-F. Swager: None declared, D. Boerwinkel: None
declared, D. de Bruin: None declared, G. Tearney Financial support for research
from: Ninepoint Medical, Other: Massachusetts General Hospital has a licensing
arrangement with Ninepoint Medical. Dr. Tearney has the rights to receive royalty income from this licensing arrangement., C. Leggett: None declared, B.
Weusten Financial support for research from: Ninepoint Medical, Other: Has
rights to receive royalty income from licensing arrangement between
Massachusetts General Hospital and Ninepoint Medical, D. Faber: None
declared, T. van Leeuwen: None declared, S. Meijer: None declared, W.
Curvers: None declared, J. Bergman: None declared

P0481 SENSITIVITY
TO
OESOPHAGEAL
MULTIMODAL
STIMULATION IN BARRETTS OESOPHAGUS PATIENTS
C. Lottrup1,*, A.L. Krarup1, P. Ejstrud2, M. Ostapiuk2, A.M. Drewes1
1
Mech-Sense, Department of Gastroenterology & Hepatology, 2Department of
Surgery, Aalborg University Hospital, Aalborg, Denmark
Contact E-mail Address: chlo@rn.dk
INTRODUCTION: Oesophageal sensitivity to mechanical and acid stimulation
in Barretts oesophagus has previously been shown to be decreased.
AIMS & METHODS: The aim was to investigate the oesophageal sensitivity in
Barretts oesophagus using a multimodal (mechanical, thermal, electrical, acid)
pain model.
Twenty-two patients with Barretts oesophagus (mean age: 64.6 years) were
compared to twelve healthy controls (mean age: 54.3 years) using oesophageal
multimodal pain stimulation following upper endoscopy. A probe with a polyurethane bag was placed in the lower oesophagus. The probe was then used to
apply mechanical, thermal, and electrical stimulation as well as a modified
Bernstein test with infusion of 0.1 N HCl. All stimulations were stopped when
the subject felt moderate pain, defined as 7 out of 10 on a visual analogue scale
(VAS 7).
RESULTS: Five of the Barretts oesophagus patients had oesophagitis (Los
Angeles grade A or B) on endoscopy.
For mechanical stimulation, the bag distension volume evoking VAS 7 was
significantly higher in the Barretts group (mean volume 42 vs 28 mL,
P 0.006). For thermal stimulation, there was a non-significant tendency in the
Barretts group towards a higher area under the curve to reach VAS 7 (949 vs.
677 s*oC, P 0.14). The stimulus required to reach VAS 7 during electrical
stimulation was significantly higher in the Barretts group (32.7 mA vs. 21.9
mA, p 0.03. During the modified Bernstein test, the acid volume required to
reach VAS 7 or a maximum infusion volume of 200 mL was lower in the
Barretts group (mean 77 vs. 127 mL, P 0.03). The time passed before feeling
the first burning sensation during acid infusion was shorter in the Barretts group,
but just failed to be significant (181 vs. 329 seconds, P 0.056).
The referred pain area defined by the subject immediately after sensing VAS 7
was insignificant between groups (P 4 0.05) for all 4 stimulation modalities.
CONCLUSION: Barretts oesophagus patients showed hyposensitivity to
mechanical, thermal and electrical stimulation, but hypersensitivity to acid stimulation. This is to some degree different from earlier findings, but the latter
finding could indicate a sensitisation to acid because of oesophagitis underlying
the disease.
Disclosure of Interest: None declared
P0482 SURVEILLANCE IN PATIENTS WITH BARRETTS ESOPHAGUS:
A COST-EFFECTIVENESS ANALYSIS
F. Kastelein1,*, S.van Olphen1, E. Steyerberg2, M. Spaander1, C. Looman2,
E. Kuipers1, M. Bruno1, E.de Bekker-Grob2 on behalf of ProBar-study group
1
Gastroenterology and Hepatology, 2Public health, ERASMUS UNIVERSITY
MEDICAL CENTER, Rotterdam, Netherlands
Contact E-mail Address: f.kastelein@erasmusmc.nl
INTRODUCTION: Surveillance is recommended for Barretts esophagus (BE)
to detect esophageal adenocarcinoma (EAC) at an early stage.
AIMS & METHODS: The aim of this study was to evaluate the cost-effectiveness of surveillance intervals and treatment strategies. 714 BE patients were
included in a multicenter prospective cohort study and followed during surveillance according to the ACG guidelines. We used a multi-state-Markov model to
calculate misclassification and true progression rates from no dysplasia (ND) to
low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC. These progression rates were incorporated in a decision-analytic model, which included
costs and quality of life data associated with different surveillance strategies.
We evaluated different surveillance intervals for ND and LGD, endoscopic
mucosal resection (EMR) followed by radiofrequency ablation (RFA), RFA
alone or esophagectomy for HGD or early EAC and esophagectomy with neoadjuvant chemoradiotherapy for advanced EAC. The incremental cost-effectiveness
ratio (ICER) was calculated in costs per quality-adjusted life year (QALY). The
willingness-to-pay threshold was set at E35.000 per QALY gained.

P0482
No dysplasia
Strategy
No surveillance
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every
Surveillance every

5 years with RFA


5 years with EMR and RFA
5 years with esophagectomy
4 years with RFA
4 years with EMR and RFA
4 years with esophagectomy
3 years with RFA
3 years with EMR and RFA
3 years with esophagectomy
2 years with RFA
2 years with EMR and RFA
2 years with esophagectomy
year with RFA
year with EMR and RFA
year with esophagectomy

Low-grade dysplasia

Costs

QALYs

ICER

Costs

QALYs

ICER

E5.695
E6.904
E7.139
E13.965
E7.695
E7.951
E15.229
E8.868
E9.148
E16.890
E10.831
E11.143
E19.325
E14.898
E15.257
E23.686

12.62
12.87
12.87
12.64
12.89
12.89
12.63
12.90
12.90
12.61
12.90
12.90
12.59
12.89
12.89
12.54

E4.823
E61.821
E104.668
E321.880

E21.806
E25.709
E27.447
E50.909
E28.006
E29.959
E51.835
E30.973
E33.210
E52.851
E34.956
E37.575
E53.960
E40.542
E43.688
E55.159

10.95
11.91
11.91
11.33
11.99
11.99
11.34
12.09
12.09
11.34
12.19
12.19
11.34
12.27
12.27
11.34

E4.040
E28.741
E31.073
E39.633
E72.257

A266
RESULTS: The true annual progression rate for ND to LGD was 0.02, for LGD
to HGD or early EAC 0.03 and for HGD or early EAC to invasive EAC 0.36. In
patients with ND, surveillance every five or four years with RFA for HGD or
early EAC and esophagectomy for advanced EAC had ICERs of E4.800 and
E61.800 per QALY respectively. Strategies with shorter intervals provided higher
costs with similar QALYs gained. In patients with LGD, surveillance every five
to two years had ICERs of E4.040, E28.741, E31.073, and E39.633 per QALY
respectively. EMR prior to RFA was slightly more expensive, but had additional
value for tumor staging.
CONCLUSION: Surveillance with EMR and RFA for HGD or early EAC and
esophagectomy for advanced EAC is cost-effective with 5-year intervals for
patients with ND and 3-year intervals for patients with LGD, based on a willingness-to-pay threshold of E35.000 per QALY.
Disclosure of Interest: None declared
P0483 BOTH ESOPHAGEAL POSTERIOR AND RIGHT WALL ARE THE
PREFERRED LOCALIZATIONS OF BARRETTS ESOPHAGUS
S. Bibbo`1, G. Ianiro1,*, L. Petruzziello2, C. Spada2, A. Larghi2, M.E. Riccioni2,
A. Gasbarrini1, G. Costamagna2, G. Cammarota1
1
Dept of Internal Medicine, Division of Gastroenterology, 2Department of Surgery
- Endoscopy Unit, CATHOLIC UNIVERSITY SCHOOL OF MEDICINE,
ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: Prevalence of Barretts esophagus (BE) is higher in patient
with gastroesophageal reflux disease (GERD) with a rate of prevalence of 10%.
The risk of cancer associated to this condition is estimated to be approximately
0.5% per year. For this reason a careful endoscopic surveillance assumes a
paramount importance. Only few literature data on the preferred esophageal
location of BE are available to date.
AIMS & METHODS: The aim of this study is to identify the preferred area
where BE can develop within esophageal circumference. We retrospectively analyzed patients with BE who underwent upper endoscopy between January 2010
and March 2014 at our Endoscopy Center. We included only patients with short
BE. In the case of multiple BE tongues, each lesion was considered individually.
The circumferential localization of the lesions was determined according to the
numbers of a clock face.
RESULTS: In the study period, a total of 204 subjects were newly diagnosed of
BE or had an endoscopic follow-up of BE. Twenty-four patients with circumferential lesions were excluded. Among the 180 remaining patients, multiple BE
lesions were diagnosed in 110 of them, for a total amount of 332 areas of mucosal
metaplasia. Our analysis of data showed a clear prevalence of BE in the position
near 3 oclock and 6 oclock of the endoscopic image. The area between 5 and 7
oclock (posterior wall) was the most affected (38.25% of the lesions). Other
localizations were respectively the arc between 2 and 4 oclock (right wall) with
27.71%, the arc 11 to 1 oclock 23.80% (anterior wall) and the arc 8 to 10 oclock
10.24% (left wall). For each of the four walls, difference between observed and
expected (dividing equally the number of lesions for the number of quadrants)
lesions was statistically significant (P50.0001 for each wall). Lesions were most
commonly located in the right (1 to 6 oclock) than in the left (7 to 12 oclock)
quadrant (207 versus 125 two-tailed P value 0.0189).
CONCLUSION: We first describe, in a large cohort of Italian patients, an
uneven localization of BE in the distal esophageal circumference, with an
higher prevalence on the posterior-right wall. Anatomical and environmental
factors could explain this finding. The circumferential asymmetry of LES pressure (in particular, a lower pressure on the right quadrant) and the preference of
supine position during sleep are two situations that may promote the reflux of
gastric fluids preferably in the right and posterior wall of the distal esophagus. A
more accurate observation of such areas during endoscopic surveillance is advisable in GERD patients.
Disclosure of Interest: S. Bibbo`: nothing to declare, G. Ianiro: nothing to declare,
L. Petruzziello: nothing to declare, C. Spada: nothing to declare, A. Larghi: nothing to declare, M. E. Riccioni: nothing to declare, A. Gasbarrini: nothing to
declare, G. Costamagna: nothing to declare, G. Cammarota: nothing to declare
P0484 A STUDY ON THE LONG-TERM PROGNOSIS AND
PERFORMANCE ENDOSCOPIC SUBMUCOSAL DISSECTION FOR
ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA
H. Kaneko1,*, K. HIRASAWA1, R. KOBAYASHI1, M. MAKAZU1, C. SATO1,
A. KOKAWA1, S. MAEDA2
1
Division of Endoscopy, Yokohama City University Medical Center, 2department
of gastroenterology, Yokohama City University graduate school of medicine,
yokohama, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) was becoming
widespread as a treatment option for superficial adenocarcinoma of the esophagogastric junction (EGJ) including Barretts esophageal adenocarcinoma; however, its long-term and treatment outcomes have not been fully evaluated.
AIMS & METHODS: The aim of this study was to assess the long-term and
treatment outcomes of ESD for patients with superficial adenocarcinoma of the
EGJ.
Between September 2000 and December 2013, we performed ESD for 104 superficial adenocarcinoma of EGJ (type II tumor according to Siewerts classification)
in 103 patients. The rates of en bloc resection, positive for lateral and/or vertical
margin, curative resection, and overall and disease-specific survival rate after ESD
were evaluated during follow-up (median observation period 55.6 months).
We divided all patients into two groups, the adenocarcinoma of Barretts esophagus (BE group: 20 lesions in 20 patients) and other adenocarcinoma of EGJ
(Non-BE group: 84 lesions in 83 patients), then each outcomes were evaluated.

United European Gastroenterology Journal 2(1S)


RESULTS: All lesions were treated by en bloc resection. None of BE group were
positive lateral margin and 7 of Non-BE group were positive lateral margin.
The rate of curative resection was 74% (77/104) in all patients, and BE group and
Non-BE group were 74% and 75%, respectively. The most frequent cause of
non-curative resection was tumor invasion into the deep submucosa.
Ninety three patients (93%) were traceable prognosis, and 5 year overall survival
rate was 91.2%. When we limited to the curative resections, 5 year overall survival rates were 66.7% in BE group and 89.4% in Non-BE group. There was no
death of adenocarcinoma of EGJ, meaning that the disease-specific survival rate
was 100%.
There was no statistical difference of the rate of positive margin, curative resection and 5 year overall survival rates between BE and Non-BE groups.
CONCLUSION: The treatment outcomes of ESD for adenocarcinoma of EGJ
were favorable regardless of the evidence of Barretts esophagus. However, the
curative resection rate was relatively low. It was assumed that pre-operative
recognition of the tumor invasion into the submucosa might be difficult for
adenocarcinoma of EGJ.
Disclosure of Interest: None declared
P0485 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE
MANAGEMENT OF PATIENTS WITH BARRETTS ESOPHAGUS: A
CLINICAL EVIDENCE-BASED CONSENSUS REPORT
J.P. Galmiche1, R. Arsenescu2, H. Bertani3, F. Caillol4, D. Carr-Locke5,
K. Chang6, E. Coron1,*, A. Dlugosz7, S. I. Gan8, M. Giovannini4, F.G. Gress9,
K. Ho10, V. Konda11, H. Neumann12, F. Prat13, P. Sharma14, S. Singh15,
K. Wang16, H. Wholfsen17
1
CHU Nantes, Nantes, France, 2Ohio State University Medical Center, Columbus,
United States, 3Nuovo Ospedale Civile SantAgositno Estense, Modena, Italy, 4I.
P. C, Marseille, France, 5Beth Israel Medical Center, New York, 6University of
California Irvine Medical Center, Irvine, United States, 7Karolinska University
Hospital Huddinge, Stockholm, Sweden, 8Virginia Mason Medical Center, Seattle,
9
N. Y Presbyterian Columbia University Medical Center, Brooklyn, United States,
10
National University Hospital, Singapore, Singapore, 11The University of Chicago
Medical Center, Chicago, United States, 12Universitatsklinikum Erlangen,
Erlangen, Germany, 13Cochin, Paris, France, 14VA Kansas City Medical Center,
Kansas City, 15VA Boston Healthcare System, Jamaica Plain, 16Mayo Clinic,
Rochester, 17Mayo Clinic, Jacksonville, United States
Contact E-mail Address: galmiche.jean-paul@orange.fr
INTRODUCTION: Confocal Laser Endomicroscopy (CLE) is a recent technology that provides microscopic imaging during endoscopy, thus in vivo and in real
time. The currently recommended Seattle protocol is intended to provide a comprehensive mapping of the Esophagus, but its inherent constraints have impaired
its application. CLE allows for unlimited sampling of the esophageal mucosa and
several recently published studies have shown its ability to provide a comprehensive assessment of Barretts Esophagus (BE) lesions.
AIMS & METHODS: The aim of thi study is to develop consensus recommendations on the role of CLE in the management of patients with BE.
Initial statements on the use of CLE for the characterization of BE were developed by a single CLE expert based on the available clinical evidence. Those
preliminary statements were edited and submitted by an external group of 20
GI physicians experts in CLE using a modified Delphi approach. After two
rounds of votes based on relevant data, quality of the evidence and strength of
recommendation, statements were validated if the threshold of agreement was
higher than 75%.
RESULTS: 12 recommendations were adopted and 4 were rejected. CLE should
be considered in the evaluation of BE. CLE is clinically indicated in patients with
BE dysplasia in lesions initially identified in surveillance, with or without electronic enhancement. CLE is able to distinguish cardia from intestinal metaplasia
(IM), based on the presence/absence of goblet cells. CLE is superior to WhiteLight Endoscopy (WLE) in identifying IM. A negative CLE random sampling in
an endoscopically benign appearing Esophagus is sufficient to reduce the need
for a physical biopsy in patients with known BE. CLE can improve the yield for
neoplasia compared to standard WLE and random biopsies. CLE and WLE
targeted biopsies are superior to WLE targeted biopsies alone in the detection
of dysplasia. A positive CLE random sampling in an endoscopically neoplastic
appearing Esophagus is sufficient for therapeutic intervention. CLE can be used
to define location and lateral extent of neoplasia prior to therapy. CLE should be
cited as a valuable tool for an increased diagnostic yield in official surveillance
guidelines. CLE should be combined with red flag techniques.
CONCLUSION: The panel of experts that participated in this initiative strongly
believes that Confocal Laser Endomicroscopy is an important adjunct to the
current endoscopy practice. This technique can improve the management of
patients by more accurately characterizing neoplasia, identifying residual neoplasia in post-treatment surveillance and rationalizing the choice of the most appropriate treatment. This consensus report is based on a review of the clinical
evidence and on a consensus opinion.
Disclosure of Interest: J. P. Galmiche Consultancy for: Mauna Kea Technologies,
R. Arsenescu: None declared, H. Bertani: None declared, F. Caillol: None
declared, D. Carr-Locke: None declared, K. Chang Other: Medical Advisory
Board Mauna Kea Technologies, E. Coron Consultancy for: Has served as a
consultant for Mauna Kea Technologies, A. Dlugosz: None declared, S. I. Gan:
None declared, M. Giovannini: None declared, F. G. Gress: None declared, K.
Ho: None declared, V. Konda Other: Honorary for Mauna Kea Technologies,
H. Neumann: None declared, F. Prat: None declared, P. Sharma: None declared,
S. Singh: None declared, K. Wang: None declared, H. Wholfsen: None declared

A267

United European Gastroenterology Journal 2(1S)


P0486 COST-EFFECTIVENESS
OF
CONFOCAL
ENDOMICROSCOPY (CLE) FOR THE MANAGEMENT OF
BARRETTS ESOPHAGUS

LASER

C.L. Pen 1, J.P. Galmiche2,*, E. Coron 2


1
Universite Paris Dauphine, Paris, 2CHU Nantes, Nantes, France
Contact E-mail Address: claude.lepen@wanadoo.fr
INTRODUCTION: The clinical impact of CLE has been demonstrated for the
management of patients undergoing surveillance or treatment of Barretts
Esophagus. This study is the first one evaluating the economic impact of using
CLE in clinical practice in a European healthcare system.
AIMS & METHODS: The aim of this study was to evaluate the cost-effectiveness of a CLE-based strategy compared to the standard Seattle protocol for the
management of patients with Barretts Esophagus and suspicion of neoplasia, in
the setting of the French public healthcare system.
We used the data published by Canto et al (1) on a multicentric randomized
controlled trial which compared 2 strategies: (i) high definition white light endoscopy (HD-WLE) CLE and targeted physical biopsies (CLE-based strategy)
and (ii) HD-WLE and random physical biopsies (Standard strategy). In that
study, the CLE-based strategy had a higher sensitivity for the diagnosis of
HGD/EC (95 versus 40%) without significant change in specificity (92%
versus 98% respectively). The average number of biopsies performed was
reduced from 5.91 to 1.26 per patient by the use of CLE. These data were entered
into a health economics model (piggyback study) to compare the costs of both
strategies when performed in public academic hospitals. French costs were associated to each procedure in order to estimate the medical cost of the two strategies from a public health payer perspective. CLE was priced as a therapeutic
endoscopy procedure that is valued 20% more than a standard diagnostic
endoscopy.
RESULTS: In spite of a higher procedure cost, the total costs for a cohort of 100
patients associated to the CLE-based strategy were 89,313.29 E compared to
90,658.90 E for the standard strategy. The cost per patient adequately diagnosed
and treated was also inferior for the CLE-based strategy (960.36 E vs. 1,054.17
E). Different sensitivity analyses (including a Monte-Carlo modeling) were performed which confirmed the robustness of previous results.
CONCLUSION: In the restricted context of this evaluation, the CLE-based
strategy is not only more effective but also less costly than the standard strategy
i.e. corresponding to the definition of a dominant strategy.
REFERENCES
1. Canto MI, Anandasabapathy S, Brugge W, et al. In vivo endomicroscopy
improves detection of Barretts esophagus-related neoplasia: a multicenter international randomized controlled trial (with video). Gastrointest Endosc 2014; 79:
211-221.
Disclosure of Interest: C. Le Pen Consultancy for: Work as a consultant for
Mauna Kea Technologies, J. P. Galmiche Consultancy for: Work as a consultant
for Mauna Kea Technologies, E. Coron Consultancy for: Was consultant for
Mauna Kea Technologies
P0487 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL
BARRETTS ESOPHAGUS ADENOCARCINOMA: CLINICAL
OUTCOMES IN A LARGE SERIES OF EUROPEAN PATIENTS
J.-B. Chevaux1,*, H. Piessevaux1, A. Jouret-Mourin2, R. Yeung1, E. Danse3,
P.H. Deprez1
1
Hepato-Gastroenterology, 2Pathology, 3Radiology, Cliniques universitaires SaintLuc, Universite catholique de Louvain, Brussels, Belgium
Contact E-mail Address: jeanbaptistechevaux@gmail.com
INTRODUCTION: The role of endoscopic submucosal dissection (ESD) in
Barretts neoplasia has not yet been well defined, although this technique
could potentially achieve a higher curative resection rate and improved histological assessment compared to endoscopic mucosal resection (EMR).
AIMS & METHODS: This study sought to assess ESD efficacy, safety, and
long-term results in a large patient cohort. Seventy-five consecutive Barretts
esophagus (BE) patients who underwent ESD between January 2007 and
February 2014 were retrospectively analyzed. ESD was performed for either
visible lesions that were multiple, over 15mm, or poor-lifting, or for suspected
submucosal infiltration. Primary endpoint was curative resection rate of carcinoma (CRC).
RESULTS: Median patient age was 68 years (IQR, 61-76), median patient
follow-up was 20 months (IQR, 8.5-37.5), and median maximum specimen diameter was 52.5mm (IQR, 43-71). Median maximum diameter of visible lesion was
20mm (IQR, 10-30). En bloc resection and CRC rates were 90% and 85%,
respectively. G3 differentiation and invasion 4pT1m2 were observed in 25%
and 55% of cases, respectively. Five early (548h) adverse events occurred
(two delayed hemorrhages; three perforations), all treated endoscopically. No
ESD-specific death was observed. Esophageal strictures manifested in 60% of
patients, all treated endoscopically. Additional treatment methods for residual
BE were proposed to 64% of patients, with a median number of two sessions
(IQR, 2-3). At latest follow-up, complete remission of neoplasia and intestinal
metaplasia was achieved in 92% and 73%, respectively.
CONCLUSION: ESD appears to be safe and effective, with a high curative
resection rate. ESD should be the favored treatment for Barretts neoplasia
cases at risk of incomplete resection or poor pathology assessment with conventional EMR.
Disclosure of Interest: None declared

P0488 AUTOFLUORESCENCE-TARGETED PROBE-BASED CONFOCAL


LASER ENDOMICROSCOPY CAN DETECT THE FIELD OF
MOLECULAR CHANGE IN BARRETTS OESOPHAGUS
M. Di Pietro1,*, E. Bird-Lieberman2, M. ODonovan1, H. Bertani3,
R. Fitzgerald1
1
MRC CANCER UNIT - University of Cambridge, Cambridge, 2Oxford
University Hospital, Oxford, United Kingdom, 3Endoscopy, Nuovo Ospedale Civile
S. Agostino Estense, Modena, Italy
INTRODUCTION: Probe-based confocal laser endomicroscopy (pCLE) allows
optical biopsies in Barretts oesophagus (BO) to predict histological outcome but
it is subject to sampling error if performed in a random fashion. We used autofluorescence imaging (AFI) to direct pCLE and added molecular biomarkers to
the histopathological diagnosis.
AIMS & METHODS: The aims of this study were to assess the diagnostic
accuracy for dysplasia of AFI-targeted optical biopsies and to investigate the
correlation between pCLE patterns and field of molecular change.
53 patients with BO (non-dysplastic BO n 22, indefinite for dysplasia (ID)
n 5, low grade dysplasia n 13, high grade dysplasia (HGD) or intramucosal
cancer (IMC) n 13) were recruited at a single centre. Patients underwent highresolution endoscopy followed by AFI and then pCLE was performed on AFI
positive (AFI) areas. Targeted biopsies were taken from AFI areas, followed
by random biopsies as per Seattle protocol. pCLE sequences were graded according to published criteria. Cyclin A and p53 expression were assessed by immunohistochemistry and aneuploidy by flow-cytometry on AFI-targeted biopsies.
Statistical analyses were performed using chi-square test
RESULTS: AFI-targeted pCLE correctly classified all the HGD/EC patients and
had a sensitivity and specificity for any grade of dysplasia of 94% and 86%,
respectively. The Seattle protocol had similar sensitivity for HGD/IMC and any
grade of dysplasia (85% and 92.5%, respectively). For the per-location analysis,
a total of 185 endoscopic areas were analyzed with pCLE and molecular biomarkers. pCLE had a sensitivity and a specificity for HGD/IMC and any grade of
dysplasia of 100%/67% and 77%/77%, respectively. Overall, 40% of pCLE
irregular sequences corresponded to non-dysplastic areas (false positive). We
found a statistically significant enrichment (p50.001) of the three molecular
biomarkers in pCLE irregular areas. After exclusion of dysplastic areas, a significant correlation between pCLE irregularity and biomarker positivity was
retained (p 0.008). The presence of at least 1 positive biomarker significantly
correlated with dysplasia both in pCLE irregular (p 0.01) and pCLE regular
areas (p 0.05). Using a cut-off of two positive biomarkers, this panel classified
as high risk all the patients with HGD/IMC and 45% of patients with LGD, but
none of the patients with ID and non-dysplastic BO
CONCLUSION: AFI-targeted pCLE has a high diagnostic accuracy for dysplasia in BO. Tissue biomarkers are a useful adjunct to characterize the field of
molecular abnormality associated with optical dysplasia. These results suggest
that the presence of pCLE irregularity, even in the absence of histological dysplasia, relates to molecular changes and may warrant close follow up. A 3-biomarker is a useful adjunct to optical biopsy to provide further stratification
Disclosure of Interest: None declared
P0489 ROLE
OF
BODY
COMPOSITION
AND
DYSFUNCTION IN BARRETTS OESOPHAGUS AND
PROGRESSION TO CANCER

METABOLIC

S. Di Caro1,*, L. Fini2, W.H. Cheung3, R. Haidry1, M. Keane1, L. Lovat1,


R. Batterham3, M. Banks1
1
Gastroenterology, UNIVERSITY COLLEGE HOSPITAL, LONDON, UK,
London, United Kingdom, 2Gastroenterology, Busto Arstizio Hospital, Milan,
Italy, 3Centre for Obesity Research, UNIVERSITY COLLEGE HOSPITAL,
LONDON, UK, London, United Kingdom
Contact E-mail Address: Simona. DiCaro@uclh.nhs.uk
INTRODUCTION: Oesophageal adenocarcinoma (OAC) arises within Barretts
oesophagus (BE). Obesity is associated with metabolic syndrome (MS) and
cancer progression. Body composition has a direct impact in obesity-related
diseases. Normal weight individuals with increased fat mass are considered metabolically obese.
AIMS & METHODS: To evaluate the prevalence of obesity, altered body composition and metabolic indexes in patients (pts) with and without BE; and association with cancer progression in BE.
In sequential pts undergoing gastroscopy, MS, waist/hip ratio (WHR) and body
fat% (BF by bioimpedance analysis) were obtained. In BE pts, histological findings were correlated with metabolic data. Pts were classified according to Body
Mass Index (BMI), abdominal obesity (AO by WHR) and in females, Normal
Weight Obese (NWO). Identified risk factors significantly associated with BE at
univariate analysis were subsequently entered into a multivariate logistic regression analysis.
RESULTS: 250 cases and 230 controls (F/M: 193/287) were enrolled. Age (cut
off: 57 years) and male gender (M/F 193/57; OR 5.01, p50.0001) were identified
risk factors for BE. AO (76 vs 51%; OR 3.13; p50.001), increased BF% (30.7 vs
17.6%; p 0.001), higher BMI (overweight: 39.6 vs 30%; OR 2.09; p 0.0008;
obese: 32 vs 22%; OR 2.3; p 0.004) and MS (33.2 vs 20%; OR 1.95; p 0.0017)
were significantly associated with BE. A positive trend, possibly related to the
small number of female cases, was demonstrated for NWO (28.1 vs 19.1%; OR
1.06; p 0.1). More cases were affected by hypertension (37.4 vs 21.3%; OR 2.4;
p5 0.001) and hyperlipidaemia (72.8 vs 53.9%; OR 2.28; p50001) but not
diabetes.
When adjusted by gender, age and race into a multivariate analysis, independent
risk factors for BE were BF% (OR 1.90; p 0.01) and AO (OR 1.67; p 0.03).

A268
Metaplasia and dysplasia were present in 57.2 and 42.8%. AO was the only
metabolic parameter independently correlated with high grade dysplasia (38 vs
21%; OR 2.44; p 0.001).
CONCLUSION: Abdominal obesity, and body fat mass are strong risk factors
for BE. A positive trend association was demonstrated in NWO. Furthermore,
abdominal adiposity plays a role in progression to OAC. BE might therefore be
considered in the metabolic syndrome spectrum and as such, in this group screening interventions may be considered.
REFERENCES
1. Ryan AM, Healy LA, Power DG, et al. Barrett esophagus: prevalence of
central adiposity, metabolic syndrome, and a proinflammatory state. Ann Surg
2008; 247: 909-15.1.
2. Anand G and Katz PO. Gastroesophageal reflux disease and
obesity.Gastroenterol Clin North Am 2010; 39: 39-46.
3. De Lorenzo A, Del Gobbo V, Premrov MG, et al. Normal-weight obese
syndrome: early inflammation? Am J Clin Nutr 2007; 85: 40-45.
4. Kendall B, Macdonald G, Hayward N, et al. The risk of Barretts oesophagus
associated with abdominal obesity in males and females. Int J Cancer 2013; 132:
2192-2199.
Disclosure of Interest: None declared
P0490 A NOVEL ENDOSCOPIC CLASSIFICATION SYSTEM USING ISCAN IMPROVES DYSPLASIA DETECTION IN BARRETTS
OESOPHAGUS
V. Sehgal1,*, D. Graham1, M. Banks1, R. Bisschops2, K. Ragunath3, L. Lovat1,
R. Haidry1
1
Gastroenterology, University College London Hospital (UCLH), London, United
Kingdom, 2Gastroenterology, University Hospitals Leuven, Leuven, Belgium,
3
Gastroenterology, Queens Medical Centre, Nottingham, United Kingdom
Contact E-mail Address: v.sehgal@ucl.ac.uk
INTRODUCTION: Dysplasia arising in Barretts oesophagus (BE) can lead to
oesophageal adenocarcinoma. Endoscopic surveillance is performed to detect
dysplasia in BE so early treatment can be offered. Current practice relies on
white-light endoscopy (WLE) to obtain random quadrant biopsies every 2cm
from the BE segment, sampling less than 5% of the surface and therefore potentially missing areas of dysplasia.
An endoscopic image enhancement technology, i-Scan (PENTAX HOYA,
Japan), has been developed to help improve lesion recognition in the gastrointestinal tract. i-Scan utilises post-processing light filtering technology to provide
real-time analysis and enhancement of different elements of the mucosa and
microvasculature to improve dysplasia detection.
Previous endoscopic classification systems for BE have used image enhancement
technologies combined with magnification endoscopy. We report the accuracy of
a novel classification system using i-Scan without magnification amongst expert
endoscopists based at 3 high-volume European tertiary referral centres for detecting BE dysplasia.
AIMS & METHODS: High definition (HD) video recordings were collected
from patients with non-dysplastic (ND-BE) and dysplastic (D-BE) BE undergoing endoscopy at University College London Hospital. A protocol was used to
record areas of interest and a corresponding biopsy was taken to confirm
pathology.
A simple classification system based on mucosal (M) and vascular (V) patterns
was used: M1 or M2 - regular oval or villous pits respectively (ND-BE), M3
irregular or featureless mucosa (D-BE); V1 regular vessels (ND-BE), V2
irregular (dilated, corkscrew) vessels (D-BE).
In a blinded manner, videos of normal and abnormal lesions were interpreted by
3 expert endoscopists using the above classification. Predicted pathology was also
recorded for each lesion. Acetic acid (ACA) chromoendoscopy was used in some
cases. Agreement in relation to predicted histology was calculated using 
statistics.
RESULTS: Videos from 47 patients (including 13 before and after ACA to
generate 60 videos in total) were analysed. 24 were ND-BE and 23 D-BE.
Cases in which ACA was used, 7 had ND-BE and 6 D-BE.
Experts accuracy for detection of D-BE and ND-BE was 69% (6272%) and
68% (39-80%) respectively. The sensitivity and specificity for dysplasia detection
using our classification system were both 68%. ACA improved the sensitivity and
specificity to 78% and 71% respectively. Inter-observer agreement for dysplasia
prediction in all cases was moderate ( 0.42) but improved to good ( 0.70)
with ACA.
CONCLUSION: Using a simple non-magnification endoscopic classification
system combined with i-Scan and ACA, experts are able to accurately diagnose
D-BE in 78% of cases. ACA chromoendoscopy appears to improve the sensitivity and inter-observer agreement for dysplasia detection over HD-WLE alone.
These data are comparable to similar classification systems using zoom enhanced
imaging and ACA previously published and could be used by the general endoscopists performing BE surveillance to target sampling and improve dysplasia
detection. The addition of zoom endoscopy to i-scan has the potential to increase
the accuracy further.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0491 IMPACT OF ABLATION VS. SURVEILLANCE ON QUALITY OF
LIFE AND ILLNESS PERCEPTION IN PATIENTS WITH BARRETTS
OESOPHAGUS CONTAINING LOW-GRADE DYSPLASIA: A MULTICENTER RANDOMISED CONTROLLED TRIAL
W. Rosmolen1,*, N. Phoa1, P. Nieuwkerk2, B. Weusten1,3, R. Bisschops4,
E. Schoon5, M. Sprangers 2, J. Bergman1
1
Gastroenterology and Hepatology, 2Medical Psychology, Academic Medical
Center, Amsterdam, 3Gastroenterology and Hepatology, Antonius Hospital,
Nieuwegein, Netherlands, 4Gastroenterology and Hepatology, University Hospital
Leuven, Leuven, Belgium, 5Gastroenterology and Hepatology, Catharina Hospital,
Eindhoven, Netherlands
Contact E-mail Address: j.j.bergman@amc.nl
INTRODUCTION: Patients with a confirmed histological diagnosis of lowgrade dysplasia in Barretts oesophagus have an increased risk of neoplastic
progression to high-grade dysplasia and oesophageal adenocarcinoma. We
recently reported on a multi-center randomised controlled trial, in which endoscopic radiofrequency ablation reduced neoplastic progression from 26.5% to
1.5% compared to endoscopic surveillance. As part of this trial, we prospectively
investigated whether these approaches also lead to differences in quality of life
and illness perception.
AIMS & METHODS: Patients with a confirmed histological diagnosis of lowgrade dysplasia in Barretts oesophagus were randomly assigned to ablation or
endoscopic surveillance. Quality of life and illness perception were assessed at
baseline, 2, 8, 14, 26, and 38 months follow-up. QOL was measured with the SF36 (general), the EORTC-QLQ-C30 (cancer-specific), and the EORTC-QLQOES18 (esophageal cancer-specific). Illness perception was measured with the
brief-illness perception questionnaire (8 dimensions (scale 0-10); overall score
(scale 0-80)). To compare ablation with surveillance for longitudinal data with
repeated measurements, a linear mixed model was used.
RESULTS: Quality of life and illness perception were investigated in 96 patients
(47 ablation, 49 surveillance) with a median follow-up of 36 months. There were
no significant differences between the groups for SF-36 (general) and the
EORTC-QLQ-C30 (cancer-specific). Apart from less reflux symptoms in the
ablation group, there was no difference between the groups for EORTC-QLQOES18 (esophageal cancer-specific).
Compared to surveillance patients, ablation patients perceived their disease as
lasting for a significantly shorter period of time (6.2 out of 10 vs 8.1 out of 10;
p50.001), experienced fewer symptoms (2.4 out of 10 vs 3.3 out of 10 p50.001),
had fewer concerns about their illness (3.6 out of 10 vs 5.2 out of 10; p50.001),
and were less emotionally affected by their illness (2.8 out of 10 vs 3.3 out of 10;
p 0.012). As a result, ablation patients experienced their disease as less threatening compared to surveillance patients (overall illness perception score 26.6 out
of 80 vs 34.2 out of 80; p50.001).
CONCLUSION: In this multi-center randomised controlled trial of ablation
versus surveillance for low grade dysplasia in Barretts oesphagus, ablation not
only reduced the neoplastic progression by 25% compared to surveillance, but
also led to fewer concerns and a less threatening view of the illness during a
median follow-up of 36 months. This further strengthens the indication for prophylactic ablation of confirmed low grade dysplasie in Barretts oesophagus.
Disclosure of Interest: W. Rosmolen Financial support for research from: Study
was sponsored by Covidien, N. Phoa Financial support for research from: Study
was sponsored by Covidien, P. Nieuwkerk: None declared, B. Weusten Financial
support for research from: Study was sponsored by Covidien, R. Bisschops
Financial support for research from: Study was sponsored by Covidien, E.
Schoon Financial support for research from: Study was sponsored by
Covidien, M. Sprangers: None declared, J. Bergman Financial support for
research from: Study was sponsored by Covidien
P0493 CLINICAL SIGNIFICANCE OF MEAN PLATELET VOLUME,
PLATELETCRIT, PLATELET-LYMPHOCYTE RATIO AND
NEUTROPHIL-LYMPHOCYTE RATIO IN THE DIFFERENTIATION
OF PATIENTS WITH GASTRIC PRECANCEROUS LESIONS
C. Kalkan1,*, C. Ates2, O. Keskin1, M. Yakut1, F. Karakaya1, X. Deda1,
I. Soykan1
1
Gastroenterology, 2Biostatistics, ANKARA UNIVERSITY, Ankara, Turkey
Contact E-mail Address: isoykan@medicine.ankara.edu.tr
INTRODUCTION: Before gastric cancer becomes clinically noticeable, a prolonged precancerous process takes place which includes atrophic gastritis and
intestinal metaplasia (IM). There is no validated evidence available to support
surveillance of gastric intestinal metaplasia. Therefore, the aim of this study was
to investigate whether systemic inflammatory response markers such as mean
platelet volume, plateletcrit, platelet/lymphocyte ratio (PLR) and neutrophil/
lymphocyte ratio (NLR) in peripheral blood may have a role in the differentiation of patients with gastric precancerous lesions.
AIMS & METHODS: 1139 patients with atrophic gastritis, intestinal metaplasia
and gastric cancer were evaluated by means of mean platelet volume, plateletcrit,
PLR and NLR. Patients were further divided into four groups according to
updated Sydney classification: Group 0: IM negative, Group I: IM 1, Group
II: IM2, Group III: IM3, also two groups consisting of Group IV: gastric
cancer and Group V: atrophic gastritis were included into the study in order to
maintain approppriate comparisons.
RESULTS: As for PLR values, there were significant differences between groups
indicating that PLR was significantly higher in group IV compared to groups 0,
I, II, III, and V (209.4216.6 vs 131.461.7, 13160.4, 132.669.7, 13176 and
141.953. p 0.001, 0.001, 0.001, 0.001 and 0.048 respectively). NLR was also
significantly higher in group IV compared to groups 0, I, II, III, and V
(3.815.33 vs 2.41.65, 2.351.65, 2.421.91, and 2.341.57, p 0.001).

United European Gastroenterology Journal 2(1S)


Plateletcrit was significantly higher in group IV compared to group II (0.250.08
vs. 0.210.05%, p 0.01). However, there were no statistically significant difference between groups by means of mean platelet volume. Receiver operating
characteristic curve (ROC) analysis suggested that optimum PLR cut-off point
according to Youden index was 137.6 (AUC: 0.718) with a sensitivity and specificity of 0.67 and 0.68 respectively, and optimum NLR ratio cut-off point was
2.2 (AUC: 0.702) with a sensitivity and specificity of 0.71 and 0.60 respectively.
CONCLUSION: No evidence from randomised studies exists to support surveillance of gastric intestinal metaplasia. Although sensitivity and specificity are not
high enough, PLR and NLR may be used in clinical practice in order to decide
which patients should be scoped and biopsied during the follow-up of patients
with IM and atrophic gastritis.
REFERENCES
1. Bhatti I, Peacock O, Lloyd G, et al. Preoperative hematologic markers as
independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio. Am J Surg
2010; 200: 197203.
2. Ozgehan G, Kahramanca S, Kaya IO, et al. Neutrophil-lymphocyte ratio as a
predictive factor for tumor staging in colorectal cancer. Turk J Med Sci 2014; 44:
365-368.
3. Kwon H-C, Kim SH, Oh SY, et al. Clinical significance of preoperative
neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable
colorectal cancer. Biomarkers 2012; 17: 216222.
Disclosure of Interest: None declared
P0494 IMPACT OF CARCINOMATOSIS AND ASCITES STATUS ON
LONG-TERM OUTCOMES OF PALLIATIVE TREATMENT FOR
PATIENTS WITH GASTRIC OUTLET OBSTRUCTION CAUSED BY
UNRESECTABLE GASTRIC CANCER: STENT PLACEMENT VERSUS
PALLIATIVE GASTROJEJUNOSTOMY
C.H. Park1,*, E.H. Kim1, H. Chung1, J.Y. An2, H.-I. Kim2, S.K. Shin1,
S.K. Lee1, J.-H. Cheong2, W.J. Hyung2, Y.C. Lee1, S.H. Noh2, C.B. Kim2,
J.C. Park1
1
Department of Internal Medicine, Yonsei University College of Medicine,
2
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea,
Republic Of
Contact E-mail Address: chan100@yuhs.ac
INTRODUCTION: Self-expandable metal stent (SEMS) placement and palliative gastrojejunostomy (GJJ) are palliative treatment options for malignant gastric outlet obstruction.
AIMS & METHODS: We aimed to compare clinical outcomes of palliative
treatments for gastric outlet obstruction caused by unresectable gastric cancer
to identify optimal treatment modalities according to carcinomatosis and ascites
status. We analyzed 217 and 39 patients who underwent SEMS placement and
palliative GJJ, respectively, for gastric outlet obstruction caused by unresectable
gastric cancer.
RESULTS: Treatment modality was not an independently associated factor of
clinical success (P 0.992). Treatment modality, however, affected re-obstruction after clinical success (P 0.001). In addition, carcinomatosis with ascites was
an independent associated factor of clinical success (P 0.006) and re-obstruction (P 0.045). In a subgroup of patients with good performance who had
neither carcinomatosis nor ascites, patency duration and overall survival duration did not differ between the two groups. In patients with good performance
who had carcinomatosis without ascites, patency duration was longer in the
palliative GJJ group than in the SEMS placement group. Overall survival, however, did not differ between the two groups. In a subgroup of patients with good
performance who had carcinomatosis with ascites, both patency duration and
overall survival were longer in the palliative GJJ group than in the SEMS placement group.
CONCLUSION: Long-term clinical outcomes of the palliative treatment modality for gastric outlet obstruction caused by unresectable gastric cancer were
affected by carcinomatosis and ascites status, according to which a palliative
treatment modality can be chosen.
Disclosure of Interest: None declared
P0495 HIGH PREVALENCE OF GASTROINTESTINAL STROMAL
TUMOURS (GISTS): A CASE SERIES IN UK SECONDARY CARE
C. Shekhar1,*, N.C. Fisher1
1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom
Contact E-mail Address: drcshekhar@gmail.com
INTRODUCTION: Gastrointestinal Stromal Tumours (GISTs) are mesenchymal tumours, predominantly affecting the GI tract. Diagnosis and classification
require specialist review and there are few published data on the incidence of
GIST in the UK. Reported incidences elsewhere vary between 6.5/ million/ year
in Norway and 14.5/ million/year in Sweden1,2. We have analysed our caseload of
GISTs in a UK secondary care setting with a population of approx 350,000, in
order to estimate incidence and review outcomes.
AIMS & METHODS: A retrospective case note reviews of all patients with
GIST, as identified from upper GI cancer multidisciplinary team meeting
(MDT) minutes, from 2008 to 2013 inclusive (6 years). The diagnosis of GIST
was considered valid, if characteristic imaging and/ or pathological features were
verified by CT scanning, endoscopic ultrasound (EUS) needle aspiration/ biopsy
and/ or surgical resection.
RESULTS: We identified 34 cases with a final diagnosis of GIST. The observed
incidence of presentation to hospital varied year on year, and estimated annualised incidence was calculated at 16.2 / million/year. The age range was 28-91
years (M 15, F19). Nineteen cases (59%) presented with signs or symptoms of GI

A269
blood loss; five (15%) with other GI symptoms and remaining cases were found
incidentally. The size of GIST at presentation ranged from 1cm to 20 cm in
diameter. One case had metastasised at the time of diagnosis. EUS was used
for diagnosis and staging in 15 cases; 13 had fine needle aspiration, of which
10/13 were diagnostic. 26/34((76%) cases underwent resection surgery. 6 cases
were treated with Imatinib (Glivec). Case follow up range from 3 months to 6
years. Two patients died, one patient presented with metastatic disease other was
managed with palliative approach due to advance age and co-morbidities.
CONCLUSION: Our review suggests a higher than expected incidence of GISTs
in this population compared with other published series1,2. Most cases present
with GI blood loss and surgery is curative in most cases with good prognosis. The
incidence of GISTs in the UK is deserving of further study.
REFERENCES
1. Cancer Eidemiol 2011; 35: 515-520.
2. Cancer 2005; 103: 821-829.
Disclosure of Interest: None declared
P0496 ENDOSCOPIC
CHARACTERISTICS
PREDICTING
LYMPHOVASCULAR INVASION OF EARLY GASTRIC CANCER: A
RETROSPECTIVE COHORT STUDY USING PROPENSITY-SCORE
MATCHING
C.N. Shim1,*, P.-S. Kim1, H. Chung2, J.C. Park2, S.K. Shin2, S.K. Lee2,
Y.C. Lee2
1
Department of Internal Medicine, International St. Marys Hospital, Incheon,
2
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: kscn99@gmail.com
INTRODUCTION: The most important factor concerning endoscopic resection
(ER) for early gastric cancer (EGC) is the prediction of regional lymph node
(LN) metastasis before treatment. Of the main risk factors associated with LN
metastasis, lymphovascular invasion (LVI) of tumor is the strongest predictor for
LN metastasis in EGC. However, risk factors of LVI have not been securely
established. The purpose of this study was to evaluate endoscopic characteristics
predictive of LVI of EGC treated by ER.
AIMS & METHODS: A total of 1214 consecutive patients with 1240 EGCs
underwent ER between January 2007 to June 2013. The lesions studied were
grouped into groups of either no LVI group (n 1166) or LVI group (n 74),
according to the presence of LVI in ER specimen. Propensity-score matching for
adjustment of confounding variables including lesion size and submucosal invasion yielded 148 matched patients. Endoscopic characteristics including macroscopic type, erythema, whitish discolorization, ulcer, marginal delineation, and
folds change were investigated among the matched cohort.
RESULTS: Lymphovascular tumor invasion was diagnosed in 6.0% of enrolled
lesions. Of clinicopathologic characteristics in the overall cohort, larger size
(P50.001) and submucosal invasion determined by endoscopic ultrasound
(P50.001) and histology (P50.001) were significantly higher in the LVI
group. In the 148 matched cohort after propensity-score matching, endoscopic
elevated macroscopic type (P 0.020) and whitish mucosal discolorization
(P 0.022) were significant endoscopic characteristics related to LVI of EGC,
while no significant difference of age, sex, lesion size, location of tumor, submucosal invasion, and histology were detected between the matched two groups.
CONCLUSION: Endoscopic elevated macroscopic type and whitish mucosal
discolorization in EGC carry a significant risk for LVI of tumor, which results
in non-curative ER for EGC. Further prospective studies of preoperative prediction for LVI are warranted.
Disclosure of Interest: None declared
P0497 MAGNIFYING
ENDOSCOPY
WITH
CRYSTAL
VIOLET
STAINING HAS NO ADDITIONAL DIAGNOSTIC VALUE
COMPARED WITH NARROW-BAND IMAGING IN THE DIAGNOSIS
OF SPORADIC NONAMPULLARY DUODENAL ADENOMA/
CARCINOMA
D. Maruoka1,2,*, M. Arai2, K. Okimoto2, S. Minemura2, T. Matsumura2,
T. Nakagawa2, T. Katsuno2, O. Yokosuka2
1
Clinical Research Center, Chiba University Hospital, 2Department of
Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University,
Chiba City, Japan
Contact E-mail Address: d-maruoka@chiba-u.jp
INTRODUCTION: Sporadic nonampullary duodenal adenomas rarely occur
but are precancerous lesions [1]. It recently became clear that high-grade dysplasia (HGD) shows a high risk of progression to adenocarcinoma [2]. Therefore,
HGD and intramucosal carcinoma (HGD/IMC) are indications for endoscopic
resection. We previously reported that magnifying endoscopy with narrow-band
imaging (NBI-ME) was extremely helpful in the differential diagnosis of sporadic
nonampullary duodenal low-grade dysplasia (LGD) or HGD/IMC. Magnifying
endoscopy with crystal violet staining (CV-ME) is useful for diagnosing colorectal adenomatous tumors [3], but no report has analyzed the utility of CV-ME
in diagnosing duodenal tumors.
AIMS & METHODS: In this study, we analyzed whether CV-ME has additional
diagnostic value compared with NBI-ME in the diagnosis of sporadic nonampullary duodenal adenoma/carcinoma. The final diagnosis was determined by
histopathological analysis of endoscopically resected specimens. Nineteen
patients with sporadic nonampullary duodenal adenoma or adenocarcinoma
without polyposis syndrome who were treated by endoscopic resection between
November 2012 and October 2013 were prospectively evaluated. Twenty lesions
were diagnosed using CV-ME after NBI-ME and then resected. In NBI-ME, we
evaluated the presence of the following: (a) irregular villi of various sizes, (b)

A270
small villi area (alternatively tubule-like structures), (c) intravillous irregular
microvessels, and (d) network-like microvessels. If any one of these findings
was observed, we diagnosed HGD/IMC. On the other hand, we diagnosed the
lesion that had none of these findings as LGD. In CV-ME, we made a final
diagnosis by adding the findings of (a) and (b) using CV-ME in addition to
NBI-ME.
RESULTS: Eight of the 20 lesions were LGD, while 12 were HGD/IMC. The
following values were obtained for NBI-ME and integrated diagnosis, respectively: sensitivity, 1.0 and 1.0; specificity, 0.375 and 0.500; positive predictive
value, 0.706 and 0.750; negative predictive value, 1.0 and 1.0; and accuracy,
0.750 and 0.800. No significant differences were noted between groups (chisquared test).
CONCLUSION: CV-ME does not have additional diagnostic value compared
with NBI-ME in the diagnosis of sporadic nonampullary duodenal adenoma/
carcinoma.
REFERENCES
1. Shepherd NA, et al. WHO classification of tumours of the digestive system.
Lyon: IARC Press, 2010, pp. 98-101.
2. Okada K, et al. Am J Gastroenterol 2011; 106: 357-364.
3. Kobayashi Y, et al. Int J Colorectal Dis 2011; 26: 1531-1540.
Disclosure of Interest: None declared
P0498 A ROLE OF PALLIATIVE SURGERY IN STAGE IV GASTRIC
CANCER
D. Yamaguchi1,*, S. Fujii1, T. Kusaka1
1
Department of Gastroenterology, Kyoto Katsura Hospital, Kyoto, Japan
Contact E-mail Address: tetsu_kumohayuni64000@msn.com
INTRODUCTION: Standard treatment for patients with Stage IV gastric cancer
is systemic chemotherapy. Some patients receive palliative surgery before chemotherapy to relieve gastric obstruction or uncontrollable bleeding. However,
few data is available about the impact of palliative surgery on following chemotherapy in patients with Stage IV gastric cancer.
AIMS & METHODS: We aimed to compare the clinical outcomes between
patients with advanced gastric cancer who initially received surgical resection
for their primary lesion and those who initiated palliative chemotherapy without
surgery. Data of consecutive 123 patients with pathologically confirmed
advanced gastric cancer who received palliative chemotherapy between January
2005 and March 2014 were reviewed. A total of 57 patients received palliative
chemotherapy following surgical resection for their primary lesion (Group A)
and 50 patients initiated palliative chemotherapy without surgery (Group B).
Overall survival was defined as the period between the date of surgery or chemotherapy initiation and the date of death for any reason or the last follow-up
visit.
RESULTS: Both groups were similar in age and gender. Median survival time
was 13.2 months (95% CI 7.2-19.2) for Group A and 10.2 months (95% CI 8.412.1) for Group B. In group A, 10 patients could not proceed to palliative
chemotherapy because of postoperative complications (n 3) and/or deteriorated general conditions (n 7). In group B, 15 patients (37.5%) developed
adverse events related to residual primary lesion: gastric hemorrhage (n 6),
gastric stenosis (n 6), gastric perforation (n 3). Among these 15 patients,
only 2 patients who developed gastric perforation could resume chemotherapy.
Duration of chemotherapy did not differ between two groups.
CONCLUSION: Our data suggested that surgical resection of primary lesion
before initiating palliative chemotherapy could reduce the risk of developing
severe adverse events related to residual primary lesion during chemotherapy
without hampering its efficacy.
Disclosure of Interest: None declared
P0499 CLINICAL
APPLICABILITY
OF
PERIOPERATIVE
CHEMOTHERAPY IN RESECTABLE GASTRIC CANCER
RESULTS FROM A PORTUGUESE CANCER INSTITUTE
D. Trabulo1,2,*, J. Moleiro2, A. Ferreira3, A. Loureiro4, C. Cardoso5,
R. Dion sio6, A. Pimenta7, S. Mao-de-Ferro2, M. Serrano2, S. Ferreira2,
J. Freire5, A. Luis5, R. Casaca8, A. Bettencourt8, D. Pereira2
1
Gastroenterology, Hospital de Sao Bernardo - Centro Hospitalar de Setubal,
Setubal, 2Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco
Gentil, EPE, Lisboa, 3Gastroenterology, Centro Hospitalar do Algarve, Portimao,
4
Radiology, 5Oncology, Instituto Portugues de Oncologia de Lisboa Francisco
Gentil, EPE, Lisboa, 6Oncology, Centro Hospitalar do Algarve, Faro,
7
Radiotherapy, 8Surgery, Instituto Portugues de Oncologia de Lisboa Francisco
Gentil, EPE, Lisboa, Portugal
Contact E-mail Address: danieltrabulo@yahoo.com
INTRODUCTION: The benefit of perioperative chemotherapy (POC) in
patients with resectable gastric cancer (GC) and esophagogastric junction
cancer (EGJC) was demonstrated in MAGIC trial (2006), which was associated
to high morbidity.
AIMS & METHODS: Aims: To evaluate the clinical applicability of perioperative chemotherapy (POC) in patients with resectable gastric and esophagogastric
junction (EGJ) cancer treated in a Portuguese cancer institute, as stated in the
MAGIC Trial. Methods: Selection of patients with GC and EGJC referred to our
institution from 2009 to 2013. Patients were staged with thoraco-abdominopelvic CT, endoscopic ultrassonography (if T53, N0 and M0) and laparoscopy
(if T42 or N and M0). POC was proposed to those staged as T42 or N and
M0 (3 pre and 3 postoperative cycles of epirrubicine, cisplatin and 5-fluorouracil;
surgery with D2 lymph node dissection). Non-surgical candidates or stage IV
patients received palliative care. Those staged as T1/2 and N0, age 4 80 years or
with an obstructive or bleeding tumor had direct surgery. Evaluation of clinical

United European Gastroenterology Journal 2(1S)


characteristics, adhesion, complications, survival and recurrence. Statistical analysis performed with chi2, t-Student tests, Kaplan-Meier.
RESULTS: We evaluated a total of 418 patients: 315 with GC and 103 with
EGJC; 57% males; mean age 65.4  21-93 years. POC proposed to 150 patients.
Preoperative chemotherapy in 143 patients; not performed due to disease progression-5; obstructive symptoms-1; associated diseases-1; major morbidity-7%,
mortality-3%. Surgery in 134 patients (94%); not performed due to death
during chemotherapy-4, toxicity-1, disease progression-1, refusal-2. R0 surgery
was performed in 102 patients (76.1%), R1 surgery in 5 patients and R2 surgery/
unressecable in 28 patients; major morbidity-16%, mortality-3%. Postoperative
chemotherapy in 74 patients (72.5%); not performed due to previous chemotherapy/surgery complications in 26 patients and disease progression in 2 patients;
major morbidity-6%; mortality-0%. Median time from chemotherapy to surgery:
50 days; from surgery to chemotherapy: 35.5 days. Surgical complications were
identical in those that had direct versus perioperative chemotherapy resections.
Overall, 69 patients (47%) did not complete the proposed protocol. Survival at 36
months: a) general 37.4%; b) proposed to POC 51.2%; c) treated with curative
intention-66.5%, d) completed the proposed protocol-70.7%.
CONCLUSION: In our series, one third of all patients were eligible for POC.
The rates of treatment conclusion, R0 surgery and postoperative chemotherapy
were higher in our series, compared with those described in the MAGIC study.
POC is feasible and applicable in clinical practice, but similar to that described in
the MAGIC study, only half of patients completed the proposed protocol, either
due to complications of treatment, either due to disease progression.
Disclosure of Interest: None declared
P0500 THE
PROGNOSTIC
SIGNIFICANCE
ANGIOGENESIS IN GASTRIC CANCER

OF

TUMOR

D. Lazar1,*, S. Taban2, M. Cornianu2, I. Sporea1, I. Ratiu1, A. Goldis1


1
Gastroenterology, 2Pathology, UNIVERSITY OF MEDICINE AND
PHARMACY TIMISOARA, Timisoara, Romania
Contact E-mail Address: lazar_daniela@yahoo.com
INTRODUCTION: Angiogenesis, the process by which new blood vessels are
formed, plays an essential role in the survival of the malignant cells, in the local
expansion and tumor invasion, as well as in the appearance of distant metastases.
The intratumoral microvessel density (MVD), which can be evaluated immunohistochemically, seems to have an influence on the prognosis of various malignant tumors. The forming of new intratumoral microvessels depends on the
elaboration of the angiogenic growth factors by the malignant cells (such as
vascular endothelial growth factor VEGF). These factors expression is correlated with the tumor angiogenesis, neoplasia progression and severe prognosis.
Among the known angiogenic factors, VEGF plays a central role in angiogenesis
process control in cancerous disease.
AIMS & METHODS: We evaluated the relation between MVD, VEGF expression, the clinicopathologic factors and the survival in patients with gastric cancer.
A prospective study has been carried out, regarding the evolution and aggressiveness of gastric cancer, with a duration of five years, 61 patients that underwent a surgery for gastric cancer being included in the study. The
immunohistochemical reactions for CD34 and VEGF were performed for all
gastric cancers cases included in the study group.
RESULTS: MVD has shown in the gastric carcinomas an average value significantly higher in comparison to the normal mucosa (38.7 vs. 12.5, p50.001). In
the intestinal type we have noticed a much lower average MVD than the average
MVD in the diffuse type of gastric carcinomas (36.8 vs. 41.6) (p 0.024).
Anaplastic carcinoma and the signet ring cell carcinoma are differentiating as
histological forms associated to an intense neoangiogenesis activity. The neoangiogenesis activity is correlated with the histologic grade, the lymphovascular
invasion, the level of extend, the lymph node metastasizing, the distant metastasizing and the TNM stage. Positive immunoreactions for VEGF are significantly
more frequent in gastric carcinomas, in comparison to the normal gastric mucosa
(65.6% vs. 6.5%, p50.001). The immunoreactions to the VEGF protein were
positive in 71.1% of the intestinal carcinomas, significantly more frequent in
comparison to the diffuse type carcinomas (52.9%) (p 0.018). Our results
show a tight correlation between the histologic grade, the level of the tumor
invasion and the VEGF expression. Our results prove the major correlation
between the VEGF expression and the 5 year survival rate of the patients with
gastric cancer, the survival rate for the carcinomas with VEGF / being
significantly lower than for the VEGF negative ones (12.5% vs. 23,8%)
(p 0.027).
CONCLUSION: Our study proves a tight correlation between the VEGF expression and the MVD (p 0.039), these factors playing an important role in the
tumoral biologic behaviour, in the progression and the prognosis.
Disclosure of Interest: None declared
P0501 GASTRIC CANCER IN PATIENTS WITH TYPE I GASTRIC
CARCINOIDS
G. Esposito1,*, E. Lahner1, E. Pilozzi2, G. Galli1, V.D. Corleto3, E. Di Giulio3,
B. Annibale1
1
Digestive and Liver Disease, 2Pathology, 3Digestive Endoscopy, Sapienza
University, Rome, Italy
Contact E-mail Address: gle.esposito@gmail.com
INTRODUCTION: Type I gastric carcinoids (T1-GCs) are rare tumors which
may arise in pts with atrophic gastritis (AG). These tumors are well-differentiated
with low proliferative index and a generally benign behavior, and constitute up to
80% of all gastric carcinoids. A major pathogenetic factor for T1-GCs is hypergastrinemia due to AG. Gastrin acts as a growth type factor for enterochromaffin-like cells, which in AG are chronically induced to proliferate, through a

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United European Gastroenterology Journal 2(1S)


Table to abstract P0501.

PatientGenderAge, yearsType of lesion


#1

40

#2

78

#3

58

#4

49

Diagnosis
cancer

of

gastric
Locali-zation

Gastroscopy according Antrum


Low-grade dysplasia
Antrum
to follow-up
(intramucosal, endoscoprotocol
pically normal mucosa,
detected on random
biopsies)
Diffuse gastric cancer
(signet-ring cells) in situ
(endoscopically normal
mucosa, detected on
random biopsies)
Intestinal-type adenocarci- New onset of anemia Angulus
noma (gastric ulcer, 3
cm)
Intestinal-type adenocarci- New onset of epigastric Antrum
noma (gastric ulcer, 2
pain
cm)
Intestinal-type adenocarci- Gastroscopy according Antrum
noma in situ (endoscoto follow-up
pically normal mucosa,
protocol
detected on random
biopsies)

multistep process passing from hyperplasia to dysplasia and then to carcinoid.


Epidemiological data suggest that AG is associated not only with T1-GCs, but
also with intestinal-type gastric cancer. The occurrence of gastric cancer in AG
pts with type I gastric carcinoids has not yet been described.
AIMS & METHODS: The aim of this study was to describe in a retrospective
case-series the occurrence of gastric cancer in AG pts with type I gastric carcinoid
in a single tertiary referral center. Between 1994 and 2012, 17 new cases of T1GCs were diagnosed amongst a cohort of AG pts. The clinical charts of these 17
T1-GCs pts were retrospectively evaluated for the occurrence of gastric cancer at
follow-up (median 4.2 years, range 0.5-13). AG diagnosis was based on the
presence of hypergastrinaemia and atrophy of the body mucosa. Diagnosis of
T1-GCs was performed when enterochromaffin-like cells proliferation was
4500m (WHO 2010 criteria).
RESULTS: In 4/17(23.5%) T1-GCs pts (3F, age 40-78yrs), gastric cancer
occurred (median follow-up 5.9 yrs, range 5.1-13; Table1). Three cases were
intestinal-type adenocarcinomas and one a signet-ring cells diffuse gastric
cancer, localized in 3 cases in the antrum. In two pts it was detected on
random biopsies during follow-up-gastroscopy, in the other two gastroscopy
was performed due to new symptoms. All pts with gastric cancer had associated
autoimmune features (pernicious anemia, autoimmune thyroid disease and a
spared antrum), compared to 77%, 46% and 54% of those without gastric
cancer.
Table1. Pts with type I gastric carcinoid who developed an epithelial neoplastic
lesion
CONCLUSION: This case-series shows that in pts with T1-GCs gastric cancer
may frequently occur at long-term follow-up. Thus, these pts should be monitored by a long-term surveillance programme, including an accurate bioptic
sampling of antral mucosa.
Disclosure of Interest: None declared
P0502 THERAPEUTIC OUTCOMES OF ENDOSCOPIC RESECTION IN
FOREGUT NEUROENDOCRINE TUMORS
H.J. Jung1,*, Y.S. Myung1, J.P. Han1, S.J. Hong1, B.M. Ko1, M.S. Lee1
Department of Internal Medicine, SoonChunHyang University School of
Medicine, Bucheon, Digestive Disease Centerand Research Institute, Bucheon,
Korea, Republic Of
Contact E-mail Address: 95970@schmc.ac.kr
1

INTRODUCTION: Endoscopic resection (ER) may benefit to treat the low


grade foregut neuroendocrine tumors (NETs). This study aimed to evaluate
therapeutic outcomes of ER for foregut NETs.
AIMS & METHODS: From January 2003 to February 2013, a total of 40
patients were confirmed histologically as foregut NETs from the ER
(stomach 16, duodenum 13) and surgical resection (SR, stomach 9,
duodenum 2). The clinicopathological characteristics and therapeutic outcomes
were evaluated retrospectively.
RESULTS: Of 29 patients underwent ER (EMR 23, ESD 6), 28 were diagnosed as NET-G1 and 1 as NEC. Of 11 patients underwent SR, 9 were diagnosed
as NET-G1 and 2 as NEC. Tumor size of ER group was significantly smaller
than SR group (7.4 mm vs. 18.2 mm, P50.01). Depth of invasion was limited to
mucosa and submucosa in 28 NETs of ER group, However, all NETs of SR
group invaded the submucosa or proper muscle. Complete resections were
achieved in 22 patients (75.9%) of ER group and achieved in 11 patients
(100%) of SR group. In ER group, immediate procedure-related complications
occurred in 2 cases (bleeding 1, perforation 1), and they were successfully
treated by conservative treatment. There was no complication in SR group.
There was no recurrence in 7 NETs reported as incomplete resection in
margin, but all of 3 NEC patients (ER 1, SR 2) had recurrence during
follow up period. They were treated by additional chemotherapy and had no

Time of occurrence
after diagnosis of type
IGC, months (years) Outcome
17 (1.4)
156 (13)

Gastric surgery alive

80 (6.7)

No surgery due to comorbidities dead

63 (5.2)

Gastric surgery dead (complications of surgery)

61 (5.1)

Gastric surgery alive

more disease progression. One metachronous recurrence occurred after complete


ER, and it was treated by ER.
CONCLUSION: ER can be used as an effective method as treatment for a small
sized and low grade foregut NETs. However, additional treatment should be
considered in the patients who diagnosed as NEC from histological result after
endoscopic treatment because it has high risk of recurrence rate.
Disclosure of Interest: None declared
P0503 SELF-EXPANDABLE METAL STENTS VERSUS SURGICAL
GASTROENTEROSTOMY FOR PALLIATION OF MALIGNANT
DUODENAL OBSTRUCTION
H. Saito1,*, M. Ito1, M. Yoshioka1, S. Saito1, F. Masakuni1, S. Ishiyama1,
A. Fujiwara1, J. Nasu1, S. Junji1
1
Internal medicine, Okayama Saiseikai General Hospital, OKAYAMA, Japan
Contact E-mail Address: itoh777-lj@infoseek.jp
INTRODUCTION: Surgical gastroenterostomy used to be the first line treatment for palliation of malignant gastroduodenal obstruction. Recently endoscopic placement of self-expandable metal stents (SEMS) has become a
broadly accepted treatment for patients with advanced malignant gastroduodenal obstruction as a minimally invasive therapy.
AIMS & METHODS: We attempted to elucidate the current status of endoscopic SEMS for palliation of malignant duodenal obstruction in comparison
with surgical gastroenterostomy. A total of 39 consecutive duodenal tumor
obstruction patients who were treated at Okayama Saiseikai General Hospital
from January 2006 to Dectmber 2011 were reviewed (23 pancreatic cancer, 5
gallbladder cancer, 4 duodenal cancer, 2 renal pelvis cancer, 2 colon cancer, 1
gastric cancer, 1 liver cancer, 1 occult primary cancer). 25 patients were treated
by SEMS and 14 patients by surgical gastroenterostomy. We compared procedure time, time from the procedure to starting oral intake, time from the procedure to starting chemotherapy, technical success rate, complication, hospital
stay, and mortality.
RESULTS: In each and every patients, treatment (eather endoscopic stent
implantation or surgical gastroenterostomy) was clinically successful.
Endoscopic stenting was found to be associated with a shorter time of procedure
(mean 31.7 vs. 146 min, P50.01), a shorter time from the procedure to starting
oral intake (mean 2.96 vs. 6.64 days, P 5 0.01) and a shorter hospital stay (mean
15.3 vs. 25.6 days, P 5 0.02) than the surgical gastroenterostomy. There was no
significant difference between the two groups in the analysis of mortality (mean
91.5 vs. 158.8 days, p 0.107) and time from the procedure to starting chemotherapy (mean 8.6 vs. 13 days, p 0.177). A single case of complication was
seen in each group, one case of intestinal perforation in SEMS group (4%) and
one case of intra-abdominal abscess in surgical gastroenterostomy group (7%).
Both cases were able to recover by conservative treatment.
CONCLUSION: Endoscopic SEMS insertion was superior against surgical gastroenterostomy in terms of procedure time, start of oral intake period and the
length of hospital stay. SEMS in duodenal obstruction is a feasible alternative of
surgical gastroenterostomy for the palliation of inoperable malignant duodenal
obstruction. With a high clinical success and low complication rate, endoscopic
implantation of SEMS seems to be a safe and tolerable procedure for palliative
treatment of malignant duodenal obstruction.
Disclosure of Interest: None declared

A272
P0504 CLINICAL OUTCOMES OF SALVAGE ENDOSCOPIC THERAPY
AFTER CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER
H. Osumi1,*, Y. Toshiyuki1, K. Chin1, A. Ishiyama1, T. Tsuchida1, J. Fujisaki1,
M. Igarashi1
1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation
for Cancer Research, Tokyo, Japan
Contact E-mail Address: hiroki.osumi@jfcr.or.jp
INTRODUCTION: Chemoradiotherapy (CRT) for esophageal cancer, especially
at stage I, has comparable survival rates to surgery, with a median survival rate
of 5 years. Therefore, in some cases, it is chosen as a first-line treatment for stage
I, II, and III esophageal cancer. However, about 30% of patients who are administered chemoradiotherapy experience a local recurrence after complete
response, so it is important to consider salvage therapy to treat such recurrences.
Commonly administered salvage therapies include surgery, endoscopic therapy,
and argon plasma coagulation (APC).
AIMS & METHODS: The aim of this study is to illuminate the results of
administering salvage endoscopic therapy in cases of recurrent esophageal
cancer that had previously been treated with chemoradiotherapy. 161 patients
with UICCI-III esophageal cancer who received chemoradiotherapy at the
Cancer Institute Hospital between 2005 and 2013 without previously being treated were retrospectively studied. 11 of these patients had local recurrences after
receiving chemoradiotherapy, and received salvage endoscopic therapy as treatment for the recurrence. Their overall survival (OS) and time of recurrence after
CRT and salvage endoscopic therapy were studied. Kaplan-Meier analysis and
Cox proportional hazard modeling were used for statistical analysis.
RESULTS: The median observation period for the 11 patients studied was 75.2
months (39.1-107.6). The clinical stages of esophageal cancer of the 11 patients
studied were as follows (stage I/II/III: 6/1/4). The salvage endoscopic therapies
administered were as follows (EMR/ESD/APC: 7/3/1). The clinical responses of
the patients to chemoradiotherapy were as follows (CR/PR: 8/3). 5 patients
experienced local recurrences again after salvage endoscopic therapy (EMR/
ESD/APC: 4/0/1). Disease-free survival in patients who received salvage EMR
therapy was a median 24 months (8.9-50.1). Patients who were administered
salvage APC therapy experienced relapses twice, and recurrence-free survival
among those patients was a median 9 months (3.4-14.6). None of the patients
who were administered ESD experienced a relapse, and disease-free survival
among those patients was a median 25.3 months (13.3-32). The complications
usually associated with endoscopic therapies were also not observed. There was
no significant difference between salvage therapies in terms of overall survival
(EMR 74.8 months (46.1-100.1), ESD 78.9months (39.1-107.6), APC 66.5
months).
CONCLUSION: ESD can be considered to be a better salvage therapy than the
other endoscopic therapies as the local recurrence rate was lower than that for
either EMR or APC. Even for less serious cases of esophageal cancer, ESD is a
preferable choice as a salvage endoscopic therapy after chemoradiotherapy. It
should be noted, however, that there was no difference in the long-term prognoses among the different salvage therapies, even after recurrence. In some cases,
ESD may not be ideal as a treatment, such as in patients who have other preexisting diseases that make long-term treatment difficult, or in cases of esophageal stenosis, which renders it difficult to use ESD scopes. For such cases, other
salvage therapies can be considered, including surgery and photo-dynamic therapy (PDT).
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
H. PYLORI I POSTER EXHIBITION HALL XL_____________________
P0505 LOW-DOSE ASPIRIN-ASSOCIATED GASTRIC AND DUODENAL
ULCERS IN JAPANESE PATIENTS WITH NO PREVIOUS HISTORY
OF PEPTIC ULCERATION
A. Tanabe1,*, Y. Ito1, Y. Yamaguchi1, N. Okaniwa1, H. Noda1, K. Yanamoto1,
Y. Tamura1, Y. Kondo1, R. Masui1, S. Izawa1, Y. Hijikata1, K. Tokudome1,
N. Kawamura1, A. Iida1, N. Ogasawara1, Y. Funaki1, M. Sasaki1, K. Kasugai1
1
Aichi medical university, Nagakute, Japan
INTRODUCTION: Long-term administration of low-dose aspirin (LDA) is
associated with a greater risk of adverse events, including gastroduodenal
ulcers and their potentially fatal complications (e.g., gastrointestinal bleeding
and perforation). The identified risk factors for ulcer bleeding with aspirin use
are history of ulcer bleeding; aspirin dose; advanced age (470 years); concomitant use of NSAIDs or anti-coagulants; use of dual anti-platelet therapy;
Helicobacter pylori infection; and history of alcohol abuse, diabetes, or renal
failure. Proton pump inhibitors (PPIs) are used to decrease LDA-associated
gastroduodenal mucosal and NSAID-induced injuries. In Japan, since 2011,
treatment with half-dose PPI (lansoprazole 15 mg/day) has been permitted as a
medical service under health insurance for the prevention of NSAID- or LDAinduced peptic ulcers in patients in the high-risk group who have a history of
peptic ulcers. However, there are few reports in which the use of PPIs reduced the
risk of LDA-associated peptic ulcers in patients without pre-existing peptic ulcers
AIMS & METHODS: AIM: To assess the risk factors and the efficacy of medications for development of peptic ulcer disease in Japanese with no prior history
of peptic ulceration.
METHODOLOGY: We conducted a matched background study using esophagogastroduodenoscopy (EGD) record collected from January 2010 through
December 2010. Consecutive 219 outpatients receiving LDA (75 mg) who had
no peptic ulcer history were matched to 1 control by age and sex who were not
receiving LDA and had no peptic ulcer history. Clinical parameters, concomitant
drugs, the reason for endoscopy, and endoscopic findings were analyzed.

United European Gastroenterology Journal 2(1S)


RESULTS: Of 219 patients receiving LDA, 20 (20%) was diagnosed endoscopically with peptic ulceration, which was significantly higher than 7 (3.2%) of 219
patients not receiving LDA (OR, 3.0; 95% CI, 1.26 7.35; P 0.016). From
multiple logistic regression analysis, LDA smoking habit, NSAID, and PPI
were detected as increased and decreased risk factors for peptic ulcer, respectively
(OR, 9.6; 95% CI, 2.27 38.63; P 0.002), (OR, 3.9; 95% CI, 1.03 14.72;
P 0.045), (OR, 7.4; 95% CI, 1.73 31.67; P 0.007), (OR, 0.11; 95% CI,
0.02 0.45; P 0.002). Age, current alcohol consumption, H2-receptor antagonists, and abdominal symptom were not significantly associated with the presence
of peptic ulcers.
CONCLUSION: Long-term administration of LDA increases the risk of peptic
ulcer even in the patients who had no peptic ulcer history, and PPIs reduces the
risk of developing gastric or duodenal ulcers. However this risk is significantly
increased in patients with concomitant smoking habit and NSAID. These results
may help identify patients who require more intensive prophylaxis against
aspirin-induced ulcerations.
Disclosure of Interest: None declared
P0506 CORRELATION BETWEEN THE PREVALENCE OF GALLSTONE
AND HELICOBACTER PYLORI INFECTION
B.J. Kim1,*, J.G. KIM1, J.-H. Jung1
1
Internal Medicine (Gastroenterology), Chung-Ang University College of
Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: gikbj@cau.ac.kr
INTRODUCTION: Several studies have reported that the presence of
Helicobacter DNA in human bile sample, although its pathological role is not
clear. Moreover, little is known about the association between Helicobacter pylori
(H. pylori) infection and gallstone.
AIMS & METHODS: The aim of this study was to determine whether H. pylori
infection is associated with an increased risk of gallstone in an asymptomatic
population.
We examined 2782 subjects (1635 men and 1147 women) who underwent both
upper endoscopy with CLO test and abdominal ultrasound at the Health
Examination Center at Chung-Ang University Yong-san Hospital in Korea
from January 2007 to December 2009. We compared the prevalence of gallstone
on ultrasound and endoscopic findings such as reflux esophagitis, gastric diseases
in the H. pylori infected subjects with that of the H. pylori uninfected subjects.
RESULTS: The overall prevalence of H. pylori infection in our study was 45.6%
(1271/2782). When the subjects were divided into two groups according to the H.
pylori infection status, there was no significant differences of the baseline characteristics between the two groups. The prevalence of gallstone in the H. pylori
infected subjects was higher than that of the H. pylori uninfected subjects (5.4%
vs 3.2%, P 0.032). The prevalence of peptic ulcer in the H. pylori infected
subjects was higher than that of the H. pylori uninfected subjects (8.2% vs
3.4%, P50.001). The prevalence of reflux esophagitis in the H. pylori infected
subjects was lower than that of the H. pylori uninfected subjects (6.2% vs 14.0%,
P 0.012).
CONCLUSION: These findings suggest that H. pylori infection is associated
with an increased risk of gallstone in asymptomatic population.
REFERENCES
1: Attaallah W, Yener N, Ugurlu MU, et al. Gallstones and concomitant gastric
Helicobacter pylori infection. Gastroenterol Res Pract 2013; 2013: 643109.
2: Takahashi Y, Yamamichi N, Shimamoto T, et al. Helicobacter pylori infection
is positively associated with gallstones: a large-scale cross-sectional study in
Japan. J Gastroenterol 2013 Jun 5.
3: Abro AH, Haider IZ and Ahmad S. Helicobacter pylori infection in patients
with calcular cholecystitis: a hospital based study. J Ayub Med Coll Abbottabad
2011; 23: 30-33.
4: Lee JW, Lee DH, Lee JI, et al. Identification of Helicobacter pylori in gallstone, bile, and other hepatobiliary tissues of patients with cholecystitis. Gut
Liver 2010; 4: 60-67.
Disclosure of Interest: None declared
P0507 HELICOBACTER PYLORI INFECTION AMONGST
ISRAELI WOMEN WITH HYPEREMESIS GRAVIDARUM- A
PROSPECTIVE, CONTROLLED STUDY

ARAB

D. Boltin1,*, S. Abu Elheiga2, T.T. Perez1, A. Sharony2, H. Shamly2, Y. Niv1,


R. Dickman1
1
Gastroenterology, Rabin Medical Center, Petah Tikva, 2Obstetrics and
Gynaecology, St. Vincent French Hospital, Nazareth, Israel
Contact E-mail Address: dboltin@gmail.com
INTRODUCTION: Helicobacter pylori has been associated with hyperemesis
gravidarum in some geographical regions. The prevalence of H. pylori in Arab
Israeli women in the Upper Galilee and its association with hyperemesis gravidarum, has not been previously studied.
AIMS & METHODS: The aim of this study was to examine whether H. pylori
infection is associated with hyperemesis gravidarum in Arab Israeli women.
Subjects with hyperemesis gravidarum carrying a singleton fetus, were prospectively recruited. Women with an uncomplicated pregnancy served as controls. All
patients underwent C13-urea breath testing to assess for H. pylori infection.
RESULTS: A total of seventy two subjects, including 24 patients with hyperemesis gravidarum and 48 controls, aged 28.85.3 years, were included. H. pylori
infection was identified in 73.9% (17/24), and 60.4% (29/48) of cases and controls, respectively (p ns). H. pylori infection did not correlate with age or the
number of previous pregnancies (p ns). Control subjects with a history of early
trimester vomiting were not more likely to be infected with H. pylori, compared
to controls without a history of early trimester vomiting (p ns).

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United European Gastroenterology Journal 2(1S)


CONCLUSION: H. pylori does not seem to increase the likelihood of hyperemesis gravidarum in Arab Israeli women. However, given the apparently high
background prevalence of H. pylori in this population, a larger study is required
to corroborate these findings.
REFERENCES
1: Gungoren A, Bayramoglu N, Duran N, et al. Association of Helicobacter
pylori positivity with the symptoms in patients with hyperemesis gravidarum.
Arch Gynecol Obstet 2013; 288: 1279-1283.
2: Shaban MM, Kandil HO and Elshafei AH. Helicobacter pylori seropositivity
in patients with hyperemesis gravidarum. Am J Med Sci 2014; 347: 101-105.
3: Vikanes AV, Ster NC, Gunnes N, et al. Helicobacter pylori infection and
severe hyperemesis gravidarum among immigrant women in Norway: a casecontrol study. Eur J Obstet Gynecol Reprod Biol 2013; 167: 41-46.
4: Mansour GM and Nashaat EH. Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum. Arch Gynecol Obstet 2011; 284: 843-847.
1: Gungoren A, Bayramoglu N, Duran N, et al. Association of Helicobacter
pyloripositivity with the symptoms in patients with hyperemesis gravidarum.
Arch Gynecol Obstet 2013; 288: 1279-1283.
2: Shaban MM, Kandil HO and Elshafei AH. Helicobacter pylori seropositivity
inpatients with hyperemesis gravidarum. Am J Med Sci 2014; 347: 101-105.
3: Vikanes AV, Ster NC, Gunnes N, et al. Helicobacter pylori infection and
severe hyperemesis gravidarum among immigrant women in Norway: a casecontrol study. Eur J Obstet Gynecol Reprod Biol 2013; 167: 41-46.
Disclosure of Interest: None declared
P0508 THE PREVALENCE OF HELICOBACTER PYLORI POSITIVITY
IN THE GENERAL POPULATION IN SWEDEN HAS DECREASED
FROM 38 PERCENT TO 16 PERCENT SINCE 1989
A. Andreasson1,2, N. Talley3, L. Engstrand4, B. Wallner5, A. Forsberg6,
P.M. Hellstrom7, L. Agreus1,*
1
Karolinska Institutet, Centre for Family Medicine, Huddinge, 2Stress Research
Institute, Stockholm University, Stockholm, Sweden, 3Faculty of Medicine,
University of Newcastle, Newcastle, Australia, 4Karolinska Institutet, Stockholm,
5
Umea University, Umea, 6Molecular Medicine and Surgery, Karolinska Institutet,
Stockholm, 7Uppsala University, Uppsala, Sweden
Contact E-mail Address: lars.agreus@ki.se
INTRODUCTION: It is assumed that the prevalence of Helicobacter pylori
(H.p.) is decreasing in wealthy countries. There are however no recent prospective population based studies confirming this.
AIMS & METHODS: We aimed to evaluate the prevalence of positive H.p.
serology in random population sample in a Swedish community over 23 years.
In 1989 we mailed the validated Abdominal Symptom Questionnaire (ASQ) (age
22-80), and 1097 (87%) responded. H.p.serology (HM-CAPTM immunoassay)
was measured on a stratified sample (n 145 with either dyspepsia, IBS or
symptom free) (1). In late 2011 the ASQ was mailed again with the same sampling procedure in the same community (age 20) and 1175 (64%) replied. A
total of 388 out of 1034 participants 20-79 years of age and suitable for an upper
endoscopy had an upper endoscopy spring 2012. H.p. serology (H. pylori IgA/
IgG ELISA) was measured on 386, 32 of those had participated in 1989. The
effect of time on H.p. prevalence was calculated using random effects logistic
regression models using H.p. as the dependent variable and gender, age and time
as independent variables. All participants in all surveys are included in the analyses (499 participants, 531 observations).
RESULTS: The prevalence of H.p. positivity in 1989 and 2012 in total and in age
groups for the 499 participants who participated in either or both studies is
presented in the table. H.p. positivity decreased significantly with time, the
odds ratio for H.p. positivity corresponding to 0.25 per decade (OR:0.25;
95%CI:0.11-0.59, p .001) independent of gender and age. There was no difference in H.p. prevalence between men and women (OR:0.92; 95%CI:0.40-2.08).
The odds of H.p. positivity increased with age by 11% per year (OR:1.11;
95%CI:1.04-1.18, p 0.001).
Table. Prevalence of Hp positivity in 1989 and 2012 in total and by age group

Total
20-39
40-59
60-80

1989
N hp positive/total

2012
N hp positive/total

55/145
8/47
21/40
26/37

37.9
17.0
34.4
70.3

61/386
4/60
17/161
40/165

15.8
6.7
10.6
24.4

CONCLUSION: In this random sample of the adult general population in


Sweden, H.p. prevalence has decreased radically over the last two decades
across all ages. Among adults below 40 years it has reached the level where the
test & treat strategy might be questioned (2). Among adults older than 60 years
the risk of complications (3) is most probably reduced.
REFERENCES
1. Storskrubb T, et al. Scand J Gastroenterol 2008; 43: 1448-1455.
2. Malfertheiner P, et al. Gut 2012; 61: 646-664.
3. Agreus L, et al. Scand J Gastroenterol 2012; 47: 136-147.
Disclosure of Interest: None declared

P0509 OBESITY AND HELICOBACTER PYLORI INFECTION: IS THERE


A LINK?
M. Sanduzzi Zamparelli1,*, A. Rocco1, D. Angrisani1, D. Compare1,
O.M. Nardone1, M.G. Iannuzzi1, G. Nardone1
1
clinical medicine and surgery, Federico II University, naples, Italy
Contact E-mail Address: marcosanduzzizamparelli@yahoo.it
INTRODUCTION: The incidence of obesity is increasing worldwide. The involvement of Helicobacter pylori (H. pylori) in the pathophysiology of obesity is still
debated. Among the possible related factors reported, H. pylori infection has
been proposed to play a role by interfering with the release of gastric hormones
involved in the regulation of appetite and food intake. However, the data available until now are conflicting are derive from small series of cases.
AIMS & METHODS: To analyze the distribution of H. pylori infection in a large
cohort of consecutive patients stratified according to sex, age and body mass
index (BMI).
We enrolled 4653 subject referred to our Gastroenterology Unit between January
2006 to January 2014 to perform 13C-urea breath test (13C-UBT). In all cases we
recorded: age, sex, weight, height, previous esophagogastroscopy results, previous eradication therapy and H. pylori status. BMI was calculated according
to the following formula: mass (Kg)/height (m)2. The 13C-UBT was performed
by administering a solution of 100 ml tap water containing 100 mg of 13C-urea
and 1.4 g of citric acid. Breath samples were taken at baseline and 30 minutes
after ingestion of the urea. The 13C enrichment in breath was determined by
isotope ratio mass spectrometer. The 13CUBT was considered positive if the
value over baseline at 30 minutes was 4 5%.
RESULTS: Overall, there were 1916 (41%) male. Mean age was 43.75 years
(range 3-88), 323 (7%) subject were 15 year-old. Forty-seven percent (2183)
subjects reported previous eradication therapy. BMI was  18 in 188 (4%),
18.1-25 in 2322 (50%), 25.1-30 in 1576 (35%) and 30.1 in the remaining
514 (11%) of the cases. H. pylori infection was detected in 1892 (40.7%) with a
progressive increasing trend according to BMI ( 18: 36%; 18.1-25: 34%,
25.1-30: 46% and 30.1: 56%; p50.0001).
CONCLUSION: H. pylori infection is significantly more frequent in obese than
in normal weight individuals, irrespective of sex and age.
Disclosure of Interest: None declared
P0510 HELICOBACTER PYLORI, DECREASED PEPSINOGEN AND
ATROPHIC GASTRITIS ARE NOT ASSOCIATED WITH BARRETTS
ESOPHAGUS AND EROSIVE ESOPHAGITIS
M. Selgrad1,*, A. Kandulski1, A. Roessner2, J. Bornschein1, P. Malfertheiner1
1
Department of Gastroenterolgy, Hepatology, 2Department of Pathology, OTTOVON-GUERICKE UNIVERSITY, Magdeburg, Germany
Contact E-mail Address: michael.selgrad@med.ovgu.de
INTRODUCTION: Helicobacter pylori (H. pylori) infection has been suggested
to protect against the development of erosive esophagitis (ERD) and Barretts
esophagus (BE). A possible explanation represents the development of corpus
pre-dominant and/or atrophic gastritis in the natural course of H. pylori infection
with an associated decrease in gastric acid secretion.
AIMS & METHODS: Aim of the study was to assess whether H. pylori infection,
decreased serum pepsinogen levels as a marker for gastric atrophy and different
forms of gastritis are associated with the occurrence of BE and ERD.
For this, we reviewed prospectively collected data of 332 patients with an age
above 50 years that underwent gastro-duodenoscopy and colonoscopy. H. pylori
status was determined by serology and serum pepsinogen I levels were measured
in fasting state by commercially available assay. Intestinal metaplasia (IM),
glandular atrophy and mucosal inflammation were diagnosed from histological
specimens and graded according to the updated Sydney-classification.
RESULTS: In H. pylori infected patients (n 101; 30.4%), the overall prevalence
of ERD (20.8%) was comparable to non-infected patients (25.5%) (p 0.215)
and the same accounted for BE (7.9% vs. 11.7%) (p 0.214). H. pylori infection
was not associated with an increased risk for both ERD (OR 0.76, 95% CI:
0.43-1.35) and BE (OR 0.65, 95% CI: 0.28-1.49). The histological proof of
intestinal metaplasia and/or gastric atrophy independently of the H. pylori
status did not show an association to neither ERD (OR 0.61, 95% CI: 0.281.49) or BE (OR 0.73, 95% CI: 0.32-1.67). The same accounted for the different
phenotypes of gastritis, including antrum- and corpus pre-dominant as well pangastritis for both ERD and BE. Furthermore, no association was seen between a
decreased pepsinogen I level and the occurrence of ERD (OR 0.75, 95% CI:
0.37-1.54) and BE (OR 0.82, 95% CI: 0.31-2.22).
CONCLUSION: H. pylori infection does not show any association to the occurrence of ERD and BE. Furthermore, different types of gastric inflammation and
a hypoacid gastric function do not have an influence on the development of ERD
and BE.
Disclosure of Interest: None declared

A274
P0511 A RETROSPECTIVE STUDY OF HELICOBACTER PYLORI AND
PEPTIC ULCER DISEASE PREVALENCE IN AN UPPER
GASTROINTESTINAL ENDOSCOPY REVIEW BETWEEN 2002 AND
2014
S. Roy1,*, D.A. Fernando2, W. Ocen3, J. Oyenuga3, S. Law3
1
Gastroenterology, Queen Marys Hospital, Sidcup, Kent, 2Medical School, Kings
College London, 3Medical School, Imperial College London, London, United
Kingdom
Contact E-mail Address: sunilroy@hotmail.co.uk
INTRODUCTION: There is a well established association between Helicobacter
pylori (H. pylori) infection and peptic ulcer disease (PUD). This association is
known to be stronger in duodenal ulcers (DU) in comparison to gastric ulcers
(GU). Over recent years, trends worldwide have shown a decreasing prevalence
of H. pylori infection with some studies suggesting the rate of decline may be as
high as 26% per decade1. Consequently due to its prominent association with
PUD it would be interesting to identify the change in prevalence of PUD over the
same timescale.
AIMS & METHODS: Using oesophagogastroduodenoscopy (OGD) as our
chosen diagnostic tool, we have set out to determine whether the trend of
decreasing H. pylori prevalence has been reflected in our sample population
over the last 12 years and whether there has also been a decrease in PUD prevalence in particular with respect to duodenal ulcers.
1781 diagnostic OGD procedures carried out by the same endoscopist in a single
District General Hospital in the South East of England were analysed retrospectively. For each procedure the age, gender, H. pylori status and PUD diagnosis
were recorded. Prevalence data was calculated for three sequential time periods
with comparable patient numbers: 2002 to 2005 (Period 1: n 346), 2006 to 2010
(Period 2: n 677), 2011 to 2014 (Period 3: n 681).
RESULTS: The data showed that prevalence of H. pylori infection decreased in
each successive period (p 0.0012). The prevalence across the three time periods
were as follows: period 1- 36 cases (10.4%), period 2- 38 cases (5.60%, p 0.005
with respect to (WRT) Period 1) and finally period 3: 32 cases (4.70%, p50.001
WRT Period 1, p 0.446 WRT Period 2).
The prevalence of PUD also decreased in each successive period (p50.001). The
prevalence across the three time periods were as follows: period 1 - 27 cases
(7.80%; DU 24; GU 3), period 2 - 32 cases (4.73%, p 0.046 WRT Period
1; DU 24; GU 8) and period 3 - 11 cases (1.62%, p50.001 WRT Period 1,
p 0.001 WRT Period 2; DU 8; GU 4). The prevalence of duodenal ulcers
decreased in each successive period (p50.001), however the prevalence of gastric
ulcers remained consistently low (p 0.502).
CONCLUSION: Prevalence of H. pylori has fallen significantly over the time
period studied. Key reasons for this include continually improving sanitation and
living conditions as well as more effective treatment of H. pylori infection,
making recurrence less frequent. The falling prevalence of H. pylori is likely to
have contributed to the significant decrease in prevalence of PUD in the same
time period. Other reasons for this trend include the introduction of effective H.
pylori treatment and increasing effective use of acid suppressive medication.
Another possible factor for the decrease in PUD prevalence is more careful
prescription of non steroidal anti-inflammatory drugs. The stronger association
between H. pylori and DU may explain the significant reduction in the prevalence
of DU in comparison to GU.
REFERENCES
1 Banatvala N, Mayo K, Megraud F, et al. The cohort effect and Helicobacter
pylori. J Infect Dis 1993; 168: 219221.
Disclosure of Interest: None declared
P0512 SECOND-LINE RESCUE THERAPY WITH LEVOFLOXACIN AND
BISMUTH AFTER FAILURE OF A HELICOBACTER PYLORI
ERADICATION TREATMENT
J.P. Gisbert1,2,*, P. Sol s-Munoz3, M. Romano4, A. Gravina5, A. Lucendo6,
J. Molina-Infante7, B. Velayos8, M. Herranz9, J. Barrio10, I. Modolell11,
J. Gomez12, F. Del Castillo13, J. Dom nguez14, A. Federico4, M. Martorano5,
T. Angueira6, L. Fernandez-Salazar8, A. Miranda4, A.C. Mar n1,2,
A.G. McNicholl1,2
1
Gastroenterology Unit, Hospital Universitario de La Princesa and IP,
2
CIBERehd, 3Gastroenterology Unit, Hospital de Madrid Norte San Chinarro,
Madrid, Spain, 4UO di Epatogastroenterologia ed Endoscopia Digestiva, AOU,
Napoli, 5UOC di Endoscopia Digestiva, Ospedale PO della Immacolata, Sapri,
Italy, 6Gastroenterology Unit, Hospital General de Tomelloso, Ciudad Real,
7
Gastroenterology Unit, Hospital San Pedro de Alcantara, Caceres,
8
Gastroenterology Unit, Hospital Clnico, Valladolid, 9Gastroenterology Unit,
Hospital N. Sra. Sonsoles, Avila, 10Gastroenterology Unit, Hospital Ro Hortega,
Valladolid, 11Gastroenterology Unit, Consorci Sanitari de Terrassa, Barcelona,
12
Gastroenterology Unit, Hospital Gregorio Maranon, Madrid, 13Gastroenterology
Unit, Hospital Don Benito, Badajoz, 14Gastroenterology Unit, Hospital Alcala la
Real, Jaen, Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: The most commonly used second-line regimens for H. pylori
eradication are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and
levofloxacin in the same regimen may be an option as rescue regimen.
AIMS & METHODS: To evaluate the efficacy and tolerability of a second-line
quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed.
Design: Prospective multicenter study. Patients: Patients in whom a standard
triple therapy (PPI, clarithromycin, and amoxicillin) or a non-bismuth quadruple
therapy (PPI, clarithromycin, amoxicillin and metronidazole, either sequential or

United European Gastroenterology Journal 2(1S)


concomitant) had failed. Intervention: Esomeprazole (40 mg b.i.d.), bismuth (240
mg b.i.d.), levofloxacin (500 mg o.d.), and amoxicillin (1 g b.i.d.) for 14 days.
Outcome: Eradication was confirmed using the 13C-urea-breath test 4-8 weeks
after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects
was evaluated by means of a questionnaire.
RESULTS: 78 patients were consecutively included. Mean age 4616 years, 64%
women, 14% peptic ulcer. Previous failed therapy included: standard clarithromycin triple therapy (57 patients), sequential (12), and concomitant (9). One
patient did not return after treatment. 92% took all medications correctly. Perprotocol and intention-to-treat eradication rates were 89.5% (95%CI 82-97%)
and 87.2% (95%CI 79-95%). Cure rates (per-protocol) were similar when compared depending on the diagnosis (peptic ulcer 100% vs. functional/uninvestigated dyspepsia 88%) and previous treatment (standard triple therapy 89% vs.
sequential 83% vs. concomitant 100%). Adverse effects were reported in 60% of
patients (95%CI 49-72%), most commonly nausea (27%), metallic taste (26%),
diarrhoea (23%), abdominal pain (22%), asthenia (17%), and vomiting (6.4%).
In 2 cases, the adverse effects (nausea) were classified as severe (one patient
discontinued the treatment), but none of them was serious.
CONCLUSION: 14-day bismuth-and levofloxacin-containing quadruple therapy
is an effective (
90% cure rate) and safe second-line strategy in patients whose
previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple and probably more effective
alternative than bismuth-quadruple or levofloxacin-triple standard regimens.
Disclosure of Interest: None declared
P0513 NON-BISMUTH QUADRUPLE CONCOMITANT THERAPIES IN
THE ERADICATION OF HELICOBACTER PYLORI: STANDARD
VS. OPTIMIZED (14 DAYS, HIGH-DOSE PPI) REGIMENS IN
CLINICAL PRACTICE
A.G. Mcnicholl1,*, J. Molina-Infante2, F. Bermejo3, Y. Harb4, I. Modolell5,
R. Anton6, J. Alcedo4, A. Perez-Aisa7, M. Barenys8, J. Barrio9, A. Huerta10,
J. Ortuno11, M. Fernandez-Bermejo2, L. Rodrigo12, N. Fernandez-Moreno7,
A. Tomas13, L. Pozzati14, M. Herranz15, P. Almela16, P. Canelles17, A.B. Vega8,
A. Cosme18, V. Andreu8, L. Ferrer-Barcelo17, J.M. Huguet-Malaves17,
A. Algaba3, A.C. Marin1, J.P. Gisbert1
1
H. La Princesa and IP, CIBERehd, Madrid, 2H. San Pedro Alcantara, Caceres,
3
Hospital, Fuenlabrada, 4Barbastro, Huesca, 5Consorci Sanitari, Terrassa,
6
Clinico, Valencia, 7Agencia Sanitaria Costa del Sol, Malaga, 8Hospital,
Viladecans, 9Rio Hortega, Valladolid, 10Sanchinarro, Madrid, 11La Fe, Valencia,
12
Central de Asturias, Oviedo, 13Sant Camil, Sant Pere de Ribes, 14Hospital,
Merida, 15Nuestra Sra de Sonsoles, Avila, 16Hospital, Castellon, 17General,
Valencia, 18Hospital, Donostia, Spain
Contact E-mail Address: adrian.mcn@gmail.com
INTRODUCTION: Non-bismuth quadruple concomitant regimen is increasingly used as first-line H. pylori eradication treatment.
AIMS & METHODS: To evaluate the efficacy and tolerability of the standard
and optimized concomitant regimens.
Design: Prospective multicenter study. Patients: Consecutive H. pylori-infected
patients. Treatment: In a first phase, patients received a standard concomitant
therapy (CONC10): omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg
and metronidazole 500 mg for 10 days b.i.d. In a second phase, patients received
the same regimen but with esomeprazole 40 mg b.i.d. and lasting 14 days
(CONC14). Outcome: Eradication confirmed with 13C-urea breath test 4-8
weeks after therapy. Compliance/tolerance: Compliance and adverse events
were determined through questioning and recovery of empty medication
envelopes.
RESULTS: 827 consecutive patients were included (mean age 48 years, 46%
males, 21% peptic ulcer): 356 in CONC10 and 471 in CONC14. Compliance
with treatment was 94% and 95% respectively (non-statistically significant differences). Per-protocol eradication rates with CONC10 and CONC14 were
86%(95%CI 83-91%) and 93%(91-96%) (p50.01). Respective intention-totreat cure rates were 86%(83-90%) and 91%(90-92%) (p50.01). Adverse effects
(mostly mild) were reported in 32% of patients in CONC10 and in 44% in
CONC14 (p50.05), the most common being metallic taste, diarrhoea,
nausea and abdominal pain.
CONCLUSION: An optimized (fourteen-day and high-dose esomeprazole) nonbismuth quadruple concomitant regimen for the eradication of H. pylori is
more effective than the standard one, and achieves over 90% cure rate.
Although the incidence of adverse events is higher with the optimized treatment,
these are mostly mild, and do not negatively impact the compliance.
Disclosure of Interest: None declared
P0514 SECOND-LINE RESCUE THERAPY WITH MOXIFLOXACIN
AFTER FAILURE OF TREATMENT TO ERADICATE
HELICOBACTER PYLORI INFECTION
J.P. Gisbert1, M. Romano2, J. Molina-Infante3, A.J. Lucendo4, E. Medina5,
I. Modolell6, M. Rodriguez-Tellez7, B.J. Gomez8, J. Barrio9, M. Perona10,
J. Ortuno11, I. Arino12, J.E. Dominguez-Munoz13, A. Perez-Aisa14, F. Bermejo15,
J.L. Dominguez16, P. Almela17, J. Gomez18, J. Millastre19, E. MartinNoguerol20, A.G. Gravina21, A.C. Marin1, A.G. Mcnicholl1,* on behalf of
Spanish H. pylori Study Group
1
H. La Princesa and IP, CIBERehd, Madrid, Spain, 2AUO, Napoles, Italy, 3H.
San Pedro Alcantara, Caceres, 4Hospital General, Tomelloso, 5Hospital General,
Valencia, 6Consorci Sanitari, Terrassa, 7Virgen Macarena, 8Quiron Sagrado
Corazon, sevilla, 9Rio Hortega, Valladolid, 10Quiron, Madrid, 11La Fe, Valencia,
12
Lozano Blesa, Zaragoza, 13Clinico, Santiago deCompostela, 14Agencia Sanitaria

A275

United European Gastroenterology Journal 2(1S)


Costa del Sol, Malaga, 15Hospital, Fuenlabrada, 16Alto Guadalquivir, Jaen,
17
Hospital, Castellon, 18Gregorio Maranon, Madrid, 19Miguel Servet, Zaragoza,
20
Carmen y Severo Ochoa, Asturias, Spain, 21PO "Immacolata", Sapri, Italy
Contact E-mail Address: adrian.mcn@gmail.com
INTRODUCTION: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing
levofloxacin is an alternative for H. pylori eradication. However, resistance to
quinolones is rapidly increasing and may jeopardize its future efficacy.
Moxifloxacin, a new generation quinolone, may be less affected by quinolone
resistance than levofloxacin.
AIMS & METHODS: To evaluate the efficacy and tolerability of a second-line
triple regimen containing moxifloxacin in patients whose previous H. pylori eradication treatment failed.
Design: Prospective multicenter study. Patients: Patients after failure of either:
- standard triple therapy (PPI, clarithromycin, and amoxicillin)
- non-bismuth quadruple therapy (PPI, clarithromycin, amoxicillin and metronidazole, either sequential or concomitant)
Intervention: Moxifloxacin (400 mg o.d.), amoxicillin (1 g b.i.d.), and esomeprazole (40 mg b.i.d.) for 14 days. Outcome: Eradication was confirmed using the
13C-UBT 4-8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes.
Incidence of adverse effects was evaluated by means of a questionnaire.
RESULTS: 250 patients were consecutively included. Mean age 4815 years,
58% women, 11% peptic ulcer. Previous failed therapy included: standard
triple therapy (179 patients), sequential (27), and concomitant (44). Four patients
did not return after treatment. 97% of patients took all medications correctly.
Per-protocol and intention-to-treat eradication rates were 85.7% (95%CI 8190%) and 82.4 (95%CI 77-87%). Cure rates were similar when compared
depending on the diagnosis (peptic ulcer 77% vs. functional/uninvestigated dyspepsia 82%) and previous treatment (standard triple therapy 83% vs. sequential
89% vs. concomitant 77%). In the multivariate analysis, age was the only variable associated with eradication success (OR 0.957; 95%CI 0.93-0.98).
Adverse effects were reported in 25% of patients (95%CI 20-30%), most commonly diarrhoea (9.6%), abdominal pain (9.6%), nausea (9.2%), metallic taste
(4.5%), asthenia (4.5%), and vomiting (2.5%). In 13 cases, the adverse effects
were classified as intense, but none of them was severe.
CONCLUSION: 14-day moxifloxacin-containing therapy is an effective (480%)
and safe second-line strategy in patients whose previous standard triple therapy
or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple or levofloxacin triple regimens.
Disclosure of Interest: None declared
P0515 THE ROLE OF A DUAL THERAPY CONTAINING HIGH-DOSE
PPI IN ERADICATION IN PATIENTS WITH HELICOBACTER
PYLORI POSITIVE DYSPEPSIA
A.T. Ince1,*, M. Tozlu1, B. Baysal1, H. Senturk1, S. Arc2, A. Ozden3
1
_
Gastroenterology, 2Pathology, Bezmialem Vakf University, Istanbul,
3
Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey
Contact E-mail Address: dralince@gmail.com
INTRODUCTION: H. pylori eradication rates vary by society and usually do
not exceed 80%. Some publications have reported that this rate was even higher
with dual therapies containing high-dose proton-pump inhibitors. H. pylori eradication is recommended in patients with dyspepsia. The objective of the present
study is to determine eradication rates with dual therapy containing high dose
omeprazole in H. pylori-positive patients with dyspepsia.
AIMS & METHODS: The patients were treated orally with either dual (n:74,
omeprazole 20mg q.i.d and amoxicillin 1g b.i.d) or triple therapy (n:116, omeprazole 20mg b.i.d and amoxicillin 1g b.i.d and clarithromycin 500mg b.i.d) for
14 days. HpSA test was requested 3 months later. The results were evaluated
statistically, p values 50.05 were considered significant.
RESULTS: The study included 190 patients (808,1109, p40.05). The mean age
was 35.611 years (p50.001). The mean duration of dyspeptic symptoms was
28.233.7 months (median:18, range:3338). Bloating was more frequent in the
triple therapy group (p50.01) while epigastric pain/burning and early satiation
did not differ significantly between the groups (p40.05). Alcohol and smoking,
endoscopic findings and H. pylori rates with pathological examinations were not
significantly different between groups whereas there was a significant difference
in HpFast tests (p50.01). When examined with HpSA tests 3 months after the
treatment, eradication rate was 81.1% in the dual therapy group versus 63.8% in
the triple therapy group (p 0.011). Dual therapy was more economic compared
to triple therapy (144USDvs.107USD,p50.001).
CONCLUSION: Dual therapy in patients with dyspepsia was more successful,
cost-effective and is less risky in terms of side effects compared to standard triple
therapy.
REFERENCES
1-Lacy BE, Talley NJ, Locke GR 3rd, et al. Review article: current treatment
options and management of functional dyspepsia. Aliment Pharmacol Ther 2012;
36: 3-15.
2-Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders.
Gastroenterology 2006; 130: 1466-1479.
3-Malfertheiner P, Sipponen P, Naumann M, et al. Helicobacter pylori eradication has the potential to prevent gastric cancer: A state-of-the-art critique. Am J
Gastroenterol 2005; 100: 21002115.
4- Villoria A, Garcia P, Calvet X, et al. Meta-analysis: high-dose proton pump
inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication.
Aliment Pharmacol Ther 2008; 28: 868-877.

5- Labenz J, Ruhl GH, Bertrams J, et al. Medium- or high-dose omeprazole plus


amoxicillin eradicates Helicobacter pylori in gastric ulcer disease. Am J
Gastroenterol 1994; 89: 726-730.
Disclosure of Interest: None declared
P0516 SECOND-LINE
REGIMENS
EFFICACY
AGAINST
HELICOBACTER PYLORI INFECTION AFTER STANDARD TRIPLE
THERAPY WITH PPI, AMOXICILLIN & CLARITHROMYCIN: METAANALYSES
A.C. Mar n1,2, A.G. McNicholl1,2, J.P. Gisbert1,2,*
1
Gasttroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid,
Spain
Contact E-mail Address: aliciacmarin@gmail.com
INTRODUCTION: Helicobacter pylori infection is usually treated with a proton
pump inhibitor (PPI), amoxicillin and clarithromycin, but it fails in  20% of
patients.
AIMS & METHODS: Aim: To estimate, by a systematic review and meta-analyses, the most effective rescue treatments after the failure of a first-line therapy
with PPI, amoxicillin and clarithromycin in H. pylori eradication. Methods:
Selection of studies: Meta-analyses were performed with randomized clinical
trials (RCT) that assessed the efficacy of second-line regimens; the generic inverse
variance was applied on prospective and retrospective studies. Inclusion criteria:
Studies treating H. pylori-positive patients after clarithromycin-amoxicillin-PPI
failure. Exclusion criteria: Second-line treatment based on the antibiotic sensitivity, or if the confirmation of eradication was made only by serology, PCR or
polyclonal stool antigen test. Search strategy: Bibliographical searches were performed in PubMed, CINAHL, Cochrane Library, ClinicalTrials.gov, and several
international congresses, up to April 2014. Data synthesis: Intention to treat
eradication rate.
RESULTS: The efficacies of the second-line treatments are shown in the table
attached. A meta-analysis comparing the triple therapy with levofloxacin-amoxicillin-PPI against the quadruple bismuth-metronidazole-tetracycline-PPI regimen showed a non-statistically significant tendency towards better results with
levofloxacin (OR 1.62; 95% C. I. 0.84-3.14; p 0.15; I2 75%; 7 studies;
1,158 patients).
SECOND-LINE
TREATMENT
Levofloxacin Amoxicillin
PPI
-Overall
-7 day treatment
-10 day treatment
-10 days with L(500 mg/24h)
A(1 g/12h)PPI
*Removing 1 outlier study
-14 day treatment
*Removing 1 outlier study
Bismuth Metronidazole
Tetracycline PPI
- Overall
-7 day treatment
-10 day treatment
-14 day treatment
Metronidazole Amoxicillin
PPI
- Overall
-7 day treatment
-7 days with M(250 mg/12h)
A(750 mg/12h)PPI
-10 day treatment
-14 day treatment
Amoxicillin PPI (14 days all
the studies were done in
Japan)
- Overall
-14 day with A (500 mg/6h)
PPI(10 mg/6h)
-14 day with A (1 g/12h) PPI
(20 mg/12h)

E. R.

N. S.

N. P.

95% C. I.

I2

75%
69%
83%
87%

21
11
11
7

2,919
632
1,946
373

70
64
77
81

80%
74%
89%
94%

88%
53%
89%
77%

92%
74%
86%

6
3
2

273
341
151

89 95%
70 78%
81 92%

0%
96%
0%

77%
75%
77%
81%

43
31
2
15

3,685
2,345
142
1,187

74
71
60
76

81%
80%
93%
86%

86%
84%
76%
83%

88%
75%
92%

24
24
12

1,642
1,160
751

85 - 91%
85 - 91%
89 - 95%

75%
75%
48%

84%
81%

4
2

314
127

77 - 91%
75 - 88%

69%
0%

82%
93%

5
3

200
106

69 - 95%
88 - 98%

87%
3%

66%

94

51 - 81%

58%

E. R.: eradication rate; N. S.: Number of studies; N. P.: number of patients.


CONCLUSION: The most effective second-line treatments, after a clarithromycin-amoxicillin-PPI failure, are the metronidazole-amoxicillin-PPI or a 10 day
levofloxacin-amoxicillin-PPI therapy. More high quality trials, performed outside Japan, are needed to verify the efficacy of the 14 day dual therapy with
amoxicillin-PPI.
Disclosure of Interest: A. Mar n: None declared, A. McNicholl: None declared, J.
Gisbert Other: Dr. P. Gisbert has served as a speaker, a consultant and advisory
member for, and has received research funding from MSD and Abbvie.

A276
P0517 SEVEN-DAY NON-BISMUTH CONCOMITANT QUADRUPLE
THERAPY IS SUFFICIENT IN ACHIEVING A GRADE A REPORT
CARD FOR FIRST-LINE ANTI-HELICOBACTER PYLORI THERAPY:
A PILOT STUDY
C.-M. Liang1,*, W.-C. Tai1, S.-K. Chuah1, K.-L. Wu1, Y.-C. Chiu1
Division of Hepato-gastroenterology, Department of Internal Medicine,
Kaohsiung Chang Gung Memorial Hospital and Chang Gung University,
Kaohsiung, Taiwan, Province of China
Contact E-mail Address: gimy54861439@gmail.com
1

INTRODUCTION: The eradication rate of the standard triple therapy has generally declined to unacceptable levels (i.e., 80% or less) recently because the
increasing incidence of clarithromycin-resistant strains of Helicobacter pylori
(H. pylori). 10-day concomitant therapy (non-bismuth concomitant quadruple
therapy) can achieve a promising success rate of 90-94% in the presence of
clarithromycin resistance. This therapy is superior to standard triple therapy
for H pylori eradication and less complex as this regimen does not involve changing drugs halfway through.
AIMS & METHODS: This study is to assess the efficacy of 7-day concomitant
therapy and to investigate the host and bacterial factors influencing the treatment
outcomes of all eradication therapies. One hundred and eighty consecutive H.
pylori-infected patients are randomly assigned to a 7-day non-bismuth quadruple
therapy (EACM group, Esomeprezole 40 mg bid., amoxicillin 1 g bid., clarithromycin 500 mg bid., and metronidazole 500 mg bid. for 7 days) or a 7-day
standard triple therapy (EAC group, Esomeprezole 40 mg bid., amoxicillin
1mg bid., clarithromycin 500 mg bid., and for 7 days). Patients are asked to
return at the 2nd week to assess drug compliance and adverse events.
Repeated endoscopy with rapid urease test, histological examination and culture
is performed at the 8th week after the end of anti- H. pylori therapy. If patients
refuse follow-up endoscopy, urea breath tests are conducted to assess H. pylori
status. Additionally, antibiotic susceptibility of H. pylori will be examined.
Finally, the rates of eradication, adverse events and compliance will be compared
between groups by chi-square test, and the host and bacterial factors influencing
each efficacy of the regimen are assessed by multivariate analysis.
RESULTS: Our results demonstrated that the eradication rates for EACM therapy and EAC standard triple therapy in intention-to-treat analysis were 86.7%
vs. 72.2%, P 0.016 and 95.1% vs. 79.2%, P 0.002) in the per-protocol analysis. Drug compliances were 100% in both groups although more adverse events
were reported in the EACM group (35.3% vs. 18.3%, P 0014). Clarithromycin
resistance was the only independent predictors of treatment failure in multivariate analysis. In the subgroup analysis according to antibiotics susceptibility, none
of the patients with clarythromycin resistant strains and 33.3% with metronidazole resistant strains were eradicated in the EAC group while 75% of those with
resistant strains were eradicated in the EACM group.
CONCLUSION: This study suggests that a 7-day non-bismuth concomitant
quadruple therapy is sufficient in achieving a grade A report card for first-line
anti-H. pylori therapy. Clarithromycin resistance was the factor responsible for
eradication failures.
REFERENCES
1. Graham DY and Fischbach L. Helicobacter pylori treatment in the era of
increasing antibiotic resistance. Gut 2010; 59: 1143-1153.
2. Wu DC, Hsu PI, Wu JY, et al. Sequential and concomitant therapy with four
drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol
Hepatol 2010; 8: 36-41.
Disclosure of Interest: None declared
P0518 EMPIRICAL
RESCUE
THERAPY
AFTER
H.
PYLORI
TREATMENT FAILURE. A 15-YEAR SINGLE CENTER STUDY OF
1,000 PATIENTS
D. Burgos Santamar a1,*, A.G. McNicholl1, J.L. Gisbert1, S. Marcos1,
M. Fernandez-Bermejo2, J. Molina-Infante2, J.P. Gisbert1
1
Hospital Universitario de La Princesa, IP, CIBEREHD, Madrid, 2Hospital San
Pedro de Alcantara, Caceres, Spain
Contact E-mail Address: diegoburgossantamaria@gmail.com
INTRODUCTION: The most commonly used empirical therapies for H. pylori
eradication fail up to 20-30% on first line, and even more in rescue therapies.
This is mainly due to increasing antibiotic resistances and poor compliance.
Therefore it is necessary to evaluate the efficacy and safety of the overall eradicating strategy, including multiple and consecutive lines of treatment.
AIMS & METHODS: To evaluate the efficacy of different rescue therapies
empirically prescribed during 15 years to 1,000 patients in whom at least one
eradication regimen had failed to cure H. pylori infection.
Design: Retrospective single-center study. Patients: 1,000 consecutive patients
who had failed at least one eradication therapy (1998-2013). Intervention: The
most common eradication treatments were: 1) PPI-Amoxicillin-Levofloxacin
(PPI-A-L), 2) Ranitidine bismuth citrate-Tetracycline-Metronidazole (Rcb-TM), 3) Classic Quadruple therapy (PPI-Bismuth-Tetracycline-Metronidazole)
(PPI-B-T-M), 4) Esomeprazole-Moxifloxacin-Amoxicillin (E-Mox-A), 5) PPIAmoxicillin-Rifabutin (PPI-A-Rif). Rifabutin was prescribed only as 4th line,
and the other treatments were used both as 2nd and 3rd line. As antibiotic
susceptibility was unknown, rescue regimens were prescribed empirically.
Rescue regimens were prescribed without retreating with the same drugs.
Outcome: Eradication was defined as a negative 13C-urea breath test 4-8 weeks
after completing therapy. Modified intention-to-treat analysis was used, considering patients with poor compliance, but not those who were lost during the
follow-up.
RESULTS: Overall eradication rates of H. pylori with 2nd, 3rd and 4th lines of
rescue therapies were 74.6%, 71.1% and 50% respectively, with a cumulative

United European Gastroenterology Journal 2(1S)


eradication rate after consecutive administration of 4 treatments of 99.2%.
Compliance with 2nd, 3rd and 4th line regimens was 95.6%, 93% and 93.5%
respectively, with an overall compliance of 95.1%. The efficacy and adverse
effects of treatments were 83.5% and 24.2% with E-Mox-A, 77.8% and 24%
with PPI-L-A, 68.9% and 21.5% with PPI-B-T-M, 66% and 33.3% with Rcb-TM, and 62% and 37.9% with PPI-A-Rif. The highest rate of eradication was
achieved with E-Moxi-A (83%) as a 2nd line treatment, regardless of the first-line
regimen prescribed.
CONCLUSION: H. pylori eradication rates may reach 99% without performing
bacterial culture by using a rescue strategy of 4 consecutive empirical treatments.
The best rescue strategy to eradicate H. pylori is the consecutive administration
of quinolones (2nd line), PPI-B-T-M (3rd line) and PPI-A-Rif (4th line).
Disclosure of Interest: None declared
P0519 LETS TRY QUINTUPLE THERAPY AS A RESCUE ERADICATION
REGIMEN FOR REFRACTORY H. PYLORI INFECTION
F. Mansour-Ghanaei1,*, A. Shafaghi1, F. Joukar1, M. Naghipour2
Gastrointestinal and Liver Diseases Research Cente, 2Epidemiology, GUILAN
UNIVERSITY OF MEDICAL SCIENCES, Rasht, Iran, Islamic Republic Of
Contact E-mail Address: ghanaie@yahoo.com
1

INTRODUCTION:
To compare the efficacy, tolerability and side effect profiles of two quintuple
regimens for helicobacter pylori (H. pylori) eradication in patients who failed the
first line quadruple therapy.
AIMS & METHODS: Between April 2011 and March 2012, a total of 208
patients with dyspepsia who failed H. pylori eradication using the standard quadruple therapy with BOAC (Bismuth subcitrate, Omeprazole, Amoxicillin,
Clarithromycin) or BOAM (Bismuth subcitrate, Omeprazole, Amoxicillin,
Metronidazole) were recruited for this study. The patients were randomized
into two equal groups using random block method. Patients in BOACT group
were treated by omeprzole 20 mg, combined with bismuth subcitrate 240 mg, and
three antibiotics clarithromycin 500 mg, amoxicillin 1000 mg and tinidazole 500
mg all twice daily for seven days. Patients in the BOTMO group were given
omeprazole 20 mg and bismuth subcitrate 240 mg along with tetracycline 500
mg and ofloxacin 200 mg in the same manner as in BOACT group. The eradication was confirmed at 12 weeks after end of therapy by C14 urea breath test.
Patients compliance and drugs side effects were evaluated at the end of treatment. The success rates were calculated separating by intention-to-treat (ITT)
and per-protocol (PP) analyses.
RESULTS: A total number of 208 patients were included in the study and 205
patients completed the treatment course. The intention-to-treat and per-protocol
eradication rates were 75.5% and 76% in the BOACT group and 86.5% and
86.7% in the BOTMO group, respectively. The eradication rates of the BOTMO
group was significantly higher than BOACT group (p 0.04). Side effects were
reported from 33.2% of the patients which were mild and did not necessitate
interfere with therapy although 3 patients (2 patient in BOACT group and 1
patient in BOTMO group were excluded from the study due to severe drug side
effects.
CONCLUSION: Quintuple therapy with BOTMO could be an alternative
second-line rescue therapy for Iranian patients who have failed one previous
standard treatment for H. pylori eradication, but its efficacy needs to be confirmed in other populations before we can generalized our findings, considering
regional antimicrobial resistance. Considering the short length of treatment in
our study, further studies to assess the effects of quintuple therapies by BOTMO
regimen with periods longer than 7 days is recommend
Disclosure of Interest: None declared
P0520 HELICOBACTER PYLORI ERADICATION RATES AND PLASMA
PANTOPRAZOLE LEVELS IN TYPE 2 DIABETIC AND
NONDIABETIC PATIENTS
F. Sapmaz1,*, I.H. Kalkan1, I. Suslu2, S. Guliter1
1
Gastroenterology, Krkkale University Faculty of Medicine, Krkkale,
2
Pharmeceutics, Hacettepe University Faculty of Medicine, Ankara, Turkey
Contact E-mail Address: ferda-sapmaz@hotmail.com
INTRODUCTION: The eradication rate of Helicobacter pylori has been
reported as being lower in patients with type 2diabetes mellitus (DM) than in
those without DM.
AIMS & METHODS: The first aim of this study was to compare the efficacy of a
bismuth-based quadruple regimen as first-line therapy for Helicobacter pylori
(HP) eradication in diabetic and non-diabetic patients. The second aim of the
study was to compare plasma Pantoprazol levels in these patient groups during
H. pylori eradication treatment.
Forty consecutive type 2 DM and 40 non-diabetic na ve H. pylori infected patients
were enrolled in this study. All patients received Pantoprazole (40 mg b.i.d.),
bismuth citrate (120 mg q.i.d.), tetracycline (500 mg q.i.d.), and metronidazole
(500 mg t.i.d.) for 14 days as the eradication regimen. We used Square-Wave
Voltammetry method to determine plasma Pantoprazole levels in both groups.
RESULTS: The overall compliance rates among the diabetic patients and control
group were 90.0% (36/40) and 92.5% (37/40), respectively. The per-protocol HP
eradication rates (63.9% vs 89.2%, p 0.01), Intention-to-treatment HP eradication rates (60% vs 87.5%, p50.001) and Plasma Pantoprazole levels (0.25mgmL-1
vs. 0.34 mgmL-1, p 0.005) were significantly lower in diabetic patients.
CONCLUSION: Our study showed that diabetic patients had lower plasma
Pantoprazole levels which led to lower H. pylori eradication rates with a bismuth
and Pantoprazole including regimen. Clinical and pharmacokinetic investigations
are required to improve plasma proton pump inhibitor levels in diabetic patients
for satisfactory H. pylori eradication rates.

A277

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
SMALL INTESTINAL I POSTER EXHIBITION HALL XL_____________________
P0521 CAUSE-SPECIFIC MORTALITY IN PEOPLE WITH COELIAC
DISEASE COMPARED TO THE GENERAL POPULATION: A
COMPETING-RISK ANALYSIS
A. Abdul Sultan1,*, C. Crooks1, T. Card1, L. Tata1, K. Fleming1, J. West1
1
University of Nottingham, Nottingham, United Kingdom
Contact E-mail Address: alyshah.sultan@hotmail.com
INTRODUCTION: Quantifying excess cause specific mortality among people
with coeliac disease (CD) compared to the general population accounting for
competing risks (which takes into account that patients may die due to other
causes before dying from the cause of death of interest) will allow accurate
information to be given on prognosis and risks of adverse outcomes.
AIMS & METHODS: This study quantifies the excess cause specific mortality
among people with CD by 10 year of diagnosis compared to the general population while accounting for competing risks. We identified from the Clinical
Practice Research Datalink (CPRD), all patients with CD for whom linkage to
Office of National Statistics (ONS) data to determine cause of death if it occurred
was available. We selected controls by frequency matching from the registered
GP population within 10 year age bands. We calculated the adjusted cumulative
incidence (including adjustment for competing risks) for different causes of death
up to 10 years from diagnosis. We also calculated the excess cumulative incidence
(eCI) for each cause of death compared to controls.
RESULTS: Of the 5,310 patients with CD, 352 died within the study period. The
overall mortality rateamong CD patients was 124 per 10,000 person-years compared to 111/10,000 in controls. By 10 years after CD diagnosis, the cumulative
incidence of death (Table 1) from cardiovascular related deaths was slightly lower
compared to those without CD diagnosis (CD 0.16% versus Controls 0.26%)
with a corresponding eCI of 0.1% (95% CI -0.14 to -0.06). Overall there was no
difference in the cumulative incidence of respiratory, digestive or cancer related
death among cases and controls. However, CD patients had 0.1% excess risk
(95%CI;0.01-0.16) of deaths death from non-Hodgkins lymphoma or
leukaemia.
Table 1: Cumulative incidence and excess risk by 10 years after diagnosis
adjusted for competing risks, gender, age and social class
Cause of death

With CD

Without CD

Excess

95% CI

Cardiovascular overall
Ischemic heart disease
Respiratory overall
Neoplasm overall
Non-hodgkins/leukemia
Digestive overall

0.16
0.10
0.07
0.78
0.13
0.15

0.26
0.15
0.07
0.72
0.04
0.11

-0.10
-0.05
0.00
0.06
0.08
0.05

-0.14
-0.08
-0.02
-0.11
0.01
-0.03

-0.06
-0.16
0.03
0.23
0.16
0.13

CONCLUSION: Overall, people with CD have no major excess risk of cancer,


digestive, cardiovascular or respiratory related mortality compared to the general
population over the 10 year period following initial diagnosis. In addition they
have only a very small excess risk of dying of haematological malignancy. These
findings should be reassuring to both patients with CD and clinicians managing
their care.
Disclosure of Interest: None declared
P0522 NUTRIENTS INTAKE IN NON CELIAC PATIENTS ON GLUTEN
FREE DIET BECAUSE OF PERCEIVED GLUTEN SENSITIVITY:
COMPARISON WITH CELIAC PATIENTS AND WITH NATIONAL
NUTRITIONAL GUIDELINES
B. Zanini1,*, M. Marullo1, A. Ferraresi1, F. Caselani1, C. Ricci1, F. Lanzarotto1,
A. Lanzini1
1
Department of Clinical and Experimental Sciences, UNIVERSITY AND
SPEDALI CIVILI OF BRESCIA, Brescia, Italy
Contact E-mail Address: b_zanini@tin.it
INTRODUCTION: Non celiac and non wheat allergic patients that spontaneously adhere to gluten free diet (GFD) because of adverse gastrointestinal
and extra-intestinal reactions to gluten containing food are frequently encountered in clinical practice and are commonly referred to as gluten sensitive (GS)
patients. In most cases GS patients do not seek dietician advice on GFD, and no
information is available on the nutritional adequacy of their self-made diet.
AIMS & METHODS: We carried out a prospective clinical study to assess
macro- and micro-nutrients of GFD in GS patients compared with that of a
cohort of patients with celiac disease (CD) matched according to gender and
age (range /-4 years), and with the recommendations of the Italian nutritional
guidelines (LARN 2012). Patients in the 2 study cohorts were asked to fill in a
standardized 7-day food diary. Data from diaries were analyzed with Microdiet
software (Downlee systems, ltd. UK) that returns very detailed information on
diet composition. Nutritional characteristics included: total Kcal, proportion of
total energy values of CHO, free sugars, proteins, fats, SFA and PUFA, and total
amounts of fibres, vitamins A, C, D, B12, folates, sodium, calcium, iron, zinc,
selenium, magnesium and alcohol. For statistical analysis Fishers exact test and
Wilcoxon matched paires test were used as appropriate.

RESULTS: Twenty-two GS patients (mean  SD 40 9 years, BMI 223) and


22 CD patients were enrolled. Total Kcal were 1767 501 Vs 1544 539 in GS
and CD respectively, with no difference in % contribution of CHO, fats and
proteins to total calories. The proportion of macro-nutrients in the diet that was
correct according to the LARN recommendations was 54%, 59% and 32% in
GS and 18%, 41% and 5% in CD for CHO, proteins and fats, respectively.
Comparison of selected nutrient composition in GS Vs CD patients and Vs
LARN are reported in the table.
Nutrients

GS

CD

GS Vs LARN %x

PUFA, % TEV
Fibres, g
Alcohol, g
Vitamin B12, mg
Vitamin D, mg
Folates, mg
Magnesium, mg
Iron, mg
Selenium, mg

4.62.2
20.024.9
2.34.4
3.91.8
2.21.2
324.5381.5
146.7101.4
9.05.4
39.016.3

3.41.2*
11.96.5
4.08.9
1.01.6*
1.50.9*
131.774.7*
44.664.4*
5.42.7*
10.416.0*

- 50
-86
NA
-14
-100
-73
-77
-68
-55

CONCLUSION: Patients spontaneously adhering to a GFD for perceived GS


have, despite no dietetic instruction, a more balanced intake of macro- and
micro-nutrients in comparison with CD patients. This phenomenon may be the
result of a behavioural attitude towards healthy food more pronounced in GS
than in CD patients, although LARN recommendations are not met for most
nutrients.
Disclosure of Interest: None declared
P0523 SPLEEN DIAMETER/RDW AS A NOVEL INDICATOR FOR
CELIAC DISEASE
D. V. Balaban1,*, A.M. Lungu1, A. Popp2, B. Macadon1, S. Bucurica1,
R. Costache1, P. Nut;a1, F. Ionit;a-Radu1, M. Jinga1,2
1
Gastroenterology Clinic, "Dr Carol Davila" Central Military Emergency
University Hospital, 2"Carol Davila" University of Medicine and Pharmacy,
Bucharest, Romania
Contact E-mail Address: vbalaban@yahoo.com
INTRODUCTION: Red cell distribution width (RDW) has been shown in previous studies to be a sensitive predictor for coeliac disease (CD), but it lacks
specificity. Splenic hypotrophy is also noted frequently in celiac patients. Our aim
was to evaluate if spleen size/RDW can be used as an indicator for celiac disease.
AIMS & METHODS: We evaluated 32 patients with small bowel disease (12
newly diagnosed CD patients and 20 patients with Crohns disease, IBD-CD) and
32 age-matched patients with irritable bowel syndrome (IBS), admitted to our
clinic over a one-year period. We evaluated the differences in spleen diameter,
RDW and their ratio among the three groups.
RESULTS: Of the 32 patients with small bowel disease, 11 were males, with a
mean age of 38.34 years. Mean RDW was significantly higher in the CD and
IBD-CD groups than the IBS group (14.49 and 16.73 vs. 13.51, p 0.0099),
whereas mean spleen size was lowest in the CD patients (84.08, 107.85 and
112.62 mm respectively). The mean spleen diameter/RDW was 5.82 in the CD
group, 6.65 in the IBD-CD group and 8.34 in the IBS group (p 0.0001). A ratio
under 6 had a sensitivity of 75% and a specificity of 88.46% in detecting CD.
CONCLUSION: Spleen diameter/RDW is a simple, widely available score,
which can be used to select patients for futher diagnostic tests. This should be
repeated in larger patient cohorts.
Disclosure of Interest: None declared
P0524 CELIAC DISEASE AND DRUG-BASED THERAPIES: INQUIRY
INTO PATIENTS DEMANDS
F. Branchi1,2,*, C. Tomba1,2, M.T. Bardella1, L. Roncoroni1, M. Locatelli1,2,
F. Somalvico1, D. Conte1,2, L. Elli1
1
Center for the Prevention and Diagnosis of Celiac Disease Gastroenterology and
endoscopy Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico,
2
Universita` degli Studi di Milano, Milano, Italy
Contact E-mail Address: lucelli@yahoo.com
INTRODUCTION: The gluten free diet (GFD) is the only available therapy for
patients with celiac disease (CD). Medical research is actively focused on the
search for drug-based solutions as an alternative to GFD, which requires lifelong, strict adherence.
AIMS & METHODS: We aimed at evaluating the actual need for other-thanGFD therapies perceived by CD patients, along with the impact of GFD itself on
their life.
During the 2012 meeting of the Lombardy section of the Italian CD Patients
Association, adult CD subjects on GFD were invited to fill in a questionnaire
investigating their clinical profile in relation to GFD compliance, health status
and quality of life as well as their opinion on GFD, alternative therapies and
research priorities.
RESULTS: 372 patients (76 M, mean age at diagnosis and at entry 29.7  16.9
and 41.7  13.9 years, respectively) completed the questionnaire. 94% patients
reported strict adherence to GFD. Patients reported a significant improvement in
health status and quality of life after the diagnosis of CD was made and GFD
was started (p50.001), with a greater improvement of health status than quality

A278
of life (82% vs 56%, p50.001). GFD was favourably considered and accepted by
88% patients, but a demand for alternative therapies was reported by 65%
patients. Subjects expressing the need for a drug-based therapy showed a significantly lower increase of quality of life on GFD (p 0.002), but no differences
were observed in health status changes. The preferred option for an alternative
therapy was the on demand assumption of drugs, i.e. enzymes (145 subjects),
followed by a vaccine-based strategy (111 subjects). Almost two thirds of the
cohort stated they would accept to be enrolled in ad hoc designed clinical trials.
CONCLUSION: GFD is favourably accepted and followed by most CD
patients, with significant health status improvement. Nevertheless, a considerable
proportion of patients pronounce themselves in favour of the development of
alternative drugs, although a chronic drug therapy is not considered a likely
opportunity.
REFERENCES
1. Schuppan D, Junker Y and Barisani D. Celiac disease: from pathogenesis to
novel therapies. Gastroenterology 2009; 137: 1912-1933.
2. Aziz I, Evans KE, Papageorgiou V, et al. Are patients with celiac disease
seeking alternative therapies to a gluten-free diet? J Gastrointestin Liver Dis
2011; 20: 27-31.
3. Mukherjee R, Kelly CP and Schuppan D. Nondietary therapies for celiac
disease. Gastrointest Endosc Clin N Am 2012; 22: 811-831.
Disclosure of Interest: None declared
P0525 IMPAIRED BONE MICROSTRUCTURE IMPROVES AFTER ONEYEAR ON GLUTEN-FREE DIET. A PROSPECTIVE LONGITUDINAL
STUDY IN WOMEN WITH ACTIVE CELIAC DISEASE
G. I. Longarini1,1,*, M.B. Zanchetta2, A.F. Costa1, V. Longobardi2,
M.P. Temprano1, H. Vazquez1, S. Niveloni1, E. Smecuol1, M.L. Moreno1,
H. Hwang1, R. Mazure1, A. Gonzalez1, E. Maurino1, J.C. Bai1
1
Medicine, Hospital Udaondo, 2IDIM, Buenos Aires, Argentina
Contact E-mail Address: mbzanchetta@idim.com.ar
INTRODUCTION: We have recently identified a significant deterioration of
trabecular and cortical microarchitecture in peripheral bones of patients with
undiagnosed celiac disease (CD) by using high resolution-peripheral quantitative
computed tomography (HR-pQCT). Such finding may underlie bone fragility
and lead to fractures in these patients. Up to now, the effect of the gluten-free
diet (GFD) on microstructural parameters of peripheral bones has not been
assessed.
AIMS & METHODS: Aim: To explore one-year changes of bone microstructure
associated with the GFD in a prospective cohort of premenopausal women with
newly diagnosed CD.
Materials: We prospectively enrolled 31 consecutive females with newly diagnosed CD. Up to now, 25 patients have been reassessed one-year after diagnosis.
Clinical and biochemical status, CD specific serology, assessment of the degree of
compliance with the GFD, bone densitometry and microstructural determinations (HR-pQCT) were performed at both time points. HR-pQCT bone volumetric and structural measurements were determined at the distal non-dominant
radius and tibia. Parameters of patients were also compared with those of 22
healthy women of similar age and body mass index.
RESULTS: Compared with the baseline z-score, the one-year bone mineral density measured by dual energy x-ray absorptiometry (DXA) improved significantly at the distal radius (meanSD) (-1.941.27 vs. -1.431.06; p50.02) but
not at the lumbar spine level. The microstructure of the trabecular compartment
in the distal radius was significantly improved (trabecular/bone volume fraction,
trabecular density and trabecular thickness: p50.0001) at the one-year time
point. At the level of tibia, treatment was associated with significant increment
of the total volumetric density (p50.01), cortical density (p50.002), trabecular
density (p50.0001), trabecular/bone volume fraction (p50.0001) and trabecular
thickness (p50.002). In contrast, the cortical thickness decreased significantly in
both sites (p50.001). Compared to the control group there were no statistically
significant differences in most trabecular parameters measured by HR-pQCT.
CONCLUSION: This is the first study exploring the effect of a one-year GFD on
microstructural parameters measured by HR-pQCT in patients with newly diagnosed CD. Our study shows that trabecular parameters impaired at the time of
diagnosis improved significantly by treatment reaching values comparable to
those in healthy controls. We postulate that bone microarchitecture improvement
underlie the decreased risk of fractures observed after treatment with a GFD.
Disclosure of Interest: G. Longarini: None declared, M. Zanchetta: None
declared, A. Costa: None declared, V. Longobardi: None declared, M.
Temprano: None declared, H. Vazquez: None declared, S. Niveloni: None
declared, E. Smecuol Financial support for research from: Astra Zeneca,
Lecture fee(s) from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, M.
Moreno: None declared, H. Hwang: None declared, R. Mazure: None declared,
A. Gonzalez: None declared, E. Maurino: None declared, J. Bai: None declared

United European Gastroenterology Journal 2(1S)


P0526 HOW DOES SPECIFIC SEROLOGY MATCH WITH ESPHGAN
SEROLOGIC GUIDELINES FOR DIAGNOSIS OF CELIAC DISEASE
IN A PROSPECTIVE COHORT OF ADULTS WITH HIGH PRETEST
PROBABILITY?
G. I. Longarini1,*, E. Sugai1, H. Hwang1, F. Nachman1, A. Cabanne1,
H. Vazquez1, M.L. Moreno1, A.F. Costa1, M. I. Pinto1, S. Niveloni1,
E. Smecuol1, R. Mazure1, E. Maurino1, J.C. Bai1
1
Medicine, Hospital Udaondo, Buenos Aires, Argentina
Contact E-mail Address: emiliasugai@yahoo.com
INTRODUCTION: Intestinal biopsy is considered mandatory for the diagnosis
of celiac disease (CD). This has been recently challenged by several studies and
the 2012 ESPGHAN guideline proposing an appropriate clinical and serological
algorithm that could be used to reduce the need for duodenal biopsy. This
provocative strategy has been confirmed by some studies but rejected by
others. However, all these studies were performed on the basis of retrospective
analyses of biased populations. Prospective evaluation of patients in whom diagnosis was based on histological grounds is important to clarify this controversy.
AIMS & METHODS: 1-To review the performance of serology tests in a prospective and consecutive series of adult patients with high pretest probability for
CD; 2- to compare performance of serologic tests with the ESPGHAN serologic
algorithm; and 3- to establish the best serologic algorithm for diagnosing CD
using antibody tests detecting different antigens.
We performed a post hoc analysis of data from all patients enrolled in a previous
prospective study (WJG 2010; 16: 3144) where consecutive adults suspected of
intestinal disorders (high pretest population) were enrolled. Diagnosis of CD was
based on histology (Marshs stages 3a) in all patients irrespective of serology.
CD-related serology consisted of seven different assays but we only report the
performance of tissue transglutaminase (tTG) IgA, deamidated gliadin peptides
(DGP) IgG and the combination of both (INOVA Diag. Inc.). Serologic performance was compared with the ESPGHAN serologic criterion (cut-off 410 times
the upper limit of normal -ULN-), the best cut-off (area under the ROC) and the
cut-off suggested by the manufacturer.
RESULTS: Sixty-three of 161 patients (39%) had histological criteria for CD.
According to the ESPGHAN criterion, IgA tTG sensitivity was 22% with 100%
positive predictive value (PPV). The best cut-off value (34 AU/mL) would detect
93.6% of patients with 100% of PPV. Finally, the manufacturer cut-off (20 AU/
mL) had 95.2% sensitivity and 97.9% PPV. The ESPGHAN criterion used for
IgG DGP was 3.2% sensitive with a PPV of 100%. The best cut-off (was similar
to that of the manufacturer: 20AU/mL) was 95.2% sensitive and had 100% PPV.
Any test was positive (420AU/mL) in all patients and both were concomitantly
positive in 90.5% of cases with100% of PPV.
CONCLUSION: This prospective study indicates that, under particular clinical
circumstances, a serologic strategy can be used to avoid duodenal biopsy in the
diagnosis of adult patients with CD. The need for biopsy could be avoided in a
minority of patients by using the ESPGHAN serologic criterion. Our results
suggest that the best serologic strategy for a high pretest population seems to
be the association of tTG IgA and DGP IgG. In such context, biopsy could be
avoided in more than 90% of the cases when both tests are positive.
Disclosure of Interest: G. Longarini: None declared, E. Sugai: None declared, H.
Hwang: None declared, F. Nachman: None declared, A. Cabanne: None
declared, H. Vazquez: None declared, M. Moreno: None declared, A. Costa:
None declared, M. Pinto: None declared, S. Niveloni: None declared, E.
Smecuol Financial support for research from: Astra Zeneca, Lecture fee(s)
from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, R. Mazure: None
declared, E. Maurino: None declared, J. Bai: None declared
P0527 HIGH RATES OF PRIOR CELIAC DISEASE OVERDIAGNOSIS
AMONG PATIENTS REFERRING TO AN ITALIAN TERTIARY
CARE CENTER
G. Ianiro1,*, G. Bruno1, S. Bibbo`1, S. De Martino1, V. Arena2, A. Gasbarrini1,
G. Cammarota1
1
Dept of Internal Medicine, Division of Gastroenterology, 2Histopathology Unit,
CATHOLIC UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: Celiac disease (CD) was formerly considered a rare condition and frequently underdiagnosed. Interest in CD has grown in recent years,
not only among gastroenterologists but also among general practitioners and
patients. Furthermore, focus of media on gluten-free diet (GFD) is increasingly
spreading worldwide. Therefore many patients are labeled as celiacs and start a
GFD even without completing the correct diagnostic process.
AIMS & METHODS: Our aim is to assess the impact of overdiagnosis in an
Italian tertiary referral center for CD. We reviewed the clinical history of all
patients referring to our Centre from October 2012 to December 2013. We
included only patients at their first examination. We questioned diagnoses for
the following reasons: EMA/TTG absence or negativity; duodenal biopsy not
performed or unclear; DQ2/DQ8 negativity. Following data of patients with a
doubtful diagnosis were extracted: people who have diagnosed CD (physicians or
patients); reasons for diagnosis (symptoms, DQ2/DQ8, specific antibodies, duodenal biopsy), gluten consumption status. Number of patients undergoing a
proper diagnostic process was determined, as well as of patients with a prior
undebatable diagnosis. Diagnosis was revaluated by repetition of serology and
by second-reading of duodenal tissue slides by an experienced pathologist. DQ2/
DQ8 was searched in pertinent cases.
RESULTS: Over the study period, 293 patients attended our Centre, of whom
150 for the first time. Of them, 47 (31.3%) presented with an undebatable diagnosis of CD, and 37 (24.7%) were newly diagnosed because of EMA/TTG positivity associated with duodenal Marsh lesions. In 15 patients (10%) referring for

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United European Gastroenterology Journal 2(1S)


family history of CD, gastrointestinal symptoms or anemia, CD was excluded by
serology and histology assessment. The remaining 51 patients (34%) came for a
revaluation of previously diagnosed CD. Forty-five of them (88%) were on a
GFD at the time of the examination. Thirty-five patients (68.6%) were diagnosed
of CD by their trusted doctor (gastroenterologist, gynaecologist, dermatologist
or general practitioner), while the remaining 16 (31.4%) believed to be affected of
CD on their own. Motivations for prior CD diagnosis were often multiple for
each patient: serologic positivity (9 AGA, 5 EMA, 2 TTG) in 16 cases, histological features in 19 cases, DQ2/DQ8 positivity in 20 cases, amelioration of symptoms after GFD in 16 cases. Reasons for questioning previous diagnosis were
also multiple for each patient: EMA/TTG absence or negativity in 45 cases; lack
of duodenal biopsy in 20 cases; unclear histology in 24 cases; DQ2/DQ8 negativity in 2 cases. Diagnosis of CD was rejected in 78.4% of doubtful cases
(n 40), being confirmed in only 19.6% (n 10) of them. In one patient, diagnosis is still ongoing.
CONCLUSION: Our retrospective study shows that a considerable number of
patients referring to an Italian tertiary care center experience previous misdiagnosis and/or overdiagnosis of CD. Such behavior may lead to both a diagnostic
delay of other diseases and a remarkable waste of economic resources (tax
exemptions, gluten-free food vouchers, diagnostic exams), with damage for
both patients and health services. Greater accuracy in the application of the
adequate diagnostic process and a higher adherence to guidelines are needed to
minimize misdiagnosis of CD.
Disclosure of Interest: G. Ianiro: nothing to declare, G. Bruno: nothing to
declare, S. Bibbo`: nothing to declare, S. De Martino: nothing to declare, V.
Arena: nothing to declare, A. Gasbarrini: nothing to declare, G. Cammarota:
nothing to declare
P0528 GLUTEN AVOIDANCE BEFORE A DEFINITE DIAGNOSIS IS
MORE COMMON AMONG NON-CELIAC SUBJECTS THAN
CELIAC ONES
G. Ianiro1,*, G. Bruno1, S. Bibbo`1, S. De Martino1, V. Arena2, A. Gasbarrini1,
G. Cammarota1
1
Dept of Internal Medicine, Division of Gastroenterology, 2Histopathology Unit,
CATHOLIC UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: Gluten is known to trigger not only celiac disease, but also
other conditions, such as non-celiac gluten sensitivity (NCGS) and wheat allergy,
recently grouped together as gluten-related disorders. Gluten has recently
shown to cause depression in subjects with NCGS. Furthermore, gluten is able
to cause gastrointestinal (GI) symptoms and to alter bowel barrier functions in
patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Glutenfree claims are increasingly spreading on the Web and other media, and many
subjects start a gluten-free diet (GFD) without any prior medical consultation.
Such a behavior may lead to a considerable waste of resources and to diagnostic
delay both in celiac and in non-celiac subjects.
AIMS & METHODS: Our aim was to assess the impact of gluten avoidance
before a definite diagnosis in both patients with and without celiac disease. We
reviewed the clinical history of all patients referring to our CD outpatient clinic
from October 2012 to December 2013. We included only patients without a
definite diagnosis of CD at their first examination at our Centre. Patients were
grouped according to their gluten consumption status at the time of examination.
Gluten was reintroduced for at least 2 months before any diagnostic assessment
in all subjects already on GFD. The following data were extracted from patients
on GFD at the time of examination: gender, age, reasons for gluten avoidance
without definite diagnosis (GI/extraintestinal symptoms, DQ2/DQ8, specific
antibodies, duodenal biopsy), proposer of GFD (physicians or the patient
itself). All patients underwent blood dosage of EMA, TTG and total IgA
levels, as well as upper endoscopy with duodenal biopsy. In all patients CD
was diagnosed because of EMA and TTG positivity associated with Marshtype intestinal lesions. Correlation between gluten avoidance and further diagnosis of CD was assessed by Chi-square test.
RESULTS: Over the study period, a total amount of 293 patients attended our
Centre, of whom 150 (M 41, F 109 mean age 39 y) for the first time. Ninety-two
patients came without a definite diagnosis of CD. Of them, 32 (34.8%) were on
GFD at the time of examination, and 60 (66.2%) were not. Reasons for GFD
without definite diagnosis were: GI symptoms (12 cases), extraintestinal symptoms (7 cases), DQ2/DQ8 positivity (9 cases), antibody positivity (6 cases), histological features (9 cases). Sixteen patients started a GFD on their own (41%),
and 23 upon medical advice (58%). Gender did not influence gluten consumption
status (p 0.8376). Respectively, CD was diagnosed in 21.9% (7/32) of patients
on GFD and 71.8% (43/60) of patients on a gluten-containing diet at the time of
first examination (P50.0001).
CONCLUSION: Our study shows that gluten avoidance before a clear definition
of diagnosis is more common among subjects in whom CD is ruled out at a later
stage than ones diagnosed of CD afterwards. The increasing interest of physicians and patients in gluten-related diseases, and unmotivated gluten-free claims
may explain such reasons. Also symptom burden and gluten influence on mental
component of patients may play a role in this phenomenon. However, the retrospective nature of our study represents a limitation in data analysis. Further,
prospective trials are warranted to clarify this issue.
Disclosure of Interest: G. Ianiro: nothing to declare, G. Bruno: nothing to
declare, S. Bibbo`: nothing to declare, S. De Martino: nothing to declare, V.
Arena: nothing to declare, A. Gasbarrini: nothing to declare, G. Cammarota:
nothing to declare

P0529 IS VISCERAL ADIPOSE TISSUE A RISK FACTOR FOR SMALL


BOWEL ANGIOECTAISA?
A. Yamada1,*, R. Niikura1, Y. Kobayashi1, H. Suzuki1, H. Watabe1, S. Yoshida2,
Y. Hirata1, K. Koike1
1
Department of Gastroenterology, Graduate School of Medicine, 2Department of
Endoscopy and Endoscopic Surgery, The University of Tokyo, Tokyo, Japan
INTRODUCTION: Small bowel angioectasia (SBA) is one of the major bleeding
sources of obscure gastrointestinal bleeding (OGIB). Little is known about etiology of SBA. Visceral adipose tissue (VAT) expresses some bioactive molecules
including vascular endothelial growth factor (VEGF), which is implicated in
normal or pathological vessel formation. In the present study, we investigated
VAT in association with the risk of small bowel angioectasia.
AIMS & METHODS: We retrospectively investigated 198 consecutive patients
(male: female; 117: 81, mean age 65.8  12.8 years) who underwent capsule
endoscopy (CE) and CT for investigation of overt and occult OGIB at the
University of Tokyo Hospital between January 2009 and September 2013.
VAT and subcutaneous adipose tissue (SAT) were measured by CT, and medical
history of concomitant disease and body mass index were obtained from their
medical records. Logistic regression analyses were used to evaluate associations.
RESULTS: Out of 198 OGIB patients, CE found SBA in 18 patients (9.1%).
Compared with patients without SBA, those with SBA had signiEcantly higher
VAT (96  76.0 cm2, vs. 63.4  51.5 cm2, p 0.016) and higher prevalence of
liver cirrhosis (11(61%) vs. 41(23%), p 0.0011). Prevalences of SBA progressively increased according to VAT; 7.2% in patients with VAT less than 100 cm2,
whereas 12.5% in those between 100 cm2 and 150 cm2, 21.4% more than 150 cm2
(p 0.058 by trend test), respectively. Multivariate analysis showed that VAT
(odds ratio for each 10 cm2 increment, 1.1; 95% confidence interval (CI), 1.011.19; p 0.025), liver cirrhosis (odds ratio, 5.5; 95% CI, 1.98-16.6; p 0.0011)
were related to significant risk factors of SBA.
CONCLUSION: In addition to liver cirrhosis, visceral adipose tissue is one of
the risk factors for small bowel angioectasia.
Disclosure of Interest: None declared
P0530 EVALUATION
OF
GASTRO-INTESTINAL
LESIONS
IN
PATIENTS UNDERGOING ORAL ANTICOAGULANT THERAPY BY
CAPSULE ENDOSCOPY
C. Marmo1,*, M.E. Riccioni1, R. Cianci2, G. Costamagna1
Digestive Endoscopy Unit, 2Institute of Internal Medicine, Catholic University of
Rome, "A. Gemelli" Hospital, Italy, Rome, Italy
Contact E-mail Address: clelia.marmo@alice.it

INTRODUCTION: Small bowel bleeding is still poorly studied in patients with


long-term anticoagulation therapy. Capsule endoscopy (CE) is the first-line
method for evaluation of bleeding in patient after negative upper endoscopy
and colonoscopy.
AIMS & METHODS: In this retrospective study, we had investigated the types
and frequency of small bowel GI bleeding lesions in patients undergoing oral
anticoagulant therapy, by CE. Of a total of 1085 CE obtained between January
2003 and June 2013, 679 were performed in patients with obscure gastrointestinal
bleeding. Of these 96 were obtained in patients undergoing oral anticoagulant
therapy, 55 males and 41 females, mean age 70.6 years (range 23-87 years). At
the time of evaluation by capsule endoscopy, the mean level of haemoglobin was
8.3 g/dl for males (normal values 14-18 g/dl) and 6.7 g/dl for females (normal
values 12-16 g/dl). The mean number of blood units used for transfusions was
5.7 per patient (range 2-20). All patients underwent upper and lower gastro-intestinal endoscopy, prior to capsule endoscopy (CE). If upper and lower examinations
were negative, CE was performed. The following data were recorded in the data
base: patient age, gender, indication for the examination, medical and surgical
history, bleeding history (including type of bleeding, total number of transfusions,
hospitalizations), number and type of prior diagnostic testing, and details of the
capsule examination.
RESULTS: In the series of patients undergoing oral anticoagulant therapy: 35/96
(36.4%) patients had negative examination; 22/96 (22.9%) had small-bowel
angiodysplasias, small bowel erosions 21/96 (21.8%), small bowel ulcerations
5/96 pts (5.2%), neoplasia 4/96 (4.1%). In the series of patients with OGIB
without anticoagulant therapy: 102/583 (17.4%) had angiodysplasias, small
bowel erosions 48/583 (8.2%), small bowel ulcerations 25/583 (4.2%), neoplasia
44/583 (7.5%)
CONCLUSION: Small bowel angiodysplasias remain the main cause of occult
GI bleeding. In our series, patients undergoing oral anticoagulant therapy had
high prevalence of small bowel angiodysplasias (36.4% for anticoagulant group
and 17.4% for control group). Furthermore in the anticoagulant group we have
seen a major occurrence of erosions (21.8% VS 8.2%).
Disclosure of Interest: None declared
P0531 FREQUENCY AND RISK FACTORS FOR REBLEEDING EVENTS
IN PATIENTS WITH SMALL BOWEL ANGIOECTASIA
E. Sakai1,*, H. Endo1, S. Umezawa1, A. Fuyuki1, S. Uchiyama1, H. Ohkubo1,
T. Higurashi1, T. Nonaka1, A. Nakajima1
1
Gastroenterology, Yokohama City University School of Medicine, Yokohama,
Japan
Contact E-mail Address: eiji525@yokohama-cu.ac.jp
INTRODUCTION: Small bowel angioectasia is reported as the most common
cause of bleeding in patients with obscure gastrointestinal bleeding (OGIB).
Although the safety and efficacy of endoscopic treatment have been demonstrated, rebleeding rates are relatively high. To establish therapeutic and

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United European Gastroenterology Journal 2(1S)

follow-up guidelines, we investigated the long-term outcomes and clinical predictors of rebleeding in patients with small bowel angioectasia.
AIMS & METHODS: A total of 68 patients were retrospectively included in this
study. All the patients had undergone CE examination, and subsequent control
of bleeding, where needed, was accomplished by endoscopic argon plasma coagulation. Based on the follow-up data, the rebleeding rate was compared between
patients who had/had not undergone endoscopic treatment. Multivariate analysis
was performed using a Cox proportional hazard regression model to identify the
predictors of rebleeding. Rebleeding was defined as evidence of recurrent visible
gastrointestinal bleeding (hematochezia or melena) with recent negative upper
and lower endoscopic examinations and/or a reccurent drop of the hemoglobin
level by more than 2 g/dl from the baseline. We defined the OGIB as controlled if
there was no further overt bleeding within 6 months and the hemoglobin level
had not fallen below 10 g/dl by the time of the final examination.
RESULTS: The overall rebleeding rate over a median follow-up duration of 30.5
months (interquartile range 16.547.0) was 33.8% (23/68 cases). The cumulative
risk of rebleeding tended to be lower in the patients who had undergone endoscopic treatment than in those who had not undergone endoscopic treatment,
however, the difference did not reach statistical significance (P 0.14). In the
majority of patients with rebleeding (18/23, 78.3%), the bleeding was controlled
with additional endoscopic treatment by the end of the follow-up period.
Multiple regression analysis identified multiple lesions (3) (OR 3.82; 95% CI
1.3011.3, P 0.02) as the only significant independent predictor of rebleeding.
CONCLUSION: In conclusion, patients with small bowel angioectasia show
relatively high rebleeding rates. Although a single session of endoscopic treatment was not sufficient to control future rebleeding, in most cases, rebleeding
could be controlled with repeated endoscopic treatment and/or iron replacement
therapy. Careful follow-up is needed for patients with multiple lesions, which was
identified as a significant risk factor for rebleeding.
Disclosure of Interest: None declared
P0532 GENE EXPRESSION LEVELS OF ANGIOGENIC FACTORS IN
SMALL BOWEL ANGIODYSPLASIA
G. Holleran1,*, B. Hall1, S. Smith1, D. McNamara1
1
Department of Clinical Medicine, Trinity College Dublin, Tallaght, Ireland
Contact E-mail Address: grainneholleran@gmail.com
INTRODUCTION: Angiodysplasias are known to account for 50% of small
bowel bleeding sources, but diagnosis and effective treatment of these lesions is
limited by a poor understanding of the pathophysiology of the condition. By
measuring serum angiogenic factors in patients with small bowel angiodysplasias
(SBA), we have already identified abnormalities in the angiopoietin pathway;
with elevated levels of Ang2 and decreased levels of Ang1, associated with the
condition. To determine the significance of these findings we need to determine
whether these factors and their receptors are specifically located in SBA tissue.
AIMS & METHODS: The aim of this study was to measure gene expression levels
of various angiogenic factors and receptors in SBA tissue compared to adjacent
normal tissue and to normal SB tissue in controls. Following informed consent,
patients aged 18-80 years of age undergoing double balloon enteroscopy for a
variety of small bowel disorders at Tallaght hospital were invited to participate.
From patients with SBA, one standard biopsy was taken from a single angiodysplasia lesion, and a further biopsy was taken from macroscopically adjacent normal
mucosa. In controls, a single small bowel mucosal biopsy was taken at random.
Biopsy samples were immediately placed in RNAlater solution and stored in a fridge
overnight before being stored at -80oC for batch analysis. Using a standard technique, RNA was isolated and a reverse transcription reaction was performed on each
sample using the Fermantas first strand cDNA synthesis kit (Thermo Scientific).
The resulting cDNA was used in quantitative PCR reactions to determine the
relative expression of Ang1, Ang2, Tie2, VEGF and TNF. Relative gene expression
was calculated using the comparative cycle threshold (CT) method and was normalised to the control gene GAPDH. Statistical analysis was performed using SPSS
version 20. Fold differences of each gene were expressed as a mean and compared
between groups, with a p value of 50.05 considered significant.
RESULTS: In total, 20 biopsy samples were collected; including 9 from angiodysplasia mucosa, 7 from adjacent normal mucosa, and 4 from normal mucosa in
controls. Detectable levels of genes encoding Ang1, Ang2, Tie2, TNF and VEGF
were found in all biopsy samples. There were significantly higher levels of Ang1
and its receptor Tie2 in angiodysplasia tissue compared to adjacent normal
mucosa and to controls, with mean fold differences of 1.77 vs 0.82 and 0.81
for Ang1 (p 0.049), and 1.66 vs 0.76 and 0.52 for Tie2 (p 0.02) respectively.
Levels of Ang2 appeared higher in angiodysplasias than both adjacent mucosa
and controls, however; this was only statistically significant between the angiodysplasias and their adjacent mucosa (p 0.04). There were no differences in
levels of TNF or VEGF expression between any of the samples.

Control
Angiodysplasia
Patient normal tissue
p value

Ang 1

Ang 2

Tie2

TNF

VEGF

0.8175
1.7667
0.8129
50.05

0.5625
0.7333
0.3957
0.04

0.76
1.66
0.9714
0.02

0.79
0.82
0.8057
0.46

1.1
1.1367
1.4057
0.42

CONCLUSION: Expression of levels of genes encoding Ang1 and Ang2 and


their receptor Tie2 are higher in the mucosa overlying small bowel angiodysplasias than unaffected mucosa. This further strengthens the identification of the
angiopoietin pathway as a key factor in the pathophysiology of SBA formation.
Disclosure of Interest: None declared

P0533 WHAT IS THE LONG-TERM SAFETY OF A NEGATIVE CAPSULE


ENDOSCOPY IN PATIENTS WITH OBSCURE GASTROINTESTINAL
BLEEDING?
I. Ribeiro1,*, R. Pinho1, A. Rodrigues1, T. Pais1, C. Fernandes1, J. Silva1,
A. Ponte1, S. Leite1, J. Carvalho1
1
Centro Hospitalar Vila Nova Gaia, Vila Nova Gaia, Portugal
Contact E-mail Address: iolandacribeiro@gmail.com
INTRODUCTION: Although capsule endoscopy (CE) is the investigation of
choice in obscure GI bleeding (OGIB), the clinical outcomes of a negative capsule
remain contradictory according to different studies.
AIMS & METHODS: The aim of the study was to compare the long-term outcome of patients with OGIB after a negative and a positive CE and identify risk
factors for rebleeding.
Methods: Retrospective study of 173 patients who underwent CE for OGIB, from
2005 to 2013; patients with a follow-up time 56 months were excluded. CE with no
lesions or with lesions P0 (petechial lesions; mucosal congestion) or P1 (isolated erosions; small angiodysplasias) were considered negative. Rebleeding was defined as a
documented fall in hemoglobin of 2 g/dL from baseline, evidence of melena or hematochezia, and the need for blood transfusion, at least 30 days after the index bleed.
We evaluated the demographic characteristics, type of OGIB (overt vs occult),
medication, rebleeding rate after a negative and a positive CE, type of treatment
(endoscopic/surgical) performed in patients with positive CE and the influence on
rebleeding. Statistical tests: t-student, 2.
RESULTS: The mean age was 61.7 years; 67% of patients underwent CE
because of occult GIB; 54.3% of CE were negative; the mean follow-up time
was 27 months ( 23.4) and the overall rebleeding rate was 22.5%. The rebleeding rate after a negative CE was significantly lower than after a positive CE (16%
vs 30.4%, p 0.024). Patients who rebleed needed more transfusions of red blood
cells (mean 6.0) prior to CE when compared with those who did not rebleed
(mean 1.2, p50.001). Age, sex, anticoagulants or anti-agregants did not influence the rebeeding rate.
Almost 50% of patients with a positive study underwent endoscopic (56.4% argon plasma coagulation) or surgical treatment (28.2%), with significantly
lower rebleeding rate than patients who did not undergo any treatment (23.1%
vs 37.5%, p 50.02).
CONCLUSION: Conclusions: A negative CE study in patients with OGIB is
associated with a low rate of recurrent bleeding in the long term (16%). It is
reasonable to take an expectant approach with these patients, thus avoiding the
need for unnecessary additional investigations. The endoscopic/surgical treatment decreases the rebeeding rate after a positive CE.
Disclosure of Interest: None declared
P0534 SMALL BOWEL CAPSULE ENDOSCOPY
PATIENTS. INDICATIONS AND FINDINGS

IN

ELDERLY

N. Viazis1, K. Katopodi1,*, M. Chanias1, E. Anastasopoulos1, G. Kechagias1,


K. Markoglou1, M. Mela1, E. Keimali1, D.G. Karamanolis1
1
Department of Gastroenterology, EVANGELISMOS HOSPITAL, Athens,
Greece
Contact E-mail Address: nikos.viazis@gmail.com
INTRODUCTION: Given the aging of the European population a growing
number of elderly patients need to be subjected to small bowel capsule endoscopy. In our study we aimed to determine the indications and findings of
patients aged 4 80 years old subjected to small bowel capsule endoscopy in
our Department, in comparison to those aged 5 80 years old.
AIMS & METHODS: From March 2003 till August 2013, 3410 patients have been
subjected to small bowel capsule endosopy (Given imaging) in our Department.
Among them, 131 were 4 80 years old. We analyzed the indications and findings of
these patients in comparison to the rest of the patients subjected to the test.
RESULTS: Among the 131 patients aged 4 80 years old, the 106 (80.9%) have
been subjected to small bowel capsule endoscopy because of obscure gastrointestinal bleeding. The corresponding percentage for patients aged 5 80 years old
was 60.2%. The remaining patients have been subjected to the test because of
suspected Crohns disease (n 9, 6.8%), chronic diarrhea (n 9, 6.8%) and
abdominal pain (n 7, 5.3%). The corresponding figures for those patients
aged 5 80 years old were 21.7%, 3.7% and 4.3% respectively. The findings of
the test in both age groups in cases of obscure gastrointestinal bleeding are
presented in table 1. No patient aged 4 80 years old had any complication
due to the small bowel capsule endoscopy investigation.
Table 1. Findings of small bowel capsule endoscopy

Angiodysplasias
Apthoid ulcers
Ulcerations
Polyps
Tumors

Patients 4 80 years old

Patients 5 80 years old

86.3%
0.9%
5.4%
2,7%
4,6%

59.2%
13.0%
12.0%
9.9%
5.8%

CONCLUSION: Small bowel capsule endoscopy in elderly patients is mainly


done for the investigation of obscure gastrointestinal bleeding. The test appears
to be safe in these cases and angiodysplasias are detected more frequently than in
younger patients.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)


P0535 NON
ANEMICS
WITH
EROSIVE
GASTRITIS
MORE
FREQUENTLY PRESENT SMALL BOWEL ULCERATIVE LESIONS

Disclosure of Interest: None declared

P. Tsibouris1, P. Apostolopoulos1, C. Kalantzis1, E. Houda1, K. Dimopoulos1,


C. Beltsidou1, E. Vlachou1,*, G. Alexandrakis1
1
GASTROENTEROLOGY, NIMTS GENERAL HOSPITAL, Athens, Greece

P0537 REDUCTION OF NSAID-INDUCED SMALL INTESTINAL


DAMAGE IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING
SULFASALAZINE

INTRODUCTION: Although erosive gastritis can cause iron deficiency anemia,


its presence cannot prevent small bowel evaluation with capsule endoscopy.
AIMS & METHODS: Aim: To define the risk to find small bowel ulcerative
lesions and anemia in patients with erosive gastritis.
Methods: 1010 patients undergone small bowel capsule endoscopy, gastroscopy
and colonoscopy were evaluated. 537 were evaluated for iron deficiency anemia
or recent obscure bleeding, 324 for diarrhea, 60 for unexplained abdominal pain
and 89 for other causes. 176 patients excluded from the analysis, as they presented either inflammatory bowel disease or celiac disease and 81 because they
presented a gastric or a duodenal ulcer, leaving a study population of 753
patients (mean age 6416 years, 421 men, 159 active smokers). Erosive gastritis
was present in 132 (mean age 6515 years, 77 men, 32 active smokers). Stat: X2,
logistic regression analysis.
RESULTS: 50 (38%) patients with erosive gastritis and 161 (26%) without presented small bowel erosions (p 0.006). 27 (48%) patients with erosive gastritis
consuming aspirin or NSAIDs and 50 (33%) NSAIDs consumers without erosive
gastritis presented small bowel erosions (p 0.04). 13 (41%) patients with erosive
gastritis on clopidogrel and 23 (29%) clopidogrel consumers without erosive
gastritis presented small bowel erosions (p 0.26). Among patients not on antiplatelets, 10 (23%) with erosive gastritis and 88 (23%) without presented small
bowel erosions (p 0.97). Among anemics, 19 (42%) patients with erosive gastritis consuming aspirin or NSAIDs and 44 (34%) NSAIDs consumers without
erosive gastritis presented small bowel erosions (p 0.04). 12 (30%) patients with
erosive gastritis on clopidogrel and 18 (28%) clopidogrel consumers without
erosive gastritis presented small bowel erosions (p 0.26). No patient with erosive gastritis not consuming antiplatelets and 40 (20%) without erosive gastritis
presented small bowel erosions (p 0.048). In logistic regression analysis old age,
erosive gastritis, AF and use of aspirin were related with increased risk for small
bowel ulcerative lesions and diabetes with reduced risk.
CONCLUSION: Non anemics with erosive gastritis are at risk for small bowel
erosions, especially if they consume aspirin or NSAIDs, because small bowel
mucosa is possibly more vulnerable to noxious stimula. On the other hand,
among anemics erosive gastritis was related with less small bowel ulcerative
lesions among no antiplatelet consumers. Possibly because erosive gastritis is
an independent cause of iron deficiency anemia.
Disclosure of Interest: None declared

P0536 PATIENTS WITH ATRIAL FIBRILLATION ON CLOPIDOGREL


ARE AT HIGH RISK TO DEVELOP SMALL BOWEL ULCERATIVE
LESIONS AND ANEMIA
P. Tsibouris1,1, P. Apostolopoulos1, I. Koumoutsos1, C. Kalantzis1, E. Chounta1,
K. Dimopoulos1, C. Beltsidou1, G. Alexandrakis1,*
1
GASTROENTEROLOGY, NIMTS GENERAL HOSPITAL, Athens, Greece
INTRODUCTION: Patients with atrial fibrillation are usually on antiplatelet
treatment or anticoagualants.
AIMS & METHODS: Aim: To define the risk to find small bowel ulcerative
lesions and anemia in patients with atrial fibrillation on antiplatelet or anticoagulant treatment.
Methods: 1010 patients undergone small bowel capsule endoscopy, gastroscopy
and colonoscopy were evaluated. 537 were evaluated for iron deficiency anemia
or recent obscure bleeding, 324 for diarrhea, 60 for unexplained abdominal pain
and 89 for other causes. 176 patients excluded from the analysis, as they presented either inflammatory bowel disease or celiac disease, leaving a study population of 834 patients (mean age 6416 years, 476 men, 176 active smokers).
Atrial fibrillation (AF) presented 78 patients (mean age 767 years, 41 men, 8
active smokers). Stat: X2, logistic regression analysis.
RESULTS: 246 (29%) patients presented small bowel ulcerative lesions; 164
(31%) anemic and 78 (26%) non-anemic (p 0.19). 33 (42%) AF patients and
213 (28%) without AF presented small bowel ulcerative lesions. Small bowel
ulcerative lesions were present in 14 (48%) AF aspirin/NSAID users, 13 (42%)
AF clopidegrel consumers and 6 (33%) AF patients not receiving antiplatelets. In
addition they were present in 132 (38%) aspirin/NSAID users without AF
(p 0.31), 23 (29%) clopidogrel consumers without AF (p 0.02) and 109
(23%) patients without AF not receiving antiplatelets (p 0.33). Thus small
bowel ulcerative lesions were more common among aspirin users without AF
(p 0.001), but not those with AF (p 0.41). Moreover there was no difference
between aspirin and clopidogrel (AF: p 0.62; no AF: p 0.14). Among anemics
small bowel ulcerative lesions were present in 14 (56%) AF aspirin/NSAID users,
14 (47%) AF clopidegrel consumers and 2 (17%) AF patients not receiving antiplatelets. In addition they were present in 67 (37%) aspirin/NSAID users without
AF (p 0.08), 17 (27%) clopidogrel consumers without AF (p 0.02) and 109
(22%) patients without AF not receiving antiplatelets (p 0.33). Thus small bowel
ulcerative lesions were more common among aspirin users with (p 0.02) and
without AF (p 0.0006). Moreover there was no difference between aspirin and
clopidogrel (AF: p 0.49; no AF: p 0.13). In logistic regression analysis old age,
erosive gastritis, AF and use of aspirin were related with increased risk for small
bowel ulcerative lesions and diabetes with reduced risk.
CONCLUSION: Small bowel ulcerative lesions are more common among
aspirin users. Clopidogrel is generally safer, nevertheless both presence of
anemia and small bowel ulcerative lesions are more common among patients
with atrial fibrillation, possibly because small bowel mucosa is more vulnerable
to develop inflammatory lesions in this patient group.

A. Balabanceva1, S. Tkach2,*
Crimea Medical University, Simferopol, Russian Federation, 2National Medical
Univercity, Kyiv, Ukraine

INTRODUCTION: Recent studies have demonstrated that nonsteroidal antiinflammatory drugs (NSAIDs) often cause damage to the small intestine, and
NSAID-induced enteropathy is mediated by different inflammatory cytokines.
Sulfasalazine is being widely used in patients with rheumatoid arthritis (RA), and
this drug have the potential to induce mucosal healing in patients with intestinal
diseases such as inflammatory bowel diseases.
AIMS & METHODS: To evaluate the preventive effect of sulfasalazine against
small intestinal damage due to chronic NSAID use in RA patients. Between
March 2009 and June 2011, capsule endoscopy was performed in 51 consecutive
RA patients who received NSAIDs for more than 3 months with or without
sulfasalazine therapy over a period of 3 months. The findings were scored as
follows according to the method described by Graham et al. (Clin Gastroenterol
Hepatol. 2005): 0, normal; 1, red spots; 2, 1 to 4 erosions; 3, 44 erosions; and 4,
large erosions/ulcers. Scores of 3 and 4 indicated severe damage. The relationship
between the use of sulfasalazine therapy and risk of severe damage (score 3 or 4)
or severest damage (score 4) were assessed using multiple logistic regression.
RESULTS: Comparative data were analyzed for 47 patients, and 4 patients were
excluded because the entire small bowel could not be visualized in these patients.
Of the 25 patients who did not receive sulfasalazine therapy, 12 (48%) had severe
damage (score of 3 [n 8] or 4 [n 4]). On the other hand, of the 26 patients
receiving sulfasalazine therapy, 5 (19.2%) had severe damage (score of 3 [n 3]
or 4 [n 2]). On stratifying the patients by sulfasalazine therapy, we obtained a
crude odds ratio (OR) of 0.26 for severe damage with a 95% confidence interval
(CI) of 0.10 to 0.66, and of 0.38 for severest damage with a 95% CI of 0.17 to
0.88. This effect of sulfasalazine therapy on NSAID-induced enteropathy
remained robust to adjustment for age, gender, history of peptic ulcers, disease
activity score-28 (a disease activity index for RA), use of selective cyclooxygenase-2 inhibitors or steroids, blood hemoglobin concentration, and all these variables, with the adjusted ORs for severe damage ranging from 0.19 to 0.25 and
those for severest damage ranging from 0.30 to 0.40.
CONCLUSION: Sulfasalazine therapy may protect against NSAID-induced
small intestinal damage in RA patients and may be effective in the treatment
of NSAID-induced enteropathy.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
NUTRITION I POSTER EXHIBITION HALL XL_____________________
P0538 IS THE TRADITIONAL DIET DISAPPEARING AT THE SAME
TIME AS THE PREVALENCE OF OBESITY IS INCREASING IN
ITALY? EVALUATION OF EATING HABITS IN A GROUP OF
ITALIAN OBESE FEMALE PATIENTS
A. Guida1,*, A. Frascari1, E. Canducci1, B. Ravani1, G. Bersani2, A. Rossi2,
R. Arena1, A. Maimone1, V. Alvisi3, G. Ricci1
1
Medical Sciences, University of Ferrara, Ferrara, 2Digestive Endoscopy Service,
3
Internal Medicine, Malaesta Novello Hospital, Cesena, Italy
Contact E-mail Address: ada.guida@student.unife.it
INTRODUCTION: The nutrition transition from traditional to Western dietary
patterns could account for the dramatic rise in the prevalence of obesity in Italy
(1).
AIMS & METHODS: We describe the dietary patterns in a group of obese
Italian female patients. A retrospective survey was conducted on the records of
113 obese (BMI 40.27.0 kg/m2) female inpatients aged 19-60 y (mean 40.5 y).
Anthropometric measurements and dietary patterns were obtained from the
records. Dietary habits were recorded by detailed questioning and computed
database determined the nutrient intakes. The recommended dietary allowances
(RDAs) for the Italian population were used as the reference range. The sample
was also divided, according to age, into three groups (19-35y, 36-45y, 46-60y).
Statistical analysis was performed by PASW 18.0.
RESULTS: The table shows the variations, as percentages, of the nutrient
intakes over or below the RDAs. The values are expressed as 50th (25th, 75th)
percentile. Animal protein intakes averaged 266% over the RDAs in the whole
sample, with median variations from 241 to 278% among the age groups. The
intake rates of total carbohydrates (CHO) were minimally higher on average (1519%) than the RDAs. The simple CHO intake averaged 67-90% over RDAs.
The !-6/!-3 fatty acid ratio was about 100% over the RDA, without significant
differences among age groups. Moreover the intakes of !-6 fatty acids was 64%
over the RDA, but in the younger group the variation rate from the RDA was
significantly higher (72%, p50.05) than in the older group (50%). Nutrients with
protective effects, such as PUFA and !-3 fatty acids, averaged 35-48% and 1119% below RDAs, respectively.

A282

United European Gastroenterology Journal 2(1S)

Nutrient intakes RDAs (g)

all (113)

19-35 y (37)

36-45 y (36)

46-60 y (40)

P0540 THE RELATIONSHIP BETWEEN OSTEOPOROSIS AND LEPTIN


IN OBESE FEMALES
D. Neagoe1,*, G. ianosi2, A. amzolini1, A. farmazon3, M. popescu4,
A. turculeanu5, C. deliu3, T. ciurea1
1
internal medicine, 2surgical, university of medicine and pharmacy, 3internal medicine, emercency hospital no.1, 4endocrinology, 5laboratory, university of medicine
and pharmacy, craiova, Romania

Protein
Animal Protein
Fat
PUFA

64 (59, 66)
74 (55, 100)
136 (112, 165)
10 (7, 13)

100 (71, 132)


266 (171, 349)
129 (88, 175)
-44 (-57, -23)

95 (75, 108)
241 (171, 316)
151 (113, 175)
-35 (-53, -15)

119 (70, 166)


248 (164, 385)
129 (85, 195)
-35 (-57, -19)

112 (80, 130)


278 (214, 354)
118 (80, 162)
-48 (-59, -31)

!-3
!-6
!-6/!-3
Total CHO
Simple CHO

1.2 (1.1, 1.3)


4.8 (4.6, 5.3)
4
363 (347, 380)
69 (66, 72)

-16 (-34, 11)


64 (27, 123)
100 (66, 123)
19 (2, 40)
84 (27, 146)

-11 (-28, 44)


72 (42, 164)
89 (49, 119)
19 (-2, 42)
90 (32, 142)

-19 (-43, 8)
74 (27, 126)
102 (69, 133)
31 (9, 51)
84 (14, 166)

-18 (-34, 9)
50 (23, 90)
102 (67, 123)
15 (-2, 28)
67 (33, 117)

CONCLUSION: We observed that the highest variation rates were not found for
total carbohydrates or simple carbohydrates, as could be expected, but for fat
and protein, and especially for animal protein. Moreover the excessive consumption !-6 fatty acid, with unbalanced !-6/!-3 fatty acid ratio, could show a
tendency to change the traditional Italian diet towards Western eating habits.
However there was no significant difference between younger and older people.
REFERENCES
1. Inelmen EM, Toffanello ED, Enzi G, et al. Differences in dietary patterns
between older and younger obese and overweight outpatients. J Nutr Health
Aging 2008; 12: 3.
Disclosure of Interest: None declared
P0539 CAN INTERVENTION ON LIFESTYLE HAVE AN IMPACT ON
CARDIORESPIRATORY FITNESS IN THE NON-OPERABLE
SEVERELY OBESE PATIENT?
D.A. L. Hoff1,*, F. Wammer2, A. Haberberger3
1
Dept.of Medicine, Div. of Gastorenterology and Hepatology, 2Dept.of Medicine,
Div. of Pulmonary diseases, Aalesund Hospital, Aalesund, 3Centre of achievement
and rehabilitation, Muritunet, Valldal, Norway
Contact E-mail Address: dagalhoff@gmail.com
INTRODUCTION: Severe obesity (BMI 4 40 kg/m2 or 35 kg/m2 and complications) is associated with higher frequency of comorbidities such as respiratory
failure and higher premature mortality compared to less obese patients. Diet
change, physical exercise and lifestyle modifications are the only therapeutic
options for a substantial proportion of patients. The literature on cardiorespiratory fitness in these patients is sparse.
AIMS & METHODS: To examine whether or not a systematic rehabilitation
program providing lifestyle intervention has a significant positive impact on
cardiorespiratory fitness in the non-operable severely obese patients.
Forty non-operable severely obese patients (F 29, M 11, mean age 44 y, range 2362 y) were consecutively enrolled in a rehabilitation program. In total 33 patients
stayed in the program 12 months after enrolment, but 6 of them did not complete
all tests due to acute illness. Eligible for enrolment was patients in groups of 1215, in all 4 groups. The first stay lasted 4 weeks, the consecutive stays 2 weeks
every 6 months. At each stay a team of nurses, physician, dietician, psychologist
and physical activity therapist provided education and physical exercise to each
patient individually or to patients assembled as a group, including matched
patients conversations. At enrolment patients were classified as respiratory
healthy or as having chronic respiratory illness. Furthermore at the beginning
of each stay body weight, peak oxygen uptake (VO2peak) and functional residual
capacity % (FRC %) were registered and body mass index (BMI) calculated. The
test was performed on a treadmill programmed in a standard fashion regarding
velocity and inclination. All tested patients reached anaerobic threshold
(VO2peak).
Mean  standard deviation are reported at inclusion and one year after inclusion. FRC% is regarded normal above 80 %.
RESULTS: We report on cardiorespiratory fitness in 27 patients (F 19, M 8,
mean age 45 y, range 23-62) 12 months beyond baseline. Ten patients were
respiratory healthy and 17 had respiratory illnesses; asthma (N 4), chronic
obstructive lung disease (N 1) and obstructive sleep apnoea syndrome
(N 12). Body weight: 125.5  21.7 kg vs 120.1  23.1 kg, p 0.004. BMI:
42.1  3.9 kg/m2 vs 40.6  5.2 kg/m2, p 0.016. FRC%:76.9  12.1 % vs
80.4  13.8 %, p 0.069. VO2peak during exercise: 22.7  3.0 ml*kg-1min-1 vs
24.0  4.5 ml*kg-1min-1, p 0.032.
CONCLUSION: We found a significant improvement in cardiorespiratory fitness in a group of 27 non-operable severely obese patients that participated in a
systematic rehabilitation program for one year. Our results should be verified in
larger scale studies. This would also make it possible to stratify patients according to respiratory health.
Disclosure of Interest: None declared

INTRODUCTION: The pathogenesis of decreased bone mineral density (BMD)


in NAFLD is unclear. Hyperleptinemia, hormone mainly secreted by white adipose tissue, is associated with inflammatory process, suppress bone formation
and increase bone resorbtion. Aim of our study was to correlate leptin level with
decreased BMD in obese females.
AIMS & METHODS: We included obese females in postmenopausal period for
at least 1 year: 54 with NAFLD and 56 without NAFLD, age, waist circumference (WC) and body mass index (BMI) matched. Exclusion criteria: diabetes
mellitus, chronic use of corticosteroids, supplementation with calcium products,
secondary obesity due endocrine diseases, renal disease, alcohol intake, smoking,
previous fractures. Blood samples were collected in both groups for lipid profile,
hepatic enzymes and leptin (references values 4.9-24ng/ml). Lumbar BMD was
measured by DEXA and abdominal ultrasonography was performed by the same
physician and steatosis was graded using a semi-quantitative scale of 1 (mild) to 3
(severe).
RESULTS: In NAFLD group mean age was 49.5 years, BMI 32,53 and WC
995cm, in second group mean age was 51,3 years, BMI 30,33 and WC 975,
without statistic significance between the two groups. In NAFLD group 24
females had mild steatosis, 18 had moderate and 12 had severe steatosis. No
evidence of steatosis in group B. Leptin level was 8.7ng/ml1.2 in group B
and 15.2ng/ml5.1 in NAFLD group, with significance statistic differences
between the two groups. In NAFLD group we found 9 patients with normal T
score, 21 patients with osteopenia and 24 with osteoporosis. In group B we found
15 patients with normal T score, 25 with osteopenia and 16 with osteoporosis.
BMD was lower in NAFLD women than these without NAFLD and osteoporosis in NAFLD group seemed to be associated a more severe liver disease. In
NAFLD group the highest levels of serum leptin were found in moderate or
severe steatosis with osteoporosis and we found a positive correlation with
BMI and WC (p 0.000 and p 0.002). In the other group, leptin level had
no significant differences in relationship with BMI, WC or decreased BMD.
CONCLUSION: In our study, leptin level was correlated with osteoporosis in
NAFLD group. In obeses females without NAFLD, leptin level was similar
despite the presence or absence of osteoporosis.
Disclosure of Interest: None declared
P0541 ENDOSCOPIC REMOVAL OF GASTRIC BANDS A HEAVY
ISSUE
D. Branquinho1,*, D. Gomes1, N. Almeida1, C. Sofia1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com
1

INTRODUCTION: One of the most popular methods in bariatric surgery is the


gastric band. However, its migration into the gastric lumen has frequently been
described as a long-term complication. There is no consensus on how to handle
such cases, but its removal through endoscopy is increasingly being documented
as a safe and effective alternative. The authors present a Gastroenterology
department 5-year experience.
AIMS & METHODS: To describe our experience in a relatively novel endoscopic technique useful to handle a common bariatric surgey complication.
Review of clinical files and endoscopic imaging.
RESULTS: A total of eight procedures were undertaken in morbidly obese
female patients (average age: 38.7 years old). Median time between initial surgery
and band removal was about 6931.9 months. Clinical manifestation was weight
increase in 5 patients and upper abdominal pain in the remaining three. All cases
were diagnosed through upper digestive endoscopy.
During such procedures, a 0.035 inch guidewire and a Soehendra lithotripter
were used to cut through the band, which was then pulled with a polypectomy
snare. Extraction of the cutaneous port was done by the assisting surgeon.
Average duration of the procedure was about 30 minutes.
A peritoneal leak was the only major complication, due to the passage of air from
the stomach lumen to the peritoneum through the band internal canal.
CONCLUSION: Considering the high number of gastric band procedures undertaken in the last few years, its intra-gastric migration will be a common clinical
issue. This endoscopic approach, although technically demanding, is a safe and
effective alternative, thereby avoiding morbidity associated with a major surgical
intervention.
Disclosure of Interest: None declared

A283

United European Gastroenterology Journal 2(1S)


P0543 FIRST REPORTS OF THE NEW SPATZ 3 ADJUSTABLE
BALLOON SYSTEM
E. Machytka1,*, Z. Kowalczyk2, S. Al Awadhi3, M. Al Falasi3, J. Mason4,
L. Bene5, S. El Asala6, V. Puig-Divi7, M. Buzga1, J. Brooks8
1
Faculty of Medicine, UNIVERSITY OF OSTRAVA, Ostrava, Czech Republic,
2
Bariatric clinic Pulsmed, Lodz, Poland, 3Rashid Hospital, Dubai, United Arab
Emirates, 4National Obesity Surgery Center, Manchester, United Kingdom,
5
Rozsakert Medical Center, Budapest, Hungary, 6Alain Hospital, Dubai, United
Arab Emirates, 7Opcion Medical Clinic, Barcelona, Spain, 8Spatz FGIA, Great
Neck, United States
Contact E-mail Address: machytka@obezita-balon.cz
INTRODUCTION: The original Spatz Adjustable Balloon System for weight
loss was introduced in 2010. It was the first intragastric balloon approved for
1 year implantation with the added feature of balloon volume adjustability. This
enabled changes to balloon volume during the course of the 1 year implantation
period. It contained a rigid catheter and metal chain that caused duodenal migration. The new Spatz 3 intragastric balloon device, CE Mark approval in 2012, has
a soft catheter to simplify the procedure and decrease complications. In addition,
reports of volume adjustments using a mean 177 ml yields additional 1.7 kg/
month wt loss. It has been suggested that adjusting with larger volumes will yield
better results. We report our experience with the Spatz 3 device in 7 centers.
AIMS & METHODS: To determine the difference between the reported results
of the original Spatz Adjustable balloon System and the new Spatz3 Adjustable
balloon System with respect to ease of use, complications, weight loss results and
the effect of larger volume adjustments. 158 patients with mean BMI 40.1; mean
weight 109 kg; mean age 37; were implanted with the Spatz3 device. Mean
balloon volume was 473 ml (400-600). Adjustments were made for intolerance
or weight loss plateau.
RESULTS: All endoscopists felt that the Spatz 3 device was easier to use than the
original Spatz adjustable balloon system device. Mean wt loss at 12 weeks was
12.5 kg with an 11.7% wt loss and 28.8 % EWL (% excess wt loss). At 24 weeks
mean wt loss was 16,2 kg; 16.7% wt loss, and 35,3 % EWL. 94 patients reached 9
months with a reported mean wt loss of 23.2 kg; 20.4 % weight loss; and 44.9 %
EWL. And 48 patients after 12 months with mean wt loss of 24.1 kg; 20.6 %
weight loss; and 48.1 % EWL. There were 49 balloon volume adjustments: 11
downward adjustments of 100 cc alleviated early intolerance, with added mean
wt loss of 15.3 kg after the adjustment; 38 upward adjustments (mean 327 ml;
range 150-500) at a mean month 4,1 yielded additional mean wt loss of 8.7kg
after the adjustment. 7 balloons were extracted; early intolerance and refusal to
adjust volume downward (4); gastric ulcer (2); deflation (1).
CONCLUSION: The Spatz 3 adjustable balloon is easier and less complicated
than the original Spatz device. Complications associated with the original catheter have not been seen in the Spatz 3 device. Larger volume adjustments yield
greater weight loss results.
Disclosure of Interest: E. Machytka: None declared, Z. Kowalczyk: None
declared, S. Al Awadhi: None declared, M. Al Falasi: None declared, J.
Mason: None declared, L. Bene: None declared, S. El Asala: None declared,
V. Puig-Divi: None declared, M. Buzga: None declared, J. Brooks Shareholder
of: Spatz FGIA
P0544 WEIGHT MAINTENANCE 2 YEARS AFTER EXTRACTION OF
THE SPATZ ADJUSTABLE BALLOON
E. Machytka1,*, L. Bene2, G. Lopez-Nava3, M. Buzga1
1
Faculty of Medicine, UNIVERSITY OF OSTRAVA, Ostrava, Czech Republic,
2
Rozsakert Medical Center, Budapest, Hungary, 3Hospital Sanchinarro, Madrid,
Spain
Contact E-mail Address: machytka@obezita-balon.cz
INTRODUCTION: The Spatz Adjustable Balloon System was developed to
provide an adjustable intragastric balloon approved for 1 year implantation.
Weight loss results 4 20 kg/year have been reported in the literature. The question is whether treatment with an intragastric balloon also leads to better weight
loss maintenance after balloon removal. A prospective study on the BIB balloon
has reported maintenance of 4 10% weight loss in 25% of patients for up to 2.5
years after BIB balloon removal.
AIMS & METHODS: 79 patients from 3 centers who were implanted with the
Spatz Adjustable Balloon for 1 year were contacted and asked to provide their
weight 1 year and 2 years post balloon extraction. Net weight changes were
recorded, and % weight loss was calculated based on weight prior to balloon
implantation. Net weight loss 4 10% was considered successful weight
maintenance.
RESULTS: 70 of the 79 patients contacted (88.6%) were responsive in providing
their weight data. The groups data at the original implantation was as follows: mean
weight 120.3 kg (80-180); mean BMI 38.8 (30-65). At the time of balloon extraction
(12 months) the groups mean weight loss was 24 kg with a 23.8% weight loss. All of
the 70 patients had reached at least 12 months post Spatz balloon extraction. Fifty
three of the seventy (75.7%) retained at least 10% weight loss at 1 year post balloon
extraction. 34 of the 70 patients had reached 2 years post extraction, and 26 (76.4%)
retained at least 10% weight loss. The groups mean weight change was 6.7 kg at 1
year and 3.4 kg at 2 years after balloon extraction.
CONCLUSION: The maintenance of 4 10% Weight loss at 1 year and 2 years
after Spatz Adjustable Balloon extraction has been retrospectively documented in
75.7% and 76.4% of patients, respectively. This study is limited by its retrospective review and the small numbers in year 2 and requires prospective
review to confirm these findings. Nonetheless, it suggests a long term benefit
to longer implantation time and/or adjustable balloon function and warrants
further study.
Disclosure of Interest: None declared

P0545 SACCHAROMYCES BOULARDII ADMINISTRATION CHANGES


GUT MICROBIOTA AND REDUCES HEPATIC STEATOSIS, LOW
GRADE INFLAMMATION AND FAT MASS IN OBESE AND TYPE 2
DIABETIC DB/DB MICE
L. Geurts1,*, A. Everard1, S. Matamoros1, N. Delzenne1, P.D. Cani1
1
Louvain Drug Research Institute, Walloon Excellence in Life sciences and
BIOtechnology (WELBIO), Metabolism and Nutrition Research Group,
Universite catholique de Louvain, Brussels, Belgium
Contact E-mail Address: patrice.cani@uclouvain.be
INTRODUCTION: Obesity and type 2 diabetes are associated with an altered
gut microbiota and inflammation. Growing evidence suggest that the gut microbiota is involved in the regulation of energy homeostasis. We and others have
shown that gut microbiota modulation using prebiotics constitute an interesting
target in the physiopathology of obesity.
AIMS & METHODS: So far, probiotic yeast have not been investigated in this
context. The aim of this study is to evaluate the role of the most studied probiotic
yeast (i.e., Saccharomyces boulardii Biocodex) on obesity and associated metabolic disorders. S. boulardii was administrated daily by oral gavage to leptinresistant obese and type 2 diabetic mice (db/db) for 4 weeks.
RESULTS: We found that S. boulardii treated mice exhibited reduced body
weight, hepatic steatosis, fat mass and both hepatic and systemic inflammation.
These effects were associated with local effects in the intestine, such as an
increased caecum weight and caecum tissue weight. Importantly, we also found
that S. boulardii induced dramatic changes in gut microbial communities at the
phylum, family and genus levels. We also found that microbial changes in
response to S. boulardii were correlated with host metabolism response.
CONCLUSION: In conclusion, our study demonstrated that S. boulardii acts as
a beneficial probiotic treatment in the context of obesity and type 2 diabetes.
Disclosure of Interest: L. Geurts: None declared, A. Everard: None declared, S.
Matamoros: None declared, N. Delzenne: None declared, P. Cani Financial
support for research from: Biocodex
P0546 CORRELATION BETWEEN DIET AND NON-ALCOHOLIC
FATTY LIVER DISEASE: INVESTIGATION OF A COHORT OF
ITALIAN PATIENTS
L. Abenavoli1,*, M. Pellegrini2, M. Busacchi2, G. Marchesini3, E. Bugianesi4,
A. Barchetti2, S. Bellentani5
1
Health Sciences, University Magna Graecia of Catanzaro, Catanzaro,
2
Diagnostic, Clinical and Public Health, University of Modena and Reggio Emilia,
Modena, 3Clinical Dietetics, Alma Mater Studiorum University of Bologna,
Bologna, 4Division of Gastro-Hepatology, University of Torino, Torino, 5Centro
studi Fegato, Azienda USL Modena, Carpi, Italy
Contact E-mail Address: l.abenavoli@unicz.it
INTRODUCTION: The Western diet is characterized by a high-energy intake,
saturated fats and refined sugars. Excess calorie intake, associated with reduced
physical activity, leads to obesity, type 2 diabetes mellitus, cardiovascular disease
and non-alcoholic fatty liver disease (NAFLD).
AIMS & METHODS: Within the FP7 - European FLIP (Fatty Liver Inhibition
Program) program we tried to investigate the role of diet in NAFLD, in a large
cohort of patients from three different Italian Centers (Modena, Bologna and
Turin). We used the EPIC questionnaire to investigate energy intake (Ei) and
intake of food in a well-characterized series of 163 NAFLD patients.
Anthropometric measurements, blood tests, insulin resistance, liver ultrasound
(Hamagouchi score) and liver stiffness were analysed. Nutrient intakes were
compared with Italian reference values.
RESULTS: The daily intake of simple sugars (18.4% vs. a reference intake
515%), saturated fats (12% vs. 510%) and the ratio between animal proteins/vegetal protein in the diet (68% vs. 550%) was higher than recommended,
whereas the fiber intake was lower (19g vs. 25g). In the patients, a significant
direct correlation (p50.005) was observed between BMI, waist circumference,
insulin resistance, transient elastography values, Hamagouchi score, and lipid
intake.
CONCLUSION: The dietary intakes of NAFLD patients are systematically
different from the recommended daily intakes for the Italian population. In
particular the higher-than-recommended intake of simple sugars might be one
of the possible causes of NAFLD (Supported by FLIP Project, (FP7/20072013)
under grant agreement no. HEALTH-F2-2009-241762).
REFERENCES
1. Ratziu V, et al. A position statement on NAFLD/NASH based on the EASL
2009 special conference. J Hepatol 2010; 53: 372-384.
2. Abenavoli L, et al. Transient elastography in non-alcoholic fatty liver disease.
Ann Hepatol 2012; 11: 172-178.
3. Centis E, et al. Stage of change and motivation to healthier lifestyle in nonalcoholic fatty liver disease. J Hepatol 2013; 58: 771-777.
Disclosure of Interest: None declared
P0547 FOOD INTOLERANCE AND OBESITY: NEW STRATEGY IN THE
TREATMENT OF OBESITY
M. Rotter1,*
1
Dietology, UKRAINIAN RESEARCH INSTITUTE OF NUTRITION, Kyiv,
Ukraine
Contact E-mail Address: rottermaria@mail.ru
INTRODUCTION: Challenges associated with the treatment of obesity still
remain high, in spite of efforts made by professionals combating the public
health issue. A low-calorie diet, which is considered as the most effective

A284
treatment, is hard for many patients to incorporate due to the discomfort
brought by hunger. An effective treatment should focus on increasing the quality
of a patients life, by creating a treatment that reduces symptoms associated with
obesity, while allowing patients to not experience hunger during the treatment
period.
AIMS & METHODS: The aim of the study was to compare the difference in
effectiveness between the traditional low-calorie diet and the elimination diet. A
Survey was completed by 60 patients, 30 women and 30 men, with the average
age 37.6  4.7 years. In addition to routine methods of investigation, all patients
were analyzed on food intolerance using the FED- test, which is based on the
immunetermistometrical principle, a new term we used to describe the conductivity and viscosity change in the blood after making contact with certain food
extract. The FED- test uses 96 different food extractions to evaluate food intolerance. To evaluate the improvement of a patients condition, questionnaires were
used before and after the treatment to receive any complaints patients had
throughout the treatment period. Information about complaints was assessed
on a Harington scale of a unit from 1 (no symptoms) to 0.1 (maximum symptom). Patients were divided into 3 equal groups - overweight, and 1 or 2 class
obesity. Each group was divided into two subgroups. Patients in the (A) subgroup were on a low-calorie diet: 1200-1600 Kcal, depending on the age, sex, and
physical activity. Patients of the (B) sub-group were on the individual eucalorie
(with normal energetic value) elimination diet, based on the results from the
FED- testing.
RESULTS: 1. The influence that the type of diet had on weight reduction.
Among the first two groups with overweight patients, greater weight loss was
observed in those patients who adhered to the elimination diet. The difference in
BMI accounted for 0.776  0.222 kg \ m2 in the group A and 1.788  0.449 kg/
m2 in the group B. In obese patients, the following similar results were observed:
in the elimination diet weight loss was 3.764 kg \ m2 and 4.065 kg \ m2 in in
patients with class 1 and 2 obesity accordingly. In low-calorie diet, BMI reduction was 1.291 kg \ m2 and 2.280 kg \ m2 in patients with class 1 and 2 obesity
accordingly.
2. Improvements in patients condition. On the elimination diet improvement of
the patients condition amounted to 0.292 in the obese group, and 0.222 in the
overweight group. In groups in which patients followed the low-calorie diet, no
significant dynamics in the state of the patients were observed: 0.046 in a group
of obese patients and 0.034 patients in the overweight group.
CONCLUSION: Under the influence of elimination diet BMI reduction was
significantly better in patients with 1 and 2 class obesity compared to the
dynamics of BMI on the standard low-calorie diet (p 0.0037). Between
groups of patients who were overweight, no significant differences were found
(p 0.087).
The patients quality of life after 6 months of treatment differed significantly in
subgroups of those treated with the elimination diet, compared to the subgroups
of those that received the standard low-calorie diet treatment (p 0.004).
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0549 ANALYSIS OF 1973 PATIENTS SUBMITTED TO ENDOSCOPIC
TREATMENT OF EXCESS WEIGHT WITH AN INTRAGASTRIC
BALLOON
R.J. Fittipaldi-Fernandez1,*, C.F. Diestel2,3, B. Sander4, A.F. Teixeira5,
M. Galvao Neto6
1
Digestive Endoscopy, 2Nutrition Division, Endogastro Med Service, 3Nutrition
Division, UNI-RIO Rio de Janeiro University, Rio de Janeiro, 4Digestive
Endoscopy, Clnica Sander, Belo Horizonte, 5Digestive Endoscopy, Gastros Bahia,
Feira de Santana, 6Digestive Endoscopy, Gastro Obeso Center, Sao Paulo, Brazil
Contact E-mail Address: ricfittipaldi@hotmail.com
INTRODUCTION: Endoscopic methods, especially the intragastric balloon
(IGB), have been shown to be effective for the treatment of excess weight.
AIMS & METHODS: OBJECTIVE: To assess the efficacy and complications of
excess weight treatment with an IGB in patients seen at the Endogastro Med
Service clinic, Gastro Obeso Center and Sander clinic.
METHODS: A total of 1973 patients were analyzed. An Allergan IGB (BIB)
with a volume of 600 to 700 ml was used. The patients had a minimum initial
body mass index (BMI) of 27 kg/m2 and were followed up by a multidisciplinary
team consisting of a nutritionist, a doctor and a psychologist. For statistical
analysis, the patients were divided into groups according to sex and degree of
excess weight (overweight and grade I, II and III obesity). Data were analyzed
using descriptive statistical methods, the Student t-test, and analysis of variance
followed by the Tukey post-test. The level of significance was set at p50.05.
RESULTS: 107 patients were excluded from the analysis: 70 (3.55%) due to early
IGB removal, 13 (0.66%) due to absence of weight loss, 14 (0.71%) due to weight
gain, and 10 (0.51%) due to incomplete data. The incidence of fungus was 0.2%
(n 4) and the incidence of leakage was 0.25% (n 5), pregnancy was 0.1%
(n 2); Wernick Korsakoff syndrome due to excessive vomiting was 0.05%
(n 1), gastric perforation and upper digestive bleeding was 0.05% each
(n 1). Of the 1866 remaining patients, 1402 were women and 464 were men.
Mean age was 37.32 years. The patients showed a significant weight loss, with a
significantly lower final BMI (mean: 28.934.71 kg/m2; range: 18.98-57.38) than
the initial BMI (mean: 36.475.61 kg/m2; range: 27-74.74) (p50.0001). Mean
BMI reduction was 7.553.49 kg/m2 (range: 0.36-29.79). Mean percent weight
loss was 20.437.82% and mean percent excess weight loss (EWL) was
73.4836.71% (range: 2.22-431.1). Percent EWL was higher in the overweight
group, followed by obesities grades I, II and III sequentially (p50.0001). Percent
EWL was also higher in women than in men (p50.0001).
CONCLUSION: Endoscopic treatment of excess weight with an IGB has been
established as an excellent therapeutic option for patients of both genders with
overweight or different degrees of obesity.
Disclosure of Interest: None declared
P0550 PREDICTIVE RISK FACTORS FOR SUCCESS OF BARIATRIC
THERAPY WITH BIOENTERICS INTRAGASTRIC BALLOON

P0548 ARGON PLASMA FULGURATION TO TREAT WEIGHT REGAIN


AFTER BARIATRIC SURGERY
R.J. Fittipaldi-Fernandez1,*, C.F. Diestel2,3
1
Digestive Endoscopy, Endogastro Med Service, 2Nutrition Division, UNI-RIO Rio
de Janeiro University, 3Nutrition Division, Endogastro Med Service, Rio de
Janeiro, Brazil
Contact E-mail Address: ricfittipaldi@hotmail.com
INTRODUCTION: The weight regain is a problem after bariatric surgery and
occurs, in part, by dilatation of the gastro-jejunal anastomosis, which causes a
faster gastric emptying and increased food intake.
AIMS & METHODS: Objective: To evaluate the efficacy of endoscopic fulguration of the anastomosis and of the gastric stump using argon plasma (APF)
aiming to reduce the diameter thereof.
Methods: We analyzed 32 patients. 30 of them underwent at least 02 sessions of
FPA. Two patients underwent only one session due to an immediate reduction of
the anastomosis to a diameter smaller than 10 mm after the first session, wich is
the procedure target. The coagulation was held at the anastomosis and in gastric
stump. 80 w power was used in the 1st session, and 70w power FPA in the
following, with an Agon flow of 2L/min. The objective is to obtain an anastomosis with a diameter less than or equal to 10 mm. Data were analyzed with
descriptive statistics, students t test and Spearman correlation.
RESULTS: Of the 32 patients, 87.5 % were women (n 28). The mean regained
weight in relation to the maximum weight lost (Nadir) after bariatric surgery was
46.9 % (14 to 76.9). The mean duration of treatment was 170 days (56-338).
There was a significant reduction in body mass index (BMI) at the end of the
analysis (32.424.45 kg/m2) compared to the initial mean BMI (mean
BMI 37.054.76 kg/m2) (p 5 0.0001). The average loss of the regained
weight was 66.92% (22.08-211.11). The average weight loss in Kg was 12.73
(6.3-25.5). There was significant correlation between the reduction in the BMI
and the highest number of sessions of FPA (p 0.0003) and between the longer
duration of the treatment (p 0.0212). The analyzed patients remain in
treatment.
CONCLUSION: The FPA has demonstrated great efficacy in the treatment of
weight regain after bariatric surgery of gastric bypass in Roux-Y.
Disclosure of Interest: None declared

R. Cerqueira1, M. Correia1,*, M.C. Manso2


1
Gastroenterology, Centro Hospitalar entre Douro e Vouga, Santa Maria Feira,
Santa Maria Feira, 2Biostatistics - Requimte-up, University Fernando Pessoa,
Porto, Portugal
Contact E-mail Address: rute.cerqueira@chedv.min-saude.pt
INTRODUCTION: In obese patients, a large amount of data shows that bariatric therapy with Bioenterics intragastric balloon (BIB) results in weight loss in
some patients. However there is a paucity of data about predictive risk factors for
BIB success.
AIMS & METHODS: The aim of this study was to determine the effectiveness of
this device on weight loss and predictive risk factors for BIB success. A prospective study with 147 patients [(75.5% females, mean age 40 (11.9)] submitted to
BIB insertion, which was removed after 41.4 (12.7) weeks. Anthropometric and
laboratory parameters were assessed when BIB was positioned and when BIB
was removed. BIB success was defined as weight loss  50% of the weight excess
(pre BIB weight calculated weight to lower the BMI to 24.9).
RESULTS: At baseline, mean weight was 97.2 Kg ( 16.1), mean body mass
index (BMI) was 36.5 (5.9) kg/m2, 19 (12.9 %) patients had type II Diabetes
Mellitus and mean insulin resistance (HOMA-IR) was 2.9 ( 2). With BIB
intervention, mean weight and mean BMI decreased, respectively, to 83.5 (
16.9), p5 0.001 and 31.4 (6.3), p50.001. Regarding laboratory parameters,
cholesterol, triglycerides and HOMA-IR were significantly reduced (p50.05).
There was no significant improvement in TGP, G-GT, HDL cholesterol and
ferritin. BIB success was observed in 57 (38.8%) patients. Predictive risk factors
for BIB success were mean pre-operative weight, 92.8 (13) vs 99.7 ( 16.9)kg,
p 0.011 and mean pre-operative BMI, 35 (3.5) vs 37.5 (6.9), p 0.007; a
trend was observed for baseline HOMA-IR, 2.7 (2.3) vs 3 (1.7), p 0.056.
CONCLUSION: BIB therapy achieves significant weight loss and significantly
improves laboratory parameters of the metabolic syndrome in obese patients.
BIB success is associated with baseline weight and baseline BMI further emphasizing that the endoscopic technic has major impact in mild obese, those that are
not surgical candidates.
Disclosure of Interest: None declared

A285

United European Gastroenterology Journal 2(1S)


P0551 PREOPERATIVE
ENDOSCOPY
IN
BARIATRIC PATIENTS IS IT STILL WORTH IT?

ASYMPTOMATIC

S.R. Fernandes1,*, L. Meireles1, L.A. Correia1, L.C. Ribeiro1, J. Velosa1


1
Gastrenterologia e Hepatologia, Hospital Santa Maria - Centro Hospitalar Lisboa
Norte, Lisboa, Portugal
Contact E-mail Address: Samuelrmfernandes@gmail.com
INTRODUCTION: Obesity represents a major public health problem associated
with increased risk of diabetes, cardiovascular and cerebrovascular disease and
cancer. Surgery has shown to be an effective long term treatment. Preoperative
endoscopy (POE) is recommended by the current "guidelines", but evidence
supporting this recommendation in asymptomatic patients is scarce.
AIMS & METHODS: We sought to determine whether endoscopic findings
justify routine POE before bariatric surgery. Obese (BMI4 30 kg/m2) and morbidly obese (BMI4 35 kg/m2) patients undergoing endoscopy in our institution
were retrospectively selected. Endoscopic and histological findings and their
impact on surgical strategy were assessed.
RESULTS: Of 557 patients (78.3 % female, mean age 46.911.5 years), 43.3 %
had a normal endoscopy. Esophageal, gastric and duodenal disease were present
in 22.6 %, 44.2 % and 11.0 % respectively. The most frequent esophageal findings were hiatus hernias (17.2 %) and esophagitis (8.0 %, 97.5 % Class A and B
of Los Angeles). Gastric changes included erosive (18.3%) and non-erosive gastritis (19.7%), polyps (4.8%) and ulcers (1.6%, all Forrest III). Bulbitis (10.4%),
ulcers (0.5%) and polyps (0.2%) composed most common duodenal findings.
From a total of 218 gastric biopsies 46.3% revealed the presence of
Helicobacter pylori (Hp) bacilli. In 3 patients Barretts esophagus was diagnosed
(without dysplasia) and in 2 gastric low grade MALT lymphoma (which
regressed after eradication of Hp).
CONCLUSION: Our findings were of little relevance and did not alter the
operative strategy. Given the high prevalence of Hp, which has been associated
with higher postoperative complications, its screening by non-invasive methods
prior to surgery may be a less expensive alternative. This study suggests that EPO
might be dispensable in asymptomatic bariatric patients.
Disclosure of Interest: None declared
P0552 MODIFIED
PROBIOTIC
ESCHERICHIA
COLI
NISSLE
INCREASES COLONIC SHORT CHAIN FATTY ACIDS AND FECAL
BIFIDOBACTERIA AND LACTOBACILLI COUNT IN RATS
A.K. Singh1,*, S. Pandey1, A.S. Parihar1, N.K. Gattupalli1
1
Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara, India
Contact E-mail Address: singhashish1186@gmail.com
INTRODUCTION: Short Chain Fatty Acids (SCFAs) are considered as one of
the most important metabolite produced by commensal organism in the gut.
Dietary consumption of complex carbohydrates such as inulin, fructo-oligosaccharides and sodium gluconate are known to increase SCFAs in the colon.
However, they limit in their efficacy if not consumed daily. E. coli represents a
major commensal population the human colon. E. coli expresses an apo- form of
membrane bound enzyme, glucose dehydrogenase, which converts glucose to
gluconic acid. However, it is unable to synthesize the cofactor, PQQ
(Pyrroloquinoline quinone). E. coli produces gluconic acid when PQQ is supplied
in the medium.
AIMS & METHODS: We hypothesized that, recombinant probiotic E. coli
Nissle 1917 (EcN) expressing PQQ synthesis genes is able to synthesize large
amount gluconic acid in the intestine and subsequently increased production of
SCFAs.
pqqABCDE gene cluster was cloned and expressed in EcN. Rats were fed with
starch containing diet along with recombinant probiotic EcN for 60 days.
RESULTS: Recombinant EcN expressing pqqABCDE gene cluster produces high
amounts of gluconic acid in M9 minimal medium supplemented with glucose
under laboratory conditions. Weekly treatment of recombinant EcN producing
gluconic acid results in increased production of gluconic acid in the colon.
Additionally, SCFAs (Butyrate and Acetate) concentration was also found to
be elevated by approximately 3 fold and 1.6 fold respectively. mRNA profile of
colon showed increased expression of mucin and intestinal trefoil factor genes in
treated rats. The treated rats also had increased fecal Bifidobacteria and lactobacilli number.
CONCLUSION: The present study suggest that engineered probiotic could be a
potent nutritional supplement against intestinal dysbiosis and other related
pathologies.
REFERENCES
Kameue C, et al. Dietary sodium gluconate protects rats from large bowel cancer
by stimulating butyrate production. J Nutrition 2004; 134: 940-944.
Rucker R, Chowanadisai W and Nakano M. Potential physiological importance
of pyrroloquinoline quinone. Alternative Med Review 2009; 14.
Biagi G, et al. Effect of gluconic acid on piglet growth performance, intestinal
microflora, and intestinal wall morphology. J Animal Sci 2006; 84: 370-378.
Asano T, et al. Effects of gluconic acid on human faecal bacteria. Microbiol Ecol
Health Dis 1994; 7: 247-256.
Sonnenborn U and Schulze J. The non-pathogenic Escherichia coli strain Nissle
1917 features of a versatile probiotic. Microb Ecol Health Dis 2009; 21: 122-158.
Disclosure of Interest: None declared

P0553 NUTRIENT INTAKES AT THE TIME OF DIAGNOSIS IN


PATIENTS WITH HIV INFECTION: COMPARISON WITH
NATIONAL NUTRITIONAL GUIDELINES AND WITH A COHORT
OF HEALTHY SUBJECTS
B. Zanini1,*, R. Bosio1, N. Brianese1, A. Ferraresi1, A. Arrighi1, E. QuirosRoldan1, F. Castelli1, A. Lanzini2
1
Department of Clinical and Experimental Sciences, 2UNIVERSITY AND
SPEDALI CIVILI OF BRESCIA, Brescia, Italy
Contact E-mail Address: b_zanini@tin.it
INTRODUCTION: Assessment of nutrient intake is an important key element in
healthcare of HIV patients because nutritional status is a determinant of HIV
outcomes and of many co-morbidities including gastrointestinal problems, osteoporosis, cardiovascular diseases, diabetes and other metabolic changes (1,2).
Little is known about nutritional adequacy among HIV patients at the time of
diagnosis and prior to pharmacological treatment.
AIMS & METHODS: We carried out a prospective clinical study to assess
macro- and micro-nutrient components of diet in a cohort of HIV patients at
the time of diagnosis, and to compare them with Italian recommended levels of
nutrient intake (LARN 2012) and with those of a cohort of healthy subjects,
matched with HIV cohort according to gender and age (range  4 years).
Patients in the two cohorts were instructed to fill in a standardized 7-day food
diary. Data from diaries were analyzed with Microdiet software (Downlee
system, ltd. UK) and nutritional characteristics studied were: total Kcal, proportion of total energy value of CHO, free sugars, proteins, fats, SFA and PUFA,
and total amounts of fibre, vitamins A, B12, C, and D, folates, sodium, calcium,
iron, zinc. For statistical analysis Fishers exact test and Wilcoxon matched pairs
test were used as appropriate.
RESULTS: 22 HIV patients signed informed consent, 21 returned the diary and
14 were at present analyzed. Eleven were male, age 42 1 year (mean  SD),
BMI 23.8 3.3 Kg/m2 with 4 patients in overweight class, 1 in grade 1 obesity
class and 9 in normal BMI class. Comparison of selected nutrient composition
with LARN and with healthy subjects are reported in the table.
Nutrients

HIV patients

Healthy subjects

HIV Vs LARNx %

CHO, % TEV
Fats, %TEV
Proteins, %TEV
Vitamin B12, mg
Vitamin D, mg
Folates, mg
Calcium, mg
Iron, mg
Zinc, mg

48.26.9
33.26.0
16.32.2
3.71.4
2.51.8
191.644.6
508.9133.0
7.01.4
8.41.5

40.05.6*
37.03.4*
16.62.6
2.50.8*
3.41.6
140.349.8*
771.0253.9
9.72.3*
8.82.1

- 21
36
79
-21
-100
-100
-100
-100
-79

CONCLUSION: Daily intake is inadequate in HIV patients at time of diagnosis


for most macro- and micro- nutrients, but is closer to LARN recommendations
than in healthy subjects. Nutritional counseling must be provided in HIV na ve
patients in order to improve their nutritional status and to contribute to prevention of gastrointestinal and metabolic co-morbidities.
REFERENCES
Hendricks KM, et al. Am J Clin Nutr 2008; 88: 1584-1592.
2) Giudici KV et al. Sao Paulo Med J 2013; 131: 145-152.
Disclosure of Interest: None declared
P0554 SUPPLEMENTATION WITH A PROBIOTIC MILK DRINK DOES
NOT ALTER GUT MICROBIOTA COMPOSITION IN PATIENTS
WITH METABOLIC SYNDROME
B. Leber1,*, N. Tripolt2, S. Trajanoski3, C. Hogenauer4, H. Sourij2,
V. Stadlbauer4
1
Transplantation Surgery, 2Endocrinology and Metabolism, 3Center for medical
Research - Bioinformatics, 4Gastroenterology and Hepatology, Medical University
of Graz, Austria, Graz, Austria
Contact E-mail Address: bettina.leber@medunigraz.at
INTRODUCTION: Metabolic syndrome (MetS) is associated with disturbances
in gut microbiota including changes in the Bacteroidetes/Firmicutes ratio. In
animal models, modulation in the composition of gut microbiota through supplementation with probiotics is possible. It is not known to date if this is also
possible in humans.
AIMS & METHODS: We therefore aimed to study whether supplementation
with a probiotic milk drink containing Lactobacillus casei Shirota (LcS) is able to
modulate gut microbiota composition in patients with MetS. In a single-center,
prospective, randomized-controlled pilot study, 28 subjects with MetS received
either LcS (YAKULT light 3 bottles a day, 65 ml each, containing LcS at a
concentration of 108/ml) for 12 weeks (LcS group; n 13) or received standard
medical therapy (n 15). 6 healthy subjects served as controls. Stool samples
were collected at baseline and after 3 months. Gut microbiota composition was
characterized using 454 pyrosequencing of the amplicon libraries from V1 to V3
hypervariable regions of 16S rRNA genes. Generated sequencing data was analyzed with Quantitative Insights Into Microbial Ecology (QIIME version 1.7.0)
pipeline in stool samples.
RESULTS: No significant differences in Unifrac distances or Bray-Curtis distances between samples from the same patients in two time points were found

A286

United European Gastroenterology Journal 2(1S)

(p 0.70 and 0 0.48, respectively). The Bacteroidetes/Firmicutes ratio was not


different compared to healthy controls and was not influenced by probiotic
supplementation (Controls: 0.783; LcS baseline: 0.961; LcS 3 months: 1.007;
Standard baseline: 0.921; Standard 3 months: 0.995). Diversity (using Shannon
index) and richness of gut microbiota in MetS showed similar distribution compared to healthy controls and was not influenced by probiotic supplementation.
LcS was only detectable in 1 individual of the treatment group after 3 months of
supplementation with LcS.
CONCLUSION: In our study no difference in gut microbiota composition was
found between healthy subjects and patients with MetS. The supplementation of
LcS did not change gut microbiota composition, so we conclude that the microbiota variations occurring in the treatment group were not larger than the normally expected variations during this time period. This is in accordance with our
previous findings that supplementation with LcS did not influence clinical and
biochemical parameters of glucose metabolism, inflammation and innate immune
response.
Disclosure of Interest: None declared
P0555 QUANTIFICATION OF IN VIVO COLONIC SHORT CHAIN
FATTY ACID PRODUCTION FROM INULIN
E. Boets1,*, E. Houben1, S. Gomand2, J. Delcour2, K. Verbeke1
1
Translational Research for Gastrointestinal Disorders, Leuven Food Science and
Nutrition Research Centre, 2Laboratory of Food Chemistry and Biochemistry,
Leuven Food Science and Nutrition Research Centre, KU Leuven, Leuven, Belgium
Contact E-mail Address: eef.boets@med.kuleuven.be
INTRODUCTION: Short chain fatty acids (SCFA; acetic (Ac), propionic (Pr)
and butyric (Bu) acid) are produced during bacterial fermentation of undigested
carbohydrates in the colon. In this study, we determined the bioavailability of
each SCFA and applied a stable-isotope dilution method to quantify the colonic
production of SCFA after consumption of inulin.
AIMS & METHODS: Six healthy subjects (3F/3M; 297y) each performed 4
test days with minimal 1 week interval. On the first 3 test days they received
either 400mg 13C-Ac or 340mg 13C-Pr or 990mg 13C-Bu in a pH-dependent colon
delivery capsule with a standard breakfast. After collection of a basal blood
sample, they received a primed constant infusion of 2H-labelled SCFA
(Ac:20mmol/kg.h; Pr:2mmol/kg.h; Bu:1mmol/kg.h) for 12h. On the 4th test day,
the SCFA production from inulin fermentation was quantified. The subjects
received 15g of inulin (Raftilin HP, Beneo-Orafti) with a standard breakfast
and an infusion with 13C-SCFA (Ac:12mmol/kg.h; Pr:1.2mmol/kg.h;
Bu:0.6mmol/kg.h) for 12h. Additional blood samples were collected at regular
times during the day. Plasma total SCFA concentrations, 13C- and 2H-SCFA
enrichments were measured using gas chromatography (GC), GC combustion
isotope ratio mass spectrometry (IRMS) and GC pyrolysis IRMS, respectively.
The bioavailability index (F) of the respective SCFA was calculated from the area
under the curve (AUC) of the 13C-SCFA concentration time curve (F AUC x
Cl x 100/administered dose). The clearance rate (Cl) was determined using the
2
H-SCFA infusion (Cl infusion rate (i)/steady state (SS) 2H-SCFA concentration). SCFA turnover was calculated using stable-isotope dilution. The infusion
with 13C-SCFA results in a constant 13C-SCFA enrichment in the blood. After
fermentation of inulin in the colon, SCFA enter the blood and dilute the 13CSCFA resulting in a decrease of 13C-SCFA enrichment. The total turnover (T) of
the SCFA at each time was calculated as follows: T i x [(Tracer enrichment/
Plasma enrichment)-1]. The turnover at SS was subtracted from the total turnover to obtain the exogenous SCFA turnover. The AUC was calculated to yield
total SCFA appearance in plasma. Finally, the bioavailability index and SCFA
plasma concentrations were used to quantify the SCFA produced in the colon.
Results are expressed as medians and interquartile ranges.
RESULTS: The bioavailability index of Ac, Pr and Bu were 37 [30-57]%, 21 [1725]% and 4 [3.5-9]%, respectively. SS turnover of Ac, Pr and Bu were 13 [8-16],
0.23 [0.19-0.31] and 0.26 [0.15-0.34] mmol/kg.min, respectively. The total amount
of Ac in plasma was 661 [512-991] mmol/kg; corresponding to a production of 112
[88-194] mmol of Ac in the colon within 12h after inulin ingestion. The AUC of
Pr and Bu were 14 [9-22] and 13 [10-15] mmol/kg, respectively. Twelve hours after
inulin ingestion a total of 0.9 [0.6-1] and 0.7 [0.6-1] mmol of Pr and Bu appeared
in the circulation. The colonic produced Pr and Bu levels were 4 [2-6] and 19 [1124] mmol, respectively.
CONCLUSION: In conclusion, inulin is mainly fermented into acetate followed
by butyrate and propionate. Stable isotope technology allows to quantify in vivo
SCFA production from carbohydrate fermentation and will facilitate the evaluation of health benefits attributed to SCFA.
Disclosure of Interest: None declared
P0556 ABDOMINAL
HEMODYNAMIC
IN
PATIENTS
MALNUTRITION AND HEREDITARY CONNECTIVE TISSUE
DISORDERS

WITH

G. Nechayeva1, M. Livzan1, E. Lialiukova1,*


Omsk state medical academy, Omsk, Russian Federation

INTRODUCTION: The aim of the research is to study the peculiarities of


abdominal hemodynamic in patients with malnutrition and hereditary connective
tissue disorders.
AIMS & METHODS: To study mechanisms of malnutrition at the patients with
hereditary connective tissue disorders.
121 patients with hereditary connective tissue disorders were included in the
research (The revised Ghent nosology for the Marfan syndrome, 2010). The
control group was represented by 40 healthy subjects to be comparable by sex
and age. The assessment of malnutrition and ultrasonic dopplerography of the
abdominal vessels (vena portae, arteria hepatica communis, arteria mesenterial

superior and arteria splenica) were performed for the patients. The investigation
was undertaken with fasting after feeding test, with the ultrasound scanner
Sonoace-8000 (Medison, South Korea).
RESULTS: The signs of malnutrition in patients with hereditary connective
tissue disorders have been revealed in 70,9% of cases. The degree of malnutrition
has been correlated with the expression of hemodynamic disturbances (r -0,55;
o50,001).
By estimating the abdominal blood flow in persons with hereditary connective
tissue disorders more lower volume rates of a blood flow were recorded: along
vena portae - 1853,0 [1688,0-2297,0] ml/min., in the group of comparison -2149,0
[1827,0-2400,0] ml/min (o50,05); along arteria mesenterial superior - 988,0
[837,0-1272,0] ml /min, in the group of comparison - 1136,5 [992,0-1465,0] ml/
min (o50,05); along the vessels of a celiac trunk: arteria hepatica communis 480,5 [425,0-587,0] ml/min, in the group of comparison - 591,5 [536,0-689,0] ml/
min. (o50,001) and splenic arteries - 600,0 [452,0-709,0] ml/min, in the group of
comparison - 700,0 [591,0-795,0] ml/min (o50,01). After meal the persons with
hereditary connective tissue disorders had fewer high-speed indicators gain and it
didnt exceed 30% from the initial indicators (o50,001).
The data of the abdominal blood flow were correlated with some central hemodynamic changes (minute volume of circulation): at the vena portae (r 0.55, o
50,05), at the arteria hepatica communis (r 0.60, o 50,05), at the splenic
artery (r 0.77 o 50,05); by the extent of vegetative sympathetic influences on
a vascular tonus: at the arteria hepatica communis (r -0,48, o50,05), at the
splenic artery (r -0,27, o50,05), at the arteria mesenterial superior (r -0,36, o
50,05); by splanchnoptosis degree: at the portal vein (r -0,210; o50,05), at the
arteria hepatica communis (r -0,38; o50,05), at the arteria mesenterial superior
(r -0,86; o50,05).
CONCLUSION: The signs of malnutrition in patients with hereditary connective
tissue disorders have been revealed in 70.9% of cases. The degree of malnutrition
has been correlated with the expression of systemic connecting tissue involvement. The postprandial period abdominal blood flow has been characterized by
the low values of volume rate at the vessels of the celiac trunk, arteria mesenterial
superior, and portal vein. Some disturbances of a cardiac hemodynamic, prevalence of sympathetic influences on vascular tonus, splanchnoptosis presence may
be considered to be the main causes of blood flow decreasing.
Disclosure of Interest: None declared
P0557 OPTIMIZATION OF DIAGNOSIS AND TREATMENT
NUTRITIONAL INSUFFICIENCY IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE

OF

A.A. Iakovlev1,*, T.S. Kazaryan1


1
gastroenterology, ROSTOV ON DON STATE MEDICAL UNIVERSITY,
Rostov on Don, Russian Federation
Contact E-mail Address: gastroklinika@yandex.ru
INTRODUCTION: Development of nutritional deficiency (ND) due to the loss
of nutrients, water and electrolytes with frequent stools, nutrients malabsorption,
anorexia and increased catabolism is typical for patients with IBD relapse. To
determine the frequency and structure of ND in patients with IBD relapse and to
evaluate the therapeutic effect of nutritional support (NS) of nutritive mixtures
during the course of therapy.
AIMS & METHODS: Two-phase three step study with prospective monitoring
in patients with IBD was conducted during 3 years in the period from 2010 to
2012. The first phase was carried out using a one-time screening scales MUST
and NRS, further in phase 2, the NS structure was refined. 520 patients with IBD
were examined: 410 with ulcerative colitis (UC) and 110 with Crohns disease
(CD).
RESULTS: The 1st, 2d and 3d degree of ND was detected in 111 (27.1%), 96
(23.4%) and 42 (10.2%) patients with UC, respectively. 2d and 3d degree of ND
was recorded in 48 (43.6%) and 29 (26.4%) cases in patients with CD, respectively. At the second stage of the study, 80 patients with UC were randomized
into two major groups, depending on the degree of NN, were divided into groups
A (2d degree of ND) and B (3d degree of ND). On basic therapy, patients of the
Ist group received a diet with a high amount of protein (HAPD) and increased
calorage (2500 kcal / day), while to the patients of the IId group in addition to the
basic therapy, nutritional mixtures: peptamen and modulen IBD (Nestle) in the
amount of 1/3 of the daily calorage were prescribed. Efficacy of treatment was
evaluated on the 3 d, 4th, 12th week. At the third stage of the study, during 3
years, the long-term results were studied using index of the relapse frequency
(IRF). Pick of the IRF was in the 1st group and by the end of the study it was 15
(75%) and 17 (85%) cases, respectively. In the second group IRF was significantly lower: 9 (45%) and 12 (60%) (p 50,05).
CONCLUSION: In patients with UC and CD relapse ND of the 1st and 3d
degree was recorded an average of 20.3% and 35%, respectively. Use of NS
provides a low rate UC relapse, and thus stable remission of the disease.
Disclosure of Interest: None declared
P0558 TEDUGLUTIDE FOR PATIENTS WITH SHORT
SYNDROME-INTESTINAL FAILURE. A SINGLE CENTER
EXPERIENCE

BOWEL

A. Ukleja1, A. Alvarez1,*, K. Alvarez2, L. Lara1


1
Gastroenterology, CLEVELAND CLINIC FLORIDA, Weston, United States,
2
Nutrition, Licda Nutricion Clnica & Bariatrica, Guatemala City, Guatemala
Contact E-mail Address: uklejaa@ccf.org
INTRODUCTION: Teduglutide (TG) is a novel agent recently approved for the
treatment of parenteral support (PS) dependent patients with short bowel syndrome (SBS). PS dependence is a major concern for patients with SBS because of
PS caries a risk of serious complications and affects quality of life. In phase III

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United European Gastroenterology Journal 2(1S)


trial, TG use lead to significant reduction in PS volume in SBS patients. Limited
data is available regarding clinical results outside the research protocols.
AIMS & METHODS: Aims: To evaluate short and long-term outcomes of SBS
patients receiving TG and assess patients interest in TG therapy. Methods:
Retrospective medical chart review was conducted. 19 pts. with SBS were identified. Demographics, length of small bowel, primary diagnosis, past surgical history, PS (TPN/IV fluids) volume and duration, TG dose and related
complications were collected. SBS patients who received TG from 04/2013 to
03/2014 were included in the final analysis.
RESULTS: 6 of 19 SBS pts. received TG (Females 4, Males 2); Race: Caucasian
4, Hispanic 1, African-American 1. Mean age: 45.8 yrs. (range 26-71). Cause of
SBS: vascular 3, RYGB/strangulation 1, surgical resections 2. SB length: range
30-120 cm. Colon in continuity 4, stoma 3 (ileostomy 2, colostomy 1). TPN
duration: range 114 years. PS volume/week 1-8 Liters. Duration of TG therapy:1-12 months. Complications: bowel obstruction (SBO) 1, stoma swelling 2,
bloating 4 (subsided). TG discontinuation 1 (SBO*), TG dose reduction 1 (stoma
swelling). PS discontinued 4. Volume reduction in 6/6 pts. Gain or stable weight
in all while on TG. No biliary/pancreatic complications, TG injection aversion
were seen. Reason for no TG therapy in 13 pts.: No TG candidates 4 (recent
cancer 2, post surgery 512 months 1, massive small bowel dilation 1), no insurance approval 1, no interest in TG therapy 8. Characteristics of SBS patients who
received TG therapy.
PS
PS
PS
SB
TG duration
length Colon Duration Volume Reduction PS
Stopped (months)
(Week) 420%
present (years)
Pts. Age Sex (cm)
1
2
3
4
5
6

52
29
26
36
61
71

F
F
F
M
F
M

90
30
70
50
120
90

N
Y
Y
Y
N
Y

1.5
14
5
2
2
2

8L
7.2L
6.4L
7.5L
1L
7L

Y
Y
Y
Y
Y
Y

N
Y
Y
Y
Y
N

1
12
9
6
5
4 (TG stopped*)

CONCLUSION: From our eligible SBS patients only 6/14 (43.8%) received TG
and 4 50% of them expressed no interest in TG therapy. Three PS/nutrient
dependent patients with colon in continuity and one with end-stoma discontinued PS completely with TG therapy. All patients had 420% reduction in PS
volume while on TG. All had significant reduction in stoma/stool output. TG
was well tolerated. Further studies with a larger sample size are needed in SBS
patients to assess clinical benefits of TG and address patient decision process
regarding this therapy.
Disclosure of Interest: A. Ukleja Consultancy for: NPS, A. Alvarez: None
declared, K. Alvarez: None declared, L. Lara: None declared
P0559 BEDSIDE ELECTROMAGNETIC GUIDED PLACEMENT OF
NASOJEJUNAL FEEDING TUBES IN PATIENTS AFTER
PANCREATODUODENECTOMY: PROSPECTIVE SINGLE-CENTER
PILOT STUDY
A. Gerritsen1,*, A.C. Duflou2, M. Ramali2, O.R. Busch1, D.J. Gouma1,
L.M. Mathus-Vliegen2, M.G. Besselink1
1
Department of Surgery, 2Department of Gastroenterology, Academic Medical
Center, Amsterdam, Netherlands
Contact E-mail Address: a.gerritsen@amc.nl
INTRODUCTION: Early oral feeding is now considered the routine feeding
strategy after pancreatoduodenectomy. Some 35-45% of patients will develop
delayed gastric emptying postoperatively and consequently require nasojejunal
tube feeding. Endoscopic placement of a nasojejunal feeding tube by gastroenterologists is relatively labour-intensive and a cumbersome procedure for
patients. Bedside electromagnetic (EM) guided placement using the Cortrak
Enteral Access System by nurses has been found to be a simple, safe and costeffective strategy in several patient categories. To date, however, an altered anatomy of the upper gastrointestinal tract is seen as a relative contraindication for
EM-guided tube placement.
AIMS & METHODS: The aim of this study was to determine the success rate of
bedside EM-guided placement of nasojejunal feeding tubes in patients after
pancreatoduodenectomy.
We performed a prospective single-center pilot study in all patients requiring a
nasojejunal feeding tube after pancreatoduodenectomy between July 2012 and
March 2014. EM-guided nasojejunal tubes were placed by two specialized nurses
with extensive experience with the technique. EM-guided placement was not
performed in patients with upper gastrointestinal stenosis or oesophageal varices
or when it was not possible for logistical reasons. Primary endpoint was the
success rate of primary tube placement confirmed on plain abdominal x-ray
(AXR). Success was defined as the tip of the tube positioned in the efferent
jejunal limb.
RESULTS: In our study period, 55 of 126 (44%) patients who underwent pancreatoduodenectomy required a nasojejunal feeding tube. In 36 patients the tube
was placed under EM-guidance at a median of 8 (6-11) days after pancreatoduodenectomy. Initial tube placement was successful according to the nurse in 25
(69%) patients and on AXR in 21 (58%) patients. Median procedure time was 25
(15-35) minutes. 22 (61%) patients underwent 50 replacement procedures after
previously failed placement attempts (n 31) or after luxation or blockage of the
tube (n 19). 36 replacements were performed endoscopically, with a success rate
of 67%, and 14 under EM-guidance, with a success rate of 71%. No tube
(re)placement related complications occurred. There was no learning curve
effect when comparing the first 10 with the subsequent 26 procedures concerning

success rate, but median procedure time decreased from 33 (18-45) to 20 (15-30)
minutes.
CONCLUSION: Bedside EM-guided placement of nasojejunal tubes after pancreatoduodenectomy was successful in 58% of patients, which seems acceptable
given the potential benefits for the patient. Based on these findings we have
included patients after pancreatoduodenectomy in an ongoing randomized multicenter trial focussing on the magnitude of benefits of EM-guided placement, such
as reduced patient discomfort and costs as compared to endoscopy.
Disclosure of Interest: None declared
P0560 PROSPECTIVE STUDY OF PERISTOMAL INFECTIONS AFTER
PERCUTANEOUS ENDOSCOPIC GASTROSTOMY OVER A FOURYEAR PERIOD
C.R. Chimakurthi1,*, S. Lewis1, N. Pitts2, V. Chudleigh3
Gastroenterology, 2Endoscopy, 3Remedial Services, Plymouth Hospitals NHS
Trust, Plymouth, United Kingdom
Contact E-mail Address: cchimakurthi@nhs.net
1

INTRODUCTION: Incidence of peristomal infections following percutaneous


endoscopic gastrotomy in the community is not well known. Data on subsequent
site infections and the organisms responsible is limited. Despite the use of prophylactic antibiotics, the incidence of peristomal infections is significant and
result in substantial morbidity in patients with PEGs.
AIMS & METHODS: We aim to evaluate the prevalence of peristomal infection
in our local community over a four year period after their PEG placement. Other
objectives were to characterise the microbiology from wound site swabs and to
identify any correlation between peristomal infection and patient characteristics.
Our study also looked at incidence of subsequent peristomal infection rates in the
community prospectively over a 4-year period.
Patients aged 16 and over who have had percutaneous endoscopic gastrostomies
placed at Derriford hospital, Plymouth, UK during years 2008 to 2012 were
included in the study period. Patients with venting gastrostomies and those
who had their gastrostomies placed while undergoing treatment for Head &
Neck cancer were not included in this study. All patients had their PEGs
placed according to British Society of Gastroenterology guidelines with pre-procedure prophylactic antibiotics. Community enteral feed dieticians followed all
patients at clinically appropriate intervals in the community following discharge
from hospital. They recorded incidence of infections and various other complications over the four-year period. Endoscopy reports, clinical case records, and
microbiological investigation results were also reviewed. Excel and Stata 10 were
used for data collection and analysis.
RESULTS: 341 patients underwent percutaneous endoscopic gastrostomy
during the study period. 110 patients (31%) needed treatment for an insertion
site infection. The median time from PEG insertion to first wound site infection
was 85 days (14, 363). Mixed skin commensals (42.7%) followed by
Staphylococcus aureus (29%) were most frequently isolated from gastrostomy
wound site swab. Only one patient had Methicillin resistant staphylococcus
aureus isolated. The spectrum of organisms for subsequent peristomal infection
was similar to those causing the first infection. The majority of infections
resolved with appropriate treatment. Indications for PEG insertion, age, sex
and residence did not correlate with peristomal infection. Two patients needed
replacement with new PEG tubes in view of infection. Both of them needed their
PEG tubes replaced thrice further. No specific organisms were associated with
the removal and replacement of PEG tubes.
CONCLUSION: Our rates of peristomal infection are similar to previous studies1. Although staphylococcus aureus was frequently isolated from insertion
site, the prevalence of MRSA was much lower in our cohort2. The time from
PEG insertion to initial infection was also much longer2.
REFERENCES
1. Zopf Y, Konturek P, et al. Local infection after placement of percutaneous
endoscopic gastrostomy tubes: a prospective study evaluating risk factors. Can J
Gastroenterol 2008; 22: 987-991.
2. Duarte H, Santos C, et al. Peristomal infection after percutaneous endoscopic
gastrostomy: a 7-year surveillance of 297 patients. Arq Gastroenterol 2012; 49:
255-258.
Disclosure of Interest: None declared
P0561 RESTORATION OF BOWEL CONTINUITY CAN REDUCE THE
RISK OF CHRONIC CHOLESTASIS IN PATIENTS WITH A SHORT
BOWEL
F. Adaba1,*, C. Vaizey1, S. Gabe1, J. Warusavitarne1, J. Nightingale1
1
St Marks Hospital, Harrow, United Kingdom, London, United Kingdom
Contact E-mail Address: f.adaba@nhs.net
INTRODUCTION: Patients with a short bowel and on home parenteral nutrition (HPN) have an increased risk of chronic cholestasis. This is may be due to
recurrent sepsis, reduced bile flow with biliary stasis or associated with HPN.
Restoration of bowel continuity can result in HPN requirements being reduced
or stopped. This study aims to determine the effect of restoration of bowel
continuity on the risk of chronic cholestasis (CC).
AIMS & METHODS: A retrospective review of patients with short bowel due to
mesenteric infarction from 2000-2010. Chronic cholestasis (CC) was defined as
two of bilirubin, alkaline phosphatase and gamma-glutamyl transferase being 1.5
times the upper limit of normal for more than 6 months.
RESULTS: Number of patients with data on liver functions was 101 (55 females,
median age 54 years). Fifteen (54%) of 28 patients with a jejunostomy had CC
while 4 (25%) of 16 patients who had a primary anastomosis and 11(19%) of 57
patients who had a delayed anastomosis had CC. Univariate analysis showed
restoration of bowel continuity reduced the risk of chronic cholestasis

A288
(p 0.002). Of 11 patients with delayed anastomosis and CC, 3 had resolution of
CC, 3 patients died and 5 had continuing CC.
CONCLUSION: Restoration of bowel continuity can reduce the risk of chronic
cholestasis in patients with a short bowel.
Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014


9:0017:00
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE
I POSTER EXHIBITION HALL XL_____________________
P0562 FACTORS RELATED TO LYMPH NODE METASTASIS AMONG
ADDITIONAL SURGICAL RESECTION AFTER NON-CURATIVE
ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC
CANCER
N. Kawata1,*, N. Kakushima1, T. Sugino2, M. Tanaka1, K. Takizawa1,
M. Yoshida1, Y. Kishida1, K. Imai1, K. Hotta1, H. Matsubayashi1, H. Ono1
1
Endoscopy, 2Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Japan
Contact E-mail Address: n.kawata@scchr.jp
INTRODUCTION: Indication of endoscopic resection for early gastric cancer
(EGC) has been determined by the analysis of node-negative cancer using a large
database of surgically resected EGC patients. Pathological assessment of tumor
depth and lymphovascular infiltration among surgically resected specimens are
likely to be underestimated compared to that of endoscopically resected specimens because the section interval is thick (five and two millimeters, respectively).
The aim of this study was to clarify the related factors for lymph node metastasis
(LNM) among additional gastrectomy in EGC patients who were judged as
having a non-curative endoscopic submucosal dissection (ESD).
AIMS & METHODS: Clinical and pathological records of 455 patients who
underwent gastrectomy with lymph node dissection for a non-curative ESD
during September 2002 to December 2013 were retrospectively studied.
Patients with (1) multiple synchronous or metachronous non-curative lesions,
(2) recurrent lesions, (3) histological special type, (4) remnant stomach and (5)
insufficient pathological data of preceding ESD were excluded. Main histological
type (differentiated-type (D-type) or undifferentiated-type (UD-type)), lesion diameter (2cm or 2cm5), tumor depth (mucosa (pT1a) or submucosa (pT1b)),
lymphovascular infiltration, vertical tumor margin (VM) and ulcerative finding
(UL) were examined.
RESULTS: A total of 359 patients (male/female: 287/72) with a median age of 70
year were enrolled. Additional gastrectomy was performed a median of 70 days
after ESD. Main histologic type were D-type/UD-type 301/58, lesion diameter
were 2cm/2cm5 109/250, tumor depth pT1a/pT1b 82/277, lymphovascular
infiltration was positive in 177, VM positive or indefinite was observed in 76,
and UL was positive in 91 patients. LNM was found in 32 patients (9%).
Univariate analysis revealed that tumor depth (OR: 4.8, 95%CI: 1.1-20.4) and
lymphovascular infiltration (OR: 11.7, 95%CI: 3.5-39.1) were significant related
factors for LNM. Multivariate analysis revealed that lymphovascular inflitration
was an independent related factor for LNM (OR: 9.78, 95%CI: 2.76-34.59).
LNM was found in 29 patients (16.4%) among 177 patients with positive lymphovascular infiltration. In contrast, LNM was found only 3 patients (1.6%)
among 182 patients with negative lymphovascular infiltration.
CONCLUSION: Lymphovascular inflitration was an independent related factor
for LNM among additional gastrectomy after non-curative ESD. Detailed search
of lymphovascular infiltration is the most important factor in the pathological
evaluation of endoscopically resected specimens.
Disclosure of Interest: None declared
P0563 METFORMIN
INHIBITS
NUCLEAR
FACTOR
KAPPAB
SIGNALING AND ENDOPLASMIC RETICULUM STRESS IN
GASTRIC EPITHELIAL CELLS, AND AMELIORATED ETHANOL
INDUCED GASTRITIS IN MICE
Y. Choi1,*, S.-J. Koh1, J.W. Kim1, B.G. Kim1, K.L. Lee1
1
Internal medicine, Seoul National University Boramae Hospital, Seoul, Korea,
Republic Of
Contact E-mail Address: spoon0820@naver.com
INTRODUCTION: Metformin has been recently reported to provide antiinflammatory or antitumor activity in colitic and colitic tumor animal models
through inhibition of nuclear factor kappaB (NF-B) signaling. There is no
evidence of metformin induced attenuation of gastric mucosal inflammation by
alcohol.
AIMS & METHODS: The aim of this study is to investigate the effect of metformin on NF-B signaling and endoplasmic reticulum (ER) stress in human
gastric epithelial cells in vitro and on ethanol-induced acute murine gastritis
in vivo. Human gastric epithelial MKN-45 cell lines were pretreated with metformin and then stimulated with tumor necrosis factor- (TNF-). Interleukin-8
(IL-8) expression was determined by real-time RT-PCR. NF-B DNA-binding
activity in the nuclear extracts was assessed by electrophoretic mobility shift
assay (EMSA). The molecular marker of ER stress, including CHOP and
XBP1 was evaluated using PCR. In the ethanol-induced acute gastritis model,
mice were given absolute ethanol (50 mg/kg, 250 mg/kg) by oral gavage with or
without metformin. Using the extracted gastric tissue, macroscopic assessment,
histological evaluation and immunohistochemical staining for phospho-IB
kinase (IKK) was performed.
RESULTS: Metformin significantly inhibited the upregulated expression of IL-8
in MKN-45 cells stimulated with TNF- in a dose dependent manner.
Pretreatment of MKN-45 cells with metformin decreased activity of NF-B in
TNF-  -stimulated cells. CHOP and XBP1 mRNA expression was enhanced in
the presence of TNF-, and it was dampened by pretreatment of metformin.

United European Gastroenterology Journal 2(1S)


Administration of metformin significantly attenuated the severity of ethanolinduced acute murine gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage.
CONCLUSION: These results indicate that metformin inhibits NF-B activation
and ER stress in gastric epithelial cells and that it ameliorates experimental
murine gastritis. These results suggest that metformin is a potential gastroprotective agent.
REFERENCES
Kim JM, Kim SH, Ko SH, et al. The guggulsterone derivative GG-52 inhibits
NF--B signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice. Am J Physiol Gastrointest Liver Physiol 2013; 304:
G193G202.
Koh S-J, Kim JM, Kim I-K, et al. Metformin inhibits NF-B signaling in intestinal epithelial cells, and ameliorates murine colitis and colitis-associated colon
cancer. J Gastroenterol Hepatol 2014; 29: 502-510.
Ma TY, Iwamoto GK, Hoa NT, et al. TNF-alpha-induced increase in intestinal
epithelial tight junction permeability requires NF-kappa B activation. Am J
Physiol Gastrointest Liver Physiol 2004; 286: G36776.
Ardite E, Panes J, Miranda M, et al. Effects of steroid treatment on activation of
nuclear factor kappaB in patients with inflammatory bowel disease. Br J
Pharmacol 1998; 124: 431433.
Li SN, Wang X, Zeng QT, et al. Metformin inhibits nuclear factor kappaB
activation and decreases serum high-sensitivity C-reactive protein level in experimental atherogenesis of rabbits. Heart Vessels 2009; 24: 446453.
Disclosure of Interest: None declared
P0564 RESTING-STATE FMRI IN PATIENTS WITH NON-SPECIFIC
DIGESTIVE TRACT DISEASES
G. Piotrowicz1,*, K. Skrobisz-Balandowska2, P. Naumczyk3, A. Sabisz4,
K. Markiet2, G. Rydzewska5, E. Szurowska2
1
Department of Gastrology, Self-Dependent Health Care Unit of Ministry of
Interior, 22nd Department of Radiology, Medical University of Gdansk, 3Institute
of Psychology, Department of Social Science, 4Institute of Experimental Physics,
University of Gdansk, Gdansk, 5Department of Gastronenterology, Central Clinical
Hospital of the Ministry of Interior in Warsaw, Warsaw, Poland
Contact E-mail Address: piotrowicz.grazyna@interia.eu
INTRODUCTION: The purpose of the study was to assess the differences in
brain activity during resting-state fMRI (rs-fMRI) in patients with non-specific
digestive tract diseases (Functional Dyspepsia-FD, Inflammatory Bowel
Diseases-IBD and Irritable Bowel Syndrome-IBS) in comparison to healthy
group.
AIMS & METHODS: Twelve patients (FD, IBS, IBD) and eleven in control
group were included into the study.
The functional and anatomical images were acquired with a 3T Achieva TX
Scanner (Philips Healthcare) with the use of the 8-channel head coil. To evaluate
and exclude subjects with brain pathology standard T1 and T2 sequences were
applied. No contrast agent was administered. For functional imaging a T2*
Gradient Echo-Planar Imaging sequence was used. The rs-fMRI analyses were
performed with the use of the standard preprocessing. Afterwards an
Independent Component Analysis was applied resulting in maps of the Default
Mode Network for each of the participants. Those were further compared across
the groups. The following psychological tests were applied: STAI, EAS, EPQ-R,
CISS, BPCQ.
RESULTS: Compared to patients with non-specific digestive tract diseases the
healthy controls DMN comprised additional areas in right hemisphere involving
the Medial Frontal Gyrus and Cingulate Gyrus. The DMN network of the
patients involved additional area in the medial frontal area. See table for detailed
stereotactic coordinates and Z-scores.
Table 1 Significant additional brain regions of the Default Mode Network of the
healthy controls compared with patients with non-specific digestive disorders

healthy 4 patients

patients 4 healthy

Anatomical region

No. of
voxels

Medial Frontal Gyrus


Cingulate Gyrus
Cingulate Gyrus
Superior Frontal Gyrus

0
12
-9
-15

66
24
0
63

9
30
36
6

4.16
4.25
4.08
4.06

9
5
6
8

Results of the 2nd level between-group analysis, p50.05 FDR corrected, x, y, z


are MNI coordinates of the most significant center of the activation within the
activated cluster. Z Z-value, BA Brodmann
CONCLUSION: Our study showed that the DMNs of the patients and the control
altered in the involvement of the medial structures of the prefrontal cortex (Medial
Frontal Gyrus and Superior Frontal Gyrus) as well as the dorsal anterior cingulated cortex (the Cingulate Gyrus). Combined with the psychological results, the
rs-fMRI indicates differences regarding emotional self-control. Further studies are
required to establish clinical significance of those findings.
REFERENCES
1. Mayer EA, Naliboff BD and Craig AD. Neuroimaging of the brain-gut axis:
from basic understanding to treatment of functional GI disorders.
Gastronenterology 2006.
2. Mayer EA, Aziz Q, Coen S, et al. Brain imaging approaches to the study of
Functional gi disorders: A rome working team report. Neurogastroenterol Motil
2009 June.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)


P0565 MEDIUM-TERM EFFICACY OF SACRAL NERVE STIMULATION
FOR IRRITABLE BOWEL SYNDROME
J. Fassov1,2,*, L. Lundby2, S. Laurberg2, S. Buntzen2, K. Krogh1
1
Neurogastroenterology Unit, Department of Gastroenterology and Hepatology,
2
Department of Surgery P, Aarhus University Hospital, Aarhus, Denmark
Contact E-mail Address: janfas@rm.dk
INTRODUCTION: In a recent randomized, controlled, crossover study we concluded that sacral nerve stimulation (SNS) is an effective treatment for severe
IBS.1
AIMS & METHODS: In the present study, we aimed at evaluating the mediumterm results of SNS in the same group of patients.
Our criteria for permanent SNS were at least 30% reduction in IBS-specific
symptom score (GSRS-IBS questionnaire) during the percutaneous nerve evaluation (PNE) test. Primary endpoint was change in the IBS-specific symptom score.
Secondary endpoint was change in the IBS-specific quality of life score.
RESULTS: Forty-three selected patients with severe diarrhoea predominant or
mixed IBS underwent a PNE test at our tertiary centre. Among these, 31 (76%,
as 2 tests were inconclusive) qualified for permanent SNS and 26 (60%) were
actually implanted. Of patients receiving permanent SNS 22 (85%) were eligible
for the present study. At follow-up after median 42 months (range; 12-60) the
median IBS-specific symptom score (26; range 13 to 64) remained significantly
lower than at baseline (62, range 45 to 80) (P50.0001). The effect was observed
in all IBS symptom clusters. Also, the median IBS-specific quality of life score
remained significantly improved at follow-up (52, range 26 to 162) compared to
baseline (134, range 82 to 180) (p 0.0001). The effect was observed in all IBS
quality of life domains. Therapeutic success was maintained in 18 patients (82%)
of whom 5 had had the stimulator for 5 years.
CONCLUSION: The positive effect of SNS for selected patients with severe IBS
is maintained at medium-term (1-5 years) follow-up.
REFERENCES
1. Fassov J, Lundby L, Buntzen S, et al. A randomised, controlled, crossover
study of sacral nerve stimulation for irritable bowel syndrome. Ann Surg. Epub
ahead of print February 2014.
Disclosure of Interest: J. Fassov: None declared, L. Lundby Lecture fee(s) from:
Medtronic Inc, S. Laurberg Other: Previously member of Medtronic Incs medical
advisory board, S. Buntzen Lecture fee(s) from: Medtronic Inc, K. Krogh: None
declared
P0567 PREVALENCE AND SEVERITY
SYNDROME IN MORBID OBESITY

OF

IRRITABLE

BOWEL

A.S. Schneck1, D. Pishvaie1, R. Anty1, R. Dainese1, M. Vivinus1, X. Hebuterne1,


J. Gugenheim1, A. Tran1, A. Iannelli1, P. Thierry1,*
1
CHU Nice, Universite de Nice Sophia Antipolis, Nice, France
Contact E-mail Address: piche.t@chu-nice.fr
INTRODUCTION: The relationship between irritable bowel syndrome (IBS)
and obesity has been poorly investigated. Only few recent reports have suggested
an interesting correlation between obesity and IBS (1,2).
AIMS & METHODS: We aimed to determine the prevalence and severity of IBS
and associated co-morbidities in a prospective cohort of obese patients. Ninety
morbid obese patients (BMI 40.94.3 kg/m2) were included prospectively before
gastric bypass. The diagnosis of IBS and each subtype (predominance of constipation, diarrhea, alternant or undetermined) was performed according to the
Rome III criteria using a Bristol scale for stool consistency. Patients were also
asked for IBS related co-morbidities including chronic fatigue, migraine, low
back pain, gastroesophageal reflux (GER), genitourinary problems and dyspepsia. Patients had to complete a set of questionnaires at the same time to assess the
severity of IBS (IBS Severity Score), gastroesophageal reflux (Reflux Qol), psychological factors including anxiety and depression scale (HAD), fatigue (Fatigue
Impact Scale), and quality of life (SF-12).
RESULTS: Among 90 obese patients, 26 of them (28.8%) fulfilled the Rome III
criteria for IBS (IBS-D, n 11, IBS-C, n 9, IBS-A, n 1, IBS-U n 5). Obese
patients with or without IBS were similar in age (41.713.1 vs 41.512.0 years
p 0.9), sex (69% vs 65% of females, p 0.3) and BMI (40.93.9 vs 41.1 kg/m2
p 0.8). Obese patients with IBS reported significantly higher prevalence of
GER (84% vs 25.9%, p50.001), migraines (75 % vs 25% p 0.01), low back
pain (80% vs 57% p 0.03), genitourinary problems (19% vs 5% p 0.03),
chronic fatigue (80% vs 43% p 0.001) and dyspepsia (69% vs 32%
p 0.001). Obese patients with IBS had significant higher score of fatigue
(3335 vs 6339, p 0.0009), anxiety (7.03.3 vs 10.43.8 p 0.0001), depression (4.93.4 vs 6.84.1 p 0.03), severity of IBS (5855 vs 165100
p 0.0001), and poorer quality of life (39.14.736.05.4, p 0.01) than
those without IBS. Obese patients having both IBS and GER had significant
higher IBS severity scores than those without GER (171.4106 vs 9542,
p 0.05). BMI did not correlated with IBS severity whatever the presence of
Rome III criteria. In a logistic regression model including BMI, anxiety, depression, fatigue and GER score, only anxiety was significantly and independently
associated with the presence of IBS (RR 1.25 CI 95% 1.1-1.51).
CONCLUSION: A relatively high 28.8% prevalence of IBS was found in obese
patients. The severity of IBS was not correlated with BMI. However, anxiety was
independently associated with IBS in obese patients suggesting that psychological
factors are key features of IBS whatever the presence of obesity.
REFERENCES
1. Delgado-Aros S, et al. Am J Gastroenterol 2004.
2. Talley NJ, et al. Neurogastroenterol Motil 2004.
Disclosure of Interest: None declared

P0568 CHRONIC INTESTINAL PSEUDO-OBSTRUCTION (CIPO): A


MULTI-LEVEL NEUROMUSCULAR-BASED DIAGNOSTIC
APPROACH
R. DAngelo1, R. Rinaldi1, V. Stanghellini2, L. Pironi2, R.F. Cogliandro2,
E. Ruggeri2, G. Cenacchi3, V. Donadio3, R. Liguori3, V. Carelli3, R. Lodi3,
C. Tonon3, R. De Giorgio2,* on behalf of CIPO Bologna Group
1
Int Med Aging Nephrol, S. Orsola-Malpighi Hospital, Bologna, Italy, 2Med Surg
Sci, 3Biom NeuroMot Sci, Univ of Bologna, Bologna, Italy
Contact E-mail Address: rdangelo81@libero.it
INTRODUCTION: Chronic intestinal pseudo-obstruction (CIPO) is a failure of
gut motility leading to recurrent episodes of intestinal sub-occlusion with no
demonstrable mechanical reason. CIPO diagnosis and management is often
very difficult because of the lack of standardized approach in relation to underlying causes.
AIMS & METHODS: We report our approach to diagnosis of CIPO patients
with the aim to identify possible underlying neurological causes by using a multilevel investigation. Forty-nine CIPO patients (M: 15; age range: 19-63 yrs; F: 34;
age range: 16-61 yrs) performed first-level exams including laboratory tests, neurological assessment and electromyography. Three patients did not comply to the
diagnostic protocol and were excluded. Second-level examinations included
muscle/skin biopsy and/or biochemical/molecular assays based on previous
results. MR imaging and spectroscopy were performed if mitochondrial encephalomyopathy was suspected. Biochemical/molecular tests included thymidine
phosphorylase activity and a-galactosidase enzyme assay as well as gene analysis
of mitochondrial disorders; transthyretin or enteric smooth muscle actin genes
were also performed. Full-thickness gut biopsies were obtained only in cases
undergoing either elective or emergency surgery (because of intestinal subocclusion).
RESULTS: At the end of the complete diagnostic work up 46 out of 49 patients
(94%) were thoroughly investigated. Three groups of CIPO patients were identified: A) n 11 had mitochondrial diseases; specifically n 6 had mitochondrial
encephalomyopathy proved by genetic analysis (4 MNGIE, 1 MERRF, 1 POLG)
and other n 5 had a likely mitochondrial encephalomyopathy, although not yet
confirmed by genetic analysis; B) n 21 had a neuromuscular non-mitochondrial
diseases; specifically n 16 had neuropathy, in particular n 3 polyneuropathy
(1 associated with lymphoma, 1 Hu-related autoantibody, 1 idiopathic polyneuropathy), n 12 small fiber neuropathy demonstrated by skin biopsy, n 1
enteric neuropathy; finally, n 5 had myopathy, in particular n 1 myofibrillar
myopathy and n 4 an undefined myopathy; C) n 14 had an idiopathic CIPO
with no underlying neurological causes including abnormalities of the intrinsic or
extrinsic innervation of the gut, as indicated by full thickness analysis and/or
intestinal manometry.
CONCLUSION: After an accurate neurological evaluation and tests, only a
third of CIPO are actually idiopathic. Mitochondrial disorders should be
always sought in patients with CIPO, while skin biopsy is suggested as an aid
to unravel a small fiber disorder, a peripheral neuropathy affecting also the
autonomic nerve component. Taken together our data suggest that a thorough
neurological evaluation and tests represent an important part in the management
of patients with CIPO.
Disclosure of Interest: None declared
P0569 THE SAME DAY SPLIT CLINIC A PRESCRIPTION FOR
EFFICIENCY IN THE GASTROENTEROLOGY OUTPATIENT
CLINIC
M.F. Jaboli1,*, M. Grimes1, H. Palmer1, C. Clayman1, T. Rayne1, C. Durcan1,
I. Mason1, O. Epstein1
1
Gastroenterology, Royal Free Hospital, London, United Kingdom
INTRODUCTION: Worldwide, healthcare providers are striving to balance
escalating costs with the patients expectation of efficient access to specialist
opinion, rapid investigation and treatment. Over the past 65 years, the NHS
gastroenterology outpatient journey has remained unchanged. Patients are
assessed at the first visit, followed by one or more hospital visits for gastrointestinal investigations and a return hospital attendance for final assessment. The
same day split clinic has been designed, wherever possible, to condense the journey from months to hours.
AIMS & METHODS: Over a period of three months, each gastroenterology
referral letter was previewed in advance of the outpatient appointment. Each
patient was triaged as solution or complex. For the solution cohort,
investigations were predicted and scheduled for the same day as the outpatient
attendance. Patients were asked to attend the clinic starved and told to expect one
or more same day gastrointestinal investigations. On the appointment day,
solution patients attended the same day split clinic for: 1) an initial specialist
assessment, 2) scheduled investigation(s), 3) a return to the specialist clinic for a
summative assessment & management plan.
RESULTS: Of 174 referrals, 95 patients were triaged from the referral letter as
Solution patients, and 81 attended the split clinic (7 did not arrive, 4 postponed, 3 direct to surveillance colonoscopy). In those who attended, 46 same day
tests were performed (14 upper endoscopies, 11 sigmoidoscopies, 5 barium swallows, 6 Eso Capsule endoscopies, 5 ultrasound scans, 1 electrogastrogram, 2 CT
abdomen and 2 CT colonoscopy). Twenty-seven patients (34%) were discharged,
and twenty-two (27 %) were discharged after a single follow up telephone consultation. Overall, 49 patients designated as Solution patients (60%) required
only a single hospital visit. Sixteen patients (17%) were re-designated as
Complex requiring further tests and 3 (3%) were referred elsewhere. Overall,
95 (46 same day tests and 49 return to follow up clinic in old system) return
hospital visits were avoided. The visits were reduced by 40% and the follow up
appointments were down by 60%.

A290
CONCLUSION: Analytical triage of GP referral letters allows identification &
triage of most solution patients. This facilitates pre-emptive investigation planning and scheduling which, in turn, supports a same day split clinic designed to
condense months of investigation and follow up into a few hours. The well
planned same day split clinic meets the patients expectation for an efficient
journey and a quick diagnosis. The inconvenience of numerous hospital attendances is minimized, whilst appointment capacity is freed up.
Disclosure of Interest: None declared
P0570 DEVELOPING A EUROPEAN CLINICAL RESEARCH NETWORK
FOR PAEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND
NUTRITION
N. Croft1,*, V. Tailor1, L.de Ridder2, S. Hussey3 on behalf of PEDDCReN
Steering Group
1
Centre for Digestive Diseases, Blizard Institute, Queen Mary University of
London, London, United Kingdom, 2Erasmus MC, Rotterdam, Netherlands,
3
University College Dublin, Dublin, Ireland
Contact E-mail Address: n.m.croft@qmul.ac.uk
INTRODUCTION: Paediatric European Digestive Diseases Clinical Research
Network (PEDDCReN) was established in April 2013. The need for this initiative
was identified by ENPR-EMA (The European Network of Paediatric Research
at the European Medicines Agency). The Project is supported by LINKS funding
from the UEG (United European Gastroenterology) and is led by the British,
Irish and Dutch Societies of Gastroenterology in collaboration with ESPGHAN
and ENPR-EMA.
AIMS & METHODS: The aim of PEDDCReN is to support the development of
large studies in paediatric patients in the speciality of Gastroenterology,
Hepatology and Nutrition (GHN).
We report the preliminary results of an online survey as a first step of
PEDDCReN, identifying investigators resources, expertise and interest in studies in this area in the UK, Ireland and the Netherlands.
The survey was designed by the steering group of PEDDCReN and utilised the
web based system REDCap. It takes 5 minutes to complete with 1 respondent per
hospital. To date the survey has had responses from paediatric gastroenterologists in the UK, Ireland and the Netherlands as members of BSG, BSPGHAN,
Irish and Dutch Gastroenterology Societies. As a result of PEDDCReN promotions in UEG & ESPGHAN newsletters one centre from Italy, Germany, Serbia
and Poland has also responded.
RESULTS: After six months 25 units (including 53 investigators) had replied
representing childrens services with a median of 211 beds (range 15-800). 10 were
stand alone childrens hospitals, 11 were childrens hospitals co-located with
adult hospitals, 2 were smaller childrens units in adult hospitals and one was
a neonatal unit. 76% of responding units had neonatal ICUs on site with almost
all of these carrying out neonatal surgery. All wished to be part of PEDDCReN
and were happy for contact details to be passed on to both industry and nonindustry investigators. The survey identified each units interest in recruiting into
a range of GI and liver diseases (eg 88% wished to recruit for IBD studies
whereas only 24% for infant diarrhoea). Less than 33% would also recruit to
liver studies including infective hepatitis. Of the respondents 60% have been a
principle investigator (in their hospital) and 40% had been chief investigators for
their country. 68% were willing to take on phase I or II studies but only 36% had
done any in the last 3 years. 64% had a clinical research facility available on site
and 68% have access to research nurses. Sites were also asked whether they
currently followed up any patients with rare GI or liver diseases such as congenital enteropathy (12/25), congenital transport defect (7/25), polyposis syndromes (17/25), chronic intestinal pseudo-obstruction (15/25).
CONCLUSION: This shows the ability of PEDDCReN to identify interest,
expertise and resources in 3 countries. This will shortly be extended to the rest
of Europe. The potential for investigators and industry to utilise this network to
support the development of large scale clinical trials and rare diseases studies
within this speciality is a major benefit.
Disclosure of Interest: None declared
P0571 THE EFFICACY OF RECOMBINANT HUMAN SOLUBLE
THROMBOMODULIN IN PATIENTS WITH SEPSIS AND
DISSEMINATED INTRAVASCULAR COAGULATION IN THE
GASTROENTEROLOGY FIELD
T. Ito1,*, A. Nagahara1, T. Osada1, J. Kato1, H. Ueyama1, H. Saito1,
S. Watanabe1
1
gastroenterology, Juntendo University, Tokyo, Japan
Contact E-mail Address: tmitou@juntendo.ac.jp
INTRODUCTION: Inpatients with digestive disease often have coexisting serious infections. Some of them result in disseminated intravascular coagulation
(DIC). Recently, recombinant human soluble thrombomodulin (rTM) was
approved and has been used in clinical practice for DIC treatment in Japan.
However, there are few studies to evaluate the efficacy of rTM for DIC in the
gastroenterology field. The purpose of this study is to make a comparison
between rTM-treated patients and patients treated other agents, and to evaluate
the efficacy of rTM.
AIMS & METHODS: The purpose of this study is to make a comparison
between rTM-treated patients and patients treated other agents, and to evaluate
the efficacy of rTM. Fifty-three inpatients at our department with sepsis-induced
DIC between January 2009 and February 2014 were retrospectively analyzed.
The patients were classified into the rTM treatment group (n 25), and conventional treatment group (rTM was not used) as the control group (n 28).
Diagnosis of DIC was made according to the criteria of acute DIC of the
Japan Association of Acute Medicine (JAAM). Platelet count, prothrombin

United European Gastroenterology Journal 2(1S)


time-international normalized ratio (PT-INR), levels of fibrin/fibrinogen degradation products (FDP), C-reactive protein (CRP), DIC scores based on JAAM
criteria were measured on days 0,3, and 7 to evaluate therapeutic results.
Furthermore, DIC resolution rate were assessed 3 and 7 days after the start of
DIC treatment.
RESULTS: Before treatment, DIC scores based on JAAM criteria were 50.95
in the rTM group, and 5.91.3 in the control group (p50.05), respectively.
However, there were no significant differences between two groups regarding
age, sex, and causative disease of DIC. The duration of rTM administration
was 3.61.44 days (range 1 to 7 days). As shown in the table, significant intragroup improvement was observed in all parameters except for FDP in both
groups. However, there were no significant inter-group differences in comparison
of all parameters. Result from the repeated measures analysis of variance, significant improvements were seen in the DIC scores in the rTM treated group
(p 0.001).

Platelet count (10 /mL)


PT-INR
FDP (mg/ml)
CRP (mg/dL)
DIC score
DIC resolution rate (%)

rTM
control
rTM
control
rTM
control
rTM
control
rTM
control
rTM
control

Day0

Day3

Day7

11.16.5
10.66.9
1.390.32
1.430.32
32.319.4
37.434.1
14.18.8
14.57.6
50.95
5.91.3

10.54.7
8.45.7
1.180.16**
1.220.3**
19.824.5
24.914.5
9.75.4*
12.26.1
3.11.8**
4.51.9**
48
28.6

17.99.0*
14.98.7**
1.210.22**
1.20.19**
17.613.7
22.213.0
6.65.6**
7.55.2**
2.01.7**
3.22.3**
68
50

Data are shown with MeanSD *p50.05 vs Day0, **p50.01 vs. Day0

CONCLUSION: These results suggest that rTM would be the useful medicine
for treatment DIC in the gastroenterology field.
Disclosure of Interest: None declared
P0572 THE EFFECT OF ACUTE SLIGHTLY INCREASED INTRA
ABDOMINAL PRESSURE ON INTESTINAL PERMEABILITY AND
OXIDATIVE STRESS IN A RAT MODEL
Y. Leng1,*, G. Yao1
1
Intensive care unit, Peking University Third Hospital, Beijing, China, Beijing,
China
Contact E-mail Address: lengyuxin1980@126.com
INTRODUCTION: The harm of Intra-abdominal hypertension (IAH) on critically ill patients has gained great attention. However, there are still 60% underIAH patients in critical care units, whose intra abdominal pressure (IAP) runs
slightly higher, at 5 to 7 mmHg. Among the frequently IAH-affected organ
systems, the intestine is initially influenced. Nevertheless, the adverse effect of
transient exposure to slightly raised IAPs on intestinal mucosa remains unclear.
AIMS & METHODS: To study the acute effects of different grade nitrogen
pneumoperitoneum on colon mucosa, male Sprague- Dawley rats were assigned
to six groups with different IAPs (baseline, 4mmHg, 8mmHg, 12mmHg,
16mmHg, 20mmHg, n 6 per group). During the 90 minutes exposure, we
dynamically monitored the heart rate and noninvasive hemodynamic paramaters.
After decompression slowly, the arterial blood gas analyses were conducted.
Then the structural injury to the colon mucosa was confirmed by light microscopy. The colon permeability was revealed by expression and localization of
tight junction proteins (claudin 5 and occludin), combined with the absorption of
fluorescein isothiocyanate dextran (FD-4, with another proportion of rats, n 6
per group). The pro-oxidantantioxidant balance of the colon was determined by
the levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT) and serum super oxide dismutase (SOD).
RESULTS: IAPs greater than 12 mmHg significantly disturbed the colonic integrity, expression of tight junction protein, mucosal permeability to FD-4 and the
pro-oxidantantioxidant balance. Interestingly, slight elevation of IAPs not
reaching the level of IAH also showed a similar undesirable effect. In 8mmHg
group, mild hyponatremia, hypocalcemia and hypoxemia occurred, accompanied
with the reduction of blood pressure and abdominal perfusion pressure. Whats
more, mild microscopically inflammatory infiltration and increase of MDA were
also detected in under-IAH groups. 8mmHg-IAP markedly inhibited the expression of claudin 5 and occludin, though no significant differences were found in
permeability to FD-4 between control and 8mmHg groups.
CONCLUSION: Acute exposure to slightly raised IAPs may bring adverse
effects on intestinal permeability and pro-oxidantantioxidant balance.
Accordingly, we concluded that for critically ill patients, IAPs should be monitored dynamically and intervened as soon as possible to avoid the intestinal
mucosal injury and the subsequent gut- derived sepsis.
REFERENCES
1. Cheng J, Wei Z, Liu X, et al. The role of intestinal mucosa injury induced by
intra-abdominal hypertension in the development of abdominal compartment
syndrome and multiple organ dysfunction syndrome. Crit Care 2013; 17: R283.
2. Gong G, Wang P, Ding W, et al. Microscopic and ultrastructural changes of
the intestine in abdominal compartment syndrome. J Invest Surg 2009; 22: 362367.

United European Gastroenterology Journal 2(1S)


3. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the international conference of experts on intra-abdominal hypertension and abdominal
compartment syndrome: I. Definitions. Intensive Care Med 2006; 32: 1722-1732.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
POSTER PLUS VIDEO II POSTER EXHIBITION HALL XL_____________________
P0573 USE OF A NOVEL SELF-EXPANDING METAL STENT TO
ALLOW FOR ENDOSCOPIC DRAINAGE AND NECROSECTOMY
OF PANCREATIC FLUID COLLECTIONS
M.T. Huggett1,*, K.W. Oppong1, S.P. Pereira2, V. Mitra1, R.M. Charnley3,
M.K. Nayar1
1
Department of Gastroenterology, Freeman Hospital, Newcastle upon Tyne, United
Kingdom, 2University College Hospital, London, United States, 3Department of
HPB surgery, Freeman Hospital, Newcastle upon Tyne, United Kingdom
Contact E-mail Address: matthewhuggett@doctors.net.uk
INTRODUCTION: Post-inflammatory peri-pancreatic fluid collections are frequent sequelae of severe acute pancreatitis. Collections are at risk of suppurative
infection complicated by pancreatic necrosis. Over the last decade there has been
an increasing emphasis on minimally invasive drainage procedures, including
EUS-guided cyst-gastrostomy, and these approaches seem to be associated
with lower morbidity and mortality. Access to the necrosis cavity has however
been severely limited by having to maintain the tract with small diameter plastic
stents. Recently, a novel flanged fully covered self-expanding metal stent
(FCSEMS; NAGI stent, Taewoong Medical, Korea) has been developed to
allow for better drainage of infected necrosis and easier endoscopic access into
the cavity. Setting: A non-randomised prospective multicentre phase II study to
determine the safety and efficacy of FCSEMS endoscopic cyst- gastrostomy in
the management of complex/infected pancreatic fluid collections.
AIMS & METHODS: Patients were included if they had evidence of a pancreatic
fluid collection which was deemed to be amenable for EUS- guided drainage after
discussion at a HPB multidisciplinary meeting. Patients selected for EUS-guided
drainage had cross sectional imaging (MR or CT) performed within 2 weeks of
the procedure and then an EUS assessment was made of the necrotic component.
The collection was punctured using a cystotome and the FCSEMS inserted over a
guidewire with fluoroscopic control. Repeat procedures were performed as
necessary.
RESULTS: A total of 11 patients (8 male, 3 female) were included in the study.
Median age was 57.3 years. The aetiology of the collection was gallstones in 6
patients, idiopathic in 3, ischaemic in 1 and drug-induced in 1. Ten patients had
evidence of at least 30% necrosis within the collection. Mean diameter of the
collection was 15cm and EUS-guided puncture was initially performed in all
patients. The tract was dilated with a balloon in 6 patients. Stent insertion was
either with a 20mm (7 patients) or 30mm (4 patients) length FCSEMS. Ten
patients underwent endoscopic necrosectomy, with a median of 3 procedures
(range 1-10). Significant reduction in the size of collection was achieved in all
patients. Adverse events included stent migration in 3 (2 spontaneously and 1
during necrosectomy). Two patients died of complications of severe acute
pancreatitis.
CONCLUSION: FCSEMS insertion is feasible and safe for drainage of pancreatic fluid collections. It allows repeated through the stent necrosectomy procedures and appears to be a major advance in the management of infected
pancreatic necrosis.
Disclosure of Interest: None declared
P0574 LUCKY LOOP: A VARIANT OF AN ENDOLOOP CLIP
WOUND CLOSURE TECHNIQUE AFTER COLONIC DEFIANT
POLYP REMOVAL
E. Rosa-Rizzotto1,*, C. Lucchini1, F. De Lazzari1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital, Padua,
Italy
INTRODUCTION: This report describes a variant of an iatrogenic wound closure technique after endoscopic mucosal
resection (EMR) or endoscopic submucosal dissection (ESD). After removal of
defiant polyps without signs of perforation or important bleeding, iatrogenic
wounds are generally not closed as second intention healing is expected. In the
past patients were often hospitalized after those procedures for 2-3 days, but
when discharged a 6.5% prevalence of delayed bleeding persists(1). The combined technique of endoloop plus clip or clip alone to close iatrogenic wounds or
perforations during operative endoscopies is a well established practice. Clips
plus endoloop technique have been coined King Closure(2) or clutching rose
stems techniques(3).
AIMS & METHODS: We propose a tobacco-pouch suture technique for
wounds that are a maximum of 4 cm diameter, anchoring a single endoloop
with 5-6 long type clips cirumferencially to the wound edge perimeter and closing
the loop using a single double channel endoscope. A hemoclip short type is
placed over the plastic tube that tightens the loop to fix the suture at the end
of the procedure.
Sixteen (8 ESD and 12 EMR) patients underwent endoscopic removal of polyps
425 mm 5 40 mm between June and December 2013. All the iatrogenic wounds
were closed with the technique described in the video. The mean time to perform
the procedure was 8 min (range 6-13 min). High definition endoscopes PCFH180AL and GF-H180J (OLYMPUS, Tokyo, Japan) with an external artificial
second channel, a 30 mm diameter endoloop (PolyLoop, OLYMPUS, Tokyo,
Japan) and Clips HX-610-090L and HX-610-135S (EZ-Clip, OLYMPUS,
Tokyo, Japan) were used. Carbon dioxide insufflation was used during all of

A291
the procedures. The patients were examined three, seven and thirty days after the
procedure.
RESULTS: All the patients were discharged 2 hours after the endoscopic procedure was completed and none had any post procedural complications (fever,
delayed bleeding, perforation or abdominal pain).
CONCLUSION: These results demonstrate that when this closure is utilized
patients can be safely discharged from the hospital 2-3 hours after endoscopic
removal of a polyp. The technique is quick, (it was coined Lucky Loop in
honor of Luky Luke the fast solitary gunslinger cartoon character created by
Maurice De Bevere) easy and economic and can be also used in cases of large
gastrointestinal perforations or in patients that cant stop double or triple antiplatelet therapy.
REFERENCES
1 Hong SP. Clin Endosc 2012; 45: 282-284.
2 Ryska O, et al. Gastroent Hepatol 2011; 65: 207210.
3 Samarasena JB, et al. Endoscopy 2012; 44: E424-E425.
Disclosure of Interest: None declared
P0575 PERFORMANCE CHARACTERISTICS OF COLORECTAL FULL
SPECTRUM ENDOSCOPY (FUSE) PROSPECTIVE, PARALLEL,
RANDOMIZED STUDY
H. Neumann1,*, G.E. Tontini1,2, M. Vieth3, C. Gunther1, M. Grauer1,4,
M.F. Neurath1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany, 2IRCCS
Policlinico San Donato, San Donato Milanese, Italy, 3Klinikum Bayreuth,
Bayreuth, 4Klinikum Neumarkt, Neumarkt, Germany
INTRODUCTION: Full Spectrum Endoscopy (FUSE) provides a 330 field of
view, thereby potentially allowing the endoscopists to see more anatomy in comparison to standard forward viewing endoscopes (FVE). Recent data has already
shown that FUSE is feasible to significantly reduce adenoma miss rates.
AIMS & METHODS: The aim of this prospective, parallel, randomized study
was to assess the performance characteristics of FUSE in comparison to FVE.
Patients were randomly assigned to undergo colonoscopy with FUSE (Group A)
or FVE (Group B) after a previous sample size calculation. Performance characteristics including time to cecum, withdrawal time, total examination time,
medication, patient and endoscopists satisfaction, and polyp detection rates
were recorded.
RESULTS: 57 patients were included (male 52%; mean age 56 years, Range 21
88 years). Time to cecum (minutes, mean  SD) was 4.05  0.6 minutes for
FUSE and 5.48  0.6 for FVE (P 50.05). Withdrawal times were 12  4.4
minutes and 15  4.5 minutes for FUSE and FVE, respectively. Total examination time was 16.5  4.4 minutes in the FUSE group and 20.1  4.5 minutes in
the FVE group. Sedation was less required in the FUSE group as compared to
FVE (mean propofol dosage, 170 mg vs. 230 mg). Significantly more patients
needed analgesia in the FVE group (meperidine; p 0.01). Patient and endoscopists satisfaction were high throughout the cases and not different between both
groups. Per patient polyp detection rates were 37% and 18% for FUSE and
FVE, respectively.
CONCLUSION: Advancement times of the scope to the cecum and withdrawal
times were faster with the FUSE scope as compared to standard FVE.
Satisfaction rates of patients and endoscopists were similar in both groups
while patients needed more sedation and analgesia in the FVE group.
Although more polyps were found in the FUSE group the study was not powered
to compare adenoma detection rates between both groups.
Disclosure of Interest: None declared
P0576 DEVELOPMENT
AND
VALIDATION
OF
A
SIMPLE
CLASSIFICATION SYSTEM FOR IN VIVO DIAGNOSIS OF
COLORECTAL POLYPS USING VIRTUAL CHROMOENDOSCOPY
THE VISIBLE STUDY
H. Neumann1,*, C. Gunther1, L.C. Fry2, M. Vieth3, G.E. Tontini1,4,
M. Grauer1,5, M.F. Neurath1, K. Monkemuller2
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany,
2
University of Alabama at Birmingham, Birmingham, United States, 3Klinikum
Bayreuth, Bayreuth, Germany, 4IRCCS Policlinico San Donato, San Donato
Milanese, Italy, 5Klinikum Neumarkt, Neumarkt, Germany
INTRODUCTION: Although the diagnostic performance of virtual chromoendoscopy (VCE) has already been reported, validated classification systems allowing both experienced and inexperienced endoscopists to apply VCE have not
been established.
AIMS & METHODS: To develop and validate a simple classification system for
differentiating hyperplasic and adenomatous colorectal lesions by using VCE.
In the first phase, the capacity of experienced endoscopists to predict the histology of colorectal polyps was assessed. In the second phase, a simplified classification was developed allowing histologic prediction. Thirdly, the validity of the
classification was evaluated among inexperienced raters, including medical students and GI fellows. Last, a pilot clinical evaluation was performed during realtime colonoscopy. The study was performed in a multicenter, international
setting.
RESULTS: A simple classification system for differentiating hyperplasic and
adenomatous colorectal lesions by using VCE was developed and validated.
Diagnosis was made in 78% to 89% (mean 82.5%) of polyps with high confidence. Sensitivity and specificity ranged from 95% to 98% and 78% to 100%,
respectively. During real-time colonoscopy, diagnosis was made with high-confidence in 84% of polyps with sensitivity of 91%, specificity of 85%, and accuracy of 93%. Positive and negative predictive values were 93% and 93%,
respectively.

A292
CONCLUSION: We developed and validated for the first time a simple classification system for differentiating hyperplasic and adenomatous colorectal
lesions by using VCE during real-time colonoscopy.
Disclosure of Interest: None declared
P0577 THE OBSERVATION OF SECOND-GENERATION AUTOFLUORESCENCE IMAGING (AFI) HELPS EASILY TO DETECT OF
FLAT COLON NEOPLASIA FOR NON-EXPERT ENDOSCOPISTS
S. Saito1,*, D. Ide1, H. Inomata1, T.R. Ohya1, N. Tamai1, T. Kato1,
M. Ikegami2, H. Tajiri3
1
Endoscopy, 2Dept. of Pathology, 3Division of Gastroenterology and Hepatology,
Dept. of Internal Medicine, THE JIKEI UNIVERSITY SCHOOL OF
MEDICINE, Tokyo, Japan
Contact E-mail Address: ssaito@jikei.ac.jp
INTRODUCTION: We reported about the features of observation for colon
polyps by using the AFI system 1). Namely, hyperplastic lesion is shown as
dark green color similar to surrounding mucosa. In contrast, most of the neoplastic lesion is changed to magenta color at the localized tumor area. And also,
this strength of change is suggested to correlate with the histological grading. In
this study, we examined the benefits of using this system to detect the colon
neoplasia for beginner endoscopists.
AIMS & METHODS: Two studies were used to clarify for the usefulness by
second-generation AFI observation. One method used four pictures (white light
conventional image (WHL), indigo carmine dye sprayed image (CE), NBI and
AFI). Another method used short movies, which recorded WHL and AFI within
about one minute, respectively. At first study, twenty-four cases (flat type intramucosal lesion 22 cases and depressed submucosal invasive cancer; 2 cases) were
retrospectively reviewed. In contrast, thirty cases (sessile serrated (SS) lesion; 12
cases, intramucosal (IM) lesion; 13 cases and submucosal invasive cancer (SM); 5
cases) were reviewed at second study. These pictures and videos were shown to a
group of 5 beginner endoscopists (non-experienced for using AFI system) and a
group of 4 expert endoscopists (experienced more than 1000 cases). The used
scope is CF: FH260AZI with second generation Lucera Elite system (Olympus
Medical Systems, Tokyo, Japan).
RESULTS: At first study, the visualization score was defined as follows: the
worst visualization was scored as 0 and the best as 10. And to evaluate the
visualization of colon neoplasia, we calculated the average visual analog scale
(VAS) scores for each groups. The mean AFI visualization score; 8.9 was significantly higher than that of WHL; 6.5, CE; 8.2 and NBI; 7.1 by non-experienced group. And there was difference in average visualization scores between
AFI; 7.5 and another modalities (WHL; 4.8, CE; 7.2 and NBI; 5.8) by experienced group. At second study, the strength changing to the magenta color from
dark green with excitation light was evaluated by 10-point VAS. In non-experienced group, the score of SS lesion, IM lesion and SM lesion were 2.3, 5.2 and
7.8, respectively. In contrast SS lesion, IM lesion and SM lesion were 2.4, 5.7 and
7.8 in experienced group, respectively. It was shown almost same as VAS scores
between non-experienced and experienced as result.
CONCLUSION: AFI provided significantly better visualization to detect and
differentiate non-neoplastic lesion and neoplastic lesion for beginner endoscopists. It suggested that it is not difficult to diagnose the indication of endoscopic
treatment for neoplastic changes within intramucosal layer using AFI system for
non-experienced endoscopist. It was also expected to detect flat elevated lesion
more easily by non-experienced endoscopists.
REFERENCES
1) Saito S, Aihara H, Tajri H, et al. Autofluorescence imaging makes it easy to
differentiate neoplastic lesions from non-neoplastic lesions in the colon. In: New
challenges in gastrointestinal endoscopy. Tokyo: Springer Inc., 2008, pp. 330-337.
Disclosure of Interest: None declared
P0578 THE ACCURACY OF REAL-TIME PROBE BASED CONFOCAL
LASER ENDOMICROSCOPY FOR DIFFERENTIATION OF
COLORECTAL POLYPS DURING COLONOSCOPY
T.D. Belderbos1,*, M.G. van Oijen1, L.M. Moons1, P.D. Siersema1
1
Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht,
Netherlands
Contact E-mail Address: t.d.g.belderbos@umcutrecht.nl
INTRODUCTION: Reliable real-time differentiation between neoplastic and
non-neoplastic colorectal polyps during colonoscopy may guide treatment decisions and reduce the need for post hoc histologic evaluation of resected polyps. In
the hands of experts, probe based confocal laser endomicroscopy (pCLE) has
been suggested to be a highly accurate technique for this. Previous studies have
shown a short learning curve for offline interpretation of pCLE images of colorectal polyps. It is however not known whether colonoscopists starting to use this
technique can also accurately differentiate colorectal polyps during routine colonoscopy by using real time pCLE to directly evaluate images.
AIMS & METHODS: The primary aim was to determine the diagnostic accuracy of real-time pCLE for the differentiation of colorectal polyps during the first
50 pCLE cases of two endoscopists routinely performing colonoscopy. The secondary aim was to compare the sensitivity for diagnosing neoplasia small polyps
(5 mm) in this study with a sensitivity threshold of 90% that is required for
selective polypectomy or resect and discard strategies. We included patients of
45 years or older undergoing colonoscopy for screening, surveillance or diagnostic work-up between August 2012 and April 2014. After a training to obtain and
interpret pCLE images two senior endoscopists performed 50 pCLE procedures
each. Intravenous fluorescein was used as contrast agent. All polyps were
resected endoscopically and histologic diagnosis by an expert pathologist was
used as reference. Primary outcome was the diagnostic accuracy, defined as the

United European Gastroenterology Journal 2(1S)


percentage of polyps for which pCLE correctly differentiated between non-adenomatous, adenomatous and carcinomatous polyps.
RESULTS: The overall diagnostic accuracy of real time pCLE for colorectal
polyps was 75% and was not different between the endoscopists (74% vs.
76%, p 0.81). Accuracy remained stable when comparing the first 25 procedures with the last 25 procedures of both endoscopists (respectively 76% vs.
72%, p 0.75 and 76% vs. 76%, p 1.00). According to the size of the
polyps, accuracy was non-significantly different (67% for 68 polyps 5 mm,
86% for 21 polyps 10 mm and 89% for 18 polyps 410 mm; p 0.08).
Sensitivity for detecting neoplasia in polyps 5 mm was 65% (59% for right
sided polyps and 73% for left sided polyps).
CONCLUSION: The diagnostic accuracy of two endoscopists starting to use real
time pCLE for colorectal polyps was 75% and remained stable during the first 50
procedures. Sensitivity for detecting neoplasia in small polyps was below the
required 90% and suggests that real-time pCLE cannot be used to guide
follow-up decisions and that histologic evaluation of removed polyps is still
required.
Disclosure of Interest: None declared
P0579 NOVEL COMPUTER-AIDED DIAGNOSIS
COLORECTAL LESIONS USING ENDOCYTOSCOPY

SYSTEM

FOR

Y. Mori1,*, S.-E. Kudo1, K. Wakamura1, M. Misawa1, Y. Ogawa1,


M. Kutsukawa1, T. Kudo1, T. Hayashi1, H. Miyachi1, F. Ishida1, S. Hamatani1,
H. Inoue1
1
Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
HOSPITAL, Yokohama, Japan
Contact E-mail Address: ibusiginjp@hotmail.com
INTRODUCTION: Endocytoscopy (EC) enables observation of nuclei at 450fold magnification during gastrointestinal endoscopy, thus allowing precise prediction of lesion pathology, however it requires training and experience.[1,2]
AIMS & METHODS: The aim of the present study was to develop and evaluate
a computer-aided diagnosis (CAD) system for EC imaging of colorectal lesions.
The proposed CAD system comprised image acquisition, nuclear segmentation,
feature extraction, and classification into three pathological groups (non-neoplastic, adenoma, and cancer). The classification algorithm was programmed
based on six features of nuclei that were significantly relevant to pathological
classification by multivariate analysis: area (p 0.009), standard deviation of
area (P50.001), circularity (P50.001), circularity of the top 20 nuclei
(P50.001), shortest diameter (P50.001), and longest diameter (P50.001). To
validate this CAD system, we conducted a pilot study using test sets of EC
images from 176 small colorectal polyps (132 neoplastic lesions and 44 nonneoplastic lesions, all 10mm). The performance of the CAD system for prediction of neoplastic change was compared with diagnoses by two expert endoscopists and two trainee endoscopists. The average time for diagnosis and intraobserver agreement (using 20 EC images at a 4-week interval) were also measured
and compared among the three groups.
RESULTS: The CAD system automatically output the pathological prediction
of all subject images immediately on their input. The CAD system provided a
sensitivity of 92.0% and an accuracy of 89.2% which were comparable with those
provided by the experts (p 0.868 and 0.256, respectively) and significantly
higher than those provided by the trainees (P50.001 and 0.002, respectively).
The CAD system achieved a feasible specificity of 79.5%, which was not significantly different from that achieved by the experts and trainees (p 0.081 and
0.728, respectively). The CAD system also enabled instant diagnosis which took
only 0.3 seconds for each lesion with perfect reproducibility (Kappa 1). (See
Table)

Sensitivitiy, %
Specificity, %
Accuracy, %
Time for diagnosis, seconds
Intra-observer
agreement

Computer-aided
diagnosis
(CAD)
Experts

Trainees

P value P value
(CAD vs (CAD vs
experts) trainees)

92.0
79.5
89.2
0.3

81.8
75.6
80.4
16.0

0.868
0.081
0.256
50.001

92.7
91.0
92.3
4.5

Almost perfect Substantial


Substantial
NA
(Kappa 1)
(Kappa 0.79)
(Kappa 0.71)

50.001
0.728
0.002
50.001
NA

CONCLUSION: This fully automated CAD system provides excellent sensitivity


and accuracy with acceptable specificity, ultra-rapidness, and perfect objectivity.
Thus, it can be a powerful tool for decision support during screening
colonoscopy.(This study was registered as UMIN000012797 and supported by
JSPS KAKENHI Grant Number 25860564.)
REFERENCES
1. Mori Y, et al. Comprehensive diagnostic ability of endocytoscopy compared
with biopsy for colorectal neoplasms: a prospective randomized noninferiority
trial. Endoscopy 2013; 45: 98-105.
2. Kudo S, et al. Diagnosis of colorectal lesions with a novel endocytoscopic
classification a pilot study. Endoscopy 2011; 43: 869-875.
Disclosure of Interest: None declared

A293

United European Gastroenterology Journal 2(1S)


P0580 TRANS-ANAL SUBMUCOSAL ENDOSCOPIC RESECTION
(TASER): A NEW ENDO-SURGICAL APPROACH TO THE
RESECTION OF BENIGN GIANT RECTAL LESIONS
Z.P. Tsiamoulos1,*, J. Warusavitarne2, T. Elliott1, B.P. Saunders1
1
Wolfson Unit for Endoscopy, 2Department of Colorectal Surgery, St Marks
Hospital/Academic Institute, London, United Kingdom
INTRODUCTION: Trans-anal surgical (TEMS/TAMIS) and advanced endoscopic resection (ESD, P-EMR) procedures have the potential to provide complete and successful eradication of giant rectal polyps. Both approaches however
have limitations in terms of practicality and safety. We describe a new endosurgery technique called Trans-Anal Submucosal Endoscopic Resection
(TASER) which combines the advantages of both the endoscopic and transanal
surgical approach.
AIMS & METHODS: The GelPoint Path trans-anal access port allows simultaneous passage of an endoscope and two laparoscopic retractors. Working with
the endoscopic image the laparoscopic retractors (Johen 33mm forceps) allow
dynamic tissue retraction to facilitate endoscopic dissection (Flush knife BT) or
snare placement (Olympus snare master/spiral snare). All procedures were performed under general anesthesia and with patients in the lithotomy position.
RESULTS: Eleven patients (mean age 55 years, 3 male/8 female) underwent
TASER for 11 lesions, distributed from the lower rectum to the recto-sigmoid
junction and with a median size of 85mm, range 40-180mm. Polyp morphology
was (3/11 flat (Paris 2a), 4/11 sessile (Paris 1s) and 4/11 mixed type (Paris 2a1s).
In all cases a circumferential mucosal incision was made and histology confirmed
free lateral margins in all cases. 10/11 rectal polyps were adenomatous and one
had a small focus of moderate differentiated adenocarcinoma (incomplete local
excision).
Complete endoscopic excision in a single session was achieved in 10/11 cases
(91%). Median completion time of the procedure was 215min, range 120480min. Tissue retraction was used in every case and resection was completed
by ESD alone (4/11), ESD EMR (4/11) ESD EMR trans-anal surgical
excision (3/11). Intra-procedural bleeding occurred in 8 cases, controlled with
hemostatic clips and Coagrasper (Olympus); surgical suturing was required in
one case (1/8). Prophylactic clips (2/11) and surgical sutures (1/11) were placed to
treat deep muscle injury. There were no perforations and no delayed bleeding
episodes. Patients were discharged the day following TASER in all cases.
Surveillance at 3-6 months revealed no recurrence in 6 cases, whereas in four
cases the follow up procedure is still pending. The malignant polyp case was
referred to surgery with a good clinical outcome (T3, N0, M0).
CONCLUSION: TASER appears to be a safe and efficient approach providing
an optimal platform for resection of large rectal lesions. In our experience it
provides the optimal platform for the minimally-invasive management of these
high risk lesions.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
LIVER & BILIARY II POSTER EXHIBITION HALL XL_____________________
P0581 EVALUATION OF FERRITIN 41000 CUTOFF POINT TO
DIAGNOSE LIVER IRON OVERLOAD
A. Castiella1,*, E. Zapata1, I. Urreta2, L. Zubiaurre1, A. Iribarren1,
J.M. Alustiza3, E. Salvador3, A. azkune4, E. zubillaga4, L. Rincon5, J.
I. Emparanza2 on behalf of Burnia Group
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro, 2clinical epidemiology, Donostia hospital, 3Radiology, Osatek Donostia, 4Internal Medicine,
Donostia hospital, Donostia, 5GASTROENTEROLOGY, Bidasoa Hospital, Irun,
Spain
Contact E-mail Address: agustincastiella@yahoo.es
INTRODUCTION: Ferritin41000 has been associated with high grade fibrosis
in hemochromatosis and in liver iron overload disorders.
AIMS & METHODS: To establish the nosologic characteristics of ferritin
41000 ng/ml to diagnose high liver iron overload (hepatic iron index4 1.9)
(HIO) and for the diagnosis of significant iron overload in liver (4 60 micromol
Fe/g) (SIO).
Cohort of consecutive patients studied by MRI for quantification of liver iron
concentration (LIC). Variables: age, sex, ferritin and LIC. We calculate the mean
and standard deviation for quantitative variables and absolute and relative frequencies for qualitative variables.
The relationship between ferritin and LIC is analyzed using a simple linear
regression model.
To establish the nosological characteristics of ferritin we calculated the sensitivity
(S), specificity (Sp), positive predictive value (PPV) and negative (NPV) with
their 95% CI.
RESULTS: Total number of patients was 538 (449 men), with a mean age of 53.6
(SD 13.4). Mean ferritin value was 804.5 (SD 655.2). 56 patients (10.4%) had
HIO and 125 (23.2%) had (SIO). Mean LIC in patients with ferritin4 1000 was
55.9 micromol Fe /g. The PPV for HIO is 27.1% (19.9 to 35.8) and NPV of
94.3% (91.6 to 96.1). With our prevalence of 10.4%, the expected results by
chance alone would have been: PPV 10.7% (5 to 21.5) and NPV 89.6 (86.6
to 92), close to the values obtained with ferritin 4 1000. To diagnose SIO, PPV
of ferritin 41000 is 50% (41.1 to 58.9) and NPV of 84.3% (80.5 to 87.5). In this
case, the expected results by chance would have been: PPV 24.6% (17.7 to 33.1)
and NPV 77.1% (72.9 to 80.9).
CONCLUSION: Ferritin4 1000 has a low value for the diagnosis of HIO or for
SIO.
Disclosure of Interest: None declared

P0582 DIAGNOSTIC ALGORITHM FOR


OVERLOAD. WHEN IS MRI INDICATED?

HIGH

LIVER

IRON

A. Castiella1,*, E. Zapata1, I. Urreta2, J.M. ALUSTIZA3, L. ZUBIAURRE1,


E. Salvador3, G. Letamendi4, B. Arrizabalaga5, U. Mendarte6, P. Otazua7,
L. Rincon8, M.D. de Juan9, J. I. Emparanza2 on behalf of Burnia Group
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro, 2clinical epidemiology, DONOSTIA HOSPITAL, 3radiology, osatek donostia, DONOSTIA,
4
hematology, Galdakao Hospital, galdakao, 5radiology, Cruces Hospital,
Baracaldo, 6GASTROENTEROLOGY, DONOSTIA HOSPITAL, DONOSTIA,
7
GASTROENTEROLOGY, mondragon hospital, mondragon,
8
GASTROENTEROLOGY, Bidasoa Hospital, irun, 9immunology, DONOSTIA
HOSPITAL, DONOSTIA, Spain
Contact E-mail Address: agustincastiella@yahoo.es
INTRODUCTION: HIO is considered if the Hepatic iron index4 1.9 (estimated
by MRI).
AIMS & METHODS: To develop and validate a diagnostic algorithm for high
iron overload (HIO) based on laboratory and genetic variables.
We collected a retrospective cohort with all consecutive patients between 2001-2008
studied by Magnetic Resonance Imaging (MRI) to determine liver iron concentration (LIC). This cohort served as the derivation set. We analyzed all variables using
univariate statistics with the MRI acting as the gold standard. We studied the best
combination of the diagnostics variables to build the algorithm.
We validated the algorithm in a prospective cohort, collecting all patients
referred to our hospital for study of iron metabolism alteration since 2009
onwards. We estimate the sensibility, specificity and predictive values with
95% CI.
RESULTS: Retrospective cohort: 242 patients (198 men/44 women), mean age
52,4 (SD 13.3). Thirty six of them had HIO. Nearly half of the patients (117/
242 48.4%) had both Transferrin saturation index (TSI) and Ferritin elevated
and 28 (11.5%) were C282Y homozygous. The final algorithm was as follows:
We consider a patient as having HIO with the simultaneous occurrence of TSI
and Ferritin elevated and C282Y homozygosis. HIO is discarded if TSI or
Ferritin are within normal values. The rest should be studied by MRI.
Prospective cohort: 177 patients (148 men/29 women), mean age 56 (SD 13.9).
The nosological characteristics of the algorithm in this validation study are:
CONCLUSION: MRI is not necessary in 77% of the patients for HIO diagnosis.
MRI is indicated inpatients not C282Y homozygous with raised TSI and
Ferritin.
Disclosure of Interest: None declared
P0583 LIVER IRON CONCENTRATION (LIC) IN PATIENTS REFERRED
FOR HYPERFERRITINEMIA (HF) TO A SECONDARY HOSPITAL:
ANALYSIS OF THE DIFFERENT GROUPS ACCORDING TO HFE
MUTATIONS AND TRANSFERRIN SATURATION INDEX (TSI)
A. Castiella1,*, E. Zapata1, L. Zubiaurre1, A. Iribarren1, M.D. De Juan2,
J.M. ALUSTIZA3, P. OTAZUA4, F. MUGICA5, E. Elosegui5, A. Arriola5,
E. Utrilla6, J. I. Emparanza7
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro,
2
IMMUNOLOGY, DONOSTIA HOSPITAL, 3osatek radiology, osatek,
4
GASTROENTEROLOGY, MONDRAGON HOSPITAL,
5
GASTROENTEROLOGY, DONOSTIA HOSPITAL, DONOSTIA, 6internal
medicine, zarauz health center, zarauz, 7clinical epidemiology, DONOSTIA
HOSPITAL, DONOSTIA, Spain
Contact E-mail Address: agustincastiella@yahoo.es
INTRODUCTION: Olynyk et al (1) analyzed in Australia in 2009 the LIC by MRI
of 52 consecutive patients who were referred for HF to a tertiary hospital. They
described three different groups according to HFE mutations and TSI (A Group: no
predisposing mutations (PM) for Hereditary Hemochromatosis (HH) and TSI 4 45
%, B Group: PM for HH: C282Y/C282Y; C282Y/H63D, and TSI 4 45 %; C
Group: no PM for HH and normal TSI). They concluded that LIC in B Group was
significantly higher than in A and C groups. In the Basque Country, predisposing
mutations differ, with relevance of the H63D/H63D mutation (2).
AIMS & METHODS: To study the relevance of HFE mutations and TSI in
determining LIC of HF patients attending the outpatient clinic at a secondary
hospital.
Prospective study of 132 consecutive patients with HF. January to December
2010. In 120 HFE study was available. In 79 LIC was obtained by MR. In 71
patients values of HFE mutations, TSI, and LIC by MR were available. The LIC
was measured in mmol / g (normal  36 mmol /g) by MR (Alustiza et al method
(3)).
RESULTS: mean age: 55.68  14.26 (23-83), 55 men and 16 women (77.5 %,
22.5 %). The mean age for men was 53.07  13.61; 64.63  13.14 in women. The
mean LIC by MR in men was 35.66  36.85; 38.81  29.75 in women. Patients in
A Group: 21, 14 with normal LIC, 7 raised LIC; B Group: 19-H63D/H63D;
C282Y/H63D-, 11 normal LIC, 8 raised LIC; C Group: 31 patients, 23 normal
LIC, 8 raised LIC. The mean LIC in A Group: 38.80  45.18 (5-210), B group:
48.96  37.51 (15-160), C group: 28.12  18.85 (5-75). We compared the LIC
mean values of the 3 groups using ANOVA, with no significant differences.
CONCLUSION: In our study, the LIC in different groups of patients referred
for HF to a secondary hospital, with different predisposition to HH (PM, raised
TSI), are similar. The different HFE mutations and TSI values do not appear to
be relevant in the LIC of these patients.
REFERENCES
(1). Olynyk, et al. Clin Gastroenterol Hepatol 2009; 7: 359-362.
(2). Castiella, et al. J Gastroenterol Hepatol 2010; 25: 1295-1298.
(3). Alustiza, et al. Radiology 2004; 230: 479-484.
Disclosure of Interest: None declared

A294
P0584 GLUCAGON-LIKE
PEPTIDE-1
(GLP-1)
ANALOGUE,
LIRAGLUTIDE, INHIBITS OXIDATIVE STRESS AND
INFLAMMATORY RESPONSE IN THE LIVER OF RATS WITH DIET
INDUCED NON-ALCOHOLIC FATTY LIVER DISEASE
H.T. Gao1, L.S. Xu1,*, Z.G. Zeng1, L.C. Guan1, W.P. Deng1
1
Guangdong General Hospital, Guangzhou, China
INTRODUCTION: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue,
has been demonstrated to reduce hepatic steatosis. However, the mechanisms
of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim
of the present study was to investigate the beneficial effect of liraglutide on diet
induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechanisms in rats.
AIMS & METHODS: NAFLD was induced by in Sprague-Dawley rats by
feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg
body weight/day) was injected intraperatoneally to the rats subjected to HFHC
diet 4 weeks before sacrificing. Body and liver weight, fasting blood glucose
(FBG), fasting insulin, serum aminotransferase (ALT) and lipid accumulation
in the liver were determined. Markers of oxidative stress, such as malondialdehyde (MDA), free fatty acid (FFAs), superoxide dismutase (SOD), and proinflammatory cytokine tumor necrosis factor-a (TNF-a) were detected with
RIA or ELISA kits. Serum and hepatic adiponectin were measured. The expression of JNK-1 and phosphorylated JNK1 were examined with Western blot.
RESULTS: Liraglutide improved insulin resistance, decreased hepatic steatosis
and reversed liver dysfunction. The hepatic levels of MDA, FFAs, TNF-a were
significantly decreased. While, the SOD and adiponectin levels in the liver were
significantly elevated by liraglutide treatment. Administration of liraglutide also
inhibited the expression of JNK-1 and phosphorylated JNK-1.
CONCLUSION: Liraglutide exerted anti-oxidative and anti-inflammatory
effects in the liver and consequently reverse hepatic steatosis and insulin resistance. Such effects might be mediated by the elevation of adiponectin levels and
the inactivation of JNK1.
Disclosure of Interest: None declared
P0585 SHORT CHAIN C6-CERAMIDE LIPOSOMAL UPTAKE AFFECTS
INFLAMMATION, PROLIFERATION, FIBROSIS AND OXIDATIVE
STRESS IN MCD-INDUCED NASH IN VIVO
F. Zanieri1, L. Longato2,*, S. Omenetti1, S. Galastri1, S. Madiai1, T. V. Luong2,
T. Fox3, S.S. S. Velandy3, M. Kester3, M. Pinzani2, K. Rombouts2
1
Department of Experimental and Clinical Medicine and Center of Excellence for
the study at molecular and clinical level of chronic, degenerative and neoplastic
diseases to develop novel therapies DENOthe, University of Florence, Florence,
Italy, 2Division of Medicine, University College of London, Institute for Liver &
Digestive Health, Royal Free, London, United Kingdom, 3Department of
Pharmacology, Penn State University College of Medicine, Hershey, United States
Contact E-mail Address: k.rombouts@ucl.ac.uk
INTRODUCTION: Ceramides are members of the sphingolipid family and are
an integral part of the lipid bilayer of cell membranes. Ceramides exert biological
effects through cellular proliferation, differentiation and cell death. The role of
changes in endogenous ceramides to the pathogenesis of NAFLD to NASH is
sparse. In this study the effect of exogenous liposomes containing short chain C6Ceramide (Lip-C6) was evaluated in a NASH model and in vitro in primary
human Hepatic Stellate Cells (hHSC) as possible Lip-C6 target.
AIMS & METHODS: NASH was induced by feeding mice for 9 weeks a methionine-and choline-deficient (MCD) diet, or control diet (CD), followed by a single
tail-vein injection of Lip-C6. The effect of Lip-C6-treatment was investigated by
measuring ALT/AST, histology, Q-PCR and protein analysis. Possible changes
in hepatic ceramide magnitude/species specificity and sphingosines were measured by employing untargeted LC-MS/MS lipidomics. The effect of Lip-C6
on primary hHSC proliferation, cytotoxicity and signaling pathways was
investigated.
RESULTS: MCD-Lip-C6 treatment did not exacerbate MCD-induced NASH
when analyzing ALT/AST, steatosis, lobular inflammation, ballooning, apoptosis and fibrosis. Protein analysis showed that Lip-C6-treatment affects the endogenous antioxidant system KEAP1-Nrf2-NQO1 in MCD-fed mice. MCD-fed
mice showed a reduction in p-JNK, cleaved caspase-3/PARP, the mRNA stabilizing protein ELAV1/HuR and its downstream target phosphorylated p62 when
compared to CD-fed mice which were not affected by Lip-C6-treatment.
Exogenous liposomal short chain ceramide C6 treatment does not affect inflammation markers TNFalpha and NFKB signalling pathway. A strong phosphorylation of AMPK was induced in Lip-C6-treated MCD-fed indicating a
stimulation of energy producing catabolic pathways. Of particular note, LipC6-treatment reverses the significant decreases in phosphatidylcholines (PC)
and phosphatidylethanolamines (PE) species and rearranges the significant
increases in specific sphingolipid species in MCD-fed mice. Moreover, Lip-C6Rhodamine was taken up by primary hHSC and Lip-C6-treatment inhibits proliferation and cytotoxicity in a concentration-dependent manner.
CONCLUSION: These results demonstrate that a single injection of short chain
C6-ceramide liposomes does not exacerbate inflammation, apoptosis, proliferation and oxidative stress in MCD-induced NASH, possibly by restoring changes
in membrane lipid content induced by NASH.
Disclosure of Interest: F. Zanieri: no conflict of interest to declare, L. Longato: no
conflict of interest to declare, S. Omenetti: no conflict of interest to declare, S.
Galastri: no conflict of interest to declare, S. Madiai: no conflict of interest to
declare, T. V. Luong: no conflict of interest to declare, T. Fox: no conflict of
interest to declare, S. S. S. Velandy: no conflict of interest to declare, M. Kester
Directorship(s) for: Penn State Research Foundation has licensed ceramide
nanotechnology to Keystone Nano, Inc. (PA, USA) and M. K. is cofounder

United European Gastroenterology Journal 2(1S)


and Chief Medical Officer of Keystone Nano, M. Pinzani: no conflict of interest
to declare, K. Rombouts: no conflict of interest to declare
P0586 APOC3
( 455T4C)
POLYMORPHISM
CONFERS
SUSCEPTIBILITY TO NONALCOHOLIC FATTY LIVER DISEASE
IN A HAN CHINESE POPULATION
M. Li1,*, S. Zhang1, X. Liao1, K. Chao1, J. Yao1, B. Zhong1
1
Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen
University, Guangzhou, China
Contact E-mail Address: sophiazhong@medmail.com.cn
INTRODUCTION: Genetic variation in apolipoprotein C3 (APOC3) was
reported to be associated with nonalcoholic fatty liver disease (NAFLD), but
its role in Chinese population is not well understood.
AIMS & METHODS: To investigate the association between the apolipoprotein
C3 (APOC3, -455T4C) polymorphism and nonalcoholic fatty liver disease
(NAFLD), we recruited 300 NAFLD patients and 300 healthy controls to a
cohort representing Han Chinese at The First Affiliated Hospital, Sun Yat-sen
University, from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were
used to genotype the APOC3 (-455T4C) variants.
RESULTS: After adjusting for age, gender, and BMI, TC and CC genotypes
were found to increase the susceptibility to NAFLD compared to that of the TT
genotype, with odds ratios (ORs) of 1.94 (95% CI, 1.26-2.98) and 3.01 (95% CI,
1.76-5.16), respectively. Further stratification analysis indicated that the CC
genotype was more susceptible to insulin resistance (IR) than the TT genotype,
with OR of 2.59 (95% CI, 1.26-5.30). The CC genotype also was associated with
a much higher risk of hypertension, hypertriglyceridemia, and low levels of highdensity lipoprotein cholesterol (P50.05). No association was found between the
APOC3 (-455T4C) polymorphism and body-mass index, level of fasting plasma
glucose, serum uric acid, total cholesterol, and low-density lipoprotein cholesterol (P40.05).
CONCLUSION: APOC3 (-455T4C) genetic variation is involved in the susceptibility to develop NAFLD, IR, and some metabolic syndrome disorders in the
Han Chinese population.
Disclosure of Interest: None declared
P0587 SERUM ADIPOKINES IN PATIENTS WITH NON ALCOHOLIC
FATTY LIVER DISEASE, IS THERE A ROLE FOR PREDICTING
THE SEVERITY OF LIVER DISEASE?
M.A. Amin1,*, K. Al-Ashmawi1, O. Shaker2, S. Mussa1
1
internal medicine, 2biochemistry, Cairo University, Cairo, Egypt
Contact E-mail Address: monasleman@hotmail.com
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is considered to
be among the most common liver diseases world-wide. NAFLD encompasses a
broad spectrum of pathological conditions ranging from simple steatosis (SS) to
steatohepatitis (NASH), fibrosis and finally even cirrhosis. Adiponectin (A) has
been associated with inhibition of fibrogenesis and liver protection while leptin
(L) contributes to fibrogenesis in various chronic liver diseases, notably in
NASH.
AIMS & METHODS: To determine the validity of serum adipokines including
leptin, adiponectin, and A/L ratio to act as a potential markers for NAFLD and
to discriminate NASH from SS.
Patients and methods: Eighty four patients who have bright liver on abdominal
ultrasonography and 28 healthy individuals served as control group. Serum
Leptin and Adiponectin were estimated by ELISA technique. Liver biopsy was
done for 46 patients and according to histopathological examination they were
divided into 21 patients with SS and 25 patients with NASH.
RESULTS: The serum concentration of adiponectin was significantly lower in
NASH than SS group (P 50.001). There was no significant difference between
serum concentration of leptin in both groups (p 0.4). A/L ratio in NASH group
was significantly lower than SS group (P 50.001). Adiponectin was negatively
correlated with BMI, total cholesterol and LDL-C in both groups. A/L ratio in
NASH group was significantly positively correlated with adiponectin (P50.001)
while it was significantly negatively correlated with leptin (P50.001). In SS
group A/L ratio was significantly negatively correlated with leptin (r -0.863,
P50.001).
CONCLUSION: In patients with NAFLD, the serum adiponectin and A/L ratio
can discriminate simple steatosis from NASH and predict the severity of liver
injury.
Disclosure of Interest: None declared
P0588 MYOSIN LIGHT CHAIN KINASE INVOLVED IN INTESTINAL
BARRIER FUNCTION CHANGE OF MICE WITH NAFLD
Y. Zhang1,*, J. Li1 on behalf of 1, Y. Chi2 on behalf of 2, Y. Liu1 on behalf of 1
Gastroenterology Department, 2Institution of Clinical Molecular Biology, Peking
University Peoples Hospital, Beijing, China
Contact E-mail Address: medicalyuan@foxmail.com
1

INTRODUCTION: Myosin Light Chain Kinase (MLCK) plays a central role in


the mechanisms of barrier dysfunction, and some studies showed nonalcoholic
fatty liver disease (NAFLD) had intestinal barrier function change. The present
study aimed to identify whether MLCK was involved in the pathogenesis of
nonalcoholic fatty liver disease (NAFLD).
AIMS & METHODS: The NAFLD mice model was established by giving highfat diet (HFD) and NASH was induced by lipopolysaccharide (LPS) administration. Mice received MLCK inhibitor ML-7 by intraperitoneal injection. The level

A295

United European Gastroenterology Journal 2(1S)


of ALT, AST was assessed. The degree of liver steatosis was observed by HE
stain. Intestinal mucosal tight junction was observed by electron microscope, and
the occludin protein was stained by immunofluorescence.
RESULTS: MLCK expression increased in NAFLD and NASH groups vs control group. ALT and AST elevated in the NAFLD and NASH group, which
could be reduced by MLCK inhibitor ML-7 (Table.1, *P50.05 vs NAFLD
group, ** P50.05 vs NASH group). The liver pathology showed no significant
change after ML-7 administration. The intestinal tight junctions occludin protein
were seemed to be ameliorated by ML-7,but there were no significant difference.
U/L Control

NAFLD

NAFLDML-7 NASH

ALT 20.330.843 20.002.014 13.800.663


AST 46.672.704 44.002.075 37.602.349

NASHML-7

31.703.208* 18.801.597**
117.612.23* 73.105.382**

CONCLUSION: MLCK inhibitor ML-7 could protect liver function via improving the intestinal barrier of NAFLD mice.
REFERENCES
1. Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and
tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009; 49:
1877-1887.
2. Wang N, Yu H, Ma J, et al. Evidence for tight junction protein disruption in
intestinal mucosa of malignant obstructive jaundice patients. Scand J
Gastroenterol 2010; 45: 191-199.
Disclosure of Interest: None declared
P0589 EPITHELIAL MYOSIN LIGHT CHAIN KINASE-DEPENDENT
BARRIER DYSFUNCTION INVOLVED IN INTESTINAL BARRIER
FUNCTION CHANGE OF MICE WITH NAFLD
Y. Zhang1,*, J. Li1 on behalf of 1, Y. Chi2 on behalf of 2, Y. Liu1 on behalf of 1
1
Gastroenterology Department, 2Institution of Clinical Molecular Biology, Peking
University Peoples Hospital, Beijing, China
Contact E-mail Address: medicalyuan@foxmail.com
INTRODUCTION: Myosin Light Chain Kinase (MLCK) plays a central role in
the mechanisms of barrier dysfunction, and a lot of studies showed the intestinal
barrier permeability increased in nonalcoholic fatty liver disease (NAFLD).
AIMS & METHODS: The research aimed to identify whether MLCK was a
regulator in the intestinal barrier permeability change of nonalcoholic fatty liver
disease (NAFLD). The NAFLD mice model was established by giving high-fat
diet (HFD) and NASH was induced by lipopolysaccharide (LPS) administration.
Mice received MLCK inhibitor ML-7 by intraperitoneal injection. The intestinal
mucosal tight junction was observed by electron microscope, and the LPS concentration of portal vein was detectedd by ELISA.
RESULTS:
MLCK expression increased significantli in fatty liver (NAFLD) and NASH,
which could be blocked by ML-7. The intestinal epithelial tight junction of
NASH were broader compared with control group, which could be improved
by MLCK inhibitor ML-7 (Table 1). The LPS in portal vein of NASH mice was
higher, suggesting the intestinal barrier permeability dysfunction. After MLCK
was blocked by ML-7, the LPS in portal vein decreased significantly.
nm Control

NAFLD

NAFLDML-7 NASH

TJ 14.900.329 19.801.197* 19.200.997*

NASHML-7

26.61.200* 14.900.666#

Table 1: The tight junction of intestinal epithelial of different groups.


CONCLUSION: The intestinal barrier function was restored by specifically
inhibiting MLCK, suggesting that MLCK activity was responsible for the
change of barrier function in NAFLD.
REFERENCES
1. Al-Sadi R, Guo S, Ye D, et al. TNF- modulation of intestinal epithelial tight
junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol 2013;
183: 1871-1884.
2. Al-Sadi R, Guo S, Ye D, et al. Mechanism of IL-1beta modulation of intestinal epithelial barrier involves p38 kinase and activating transcription factor-2
activation. J Immunol 2013; 190: 6596-6606.
Disclosure of Interest: None declared
P0590 ABACAVIR AND DIDANOSINE ENHANCE ACETAMINOPHENINDUCED HEPATOTOXICITY THROUGH GSH DEPLETION
A. Blas-Garc a1,2,*, V.M. V ctor2,3, M. Polo1,2, H.A. Funes1, A. Mart -Rodrigo1,
N. Apostolova3,4, J. V. Esplugues1,2
1
Pharmacology, Universidad de Valencia-CIBERehd, 2FISABIO-Hospital
Universitario Dr. Peset, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
Universidad Jaime I, Castellon de la Plana, Spain
Contact E-mail Address: ana.blas@uv.es
INTRODUCTION: Liver disease is a leading cause of mortality among HIVinfected patients and has been related in some cases to combined Antiretroviral
Therapy (cART). Little is known about the acute effects of nucleoside/nucleotide
reverse transcriptase inhibitors (NRTI) on hepatic cells, although the purine
analogue abacavir (ABC) has been reported to induce an acute mitotoxic effect
in vitro. Since acetaminophen (APAP), a well-known hepatotoxic drug, is commonly prescribed to HIV-infected patients and also interferes with mitochondria,

we hypothesised that its combination with antiretrovirals can specifically exacerbate the hepatotoxic effects of the latter drugs.
AIMS & METHODS: To analyse the acute mitochondrial effects of clinically
relevant concentrations of the purine analogues ABC and didanosine (ddI), to
assess their impact on mitochondrial function and the viability of hepatic cells,
and to explore potential synergisms with APAP and other hepatotoxic drugs.
Several parameters of mitochondrial function (oxygen consumption, mitochondrial membrane potential - m-, reactive oxygen species ROS- production,
intracellular ATP levels, GSH levels) and cellular viability were assessed in
non-HIV-infected Hep3B and hepatocyte-like HepaRG cells treated (1-48h)
with the purine analogues ABC and ddI. Further experiments were performed
in the presence of sub-damaging concentrations of different hepatotoxic stimuli
(APAP, the antiretroviral drugs ritonavir and nevirapine, and ethanol). Data
were reported as mean/-SEM, and their statistical significance versus vehicle
was analyzed by one-way ANOVA. Correlations were analysed using
Spearmans correlation coefficient.
RESULTS: Clinical concentrations of purine analogues produced an immediate
and significant decrease in mitochondrial function, evident in a concentrationdependent inhibition of O2 consumption, increased ROS production, and a
reduction of  m and intracellular ATP levels. This mitochondrial dysfunction
did not compromise cell survival, as the aforementioned parameters returned to
previous values after 24h treatment. However, co-administration of these drugs
with APAP concentrations below those considered toxic in hepatic cellular
models exacerbated the deleterious effects of both treatments on mitochondrial
function and cellular viability, thus decreasing intracellular GSH concentrations.
Such effect was not observed with the other hepatotoxic stimuli evaluated.
Interestingly, a significant positive correlation was detected between GSH
levels and cell viability.
CONCLUSION: The combination of ABC or ddI with low concentrations of
APAP significantly effects GSH concentrations in a way that increases the risk of
APAP-mediated liver injury. Our findings are of considerable relevance given
that APAP is currently prescribed to patients taking NRTI and that HIV infection itself has been reported to undermine intracellular GSH levels.
Disclosure of Interest: None declared
P0591 THE
NON-NUCLEOSIDE
REVERSE
TRANSCRIPTASE
INHIBITOR EFAVIRENZ MODIFIES THE INFLAMMATORY
RESPONSE OF HEPATIC CELLS
A. Blas-Garc a1,2,*, F. Alegre1,2, D. Ortiz-Masia2, L. Milian-Medina1,
N. Apostolova3,4, J. V. Esplugues1,2
1
FISABIO-Hospital Universitario Dr. Peset, 2Pharmacology, Universidad de
Valencia-CIBERehd, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
Universidad Jaime I, Castellon de la Plana, Spain
Contact E-mail Address: ana.blas@uv.es
INTRODUCTION: Efavirenz (EFV) is the most widely used drug in the treatment of HIV-infection, but has recently been associated with oxidative stress,
mitochondrial dysfunction and endoplasmic reticulum stress in hepatocytes. As
mitochondrial damage and ER-stress are frequently related to inflammatory
disease, we have evaluated the effects of EFV on the cytokine/chemokine expression pattern of hepatic cells. In addition, we have explored the possible involvement of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kB)
and NLRP3 inflammasome, both of which trigger signalling pathways implicated
in hepatic inflammation and liver injury.
AIMS & METHODS: Non-HIV-infected Hep3B cells were treated with clinically-employed concentrations of EFV (10 and 25mM). Inflammation-related
gene expression was studied with Real time PCR. Activation of NF-kB was
confirmed by Western blot. An electrophoretic mobility shift assay (EMSA)
was carried out to determine the binding of NF-kB to promoters of some of
the genes whose expression was found to be up-regulated. Chemokine secretion
was evaluated in culture supernatant samples using an immunoassay kit. Data
(n3) were analysed with one-way ANOVA followed by a Newman-Keuls test.
*p50.05, **p50.01, ***p50.001 (vs control).
RESULTS: EFV induced mRNA expression of the inflammatory mediators
TNF, IL-6, PAI-1, TXNIP and NLP3 in a significant and concentration-dependent manner. Furthermore, EFV reduced IkBa protein levels, thus increasing
NF-kB translocation to the nucleus. The EMSA assay demonstrated that
trans-activation of PAI-1 was mediated by interaction of NF-kB with a consensus sequence located within the PAI-1 promoter. Nevertheless, EFV also significantly reduced the production and secretion of IL-8 and IP-10, chemokines
involved in the progression of liver injury.
CONCLUSION: Due to its inhibitory effects on mitochondrial function, EFV
promotes a pro-inflammatory response through NF-kB- and NLRP3-dependent
pathways. Interestingly, EFV also reduced the secretion of IL-8 and IP-10, thus
playing a dual role in regulating the inflammatory response. In the context of
lifelong use of EFV, these effects could accumulate and exacerbate the liver
toxicity induced by other stimuli such as other antiretroviral drugs, co-infections
(hepatitis B and/or C) or co-morbidities associated with HIV infection.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)

P0592 LIVER FUNCTION AND ELASTICITY MONITORING DURING


RHEUMATOID ARTHRITIS DISEASE MODIFYING TREATMENT
A.A. Popov1,*, E.G. Martemyanova2
1
Internal Medicine Dept.#2, URAL STATE MEDICAL UNIVERSITY,
2
Preobrazhenskaya Clinic, Ekaterinburg, Russian Federation
Contact E-mail Address: art_popov@mail.ru
INTRODUCTION: Rheumatoid arthritis (RA) requires early intervention with
disease modifying drugs (DMARDs) in order to prevent disease progression and
disability [1]. Liver safety issues may delay or limit DMARDs administration [2].
AIMS & METHODS: Aim: to assess liver function tests and liver elasticity
during first year of RA DMARDs treatment in everyday clinical practice.
Methods: 20 consecutive rheumatologists out-patients (16 females) aged from 26
to 56 (mean 47.7) were enrolled in a prospective cohort study. All had newly
diagnosed established seropositive RA according to ACR/EULAR 2010 criteria.
Viral hepatitides being preliminarily excluded, anthropometry, serum ALT, AST,
GGTP, bilirubine levels, were registered as safety measures by 2, 4, 12, 24, 36, 48
week. Liver ultrasound elastography (FibroScan, Echosens, France) was performed twice: at enrollment and end of study visit. RA disease activity was
assessed by DAS28 index by 12, 24, 26 and 48 week. All patients were administered oral methotrexate 10-25 mg weekly or leflunomide 20 mg daily as
DMARDs. Ibuprophen up to 1200 mg per 24 hours was allowed as on
demand rescue treatment. Rescue medication consumption was registered by
tablets count. All patients received advices on smoking cessation, diet optimization, physical exercises and daily activies adjusted to body mass index and
comorbidities.
RESULTS: All patients had comorbidities by DMARDs initiation. The most
frequent were arterial hypertension (11 pts.), dyslipidemia (20 pts.), obesity (5
pts.), high fasting glucose (7 pts.), type 2 diabetes mellitus (5 pts.). In 13 subjects
metabolic syndrome (MS) was diagnosed. Non-alcocholic steatohepatitis
(NASH) was diagnosed in 8 patients, while normal liver elasticity was found in
only 1 subject.
DMARDs administration during 1 year resulted in DAS28 20% reduction in all
subjects, 50% DAS28 reduction was registered in 16 subjects, and 70% response
was found in 7 subjects. Liver elasticity has increased in 1 person with Type 2
diabetes mellitus. There had been 7 liver test worsening episodes during 1 year
study. All liver test increases were seen in obese subjects with glucose metabolism
disorders. No difference between methotrexate and leflunomide groups was
found.
CONCLUSION: NASH had been frequent in RA patients before DMARDs
were started. All liver test abnormalities during DMARDs administration were
likely to be NASH related. The data support the hypothesis that conventional
RA treatment is safe and does not cause liver lesions.
REFERENCES
1. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for
the management of rheumatoid arthritis with synthetic and biological diseasemodifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73: 492-509.
2. Curtis JR., Beukelman R, Onofrei A, et al. Elevated liver enzyme tests among
patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate
and/or leflunomide. Ann Rheum Dis 2010; 69: 43-47.
Disclosure of Interest: None declared

n
w
a
r
d
h
t
i
W

P0593 OSTEOPOROSIS AND BONE FRACTURES IN ALCOHOLIC


LIVER DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
C.S. Bang1, D.J. Kim1, G.H. Baik1, S.H. Park1, H.S. Kim1, E.J. Kim1,*,
K.T. Suk1
1
Department of Internal Medicine, Hallym University College of Medicine,
Chuncheon, South Korea, Chuncheon, Korea, Republic Of
Contact E-mail Address: cloudslove@naver.com
INTRODUCTION: Excessive alcohol consumption is an well-established risk
factor for osteoporosis and bone fractures. However, moderate amount of alcohol ingestion is known to be associated with higher bone mineral density (BMD).
Osteodystrophy is a frequently overlooked complication in patients with chronic
liver disease, which could result in serious outcome. However, the exact prevalence or mechanism of osteodystrophy in patients with alcoholic liver diseases
(ALD) have not been described.
AIMS & METHODS: The aim of this study was to evaluate the current evidence
on osteoporosis and bone fractures in ALD. Case-control or cohort studies were
identified from databases (Pubmed, EM-BASE, and the Cochrane Library). The
searching keywords were alcoholic liver diseases, osteoporosis, or bone fractures using Boolean operators. The prevalence of any fractures or osteoporosis,
and BMD score were extracted and analyzed using risk ratios (RRs) and standardized mean difference (SMD). A random effect model was applied based on
Higgins I2 tests. Publication bias was evaluated using a funnel plot, Eggers test,
trim and fill, and the rank correlation test.
RESULTS: In total, 16 studies performed between 1986 and 2011 were identified
and analyzed. Overall, ALD showed an RR of 1.944 (95% CI: 1.354-2.791, P 5
0.001) for the development of bone fractures. However, ALD showed an RR of
0.849 (95% CI: 0.523-1.38, P 0.509) for the development of osteoporosis. BMD
was not statistically different between ALD and control group, although lower
trend in patients with ALD (SMD in femur BMD: -0.192, 95% CI: -0.48-0.096,
P 0.191) (SMD in spine BMD: -0.429, 95% CI: -0.925-0.067, P 0.09).
Subgroup analysis showed consistent results. Publication bias was only detected
in the analysis of bone fractures.
CONCLUSION: Current publications indicate significant association between
bone fractures and ALD, however insignificant association between osteoporosis
and ALD. Due to the qualitative and quantitative heterogeneity among studies,
further researches using homogenous population with common validated

measurement of BMD and risk factors are needed to elucidate the mechanism
of bone fractures in ALD.
Disclosure of Interest: None declared
P0594 IS SQSTM1/P62
HEPATOTOXICITY?

DEFENCE

AGAINST

EFV-INDUCED

F. Alegre1,2,*, A. Blas-Garc a1,2, M. Polo1,2, H.A. Funes2, N. Apostolova3,4, J.


V. Esplugues1,2
1
FISABIO-Hospital Universitario Dr. Peset, 2Pharmacology, Universidad de
Valencia-CIBERehd, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
Universidad Jaime I, Castellon de la Plana, Spain
Contact E-mail Address: fernando.alegre@uv.es
INTRODUCTION: Sequestome 1/p62 is a multifunctional protein known to be
involved in autophagy, during which it acts as a substrate carrier and becomes
degraded. It has also been reported that p62 plays important roles in other
cellular events, including oxidative stress responses, proteostasis, inflammation
and cell survival, while, interestingly, it is implicated in several liver diseases, such
as non-alcoholic steatohepatitis. The non-nucleoside reverse transcriptase inhibitor Efavirenz (EFV) is widely employed in combined antiretroviral therapy to
treat HIV1 infection, and, though generally considered safe, has been associated
with hepatotoxic events. Although the underlying mechanisms of the deleterious
hepatic effects of EFV are still unclear, evidence points to altered lipid metabolism, mitochondrial dysfunction/mitophagy and endoplasmic reticulum stress in
human hepatocytes.
AIMS & METHODS: To analyse the implication of p62 in EFV-induced toxicity
in hepatocytes. The human hepatoma line Hep3B and cells lacking functional
mitochondria (Hep3B rho-zero obtained through pharmacological interruption
of mtDNA replication) were exposed to clinically relevant concentrations (10 and
25M) of EFV for 4, 8, 24 and 48h. Key experiments were carried out with
pharmacological inducers of oxidative stress (rotenone) or endoplasmic reticulum stress (thapsigargin). Quantitative PCR was performed to analyse p62 gene
expression. Western Blot was employed to measure LC3 II (a marker of autophagy induction) and p62 protein levels and translocation to the nucleus of the
transcription factors NF-kB and Nrf2, which have been reported to regulate p62
expression and to be involved in ER/oxidative stress and autophagy.
RESULTS: EFV clearly enhanced the protein expression of LC3 II
(Microtubule-associated protein 1A/1B-light chain 3), but no reduction of p62
levels was observed. Conversely, both mRNA and protein expression of p62 were
increased in EFV-treated cells in a concentration- and time-dependent manner.
Western blot studies demonstrated that EFV promoted translocation of NF-B,
but not of Nrf2, to the nucleus. Moreover, the increase in p62 protein level
triggered by EFV in wild type hepatocytes was less pronounced in rho-zero
cells and completely absent in rotenone.
CONCLUSION: Despite inducing autophagy, clinical concentrations of EFV
increase p62 expression, an effect that maybe related to NF-kB translocation
to the nucleus. The results obtained in rho-0 cells suggest that overexpression
of p62 is a defence mechanism against the mitochondrial and ER dysfunction
triggered by EFV.
Disclosure of Interest: None declared
P0595 THE INCIDENCE RATE OF ALCOHOLIC
RELATED TO ALCOHOL CONSUMPTION: A 4-YEAR
RETROSPECTIVE COHORT STUDY

FATTY

LIVER

M.Y. Lee1,*, Y.K. Cho2, K.B. Bang2, D.S. Lee2, J.H. Yu2, H.A. Lee2, E.H. Park2,
C. I. Sohn2
1
Sungkyunkwan University Kangbuk Samsung Hospital, Seoul, Korea, Republic
Of, 2Internal Medicine, Sungkyunkwan University Kangbuk Samsung Hospital,
Seoul, Korea, Republic Of
Contact E-mail Address: choyk2004.cho@samsung.com
INTRODUCTION: Alcohol consumption is one of the most well-known
common causes of fatty liver. There is a lack of studies on incidence rate of
alcoholic fatty liver related to alcohol consumption. We conducted a retrospective cohort study design to examine the relationship between alcohol consumption and alcoholic fatty liver among healthy Koreans.
AIMS & METHODS: A healthy cohort of 29,281 individuals, who had participated in a medical health check-up program in 2008, was followed up until 2012.
Alcoholic fatty liver was diagnosed and defined based on both ultrasonographic
finding and serum AST/ALT ratio  2. Alcohol consumption was divided into
four groups (non-drinker, 520g/d in Female & 540g/d in Male, 20-40g/d in F &
40-60g/d in M, 440g/d in F & 460g/d in M). Cox proportional hazard model
was used to determine if alcoholic fatty liver was associated with baseline alcohol
consumption level.
RESULTS: During 100,233 person-years of follow-up, 4,889 cases of alcoholic
fatty liver was diagnosed between 2009 and 2012. After adjusted for sex, age,
interaction effect between sex and alcohol consumption level, the Hazard ratios
(HRs) for incidence rates of alcoholic fatty liver increased according to the baseline alcohol consumption levels (HR: 0.926, 95% CI 0.827-1.038, HR: 3.257,
95%CI 2.323-4.565, HR: 3.728, 95%CI 2.238-6.213), compared to the nondrinker.
CONCLUSION: Alcoholic consumption was associated with an increased rate
of alcoholic fatty liver. In female, incidence of alcoholic fatty liver was higher
than the male. In addition, obesity was independent risk factors for incidence of
alcoholic fatty liver.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)


P0596 UNIVERSAL SCREENING FOR ALCOHOL MISUSE IN ACUTE
MEDICAL ADMISSIONS IS ACHIEVABLE AND IDENTIFIES
PATIENTS AT HIGH RISK OF LIVER DISEASE
P. Meredith1, P. Schmidt2, S. Atkins3, P. Greengross4, G. Westwood5,
R. Aspinall6,*
1
TEAMS Centre, 2Acute Medicine, 3Alcohol Specialist Nursing Service,
Portsmouth Hospitals NHS Trust, Portsmouth, 4Primary Care & Public Health,
Imperial College Healthcare NHS Trust, London, 5Faculty of Health Sciences,
University of Southampton, 6Gastroenterology & Hepatology, Portsmouth
Hospitals NHS Trust, Portsmouth, United Kingdom
Contact E-mail Address: r.j.aspinall@doctors.org.uk
INTRODUCTION: Many people who die from Alcohol Related Liver Disease
(ARLD) have a history of recurrent hospital admissions. These episodes may
represent missed opportunities for intervention. Universal screening of medical
patients has been advised but little is known of the feasibility of this or its
efficiency at detecting high risk cases. In 2011, we introduced a 7-day Alcohol
Specialist Nursing Service (ASNS) coupled with universal screening of medical
patients using a novel electronic data capture system. We now present our data
on the feasibility of unselected screening and the resulting alcohol profiles of over
28,000 medical admissions in a major acute hospital serving a catchment population of 650,000.
AIMS & METHODS: From July 2011 to December 2012, all admissions via the
Acute Medical Unit (AMU) were screened using the VitalPAC clinical observation system with a VitalPAC Alcohol Assesment Score (VPAAS) based on the
Paddington Alcohol Test. At-risk patients (VPAAS of 6 or more) were referred
to the ASNS and an Alcohol Use Disorders Identification Test (AUDIT) performed. Data analysis was performed on patient demographics, unit consumption, diagnosis, mortality and previous Emergency Department (ED) attendances
and admissions.
RESULTS: There were 29,361 admissions of whom 28,098 (96%) completed
VPAAS alcohol screening. Mean AMU population age was 67.4 years, 52.3%
female. Of 1,123 high risk cases, 770 were seen by the ASNS and 636 defined as
dependent (AUDIT 420). Compared to the general AMU cohort, the at-risk
group had more ED attendances (7.8 vs 2.9) and hospital admissions (4.8 vs 3.1)
in the previous 3 years and a lower age of death (58.3 vs 81.5). Dependent women
had fewer recurrent attendances and admissions than men but had a higher
mortality rate and lower age of death (52.2 vs 62.4). The maximum AUDIT
score of 40 was recorded in 41% of cases seen by the ASNS and this subgroup
had a mean age of death of 52.7 with 6.2 admissions and 10.8 ED attendances
previously. The most frequent primary diagnoses in those with a VPAAS of 6
were liver disease, mental health disorders and GI bleeding.
CONCLUSION: Our analysis of over 28,000 admissions demonstrates that
screening of all medical patients for alcohol misuse is achievable. We successfully
identified a cohort of high risk patients with recurrent admissions and ED attendances, high unit consumption and an elevated risk of liver disease and early
death. This cohort can be targeted with interventions to reduce the burden of
alcohol related harm.
Disclosure of Interest: P. Meredith: None declared, P. Schmidt Consultancy for:
Unpaid research advisor to The Learning Clinic, who created & licenced
VitalPAC, S. Atkins: None declared, P. Greengross Consultancy for: Part-time
Medical Director of The Learning Clinic, who created & licenced VitalPAC, G.
Westwood: None declared, R. Aspinall: None declared
P0597 CHEMOPROPHYLAXIS
IN
PORTUGUESE
MILITARY
PERSONNEL. SHALL MEFLOQUINE BE CONSIDERED A SAFE
DRUG FOR THE LIVER?
T. Meira1,2,*, D. Fernandes1, L. Lopes2
1
Operational Health, Portuguese Navy Medical Center, 2Healthcare Department,
Portuguese Frigate D. Francisco de Almeida, Lisbon, Portugal
Contact E-mail Address: tania_meira@hotmail.com
INTRODUCTION: Mefloquine is a drug administered in the chemoprophylaxis
of malaria (Plasmodium falcipurum). The arising migration to malaria endemic
areas has contributed to the increase of mefloquine prescription. This drug has a
low potential hepatotoxicity induction, with only two reported cases of acute
hepatitis.
AIMS & METHODS: Observational and analytical study. The military personnel who took part in NATO Operation Ocean Shield, on board Portuguese Navy
Frigate D. Francisco de Almeida in 2011, having port visits of malaria endemic
regions, such as Djibouti, were suggested to perform chemoprophylaxis (mefloquine 250mg / week), starting a week before entering Djibouti territorial waters
and finishing 12 weeks after departure. A survey was conducted on the 11th week
of prophylaxis, in order to assess the degree of adherence and adverse effects.
Serum analyses before and after the mission were cumulatively conducted at the
home port.
RESULTS: 85 military personnel participated in this study, showing no disease
or chronic medication, reduced alcohol consumption, no remarkable pre-deployment blood analysis issues and that had completed the full course of chemoprophylaxis. 75% of the side effects were the gastroenterological related (29% upper
abdominal pain, 24% diarrhea, 22% heartburn). Two weeks after the end of the
deployment, analytical blood analysis of the military personnel revealed liver
enzymes changes in 14% of the cases (mean values: AST 67 IU/ L, ALT 82
IU/L, gamma GT 98 IU/L, alkaline phosphatase174 UI/L). There were no
changes in bilirubin values. Six weeks after chemoprophylaxis, an analytical
reassessment was performed revealing that changes only persisted in two individuals, in who the presence of hepatic steatosis was found, on completion of
further ecographic investigation.

CONCLUSION: Whereas a significant proportion of individuals had an increase


in liver enzymes levels, the theoretical potential for liver injury is not to be
discharged when planning prophylaxis, particularly when in synergy with other
factors such as medication, alcohol consumption, and liver disease.
Disclosure of Interest: None declared
P0598 IS ALCOHOLIC FATTY LIVER DISEASE ASSOCIATED WITH
THE METABOLIC SYNDROME?
Y.K. Cho1,*, K.B. Bang1, D.S. Lee 1, D. I. Park1, W.K. Jeon1, B. I. Kim1, C.
I. Sohn1, J.H. Park1
1
Internal Medicine, Sungkyunkwan University Kangbuk Samsung Hospital, Seoul,
Korea, Republic Of
Contact E-mail Address: choyk2004.cho@samsung.com
INTRODUCTION: Accumulating evidence supports an association between
nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS).
However, there still are not enough studies to date showing association between
alcoholic fatty liver disease (AFLD) and metabolic abnormalities.
AIMS & METHODS: We conducted this study to investigate whether AFLD is
associated with the MetS and its components. A total of 52303 subjects (63.1%
men, and 36.9% women) were included in this cross-sectional study. The presence of fatty liver was assessed using standard ultrasound criteria. The term
significant alcohol consumption was defined as weekly alcohol consumption
exceeding 210 g in men and 140 g in women for the previous 2 years. The
presence of metabolic abnormalities were compared according to the fatty liver
status and its etiology. Logistic regression model was performed to assess the
odds ratios (ORs)
RESULTS: The prevalence of NAFLD and AFLD was 29.1% and 4.6%, respectively. The MetS was more prevalent in AFLD (31%) and NAFLD (23.2%) than
in control group (3.6%, p50.001). All metabolic components of AFLD group,
including waist circumference, blood pressure, serum triglyceride, high density
lipoprotein, and fasting blood glucose were statistically worse or more severe
than those of NAFLD group (P50.001). After adjusting for other multiple
covariates, the ORs (95% confidence interval [CI]) for MetS was higher in the
AFLD (3.86; 3.44-4.34) than NAFLD group (2.89; 2.68-3.12).
CONCLUSION: MetS and its components are associated with both NAFLD
and AFLD. However, AFLD has a higher risk of MetS than NAFLD. Further
prospective studies are needed to investigate the effects of AFLD on the development of MetS.
Disclosure of Interest: None declared
P0599 THE BETA-BLOCKERS HAVE A BENEFICIAL OR A HARMFUL
EFFECT IN PATIENTS WITH CIRRHOSIS AND PORTAL
HYPERTENSION?
C. Sfarti1,*, A. Trifan1, A.-M. Singeap1, C. Cojocariu1, O. Chiriac1, C. Stanciu1
1
Institute of Gastroenterology and Hepatology, UNIVERSITY OF MEDICINE
AND PHARMACY IASI, Iasi, Romania
INTRODUCTION: The possible harmful effect of non-selective beta-blockers
for the treatment of portal hypertensive-related complications (esophageal
varices and advanced ascites) in patients with cirrhosis has been suggested by
few recent studies.
AIMS & METHODS: Thus, the aim of the study was to determine the risk of
mortality in patients with cirrhosis and portal hypertension taking non-selective
beta-blocker therapy for the prevention of variceal hemorrhage.
We performed a retrospective analysis of 3215 patients admitted with cirrhosis
and portal hypertension to Institute of Gastroenterology and Hepatology Iasi
from 2009-2013. There were considered two groups: patients with varices only
(1436 cases) and those with both varices and ascites (1779 cases) (Table).
RESULTS: The primary outcome measure for this study was the in-hospital
mortality by any cause. Overall, the mortality was 102/1851 (5.51%) for the
patients in treatment with beta-blockers and significantly higher for patients
not taking beta-blockers 189/1364 (13.85%) (p 5 0.01).
When we assessed the correlation between the beta-blockers use and mortality in
each sub cohort we obtained similar results (Table); In the sub cohort with
varices only, the mortality was 4.62% (40/864) for the patients taking beta-blockers and 11.19% (64/572) in the group without treatment (p50.05). In the sub
cohort with varices and ascites the mortality was 6.28% (62/987) for the patients
taking beta-blockers and 15.78 (125/792) in the group without treatment
(p50.01)
We evaluated several parameters for correlation with the in-hospital mortality.
Multivariable regression analysis revealed that Child-Pugh score was associated
with increased mortality, while the use of beta-blockers was associated with
reduced mortality. The other parameters which were evaluated (hemoglobin,
platelets, bilirubin, INR, creatinine) didnt influenced significantly the mortality.
Beta-blockers therapy

Varices only
Mortality
Varices and ascites
Mortality
All patients
Overall mortality

Yes

No

N 864
4.62%
N 987
6.28%
1851
5.51%

N 572
11.19%
N 792
15.78%
1364
13.85%

P-value

50.05
50.01
50.01

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United European Gastroenterology Journal 2(1S)

CONCLUSION: In a very large cohort of cirrhotic patients with portal hypertension, the mortality was significantly lower in patients treated with non-selective beta-blockers than in those not taking beta-blockers. These data confirm that
the use of non-selective beta-blockers provides a significant survival benefit in
patients with cirrhosis and portal hypertension. Thus, we recommend the use of
non-selective beta-blockers in patients with portal hypertension and its
complications.
Disclosure of Interest: None declared
P0600 EVALUATION OF THE RELATIONSHIP BETWEEN
CHRONIC LIVER DISEASE QUESTIONNAIRE AND THE EQ-5D
INDEX IN HEPATIC ENCEPHALOPATHY PATIENTS TREATED
WITH RIFAXIMIN-A

THE

E. Berni1,*, C.A. Bannister2, C.D. Poole3, P. Conway4, K. Nanuwa4, C.J. Currie2


1
Global Epidemiology, Pharmatelligence, 2Cochrane Institute of Primary Care &
Public Health, 3School of Medicine, Cardiff University, Cardiff, 4Norgine,
Uxbridge, United Kingdom
Contact E-mail Address: ellen.berni@pharmatelligence.co.uk
INTRODUCTION: Estimation of health-related utility is a vital component of
the evaluation of the relative cost-effectiveness of healthcare interventions. The
correlation between different measures of quality of life and health-related utility
in hepatic encephalopathy (HE) has not been explored.
AIMS & METHODS: The aim of this study was to characterize for the first time
the relationship between scores for the Chronic Liver Disease Questionnaire
(CLDQ) and health-related utility as measured by the EQ-5D index in patients
with HE. Data were available from a phase three trial of rifaximin- in patients
with recurrent HE. CLDQ and SF-36 scores were recorded at monthly visits. EQ5D scores were derived from the SF-36 using a recognized mapping technique.
Generalized, linear, mixed modelling methods were used to examine for any
association in order to allow for repeated measures.
RESULTS: 202 of the 299 trial patients, with 920 corresponding observations,
were included in this analysis, having excluded those with missing values at baseline. The average age of the cohort was 57 years, and 133 (66%) were males, with
an average baseline MELD score of 13.8 units. The average time since diagnosis
of HE was 23 months. The model had an r-squared value of 0.827, indicating a
strong relationship between EQ-5D index and CLDQ. The model equation was
EQ-5D -0.010 0.136*CLDQ. Other potential covariates, such as age and sex,
were tested but were not significant (at 0.05).
CONCLUSION: This is the first time that a direct association between the EQ5D index and the CLDQ score has been reported. The r-squared value of this
association suggests that liver-related morbidity may explain the majority of
differences in health-related utility in these subjects.
Disclosure of Interest: E. Berni Consultancy for: Norgine, C. Bannister
Consultancy for: Norgine, C. Poole Consultancy for: Norgine, P. Conway
Other: Employee of Norgine, K. Nanuwa Other: Employee of Norgine, C.
Currie Consultancy for: Norgine
P0601 OUTCOMES OF SECONDARY PROPHYLAXIS FOR GASTRIC
VARICEAL BLEED WITH BETA BLOCKER AFTER GASTRIC
VARICEAL OBTURATION FOR GASTRIC VARICEAL BLEEDING
G. Muzzaffar1,*, S.M. Gill1, M. Malik1 on behalf of Gastroenterology,
Maroof International Hospital, Islamabad
1
Gastroenterology, Maroof International Hospital, Islamabad, Pakistan
INTRODUCTION: Gastric variceal obturation therapy using Histoacryl for the
gastric variceal bleeding is the most appropriate treatment. However, the secondary prophylactic efficacy of beta blocker after gastric variccal obturation therapy
has not been established. We wanted to evaluate the secondary prophylactic
efficacy of beta blocker after gastric variceal obturation therapy. We conducted
this study from January 2011 to January 2014.
AIMS & METHODS: We enrolled 100 consecutive patients, with gastric variceal
bleeding who received gastric variceal obturation therapy using Histoacryl.
Gastric variceal obturation therapy was continued until gastric variceal eradication. Among these 100 patients 48 patients underwent only gastric variceal
obturation therapy (Group I) and 52 patients along with gasstric variceal obturation therapy did receive beta blocker therapy (Group II). We gave Carvedalolo
12.5 to 25 mg daily doses. In all patients, the desired heart rate was achieved. The
rate of rebleeding free overall survival was observed in two groups by KaplanMeyer analysis.
RESULTS: This is ongoing study, we are reporting the interim results. The mean
follow-up period was 24 months. During follow-up period, rebleeding occurred
in 10 patients (20%) in group 1 and 20 patients (40%) in group 11 respectively.15
patients died in group 1 and 25 patients in group 11 over 2 years period, which
was statistically significant at p 0.05. The mean rebleeding free survival times
were 70 and 40.months, respectively, and were statistically significant (p 0.05).
The mean overall survival time were 60 versus 40 months, respectively, and were
significant differences between two groups (p 0.001).
CONCLUSION: The beta blocker adding therapy after gastric variceal obturation therapy using Histoacryl for first gastric variceal bleeding could decrease
rebleeding and mortality, as compared with gastric variceal obturation therapy
alone. Further prospective large-scale studies are needed to confirm or refute our
observation.
Disclosure of Interest: None declared

P0602 SPLEEN STIFFNESS AS A PREDICTOR OF DECOMPENSATION


IN LIVER CIRRHOSIS
H. Stefanescu1,*, B. Procopet1,2, A. Bugariu3, A. Horhat3, C. Radu2, M. Tantau2
Hepatology Department, Regional Institute of Gastroenterology and Hepatology,
2
3rd Medical Clinic, 3University of Medicine and Pharmacy, Cluj-Napoca,
Romania
Contact E-mail Address: drhstefanescu@gmail.com
1

INTRODUCTION: Noninvasive assessment of chronic liver disease is of major


importance. Spleen stiffness measurement (SSM) was proposed as a surrogate
noninvasive marker for prediction of large esophageal varices (LEV) or clinically
significant portal hypertension (CSPH). It was recently hypothesised that SSM
may predict clinical decompensation (CD) during follow up in cirrhotic patients.
AIMS & METHODS: The aim of this study was to evaluate SSM as a predictor
of decompensation in patients with cirrhosis.
Fifty-two consecutive compensated cirrhotic patients due to viral (HCV and/or
HBV) or alcoholic aetiology were included. They were mainly men (27; 52%)
with a mean age of 55.9 years. 25 patients (48%) had large (grade 2 and 3)
oesophageal varices at inclusion. All patients underwent liver and spleen stiffness
measurement at baseline as previously described, abdominal ultrasound and liver
function was assessed by usual biochemical tests. Modified SSM (mSSM) was
also calculated from each spleen elastogram using an alternate calculation algorithm so that an extension of the scale (up to 150 kPa) could be obtained. Clinical
decompensation was defined as the occurrence of one of the following: variceal
bleeding, development of ascites, hepatic encephalopathy (HE), jaundice (total
bilirubin 4 3 mg/dl), infection, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), hepatocellular carcinoma (HCC) or death or liver
transplantation.
RESULTS: During the median follow-up period of 13 months (range 4-28), 23
patients (44%) decompensated. Most frequent cause of CD was ascites (7
patients, 30.4%), followed by infection/SBP (6 patients, 26.1%), variceal bleeding (4 patients, 17.4%), HE and HCC (3 patients, 13.05% in each group). 14
patients (26.4%) had more than one episode of decompensation and 3 (5.6%)
died during the follow-up.
In multivariate analysis baseline values of mSSM (HR 1.085; p 0.01), albumin (HR 0.17; p 0.02) and total bilirubin (HR 1.642; p 0.05) were the
only variables associated with CD in the follow-up, overcoming LSM, SSM
and MELD.
CONCLUSION: Although conducted in a small heterogeneous population of
cirrhotic patients for a limited period of time, the findings of this study supports
the conclusion that modified SS measurement by transient elastography together
with simple biological parameters (Albumin and Bilirubin) may have an important clinical relevance by selecting patients with high risk of decompensation.
Disclosure of Interest: None declared
P0603 SMALL BOWEL CAPSULE ENDOSCOPY AS A TOOL TO
DIAGNOSE PORTAL HYPERTENSIVE ENTEROPATHY IN
CIRRHOTICS: THE EDINBURGH EXPERIENCE
K.J. Dabos1,*, A. Koulaouzidis1, P.C. Hayes2, J.N. Plevris1
1
Gastroenterology, 2Hepatology, Royal Infirmary of Edinburgh, Edinburgh, United
Kingdom
Contact E-mail Address: konstantinos.dabos@nhslothian.scot.nhs.uk
INTRODUCTION: Portal hypertensive enteropathy (PHE) remains difficult to
diagnose in patients with cirrhosis and portal hypertension. Small bowel capsule
endoscopy (SBCE) would be ideal in this situation but it is rarely performed
AIMS & METHODS: We aimed to determine the prevalence of PHE using
SBCE in a cirrhotic patient population from our centre
Methods. This was a retrospective study using the SBCE data base of our unit.
We searched through 1,477 patients that had SBCE between 2005 and 2013.
Patients with cirrhosis who underwent SBCE were identified, data retrieved
and abstracted. The Fischers exact test or the chi square test were used to
compare between groups. A two-tailed P value of 50.05 was considered statistically significant.
RESULTS: We identified 53 patients with cirrhosis who underwent SCBE. We
used PillCamSB (GivenImaging Ltd, Israel) system on 36 patients and the
MiroCam capsule (IntroMedic Co, Korea) on 17 patients. Thirty patients
were referred for iron deficiency anaemia, 15 for obscure gastrointestinal bleeding and 4 for other indications. Four data sets were not available for review at the
time of the study, leaving 49 patients to be reviewed. Mean age was 61.1914.54
years (M/F 27/22). The most common aetiology for cirrhosis in our patients
was alcoholic liver disease (15 patients) followed by NAFLD (9 patients) and
hepatitis C (7 patients). Thirty three patients had evidence of portal hypertensive
gastropathy (PHG) and 17 patients had evidence of oesophageal varices. In total,
29 patients had SCBE evidence of PHE (67%). 28/29 (96.5%) of patients with
PHE had also evidence of PHG. 13/17 (76.4%) patients with oesophageal varices
had also evidence of PHE. Mean gastric transit time was 54  9 minutes and
mean small bowel transit time was 204  64 minutes. There were no statistically
significant differences between the mean gastric transit times in cirrhotic patients
with and without PHE (p 0.235) or the small bowel transit time (p 0.49). Our
mean follow up was 58.0  13.7 months. Twenty patients died during the follow
up period. There was no correlation between the presence of PHE and aetiology
of liver disease (p 0.4261) or subsequent death (p 0.2145).
CONCLUSION: The prevalence of PHE in our study was 67%. SBCE is a useful
tool in evaluating PHE in cirrhotic patients irrespective of aetiology.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)


P0604

Parameter

HPS
(n14)
XSD (Range)

PPH
(n14)
XSD (Range)

Other
(n42)
XSD (Range)

CSV (mL)
MAP (mm Hg)
CI
SVR
NT-proBNP (pg/mL)
PRA (mg/ml/h)
NA (nmol/L)

75,9620,68 (54,4-116,96)
88,438,94 (76,66-100)
3,311,32 (2,05-6,26)
2421,46878,65 (979,01-3900,43)
1264,642188,45 (88,78-6052,5)
4,415,85 (0,1-16,8)
5,974,18 (1,46-11,51)

8420,94 (61-116,74)
83,384,39 (78,33-90)
3,520,92 (2,7-4,10)
1992,76420,35 (1595,28-2321,15)
1323,392028,7 (127,52-5849,1)
12,6620,26 (0,6-57,6)
586,291532,21 (0,3-4061)

86,6918,81(46,78-132,2)
93,87,5 (78,33-110)
3,690,89 (1,97-5,74)
2129,18533,9 (1347,72-3865,03)
607,931149,73 (11,31-5849,1)
6,2111,28 (0,1-57,6)
149,90759,51 (0,3- 4061)

P0604 THE SENSITIVITY AND SPECIFICITY OF INHIBITORY


CONTROL TEST IN THE DIAGNOSIS OF MINIMAL HEPATIC
ENCEPHALOPATHY: A META-ANALYSIS
M.T. T. Panlilio1,*, A.Q. Taguba1, M.E. VIllamayor1, J.P. Ong1
1
Section of Gastroenterology, University of the Philippines Manila-Philippine
General Hospital, Manila, Philippines
Contact E-mail Address: mttpanlilio@gmail.com
INTRODUCTION: Minimal hepatic encephalopathy (MHE) is a complication
of liver cirrhosis that does not show symptoms of overt hepatic encephalopathy
(OHE). This state reflects alterations in cognitive function, but clinically exhibit a
normal mental status examination. Patients with MHE have been shown to have
higher rates of automobile accidents, it predicts the development of OHE, and is
associated with poor survival.
Diagnosis of MHE is difficult, as the absence of clinical evidence of encephalopathy is key to its diagnosis. Neuropsychological testing, specifically the
Psychometric Hepatic Encephalopathy Score (PHES), is accepted as a reference
standard in the diagnosis of MHE. Newer computer-assisted techniques, such as
the Inhibitory Control Test (ICT), have been studied to improve the detection of
MHE. ICT is a simple computer-based test, consisting of presentation of several
letters at 500-millisecond intervals. The ease of performing the test in the outpatient setting may make it a good test for detecting MHE.
AIMS & METHODS: This study aims to determine the sensitivity and specificity
of Inhibitory Control Test in diagnosing minimal hepatic encephalopathy.
COCHRANE and MEDLINE were searched for articles published between
January 2003 to October 2013. Studies that compared ICT with psychometric
tests in cirrhotics were included. Data analysis was performed using the validated
application Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain). The
DerSimonian-Laird random effects method was used to produce summary estimates
of sensitivity, specificity, likelihood ratios (LR), and diagnostic odds ratio (DOR).
RESULTS: The search strategy identified 133 studies. Based on pre-stated criteria, three studies were included in the final review. There were 235 patients with
liver cirrhosis and a matched control group that underwent both psychometric
testing and ICT. Pooled data showed that the ICT had a sensitivity of 88%
(I2 0%), specificity of 72% (I2 69.2%), and DOR was 21.2 (95% CI: 8.08
55.24). A symmetrical sROC depicted an area under the receiver operator curve
(AUC) of 0.89 (standard error 0.03).
CONCLUSION: Inhibitory Control Test is a good tool to exclude cirrhotic
patients without minimal hepatic encephalopathy. It is effective in discriminating
patients with MHE from those without MHE and therefore has potential as a
screening test. However, more high-quality studies are needed to establish test
accurarcy.
REFERENCES
Stinton LM and Jayakumar S. Minimal hepatic encephalopathy. Can J
Gastroenterol 2013; 27: 572-574.
Hisamuddin K, et al. Is the ICT as accurate as standard psychometric testing for
diagnosing hepatic encephalopathy? Nat Clin Pract Gastroenterol Hepatol 2008;
5: 132-133.
Bajaj JS, et al. Inhibitory control test for the diagnosis of MHE. Gastroenterol
2008; 135: 15911600.
Bajaj JS, et al. Inhibitory Control Test Is a Simple Method to Diagnose MHE
and Predict Development of OHE. American J Gastroenterol 2007: 754-760.
Sharma P, et al. Inhibitory control test, critical flicker frequency, and psychometric tests in the diagnosis of MHE in cirrhosis. Saudi J Gastroenterol 2013; 19:
4044.
Disclosure of Interest: None declared
P0605 SYSTEMIC HEMODYNAMICS IN PATIENTS WITH ALCOHOLIC
LIVER CIRRHOSIS AND HEPATOPULMONARY SYNDROME OR
PORTOPULMONARY HYPERTENSION
N. Ljubicic1,*, D. Zekanovic1, T. Pavic1, M. Nikolic1, I. Budimir1, A. Biscanin1
Division of Gastroenterology, Department of Internal Medicine, Sestre milosrdnice University Hospital, University of Zagreb School of Medicine and University
of Zagreb School of Dental Medicine, ZAGREB, Croatia
Contact E-mail Address: neven.ljubicic@kbcsm.hr
1

INTRODUCTION: There is a lack in knowledge about the correlation of systemic circulation parameters and the degree of liver failure with respect to the
presence of hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH).
AIMS & METHODS: The aim of this study was to evaluate the changes in the
systemic circulation by using non-invasive diagnostic approach in the patients

fulfilling the criteria for HPS and PPS. The study sample included 70 patients
with alcoholic liver cirrhosis;22 patients with grade A, 24 patients with grade B,
and 24 patients with grade C according to the Child-Pugh clinical score. Systemic
circulation measurements included: heart rate (HR), mean arterial pressure
(MAP), cardiac index (CI), systemic vascular resistance (SVRI) and cardiac
stroke volume (CSV)1. Neurohumoral parameters included: NT-proBNP, noradrenalin (NA) and plasma renin activity (PRA). HPS was diagnosed if the presence of impaired arterial oxygenation (PaO2580mmHg and alveolar-arterial
oxygen gradient 15mmHg; for patients older than 64 years PaO270 mmHg,
and A-a gradient 20 mmHg) and pulmonary vascular abnormalities were
found. PPH was characterized by increased mean pulmonary artery pressure
425 mmHg at rest and if the diameter of the main pulmonary artery is 29
mm with concomitant segmental arteryto-bronchus ratio 4 1:1 at least in three
out of four pulmonary lobes, or the ratio of the main pulmonary artery diameter
to the aortic diameter 41.
RESULTS: HPS and PPH were found in 28 (40%) patients. Patients with HPS
were mostly patients from group B (57.2%) and C (42.8%) with respect to the
degree of liver failure, while all patients with PPH were patients with advanced
liver failure. When correlating systemic hemodynamic and neurohumoral parameters in relation to the presence of HPS and PPS no significant difference was
found. (Table 1).
CONCLUSION: The combined application of the Doppler and contrast echocardiography is a simple, non-invasive and reproducible method that enables the
diagnosis of both HPS and PPH. Systemic hemodynamic parameters remained
unchanged among patients with HPS and PPS.
REFERENCES
1. Zekanovic D, LJubicic N, Boban M, et al. Doppler ultrasound of hepatic and
system hemodynamics in patients with alcoholic liver cirrhosis. Dig Dis Sci 2010;
55: 458-466.
Disclosure of Interest: None declared
P0606 DO COAGULATION AND PLATELET FUNCTION DISORDERS
INFLUENCE THE PREVALENCE OF VARICEAL BLEEDING IN
PATIENTS WITH LIVER CIRRHOSIS?
P. Rogalski1,*, E. Wroblewski1, M. Rogalska-Plonska2, A. SwidnickaSiergiejko1, A.A. Baniukiewicz1, A. Dabrowski1
1
Department of Gastroenterology and Internal Medicine, 2Department of Infectious
Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
INTRODUCTION: Bleeding from gastro-esophageal varices is a life-threatening
condition and occurs in approximately one third of patients with liver cirrhosis
during their lifetime. On the other hand patients with history of variceal bleeding
have 70% risk of recurrent bleeding within the next year since the first episode.
Coagulation disorders in patients with liver cirrhosis are complex, and their role
in variceal bleeding remains unclear. Previous studies have shown that the results
of standard laboratory tests such as prothrombin time (PT) and activated partial
thromboplastin time (APTT) provide a narrow measure of procoagulant system
only and do not predict bleeding in cirrhotic patients. Thromboelastometry has
been used for decades for intraoperative transfusion guidance and it can show
defects in multiple components of hemostasis. Multiplate impedance platelet
aggregometry (IPA) allows rapid evaluation of platelet aggregation in whole
blood.
AIMS & METHODS: The aim of our study was to compare the character of
coagulation disorders in patients with liver cirrhosis and a history of variceal
bleeding with non-bleeding cirrhotic patients. We compared standard laboratory
clotting tests, thromboleastometry (ROTEM thromboelastometer) and IPA
parameters of cirrhotic patients with medium-large varices who have never
bled (non-bleeding group) with patients with a history of variceal bleeding at
least 3 weeks before (bleeding group). The following thromboelastometry parameters were measured: clotting time (CT), clot formation time (CFT), maximum
clot firmness (MCF) and the clot amplitude at 5, 10 and 15 minutes in three tests
with specific activators to evaluate the extrinsic (EXTEM) and intrinsic
(INTEM) systems, and the clotting factors alone after platelet inactivation
(FIBTEM). In addition, IPA was performed with ADP as an activator and
aggregation was quantified as area under the curve (AUO).
RESULTS: Blood was sampled from 44 patients (23- non-bleeding group, 21bleeding group). Baseline characteristics of the bleeding and non-bleeding groups
were comparable apart from a more prolonged PT in the bleeding group [15,8
(14,1 - 17,3) vs 14,3 (13,5-16,0), p 0.045]. The severity of liver disease according
to ChildPough score was comparable in both groups [8,00 points (8,0-10,0)
non-bleeding group vs 9,0 (8,0-10,0) bleeding group, p 0.889]; 5 patients
class A, 23 patients - class B, 16 patients - class C. In FIBTEM there was
significantly lower amplitude at 15 minutes in the bleeding group compared
with non-bleeding group [12.0 (9,5-14,5) vs 15.0 (11,0-19,0), p 0.049]. The

A300
other results of thromboelastometry and aggregometry parameters did not differ
significantly between both groups, which suggest a compensatory role of platelets
in EXTEM and INTEM tests. The compensatory role of platelets is also supported by the results of IPA in which we demonstrated higher value of AUO in
bleeding group in comparsion with non-bleeding group [273.0 (99,0-557,0) vs
189.00 (132,0-640,0), NS].
CONCLUSION: Despite prolonged PT in bleeding group, the patients with liver
cirrhosis with and without history of variceal bleeding have similar efficiency of
blood clotting, which may suggest compensatory role of platelets in these
patients.
Disclosure of Interest: None declared
P0607 REAL WORLD EXPERIENCE OF RIFAXIMIN FOR HEPATIC
ENCEPHALOPATHY - EFFECTIVE MAINTENANCE OF
REMISSION AND REDUCTION OF HOSPITAL ADMISSIONS IN A
LARGE SECONDARY CARE PATIENT COHORT
H. Preedy1, A. Fowell1, R. Aspinall1,*
1
Gastroenterology & Hepatology, Portsmouth Hospitals NHS Trust, Portsmouth,
United Kingdom
Contact E-mail Address: r.j.aspinall@doctors.org.uk
INTRODUCTION: Rifaximin has been shown to maintain remission of chronic
hepatic encephalopathy (HE) and reduce hospital admissions (Bass et al 2010).
However, the literature mainly reflects tertiary centres and could include referral
bias. Therefore, we examined the real world utility of rifaximin in a large
secondary care acute hospital, serving a population of 650,000.
AIMS & METHODS: All patients with cirrhosis and chronic HE who were
commenced on rifaximin between May 2010 and November 2012 were identified
from a departmental database and pharmacy records. Analysis included formal
review of casenotes, pathology, hospital admission statistics and calculation of
MELD, UKELD and Childs-Pugh scores. Data were analysed for the 6 months
prior to rifaximin usage and at 3, 6 and 12 months later.
RESULTS: The study population comprised 42 patients, 62% male, mean age 59
years. Cirrhosis aetiology was alcohol 55%, NASH 24%, autoimmune 10%,
HCV 5%, miscellaneous 6%. At initiation, 24% of patients were using alcohol
and 19% took quinolone secondary prophylaxis against spontaneous bacterial
peritonitis. Mean baseline prognostic scores were Childs-Pugh 9.4 (SD 2.1),
MELD 15.0 (SD 7.9), UKELD 51.2 (SD 5.1). Survival at 3, 6 and 12 months
post-rifaximin was 78%, 67% and 62% respectively. There was a significant
reduction in Childs-Pugh scores at 3 and 6 months (p50.01) but not 12
months and no significant change in MELD or UKELD. Comparing the 6
months pre/post rifaximin, hospitalisation days fell from 233 to 143, a mean of
5.6 per patient, representing a saving of E1,829 in healthcare tariff costs. The
number of admission episodes fell from 25 to 11.
CONCLUSION: In an unselected real world cohort of patients with chronic
hepatic encephalopathy, rifaximin was associated with fewer readmission spells
and a reduction in bed days with potential savings in healthcare utilisation costs.
The efficacy of rifaximin for the maintenance of remission in patients with
chronic HE can be demonstrated in a secondary care environment.
REFERENCES
Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010; 362: 1071-1081.
Disclosure of Interest: H. Preedy: None declared, A. Fowell: None declared, R.
Aspinall Consultancy for: RA has received consultancy fees from Norgine UK
P0608 NON-INVASIVE
PORTAL
HYPERTENSION
AND
OESOPHAGEAL VARICES EVALUATION BY LIVER AND SPLEEN
TRANSIENT ELASTOGRAPHY IN PATIENTS WITH CHRONIC
LIVER DISEASE
R. Zykus1,*, L. Jonaitis1, V. Petrenkiene_1, I. Valantiene_1, L. Kupcinskas1,2
1
Gastroenterology, 2Institute of Digestive Diseases, Lihuanian University of Health
Sciences, Kaunas, Lithuania
Contact E-mail Address: rzykus@gmail.com
INTRODUCTION: Liver transient elastography (TE) can predict liver fibrosis
with high specificity and sensitivity. However, there is only limited data if TE
could predict clinically significant portal hypertension or presence of oesophageal
varices.
AIMS & METHODS: The aim of our study was to assess correlation between
liver and spleen transient elastography, hepatic venous pressure gradient (HVPG)
and presence of oesophageal varices. In this prospective study the correlations of
liver and spleen TE with HPVG and presence of oesophageal varices were
assessed in 78 chronic liver disease patients (50 patients had chronic hepatitis
C). Spleen TE was feasible in 72 of them. TE was measured at the same day
before HPVG measurement. Interquartile range/median 520% and success rate
460% were considered as good quality criteria during TE both for spleen and
liver investigations. Endoscopy was performed in one week period after TE was
done. Oesophageal varices were classified into 0 - III grades (according Baveno
consensus). Patients were categorised into those with and without oesophageal
varices. HPVG was measured using catheter occlusion technique by experienced
radiologist. Patients were classified in to 4 12mmHg (clinically significant
portal hypertension), and 512mmHg HPVG groups. Cut-off values were established by ROC analysis.
RESULTS: Strong correlation of liver stiffness R 0.74 (p50.01) and moderate
correlation of spleen stiffness R 0.52 (p5 0.01) with HVPG were established.
To determine the patients with HVPG 4 12mmHg, liver TE cut-off value
18.5kPa had sensitivity 0.91 and specificity 0.74; spleen TE cut-off value 57.0
kPa had sensitivity 0.75 and specificity 0.77. Area under the ROC curve was 0.90
for liver TE and 0.83 for spleen TE.

United European Gastroenterology Journal 2(1S)


Strong correlation of liver stiffness R 0.61 (p50.01) and moderate correlation
of spleen stiffness R 0.48 (p5 0.01) with oesophageal varices grade were
established. To predict the presence of oesophageal varices liver TE cut-off
value 21.5kPa had sensitivity 0.86 and specificity 0.83; spleen TE cut-off value
57.0 kPa had sensitivity 0.73 and specificity 0.75. Area under the ROC curve was
0.86 for liver TE and 0.76 for spleen TE.
CONCLUSION: Liver transient elastography strongly correlates and spleen TE
moderately correlates with HVPG and oesophageal varices grade. Liver TE
accurately predicts significant portal hypertension and oesophageal varices in
patients with chronic liver disease and is more sensitive and specific than
spleen TE. Therefore liver transient elastography could be reproducible outpatient screening tool for portal hypertension or oesophageal varices.
Disclosure of Interest: None declared
P0609 NUTRITIONAL EVALUATION OF THE CIRRHOTIC PATIENT
WITHOUT ASCITES: IS THERE A ROLE FOR ANTHROPOMETRIC
PARAMETERS?
S.M. D. Giestas1,*, A. Giestas1, C. Agostinho1, C. Sofia1
1
Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal
Contact E-mail Address: silviagiestas@gmail.com
INTRODUCTION: Malnutrition due to chronic liver disease is common and its
assessment is difficult. The anthropometric parameters, often used in clinical
practice, have limited use in the nutritional evaluation of cirrhotic patients
mainly those with ascites/edema. Some studies demonstrate that Maastricht
Nutritional Index (MI) is the best assessment in early stages of the disease,
however the best method of nutritional evaluation in cirrhotic patients remains
controversial.
AIMS & METHODS: Aim: To determinate the role for anthropometric parameters in the nutritional evaluation of cirrhotic patients without ascites and
compare it with the MI.
Patients and Methods: Prospective study of cirrhotic outpatients without ascites
(diagnosis based on histological evidence and/or high clinic/ biochemical /imagiological suspicion). Exclusion criteria: enteric nutrition, amputation, malabsorption syndrome, chronic pancreatitis, inflammatory bowel disease, chronic kidney
disease, acquired immunodeficiency syndrome, neuromuscular diseases and
oncologic advanced disease. Included patients where classified according ChildPugh Score; weight (kg), height (cm) and body mass index (BMI) were evaluated;
and based in MI they were stratified in mild (40-3), moderate (43-6) and severe
(46) impaired nutritional status.
RESULTS: 50 cirrhotic patients were included in the study, 84% (n 42) had
alcoholic cirrhosis, the mean age was 58/-11.4 years and 60% were male
(n 30). Concerning cirrhosis severity: 88% (n 44) were Child-Pugh A and
12% (n 6) Child-Pugh B. 8% (n 4) had a BMI518.5%, regardless of age,
gender or etiology. MI detected malnourishment/malnutrition in 38% (n 19) of
patients: 24% (n 12) mild and 14% (n 7) moderate impaired nutritional
status. In MI evaluation no statistically difference was found between etiology,
gender and age. No association between malnutrition and disease severity (ChildPugh Score) was found with both methods.
CONCLUSION: In this study anthropometric parameters underestimate malnutrition in cirrhotic patients when compared with the Maastricht Nutritional
Index, which detected malnutrition in early stages of hepatic disease.
Disclosure of Interest: None declared
P0610 EFFICACY
OF
TRANSJUGULAR
INTRAHEPATIC
PORTOSYSTEMIC SHUNT FOR THE PREVENTION OF VARICEAL
REBLEEDING IN CIRRHOTIC PATIENTS WITH PORTAL VEIN
THROMBOSIS
P. Chen1, Y. Zhuge1,*
Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical
School, China, Nanjing,Jiangsu, China
Contact E-mail Address: 304293942@qq.com
1

INTRODUCTION: Although several studies have elucidated the beneficial


effects of TIPS on PVT in patients with cirrhosis[1, 2, 3] in short term, it is
regrettable that the long term effects of TIPS in cirrhotic patients with PVT is
not very clear, especially in patients with a history of oesophageal and gastric
varices bleeding, therefore the aim of this retrospective study was to evaluate the
feasibility, safety, and efficacy of TIPS for the prevention of variceal rebleeding
in cirrhotic patients with PVT.
AIMS & METHODS: Aim The aim of this study was to evaluate the efficacy of
TIPS for the prevention of variceal rebleeding in cirrhotic patients with PVT
retrospectively.
Methods Forty consecutive cirrhotic patients with a history of variceal bleeding
were referred for TIPS between August 2008 and December 2013. All patients
were diagnosed with non-malignant PVT, including 37 partial PVT and 3 portal
cavernoma. Patients were followed until last clinical evaluation, diagnosis of
hepatocellular carcinoma, liver transplantation, or death.
RESULTS: TIPS were successfully placed in 85% of patients (34/40), 86.5% (32/
37) in patients with partial PVT and 66.7% (2/3) with portal cavernoma, without
complication or TIPS-related mortality. Patients with successful TIPS were followed up for a mean of 12.9 months (range1-37 months) and portosystemic
pressure gradient (PSG) was reduced from a mean 21.6 4.0 to 14.4 5.2mm
Hg after TIPS placement, the decreasing amplitude of PSG reached 29.4% 
5.0% from baseline. The 1- and 2-year cumulative variceal rebleeding rates were
11.8% and 48.5% in the success group and 16.7% and 37.5% in the failure
group, respectively (p 0.438). The only independent predictor for variceal
rebleeding in the success group was TIPS shunt flow velocity. The cumulative
rate of TIPS dysfunction at 1-and 2-year was 11.8% and 31.4%. Hepatic

A301

United European Gastroenterology Journal 2(1S)


encephalopathy occurred in 44.1% (15/34) of patients, and all of them happened
within the first year after TIPS. The 1- and 2-year cumulative survival rates were
80.1% and 49.9% in the success group and 100% and 75.0% in the failure group,
respectively (p 0.471).
CONCLUSION: TIPS placement is safe, feasible and has a fairly high success
rate to prevent variceal rebleeding in cirrhotic patients with PVT. Moreover,
TIPS can highly decrease the risk of variceal rebleeding because of the reduction
of PSG, and the only independent predictor for variceal rebleeding was TIPS
shunt flow velocity. We suggest TIPS should be considered a viable treatment
option for cirrhotic patients with PVT, especially in patients with a high risk of
variceal rebleeding.
REFERENCES
1. Han G, et al. Transjugular intrahepatic portosystemic shunt for portal vein
thrombosis with symptomatic portal hypertension in liver cirrhosis. J Hepatol
2011; 54: 78-88.
2. Perarnau JM, et al. Feasibility and long-term evolution of TIPS in cirrhotic
patients with portal thrombosis. Eur J Gastroenterol Hepatol 2010; 22: 10931098.
3. Luca A, et al. Short- and long-term effects of the transjugular intrahepatic
portosystemic shunt on portal vein thrombosis in patients with cirrhosis. Gut
2011; 60: 846-852.
Disclosure of Interest: None declared
P0611 CO-LOCALIZATION OF HBX AND COXIII PROMOTES HL-7702
CELL PROLIFERATION THROUGH CROSSTALK AND SYNERGY
OF COX-2 AND B-CATENIN SIGNAL PATHWAYS
B. Zheng1,*, X. Fang1, L. Zou2, D. Li1, Y. Huang1, Z. Chen1, L. Zhou3,
X. Wang1
1
Gastroenterology, 2Infection, Union Hospital of Fujian Medical University, 3 Lab
of Electron Microscopy, Fujian Medical University, Fuzhou, China
Contact E-mail Address: drzhengby@163.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most
common malignant diseases, and HBx leads to the development of HBV-associated HCC. Our recent studies have revealed that HBx can interact with the
inner mitochondrial membrane protein, COXIII, by yeast two-hybrid system,
mating experiment and coimmunoprecipitation.
AIMS & METHODS: To futher explore the co-localizaiton of HBx and COXIII
in HL-7702 cell and to investigate the molecular mechanism of HBx in HL-7702
cell proliferation. A HL-7702 cell line stably expressing the HBx gene by lentivirus vectors were constructed. Confocal microscopy was utilized to assess the
interaction between HBx protein and COXIII. The functional relevance of HBx
proteinCOXIII interaction was investigated in cell cultures.
RESULTS: Our studies first demonstrated that HBx co-localized with the inner
mitochondrial protein, COXIII, in HL-7702 cells, causing the up-regulation of
COXIII protein expression as well as COX activity. HBx elevated the generation
of mitochondrial ROS and ROS was necessary for it to activate the expression of
COX-2. Moreover, HBx promoted cell proliferation through COX-2/-catenin
signaling pathways.
CONCLUSION: Collectively, the major finding of this study is that the colocalization of HBx and COXIII leads to the changes of mitochondrial biogenesis
and morphology. Besides, COX-2 and -catenin signal pathways stimulated by
mitochondrial ROS have crosstalk and synergy in the oncogenesis of HBV-associated HCC.
REFERENCES
1. Tian Y, Yang W, Song J, et al. Hepatitis B virus X protein-induced aberrant
epigenetic modifications contributing to human hepatocellular carcinoma pathogenesis. Mol Cell Biol 2013; 33: 2810-2816.
2. Xu C, Zhou W, Wang Y, et al: Hepatitis B virus-induced hepatocellular
carcinoma. Cancer Lett 2013.
3. Wang XZ, Li D, Tao QM, et al. A novel hepatitis B virus X-interactive
protein: cytochrome C oxidase III. J Gastroenterol Hepatol 2006; 21: 711-715.
4. Li D, Wang XZ, Yu JP, et al. Cytochrome C oxidase III interacts with
hepatitis B virus X protein in vivo by yeast two-hybrid system. World J
Gastroenterol 2004; 10: 2805-2808.
Disclosure of Interest: None declared
P0612 RISK FACTORS ASSOCIATED WITH MORTALITY
HEPATITIS E RELATED ACUTE LIVER FAILURE DURING
PREGNANCY

IN

S. Sharma1,*, A. Kumar1, P. Kar2, S. Agarwal3, S. Prasad1


1
Obstetrics and Gynaecology, 2Medicine, 3Biochemistry, Maulana Azad Medical
College, Delhi, India
Contact E-mail Address: sheetal02sharma@gmail.com
INTRODUCTION: HEV infection is fatal during pregnancy. The mortality rate
in pregnant women with ALF is 15-20%, which is associated with an altered
status of hormones and difference in immune response.
AIMS & METHODS: Aim of the study is to determine biochemical and haemotological factors associated with mortality in Hepatitis E related acute liver
failure during pregnancy. A total of 73 consecutive ALF pregnant patients with
HEV infection were recruited in the study during July 2008 to August 2013 and
patients were followed up until death or complete recovery. Patients with viral
co-infections and with history of pre-existing liver disease were excluded.
Biochemical and pathological parameters included detailed liver function tests
(AST, ALT, alkaline phosphatase and total serum bilirubin), total proteins,
prothrombin time and complete haemogram. All the cases were screened for
hepatitis virus markers by ELISA. ROC curve was drawn to predict cut-off
level of serum albumin in ALF pregnant patients.

RESULTS: The mean maternal age and gestational at delivery were 25.32
3.62years and 29.534.62 weeks respectively. Forty six out of 73 (63.01%)
ALF pregnant patients were non survived and twenty seven out of 73
(36.98%) were survived. HEV was found to be the commonest cause of ALF
in pregnancy. It was found that in univariate logistic regression analysis AST,
ALP, bilirubin, prothrombin time, total protein and albumin were the statistically significant factors between survival and non-survival group. A multivariate
logistic regression analysis was performed using significant independent variables, and it was found that variables that independently predicted mortality
were serum alkaline phosphatase (OR 5.21, 95% CI 1.27-21.42; p50.05),
prothrombin time (OR 6.47, 95% CI 1.6924.77; p50.01), serum albumin
(OR 7.85, 95% CI 1.73-35.55; p 0.01) and serum total protein (OR 3.88;
95% CI 1.0114.94; p50.05). A receiver operating characteristic curve was
drawn for serum albumin. The area under the curve was 0.643. The serum
albumin level of 2.1g/dl was found to be the cut-off for ALF pregnancy patients
with 67% sensitivity and 63% specificity.
CONCLUSION: Serum albumin, serum total protein, serum alkaline phosphatase and prothrombin time were significant independent risk factors associated
with mortality in ALF pregnant patients.
Disclosure of Interest: None declared
P0613 FAVORABLE
ANTIVIRAL
EFFECT
OF
NUCLEOSIDE
ANALOGUES REDUCES HEPATOCELLULAR CARCINOMA
DEVELOPMENT IN HIGH RISK PATIENTS WITH CHRONIC
HEPATITIS B VIRUS INFECTION
A. Kawano1,*, S. Onohara2, H. Shigematsu1, K. Miki1, T. Maruyama1,
H. Nomura3, S. Shimoda2 on behalf of Fukuoka Study Group for the Treatment
of Liver Diseases
1
Department of Internal Medicine, Kitakyushu Municipal Medical Center,
Kitakyushu, 2Department of Medicine and Biosystemic Science, Graduate School
of Medical Sciences, Kyushu University, Fukuoka, 3The Center for Liver Disease,
Shin-Kokura Hospital, Kitakyushu, Japan
Contact E-mail Address: k-akira1971july@jcom.home.ne.jp
INTRODUCTION: Chronic hepatitis B virus (HBV) infection leads to cirrhosis
and hepatocellular carcinoma (HCC). Recently, HCC risk scales enable us to
estimate the risk of developing HBV related HCC (REACH-B score, Lancet
Oncol 2011;12:568). The objective of this study was to evaluate the on-treatment
predictive factors of nucleoside analogues (NAs) to reduce HBV related HCC
development for the high risk patients of chronic HBV infection in Japan, where
genotype C is the most prevalent.
AIMS & METHODS: This study was retrospective cohort study including the
patients treated with NAs for at least 12 months. The patients were applied into
REACH-B score and risk scores were generated based on sex, age, serum ALT
concentration, HBeAg status, and serum HBV DNA level. The favorable
responses of NAs were defined as each of these cases, (1)decrease in serum
ALT levels to within the normal range by 24 weeks, (2)decrease in HBV DNA
less than 4.0 log copies/mL by 24 weeks, (3) achievement of HBeAg seroconversion or (4)decrease in HBsAg less than 100 IU/mL. We compared the incidence
of HCC between favorable responder and poor responder.
RESULTS: A total of 76 Japanese patients with nucleoside-na ve chronic HBV
infection were included. Thirty two patients were started with lamivudine, 44
patients were started with entecavir. Mean treatment duration was 1387 days
(range 374-4360). Mean pre-treatment HBV DNA and ALT levels were 7.14 log
copies/mL and 282 IU/L, respectively. The mean age was 50.011.9 years and 47
(61.8%) patients were male. Forty (52.6%) patients were HBeAg positive, 18
patients (23.7%) had clinical evidence of liver cirrhosis. Genotype C was the
most prevalent (43 of 48, 89.6%). Nine patients developed HCC during followup. All 9 patients were from the group whose REACH-B scores were 11 points or
more (52 patients, defined as high risk patients, in this study). Of the high risk
patients, those who had achieved HBeAg seroconversion reduced HCC development significantly (p 0.0478). The cumulative HCC incidence rates at 5-year
were 4.7% and 40.0% for the patients who achieved HBeAg seroconversion
(favorable responder) and those who did not (poor responder), respectively.
CONCLUSION: The high risk patients still have the risk of developing HCC.
NAs can reduce HCC development for the high risk patients with chronic HBV
infection (Hepatology 2013;58:98). From our study, favorable antiviral effect (for
example, achievement of HBeAg seroconversion) of NAs may reduce HCC
development in the high risk patients with chronic HBV infection.
Disclosure of Interest: None declared
P0614 PREVIOUS INTERFERON THERAPY DOES NOT LEAD TO A
BETTER VIROLOGICAL RESPONSE IN PATIENTS TREATED
WITH ENTECAVIR: A COHORT STUDY
C.M. Preda1,*, C. Baicus2, L. Tugui1, S. V. Olariu1, A. Andrei1, N. Grecu1,
M.M. Diculescu1
1
Gastroenterology and Hepatology, Institutul Clinic Fundeni, 2Internal Medicine,
N. Ghe. Lupu Hospital, Bucharest, Romania
Contact E-mail Address: preda_monicaa@yahoo.com
INTRODUCTION: Entecavir (ETV) is a potent inhibitor of HBV replication.
AIMS & METHODS: The aim of the study was to explore if previous interferon
(IFN) therapy might influence response to Entecavir in chronic hepatitis B.
A retrospective cohort study was performed, including all subjects who received
ETV for chronic hepatitis B, in the south-Eastern Romania. We assessed viral
response, HBeAg loss and seroconversion, HBsAg loss and seroconversion, biochemical response. Comparison of categorical data was performed by c2-test or
Fishers exact were applicable.

A302
RESULTS: 533 patients were followed for a median period of 24 months. The
cohort was 64% male, 23% HBeAg-positive, 23% IFN-pretreated, 17%
Lamivudine-pretreated, 8% cirrhotics. At baseline, the median hepatitis B
virus DNA was 5.95 (interquartile range 1.08-9.97) log10 IU/ml. At week 48,
71% of the patients (32% HBeAg-positive; 82% HBeAg-negative) achieved a
virological response and 91% (78% HBeAg-positive; 95% HBeAg-negative) of
those with elevated baseline alanine aminotransferase showed a biochemical
response. Thirty-two per cent (39/123) of the HBeAg-positive patients lost
HBeAg and 23% (28/123) achieved seroconversion to anti-HBe. Positive predictive factors for virologic response are: low score of fibrosis (p-0.006), low level of
HBV DNA (p-0.003). Negative predictive factors for virologic response are: HBe
antigen positive status (OR odds ratio 0.15, 95%CI confidence interval 0.070.30; p-value50.001), prior IFN therapy. (OR 0.45, 95% CI 0.24-0.86; p-value
0.015). Baseline level of ALT, age, sex, previous Lamivudine therapy had no
impact on virologic response. Virological breaktrough was found in 0.8% of
patients. Seven patients (1.31%) showed clearance of hepatitis B surface antigen.
CONCLUSION: ETV maintained and even increased the high initial response
rate (from 71% to 90.6%). Low score of fibrosis, low level of HBV DNA, HBe
antigen negative status, absence of prior interferon therapy predict a good virologic response. Lamivudine-resistant patients usually respond well to ETV, but
15.62% are non-responders, suspect of Entecavir resistance.
REFERENCES
1. European Association for the Study of the Liver. EASL Clinical Practice
Guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012,
http://dx.doi.org/10.1016/j.jhep.2012.02.010
2. Caruntu FA, Streinu-Cercel A, Gheorghe LS, et al. Efficacy and safety of
peginterferon alpha-2a (40 kD) in Hbe Ag-positive chronic hepatitis B patients.
J Gastrointestin Liver Dis 2009; 18: 425-431.
3. Shouval D, Lai C-L, Chang T-T, et al. Three years of entecavir (ETV) retreatment of HbeAg-negative ETV patients who previously discontinued ETV
treatment: results from study ETV-901. Hepatology 2008; 48: 722A.
4. Gheorghe L, Csiki IE, Iacob S, et al. The prevalence and risk factors of
hepatitis B virus infection in Romania: a nationwide survey. Eur J
Gastroenterol Hepatol 2013; 25: 56-94.
5. Buti M, Morillas RM, Prieto M, et al. Efficacy and safety of entecavir in
clinical practice in treatment-naive Caucasian chronic hepatitis B patients. Eur
J Gastroenterol Hepatol 2012; 24: 535-542.
Disclosure of Interest: None declared
P0615 BENEFITS
OF
LONGER
DURATION
NUCLEOS(T)IDE
ANALOGUES THERAPY IN PATIENTS WITH CHRONIC
HEPATITIS B: A NATIONWIDE COHORT STUDY
C.-Y. Wu1,*, J.-T. Lin2, H.J. Ho2, T.-Y. Lee1, J.-C. Wu3
1
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung,
2
School of Medicine, Fu Jen Catholic University, New Taipei City, 3School of
Medicine, National Yang-Ming University, Taipei, Taiwan, Province of China
Contact E-mail Address: dr.wu.taiwan@gmail.com
INTRODUCTION: Nucleos(t)ide analogues (NUCs) therapy reduced the risk of
hepatitis B virus (HBV) disease progression. However, whether NUCs long-term
therapy is more effective than short-term therapy remains controversial.
AIMS & METHODS: We conducted a nationwide cohort study based on
Taiwans National Health Insurance Research Database (NHIRD) between
October 1, 2003 and December 31, 2011. Among the CHB patients, we used
propensity scores to match 8,631 patients with NUCs therapy for at least 1.5
years (long-term therapy cohort) with 8,631 patients with NUCs therapy for at
least 90 days, but less than 1.5 years (short-term therapy cohort). Major outcomes, including liver decompensation, hepatic failure, or overall mortality,
between the 1.5 and 3 years after date of starting NUCs therapy were analyzed.
Cumulative incidences and multivariable analyses were calculated after adjusting
for competing mortality.
RESULTS: Compared with short-term therapy cohort, long-term therapy cohort
had significantly lower risk of liver decompensation (1.05%; 95% confidence
interval [CI], 0.81-1.30% vs. 2.13%; 95%CI, 1.82-2.45%; P50.001), hepatic failure (0.35%; 95% CI, 0.21-0.49% vs. 0.63%; 95% CI, 0.46-0.80%; p 0.008), and
overall mortality (1.67%; 1.37-1.98% vs. 2.44%; 95% CI, 2.10-2.77%; P50.001).
After adjusting for competing mortality and other confounders, long-term therapy was associated with a reduced risk of liver decompensation (adjusted hazard
ratio, aHR: 0.47; 95%CI, 0.36-0.62, P50.001), hepatic failure (aHR: 0.53;
95%CI, 0.33-0.86, p 0.01) and overall mortality (aHR: 0.67; 95% CI, 0.530.84, p 0.001).
CONCLUSION: NUCs long-term therapy was associated with reduced risks of
liver decompensation, hepatic failure and overall mortality in CHB patients.
Disclosure of Interest: None declared
P0616 THE INACTIVE HBV-CARRIER PROFILE: THE LONG-TERM
OUTCOME
H. Zejly1,*, R. Afifi1, Y. Cherradi1, H. Benbrahim1, I. Benelbarhdadi1,
F.Z. Ajana1, W. Essamri1, A. Essaid ElFeydi1
1
Hepatogastroenterology (Medecine C), Ibn Sina Hospital, Rabat, Morocco
Contact E-mail Address: hindzejly@gmail.com
INTRODUCTION: The inactive HBV profile is one of the aspects of natural
history of chronic hepatitis B (HVB). We aimed to define epidemiological, clinical and virological features of inactive HVB-carriers and to evaluate their longterm outcome
AIMS & METHODS: Its a monocentric and descriptive study including 575
chronic HVB-carriers - over 18 years old- followed since 1998. The inactive HBV
profile was defined by normal serum aminotransferases, HBeAg-negative state

United European Gastroenterology Journal 2(1S)


and DNA levels 52000 IU/ml. We excluded patients with HIV and/or HCV coinfection and alcohol consumers. HBV-reactivation was defined by an HVB
DNA load up to 2000 IU/ml. All clinical, biological and serological data were
collected. Serum HBV DNA levels were measured using real-time PCR quantification assays. Liver biopsy was indicated according to international
recommendations
RESULTS: Of 575 considered patients, the inactive HVB-carriers represented
49.7% (n 286). Mean age was 35.5 years old [18-63], male gender was prominent (sex-ratio 1.93). Mean time of follow-up was 6 years [1- 15]. The most
probable ways of HVB transmission were unprotected sexual practices and
unsafe tooth-care (respectively 57 % and 34.5%). Ultrasonography found an
heterogeneous hepatic parenchyma in 12% and steatosis in 4%. Liver biopsy
was indicated in 6 patients: fibrosis was less than F2 according to Metavir
score. HVB-reactivation was reported in 2 patients (0.01%) which indicates antiviral treatement. Spontaneous HBsAg loss was achieved in 5 patients. No case of
hepatocellularcarcinoma was reported.
CONCLUSION: Our real-life experience confirms that the inactive HVB profile is associated to less complications and better long-term outcome.
Disclosure of Interest: None declared
P0617 ANTIVIRAL EFFICACY OF ENTECAVIR VERSUS ENTECAVIR
PLUS ADEFOVIR FOR HEPATITIS B VIRUS RTA181V/T MUTANTS
ALONE
M.J. Oh1,*
1
Department of Internal Medicine, CHA Gumi Medical Center, CHA University
School of Medicine, Gumi, Korea, Republic Of
Contact E-mail Address: zenus1@hanmail.net
INTRODUCTION: Hepatitis B virus (HBV) rtA181V/T mutants developed by
long-term nucleos(t)ide analogues therapy are known to confer cross-resistance
for other nucleos(t)ide analogues, except entecavir (ETV). Although ETV has
primarily been used as rescue therapy for rtA181V/T mutants, some studies have
reported that rtA181V/T mutants could induce cross-resistance to ETV. In practice, a clinical investigation reported that rtA181V/T mutants might confer HBV
DNA persistence, and showed an association with incomplete response, despite
rescue therapy with ETV.
AIMS & METHODS: The aim of this study was to investigate antiviral efficacy
of ETV alone and in combination with adefovir (ADV) as rescue therapy for
HBV rtA181V/T mutants alone. A total of 30 patients who received ETV (1.0
mg/day) monotherapy or ETV plus ADV (10 mg/day) therapy over 48 weeks
against HBV rtA181V/T mutants only without other concomitant mutation
between April 2008 and October 2011 were enrolled. The subjects were divided
into the ETV group (n 16) and the ETV ADV group (n 14). Virological,
biochemical, and serological response after 48 weeks of rescue therapy were
investigated retrospectively.
RESULTS: No significant difference in baseline characteristics, including serum
HBV DNA levels (4.8  1.7 vs. 4.1  1.8log10IU/mL) and the rate of HBeAg
positivity (93.8 vs. 100%) was observed between the two groups (p40.05).
Virological response at 48 weeks showed complete virological response (serum
HBV DNA 5 20 IU/mL) (62.5 vs. 42.9%), partial virological response (6.3 vs.
28.6%), non-response (25.0 vs. 28.6%), and virological breakthrough (6.3 vs.
0%), respectively. No statistical significance was observed in virological response
(p 0.278). No significant difference in mean reduction of serum HBV DNA and
biochemical response rates was observed between both groups, respectively (4.3
 2.9 vs. 4.1  1.8log10IU/mL; p 0.294, 88.9 vs. 100%; p 1.000). In addition,
no significant difference in HBeAg loss or seroconversion was observed between
the two groups (26.7 vs. 28.6%; p 1.000).
CONCLUSION: As rescue therapy for HBV rtA181V/T mutants alone, ETV
monotherapy was clinically as effective as ETV plus ADV therapy.
REFERENCES
1. Villet S, Pichoud C, Billioud G, et al. Impact of hepatitis B virus rtA181V/T
mutants on hepatitis B treatment failure. J Hepatol 2008; 48: 747-755.
2. Warner N and Locarnini S. The antiviral drug selected hepatitis B virus
rtA181T/sW172* mutant has a dominant negative secretion defect and alters
the typical profile of viral rebound. Hepatology 2008; 48: 88-98.
Disclosure of Interest: None declared
P0618 HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B
PATIENTS UNDER ANTIVIRAL TREATMENT - RISK FACTORS
AND THE PERFORMANCE OF A VALIDATED PREDICTIVE RISK
SCORE
P. Magalhaes-Costa1,*, L. Lebre1, M. Bispo1, T. Bana1, P. Peixe1, C. Chagas1
1
Gastrenterology, Hospital Egas Moniz - Centro Hospitalar Lisboa Ocidental,
Lisboa, Portugal
Contact E-mail Address: pmagalhaescosta@gmail.com
INTRODUCTION: Antiviral therapy reduces but does not eliminate the risk of
hepatocellular carcinoma (HCC) in chronic hepatitis B patients with or without
cirrhosis. Retrospective or prospective observational cohort studies that provide
HCC data for patients mainly treated with tenofovir are lacking.
AIMS & METHODS: We performed a single-center retrospective cohort study
of 120 patients with chronic hepatitis B (age, 4714; 83 male), 20% (n 24) with
clinical cirrhosis, who were treated with tenofovir 300mg daily (n 85; 72%) or
entecavir 0.5/1mg daily (n 33; 28%) for at least 12 months. Patients co-infected
with hepatitis C virus or human imunodeficiency virus were excluded. Univariate
and multivariate analysis of risk factors associated with HCC development were
performed. Accuracy of a recent validated HCC-risk score (REACH-B) was
assessed.

United European Gastroenterology Journal 2(1S)


RESULTS: Our population was mainly caucasian (n 80; 67%) and african
(n 37; 31%). The most common serological profile was AgHBe negative
(n 82; 73%). 69 patients (60%) were treatment-na ve. Alcohol abuse was
reported in 14 patients (12%). The rates of biochemical, total and partial virological response were: 96.5%, 89.2% and 8.3%. The mean time under antiviral
therapy was 4119 months. After a 8254 months of follow-up, 9 patients
(7.6%) developed HCC. The 1 and 3-year cumulative incidence of HCC was
2.7% and 11.1%. Patients who developed HCC were older (p 5 0.001), alcoholics (p 5 0.05), cirrhotic at baseline (p 5 0.05; OR 15.469; 95%CI: 3.45469.272) and displayed a higher REACH-B score at baseline (p 5 0.05). On an
univariate analysis, a REACH-B baseline score  8 predicted relatively well HCC
occurrence (p 0.071; OR 6.352; 95%CI: 0.754-53.486) however, a score  12
points predicted better (p 5 0.05; OR 10.595; 95%CI: 2.275-49.338). Gender,
ethnic origin, AgHBe status, baseline viremia, previous treatment and time under
antiviral therapy were not associated with HCC occurrence. Through logistic
regression, multivariate analysis identified as risk factors associated with HCC
occurrence: cirrhosis at baseline (p 0.016; OR 7.975; 95%CI: 1.464-43.432) and
REACH-B score baseline  12 (p 0.015; OR 7.603; 95%CI: 1.480-39.070). The
1 and 3-year cumulative incidence of HCC in patients with REACH-B score
baseline  8 was 7.4% and 16.8%, while a score  12 confered a risk of
12.6% and 42.7%, respectively. By Kaplan-Maier analysis, excluding alcohol
abusers, patients who scored  8 points in REACH-B had a significantly
higher risk of developing HCC (p 0.029) compared with those with 5 8
points. At baseline, the REACH-B score performed well, with a AUC of 0.811
(95%CI: 0.668-0.954). A cut-off score of  8 (at baseline) yielded 87.5% sensitivity, 47.6% specificity, 11.5% positive predictive value (PPV) and 98% negative
predictive value (NPV).
CONCLUSION: Even with long periods under antiviral therapy, the occurrence
of hepatocellular carcinoma in patients with chronic hepatitis B remains a problem. In our cohort, HCC mostly occured in older ( 50 y/o) and alcohol consuming patients, probably with an underlying cirrhotic liver. The performance of
REACH-B score (with a cut-off  8) in non-alcoholic patients seems to perform
well in predicting the risk of developing HCC.
Disclosure of Interest: P. Magalhaes-Costa: None declared, L. Lebre: None
declared, M. Bispo: None declared, T. Bana: None declared, P. Peixe Lecture
fee(s) from: Gilead, Bristol-Myers Squibb, Roche and Bayer, Consultancy for:
Gilead, Bristol-Myers Squibb, Roche and Bayer, C. Chagas Lecture fee(s) from:
Abbvie
P0619 REACTIVATION OF HEPATITIS B VIRUS IN HBSAG-NEGATIVE
HBCAB-POSITIVE PATIENTS WITH PSORIASIS UNDERGOING
IMMUNOSUPPRESSIVE THERAPY
R. Granata1,*, N. Balato2, F. Ayala2, M. Guarino1, S. Labella2, F. Auriemma1,
I. Loperto1, N. Caporaso1, F. Morisco1
1
Department of Clinical Medicine and Surgery, Gastroenterology Unit,
2
Department of Clinical Medicine and Surgery, Dermatology Unit, University of
Naples "Federico II", Naples, Italy
Contact E-mail Address: filomena.morisco@unina.it
INTRODUCTION: Viral hepatitis reactivation has been widely reported in
patients undergoing immunosuppressive therapy; however, few data are available
on the risk of HBV reactivation in patients with psoriasis receiving immunosuppressive drugs.
AIMS & METHODS: We conducted a retrospective study to value the effect of
immunosuppressive therapy on HBV infection in psoriatic patients.
The study included all consecutive psoriatic patients who attended an Italian
tertiary referral hospital from 2008 to 2012. A total of 412 patients were consecutively enrolled. We evaluated: HBV markers, type of immunosuppressive
treatment and the occurrence of HBV reactivation. Reactivation was defined
as reappearance of HBsAg, increase in HBV-DNA at least 1 log in comparison
to basal level, in association with or without increase of aminotransferase levels.
The observational period ranged from the beginning of immunosuppressive
treatment to 6 months after the end of therapy.
RESULTS: A total of 225/412 (54.6%) patients with psoriasis and receiving
immunosuppressive therapy (cyclosporine or methotrexate, and/or biological
drugs, such as adalimumab, infliximab, etanercept, golimumab, ustekinumab)
were tested for markers of HBV infection. We identified 23/225 subjects
(10.2%) with isolated HBcAb positivity and 36/225 (16%) with HBcAb/
HBsAb positivity. No patient was HBsAg positive. No patient underwent preemptive therapy with Lamivudine or other antiviral drugs. No patient showed
episodes of HBV reactivation.
CONCLUSION: In dermatological setting the immunosuppressive therapy, in
HBcAb and HBcAb/HBsAb patients, seems to be safe regardless to the type
of treatment schedule.
Disclosure of Interest: None declared
P0620 SPANISH MULTICENTRE STUDY PIBHE: PREVALENCE OF
HEPATITIS B VIRUS INFECTION AND IMMUNIZATION IN
HEMODIALYSIS PATIENTS
S. Aoufi Rabih1,* on behalf of Dialysis Virus Group of the Spanish Society of
Nephrology, R. Garc a Agudo2 on behalf of Dialysis Virus Group of the Spanish
Society of Nephrology, G. Barril Cuadrado3 on behalf of Dialysis Virus Group
of the Spanish Society of Nephrology, F. Perez Roldan1, P. Gonzalez Carro1 on
behalf of Dialysis Virus Group of the Spanish Society of Nephrology
1
Gastroenterology and Hepatology, 2Nephrology Department, La Mancha-Centro
Hospital, Alcazar de San Juan, Ciudad Real, 3Nephrology Department, La
Princesa Universitary Hospital, Madrid, Spain
Contact E-mail Address: samiaoufi@hotmail.com

A303
INTRODUCTION: The estimated prevalence for chronic hepatitis B virus
(HBV) infection is 0-10 % in hemodialysis patients, with wide variations geographically and between units in the same country. The estimated prevalence in
Spain was 3.1 % in 2003. Immunization in the vaccinated patients is 40-70 %
compared to 97% of the general population.
AIMS & METHODS: National multicenter cohort study, approved by the
Ethics and Clinical Investigation Committee of the coordinating center, conducted between January 2013 and January 2014. The aim of this study was to
determine the prevalence of HBV in hemodialysis patients in Spain and their
situation regarding immunization. A case report form was sent to all the hemodialysis units of Spain to collect information about the patients after informed
consent. The data were included in a central database.
RESULTS: One hundred and forty two hemodialysis units participated (104
hospitals, 38 satellite centers). Of the 13,845 patients included, 125 were HBVpositive, resulting in a prevalence of 0.9%. A third of the centers had a HBVpositive patient. The mean age was 66.6 (20-98) in the HBV-negative patients and
45.5 years old in HBV-positive patients (26-72).
In HBV-positive patients, 17.3 % were coinfected with hepatitis C and/or human
immunodeficiency viruses. 70 % of patients had positive antiHBe. 82% had a
viral load below 2,000 IU/ml. The AST and ALT levels were 18.3  10.5 IU / ml
and 14.5  9 IU / ml, respectively. 8.7 % had undergone a liver biopsy; 32% had
received antiviral treatment; 37.5 % were candidates for renal transplantation
and 65.2 % were followed for Gastroenterology.
In HBV-negative patients, 33.6 % had not been vaccinated; 14.2% had positive
anti-HBc. Fourteen different vaccination schedules were used. The immune
response stood at 66.4 %. The levels of anti-HBs after vaccination were 10-99
mIU/ml in 29.5 %, 100-999 mIU/ml in 23.9% and equal to or greater than 1000
mIU/ml in 8.4%. More than a half (56.7%) had received a vaccination course;
22.6 %, two cycles; 0.6%, three cycles; and 9.5%, an annual booster. The most
likely to achieve an immune response was achieved with four doses of 40 mcg of
adjuvanted vaccine (OR 4.9), for the same age and number of revaccination
cycles and boosters. Age and dose and adjuvant vaccine usage influenced the
immune response and the title of antiHBs reached (p 5 0.05). 81.1 % of
researchers agreed that the questionnaire had helped them to assess the management of HBV infection that performed on their patients.
CONCLUSION: Prevalence of chronic HBV infection in hemodialysis in Spain
is low, and so are the rates of immunization against HBV. The vaccination
schedules are diverse and have been correlated with the immune response. It
would be necessary to formalize the most effective schedule in increasing immunization in these patients.
Disclosure of Interest: None declared
P0621 REACTIVATION OF HBV INFECTION IN HBSAG NEGATIVE
ONCOHAEMATOLOGICAL PATIENTS TREATED WITH
CHEMOTHERAPY CONTAINING OR NOT RITUXIMAB
S. Camera1,*, M. Picardi2, N. Pugliese2, G. Maria1, A. Vitiello1, M. Raimondo2,
I. Loperto1, C. Nicola1, F. Pane2, F. Morisco1
1
Department of Clinical Medicine and Surgery, Gastroenterology Unit,
2
Department of Clinical Medicine and Surgery, Haematology Unit, University of
Naples "Federico II", Naples, Italy
INTRODUCTION: Routine prophylaxis for hepatitis B reactivation is recommended for oncohaematological HBsAg subjects undergoing immunosuppressive therapy, due the risk of reactivation. In particular, HBV reactivation occurs
more frequent in patients receiving Rituximab. Nonetheless,the incidence in
those receiving Rituximab-free therapy needs to be better investigated
AIMS & METHODS: This study evaluates the effects of chemotherapy with or
without Rituximab in patients HBsAg negative/HBcAb positive with NonHodgkin Lymphoma (NHL) or Hodgkin Lymphoma (HL).
123 patients (21 with NHL and 102 with HL) were consecutively enrolled. We
evaluated HBV markers, treatment schedule and occurrence of HBV reactivation
(reappearance of HBsAg, increase in HBV-DNA at least 1 log in comparison to
basal level with or without increase of aminotransferase levels during therapy and
6 months after the end of therapy).
RESULTS: 46 patients (M/F 24/22, median age 49 yrs, range 21-74 yrs), 33 with
isolated HBcAb and 13 with HBcAb/HBsAb positivity, were observed. Six/46
were treated with therapeutic schedule containing Rituximab. Five/6 received
successfully preemptive therapy with Lamivudine. HBV reactivation was
observed in the only patient (HBcAb/HBsAb positive) treated with R-CHOP
without Lamivudine prophylaxis. None of the other 40 patients treated with
cytotoxic chemotherapy without Rituximab (ABVD-VEBEP) and without
receiving preemptive therapy, showed HBV reactivation.
CONCLUSION: HBV reactivation is mainly related to the type of therapy. Our
data revealed that patients with occult HBV infection receiving chemotherapy
with Rituximab, in absence of prophylactic therapy, may be at high risk of
reactivation. Otherwise, prophylaxis is not mandatory in patients HBcAb positive with or without HbsAb positivity undergoing Rituximab-free schedule. This
results suggest that preemptive therapy will be tailored to the cytotoxic chemotherapeutic schedule.
Disclosure of Interest: None declared

A304

United European Gastroenterology Journal 2(1S)

P0622 HEPATITIS B SEROLOGIC MARKERS AFTER 14 YEARS OF


UNIVERSAL NEW-BORN VACCINATION
S. Carvalhana1,2, R. Pinto3, J. Leitao4, A.P. Silva5, C. Alves6, M. Bourbon6,
A. Carvalho4, H. Cortez-Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e
metabolismo, FML, 3Hospital Prisional de S. Joao de Deus, Caxias, Lisbon,
4
Internal Medicine, CHUC, Coimbra, 5Gastroenterology, CHVNG, Vila Nova de
Gaia, 6INSA, Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: The burden of hepatitis B infection around the world is very
high. In Portugal, hepatitis B vaccination was part of the National Vaccination
Programme, with vaccination of all adolescents, since 1995, extended to all newborns in the year 2000. The aim of the present study was to evaluate how it
affected serological markers of hepatitis B in the general population and in highrisk groups.
AIMS & METHODS: Prevalence of HBs Ag was evaluated in a sample of three
groups: adult general population (GP): 989 individuals, prison population (PP):
784, and drug-users (DU): 18305. Prevalence of HBsAg, HBsAb, HBcAb, and
ALT and AST serum levels were determined in the general population.
RESULTS: Prevalence of HBsAg was GP: 12/989(1.2%); PP: 32/784 (4.1%) and
DU: 927/18305 (5.0%). In the GP, the prevalence of HBsAg negative, HBsAb
positive with HBcAb negative (suggesting effective previous vaccination) was:
315/989 (31.8%), with mean age: 38.8 years. Furthermore two thirds of the
individuals aged less than 30 years had the latter pattern. Prevalence of
HBcAb positive was 107/989 (11%): in 29 (2.9%) cases isolated, and in 75
(7.5%) associating with HBsAb positive, the latter suggesting past infection.
CONCLUSION: Prevalence of HBs Ag was higher in the risk populations,
although no major differences were found. There is evidence of effective vaccination status in the younger population. Emphasis on continuing universal hepatitis
B programmes is of utmost importance.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
P0623 IL28B POLYMORPHISM CORRELATES WITH
HEPATITIS IN HBEAG-POSITIVE CHRONIC HEPATITIS B
PATIENTS

ACTIVE

Y.K. Jung1,*, S.K. Shin2


1
Internal Medicine, Korea University Ansan Hospital, Gyenggi-do, 2Internal
Medicine, Gachon Gil Hospital, Incheon, Korea, Republic Of
Contact E-mail Address: 93cool@hanmail.net
INTRODUCTION: In recent studies, polymorphisms near the IL28B gene are
strongly associated with spontaneous and treatment-induced viral clearance in
chronic hepatitis C patients. However, the role of IL28B in the prediction of
treatment outcome in chronic hepatitis B (CHB) patients and association with
the natural course of CHB is currently debated. This study aimed to determine
the relationship between IL-28B polymorphisms and hepatitis activity in CHB.
AIMS & METHODS: 190 treatment-na ve CHB patients were identified and
IL28B related SNPs were determined by pyrosequencing method. Active hepatitis in patients without liver cirrhosis was defined as persistent ALT 4 2 x upper
limit of normal (ULN) for over 3 months or a peak ALT level 4 5x ULN. In
patients with liver cirrhosis, active hepatitis was defined as persistent ALT4
ULN for over 3 months.
RESULTS: 143 patients were enrolled and 41(38%) had active hepatitis.
rs12979860 CC and rs8099917 TT were 87%. and the two SNPs were found to
be in strong linkage disequilibrium (D 1.0, r2 0.9082). The IL28B SNP
rs12979860 minor allele T and rs8099917 minor allele G were correlated
with active hepatitis in patients with HBeAg positve CHB (p 0.029). On the
contrary, in HBeAg negative CHB there was no relationship between IL28B
SNPs and active hepatitis.
CONCLUSION: We could find that host immune response related to IL28B
polymorphism considering viral factor like genotype plays an important role in
active hepatitis in HBeAg positive CHB patients.
Disclosure of Interest: None declared
P0624 TREATMENT OF HEPATITIS C IN PRISON IN FRANCE IN 20112012: MORE PATIENTS TREATED IN FEWER MEDICAL
JAILHOUSE UNITS: RESULTS OF NATIONAL PRACTICE SURVEY
A.J. Remy1,* on behalf of UCSA DE FRANCE
1
hepatogastroenterology, centre hospitalier, perpignan, France
Contact E-mail Address: andre.remy@ch-perpignan.fr
INTRODUCTION: In France inmates health care was done by public hospitals
since 1994. Access to antiviral treatment was normally equal as people outside.
Treatment of hepatitis C was until 2011 dual therapy (peg-interferon and ribavirin); in 2011, two direct antiviral agents (AAD), telaprevir INCIVO* and
boceprevir VICTRELIS*, were available in triple therapy. National 2005 study
of practices had demonstrated that at time of dual therapy, only 14 % of inmates
with hepatitis C were treated. Recent national health institute studies (PRI2DE
and PREVACAR) did not allow to answer the question of percentage of inmates
treated for hepatitis C. Did arrival of triple therapy increase or decrease patients
percentage treated in prison?
AIMS & METHODS: Our objective was to study in national survey, in retrospective vision (since compassionate use of AAD in January 2011) and prospective vision over 2011 and 2012, number of patients treated by dual therapy and
triple therapy in MJU. It was postal and/or mail survey.

RESULTS: On December 31th 2013, 77 MJU over 182 participated and were
already analyzed: they took care of 38998 inmates; hepatitis screening was systematically proposed in 100 % of MJU; 30290 serology C were annually realized
in 2011 and 31580 in 2012; 2012 rate was 4.5 % positivity (677 patients).
Followed patients were 1579 in 2011 and 1717 in 2012; 49 % of MJU had regular
hepatology consultation (one per month to two per week) and 33 % regular
infectious diseases consultation; to evaluate liver fibrosis 227 FIBROSCAN*
and 511 FIBROTEST / FIBROMETRE were realized in 2012 but only 2 liver
biopsy. In 2011, 301 patients were treated (19 % of patients with serology C
positive) and in 2012, 497 patients (29 %). Triple therapy constituted 12 % of
treatment in 2011 and 39 % in 2012 (telaprevir 80/72 %, boceprevir 20/28 % in
2011/2012); 42 % of the MJU introduced no treatment in 2011 (77 % any triple
therapy) and 56 % in 2012 (66 % any triple therapy).
CONCLUSION: These results allowed following conclusions: 1/ frequent positive patients VHC in jailhouses, 2/ good screening and diagnosis and using widely
not invasive methods of fibrosis 3/ but very different practices for hepatitis
treatment between few MJU treating a lot of patients and a lot of MJU treating
none. Compared with national study of 2005, percentage of treated patients was
doubled but percentage of MJU involved decreases in 45 %. A score of care of
people infected by hepatitis C will be calculated from answers to items screening,
specialized consultation, treatments 2011 and treatments 2012.
REFERENCES
Coquelicot 2004. Jauffret-Roustide, et al. BMC Infect Dis 2009; 9-113.
Coquelicot 2011. Jauffret-Roustide, et al. BEH 2013; 39-40: 504-509.
Remy, et al. Presse Med 2005; 35: 1249-1254.
Meffre, et al. INVS, http://www.invs.sante.fr/publications/2006/prevalence_b_c/
vhb_france_2004.pdf
Prevacar.
http://www.sante.gouv.fr/IMG/pdf/Enquete_PREVACAR_
-_Volet_offre_de_soins_-_VIH_hepatites_et_traitements_de_substitution_en_
milieu_carceral_octobre_2011.pdf
PRI2DE Michel, et al. BEH 39: 409-411.
Disclosure of Interest: A. J. Remy Financial support for research from: ROCHE
JANSSEN, Consultancy for: ROCHE JANSSEN
P0625 SAFETY COMPARISON OF 12- AND 24-WEEK TREATMENTS IN
HCV GENOTYPE 1-INFECTED PATIENTS WITH CIRRHOSIS:
RESULTS FROM TURQUOISE-II
H. Wedemeyer1,*, X. Forns2, A. Craxi3, N. Reau4, P. Kwo5, S. Bourgeois6,
M. Bennett7, S. Ryder8, D. Larrey9, D. Mutimer10, S. Lovell11, M. Abunimeh11,
M. Pedrosa11, R. Trinh11
1
Medizinische Hochschule Hannover, Hannover, Germany, 2Liver Unit, Hospital
Clinic, IDIBAPS, CIBEREHD, Barcelona, Spain, 3A. O. U Policlinico "P.
Giaccone" Dip. Di Gastroenterologia ed Epatologia D. B. M. I. S., Palermo, Italy,
4
University of Chicago Medical Center, Chicago, 5Indiana University, Indianapolis,
United States, 6ZNA Stuivenberg, Antwerpen, Belgium, 7Medical Associates
Research Group, San Diego, United States, 8Nottingham Digestive Diseases Centre
and Biomedical Research Unit, Nottingham, United Kingdom, 9CHU de
Montpellier, Hopital Saint Eloi, Montpellier, France, 10Queen Elizabeth Hospital
and NIHR Liver Biomedical Research Unit, Birmingham, United Kingdom,
11
AbbVie Inc., North Chicago, United States
INTRODUCTION: Interferon-containing protease inhibitor regimens have been
associated with a high rate of serious adverse events (AEs) in patients with
cirrhosis.1 We report the safety of the 3 direct-acting antiviral (3D) regimen of
ABT-450 (identified by AbbVie and Enanta) co-dosed with ritonavir (r), ombitasvir (formerly ABT-267) and dasabuvir (formerly ABT-333) with ribavirin
(RBV) in the treatment of 380 HCV genotype 1-infected patients with cirrhosis.
AIMS & METHODS: Patients were randomized to receive the 3DRBV regimen for 12 (N 208) or 24 weeks (N 172). Key eligibility criteria included:
Child-Pugh A cirrhosis, platelet count 60.000 cells/mm3, serum albumin 2.8
g/dL, and total bilirubin 53 mg/dL. Treatment-emergent AEs from the time of
study drug administration until 30 days after last dose for all patients who
received 1 dose of study drug are reported.
RESULTS: The percentage of patients experiencing any AE, severe, or serious
AEs were similar in both arms. AEs were mostly mild or moderate in severity.
The most common AEs in the 12- and 24-wk arms respectively, were fatigue
(32.7% vs. 46.5%), headache (27.9% vs. 30.8%), and nausea (17.8% vs.
20.3%). Four (1.1%) patients experienced AEs consistent with hepatic decompensation but were considered unrelated to study drugs. Five of 380 (1.3%)
patients experienced serious AEs that were assessed by the investigator to have
reasonable possibility of being related to the 3D regimen. All patients who modified RBV dose for any reason, 4 patients who received erythropoietin, and 2
patients who received a transfusion all achieved SVR12.

Treatment-Emergent AEs, n (%)

12-Wk
3DRBV
(N 208)

24-Wk
3DRBV
(N 172)

Any AE
Severe AE
Serious AE
AE Leading to Study Discontinuation
AE Leading to RBV Dose Reduction
Death

191 (91.8)
14 (6.7)
13 (6.3)
4 (1.9)
17 (8.2)
0a

156 (90.7)
13 (7.6)
8 (4.7)
4 (2.3)
22 (12.8)
0

a
One patient died due to non-treatment emergent AEs that began 80 days after
the last dose of study drug.

United European Gastroenterology Journal 2(1S)

A305

CONCLUSION: The 3DRBV regimens were generally well tolerated, with no


clinically significant differences in safety profiles based on treatment duration.
AEs reported in this study of 380 patients with cirrhosis were generally consistent
with those demonstrated for the 3DRBV regimen in previous studies of patients
without cirrhosis.
REFERENCES
1. Hezode C, Fontaine H, Dorival C, et al. J Hepatol 2013; 59: 434-441.
Disclosure of Interest: H. Wedemeyer Financial support for research from:
Abbott, BMS, MSD, Novartis, Roche, Lecture fee(s) from: Abbott, AbbVie,
Achillion, BMS, Boehringer Ingelheim, Gilead, GSK, ITS, Janssen, Merck,
Novartis, Roche, Roche Diagnostics, Siemens, Transgene, Consultancy for:
Abbott, AbbVie, Achillion, BMS, Boehringer Ingelheim, Gilead, GSK, ITS,
Janssen, Merck, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, X.
Forns Financial support for research from: Roche, MSD, Consultancy for:
Janssen, MSD, Gilead, AbbVie, A. Craxi: None declared, N. Reau: None
declared, P. Kwo Financial support for research from: AbbVie, Anadys,
Bristol Myers Squibb, Conatus, Gilead, Merck, Novartis, Roche, Vertex,
Consultancy for: AbbVie, Bristol Myers Squibb, Gilead, Johnson and
Johnson, Merck, Novartis, Vertex, Other: Gilead, Merck, Vertex, S. Bourgeois
Financial support for research from: Roche, Janssen, MSD, Consultancy for:
Gilead, AbbVie, Janssen, BMS, M. Bennett Shareholder of: AbbVie, S. Ryder
Financial support for research from: AbbVie, Consultancy for: Boehringer
Ingelheim, MSD, Conatus, Gilead, D. Larrey: None declared, D. Mutimer
Consultancy for: AbbVie, Gilead, Janssen, BMS, S. Lovell Shareholder of:
AbbVie, Other: AbbVie, M. Abunimeh Shareholder of: AbbVie, Other:
AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: AbbVie, R. Trinh
Shareholder of: AbbVie, Other: AbbVie

groups, was 132 months (range: 67-290). There was no statistical differences
between groups regarding age, gender, ethnic origin, previous dialytic support
(or kind of dialytic support) or primary kidney disease. HCV infected patients
remained longer on dialysis waiting-time period (median: 60 months; P25/75: 48/
132) and were younger at transplantation timing (3712 y/o). Imunossupressive
regimens using calcineurin inhibitors (75% vs 40%; p 5 0.05) and azathioprine
(44% vs 16%; p5 0.05) were more frequently applied on HCV infected patients.
On the other hand, there was a significant lesser use of tacrolimus (28% vs 55%;
p 5 0.05). Regarding hospitalization (69% vs 65%), septic complications (35%
vs 43%), primary allograft disfunction (31% vs 26%), new-onset diabetes after
transplant (4% vs 13%) or malignancy, there were no significant differences
between groups. A higher frequency of major cardiovascular events was detected
on HCV infected group (32% vs 9%; p 5 0.05). The global rate of allograft loss
was significantly higher among HCV group (50% vs 20%; p 5 0.05). The 1, 5
and 10 year-allograft survival rate in HCV group was 94.1%, 78.1% and 66.9%;
for the sample group: 94.9%, 89.1% and 80.4%. Using a survival model
(Kaplan-Meier), there was no statistical difference (log rank test: p 0.154) in
allograft survival between HCV positive and negative patients. In order to isolate
the effect of HCV on allograft survival we used a Cox regression model, showing
that HCV infection, althought negatively impacted on allograft survival (HR:
1.657; IC95%: 0.817-3.364; p 0.162), that effect had no statistical significance.
CONCLUSION: Our findings suggest that, whilst HCV may play an ominous
effect on allograft survival of renal transplants, its global effect is minor. Hence,
in light of our findings, renal transplantation in HCV infected patients seem to
foretell similar allograft survival as that in general population.
Disclosure of Interest: P. Magalhaes-Costa: None declared, L. Lebre: None
declared, D. Machado: None declared, C. Chagas Lecture fee(s) from: Abbvie

P0626 STUDY ON IL28B SNP RS12979860 AND SNP RS8099917


GENOTYPING AND TREATMENT RESPONSE WITH PEGYLATED
INTERFERON AND RIBAVIRIN IN EGYPTIAN PATIENTS WITH
CHRONIC HEPATITIS C VIRUS INFECTION

P0628 ASSOCIATIONS OF REACTIVE OXYGEN SPECIES AND IRON


METABOLISMS WITH DEVELOPMENT OF HEPATOCELLULAR
CARCINOMA AFTER PEGYLATED INTERFERON THERAPY IN
JAPANESE PATIENTS WITH CHRONIC HEPATITIS C

M.A. Amin1,*, N. Algarem1, D. Sabri2, E. Qasem3, E. hasan4


1
internal medicine, 2biochemistry, Cairo University, 3internal medicine, 4pathology,
National liver institute, Cairo, Egypt
Contact E-mail Address: monasleman@hotmail.com

S. Nanba1,*, F. Ikeda1, H. Seki1, K. Yamamoto1


1
Department of Gastroenterology and Hepatology, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, okayama, Japan

INTRODUCTION: Hepatitis C virus (HCV) infection is a common universal


problem especially in the Arab world. A single nucleotide polymorphism near the
IL28B gene on chromosome 19 coding for interferon-lambda-3 is associated with
an approximately 2-fold difference in SVR rates among patients of different
ethnicities.
AIMS & METHODS: The aim was to assess the value of IL28B SNP rs12979860
and SNP rs8099917 as a predictor of virological response to Pegylated interferon
plus ribavirin in treatment of Egyptian patients with chronic hepatitis C virus
infection. Our study included 604 HCV infected Egyptian patients with genotype
4. All patients received pegylated Interferon 2a and 2b plus ribavirin. We divided
our cases according to their response to treatment into two groups: group I (344
patients) responded to treatment and group II (260) non responder patients.
Analysis of both IL28 rs8099917 and IL28rs12979860 by real time PCR technique were done to all patients.
RESULTS: TT genotype of IL28 rs8099917 was associated with a higher
response rate to treatment than other genotypes. TT genotype was present in
53.2% of responders Vs 17.7% of non responders (P50.001) while GG genotype
was present in 6.4% of responders Vs 37.7% of non responders (P50.001). T
allele was present in 73.4% of responders Vs 40 % in non responders while G
allele were present in 26.6% of respnders Vs 60% in non responders (P50.001).
The response rate was lower in patients with T allele compared to those with C
allele of IL28 rs12979860 and CC genotype were present in 47.4% of responders
Vs 5% of non responders and TT genotype were present in 6.1% of responders
Vs 33.1 % of non responders (P50.001). The C allele was present in 70.6% of
responders Vs 36% of non responders while T allele was present in 29.4% of
responders Vs 64% of non responders (P 5 0.001).
CONCLUSION: IL28B polymorphisms are strong predictors of virological
response in chronic hepatitis C with genotype 4 and analysis of IL-28B genotype
might be used to guide treatment for these patients.
Disclosure of Interest: None declared

INTRODUCTION: Chronic hepatitis C (CHC) may induce reactive oxygen


species (ROS) and excessive iron deposition in the liver.
AIMS & METHODS: The present study was planned to clarify the impact of
surplus ROS and iron deposition on virological response to the therapy with
pegylated interferon plus ribavirin and development of hepatocellular carcinoma
(HCC) thereafter for CHC patients. A total of 210 CHC patients who received
combination therapy of pegylated interferon and ribavirin are enrolled. Liver
histology was evaluated for all the patients before the therapy. Hepatic ROS
was assessed with immunohistochemical staining of 8-hydroxy-2-deoxyguanosine
(8-OHdG). Hepatic iron deposition was assessed by Prussian blue staining.
Factors associated with hepatic 8-OHdG levels were analyzed by stepwise logistic
regression analysis. Proportional hazard models were utilized to identify patient
characteristics associated with HCC development after interferon therapy.
RESULTS: Severe hepatic iron deposition was significantly associated with high
level of 8OHdG in stepwise logistic regression analysis (p 50.0001). Interferon
therapy resulted in sustained virological responses (SVR) in 104 patients. Hepatic
8OHdG was significantly associated with SVR in univariate analysis for the
patients with HCV genotype 1, without statistical significance in multivariate
analysis. Hepatic iron deposition showed no significant associations with SVR
for the patients with HCV genotypes 1 or 2. During the follow-up after interferon
therapy (median period of 4.6 year), HCC development was observed in 14
patients (16%). Heavy alcohol drinking, low platelet counts, non-SVR and
high levels of hepatic 8OHdG had significant associations with HCC development (p 0.0276, 0.0102, 0.0067, and 0.0003, respectively).
CONCLUSION: Hepatic 8OHdG level was useful in prediction of HCC development after interferon therapy for CHC patients.
Disclosure of Interest: None declared
P0629 HCV AND HBV PREVALENCE IN THE POPULATION: LARGE
DISPARITY BETWEEN HEPATITIS C IN THE GENERAL
POPULATION, COMPARING WITH HIGH RISK GROUPS

P. Magalhaes-Costa1,*, L. Lebre1, D. Machado2, C. Chagas1


1
Gastrenterology, Hospital Egas Moniz - Centro Hospitalar Lisboa Ocidental,
2
Nephrology and Renal Transplantation, Hospital Santa Cruz, Lisboa, Portugal
Contact E-mail Address: pmagalhaescosta@gmail.com

S. Carvalhana1,2, R. Pinto3, J. Leitao4, A.P. Silva5, C. Alves6, M. Bourbon6,


A. Carvalho4, H. Cortez-Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e
metabolismo, FML, 3Hospital prisional de Sao joao de Deus, Caxias, Lisbon,
4
Internal medicine, CHUC, Coimbra, 5Gastroenterology, CHVNG, Vila Nova de
Gaia, 6INSA, Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com

INTRODUCTION: The long-term impact of hepatitis C virus (HCV) infection


on kidney allograft survival remains controversial. Some studies found a significant deleterious effect of HCV infection on allograft survival and also higher
mortality in this group of patients.
AIMS & METHODS: In this retrospective, single-center study, we aimed to
compare the differences in kidney allograft survival over a long-term follow-up
period between non-infected vs infected patients. Study population (HCV
infected patients) was selected from a kidney transplant center database (1985 2013) and compared to a random sample extracted from the same database.
Groups were compared using Chi-square test, student-T test, Mann-Whitney
U test and survival methods (Kaplan-Meier) when appropriate. Statistical analyses were carried using SPSS 20.0 IBM@ (Chicago, IL, United States).
RESULTS: We identified 34 patients with HCV infection and the random
sample population was 80 patients. The mean follow-up period, for both

INTRODUCTION: The burden of hepatitis B and C infections around the world


is high. With the upcoming very effective treatments for hepatitis C and the
rather effective treatments for hepatitis B, there is urge to identify these patients
and estimate their prevalence in each country.
AIMS & METHODS: Hepatitis B and C prevalence was evaluated in a sample of
three groups: adult general population (GP): 989 individuals, prison population
(PP): 784, and drug-users (DU): 19832. HBsAg, HBsAb, HBcAb, anti-HCV
(Cobas, Roche), ALT and AST were done. In the general population, antiHCV positive individuals were tested for HCV PCR.
RESULTS: Prevalence of Anti-HCV was: GP: 5/989 (0.5%); PP: 147/784
(18.8%) and DU: 11862/19839 (59.8%). Prevalence of HBsAg was GP: 12/
989(1.2%); PP: 32/784 (4.1%) and DU: 927/18305 (5.0%). Interestingly,
among individuals that were anti- HCV positive in the GP, only 20% were
HCV PCR positive. In Portugal, adult GP is estimated about 8 600 000

P0627 IMPACT OF HEPATITIS C VIRUS ON ALLOGRAFT SURVIVAL


AFTER RENAL TRANSPLANTATION

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United European Gastroenterology Journal 2(1S)

individuals, PP are about 14 000, and DU are about 30 000. So, according to the
percentages found, it is expected that we have about 69 000 individuals with antiHCV, and it is expected that 105 000 are HBs Ag positive. It is possible that the
prevalence of HCV PCR positive individuals is much lower in the general asymptomatic population. Even assuming a 50% prevalence of HCV RNA positive
among anti-HCV positive patients, it would result in about 34 500 individuals
with active infection and potentially needing treatment. Prevalence of elevated
aminotransferases among patients with either hepatitis B or C in the GP was not
different from those with negative markers (17.6% vs. 8.1%, p n.s.).
CONCLUSION: Hepatitis C showed high disparity in prevalence according to
the risk groups, with low prevalence on the general population and very high in
risk groups. Differently, the prevalence of hepatitis B showed a more homogeneous pattern of distribution. These results suggest that screening for hepatitis C
in the general population is not cost-effective, but risk groups such as drug-users
or people in prisons should be regularly screened.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
P0630 THE MITOGEN-ACTIVATED PROTEIN KINASE
INVOLVED IN HEPATOCELLULAR CARCINOMA CELL
PROLIFERATION IN VITRO AND IN VIVO

ERK5

IS

G. Di Maira1, E. Rovida2,3, N. Navari1, S. Cannito4, P. Dello Sbarba 3,


M. Parola4, F. Marra1,*
1
Dip. Medicina Sperimentale e Clinica, 2University of Florence, Florence, Italy,
3
Dip. Patologia Oncologia Sperimentale, University of Florence, Florence, 4Dip.
Medicina Oncologia Sper. Universita` di Torino, University of Turin, Turin, Italy
Contact E-mail Address: giovanni.dimaira@unifi.it
INTRODUCTION: Despite great progress in the diagnosis and management of
hepatocellular carcinoma (HCC), the molecular mechanisms underlying the
tumor development and progression remain poorly understood, overall limiting
the patients outcome. ERK5 is a member of the MAPK family and has been
implicated in fundamental biologic processes relevant for tumor development.
AIMS & METHODS: The aim of this study is to evaluate the relevance of this
pathway ERK5 in HCC biology.
Huh-7 and HepG2 were cultured by standard methods. ERK5 was silenced by
siRNA transfection or with shRNA and lentiviral vectors. The specific ERK5
inhibitor XMD8-92 was also used. In vivo development of HCC was evaluated
using the Huh-7 xenograft model in athymic nude mice.
RESULTS: In vitro experiments demonstrated that ERK5 silencing or specific
inhibition, using an inhibitor called XMD8-92, causes growth arrest of HCC
cells, affecting in particular the G1/S transition. This phenotype was associated
with an increase in p27Kip protein expression a critical negative regulator of cell
cycle progression typically expressed in G0/G1 arrested cells. Additionaly knock
down of ERK5 activity induces a marked inhibition of c-Rel expression, a
member of NFk family required for the normal proliferative regeneration of
hepatocytes. In a mouse model of HCC xenograft, administration of XMD8-92
significantly decreased tumor volume This reduction is associated with a reduced
proliferation, as observed by Brdu incorporation assay. Moreover XMD8-92treated xenografts the expression of c-Jun, a proto-oncogene essential for cell
proliferation, was reduced compared to control samples. Finally as already
observed in vitro, XMD8-92 treatment induced a strong decrease of c-Rel transcription factor expression.
CONCLUSION: This study disclose a strong regulation of cell proliferation in
HCC, affecting the biological activity of different oncogenic targets. Affecting
this pathway could be considered a novel and effective approach for the treatment of HCC.
Disclosure of Interest: None declared
P0631 HEAT SHOCK FACTOR 1 (HSF1) INVOLVEMENT IN TUMOUR
RECURRENCE AFTER RADIOFREQUENCY ABLATION IN AN
ANIMAL MODEL OF SECONDARY LIVER CANCER
F. Zanieri1, V. Carloni1, S. Omenetti1, C. Amabile2, N. Tosoratti2, S. Cassarino2,
S.S. S. Velandy3, M. Kester3, M. Pinzani4, K. Rombouts4,*
1
Department of Experimental and Clinical Medicine and Center of Excellence for
the study at molecular and clinical level of chronic, degenerative and neoplastic
diseases to develop novel therapies DENOthe, University of Florence, Florence,
2
R&D Unit, Hospital Service S.p. A, Aprilia, Italy, 3Department of Pharmacology,
Penn State University College of Medicine, Hershey, United States, 4Division of
Medicine, University College of London, Institute for Liver & Digestive Health,
Royal Free, London, United Kingdom
Contact E-mail Address: k.rombouts@ucl.ac.uk
INTRODUCTION: Heat shock factor 1 (HSF1), is the master regulator of genes
encoding molecular chaperones and is involved in cellular processes such as stress
response, cell differentiation and carcinogenesis. Recent studies identified a
HSF1-regulated transcriptional program specific to high malignancy and distinct
from the classical HSF1-induced heat shock response. We investigated the
expression of HSF1 during tumour formation and after Radiofrequency
Ablation (RFA) in vivo. In vitro experiments were employed to mimic radiofrequency ablation and to analyse the effect of shRNA-HSF1-nanoliposomes as
a possible adjuvant thermo-sensitizing therapy in combination with radiofrequency ablation (RFA) in metastatic liver cancer.
AIMS & METHODS: Colon carcinoma CT26 cells, expressing HSF1, HSP70
and HSP90, were used to assess shRNA-HSF1-nanoliposomal uptake, toxicity/
efficiency by employing immunofluorescence, Q-PCR and protein analysis.
In vitro sub-lethal heat experiments were performed to mimic radiofrequency
ablation, and this by using different time points/temperatures. An orthotopic
murine model of coloncarcinoma cancer - liver metastasis was used to analyse

HSF1 expression during tumour formation. Radiofrequency ablation (RFA) in


small animals was optimized to investigate the HSF1-induced-and related signalling pathways in the treatment of liver metastasis.
RESULTS: shRNA-HSF1-nanoliposomes were taken up by 99% of cells without inducing cytotoxicity. Sub-lethal heat treatment of 45 and 50 degrees Celsius
induced p-ERK, p-AKT and HSF1-related proteins at different timepoints investigated and this coincided with a nuclear to cytosolic shift of HSF1, HSP70/90,
AKT and ERK. Apoptosis was only significantly induced after 10 days post-heat
treatment. In vivo, tumours highly expressed HSF1, HSP70/90, AURBK and pERK and p-AKT. Radiofrequency-ablated tumours showed an increase in HSF1
and HSP70/90 protein expression after 6 and 10 days post-RFA, suggesting the
involvement of HSF1 during the process of tumour recurrence.
CONCLUSION: This study demonstrates that HSF1 is highly expressed in CRC
liver metastasis and suggest its possible involvement in tumour recurrence after
employing radiofrequency ablation.
Disclosure of Interest: F. Zanieri: no conflict to declare, V. Carloni: no conflict to
declare, S. Omenetti: no conflict to declare, C. Amabile: no conflict to declare, N.
Tosoratti: no conflict to declare, S. Cassarino: no conflict to declare, S. S. S.
Velandy: no conflict to declare, M. Kester: no conflict to declare, M. Pinzani: no
conflict to declare, K. Rombouts: no conflict to declare
P0632 BASIC FIBROBLAST GROWTH FACTOR MEDIATES ACQUIRED
RESISTANCE TO SORAFENIB IN HEPATOMA CELLS
M. Osawa1,*, Y. Matsuda2, T. Wakai3, M. Kubota1
1
Division of Pediatric Surgery, Niigata University Graduate School of Medical and
Dental Sciences, 2Department of Medical Technology, Niigata University Graduate
School of Health Sciences, 3Division of Digestive and General Surgery, Niigata
University Graduate School of Medical and Dental Sciences, Niigata, Japan
Contact E-mail Address: mamix.3211@gmail.com
INTRODUCTION: Sorafenib is a multikinase inhibitor used to treat patients
with hepatocellular carcinoma (HCC). The main obstacle to efficient cancer
treatment with this agent is the acquired drug resistance that develops in many
patients. We aimed to determine whether sorafenib-treated hepatoma cells
release soluble factors that cause sorafenib resistance.
AIMS & METHODS: HepG2 cells were incubated with sorafenib for 24 hours.
The culture medium was rinsed, the cells were maintained for 24 more hours, and
cytokines released into the medium were analysed by enzyme-linked immunosorbent assay. The culture medium was transferred to the newly seeded HepG2 cells,
which were then maintained with a different concentration of sorafenib for 2 to
48 hours. Cell growth and apoptosis in sorafenib-treated cells were analysed by
MTT and annexin V assay. Cell signalling was analysed by western blotting.
RESULTS: The level of basic fibroblast growth factor (FGF-2) in the culture
medium of sorafenib-treated cells was increased to 1.8-fold that of the controls
(14.3 vs. 7.7 pg/mL, respectively; p 5 0.05), while other growth factors such as
transforming growth factor beta and insulin growth factor were unchanged.
When the cells were maintained in the culture medium of sorafenib-treated
cells, the cell numbers were increased by 1.35-fold (p 5 0.05), and the levels of
phosphorylated Akt, extracellular signal-regulated kinases 1/2, and nuclear
factor kappa B were increased by 2.5- to 4.0-fold. The annexin V assay
showed that the effect of sorafenib on cell apoptosis was inhibited in the cells
maintained in the medium of sorafenib-treated cells (apoptotic rates after sorafenib treatment in control cells vs. cells maintained in the medium of sorafenibtreated cells: 76.5% vs. 17.7%, respectively; p 5 0.05), which was rescued by
pretreatment with the FGF receptor inhibitor PD173074.
CONCLUSION: FGF-2 might be an essential mediator of acquired resistance to
sorafenib. Combination treatment with sorafenib and FGF-2 inhibitor may be
effectively used to treat patients with HCC in the future.
Disclosure of Interest: None declared
P0633 HEPATOMA CELLS CAN BE REVERTED TO ORIGINAL
NORMAL CELLS BY SINGLE SMALL RNA
N. Miura1,*, S. Tsuno1, J. Hasegawa1
1
Pharmacotherapeutics, TOTTORI UNIV., Yonago, Japan
Contact E-mail Address: mnmiura@med.tottori-u.ac.jp
INTRODUCTION: The human ncRNA gene RGM249 regulates the extent of
differentiation of undifferentiated cancer cells. Because shRNA for RGM249
induced the upregulation of hsa-miR-520d that converted 293FT cells to
hiPSCs, we attempted to perform the functional analysis to examine the anticancer effects of it on an undifferentiated hepatoma cell.
AIMS & METHODS: To identify the crucial factors underlying this process, we
investigated the effects of lentivirally inducing miR-520d expression in HLF cells
(520d-HLF) in vitro. To clarify the underlying mechanism, we performed gene
expression analysis, cell cycle analysis, cell sorting, metabolomic analysis, migration assay and DNA methylation assay in transfectants. Subsequently, we evaluated tumor formation in a xenograft model using 520d-HLF.
RESULTS: 520d-HLF cells or the cells sorted by both alkaline phosphatase and
GFP were Oct4 and Nanog positive within 24 h, showed p53 upregulation and
hTERT downregulation, and mostly lost their migration abilities. Cell cycle
analysis revealed homogeneous growth and metabolomic analysis showed that
the TCA cycle was not elevated. Methylation level in transfectants decreased to
the similar level to that in hiPSC. After lentiviral infection, the cells were intraperitoneally injected into mice, resulting in benign teratomas (6%), the absence of
tumors (87%) or differentiation into benign liver tissues (7%) at the injection site
after 1 month.
CONCLUSION: We are the first to demonstrate the loss of malignant properties
in cancer cells in vivo through the expression of a single microRNA (miRNA).
This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like

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United European Gastroenterology Journal 2(1S)


cells partly or mainly via both stemness- and demethylation-mediated process.
The regulation of malignancy by miR-520d appears to be through the conversion
of cancer cells to normal stem cells, maintaining p53 upregulation.
Disclosure of Interest: None declared
P0634 MATRINE
INDUCED
MITOCHONDRIAL-DEPENDENT
APOPTOSIS AND AUTOPHAGY IN HEPATOMA CELLS
S. Yao1,* on behalf of Li Wang, Chun Gao
1
Department of Gastroenterology, China-Japan Friendship Hospital, Beijing,
China
Contact E-mail Address: shukyao@126.com
INTRODUCTION: Matrine is an active component monomer that is extracted
from Sophora flavescens. Our previous study found that matrine could induce
cell apoptosis, and dramatically increase the generation of autophagosomes in
hepatocellular carcinoma cell lines. Autophagy, a self-defense mechanism, has
been found to be associated with drug resistance in hepatocellular carcinoma
(HCC) therapy. However, the effect and exact mechanisms of matrine-induced
autophagy and apoptosis in therapy of HCC are still not very clear.
AIMS & METHODS: Our study was aimed to investigate the role and related
mechanisms of matrine-induced apoptosis and autophagy in hepatoma cells
HepG2 and Bel7402.
Cell apoptosis was detected by flow cytometry analysis (Annexin VFITC/PI
double-staining assay), JC-1 probe, the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the
effect of matrine on viability and proliferation of HCC cells. Autophagic flux in
HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1,
GFP-LC3 transfection and LysoTracker staining, and transmission electron
microscopy. Moreover, regarding to the associated mechanisms, Genechip technique was used to find matrine-induced autophagic related gene.
RESULTS: 1. Matrine at different concentrations could inhibit the viability and
proliferation of HepG2 and Bel7402 cells, and induce apoptosis in a concentration-dependent manner (p50.05).
2. Matrine could induce the decrease of mitochondrial membrane potential
(MMP) and up-regulation of cytochrome-c expression. After treated with
matrine, the expression of pro-caspase decreased and the cleaved caspase-8,-9,3 increased.
3. The turnover of LC3BI/IIratio, the increasing number of GFP-LC3 positive
cells (P50.05) and the formation of phagophores, autophagosomes, autolysosomes observed by transmission electron microscopy, implied that autophagy
was induced in matrine-treated HCC cells.
4. Genechip results showed that the level of lamp-1 elevated at 7.4 times. The
result was further proved by the detection of Realtime PCR and western blot.
Immunofluorescence results showed that Lamp-1 colocalized with lysosomes in
HepG2 cells, and localized at the autolysosomes after autophagy was induced.
CONCLUSION: 1. Matrine has the inhibitory effect of HCC celllines HepG2
and Bel7402,and could induce apoptotic cell death via mitochondrial mediated
caspase dependent way.
2. Matrine could induce autophagy in HepG2 and Bel7402 cells, and lamp-1 is
related to the formation of autolysosomes, and possibly involved in matrineinduced autophagy.
Disclosure of Interest: None declared
P0635 EXPRESSION OF FERRITIN LIGHT CHAIN IN HEPATIC OVAL
CELLS IS A USEFUL BIOMARKER OF HEPATOCELLULAR
CARCINOMA DEVELOPMENT
Y. Matsuda1,*, M. Osawa2, T. Wakai3, M. Kubota2
1
Department of Medical Technology, Niigata University Graduate School of
Health Sciences, 2Divisions of Pediatric Surgery, 3Digestive and General Surgery,
Niigata University Graduate School of Medical and Dental Sciences, Niigata,
Japan
Contact E-mail Address: yasunobu@med.niigata-u.ac.jp
INTRODUCTION: Hepatic oval cells are unique bipotential progenitor cells
that differentiate into both bile duct cells and hepatocytes. Although it has
been widely recognised that oval cell-derived hepatocytes are possible progenitors
of hepatocellular carcinoma (HCC), the functional properties of these cells are
unclear.
AIMS & METHODS: To investigate the protein expression profile in oval cellderived hepatocytes, we compared proteomes from lysates from normal hepatocytes and oval cell-derived hepatocytes using two-dimensional (2D) gel sodium
dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and matrixassisted laser desorption ionization time-of-flight tandem mass spectrometry
(MALDI-TOF/TOF MS). Hepatocytes were isolated from normal rat livers by
the collagenase perfusion method, while oval cell-derived hepatocytes were
obtained from cultured rat oval WB-F344 cells or rat littermates treated with
2-acetamidofluorene plus partial hepatectomy. To verify the results of 2D SDSPAGE, the protein expression levels of ferritin light chain (FLC) in human liver
tissue samples (33 patients without HCC and 28 with HCC) were examined by
western blotting and immunohistochemical analysis.
RESULTS: Two-dimensional SDS-PAGE showed 11 major protein spots that
changed in abundance between normal hepatocytes and oval cell-derived hepatocytes. Three of these differently expressed protein spots were analysed by
MALDI-TOF/TOF MS. The level of FLC expression was significantly higher
in oval cell-derived hepatocytes (7- to 10-fold, p 5 0.05). Western blotting of
human liver tissue samples showed that the levels of FLC expression were 4- to 8fold higher in patients with than without HCC. Immunohistochemical analysis
showed that hepatocellular FLC was strongly expressed in 21 of 28 patients with

HCC, while strong expression of FLC was detected in 12 of 33 patients without


HCC (p 5 0.05).
CONCLUSION: Several proteins, including FLC, are distinctly overexpressed in
oval cell-derived hepatocytes. FLC expression is increased in human liver tissues
adjacent to HCC, indicating that FLC might be a useful biomarker for identification of the development of HCC.
Disclosure of Interest: None declared
P0636 RNA BINDING PROTEIN NOVA1 PROMOTES TUMOR
GROWTH IN VIVO AND ITS POTENTIAL MECHANISM AS AN
ONCOGENE MAY DUE TO ITS INTERACTION WITH GABAAR2
Y. Zhang1,*, T. Liu1, X. Shen1
Gastroenterology, Zhongshan Hospital affiliated to Fudan University, Shanghai,
China
Contact E-mail Address: zyian2020@gmail.com
1

INTRODUCTION: Our previous study discovered the expression of Nova1 in


hepatocellular carcinoma and proved that high expression of Nova1 is associated
with poor prognosis of HCC. Recent research proved that Nova1 regulates the
alternative splicing of GABAA receptor 2(GABAAR2) pre-mRNA in central
nervous system. Moreover, the theory that the GABAergic system is involved in
HCC progression has also been illustrated before. However, the expression of
GABAAR2 and its relations with Nova1 in hepatocellular carcinoma remain
elusive.
AIMS & METHODS: The aim of this study is to explore the potential mechanism of Nova1 as an oncogene for HCC. To make clear the existence of interactions between Nova1 and GABAAR2 in HCC and their relations with
tumorigenesis. Immunohistochemical staining were used to identify the protein
expression level of GABAAR2 in HCC and its paired non-tumor tissue. Its
relations with clinicopathologic features were calculated. The HCC tumor xenografts animal models were established. The tumor size was estimated and then
removed for western blot analysis. For double immunofluorescence staining, the
slides were incubated with DyLight 448 Affinipure Rabbit Anti-Goat IgG and
DyLight 594 Affinipure Goat Anti-Rabbit IgG and analyzed via the microscope.
The cell-lysated proteins were precleared with 2 g anti-Nova1 or anti-GABA
AR2 antibodies and then incubated with protein G-agarose and antibodies. The
precipitates were analyzed by western blotting.
RESULTS: The expression level of GABAAR2 positive cell in the cancerous
tissue was lower than para-cancerous tissues. Univariate analysis and multivariate Cox analysis showed that intratumoral Nova1 was significantly associated
with OS and TTR. Patients with higher intratumoral GABAAR2 had longer OS
rate and TTR time. In vivo test, our results showed that, the volume of the
xenotrans in the over-expression group surpassed that in the control group,
and the volume of the xenotrans in the knockdown group far smaller than its
control group. Immunohistochemical staining and Western blot showed downregulation of Nova1 accompanied with increased expression of GABAAR2 and
GABA. Up-regulation of Nova1 resulted decreased expression of GABAAR2
and GABA. Furthermore, the localizations of GABA and GABAAR2 were
visualized under microscopy. The SMMC-7721 cells expressing the GABA and
GABAAR2 protein exhibited fluorenscence concentrated in the cytoplasm, and
also in the nucleus. Co-localization of Nova1 and GABAAR2 proteins in the
cytoplasm was evidenced by overlapping fluorescence signals in Huh7 cell. Co-IP
results showed that Nova1 was easily detected through anti-Nova1 antibody in
the GABAAR2-immunoprecipitates. Reciprocal co-IP experiments using antiNova1 antibody indicated the existence of GABAAR2, as confirmed by
immunoblotting.
CONCLUSION: Nova1 not only interacts with GABAAR2 in CNS but also in
the peripheral HCC tumor tissue. It is hypothesized that ectopic expression of
Nova1 may down regulate the expression of GABAAR2, and decrease the
influx of cl- and tumor cells membrane potential diffences, thus leading to the
proliferation of HCC.
Disclosure of Interest: None declared
P0637 EPIGENETIC SILENCING OF THE TUMOR SUPPRESSOR
MICRORNA-122 DURING HEPATOCARCINOGENESIS FROM
NONALCOHOLIC STEATOHEPATITIS
Y. Saito1,*, Y. Takaki1, K. Toshimitsu1, T. Muramatsu1, M. Kimura1,
H. Suzuki2, K. Sugiyama2, T. Kanai2, H. Saito1
1
Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy,
2
Division of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
INTRODUCTION: Nonalcoholic steatohepatitis (NASH) has emerged as a
common cause of chronic liver disease and virus-independent hepatocellular
carcinoma (HCC) in patients with obesity, diabetes and metabolic syndrome.
However, little is known about the pathogenesis of HCC derived from NASH.
AIMS & METHODS: To reveal the molecular mechanism underlying hepatocarcinogenesis from NASH, microRNA (miRNA) expression profiles were analyzed. HCCs and non-tumor liver tissues from STAM mice, an animal model
developing HCC from NASH, and tissue specimens obtained from primary HCC
patients were used in this study. MiRNA expression profiles were analyzed by
microarray and quantitative RT-PCR. To investigate the regulatory mechanism
of miRNAs, DNA methylation assay and chromatin immunoprecipitation
(ChIP) assay were performed in liver cancer cells treated with the DNA methylation inhibitor 5-aza-2-deoxycytidine (5-Aza-CdR).
RESULTS: Histopathological images of the liver in STAM mice at the ages of 6,
8, 12, 18 weeks showed findings compatible with fatty liver, NASH, liver cirrhosis (LC), and HCC, respectively. MiR-122 expression in non-tumor LC at the age
of 18 weeks was significantly lower than that in LC at the age of 12 weeks. MiR122 expression was further decreased in HCCs compared with non-tumor LC at

A308
the age of 18 weeks. MiR-122 expression was also decreased in clinical HCC
samples. Treatment of liver cancer cells with 5-Aza-CdR reactivated miR-122
expression with decreased cell proliferation and down-regulation of its target,
CyclinG1. The results of ChIP assay indicated that 5-Aza-CdR activated miR122 expression by enhancing binding of peroxisome proliferator activated receptor-gamma (PPAR-) to the miR-122 promoter region.
CONCLUSION: These findings indicate that epigenetic silencing of the tumor
suppressor miR-122 plays a critical role during hepatocarcinogenesis from
NASH. DNA methylation inhibitors such as 5-Aza-CdR may have clinical promise for the prevention and treatment of HCC derived from NASH.
Disclosure of Interest: None declared
P0639 PLASMA CYCLASE-ASSOCIATED PROTEIN 2 IS A NOVEL
BIOMARKER IN EARLY STAGE AND ALPHA-FETOPROTEIN
NEGATIVE HEPATOCELLULAR CARCINOMA PATIENTS
M. Chen1, Y. Yang1,*
1
Department of Gastroenterology and Hepatology, Peoples Hospital of Zhengzhou
University, Zhengzhou, China
INTRODUCTION: Hepatocellular carcinoma (HCC) is the third leading cause
of cancer related deaths worldwide, early detection of HCC is critical to monitor
disease progression, selection of therapeutic options and post-surgery surveillance. Alpha-fetoprotein (AFP) is traditionally an indispensible marker for the
diagnosis of HCC, since 33.3% of small HCC patients are AFP negative, it is
crucial to discover new sensitive marker to compensate the negative AFP in HCC
diagnosis and surveillance. Cyclase-associated protein 2 (CAP2) has recently
been proposed to be a candidate biomarker for detection of early HCC.
AIMS & METHODS: We aim to evaluate the sensitivity and specificity of CAP2
as a biomarker for HCC patients with special attention to those at early stage and
AFP negative. The CAP2 and AFP plasma levels were analyzed by enzymelinked-immunosorbent assay in 86 HCC, 59 cirrhotic patients, and 30 normal
individuals.
RESULTS: The results showed that both CAP2 and AFP plasma levels in HCC
patients were significantly elevated when compared to cirrhosis. CAP2 level
correlates well with HCC patients histological grade, clinical stage and tumor
size; but not with patients age, gender, hepatitis B virus infection status and
plasma AFP level. CAP2 had better sensitivity (82.6%) as compared to AFP
(59.3%) alone for general HCC patients, and in early stage of HCC patients
(78.6% vs 40.4%). In addition, CAP2 is able to complementary to AFP to
predict 82.9% of HCC in AFP negative patients.
CONCLUSION: We concluded that CAP2 is a promising biomarker for the
prediction of HCC in both AFP negative and early stages of HCC patients.
Disclosure of Interest: None declared
P0640 USEFULNESS OF CONTRAST-ENHANCED SONOGRAPHY
(CEUS) IN THE SURVIVAL OF PATIENTS WITH
HEPATOCELLULAR CARCINOMA (HCCC) SUBMITTED TO NONSURGICAL TREATMENTS
F. Giangregorio1,*, R. Solimando1, G. Prati1, G. Marinone1, M.D. Stasi1,
G. Comparato1, G. Aragona1, F. Fornari1
1
Gastroenterology Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy, Piacenza,
Italy
Contact E-mail Address: f.giangregorio@alice.it
INTRODUCTION: CEUS is an ultrasound technique with a good diagnostic
agreement with spiral CT in the evaluation of efficacy of non-surgical treatments
of HCC. The early evaluation of these treatments with CEUS may allow to
obtain a more complete necrosis of the tumoural nodules.
AIMS & METHODS: We evaluated if CEUS is able to affect the outcome of
these patients. 181 cirrhotic with HCC (M/F:112/69; mean age 71 yrs; Child A/B:
151/30), treated from 1/1999 to 12/2012 with non-surgical treatments for unresectable lesions: 116 with RFTA; 44 with combined treatment of RFTA and
TACE and 21 with PEI; solitary nodule:132 pts; 2-3 hcc:32; multinodular
HCC:17 cases. All patients underwent to spiral CT one month after the procedure; the first 66 patients (treated before January 2002), didnt perform CEUS,
(group-A); 115 patients were submitted to CEUS (after January 2002) 24 hours
after the treatments (group-B). We correlated the following variables with the
survival (S) and the disease-free-survival (DFS): number and diameter of HCCs;
AFP values; type of treatment; aetiology and class of Child; the early evaluation
of the treatment with CEUS. Statistics was performed with chi-square and
Kaplan-Meyer curves (SPSS release-18)
RESULTS: Mean follow-up of 181 pts: 52 months (group-A: 41,4; group-B:
60,2). During the follow-up 52/66(78,8%) pts in group-A and 49/115(42,6%)
pts in group-B died. Recurrence was found: group-A:45/56(80.3%) pts, groupB:73/115 (63.47%) pts. The patterns of recurrence were: new lesions away from
the treated nodules: group-A: 23 cases; group-B: 47 cases; local tumour regrowth:
group-A: 22 pts; group-B:26 pts. At multivariate analysis the number and diameter of the nodules, sex, and type of the treatment werent statistically correlated with S and DFS. Value of AFP and Child class were correlated with S
(S:p 0.001), the early evaluation of the efficacy of the treatment with CEUS and
the association CEUS-AFP were statistically correlated (CEUS: DFS:
p 0.042);(CEUS and AFP: DFS: p 0.036)
CONCLUSION: The early evaluation of the efficacy of the non-surgical treatments of HCC with CEUS lets to obtain a more complete necrosis of the tumour
and to reduce the recurrence for local regrowth of the HCC achieving a higher
percentage of disease-free survival
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0641 CUMULATIVE OPERATOR VOLUME IN RELATION TO TUMOR
RECURRENCE AFTER RADIOFREQUENCY ABLATION FOR
HEPATOCELLULAR CARCINOMA
J.-T. Lin1,*, T.-Y. Lee2, C.-Y. Wu2, H.J. Ho1, M.-S. Wu3
1
School of Medicine, Fu Jen Catholic University, New Taipei City, 2Division of
Gastroenterology, Taichung Veterans General Hospital, Taichung, 3School of
Medicine, National Taiwan University, Taipei, Taiwan, Province of China
Contact E-mail Address: dr.taiwan@yahoo.com.tw
INTRODUCTION: Radiofrequency ablation (RFA) is the main minimal-invasive curative therapy for hepatocellular carcinoma (HCC). However, the recurrence rate remains unsatisfactory.
AIMS & METHODS: We aim to investigate the role of cumulative operator
volume on HCC recurrence after RFA. We conducted a retrospective cohort
study based on Taiwans National Health Institute Research Database
(NHIRD). We identified 52,096 patients with newly diagnosed HCC between
2004 and 2011. Among them, 5,890 received radiofrequency ablation (RFA) as
their first therapy for HCC. Patients were categorized into five quintiles according the physicians experience (RFA volume). Patients in the lowest and highest
RFA volume quintiles were 1:1 matched by propensity score. Cumulative incidences of HCC recurrence was analyzed.
RESULTS: Patients in the highest RFA volume quintile had significantly lower
5-year HCC recurrence cumulative incidence (65.8%; 95% CI: 59.5-72.1%) compared to the risk for lowest RFA volume quintile (71.4%; 95% CI: 66.2-76.5%)
(P50.05). On multivariate analyses, the highest RFA volume was an independent protective factor for HCC recurrence (HR 0.80; 95% CI: 0.67-0.97).
Multivarate stratified analyses confirmed the association between higher RFA
volume and lower HCC recurrence risk in nearly all subgroups.
CONCLUSION: More RFA experience was associated with reduced risk of
HCC recurrence.
Disclosure of Interest: None declared
P0642 INCIDENTAL
HEPATOCELLULAR
CARCINOMA:
FACTORS AND LONG-TERM OUTCOME AFTER LIVER
TRANSPLANTATION

RISK

R. Senkerikova1, S. Frankova1, J. Sperl1, M. Oliverius2, E. Kieslichova3,


H. Filipova4, D. Kautznerova4, E. Honsova5, P. Trunecka6, J. Spicak1,*
1
Department of Hepatogastroenterology, 2Department of Transplant Surgery,
3
Department of Anesthesiology and Resuscitation, 4Department of Radiodiagnostic
and Interventional Radiology, 5Department of Clinical and Transplant Pathology,
6
Transplantacentre, Institute for Clinical and Experimental Medicine, Prague,
Czech Republic
Contact E-mail Address: renata.senkerikova@ikem.cz
INTRODUCTION: Orthotopic liver transplantation (OLT) currently represents
the treatment of choice for early hepatocellular carcinoma (HCC). Preoperatively
known HCC (pkHCC) is diagnosed via imaging methods prior to OLT or HCC,
denoted as incidental HCC (iHCC), is found postoperatively in the liver explant.
AIMS & METHODS: The aim of our study was a comprehensive analysis of
post-transplant survival of patients with iHCC and identification of risk factors
of iHCC occurrence in cirrhotic liver.
We retrospectively reviewed 33 adult cirrhotic patients with incidentally found
HCC comparing them with 606 tumor-free adult cirrhotic patients with end-stage
liver disease (group Ci) who underwent OLT in our center between January 1995
and August 2012. Within the same period, a total of 84 patients were transplanted for pkHCC. We compared post-transplant survival of iHCC, Ci group
and pkHCC patients. In the group of cirrhotic patients (Ci iHCC) we searched
for risk factors of iHCC occurrence.
RESULTS: There was no difference in sex, MELD score and time spent on the
waiting list in either group.
In the multivariate analysis we identified the age457 years (OR 3.37, 95% confidence interval (CI) 1.75-8.14, P5.001), HCV or alcoholic liver disease (ALD)
(OR 3.89, 95% CI 1.42-10.7, P5.001) and alpha-fetoprotein (AFP) level46.4
mg/l (OR 6.65, 95% CI 2.82-15.7, p .002) to be independent predictors of iHCC
occurrence. Either 1-, 3- and 5-year overall survival (OS) or 1-, 3- and 5-year
recurrence-free survival (RFS) differed in iHCC patients compared with Ci group
(iHCC: OS 79%, 72% and 68%, respectively; RFS 79%, 72% and 63%, respectively, vs. Ci group: OS RFS 93%, 94% and 87%, respectively; P5.001).
CONCLUSION: We conclude that the survival of iHCC patients is worse than in
tumor-free cirrhotic patients, but comparable with survival of pkHCC patients.
Independent risk factors for iHCC occurrence in cirrhotic liver are age, HCV or
ALD etiology of liver cirrhosis and AFP level.
Disclosure of Interest: None declared
P0643 SINGLE-STEP
BALLOON-OCCLUDED
PERCUTANEOUS
RADIO-FREQUENCY THERMAL ABLATION (RFA) PLUS
TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE)
FOR TREATMENT OF COMPLEX UNRESECTABLE
HEPATOCELLULAR CARCINOMA
M. Campanale1,*, C. Valentina2, F. Barbaro2, T.A. Di Rienzo2, M.L. Torre2,
A. Guerra2, S. Pecere2, G. Gigante2, R. Emanuele2, G. Caracciolo2,
F.R. Ponziani2, M. Siciliano2, B.E. Annicchiarico2, M.A. Zocco2, L. Riccardi2,
M. Pompili2, G.L. Rapaccini2, A. Grieco2, A.M. De Gaetano2, G.B. Gasbarrini3,
R. Iezzi2, L. Bonomo2, A. Gasbarrini2 on behalf of Hepatocatt Study Group
1
Internal Medicine and Gastroenterology, CATHOLIC UNIVERSITY OF
ROME, 2CATHOLIC UNIVERSITY, ROME, 3Fondazione Ricerca in Medicina

A309

United European Gastroenterology Journal 2(1S)


"Falcone e Borsellino", BOLOGNA, Italy
Contact E-mail Address: chiaracampanale@hotmail.com
INTRODUCTION: To evaluate the feasibility, safety and efficacy of single-step
balloon-occluded-RFA followed by TACE in patients with complex unresectable HCC, previously not suitable to RFA alone due to their localization.
AIMS & METHODS: 63 consecutive patients with at least one HCC lesion
(mean diameter 4.351.8cm), adjacent to the diaphragm (25 lesions), proximal
to the hepatic veins (17), portal vein (19), glissons capsule (34), cholecistis (6)
and/or located on the intra-abdominal free surface (5), considered as complex
for their unfavourable location, and not suitable for RFA alone, were enrolled in
our single-center multidisciplinary pilot study. The treatment was composed of
RFA (single 2-cm or 3-cm monopolar needle insertion) during occlusion of the
feeding artery followed by superselective TACE (conventional-TACE or with
DC-BEAD). Adverse events and intra/periprocedural complications were clinically assessed. Tumor response was evaluated on 1-month, 6 months and 1 year
follow-up multiphasic CT based on mRECIST criteria.
RESULTS: Technical success was achievied in all patients. 7 patients (11.2%)
experienced intra and periprocedural complications, such as fistuale (2), bleeding
(3), cholecistitis (1) and ascites (1), that resolved spontaneously. A mean total
treated diameter (necrotic diameter plus circonferential peripheral lipiodol
uptake for conventional TACE; mean necrotic diameter for TACE with DCBead) of 4.962.37 was obtained. Based on mRECIST criteria, on 1- and 3months follow up CT, a tumor response was obtained in all patients, with a
complete response achieved in 31 out of 63 patients (49.2%), a partial response
in 38.1% (24 patients: residual tumor 5 30% in 14 patients, 430%4550% in 6
patients, 450% in 4 patients), and no response in 3 patients, without any progressive disease. 5 patients were lost to follow up. 18 out of 27 patients (66.6%)
that underwent a CT-scan on 6-months follow up maintained a complete
response.
CONCLUSION: Balloon-occluded-RFA plus TACE seems to be a safe and
effective therapy for the treatment of complex HCC, allowing to obtain a
high complete local response rate, without complications, also in patients not
suitable to RFA alone.
Disclosure of Interest: None declared
P0644 COMPARISON
OF
CLINICAL
PRESENTATIONS
AND
OUTCOME OF HEPATOCELLULAR CARCINOMA BETWEEN
HEPATITIS C AND NONALCOHOLIC FATTY LIVER CIRRHOSIS: A
SINGLE CENTRE EXPERIENCE
N.N. Than1,*, N. Tehami1, J. Hodson2, C. Coldham3, S. Shetty 3, P. Newsome3
1
Liver unit, 2University Hospital Birmingham NHS Trust, Birmingham, UK,
3
Centre for Liver Research and NIHR BRU, University of Birmingham,
Birmingham, United Kingdom
Contact E-mail Address: sophiathan@ymail.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common primary liver tumor, and represents the third leading cause of cancer death worldwide [1, 2]. Chronic hepatitis C cirrhosis is one of the leading risk factors for
HCC but increasing cases are seen in nonalcoholic fatty liver disease (NAFLD).
AIMS & METHODS: The aim of the study was to compare demographics,
treatments and survival among hepatitis C virus (HCV/HCC) and NAFLD
(NAFLD/HCC) cohort of patients. Data were collected from medical electronic
case notes, imaging reports and reports from HCC multidisciplinary meetings.
RESULTS: Among 289 patients, 210 patients (73%) had underlying HCV/HCC
and 79 patients (27%) had NAFLD/HCC. The median age at diagnosis was
significantly higher in NAFLD/HCC patient cohorts (p50.001). The majority
(more than 80%) were male. Body mass index (BMI) was significantly higher in
NAFLD/HCC than HCV/HCC (p50.001). The majority of the patients in
NAFLD. HCC were Caucasian (96%), whilst the HCV/HCC cohort was significantly more ethnically diverse (p50.001). Diabetes mellitus was more common
in NAFLD/HCC patients (p50.001). The median alpha fetoprotein level in
HCV/HCC patients were 33.0 compared to 14.1 in NAFLD/HCC although it
did not reach the statistical significance (p 0.100). The size of HCC and the
numbers of HCC were similar between the two groups. Majority of patients in
HCV/HCC and NAFLD/HCC were Barcelona stage A (51% vs 48%) and stage
B (28% vs 39%). Treatment modalities such as radiofrequency ablation (RFA),
trans arterial chemoembolization (TACE) or sorafenib used in both groups of
patients were similar. Overall survival between the two groups did not differ
significantly (p 0.122), however we have found that HCV/HCC patients were
more likely to be transplanted (p 0.003).
Among 298 patients, 61 patients (29%) from HCV/HCC cohort and 11 patients
(14%) from NAFLD/HCC were transplanted. The only significance factors were
BMI (p 0.013) and presence of underlying diabetes mellitus (p 0.002) which
were more common in NAFLD/HCC patients. 15% were treated with RFA and
18% received TACE therapy prior to liver transplantation (LT) in HCV/HCC
compared to 18% and 9% in NAFLD/HCC respectively. Tacrolimus and
Mycophenolate Mofetil were two most common immunosuppression regimes
used post LT. Post transplant survival appeared to be slightly worsen in HCV/
HCC patients compared to NAFLD/HCC, although it did not reach statistical
significance (p 0.113). Post LT freedom from recurrence of HCC among the
two cohort was similar (p 0.848).
CONCLUSION: Despite the NAFLD/HCC being older and with higher metabolic risk factors, a significant proportion could undergo active therapy.
Furthermore, patients with NAFLD/HCC selected for transplantation seemed
to have better long term outcomes, possibly due to stricter selection for transplantation as well as variations in tumor biology between the two groups.
REFERENCES
1. Mittal S and El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 2013; 47(Suppl.): S2-S6.

2. Lu T, et al. Prevention of hepatocellular carcinoma in chronic viral hepatitis B


and C infection. World J Gastroenterol 2013; 19: 8887-8894.
Disclosure of Interest: None declared
P0645 HIGH ALPHA-FETOPROTEIN LEVELS AND PRESENCE OF
CLINICALLY SIGNIFICANT PORTAL HYPERTENSION CAN
PREDICT THE OCCURRENCE OF HEPATOCELULLAR
CARCINOMA IN CIRRHOTIC PATIENTS
S. Bota1,*, F. Hucke1, M. Pinter1, M. Mandorfer1, T. Reiberger1, A. Ferlitsch1,
M. Trauner1, W. Sieghart1, M. Peck-Radosavljevic1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
III, Medical University of Vienna, Vienna, Austria
Contact E-mail Address: bota_simona1982@yahoo.com
INTRODUCTION: The international guidelines strongly recommend the screening of hepatocellular carcinoma (HCC) in cirrhotic patients by ultrasound every
6 months  tumor markers (such as alfa feto protein AFP), but because of the
large number of patients and often limited resources some biomarkers for prioritizing patients for screening would be very helpful.
AIMS & METHODS: Our aim was to assess the HCC occurrence according to
AFP values, presence of clinically significant portal hypertension (HVPG  10
mmHg), Child-Pugh score, MELD score, liver stiffness values assessed by
Transient Elastography (TE), and liver disease etiology (viral vs. non-viral).
We retrospectively collected data of cirrhotic patients evaluated in our center
between January 2007-July 2013. In the same session HVPG measurements,
TE, lab values (used to calculate Child-Pugh and MELD score), and tumors
markers (AFP) were determined. The presence of HCC at baseline was excluded
by imaging techniques and patients were followed-up.
RESULTS: We identified 274 individual cirrhotic patients evaluated with all
tests. We had to excluded 11 patients whose follow-up was not available. Thus
in the final analysis 263 patients were included.
The median follow-up time was 21 months (3-83 months).
In our cohort of cirrhotic patients the HCC incidence was 5.7% and the median
time until the HCC diagnosis was 15 months (3 -72 months).
In univariate analysis the AFP values (r 0.174, p 0.006) and presence of
clinically significant portal hypertension (r 0.154, p 0.012) were statistically
correlated with HCC occurrence, while MELD score (r 0.092, p 0.13), viral
vs. non-viral etiology (r 0.050,p 0.41), TE (r 0.042, p 0.56) and ChildPugh score (r 0.042, p 0.49) were not correlated.
The HCC incidence was 13.7% in patients with AFP values  10 ng/ml, 7.9% in
cirrhotic with clinically significant portal hypertension and 16.6% in patients
with both risk factors.
All the patients which developed HCC had clinically significant portal hypertension (HVPG  10 mmHg), while in the group without HCC it was present in
70.1% of patients (p 0.02).
The proportion of cirrhotic patients with AFP 10 ng/ml at baseline was significantly higher in the cohort of patients that developed HCC as compared with
the ones who did not: 46.6% vs. 20.4%, p 0.02.
Combining both HVPG and AFP values, we observed that the percentage with
both risk factors present (HVPG10 mmHg and AFP10 ng/ml) was three times
higher in cirrhotic patients developing HCC compared with those without HCC
during follow-up: 46.6% vs. 15.2%, p 0.005.
No patient with HVPG 5 10mmHg developed HCC during follow-up.
CONCLUSION: The absence of clinically significant portal hypertension seems
to be a protective factor against HCC development. The combination of HVPG
and APF values can identify the cirrhotic patients with high risk of HCC occurrence and probably a closer surveillance of patients with clinically significant
portal hypertension and AFP values  10 ng/ml should be performed.
Disclosure of Interest: None declared
P0646 OVERALL SURVIVAL IN RESPONSE TO SORAFENIB VERSUS
RADIOTHERAPY IN UNRESECTABLE HEPATOCELLULAR
CARCINOMA WITH MAJOR PORTAL VEIN TUMOR
THROMBOSIS: PROPENSITY SCORE ANALYSIS
T. Nakazawa1,*, H. Hidaka1, Y. Okuwaki2, A. Shibuya2, S. Kokubu3,
W. Koizumi2
1
Department of Gastroenterology, 2Kitasato University East Hospital,
Sagamihara, 3Shinyurigaoka general hospital, Kawasaki, Japan
Contact E-mail Address: tnakazaw@kitasato-u.ac.jp
INTRODUCTION: This study investigated the survival benefits of sorafenib vs.
radiotherapy (RT) in patients with unresectable hepatocellular carcinoma (HCC)
and portal vein tumor thrombosis (PVTT) in the main trunk or the first branch.
AIMS & METHODS: Ninety-seven patients were retrospectively reviewed.
Forty patients were enrolled by the Kanagawa Liver Study Group and received
sorafenib, and 57 consecutive patients received RT in our hospital. Overall survival was compared between the two groups with PVTT by propensity score (PS)
analysis. Factors associated with survival were evaluated by multivariate
analysis.
RESULTS: The median treatment period with sorafenib was 45 days, while the
median total radiation dose was 50 Gy. The Child-Pugh class and the level of
invasion into hepatic large vessels were significantly more advanced in the RT
group than in the sorafenib group. Median survival did not differ significantly
between the sorafenib group (4.3 months) and the RT group (5.9 months;
P 0.115). After PS matching (n 28 per group), better survival was noted in
the RT group than in the sorafenib group (median survival, 10.9 vs. 4.8 months;
P 0.025). A Cox model showed that des-g-carboxy prothrombin 51000 mAU/
mL at enrollment and RT were significant independent predictors of survival in

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the PS model (P 0.024, HR, 0.508; 95% CI, 0.282 to 0.915; and P 0.007, HR,
0.434; 95% CI, 0.235 to 0.779; respectively).
CONCLUSION: RT is a better first-line therapy than sorafenib in patients who
have advanced unresectable HCC with PVTT.
Disclosure of Interest: None declared
P0647 PROGNOSTIC SIGNIFICANCE OF AFP AND PIVKA-II
RESPONSES TO INITIAL TRANSARTERIAL
CHEMOEMBOLIZATION IN PATIENTS WITH UNRESECTABLE
HEPATOCELLULAR CARCINOMA
T. Ichikawa1,*, N. Machida1, H. Sasaki1, Y. Tawa1
1
Department of Gastroenterology, Itabashi Chuo Medical Center, Itabashi-ku,
Tokyo, Japan
Contact E-mail Address: ichikawtakeshi@gmail.com
INTRODUCTION: It remains unclear whether response of alpha-fetoprotein
(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II)
to initial transarterial chemoembolization (TACE) are associated with improved
survival in patients with unresectable hepatocellular carcinoma (HCC).
AIMS & METHODS: The aims of this study were to evaluate the prognostic
significance of response of AFP and PIVKA-II to initial TACE and to identify
risk factors associated with outcomes in patients with unresectable HCC. We
retrospectively analyzed 114 patients with unresectable HCC not amenable to
surgery and radiofrequency ablation who had been treated with TACE between
September 2005 and October 2013. All laboratory values including AFP and
PIVKA-II were measured 1 week before TACE and 1 month after TACE. The
AFP or PIVKA-II response was assessed for patients who had a level before
TACE of 100 ng/ml or  100mAU/ml; a positive response was defined as a
reduction by 4 50% compared with the level before TACE. We compared
three groups of pre-TACE AFP  100 ng/ml with response vs. pre-TACE
AFP  100 ng/ml and no response vs. pre-TACE AFP 5 100 ng/ml using
univariate analysis. Three PIVKA-II groups were also compared. Prognostic
factors were evaluated using univariate (log-rank test) and multivariate analyses
(Cox proportional hazard model).
RESULTS: The median overall survival (OS) was 20.9 months. Pre-TACE AFP
level 100 ng/ml and tumor diameter 3 cm were associated with poor OS (AFP
100 ng/ml vs. AFP 5 100 ng/ml; 9.3 vs. 31.3 months; P 5 0.0001, tumor
diameter  3 cm vs. diameter 5 3cm: 12.5 vs. 31.3 months; p 0.0013) and
remained significant negative predictors for OS on multivariate analysis (AFP
4100 ng/ml; hazard ratio (HR) 3.5; p 0.0003, tumor diameter  3 cm; HR 3.1;
p 0.0015). In the difference of AFP response to TACE, the OS of pre-TACE
AFP  100 ng/ml with response compared with that of pre-TACE AFP  100
ng/ml and no response showed no significant difference (p 0.992). Although
there were not significant differences in OS between patients with pre-TACE
PIVKA-II 5 100 mAU/ml and those with pre-TACE PIVKA-II  100 mAU/
ml (p 0.1642), the OS of responders of PIVKA-II to initial TACE was significantly longer than that of non-responders in those with pre-TACE PIVKA-II 
100 mAU/ml (p 0.0032).
CONCLUSION: The response of AFP to initial TACE does not prolong survival
in patients with unresectable HCC. The response of PIVKA-II to initial TACE is
associated with improved survival. Elevated AFP (100 ng/ml) and tumor diameter  3 cm at diagnosis are associated with a dismal treatment response and
prognosis after TACE.
Disclosure of Interest: None declared
P0648 NEW ASSESSMENT OF THERAPEUTIC RESPONSE TO
SORAFENIB FOR ADVANCED HEPATOCELLULAR CARCINOMA:
AUTOMATIC MEASUREMENTS OF TUMOR VOLUME AND
DENSITY ON COMPUTED TOMOGRAPHY
Y. Kawaguchi1,2,*, T. Otsuka1, S. Nakashita1, T. Kumagai2, T. Akiyama2,
H. Mizobe3, J. Yamamichi3, S. Kawazoe2, T. Mizuta1, I. Ozaki1, Y. Eguchi1,
S. Kimura1
1
Department of Internal Medicine, Saga Medical School, 2Department of
Hepatobiliary and Pancreatology, Saga-ken Medical Centre Koseikan, Saga,
3
Global Healthcare IT Project, Canon Inc., Tokyo, Japan
Contact E-mail Address: kawaguy222@gmail.com
INTRODUCTION: Although sorafenib has been shown to have significant survival advantages in patients with hepatocellular carcinoma (HCC), Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 may underestimate the efficacy because of modest tumor shrinkage. Additionally, discrepancy among evaluators may occur in the manual assessments.
AIMS & METHODS: The present study aimed to establish an objective evaluation method for anti-tumor response of sorafenib with regard to survival, using
software that can automatically measure the diameter, volume and density of
target tumors on computed tomography (CT). Among 81 patients with advanced
HCC who were treated with sorafenib, 23 with ChildPugh class A, Barcelona
Clinic Liver Cancer stage C and performance status 0 or 1 were enrolled.
Automatic measurements on CT were performed using MEDIAN Lesion
Management Solutions. Conventional RECIST1.1 was compared with new
methods: automated RECIST (a-RECIST), enhanced RECIST (e-RECIST)
and Saga criterion. a-RECIST was RECIST1.1 using automatic measurements.
e-RECIST used volume evaluation classified as follows: partial response (PR) as
50% reduction in tumor volume; progressive disease (PD) as 50% increase in
tumor volume; and stable disease (SD) as 550% reduction or 550% increase in
tumor volume. Saga criterion was the same as e-RECIST except that SD with
15% reduction in tumor density in the arterial phase was classified as PR.
Overall survival (OS) time was estimated using the KaplanMeier method and

United European Gastroenterology Journal 2(1S)


expressed as median (95% confidence interval). The survival curves according to
best response were compared using the log-rank test.
RESULTS: Conventional RECIST1.1 could not stratify OS. Meanwhile, OS was
significantly stratified according to anti-tumor response in a-RECIST. Disease
control rate (DCR) 60.9%, DC vs. PD, 17.2 (6.328.1) vs. 9.3 (5.013.6)
months (p 0.048); objective response rate (ORR) 8.7%, OR vs. non-OR,
N/A vs. 10.4 (7.113.6) months (p 0.048). e-RECIST was superior to aRECIST: DCR 56.5%, DC vs. PD, 20.4 (13.926.8) vs. 9.0 (4.513.4)
months (p 0.011); ORR 8.7%, OR vs. non-OR, N/A vs. 10.4 (7.113.6)
months (p 0.048). In addition, Saga criterion was superior to e-RECIST:
DCR 56.5%, DC vs. PD, 20.4 (13.926.8) vs. 9.0 (4.513.4) months
(p 0.011); ORR 30.4%, OR vs. non-OR, 20.4 (14.226.6) vs. 9.0 (5.412.5)
months (p 0.007).
CONCLUSION: Our findings suggest that Saga criterion, a new imaging assessment using automatic measurements of tumor volume and density on CT, has
potential as a surrogate marker for anti-tumor response to sorafenib with regard
to survival.
Disclosure of Interest: None declared
P0649 POPULATION SCREENING FOR
HEPATIC TRANSIENT ELASTOGRAPHY

LIVER

DISEASE

USING

B.M. Goncalves1,*, L. Malheiro1, D. Fernandes1, J.-B. Soares1, C. Rolanda1,


R. Goncalves1, P. Bastos1
1
Gastroenterology, Hospital de Braga, Braga, Portugal
Contact E-mail Address: brunommgoncalves@gmail.com
INTRODUCTION: Transient Elastography (TE), a noninvasive technique for
liver fibrosis evaluation, has been used in patients with various types of chronic
liver diseases. It is a simple, fast, painless, reproducible and well-accepted technique with instantaneous results that could be a valuable screening tool.
However, there is a shortage of studies on its usefulness as a screening procedure
in apparently healthy people.
AIMS & METHODS: The purpose of the study was to evaluate the impact of TE
in the population screening of liver disease. It was conducted a prospective study
where TE was performed in 365 individuals without known liver disease that
attended general gastroenterology clinic in a referral hospital. A positive screening was defined for values of liver stiffness (LS) 8 kPa. For these individuals
additional clinical, laboratory and ultrasonographic investigation was proposed
for determination of liver disease.
RESULTS: Of the 365 individuals evaluated, 89 were excluded for invalid
(n 47) or failed (n 42) TE. In the multivariate analysis, body mass index
430Kg/m2 and waist circumference 4102cm in men or 488cm in women
were associated with failure of LS measurement (p 0.031 and 0.001, respectively). Of the 276 valid exams, 21 (7.6%) obtained a LS value 8 kPa, including
nine patients with LS  13 kPa. The average value of LS in the remaining
participants with negative screening was 4.9  1.2 kPa. In the group with positive
screening it was observed that 28.6% patients had normal liver tests. In 17 (81%)
patients a cause of liver disease was determined, while all participants with LS 
13 kPa had a diagnostis. Alcoholic liver disease was the most prevalent etiology
(47%) followed by non-alcoholic fatty liver disease (41%).
CONCLUSION: TE revealed to be a useful method to screen liver disease in the
general population, diagnosing a significant number of asymptomatic patients.
In the presence of an abnormal LS, the patient should be referenced for further
evaluation.
Disclosure of Interest: None declared
P0650 MORBIDITY RISK IN AN ITALIAN COHORT OF HCV AND HBV
PATIENTS
C. Stasi*1,2,*, C. Silvestri*1, S. Bravi1, F. Voller1, F. Cipriani3
Epidemiology Unit, Health Agency of Tuscany, Florence, Italy, 2Department of
Experimental and Clinical Medicine, University of Florence, 3Health Agency of
Tuscany, Florence, Italy, Florence, Italy
1

INTRODUCTION: In Italy the HBV incidence progressively decreased from


1991 to 2005, because in 1991 infants and adolescents vaccination became
mandatory. Effective screening since the early 90s has reduced the risk of HCV
transmission through blood transfusion. Recently, World Health Organization
(WHO) for the first time produced guidelines for the screening, care and treatment of persons with HCV infection. These guidelines are primarily targeted at
policy-makers in ministries of health working in low- and middle-income countries that formulate country-specific guidelines for treatment. Treatment for
HCV and HBV can reverse hepatic fibrosis and/or delay the development of
long-term complications such as decompensated cirrhosis. A recent study
shows that treatment of patients with compensated cirrhosis is cost-effective.
AIMS & METHODS: Therefore, the aims of this study were to evaluate the
HBV and HCV epidemiology in Florence (Tuscany, region in central Italy) in
2012 and to investigate the hospital admissions of these patients at least once, as
a risk of morbidity for cirrhosis, from 2000 to 2012. Methods: We analyzed the
database of one Hospital in Florence (Careggi University Hospital) and prevalence of hospital admissions from 2000 to 2012 of HBV (based on the presence of
antigene surface - HBsAg) and HCV patients (based on the presence of HCV
RNA; limit of detection: 15 IU/mL) for chronic liver disease and cirrhosis,
Fibrosis and cirrhosis of the liver, bleeding from esophageal varices, using
the International Classification of Diseases, 9th Revision, Clinical Modification
(ICD-9-CM) and 10th revision (ICD-10).
RESULTS: Out of 24,368 individuals, a total of 2,697 hepatitis cases were
reported, including 1,237 HBV and 1,460 HCV RNA positive patients. HBV
occurred more often in males (63%) than in females (37%). HCV occurred
slightly more often in males (59%) than in females (41%). In HCV group

A311

United European Gastroenterology Journal 2(1S)


1,270 (87%) had at least one hospital admission, while in HBV group were
reported 492 hospital admissions (40%). When we divided the HBV patients
into 5 age groups, hospital admission was detected in 1% of people aged 15-30
years; in 10% of people aged 31-45; in 50% of people aged 46-60; in 39% of
people aged over 61 years; HCV hospital admission was detected in 1% in people
aged 15-30; 6% in people aged 31-45; 48% in people aged 46-60; 45% in people
aged over 61 years.
CONCLUSION: Our results show that there is a high prevalence of HCV and
HBV hospital admissions in the central of Italy, especially in people aged over 46
years, with the higher prevalence for HCV than HBV patients. Therefore, its
impact on the National Health Service could be important in the future. This
study also suggests that early screening creates the conditions for early treatment
in order to avoid the possibility of worsening of viral hepatitis on to develop
cirrhosis of the liver.
REFERENCES
http://apps.who.int/iris/bitstream/10665/111747/1/
9789241548755_eng.pdf?ua 1&ua 1
Obach D, Deuffic-Burban S, Esmat G, et al. Effectiveness and cost-effectiveness
of immediate vs. delayed treatment of HCV-infected patients in a country with
limited resources: the case of Egypt. Clin Infect Dis 2014; 58: 1064-1067.
Disclosure of Interest: None declared
P0651 A COST-CONSEQUENCE ANALYSIS OF SCREENING AND
TREATMENT FOR CHRONIC HEPATITIS B (CHB) VIRUS
INFECTION IN RESIDENT IMMIGRANTS OF AN ITALIAN NORTHEAST REGION
E. Rosa-Rizzotto1,*, A. Buja2, D. Martines1, A. Vinelli2, G. Bardelle2,
S. Lopatriello2, L. Peraro1, D. Caroli1, L. Scribano1, F. De Lazzari1, S. Lobello1,
V. Baldo2
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital,
2
Department of Molecular Medicine, Laboratory of Public Health and Population
Studies, Padua University, Padua, Italy
INTRODUCTION: Chronic hepatitis B virus (HBV) infection is a serious health
problem affecting 350 million to 400 million people worldwide. Although HBV
infection occurs everywhere in the world, nationality is strongly associated with
the prevalence of HBV infection. The epidemiology of hepatitis B in Europe is
changing, with migration causing significant increases in prevalence rates.
Immigration to Italy is a relatively new phenomenon that became relevant
only at the end of the 1990s. As of January 2013, there were 4,387,721 foreign
nationals resident in Italy.[ISTAT (2013). Statistiche report, 26 Luglio 2013.
Rome, Italian National Institute of Statistics]. This amounted to 7,4% of the
countrys population, mainly concentrated in the northern part of the country.
Veneto region is one of the main immigration destination areas. With about
500.000 foreign people staying in its territory, Veneto is the third Italian region
for the number of immigrants and the fourth one if you consider the immigration
rate on the overall population (10.2%). These influxes involve a considerable
proportion of citizens from countries where hepatitis B is highly (4 8%) endemic, such as eastern Europe (Moldovans, Romanians and Ukrainians), from
Africa (especially Ghana and Morocco), Balkan states (especially Albania,
Montenegro and Serbia) and China, compared with less than 1 % of overall
Italian population. Systematic screening and early treatment of migrants for
chronic hepatitis B virus infection may have a large impact on liver-related
health outcomes and is likely to be cost-effective. In four cost-effectiveness analyses, the estimated average cost per life-year gained of screening ranged from E
8966 to E 46260 per QALY gained. A cost-consequence analysis (CCA) provides
an estimation of the costs as well as the expected health outcomes in terms of liver
disease progression and mortality. Cost-consequence analyses play an essential
part in the comprehensive economic assessment of a health care intervention.
AIMS & METHODS: We used the Markow model to examine the cost-consequence of screening and treatment vs a no screening strategy in a cohort of
348,991 adult migrants resident in the Veneto Region. The rate of adherence
to the HBV screening program was judged to be 40%. The prevalence of HBV
infection and the chance of having active CHB was based on our recent screening
campaign in Padua involving 465 migrants (Tab.) Likelihood of HBV-related
events were obtained from literature.
RESULTS:
Rate of adherence
AGE GROUP HBsAg ACTIVE
to screening
POPULATION 4 20 y
N (%)
CHB N (%) program n (%)
465322

348991

21048 (6) 6314 (30)

2525 (40)

The screening-treatment strategy prevented 273 cases of cirrhosis, 18 decompensated cirrhosis, 28 HCC, and 54 CHB related deaths, over a period of 5 years.
The incremental cost of the screening strategy totaled 51.597.980 E in five years
(0,1% of the Veneto annual health budget).
CONCLUSION: This study provides information useful mainly to policy
makers, who need to establish whether the cost generated by a screening strategy
is affordable when set against the better health outcomes for resident immigrants.
Disclosure of Interest: None declared

P0652 HEPATITIS VIRUSES IN HEALTHY IMMIGRANTS: TO SCREEN


OR NOT TO SCREEN?
E. Rosa-Rizzotto1,*, L. Peraro1, D. Caroli1, L. Scribano1, S. Gallo1, C. Magro1,
F. De Lazzari1, D. Martines1, S. Lobello1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital, Padua,
Italy
INTRODUCTION: Over the past four decades international migrations have
increased up to an unprecedented rate. New migrants come from countries at
low hepatitis B prevalence [hepatitis B surface antigen (HBsAg) seroprevalence
52 per cent], intermediate (HBsAg seroprevalence between 2 per cent7 per cent)
or high hepatitis B prevalence (HBsAg seroprevalence 8 per cent). Over this
period both chronic HBV infection and HCC prevalence are increased in North
America and Western Europe, also because migrants have higher incidence of
chronic HBV infection and an increased mortality for cirrhosis and HCC compared to host populations. Hepatitis viruses screening is a form of secondary
prevention to find early diseases amenable to antiviral treatments in order to
prevent liver diseases. Moreover the screening helps to vaccinate the people
cohabiting with HBsAg ve subjects. Worldwide HCV prevalence is generally
low and only in few countries it is over 3.5 per cent. Immigrants in Italy come
mainly from Eastern Europe, Asia and Africa. In all these areas HCV prevalence
is lower than HBV.
AIMS & METHODS: Regular healthy immigrants were sent to our clinic by
community leaders from March 2013 to October 2013, questioned about their
socio-demographic characteristics, tested for HBcAb and, when positive, for
HBsAg. HBsAgve subjects were studied for HBVDNA levels and enrolled
for clinic controls of liver disease. This population was also tested for HCVAb. HCV-Abve subjects were tested also for HCV-RNA and HCV genotype.
RESULTS: 450 (264- M 58,7% - and 185 - F 41,3%) immigrants were screened.
39% were from Eastern Europe, 23% from Asia, 36% from Africa, and 2% from
other areas. This distribution is comparable with immigrants residing in Padua.
144 (32%) were anti-HBcAg ve, 31 (7%) HBsAg ve, 4 (1%) HBeAg ve.
HBVDNA levels were over 2000 IU/ml in 11/31 (35.5%). The prevalence of
HBsAg ve in the Eastern European group was 11.4%, 7.9% in the Asiatic
group and 1,2% in the African group. Eight immigrants resulted positive for
HCV (1.8%), but only 6 were HCV-Rna positive, all were Moldavian (8.4%).
CONCLUSION: The seroprevalence of chronic HBV infection in migrants is
similar to that of their countries of origin: high among migrants from East
Asia and Eastern Europe, where 32% were found to be anti-HBcAgve.
Hepatitis B virus screening on healthy migrants in our area is effective to identify
HBsAgve subjects and it seems useful to define the amount of patients with
HBV related liver disease. Targeted screening and vaccination of international
migrants can become an important aspect of HBV disease control efforts in
immigrant-receiving countries, thus changing the natural history of HBV chronic
infection. The prevalence of HCV in Padua immigrants seems to be very low
unlike HBV. HCV screening for immigrants does not appear useful to detect
Hepatitis C virus affected subjects. The HCV screening strategy could be effective
only in special populations of immigrants with higher HCV prevalence (i.e. East
Europe).
Disclosure of Interest: None declared
P0653 METABOLIC PHENOTYPING OF BILE ACIDS - STANDARDIZED
QUANTITATIVE BILE ACIDS ANALYSIS IN HUMAN PLASMA/
SERUM AND MOUSE PLASMA ON DIFFERENT LIQUID
CHROMATOGRAPHY TANDEM MASS SPECTROMETRY
PLATFORMS
H.P. Pham Tuan1,*, D. Kirchberg1, I. Zitturi1, F. Polato1, D. Seppi1, T. Koal1
Product/Method Development, BIOCRATES Life Sciences AG, Innsbruck,
Austria
Contact E-mail Address: Hai. Pham-Tuan@biocrates.com
1

INTRODUCTION: Bile acids are considered not only as endogenous markers


for liver cell functions, but also as signaling molecules regulating triglycerides,
cholesterol and glucose metabolism as well as inflammatory processes and apoptosis. Accurate determination of individual bile acids and their conjugates is very
important in assessing liver damage as well as hepatic and biliary tract diseases,
colon cancer, atherosclerosis and type 2 diabetes. Therefore, bile acid analysis
could provide a powerful tool for applications in precision medicine, toxicology,
and clinical biomarker research. We have developed and validated a standardized
(U)HPLC-ESI-MSMS assay for the analysis of ca. 20 bile acids from only 10 mL
human plasma/serum or mouse plasma samples. The panel consists of cholic
acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, hyodeoxycholic acid, muricholic acids and their glycine as well as taurine conjugates.
AIMS & METHODS: 10 mL sample and 10 mL IS mixture are pipetted onto the
paper filter spot suspended in a 96-well filter plate. After a short drying under
nitrogen stream, bile acids are extracted with 100 mL methanol. The methanolic
extract is filtered through the plate into the 96- deep well receiving plate, under
light centrifugation. 60 mL water is added to the extract before injecting into the
(U)HPLC-ESI-MSMS for analysis. The analysis runtime for UHPLC and HPLC
is 5 and 11 min, respectively. Bile acids detection is performed using MRM in
negative ESI mode. 7-points calibration curves are used for quantitation. The
assay has been rigorously validated according to the EMA guideline.
RESULTS: Due to the special arrangement of the paper filter spot, proteins
which have been precipitated are largely captured by the filter, while allowing
the target metabolites to be extracted and filtered through. Only 3 steps are
needed to complete the sample preparation. Seven calibrators levels and three
quality control levels are used to guarantee the accuracy and precision of the
measurements. This new assay in kit format has been validated for different LCMS/MS platforms from AB Sciex, Waters, and Thermo Scientific. In general an

A312
LLOQ of 0.01 to 0.02 mM have been achieved for all target bile acids. Among the
tested LC-MS/MS platforms, increasing sensitivity for bile acids analysis can be
graded as follows: Xevo TQ MS 5 TSQ Vantage 5 400QTRAP5 QTRAP5500.
CONCLUSION: With the help of the very simple and robust bile acids kit, the
analysis of several human plasma/serum samples and mouse plasma samples
reveals that the bile acid profile of mice is quite different from that of human.
While taurine conjugates of bile acids are prevalent and glycin conjugates are
amost absent in mouse plasma, the situation is reversed in human plasma/serum.
Moreover, the male/female differences found in mouse plasma is much more
profound than that found in human samples.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
PAEDIATRIC: LIVER, BILIARY AND PANCREAS POSTER EXHIBITION HALL
XL_____________________
P0654 MACROAST - THE DIAGNOSTIC USEFULNESS AND CLINICAL
OBSERVATIONS IN CHILDREN
A. Wierzbicka-Rucinska1,*, W. Janczyk2, B. Oralewska3, M. Teisseyre3,
P. Socha3
1
Biochemistry, Radioimmunology and Experimental Medicine, 21Gastroenterology,
Hepatology and Eating Disorders, 3Gastroenterology, Hepatology and Eating
Disorders, Childrens Health Memorial Institute, Warsaw, Poland
Contact E-mail Address: aldona.wierzbicka@wp.pl
INTRODUCTION: Elevated aspartate aminotransferase (AST) may not be associated with liver or muscle injury and can be caused by the presence of macroAST
which results from unusual combination of molecules of AST with serum macroglobulins. MakroAST may be present in both healthy subjects and in the course
of other diseases, including autoimmune diseases. Only few reports in limited
number of patients described Macro AST and proposed diagnostic criteria.
AIMS & METHODS: The aim of this study was to evaluate the prevalence of
macroenzymes in children with increased activity of aspartate aminotransferase
and to compare two diagnostic methods- polyethylene glycol precipitation (PEG)
and electrophoresis.
Methods: 247 children with mean age of 6.2 years (from 0.03 to 16.19 years) with
isolated hypertransaminasemia were included in the study. The presence of
macroenzymes was first based on polyethylene glycol precipitation (PEG),
according to Levitt and Ellis [1]. Electrophoresis was used to confirm the presence of a macroAST.
RESULTS: In a group of 247 children with hypertransaminasemia (all with
increased AST, 48 children presented with increased AST and ALT) we received
the following results according to the different cut off values for precipitable
activity (% PPA) of the PEG test:
1/ according to Davidson and Watson [2] with a cut-off point of 54% PPA macro
AST was observed in 67 children (27.1% of the patients).
2/ according to Caropreso M, et al [3] with a cut-off point of 73.3% PPA macro
AST was observed in 5 children (2.0% of the population studied).
Samples with AST activities 450 U/l were analyzed with both PEG precipitation
and electrophoresis. AST isoenzyme electrophoresis showed macroAST in 35
children which is 14% of the population studied.
CONCLUSION: MacroAST has to be considered in differential diagnosis of
increased AST activity.
The cut off values for polyethylene glycol precipitable activity test need to be
further evaluated and requires further confirmation with electrophoresis.
The cut off value of 54% PPA can be used as a screening test for macroAST.
REFERENCES
1) Caropreso M, Fortunato G, Lenta S, et al. Prevalence and long-term course of
macro-aspartate aminotransferase in children. J Pediatr 2009; 154: 744-748.
2) Sakakibara S, Katsuhiko S, Kobayashi S i wsp. A convenient and sensitive
method for the determination of serum aspartate aminotransferase isoenzymes
after electrophoresis. Clin Chim Acta1983; 133: 119-123.
3) Fortunato G, Iorio R, Esposito P, et al. Macroenzyme investigation and
monitoring in children with persistent increase of aspartate aminotransferase
of unexplained origin. J Pediatr 1998; 133: 286-89.
4) J Remaley AT and Wilding P. Macroenzymes: biochemical charakterization
characterisation, clinical significance and laboratory detection. Clin Chem 1989;
35: 2261-2270.
Disclosure of Interest: None declared
P0655 ENVIROMENTAL RISK FACTORS OF PAEDIATRIC ONSET
AUTOIMMUNE LIVER DISEASE
A. Tenca1,*, M. Farkkila1, H. Jalanko2, K. Vapalahti3, O. Vapalahti4, K.L. Kolho5
1
Department of Medicine, Clinic of Gastroenterology, Helsinki University Central
Hospital, 2Department of Pediatric Nephrology and Transplantation, Childrens
Hospital, University of Helsinki, 3University of Helsinki, 4Department of Virology
and Immunology, Helsinki University Central Hospital, 5Childrens Hospital,
University of Helsinki, Helsinki, Finland
Contact E-mail Address: ante14@hotmail.it
INTRODUCTION: Primary sclerosing cholangitis (PSC), autoimmune hepatitis
(AIH) and PSC/AIH overlap syndrome are three autoimmune liver diseases
(AILD) of unknown origin.
AIMS & METHODS: Aim of this population-based observational case-control
questionnaire study was to investigate the environmental risk factors associated
with a paediatric onset AILD. All the patients (n 85) with a paediatric onset (5
16 years) AILD diagnosed between 1985-2011 at Helsinki University Central
Hospital (HUCS) were mailed a questionnaire, evaluating contact with

United European Gastroenterology Journal 2(1S)


environmental risk factors before the AILD diagnosis in 22 items, e.g., number
of siblings, place of living (i.e., country/town, downtown/suburb), type of housing (i.e., block of flats, town house, terraced house, duplex), having pets or
domestic animals (e.g., cat, dog, horse), smoking and other items. Two control
groups -matched for sex, age and place of residence- were used: 1) as AILD are
more frequent in patients affected by inflammatory bowel disease (IBD)1 a paediatric group of patients with IBD without AILD (n 91; selected from IBD
Register of HUCS) was included and 2) a group of healthy subjects (n 716;
selected from Population Register Center). Univariate analysis (ORs; 95%CI)
was performed using the two control groups separately. A logistic regression
model for the multivariate analysis including (i) variables statistically significant
in univariate analysis and (ii) confounders and interactive factors, was calculated;
two models were constructed for controls: model 1 IBD and healthy controls,
model 2 healthy controls.
RESULTS: Baseline characteristics (Percentage of respondents. F female.
Median age: range years) AILD cases: 51/85 (60%; F 26; 22:8-36), IBD controls: 59/91 (65%; F 34; 21:9-37), healthy controls: 292/716 (41%; F 162;
21:8-38). No difference between respondents and non-respondents. Median age
and range at AILD onset 10 years: 2-15. Univariate analysis Protective and risk
factors are shown in Table 1; others factors were not associated with AILD.
Multivariate analysis Children traveling abroad except those living in a block
of flats seemed to be protected for developing AILD (Model 1 OR: 0.07;
95%CI: 0.02-0.2. Model 2 OR: 0.06; 95%CI: 0.02-0.2). Living with a cat or a
dog was a risk factor (Model 1 OR: 2.7; 95%CI: 1.3-5.7. Model 2 OR: 2.1;
95%CI: 1.0-4.2). In models studying the effect of pet species individually,
those living in a block of flats with a cat had the highest risk (e.g., Model 2
OR: 6.4; 95%CI: 1.8-22.7).Table 1

Traveling abroad
Having a pets (cat or dog)

IBD controls

Healthy controls

OR

95%CI

OR

95%CI

0.3
3.4

0.1-0.7
1.5-7.8

0.2
2.5

0.1-0.4
1.2-5.0

CONCLUSION: In this postal questionnaire based survey of environmental risk


factor of AILD, children traveling abroad and living in a town house, terraced
house or duplex were less susceptible to develop AILD, suggesting a protective
role of a higher socioeconomic status. Intriguingly, living in a close contact with a
pet was a risk factor, suggesting an involvement of an unidentified agent (i.e.,
toxin or microbe) as a trigger of paediatric AILD.
REFERENCES
1 Deneau M, et al. Hepatology 2013; 58: 1392-400.
Disclosure of Interest: None declared
P0656 NOVEL JAG1 MUTATIONS IN PATIENTS WITH SUSPECTED
EXTRAHEPATIC BILIARY ATRESIA AND ALAGILLE SYNDROME
T. Dedic1,*, M. Jirsa2, R. Kotalova1, J. Snajdauf3, R. Keil4, M. Rygl3
1
Department of Pediatrics, Charles University 2nd Medical School and Motol
University Hospital, 2Laboratory of Experimental Hepatology, Institute for
Clinical and Experimental Medicine, 3Department of Pediatric Surgery,
4
Department of Internal Medicine Gastroenterology and Endoscopy, Charles
University 2nd Medical School and Motol University Hospital, Prague, Czech
Republic
Contact E-mail Address: dedict@seznam.cz
INTRODUCTION: Alagille syndrome (AGS, OMIM #118450) is an autosomal
dominant multisystem disorder affecting the liver, heart, face, eyes and skeleton.
In early infancy AGS may mimic biliary atresia (BA) and extrahepatic bile ducts
might not be visualised by endoscopic retrograde cholangiopancreatography
(ERCP) or postoperative cholangiography.
AIMS & METHODS: Our aim was to confirm the diagnosis in patients with
suspected AGS (n 4) and to identify carriers of JAG1 mutations among patients
with BA (n 72), all aged 2 months on average.
310 children with neonatal cholestasis were hospitalized at the Department of
Peaditrics, Faculty Hospital Motol, Prague, between January 1998 and January
2012. ERCP was indicated in 127 patients with suspected BA based on clinical
and laboratory examinations. Subsequent surgical revision was performed in 96
patients with pathological findings on the bile ducts. Mutational analysis of the
JAG1 gene was done in a subset of 72 living patients with isolated BA and in 4
patients with suspected AGS and normal extrahepatic biliary tree.
RESULTS: Sequence analysis of JAG1 revealed seven novel mutations including
one missense [c.401G4T (p. Leu135Phe)], one nonsense [c.1998T4A (p.
Cys633*)] and five frameshift mutations [c.327_330delCAAG (p.
Lys110Profs*50), c.1313_1314delGT (p. Cys438Serfs*10), c.879_880delTG (p.
Cys293*),
c.2913-2914delAC
(p.
Pro971Argfs*10),
c.2050delG
(p.
Asp684Thrfs*59)], and one known nonsense mutation [c.960T4A (p.
Tyr320*)]. All 5 patients with proven JAG1 deficiency presenting initially as
BA developed clinical signs typical for AGS before 3 years of age. By contrast,
no JAG1 mutation were present in the remaining 67 patients with isolated BA.
CONCLUSION: Biliary atresia is not associated with JAG1 mutations in Central
Europeans. In addition to liver histology, early molecular diagnosis of AGS
could be useful in diagnosis of the gray zone AGS patients presenting as
extrahepatic biliary atresia in early infancy.
Disclosure of Interest: None declared

A313

United European Gastroenterology Journal 2(1S)


P0657 STEATOSIS OF PANCREAS IN THE STRUCTURE
METABOLIC SYNDROME IN OVERWEIGHT AND OBESE
CHILDREN

OF

M. Gurova1,*, A. GusevA2, V. Novikova3


Department of Pediatrics, Belgorod State National Research University,
Belgorod, 2Department of Pediatrics, Kursk Regional Children Hospital, Kursk,
3
Department of Pediatrics, Federal Centre of the Heart, Blood and Endocrinology,
named after V. A. Almazof, Saint-Petersburg, Russian Federation
1

INTRODUCTION: Involvement of pancreas in pathological process in case of


obesity is caused by its important role in regulation of metabolic processes, of
energetic balance and body weight.
AIMS & METHODS: This study is aimed at assessing frequency of detectability
of ectopic fat deposition in the pancreas in obese and overweight children and at
comparing this detection frequency of other components of metabolic syndrome
(MS).
Methods: The cross-sectional study was conducted among 120 children aged 1115 years, separated into 2 groups: 60 overweight children (1st group) and 60
obese children (2nd group). Diagnosis of the non-alcoholic fatty liver disease
(NAFLD) and non-alcoholic fatty pancreas disease (NAFPD) was based on
sonographic data. Peculiarities of carbohydrates and lipid metabolism and pancreatic exocrine function were investigated.
RESULTS: Complete MS was diagnosed only in 15% of children with obesity.
Some components of MS according IDF recommendations (2005) were found in
88.3% of obese children and 66.7% of overweight ones (p 0.002). The most
common components were the following hyperinsulinemia (90% vs 66.7%,
p 0.0027), insulin resistancy according results of HOMA-index (51.7% vs
65%, p 0.12), increasing triglycerides level (36.7% vs 6.7%, p 0.00l), decreasing level of LPHD (78.3% vs 40%, p 0.001). Sonographic data compatible with
NAFLD were two times higher in children with obesity 56.7% vs. 30%
(o 0.005), whereas NAFPD data were found with equal frequency in overweight and obese children - 85% and 86.7% accordingly (p 0.88). These results
were associated with decreasing level of the elastase-1 in 23.3% children with
obesity.
CONCLUSION: Sonographic results compatible with NAFPD were found more
than in 2/3 cases in overweight and obese children and they had appeared earlier
than sonographic results of NAFLD which were found only in 1/3 cases of
overweight children and cases of obese patients. These results were associated
at first with carbohydrate metabolism disturbances (insulin resistancy), whereas
atherogenic dyslipidemia in our study was not prominent. In 23% obese children
with sonographic changes considered as pancreatic steatosis signs of mild exocrine insufficiency were found.
Disclosure of Interest: None declared
P0658 A REPORT OF 267 CASES OF CHILDHOOD PANCREATITIS:
INCREASING PREVALENCE, ETIOLOGIC CATEGORIZATION,
DYNAMICS, SEVERITY ASSESSMENT AND OUTCOME
U. Poddar1,*, S.K. Yachha1, A. Srivastava1, S.S. Baijal2, S. Kumar2, R. Lal3,
V.A. Saraswat4
1
Pediatric Gastroenterology, 2Radiology, 3Pediatric Surgery, 4Gastroenterology,
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Contact E-mail Address: ujjalpoddar@hotmail.com
INTRODUCTION: Paediatric pancreatitis although reported has not emanated
from developing world as a large single center study. More so, natural history of
acute pancreatitis as a continuum of recurrent acute and chronic pancreatitis is
not well established.
AIMS & METHODS: To look at prevalence, aetiologic categorization,
dynamics, severity assessment and outcome in children with pancreatitis.
METHODS: From January 2002 to December 2013 consecutive children (18
years of age) diagnosed to have pancreatitis were included for analysis.
Pancreatitis was classified as acute (AP), acute recurrent (ARP) and chronic
pancreatitis (CP) as per standard definitions. Severity of acute pancreatitis was
assessed by 2012: revised Atlanta classification. Follow-up data was assessed till
March 2014.
RESULTS: Pancreatitis was diagnosed in 267 children (mean age of 11.29  3.49
years). AP in 50% (n 133), ARP in 22% (60) and CP 28% (74). The number of
cases increased progressively from 18 in the 1st quarter of the study to 37 in 2nd
quarter, 64 in 3rd quarter and 148 in the last quarter. Aetiology of AP was trauma
in 22% (n 29), biliary 10.5% (14), viral infection 7% (9), drugs 5% (7), others
causes in 4.5% (6) and idiopathic 51% (68). Grading of pancreatitis was severe in
13% (17, 6 died), moderately severe (local complications) 55% (73) and mild
32% (43). Over a median follow-up of 12 (range, 3 to 96) months, 23.5% (27 /
115) developed either acute recurrent (n 9) or chronic pancreatitis (18).
Progression from acute to ARP/CP was observed mostly in idiopathic group
(22/27). In ARP group, 10 were due to biliary causes (choledochal cysts 8, gallstones 2), pancreas divisum 3, duodenal diverticulum 1 and the remaining 46
(76.6%) were idiopathic. Over a median follow-up of 12 (range 3 to 120) months
31% (11/35) of idiopathic ARP cases developed CP. Almost half of CP (39 /74)
were chronic calcific, 6 were familial, 4 had associated pancreas divisum and the
remaining 64 (86%) were idiopathic. Among CP (n 63), over a median followup of 13 (range, 3-120) months, 3 cases developed diabetes mellitus, one steatorrhoea, none had cancer and there was no mortality.
CONCLUSION: There is almost eight fold increase in the prevalence of pancreatitis over last 12 years. Among AP (mainly idiopathic subgroup) 23% progressed to ARP and chronic pancreatitis. The majority of ARP was idiopathic
(77%) and a third of them progressed to CP. Thus a subset of pancreatitis seems
to be a continuum of acute to ARP and CP.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
PANCREAS II POSTER EXHIBITION HALL XL_____________________
P0659 EUS
GUIDED
NECROSECTOMY
CYSTOGASTROSTOMY WITH COVERED STENT FOR
PANCREATIC NECROSIS

TEMPORARY

A. Krishnan1,*, R. Ramakrishnan1 on behalf of None


1
Fortis Malar Hospitals, Chennai, India
Contact E-mail Address: dr.arunkumarpillai@gmail.com
INTRODUCTION: Pancreatic pseudocyst with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open
necrosectomy but is associated with significant morbidity, mortality, and prolonged hospital stay. Endoscopic cyst drainage with necrosectomy is an alternative and less invasive technique.
AIMS & METHODS: Aim: to evaluate pseudocyst drainage with cystogastrostomy and endoscopic necrosectomy for infected pancreatic necrosis with fully
covered self-expanding metallic stents (CSEMS).
12 patients underwent endoultrasound guided endoscopic necrosectomy and temporary cystogastrostomy for infected pancreatic necrosis by using CSEMSs.
Patient details, disease severity scores, scores for severity assessed at CT, treatment procedures, length of hospital stay, and outcome for patients undergoing
endoscopic therapy were recorded. Patients proceed to intervention if infection is
strongly suspected on clinical and radiological grounds or is confirmed bacteriologically. After the necrosis cavity had been accessed, with the assistance of
endoscopic ultrasound, a large orifice was created and necrotic debris was
removed using special short fully covered 15mm diameter SEMS with large
flares was deployed across the tract under radiological control. Completeness
of the necrosectomy procedure was ascertained by visualization of a clear pseudocyst cavity on endoscopy.
RESULTS: A total of 12 patients (10 men, 2 women; median age 39, range 19 76) were treated successfully. Median APACHE 2 score on presentation was 11
(range 318). Two patients presented with organ failure and needed intensive
care. Necrosis was successfully treated endoscopically in all patients, requiring a
median of 2 endoscopic interventions (range 14). The tissue samples obtained at
the first necrosectomy confirmed infection in 12 patients. Complication included
superinfection in patient who made an uneventful recovery. After median of 5
weeks the metal SEMS was extracted by endoscopy. The patients have remained
asymptomatic and median follow-up was 4 (211) months.
CONCLUSION: Endoscopic necrosectomy and temporary cystogastrostomy
with self-expanding metallic stent approach is feasible, safe, and effective in
patient with infected pancreatic necrosis. The benefits of this endoscopic
approach using fully covered self-expandable metallic stent in terms of less morbidity is conceivable and our report demonstrates that such an approach is
feasible.
Disclosure of Interest: None declared
P0660 EUS-GUIDED PANCREATIC PSEUDOCYST DRAINAGE: AN
ASSESSMENT OF EFFICACY, SAFETY, LONG-TERM FOLLOW-UP,
AND TECHNICAL FEASIBILITY OF SINGLE-STEP APPROACH
A. Krishnan1,*, R. Ramakrishnan1 on behalf of None
1
Fortis Malar Hospitals, Chennai, India
Contact E-mail Address: dr.arunkumarpillai@gmail.com
INTRODUCTION: Pancreatic pseudocyst is common complication of acute and
chronic pancreatitis. While surgery is associated with significant complications
and mortality, percutaneous drainage is associated with prolonged hospitalization and often times the need for other adjunctive treatment.
AIMS & METHODS: Assess the safety and efEcacy of single-step EUS-guided
pseudocyst drainage, evaluate the technical Feasibility.
69 patients who had undergone Single-step EUS guided drainage of pancreatic
pseudocyst were included. Controlled radial expansion wire guided balloon dilation of the puncture tract was performed followed by insertion 10 Fr double
pigtail stents were inserted into the pseudocyst from either the stomach or the
duodenum in adults and 7F stents in children.
RESULTS: The mean age of 39 years. Median size was 12.5 cm in diameter. 56
patients had infected and rest had non-infected pseudocyst. Stent placement was
successful in all. The technical success rate was 100%, and the treatment success
rate was 98.5%. 54 patients had cystogastrostomy and rest of the patients had
cystoduodenostomy with cyst drainage. There was one case with perforation and
required an emergency operation. 98.5% patients had complete resolution of a
pseudocyst. The double pigtail stent was removed in all cases after median duration of 10 weeks. Regarding long-term outcomes, recurrence of a pseudocyst was
not observed over a median follow-up of 58 weeks.
CONCLUSION: Single-step EUS-guided transmural drainage is safe and associated with high success rate. It can be the first choice for therapy of pancreatic
pseudocyst with good technical feasibility, efficacy, and safety with long-term
results are acceptable.
Disclosure of Interest: None declared

A314

United European Gastroenterology Journal 2(1S)

P0661 EUS-GUIDED INTERVENTION IN WALLED-OFF PANCREATIC


NECROSIS (WOPN): SINGLE CENTER EXPERIENCE WITH LONG
TERM FOLLOW-UP
M.C. Sulz1, C. Meyenberger1,*
Department of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St.
Gallen, Switzerland
Contact E-mail Address: michael.sulz@kssg.ch
1

INTRODUCTION: Necrotising pancreatitis is associated with high morbidity


and mortality [1-3]. Walled-off pancreatic necrosis (WOPN) is defined as a
mature, encapsulated necrotic collection with well defined wall. Early intervention (5 4 weeks) should be avoided whenever possible [4, 5]. Compared to the
traditional surgical necrosectomy, the endoscopic treatment shows significant
reduction of major complications, of pancreatic fistula, and of pro-inflammatory
response (IL-6). We present the largest prospective single-center experience
regarding endoscopic treatment of WOPN in Switzerland with long term
follow-up and add data to the increasing experience with this technique.
AIMS & METHODS: To evaluate the short- and long term outcome of patients
with walled-off pancreatic necrosis (WOPN) after endoscopic treatment. This
retrospective, observational study at a single center with tertiary care endoscopy
in Switzerland included all patients with necrotising pancreatitis from 2002 until
2013 complicated by WOPN who underwent endoscopic treatment (two experienced interventionalists). Clinical short term success (530 days) was defined as
resolution of patients symptoms requiring no further interventions. Clinical failure was defined as failure to either resolve the collection, or requiring other
interventions, and/or complications requiring other therapeutic modalities (e.g.
surgery), and/or death. Approval was obtained by the local Ethical committee.
RESULTS: 35 Caucasian patients with WOPN (median age 64.1 y, range 40-85
y; ASA II and III 51.3% and 35.9%; 73.1% males) underwent endoscopic treatment. The biliary disease was the primary cause of necrotising pancreatitis
(57.1%). The median duration of pigtails was 52 days (range 8-552 days), the
median duration of transpapillary stents was 82.5 days (range 5-563 days). The
short- and long term results results are shown in Table 1.
Short- and longterm outcome

Complete clinical success


Radiological success
complete/ partial
Short term mortality (530d)
Complication rate
Overall/related to endotherapy/to drainage
Rate of additive radiological drainage
Rate of additive surgery
Hospital stay, days, median (range)
Time of follow-up, months (median, range)
Longterm clinical well-being
Long term mortality (related to disease)
After endoscopic treatment/after surgery
Secondary clinical failure (%)
Re-treatments (%)
Elective surgery

62.3
75.3
20.8/54.5
11.5
26.7/15.4/11.5
15.4
23.1
41 (3-114)
30.5 (1-180)
76.9 %
12.0 %
4.0/8.0%
21.7 %
14.3 %
23.8 %

CONCLUSION: Our short term and long term follow-up data confirm that
endoscopic interventions in WOPN are effective and safe. Future randomized
prospective multicenter trials are needed to increase the generalizability.
REFERENCES
1 Banks PA, et al. Am J Gastroenterol 2006; 101: 2379.
2 Martinez J, et al. Pancreatology 2006; 6: 206.
3 Chauhan S, et al. Am J Gastroenterol 2010; 105: 443.
4 Freeman ML, et al. Pancreas 2012; 41: 1176-1194.
5 Baron TH, et al. Clin Gastroenterol Hepatol 2012; 10: 1202-1207.
Disclosure of Interest: None declared
P0662 SINGLE-CENTER PROSPECTIVE, COHORT STUDY OF THE
NATURAL HISTORY OF ACUTE PANCREATITIS
G.M. Cavestro1,*, G. Leandro2, M. di leo1, R.A. zuppardo1, O.B. Morrow3,
C. Notaristefano1, G. Rossi1, S.G. G. Testoni1, G. Mazzoleni1, M. Alessandri1,
E. Goni1, S.K. Singh4, A. Giliberti2, M. Bianco2, L. Fanti1, E. Viale1,
P.G. Arcidiacono1, A. Mariani1, M.C. Petrone1, P.A. Testoni1
1
Division of Gastroenterology and Gastrointestinal Endoscopy, Gastroenterology
and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, Scientific
Institute San Raffaele, Milan, 2Gastroenterology Unit 1, Gastroenterological
Hospital S. De Bellis IRCCS, Castellana Grotte, 3Gastroenterology and
Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, Scientific
Institute San Raffaele, Milan, Italy, 4Section of Gastroenterology, Boston
University School of Medicine and Boston Medical Center, Boston, United States
Contact E-mail Address: cavestro.giuliamartina@hsr.it
INTRODUCTION: The natural history of acute pancreatitis(AP) is based on
retrospective studies that elucidate the possible course of disease. The aim of this
prospective, observational study was to evaluate the long-term occurrence of
recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP), in a cohort

of patients affected by an initial episode of AP admitted to a single tertiary


referral center.
AIMS & METHODS: 196patients admitted to our center for an initial episode of
AP were consecutively enrolled and prospectively followed for 52.5 (26.8) months[mean (SD)]. Clinical characteristics,exogenously and endogenously associatedfactors,and evolution to RAP and CP were analyzed.
RESULTS: 40patients developed RAP and 13 of these developed CP. The annual
relapse rate was 5.4 (CI 95% 4.0-7.4) per 100 person-years. In univariate analysis,
RAP was associated with idiopathic etiology (p50.001), pancreas divisum (PD)
(p 0.001), higher cigarettes and alcohol intake (p50.001; p 0.023). CP was
associated with severe AP first-episode (p 0.048), PD (p 0.03), and cigarettes
smoking (p 0.038). By multivariate analysis,PD was an independent risk factor
for RAP development (OR 11.5, 95% CI 1.6-83.3). Severe AP first episode
increased the risk of progressing to CP by nine-fold (OR 9.3, 95% CI 1.847.2). Mutation frequencies of CFTR and SPINK-1 N34S were substantially
higher compared to the general population but not statistically significant.
CONCLUSION: Understanding the factors that may predispose to RAP and CP
holds important clinical implications for the prevention of disease progression.
Special attention should be given to patients who experienced a severe first attack
of AP, given the increased risk of developing CP.
Disclosure of Interest: None declared
P0663 A PROSPECTIVE MULTICENTER EVALUATION OF THE
RADIOLOGICAL PERFORMANCE OF THE REVISED ATLANTA
CLASSIFICATION
H. Sternby1,*, R.C. Verdonk2, A. Dimova3, P. Ignatavicius 4, L. Ilzarbe5,
P. Koiva6, A. Nieminen7, T.L. Bollen8 on behalf of Pancreas 2000 Atlanta Group
1
Dep of Surgery, ICS, Malmo, Sweden, 2Dep of Gastroenterology, AZ,
Nieuwegein, Netherlands, 3Dep of Surgery, UHP, Sofia, Bulgaria, 4Dep of
Surgery, HLUHS, Kaunas, Lithuania, 5Dep of Gastroenterology, HdM,
Barcelona, Spain, 6Dep of Gastroenterology, ETCH, Tallinn, Estonia, 7Dep of
Surgery, HUS, Helsinki, Finland, 8Dep of Radiology, AZ, Nieuwegein,
Netherlands
Contact E-mail Address: hannasternby@gmail.com
INTRODUCTION: The Revised Atlanta Classification defines morphological
features and descriptions of acute pancreatitis (AP) and its complications to
enable standardized reports and communication. New computer tomography
(CT) criteria are introduced to describe local complications in AP. However,
these CT criteria have not yet been validated in an international setting.
AIMS & METHODS: The aim of this study was to analyze the interobserver
agreement of the revised Atlanta criteria for CT findings in AP. Patients with a
first episode of AP who obtained a CT were consecutively enrolled at six
European centers. The CTs of each center were prospectively scored separately
by a local radiologist at each center and an expert central radiologist (representing the reference standard) using the criteria stated in the Revised Atlanta
Classification. No specific training was provided for the local radiologists before
scoring. Interobserver agreement was determined using Kappa statistics. Clinical
data was collected retrospectively.
RESULTS: 285 patients (56 % males) with a median age of 58 years with 388
CTs in total were enrolled. Aetiology of AP was gallstones in 36.6 %, alcohol in
35.9 %, and idiopathic in 27.5 % of the patients. AP was mild in 37,5 % of the
patients, in 51.5 % moderately severe, and severe in 10.9 %. Overall interobserver agreement was moderate to substantial. However, the agreement differed
substantially between the participating centers. The center independent kappa
values for the different categories are shown in the table below.
Category scored

Kappa value - Agreement

Type of pancreatitis
Parenchymal necrosis
Extrapancreatic necrosis (EXPN)
Presence of Collections
Location of Collections
Characteristics of Collections
Presence and Characteristics of Wall
Presence of gas/fluid level
Collection most appropriate term

0,370
0,539
0,326
0,756
0,633
0,408
0,675
0,764
0,356

- Fair
- Moderate
- Fair
Substantial
- Moderate
- Fair
- Substantial
- Substantial
- Fair

In four categories agreement was merely fair. Detailed analysis showed that the
low kappa values can be explained by discrepancies in the identification of extrapancreatic necrosis (EXPN). In most centers, the local radiologists identified
EXPN less frequently than the expert central radiologist (126 vs 230 cases).
CONCLUSION: For most findings, interobserver agreement is moderate to
good when CTs are scored according to the Revised Atlanta Classification
even without prior training or instructions. However, the identification of
EXPN remains problematic with poor interrater agreement. Previous studies
suggest that EXPN might be considered a separate entity in acute pancreatitis.
Given the results of this study, the definition and recognition of EXPN deserves
further study.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)

A315

P0664 ORAL UDENAFIL AND ACECLOFENAC FOR THE PREVENTION


OF POST-ERCP PANCREATITIS IN HIGH-RISK PATIENTS: A
RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY

P0666 CLINICAL PREDICTABILITY OF FLUID COLLECTIONS IN


ACUTE PANCREATITIS USING INTERLEUKIN-6 LEVEL AND
NOVEL APACHE-IL SCORE

H.-C. Oh1,*, T.Y. Lee2, J.S. Choi3, T.Y. Park1, J.H. Do1, Y.K. Cheon2,
T.J. Song4
1
GASTROENTEROLOGY, CHUNG-ANG UNIVERSITY COLLEGE OF
MEDICINE, 2GASTROENTEROLOGY, Konkuk University, Seoul,
3
GASTROENTEROLOGY, Inje Univ Busan Paik Hosptial, Busan,
4
GASTROENTEROLOGY, Asan Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: ohcgi@cau.ac.kr

S. Appasani1,*, J. Basha1, M. manrai1, P. Siddappa1, T. Yadav2, V. Gupta2,


P. Sarotra3, S.K. Sinha1, R. Kochhar1
1
Gastroenterology, 2Surgery, 3Clinical Pharmacology, PGIMER, Chandigarh,
India
Contact E-mail Address: drasreekanth@gmail.com

INTRODUCTION: Acute pancreatitis is a common complication of ERCP.


Combination therapy with oral udenafil and aceclofenac may reduce the occurrence of post-ERCP pancreatitis by targeting different pathophysiological
mechanisms underlying acute pancreatitis. This study aimed to determine
whether combining udenafil and aceclofenac reduces the rates of occurrence of
post-ERCP pancreatitis.
AIMS & METHODS: A prospective, randomized, double-blind, placebo-controlled, multicenter study was conducted in four academic medical centers.
Between January 2012 and June 2013, a total of 216 patients who underwent
ERCP were analyzed for the occurrence of post-ERCP pancreatitis. Patients
were determined to be at high risk for pancreatitis on the basis of validated
patient and procedure-related risk factors.
RESULTS: Demographic features, indications for ERCP, and therapeutic procedures were similar in each group. There was no significant difference in the rate
(15.8% [17/107] vs. 16.5% [18/109], p .901) and severity of post-ERCP pancreatitis between the udenafil/aceclofenac and placebo groups. One patient in
each group developed severe pancreatitis. On multivariate analyses, suspected
sphincter of Oddi dysfunction and endoscopic papillary balloon dilatation without sphincterotomy were associated with post-ERCP pancreatitis.
CONCLUSION: Combination therapy with udenafil and aceclofenac was not
effective for the prevention of post-ERCP pancreatitis.
Disclosure of Interest: None declared
P0665 NASOGASTRIC TUBE FEEDING VERSUS NASOJEJUNAL TUBE
FEEDING IN SEVERE ACUTE PANCREATITIS
J.M. Rubio1,*
1
Section of Gastroenterology, Philippine General Hospital, Manila, Philippines
Contact E-mail Address: jowi5271@yahoo.com
INTRODUCTION: Severe acute pancreatitis is a major cause of morbidity and
mortality. Reviews have advocated enteral nutrition over parenteral nutrition in
its management. Nasogastric tube is easier to insert than nasojejunal tube. The
objective of this study is to determine the efficacy of nasogastric tube feeding in
terms of exacerbation of pain, mortality, pancreatic infection and complications
such as diarrhea in comparison to nasojejunal feeding.
AIMS & METHODS: RCTs among patients with severe acute pancreatitis
comparing NGT feeding to NJT feeding were selected for inclusion. Search for
randomized controlled trials was carried out using search engines such as
PubMed, Ovid, Google scholar. Search terms were severe acute pancreatitis,
enteral nutrition and other synonyms listed in MeSH. The data were analyzed
using Review Manager RevMan5.
RESULTS: 86 studies were found. Only 3 studies were included. NGT feeding
did not result in an increase in exacerbation of pain as compared to NJT feeding
(CI 0.31-3.22, p value 0.99). There was no significant difference between NGT
and NJT feeding in terms of mortality (CI 0.38-2.06, p value 0.77). NGT feeding
showed a trend towards benefit in reducing pancreatic infection (CI 0.17-1.76, p
value 0.31). NGT feeding showed a trend toward causing diarrhea (CI 0.56- 4.05,
p value 0.42).
CONCLUSION: NGT feeding is comparable to NJT feeding in exacerbation of
pain, incidence of infection, complications such as diarrhea and mortality. NGT
feeding can be used as an alternative to NJT feeding in institutions where an
endoscopy guided NJT insertion cannot be done
REFERENCES
1. Kumar A, Singh N, Prakash S, et al. Early enteral nutrition in severe acute
pancreatitis: A prospective randomized controlled trial comparing nasojejunal
and nasogastric routes. Clin Gastroenterol 2006; 40: 431-434.
2. Eatock FC, Chong P, Menezes N, et al. A randomized study of early nasogastric tube versus nasojejunal feeding in severe acute pancreatitis. Am J
Gastroenterol 2005; 100: 432-439.
3. Singh N, Sharma B, Sharma M, et al. Evaluation of early enteral feeding
through nasogastric and nasojejunal tube in severe acute pancreatitis. Pancreas
2012; 41: 153-159.
4. Petrov M, Correia M and Windsor J. Nasogastric tube feeding in predicted
severe acute pancreatitis. A systematic review of the literature to determine safety
and tolerance.
5. McClave S, Chang W, Dhaliwal R, et al. Nutrition support in acute pancreatitis: A systematic review of the literature. J Parenter Enteral Nut
6. Feldman M, Friedman L and Brandt L. Sleisenger and Fordtrans gastrointestinal and liver disease. 9th ed., 2010.
Disclosure of Interest: None declared

INTRODUCTION: Cytokine storm occurring in early phase of acute pancreatitis (AP) plays an important role in development of local & systemic complications. Fluid collections contribute significantly to the morbidity of this illness,
hence its predictability in early phase could help in clinical triage.
AIMS & METHODS: AIMS
To prospectively evaluate the role of cytokine estimation at admission to predict
the formation of fluid collections and correlate it with standard scoring systems.
MATERIALS AND METHODS
110 consecutive patients (69% males, age 1770yrs) with AP were evaluated after
an informed consent from Jan2012-March2013. Patients were stratified into
mild, moderate & severe pancreatitis as-per revised Atlanta criteria and were
treated with nutritional & organ support. Serum cytokine (Interleukin (IL) 6,
10, Tumor Necrosis Factor (TNF) Alpha) and fibronectin levels were analyzed
quantitatively at admission (ELISA). APACHE, BISAP & SIRS scores were also
calculated. Cytokine levels were compared with standard parameters while analyzing severity, development of fluid collections and outcome of AP using SPSS
v17.0.
RESULTS: The median levels of IL-6 were higher in patients with severe pancreatitis (761.78pg/ml, n 42) than in those with mild pancreatitis (277.80pg/ml,
n 40) and moderate pancreatitis (397.50pg/ml, n 28, p 0.038). At a cut off
of 488pg/ml, IL-6 had a sensitivity of 85% & specificity of 75% in predicting
severe pancreatitis (AUC 0.702, p 0.016). The median IL-6 levels were higher
in patients with necrosis (635.0pg/ml) than in those without (372.5pg/ml,
p 0.008) as well in patients with organ failure than those without (540.35pg/
ml vs. 406.42pg/ml, p 0.046). Serum IL-10, TNF Alpha and fibronectin levels
did not correlate with these events. Pearson & Spearman bivariate analysis
revealed good correlation of IL-6 with CTSI (0.432, p 0.001), APACHE
score (0.354, p 0.032), BISAP score (0.316, p 0.019) and SIRS score (0.487,
p 0.007).
Patients who developed fluid collections had higher IL-6 levels than those who
did not (524.28pg/ml vs 358.21pg/ml, p 0.031). IL-6 levels also correlated with
the type of collection (acute necrotic collection vs. acute peripancreatic fluid
collection, p 0.017). Standard APACHE score predicted only severity and
necrosis but did not correlate with fluid collections. Hence we postulated a
new APACHE-IL score by adding 2 points to standard APACHE score if IL6 levels were elevated (4488pg/ml). At a cut off of 6, APACHE-IL score had a
sensitivity of 85% and specificity of 80% in predicting development of fluid
collections (AUC 0.746, p 0.027).
CONCLUSION: IL-6 level at admission is an effective predictor of severity of
acute pancreatitis (as per revised Atlanta) as well as of development of organ
failure, necrosis and fluid collections. We recommend IL-6 to be measured for
early risk stratification and APACHE-IL score for fluid collection prediction.
Disclosure of Interest: None declared
P0667 SLC26A6 VARIANTS ARE NOT ASSOCIATED WITH CHRONIC
PANCREATITIS
A. Balazs1,*, E. Hegyi1,2, B.C. Nemeth3, I. Hritz1, F. Izbeki4, J. Gervain5,
A. Szepes6, G. Gyimesi7, Z. Dubravcsik7, A. Csiszko8, D. Kelemen9,
Z. Szentkereszty8, B. Bod10, J. Sumegi11, J. Novak12, A. Parniczky13,
N. Lasztity13, G. Veres14, C. Andorka14, R. Szmola15, J. Czelecz16, A. Vincze17,
J. Bajor17, G. Farkas18, L. Czako1, T. Takacs1, Z. Rakonczay19, J. Maleth19,
A. Pap15, P. Hegyi1 on behalf of Hungarian Pancreatic Study Group
1
First Department of Medicine, University of Szeged, Szeged, Hungary, 22nd
Department of Pediatrics, University Childrens Hospital, Comenius University
Medical School, Bratislava, Slovakia, 3Department of Molecular and Cell Biology,
Boston University, Boston, United States, 4Fejer Megyei, Szent Gyorgy Hospital,
5
Fejer Megyei, Szent Gyorgy Hospital, Szekesfehervar, 6Bacs-Kiskun County,
7
Bacs-Kiskun County, Municipality Hospital, Kecskemet, 8Department of Surgery,
University of Debrecen, Debrecen, 9Department of Surgery, University of Pecs,
Pecs, 10Dr Bugyi Istvan, Hospital, Szentes, 11B-A-Z County, Hospital, Miskolc,
12
Pandy Kalman, County Hospital, Gyula, 13Heim Pal Childrens Hospital,
14
Paediatric Department, Semmelweis University, 15National Institute of
Oncology, 16Bethasda Childrens Hospital, Budapest, 17Department of Internal
Medicine, University of Pecs, Pecs, 18Department of Surgery, University of Szeged,
19
First Department of Medicine, University of Szeged, Szeged, Hungary
Contact E-mail Address: anitabalazs@outlook.com
INTRODUCTION: Cystic Fibrosis Transmembrane Conductance Regulator
(CFTR) mutations are established risk factors for chronic pancreatitis (CP).
CFTR variants increase disease risk by causing impairment of pancreatic
ductal bicarbonate secretion. However, the role of genetic variations in the bicarbonate secreting SLC26A6 anion transporter has remained largely unexplored so
far.
AIMS & METHODS: Our aim was to investigate the role of the SLC26A6 gene
in CP. 96 subjects with CP (cases) and 99 subjects with no pancreatic disease
(controls) were recruited from the Hungarian National Pancreas Registry. In a
discovery cohort of 30 idiopathic CP cases the entire SLC26A6 coding sequence,
including 21 exons and the exon-intron boundaries were amplified and
sequenced. Further genotyping of p. V206M and p. P397P mutations in CP
and controls was carried out by RFLP.

A316
RESULTS: Sequencing analysis of the discovery cohort revealed four common
mutations: intronic mutations c.2371_23103del, c.183-4C4A and
c.113432C4A; and exonic missense mutation p. V206M. These four mutations
were found in linkage disequilibrium indicating a conserved haplotype. We found
this haplotype in 18 heterozygous and 2 homozygous cases, and in 24 heterozygous and 2 homozygous controls (allele frequency 11.4% and 14.1% respectively). A synonymous mutation p. P397P was also detected in a single case.
CONCLUSION: We found a novel, common haplotype in the SLC26A6 gene,
which did not show association with CP. Supported by TAMOP and OTKA
Disclosure of Interest: None declared
P0668 PANCREATIC EXOCRINE INSUFFICIENCY IN PATIENTS WITH
HIV AND CHRONIC DIARRHOEA
A. Jeevagan1,*, M. AUSTIN1, S. Soni2
1
Gastroenterology, 2Sexual Health and HIV, Lawson Unit, Royal Sussex County
Hospital, BRIGHTON, United Kingdom
Contact E-mail Address: arun.jeevagan@nhs.net
INTRODUCTION: Chronic Diarrhoea (CD) in HIV-infected patients is an
important cause of morbidity and has significant impact on their quality of
life. Pancreatic exocrine insufficiency has been shown to be associated with
HIV and has been suggested as an important non-infective cause of diarrhoea
and fat malabsorption in these individuals.
AIMS & METHODS: HIV-positive patients undergoing investigation for CD
between January 2011 and August 2013 were identified. Demographics and clinical data including measurement of faecal elastase were taken from the patients
medical records.
RESULTS: 60 patients were referred by the HIV team to Gastroenterology clinic
for investigation of CD. There were 55 (92%) male and mean age was 44 years.
All were receiving antiretroviral therapy. No patients had a diagnosis of chronic
pancreatitis. 31/60 patients had raised faecal calprotectin, one had stool culture
positive for giardiasis, one had lymphocytic gastritis and so 34 patientswere
excluded from the study. Out of these, 27 patients who had faecal elastase measurements and 9/27 (30%) had pancreaticin sufficiency.
CONCLUSION: In patients with HIV on antiretrovirals, in whom inflammation
and infection had been excluded, approximately 30% of patients were confirmed
to have pancreatic exocrine insufficiency. This prevalence is greater than that
seen in HIV-negative individuals with chronic diarrhoea. HIV treatment with
didanosine or stavudine-containing antiretroviral regimens used to be the main
culprit but these drugs are seldom used in the management of HIV nowadays and
other causes must be considered. Faecal elastase sampling should form part of
the routine work-up for HIV-positive patients with chronic diarrhoea. Treatment
with pancreatic enzyme supplementation is effective treatment of chronic diarrhoea in these patients.
Disclosure of Interest: None declared
P0669 THE ROLE OF SPINK1 PROXIMAL PROMOTER VARIANTS IN
CHRONIC PANCREATITIS
E. Hegyi1,2, A. Geisz3, T. Takacs2, G. Farkas, Jr4, Z. Szepes2, J. Novak5,
F. Izbeki6, J. Gervain6, I. Hritz2, A. Szepes7, D. Kelemen8, Z. Dubravcsik7,
B. Bod9, R. Szmola10, J. Sumegi11, Z. Szentkereszti12, Z. Rakonczay, Jr2,
A. Balazs2,*, P. Hegyi2, M. Sahin-Toth3, L. Czako2 on behalf of Hungarian
Pancreatic Study Group
1
2nd Department of Pediatrics, Comenius University Medical School, University
Childrens Hospital, Bratislava, Slovakia, 2First Department of Medicine,
University of Szeged, Szeged, Hungary, 3Department of Molecular and Cell
Biology, Boston University Medical Center, Boston, United States, 4 Department
of Surgery, University of Szeged, Szeged, 5Bekes Megyei Pandy Kalman Hospital,
Gyula, 6Fejer Megyei Szent Gyorgy Hospital, Szekesfehervar, 7Bacs-Kiskun
Megyei Hospital, Kecskemet, 8Department of Surgery, University of Pecs, Pecs,
9
Dr. Bugyi Istvan Hospital, Szentes, 10National Institute of Oncology, Budapest,
11
Borsod-Abauj-Zemplen Megyei Hospital, Miskolc, 12 Department of Surgery,
University of Debrecen Medical School and Health Science Center, Debrecen,
Hungary
Contact E-mail Address: hegyi.peter@med.u-szeged.hu
INTRODUCTION: Serine protease inhibitor Kazal type 1 (SPINK1) provides
an important line of defense against premature trypsinogen activation within the
pancreas. The most common SPINK1 mutation p. N34S seems to increase the
risk of chronic pancreatitis (CP), but the precise pathophysiological mechanism
of this mutation remains a subject of debate.
AIMS & METHODS: To determine the frequency of the p. N34S SPINK1
mutation in Hungarian patients with alcoholic chronic pancreatitis (ACP) and
idiopathic chronic pancreatitis (ICP) and to identify a possible pathogenic promoter variant linked with the p. N34S mutation. 70 subjects with CP (cases) (34
ACP and 36 ICP) and 70 subjects with no pancreatic disease (controls) were
enrolled from the Hungarian National Pancreas Registry. Direct sequencing of
the SPINK1 proximal promoter region (1 kb) was performed. The p. N34S
SPINK1 mutation was analysed by RFLP.
RESULTS: The p. N34S mutation was present in 3/70 patients, all with the
diagnosis of ICP, while it was absent in healthy controls (P 0.24). Two promoter variants (c.-253T4C and c.-807C4T) were found as common polymorphisms indicating no clinical significance. Additionally, three rare promoter
variants (c.-14G4A, c.-108G4T, and c.-215G4A) were identified in cases.
The c.-215G4A variant was linked with the pathogenic c.1942T4C mutation.
The clinical significance of the c.-14G4A and c.-108G4T variants is unclear so
far.
CONCLUSION: We identified two novel variants in the proximal promoter
region of SPINK1 which will be further investigated to determine their possible

United European Gastroenterology Journal 2(1S)


association with CP. No associations were found between the p. N34S mutation
and promoter region variants of the SPINK1 gene.
Supported by TAMOP, OTKA and MTA and Collegium Talentum scholarship
(to E. H.).
Disclosure of Interest: None declared
P0670 QUANTIFICATION OF EXOCRINE DUCTAL PANCREATIC
FUNCTION USING A SHORT ENDOSCOPIC SECRETIN TEST AND
AUTOMATIC DUODENAL BICARBONATE MEASUREMENT
F. Erchinger1,2,*, O.A. Gudbrandsen2, T. Engjom2,3, E. Tjora4, D. Hoem5,
T. Hausken2,3, O.H. Gilja2,6, G. Dimcevski2,3
1
Medical Department, Voss Hospital, Voss, 2Department of Clinical Medicine,
University of Bergen, 3Department of Medicine, 4Department of Pediatrics,
5
Surgical Department, 6National Centre for Ultrasound in Gastroenterology,
Haukeland University Hospital, Bergen, Norway
Contact E-mail Address: friedemann.erchinger@helse-bergen.no
INTRODUCTION: A short endoscopic secretin test has recently been evaluated
in different patient groups and provides useful information about exocrine ductal
pancreatic function(1-3). Bicarbonate in duodenal juice is an important parameter
in direct pancreas function testing. Gold standard is measurement of bicarbonate
by back titration right after endoscopy, but this is time consuming, and requires
specialised equipment and highly skilled laboratory staff. A simplified method is
warranted.
AIMS & METHODS: The aim was to determine if back titration can be replaced
by an automated spectrophotometric method.
Patients examined with short endoscopic secretin test suspected to have decreased
pancreatic function of various reasons. Bicarbonate in duodenal juice was analysed both by back titration and automatic spectrophotometry. In our short
endoscopic secretin test duodenal juice is suctioned in three aliquots of 5 minutes.
Both fresh and thawed samples were analysed.
RESULTS: 122 samples from 49 patients (25 men/24 women) were analysed.
Correlation coefficient of all measurements was r 0.98. Correlation coefficient
of fresh versus frozen samples conducted with automatic spectrophotometry
(n 27): r 0.96.
CONCLUSION: The measurement of bicarbonate in both fresh and thawed
samples, by automatic spectrophotometric analysis correlates excellent with measurements made by back titration. This is a major simplification of direct pancreas function testing, and makes it possible to perform such tests standardised in
all hospitals, in a time- and centre-independent way.
REFERENCES
(1) Erchinger F, Engjom T, Tjora E, et al. Quantification of pancreatic function
using a clinically feasible short endoscopic secretin test. Pancreas 2013.
(2) Tjora E, Wathle G, Erchinger F, et al. Exocrine pancreatic function in hepatocyte nuclear factor 1beta-maturity-onset diabetes of the young (HNF1BMODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas. Diabet Med 2013.
(3) Tjora E, Wathle G, Engjom T, et al. Severe pancreatic dysfunction but
compensated nutritional status in monogenic pancreatic disease caused by carboxyl-ester lipase mutations. Pancreas 2013.
Disclosure of Interest: None declared
P0671 EFFICACY OF ANTIOXIDANT THERAPY IN IMPROVING
PAINFUL CHRONIC PANCREATITIS: A SYSTEMATIC REVIEW
G. Ianiro1,1,*, L. Valerio2, M. Siciliano1, F. Scaldaferri1, I. Boskoski3,
G. Costamagna3, A. Gasbarrini1
1
Dept of Internal Medicine, Division of Gastroenterology, CATHOLIC
UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy, 2Dept of
Cardiovascular Medicine, Amsterdam Medical Center, Amsterdam, Netherlands,
3
Digestive Endoscopy Unit, CATHOLIC UNIVERSITY SCHOOL OF
MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: To date, there is no standardized treatment for pain caused
by chronic pancreatitis. Medical, endoscopic or surgical therapy are the currently
available approaches. Antioxidants have been proposed on the rationale that
they may slow down the damage of the gland produced by oxidative stress.
Although several trials have been carried out over the years, no one of them
showed convincing results.
AIMS & METHODS: Our aim was to systematically review the literature related
to the efficacy of antioxidants in improving painful chronic pancreatitis. This
systematic review was conducted in accordance with the PRISMA guidelines. All
the original reports in which human subjects, both children and adults, with
chronic pancreatitis were treated with antioxidants were considered for inclusion.
Inclusion criteria also required the pain as endpoint, and the report of efficacy
outcomes. No language restriction was set up. Animal model studies, studies
presented only as abstracts, case reports and case series with less than 10 patients
were excluded. The following databases were used to perform the literature
search: PubMed, SCOPUS, Web of Science, the Cochrane Library. The last
search was run on 27 February 2013. The following MeSH terms and keywords
were used alone or in combination: antiox*; vitamin supplement; antioxidant
supplement; vitamin A supplement; vitamin B6 supplement; vitamin B12 supplement; folic acid supplement; vitamin C supplement; vitamin D supplement; vitamin E supplement; selenium supplement; beta-carotene supplement; lycopene
supplement; isoflavone supplement; chronic pancreatitis. A quality appraisal of
the selected studies was performed.
RESULTS: The literature search retrieved 3590 studies; of these, 9 met our
inclusion criteria. Six were blinded randomized clinical trials, 2 open trials, and
1 a prospective cohort study. Their comparability was severely limited because of

A317

United European Gastroenterology Journal 2(1S)


differences in the endpoints chosen, which include pain-free days, pain scores,
quality of life scores, and supportive care needed; possibly severe selection bias
and low statistical power due to small sample size were found in some studies.
The few points of partial convergence include a potential reduction in the need of
supportive therapies and inefficacy of antioxidants in alcoholic pancreatitis.
CONCLUSION: Available evidence is inconclusive: confirmation or refusal of
the efficacy of antioxidant therapies against pain in chronic pancreatitis needs to
be investigated by further randomized controlled trials, with adequate design and
standardized outcome variables, so as to allow for comparison.
Disclosure of Interest: G. Ianiro: nothing to declare, L. Valerio: nothing to
declare, M. Siciliano: nothing to declare, F. Scaldaferri: nothing to declare, I.
Boskoski: nothing to declare, G. Costamagna: nothing to declare, A. Gasbarrini:
nothing to declare
P0672 AUTOIMMUNE PANCREATITIS
CENTRE EXPERIENCE

IN

CHILDREN-

remaining biopsy revealed pancreatic tissue with some areas of fibrosis. Samples
from the other seven patients (70%) were not adequate for cytohistological
diagnosis due to the absence of tissue and a poor cellularity. There was one
complication (10%), a mild acute pancreatitis requiring hospitalization for 48
hours.
CONCLUSION: EUS-FNB is feasible in the context of patients with EUS findings of early CP. Samples obtained by the commercially available needles are
however not adequate for histological evaluation. In addition, the risk of complications exists. EUS-FNB for the diagnosis of early CP should be avoided
unless new more appropriate needles are developed and can be evaluated for
efficacy and safety in well-designed clinical trials.
Disclosure of Interest: J. Iglesias-Garc a Lecture fee (s) from: Cook-Medical,
Consultancy for: Cook-Medical, J. Larino-Noia: None declared, I.
Abdulkader: None declared, B. Lindkvist: None declared, J. E. DominguezMunoz: None declared

SINGLE

G. Oracz1,*, B. Cukrowska2, K. Wejnarska1, E. Kolodziejczyk1, J. Kierkus1,


J. Ryzko1
1
Dep. of Gastroenterology, Hepatology and Feeding Disorders, 2Dep. of Pathology,
The Childrens Memorial Health Institute, Warsaw, Poland
Contact E-mail Address: grzegorz_oracz@poczta.onet.pl
INTRODUCTION: The etiology of chronic pancreatitis in children is varied and
includes gene mutations, anatomic anomalies, and others. The reported paediatric experience with chronic pancreatitis (CP) is small and little is known about
the role of autoimmune pancreatitis (AIP).
AIMS & METHODS: The aim of the study was to assess the frequency of
autoimmune markers in children with CP.
136 children with CP hospitalized at the Department of Gastroenterology, The
Childrens Memorial Health Institute, between 2005 and 2014 were examined for
the presence of AIP; the level of IgG4 was determined, and the tests for antitissue antibodies were conducted. AIP was diagnosed according to the IAP
guidelines, i.e. on the basis of immunological criteria (presence of antibodies:
IgG4 and autoantibodies), radiological criteria (swelling of the pancreatic
head, and changes in the pancreatic duct), and response to corticosteroid therapy. Clinical data were recorded and analyzed.
RESULTS: Anti-tissue antibodies were detected in 85/136 children (62.5%), and
29/75 patients (38.6%) showed an increased IgG4 level. Based on the IAP criteria, a suspicion of AIP was raised in 8 patients. This diagnosis was definitely
confirmed in 4 cases, based on clinical improvement observed after corticosteroid
therapy. Due to the inactive phase of the disease, the immunosuppressive therapy
was not implemented in the remaining suspected patients. In 41/85 (48.2%)
patients with autoimmune markers we found gene mutations predisposing to
CP. In 18/85 children (21.2%) anatomic anomalies were fund. There was no
difference in the severity of the disease and clinical course between children
with autoimmune stigmata and patients without autoimmune markers.
CONCLUSION: In children with CP, similarly to adults, there is a high frequency of biochemical markers of autoimmunity. AIP can be the cause of CP in
children.
Disclosure of Interest: None declared
P0673 MATERIAL OBTAINED BY ENDOSCOPIC ULTRASOUNDGUIDED FINE NEEDLE BIOPSY IS NOT ADEQUATE FOR THE
HISTOLOGICAL DIAGNOSIS OF EARLY CHRONIC PANCREATITIS
J. Iglesias-Garc a1,*, J. Larino-Noia1, I. Abdulkader2, B. Lindkvist3,
J.E. Dominguez-Munoz1
1
Gastroenterology, 2Pathology, University Hospital of Santiago de Compostela.
Foundation for Research in Digestive Diseases, Santiago de Compostela, Spain,
3
Institute of Medicine, Sahlgrenska Academy, University of Gothenburg,
Gothenburg, Sweden
INTRODUCTION: Diagnosis of early chronic pancreatitis (CP) is a clinical
challenge and it is hampered by the lack of methods for histological confirmation. Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB), with the use
of ProcoreTM histology needles provides adequate samples for the histological
evaluation of solid pancreatic lesions, but the efficacy and safety of this technique
for early CP is unknown.
AIMS & METHODS: We aimed at evaluating the efficacy and safety of EUSFNB with ProcoreTM needles for the histological diagnosis of early CP.
Methods: A prospective, pilot study with consecutive inclusion of patients
between January and September 2013 was designed. Inclusion criteria: Patients
4 18 years old submitted to our Endoscopy Unit to undergo EUS examination
because of the clinical suspicion of chronic pancreatitis. Only patients with 3-4
EUS criteria of CP were finally included. EUS-guided FNB was performed by
two experienced endosonographers in these patients under deep sedation after
signing the informed consent. A linear slim Pentax echoendoscope (EG 3270 UK)
attached to a Hitachi Ascendus ultrasound device was used for EUS. FNB of the
body of the pancreas was performed with ProcoreTM needles of different sizes.
Samples obtained were immersed into a Cytolit solution for cytohistological
evaluation. All samples were evaluated by a single expert pathologist. The quality
of the samples obtained and the histological findings (inflammatory cells infiltration and fibrosis) were evaluated. Complications were recorded.
RESULTS: The study was stopped after the inclusion of 10 patients (mean age
50.3 years, range 33-70 years, 6 male) due to unsatisfactory results. Pancreatic
EUS-FNB was feasible in all cases. A 19G ProcoreTM needle was used in 5 cases,
a 22G needle in 2 and a 25G needle in 3 cases. Sample quality was considered
adequate for histological evaluation in only 3 cases (30%), (2 performed with a
19G needle and one with a 25G needle). Two out of these three biopsies revealed
a normal pancreatic tissue and the diagnosis of CP could not be confirmed. The

P0674 A CROSS SECTIONAL STUDY TO ASSESS THE PREVALENCE


OF PANCREATIC EXOCRINE INSUFFICIENCY AMONG DIABETES
MELLITUS PATIENTS IN TURKEY
K. Demir1,*, C. Karaca1, E. Ahishali2, M. Mastanzade3, N. Gul4, F. Turker4,
S. Celik4, F. Akyuz1, F. Besisik1, K. Karsidag4
1
Gastroenterology Department, Istanbul University Medical School,
2
Gastroenterology Department, Dr. Lutfi Kirdar Kartal Training and Research
Hospital, 3Internal Medicine Department, 4Endocrinology Department, Istanbul
University Medical School, Istanbul, Turkey
Contact E-mail Address: mehmet.berktas@kappa-crt.com.tr
INTRODUCTION: Pancreatic exocrine function insufficiency (PEI) is common
in diabetes mellitus patients. Apparently, some patients with decreased exocrine
function are type 3c diabetes mellitus (DM) and misdiagnosed as type 2 or type 1
DM. There are only few data about PEI in DM patients in Turkey. This study
aims to investigate exocrine insufficiency among DM patients in Turkey.
AIMS & METHODS: The objective of the study is to assess the prevalence of
pancreatic exocrine insufficiency among type 1 and type 2 diabetes mellitus
patients in Turkey. The abstract aims to present preliminary results of the study.
This is a cross sectional, non-interventional study which was conducted in
Turkey between October 2013 and February 2014. Adult patients (older than
18 years) previously diagnosed type 1 or 2 DM, admitted to endocrinology
department with or without symptomatic gastrointestinal problems, followed
for more than five years were included to the study.
PEI was evaluated by measuring faecal elastase-1 concentration, level 5100 g/g
stool was evaluated as severe PEI, whereas 100, 5200 g/g stool as mild-tomoderate PEI and  200 g/g stool as normal (1). Upper detection limit of
method used for faecal elastase-1 concentration was 500 g/g stool.
RESULTS: Based on data of 211 DM patients [58.8% female, median (min-max)
age 58.2 (18.5-85.7) years], 146 (69.2%) were previously diagnosed type 2 DM
whereas others were type 1 DM. Median (min-max) DM duration of type 1 and 2
patients was 15.6 (5.0-43.6) and 13.5 (5.5-37.5) years, respectively.
Median (min-max) faecal elastase-1 concentration of type 1 and 2 DM patients
was 465.5 (104.0-500.0) and 474.0(52.0-500.0) g/g stool, respectively.
In entire study population, severe PEI prevalence was 1.9% (0.0% for type 1
DM, 2.7% for type 2 DM) whereas mild-to-moderate PEI prevalence was 12.3%
(17.2% for type 1 DM, 10.3% for type 2 DM). Overall; 14.2% of patients (17.2
% of type 1 DM, 13.0% of type 2 DM patients) have reduced PEI.
CONCLUSION: Preliminary results of the study revealed that PEI prevalence
among type 1 and type 2 patients was higher in Turkey and many DM patients
might be misclassified. In conclusion, evaluation of pancreatic exocrine function
in DM patients should be essential part of daily practice.
REFERENCES
1. Luth S, Teyssen S, Forssmann K, et al. Fecal elastase-1 determination: gold
standard of indirect pancreatic function tests? Scand J Gastroenterol 2001; 36:
1092-1099.
Disclosure of Interest: K. Demir Financial support for research from: Research
grant from Abbott Turkey, C. Karaca: None declared, E. Ahishali: None
declared, M. Mastanzade: None declared, N. Gul: None declared, F. Turker:
None declared, S. Celik: None declared, F. Akyuz: None declared, F. Besisik:
None declared, K. Karsidag: None declared
P0675 STUDY OF THE LIPID PROFILE AND THE OXIDATIVE STRESS
OF DIABETIC PATIENTS WITH CHRONIC PANCREATITIS
M. Sliwinska-Mosson1,*, S. Milnerowicz2, W. Sajewicz1, H. Milnerowicz1
1
Department of Biomedical and Environmental Analyses, 2Department of
Gastrointestinal and General Surgery, University of Medicine Wroclaw, Wroclaw,
Poland
Contact E-mail Address: mariola.sliwinska-mosson@umed.wroc.pl
INTRODUCTION: Smoking patients with chronic pancreatitis (CP) are at high
risk for antioxidant deficiencies (1). Moreover, this disease may lead to the
development of diabetes mellitus type II (DM2), which additionally enhances
the oxidative stress (2). The main characteristics of DM2 are insulin resistance
in muscle and liver cells accompanied by loss of -cell function. However, adipose tissue and pancreatic cell activity, may be involved in disease development
(3). Most recently a trend for positive correlation between HDL cholesterol and
amylase in DM2 patients was shown.
AIMS & METHODS: In the present study we evaluated the lipid profile and
total peroxyl radical trapping potential (TRAP), glutathione (GSH), thiobarbituric acid reactive substances (TBARS) in non-smoking and smoking patients
with CP suffering from diabetes. The relationship between different parameters
was examined. The blood was collected from 50 healthy persons and 63 patients

A318
with diagnosed chronic pancreatitis (CP). Diabetes mellitus was diagnosed in 24
patients. The concentration of cotinine and lipid profile in plasma was estimated
by the ELISA and diagnostic tests, respectively. Lipid peroxidation levels were
assessed by TBARS, and TRAP was measured by using luminescence.
Glutathione level was determined in blood hemolysates with the colometric
method.
RESULTS: The concentration of HDL were statistically lower in smoking
patients with CP with or without diabetes as compared to the control group,
while the concentration of TG and LDL were statistically highest in smoking
diabetics compared to all groups (p50.001). It was also observed that the concentration of TBARS was statistically significant increased in non-smoking and
smoking patients with CP (3.5  1.3 [mmol /l], 4.75  1.0 [mmol /l]), and patients
with CP and DM (5.3 2.6 [mmol/l]) as compared with control group (3.41.9
[mmol/l]). In smoking patients with DM, a statistical highest level of TRAP
compared to all study groups was found (p50.0001). Statistical analysis of the
results showed that the decline in the concentration of GSH is associated with
cigarette smoking and diabetes. The lowest concentration of GSH was observed
in smoking patients with CP and diabetes, the highest in non-smoking control
group (p50.0001).
CONCLUSION: The lipid profile is altered in smoking patients with CP, particularly in those who also have DM. In these patients, a glutathione deficiency
and an elevated plasma concentration of lipid peroxidation products were associated with significantly higher LDL. In the diabetic patients group, a positive
correlation between TRAP and TBRAS was found, which points to the induction
of the antioxidant potential on intensification of lipid peroxidation.
REFERENCES
1.Sliwinska-Mosson M, et al. Pancreatology 2012; 12: 295-304.
2.de M Bandeira S, et al. Int J Mol Sci 2013; 5: 3265-3284.
3. Eleftheriou P, et al. Hell J Nucl Med 2014; 17(Suppl. 1): 35-39.
Disclosure of Interest: None declared
P0676 CLINICAL FEATURES OF PANCREATIC INVOLVEMENTS OF
VON HIPPEL-LINDAU DISEASE IN KOREA
T. Park1,*, S. Lee1
1
Department of Gastroenterology, Asan medical center, University of Ulsan
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: ptymd@hotmail.com
INTRODUCTION: Von Hippel-Lindau disease (VHL) is autosomal dominant
disorder characterized by development of multiple tumors in central nervous
system and visceral organs. There have been reported a few studies about clinical
courses of pancreatic involvements of VHL.
AIMS & METHODS: In this study, we report clinical features of pancreatic
involvements of VHL in Korea. We conducted retrospective cohort study of
55 patients who were diagnosed with VHL-associated pancreatic lesions from
1995 to 2013 in Asan Medical Center. Demographic, genetic, radiologic features
and clinical features of VHL-associated pancreatic lesions were analyzed by
medical record review.
RESULTS: 55 patients had VHL-associated pancreatic lesions (87.3%). Median
onset of age was 33 years (12-67 years) and male and female ratio was 31:24.
Median observation period was 1731 days (3-5077). Genetic test was performed
in 35/55 patients (63.6%) and VHL gene mutations were confirmed in 28/35
patients (80%). VHL gene mutation was located on exon 1 in 13 patients
(46.4%), exon 2; 4 (14.3%), exon 3; 9 (32.1%) and others 2 (7.2%). Mean
involved number of organs was 2.51  0.72. Most common subtype of VHL
was type I as 44/55 patients (80%). Pancreatic involvements were included single
simple cyst (n 5, 9.1%), multiple simple cysts (n 14, 25.5%), serous cystadenoma (n 29, 52.7%) and neuroendocrine tumor (n 17, 30.9%). Initial presented VHL-associated tumors as only pancreatic lesions were observed in only 2
of 55 patients (3.6%) and pancreatic symptoms were only 4 patients (7.3%). Of
55 patients, 11 patients received surgical treatment and 2 patients received EUSguided ethanol ablation therapy as local treatment for neuroendocrine tumor and
42 patients were observed regularly without intervention (20%, 3.6%, 76.4%
respectively). One patient received distal pancreatectomy as radiologic diagnosis
of neuroendocrine tumor, however, final pathologic diagnosis was serous cystadenoma, which was thought to be solid microcystic serous adenoma (SMSA).
One patient was died of pulmonary hemorrhage due to pulmonary metastasis of
VHL-associated renal cell carcinoma.
CONCLUSION: Most common presentation of pancreatic involvement in VHL
was serous cystadenoma. Pancreatic tumors as primary presenting lesion in VHL
are relatively rare and most of pancreatic lesions were asymptomatic. Nationwide
epidemiologic study is needed to verify natural course and prognosis of pancreatic involvement in VHL.
REFERENCES
1. Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet
2003; 361: 2059-2067.
2. Lee KH, Lee JS, Kim BJ, et al. Pancreatic involvement in Korean patients with
von Hippel-Lindau disease. J Gastroenterol 2009; 44: 447-452.
3. Hammel PR, Vilgrain V, Terris B, et al. Pancreatic involvement in von HippelLindau disease. The Groupe Francophone dEtude de la Maladie de von HippelLindau. Gastroenterol 2000; 119: 1087-95.
4. Igarashi H, Ito T, Nishimori I, et al. Pancreatic involvement in Japanese
patients with von Hippel-Lindau disease: results of a nationwide survey. J
Gastroenterol 2014; 49: 511-516.
5. Neumann HP, Dinkel E, Brambs H, et al. Pancreatic lesions in the von HippelLindau syndrome. Gastroenterology 1991; 101: 465-471.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0677 CONTRAST ENHANCED ULTRASOUND OF THE PANCREAS
SHOW IMPAIRED PERFUSION IN PANCREAS INSUFFICIENT
CYSTIC FIBROSIS PATIENTS
T. Engjom1,2,*, K. Nylund1,2, F. Erchinger2,3, B. Lrum4,5, G. Dimcevski1,2,
R. Jirik6, O.H. Gilja2,7
1
Department of gastroenterology, Haukeland University Hospital, 2Department of
Clinical Medicine, University of Bergen, Bergen, 3Department of medicine, Voss
Hospital, Voss, 4Department of Thoracic Medicine, Haukeland University
Hospital, 5Department of Clinical Science, University of Bergen, Bergen, Norway,
6
International Clinical Research Center - Center of Biomedical Engineering, St.
Annes University Hospital, Brno, Czech Republic, 7National Centre for
Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
Contact E-mail Address: trond.engjom@helse-bergen.no
INTRODUCTION: Pancreatic insufficiency is a prevalent feature of cystic fibrosis (CF). The affected CF pancreas is dominated by fatty infiltration, atrophy
and necrosis. Little is known about pancreatic perfusion in CF.
AIMS & METHODS: We aimed to evaluate pancreatic perfusion assessed by
contrast-enhanced ultrasound (CEUS) in CF patients with known exocrine pancreatic function.
CEUS was performed in CF patients (n 39) and healthy controls (n 32).
Exocrine pancreatic function was assessed by secretin-stimulated endoscopic
short test and/ or faecal elastase. The CF patients were defined as pancreas
sufficient through fecal elastase 4200mg/g or duodenal bicarbonate 480mmol/
L. Perfusion data was analyzed on stored DICOM-files using DCE-US software
(http://www.isibrno.cz/perfusion/) and a dedicated perfusion model. Mean transit-time (MTT), blood flow (BF) and blood-volume (BV) was calculated.
Exclusions due to image quality and image analysis in the CF group were
made without knowledge of pancreatic function.
RESULTS: 26 CF patients and 20 controls were included. 13 CF patients and 12
controls were excluded due to poor image quality. Subjects were divided as
follows: CF, pancreatic insufficient (CFI, n 13), CF pancreatic sufficient
(CFS, n 13) and healthy controls (HC, n 20). Results are displayed in the
table (meanSD) (s seconds, ml millilitre)

MTT (s)
BF (ml/min/100ml)
BV (ml/100mL):

CFI (n 13)

CFS (n 13)

HC (n 20)

8.03.2
18.410.5
2.31.3

4.01.9
76.8.054
4.12.5

2.91.4
117.470
4.82.5

P50.001
P50.001
P50.05

CONCLUSION: The pancreatic insufficient CF patients had significantly longer


MTT (p50.001), lower BF (p50.001) and lower BV (p50.05) compared to
healthy controls and pancreatic sufficient CF patients. CEUS can non-invasively
differentiate between healthy pancreatic tissue and exocrine insufficient pancreatic tissue due to cystic fibrosis.
Disclosure of Interest: None declared
P0678 PARADUODENAL PANCREATITIS MANAGED BY PANCREASSPARING DUODENAL RESECTIONS. WHY, WHEN AND HOW
V. I. Egorov1,*, A. Vankovich2, R. Petrov3, N. Starostina4
1
Surgical Oncology, 5th City Hospital, Sechenov First State Medical University,
2
Surgical Oncology, Vishnevsky Institute of surgery, 3Surgical Oncology,
Ostroumov 14th City Hospital, Sechenov First State Medical University,
4
Radiology, 5th City Hospital, Moscow, Russian Federation
Contact E-mail Address: v.egorov61@gmail.com
INTRODUCTION: The term paraduodenal pancreatitis (PP) was proposed as
an umbrella for cystic dystrophy in heterotopic pancreas (duodenal dystrophy),
paraduodenal cyst and groove pancreatitis, by reasoning that these conditions
mimic pancreatic head tumors and share certain histological evidences. It is still
unclear what organ paraduodenal pancreatitis originates of.
AIMS & METHODS: To assess the results of different types of treatment for
paradudenal pancreatitis.
1. Prospective analysis of 65 cases of PP (2004-2013), comparing preoperative
and histopathological findings in 42 surgical specimens; 2. Assessment of clinical
presentation and the results of DD treatment.
RESULTS: Preoperative diagnosis was correct in all the cases except one, when
cystic tumor of the pancreatic head was suspected (1.9%). Patients were presented with abdominal pain (100%), weight loss (76%), vomiting (30%) and
jaundice (18%). CT, MRI and endoUS were the most useful diagnostic modalities. Ten patients were treated conservatively, 26 underwent pancreaticoduodenectomies (PD), pancreatico- and cystoenterostomies(8), Nakao procedures(4),
duodenum-preserving pancreatic head (DPPH) resections(5), and 12 pancreaspreserving duodenal resections (PPDR). No mortality. Full pain control was
achieved after PPRDs in 83%, PDs in 85%, and after PPPH resections and
draining procedures in 18% of cases. Diabetes mellitus developed thrice after PD.
CONCLUSION: 1. The diagnosis of PP can be confidently determined by
modern methods prior to surgery; 2. PD is the main surgical option for PP
treatment at present; 3. Early diagnosis makes pancreas-preserving duodenal
resection the treatment of choice for PP; 4. The effectiveness of PPDR provides
compelling proof that paraduodenal pancreatitis is an entity of duodenal
origin.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0679 CHANGED PLASMA ADIPONECTIN CONCENTRATION AND
ITS CORRELATION WITH CLINICOPATHOLOGICAL
PARAMETERS IN PANCREATIC ADENOCARCINOMA PATIENTS
A. Saray1,*, R. Mesihovic1, Z. Vukobrat-Bijedic1, N. Vanis1, S. Gornjakovic1,
A. Husic-Selimovic1, A. Mehmedovic1, V. Papovic1, S. Glavas1, A. Valjevac2
1
Dept. of gastroenterology and hepatology, CLINICAL CENTER UNIVERSITY
OF SARAJEVO, 2Laboratory for molecular medicine, Medical Faculty, University
of Sarajevo, Sarajevo, Bosnia and Herzegovina
Contact E-mail Address: sarayaida19@gmail.com
INTRODUCTION: Recently it has been shown that low prediagnostic plasma
adiponectin levels are associated with an elevated risk of pancreatic cancer (PC).
However, no studies exist in which association between adiponectin levels and
pancreatic tumor stage were tested.
AIMS & METHODS: The aim of the study was to analyze plasma concentrations of adiponectin in PC patients and to compare these concentrations to
clinicopathological parameters. Baseline levels of adiponectin were determined
in 40 consecutive patients with newly diagnosed pancreatic adenocarcinoma and
40 healthy control subjects. The association between adiponectin and tumor
stage (TNM classification) and tumor grade were evaluated using nonparametric
Spearmans correlation test. Control subjects were matched to case patients by
smoking status, age and BMI.
RESULTS: Overall median adiponectin concentrations were lower in PC
patients versus control subjects (7.1 vs 9.3 mg/mL, p50.001). In PC patients
with TNM stage III-IV (n 21) median adiponectin concentrations were significantly lower than in PC patients with TNM stage I-II (n 19) (5.7 vs 7.3 mg/mL,
p50.001). Mean adiponectin concentrations were lower in high grade intraepithelial neoplasia tumors (n 18) compared to low grade tumors (n 13) (5.1
vs 6.5 mg/mL, p50.05). Adiponectin concentrations were inversely correlated
with tumor size and tumor TNM stage (r -0.834, p50.01) and tumor grading
(r -0.615, p50.01) of pancreatic adenocarcinoma patients.
CONCLUSION: This study identified, for the first time, an inverse correlation
between adiponectin levels and tumor size and TNM stage suggesting a potential
role for adiponectin in progression of pancreatic adenocarcinoma.
Disclosure of Interest: None declared
P0680 PREOPERATIVE
ENDOSCOPIC
BILIARY
DRAINAGE
PROCEDURES INFLUENCE SURVIVAL FOLLOWING RESECTION
FOR AMPULLARY CARCINOMAS
K. Urbonas1, A. Gulbinas2,*, J. Pundzius1, G. Barauskas1
Surgery, 2Institute for Digestive Research, Lithuanian University of Health
Sciencies, Kaunas, Lithuania
Contact E-mail Address: kestasu@gmail.com

A319
AIMS & METHODS: We have evaluated the therapeutic effect of HIFU therapy
for locally advanced pancreatic body cancer (PBC). We treated PBC patients
using HIFU therapy as optional local therapy as well as systemic chemo /
chemo-radiotherapy, with whom an agreement was obtained in adequate IC,
from the end of 2008 in our hospital. This study took approval of member of
ethic society of our hospital. HIFU device used is FEP-BY02 (Yuande BioMedical Engineering, Beijing, China). The subjects were 20 locally advanced
PBC patients.
RESULTS: The mean tumor size after HIFU therapy changed to 36.5 (15-57)
mm from 39.5 (20-57) mm at pre-therapy. There were no significant changes in
tumor size. The mean treatment data was the following; mean number of treatment sessions, 2.7 (2-5); mean total treatment time, 2.3 (1.8-4.7) hours, and mean
total number of ablation: 2852 (760-6420) shots. The effects of HIFU therapy
was the following; the rate of complete tumor ablation was 75%, the rate of
symptom relief effect was 82%, the effectiveness of primary lesion was CR:0, PR:
3, SD:14, PD:3, and primary disease control rate (DCR) more than SD was
83.3%. There was no adverse event. The following therapy after HIFU therapy
was; operation 2, chemotherapy 15, and BSC 3 cases, respectively. Mean survival
time (MST) after diagnosis was 41.5 months, and MST after HIFU therapy was
19.1 months. Mean duration time from diagnosis till HIFU therapy was 16.3
months. MST after diagnosis in HIFU with chemotherapy or chemo-radiotherapy and chemotherapy alone (10 patients in our hospital) was 41.5 vs 23.1
months, respectively (p50.05, p 0.04, Log-rank). Combination therapy with
HIFU was better result than common chemotherapy alone.
CONCLUSION: This study suggested that HIFU therapy has the potential of
new method of combination therapy for locally advanced pancreatic body
cancer.
Disclosure of Interest: None declared
P0682 EVALUATION OF UPFRONT SURGERY AS CURATIVE-INTENT
THERAPY CONCEPT IN LOCALLY ADVANCED PANCREATIC
CANCER
C. Ansorge1,*, G. Saliba1, M. Karimi2, N. Kartalis3, L. Lundell1, M. Del Chiaro1,
J. Blomberg1, R. Segersvard1
1
Department of Surgical Gastroenterology, Karolinska University Hospital,
2
Department of Oncology, Karolinska University Hospital, Division of Surgery,
Department of Clinical Science, Intervention and Technology (CLINTEC),
Karolinska Institutet, 3Department of Radiology, Karolinska University Hospital,
Division of Medical Imaging and Technology, Department of Clinical Science,
Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm,
Sweden

INTRODUCTION: Carcinoma of Papilla of Vater has the best survival rate of


all periampullary carcinomas. Patients typically manifest symptoms early in the
course of the disease with abdominal pain, jaundice, and weight loss. This may
account for early diagnostic and relatively high resection rate. Aim of our study
was to identify the independent factors influencing a long term survival for
patients who underwent pancreatodudenectomy for ampullary adenocarcinoma.
AIMS & METHODS: of our study was to identify the independent factors
influencing a long term survival for patients who underwent radical surgical
treatment for ampullary adenocarcinoma.
Methods. Data of 64 patients with ampullary adenocarcinoma who underwent
major surgery was prospectively collected and analyzed. Demographic, clinical
and histopathological examination data were assumed to have the impact on
survival. The Kaplan-Meier method and log-rank tests were used for univariate
analysis. Cox proportional hazard model was applied to indentify prognostic
factors that were independently associated with survival.
RESULTS: The mean of survival time was 109 months, whereas five years
cumulative survival was 62 percent. Univariate analysis revealed preoperative
endoscopic biliary drainage (stenting) (p50.001), microvessels infiltration
(p50.001), patients age over 70 years (p50.005), lymphonodes infiltration
(p50.021) and T stage (p50.048) as a factors influencing survival.
Preoperative endoscopic biliary drainage (HR 5.25; CI (1.94-14.21)), microvessels
infiltration (HR 3.85; CI (1.09-13.51)) and patients age 470yrs (HR 2.35; CI
(1.03-5.39) were independent factors influencing survival in multivariate analysis.
CONCLUSION: Preoperative endoscopic biliary drainage seems to have the
most significant influence on survival, therefore necessity of procedure should
be carefully assessed before the operation.
Disclosure of Interest: None declared
P0681 HIGH-INTENSITY FOCUSED ULTRASOUND (HIFU) THERAPY
FOR LOCALLY ADVANCED PANCREATIC CANCER
A. Sofuni1,*, F. Moriyasu1, T. Sano1, M. Fujita1, T. Tsuchiya1, K. Ishii1,
N. Ikeuchi1, J. Umeda1, R. Tanaka1, R. Tonozuka1, S. Mukai1, K. Kamata1,
S. Tsuji1, F. Itokawa1, T. Itoi1
1
Gastroenterology and hepatology, TOKYO MEDICAL UNIVERSITY, Tokyo,
Japan
Contact E-mail Address: a-sofuni@amy.hi-ho.ne.jp
INTRODUCTION: Even with recent advances in the diagnostic imaging technology, most cases of pancreatic cancer (PC) are diagnosed at an unresectable
stage. The results of chemotherapy and chemo-radiotherapy for the condition
were not satisfactory. However, locally advanced PC can expect the possibility of
additional therapy including the surgical treatment and the prolongation of the
prognosis by the strategy of combination therapy. HIFU therapy being promoted as a new method to ablate the tumor is expected for locally advanced PC.

INTRODUCTION: Representing the 4th most common cancer mortality, pancreatic cancer remains an unsolved health problem. The majority of patients are
diagnosed at an advanced disease stage with limited therapy options. Currently,
in addition to the limitations, the treatment of non-metastatic locally advanced
pancreatic cancer (LAPC) is characterized by substantial methodological heterogeneity among pancreatic centers due to variation of applied definitions, regimes
and surgical procedures. Based on radiological criteria of mesenteric vessel involvement, the radiological assessment of technical resectability in our institution
distinguishes between primarily resectable LAPC (B-tumors, superior mesenteric/
portal vein involvement 450% of the circumference, 52cm length) and primarily unresectable LAPC assessed as potentially resectable after neoadjuvant chemoradiotherapy (NACRT, C-tumors, SMV/PV 450%, 42cm and/or superior
mesenteric artery involvement 550%, 52cm).
AIMS & METHODS: The aim of the present study was to evaluate the performance of primary resection and neoadjuvant treatment followed by attempted
resection as curative-intent concepts in LAPC. A single-center prospective cohort
study was conducted including patients with B- and C-tumors in the pancreatic
head between 2008 and 2013. Histological confirmation preceded NACRT
(Gemcitabine and Capecitabine). Toxicity, therapy response and postoperative
complications were recorded according to established classifications. Overall
(OS) and progression-free survival (PFS) was analyzed; OS was calculated
from date of decision until death, PFS either from date of surgery or date of
confirmed stable disease/partial remission (SD/PR) after NACRT until date of
tumor progression. Patients with specimen histology other than ductal adenocarcinoma were retrospectively excluded.
RESULTS: Ninety-nine patients with histologically confirmed pancreatic cancer
were included. Of 30 patients with B-tumors, 22 underwent curative-intent resection (CIR). Of 69 patients with C-tumors, 64 underwent NACRT, 22 had SD/
PR, and 15 underwent CIR. The resection rate in B-tumors was significantly
higher (73%) than in C-tumors (22%); however, both groups had comparable
median OS rates (B-tumors 10.5, C-tumors 11 months). In B-tumors, median OS
in intra-operatively confirmed unresectability was 8, in CIRs 11.5, and if followed by adjuvant treatment 14 months (median PFS in CIRs 9.6 months). In Ctumors, median OS in patients with discontinued NACRT was 4, with postNARCT tumor progression 11, and with confirmed SD/PR 19 months
(median PFS after CIR 21 months).
CONCLUSION: In patients with technically resectable LAPC, primary resection
was not proven to be a sustainable therapy concept, and the preoperative radiological resectability assessment does not seem to have prognostic significance.
Provided that a timely histological confirmation can be guaranteed, the indication for NACRT, and followed by attempted resection in SD/PR cases, should be
extended to patients with technically resectable LAPC.
Disclosure of Interest: None declared

A320

United European Gastroenterology Journal 2(1S)

P0683 STENT ON DEMAND IS SAFER THAN PROPHYLACTIC


DOUBLE BYPASS SURGERY WHEN A PLANNED RESECTION
FOR PANCREATIC CANCER CANNOT BE PERFORMED
J. Wennerblom1,*, C. Williamsson2, B. Tingstedt2, C. Jonsson1
1
Dept. of Surgery, Gothenburg University, Gothenburg, 2Dept. of Surgery, Lund
University, Lund, Sweden
INTRODUCTION: For decades routine use of prophylactic hepaticojejunostomy and gastroenterostomy has been advocated when a curative intention must
be abandoned due to peroperative findings of locally advanced or metastatic
disease in pancreatic cancer (1). The development of Self Expanding Metal
Stents (SEMS) has challenged this routine.
AIMS & METHODS: The aim of the present study was to retrospectively compare the results for patients operated 2004-2013 from two Swedish referral centres with local guidelines for different surgical strategies when signs of
irresectability were discovered during surgery.
At Lund University Hospital, Lund the abdomen was closed immediately in
patients without gastric outlet syndrome (GOS) and if the patient later developed
jaundice and/or GOS a SEMS was inserted (n 74). At Sahlgrenska University
Hospital, Gothenburg prophylactic double bypass surgery (DBS) was performed
when the patient was found to have a non-curable disease (n 77).
RESULTS: There was no difference between the cohorts regarding age, sex and
ASA-class. The need for immediate reoperations did not differ between the two
groups. However, delayed gastric emptying (DGE) as well as other complications
according to the Clavien-Dindo system (2) was significantly more frequent after
DBS than when using the stent strategy. These findings probably explain the
longer post operative hospital stay in the DBS group (11 vs. 9 days
(p 0.001). The long term survival after surgery was not better in the DBSgroup than for the SEMS patients (318 vs. 380 days, p 0.075).

Survival
Length of Stay
Removal nasogastric tube
Fluid intake
Food intake
DGE (A,B or C)*
Reoperations *
Complications*
Overall Clavien-Dindo Score

Double Bypass

SEMS

P-value

318 (23-808)
11 (6-66)
2 (1-17)
4 (1-18)
6 (3-19)
27 (35%)
5 (6.5%)
42 (55%)

380 (15-1151)
9 (4-42)
1 (1-22)
2 (1-23)
4 (1-31)
14 (19%)
7 (9.4%)
25 (34%)

0.075
0.001
0.046
0.005
0.0001
0.03
0.55
0.013
0.001

CONCLUSION: The more conservative approach to primarily close the abdomen and to treat the patient with SEMS on demand seems safer and results in a
shorter initial hospital stay and does not seem to impair the long time survival for
the patients compare to the DBS-routine.
REFERENCES
1. Lillemoe KD, Cameron JL, Hardacre JM, et al. Ann Surg 1999; 230: 322-328.
2. Dindo D, Demartines N and Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a
survey. Ann Surg 2004; 240: 205-213.
Disclosure of Interest: None declared
P0685 POTENTIAL BIOMARKERS EVALUATED FROM TISSUE
SAMPLES OBTAINED BY ENDOSCOPIC ULTRASOUND-GUIDED
FINE NEEDLE BIOSPY (EUS-FNB) MAY PREDICT PROGRESSION
AND RESPONSE TO GEMCITABINE THERAPY IN UNRESECTABLE
PANCREATIC CANCER
J. Iglesias-Garc a1,*, M. Luaces-Regueira2, L. Nieto-Garc a2, M. CastineiraAlvarino2, I. Abdulkader3, J. Larino-Noia1, J.E. Dominguez-Munoz1
1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Research in Digestive Diseases, 2Foundation for Research in Digestive Diseases,
3
Pathology, University Hospital of Santiago de Compostela, Santiago de
Compostela, Spain
INTRODUCTION: Due to the poor prognosis of advanced unresectable pancreatic cancer (PC), predicting response to palliative chemotherapy is essential to
avoid adverse events of otherwise unnecessary treatments. The majority of studies on expression of tumor proteins have been performed on surgical specimens
of resectable PC. We hypothesize that the expression of some tumor proteins may
predict prognosis and response to gemcitabine in patients with unresectable PC.
AIMS & METHODS: Aim of the present study was to analyze the role of several
tumor proteins evaluated in EUS-FNB samples as biomarkers of progression and
response to treatment in patients with unresectable PC.
Patients diagnosed with unresectable PC by EUS-FNB, who received palliative
treatment with gemcitabine were retrospectively included. Availability of EUSFNB tissue samples embedded in paraffin block was required for final inclusion.
Candidate proteins (collagen-I, annexinA1, FAK, FAS, HSP70, SSH and MMP)
were evaluated by specific immunohistochemistry. Statistical analysis was performed by Mann-Whitney U and McNemar test.
RESULTS: From 277 EUS-FNB samples of patients with unresectable PC, an
adequate sample for ancillary studies in patients who received palliative treatment with gemcitabine was available in 37 patients (65.111.7 years, 62.2%
men). Mean survival time was 220 days (range 16 to 519 days). Tumor size
was 41.212.8mm. Frequencies of protein expression in tumor areas were

AnnexinA1: 96.9%; SSH: 93.6%; FAK: 59.4%; collagen-I: 32.3%; FAS:


28.6%; MMP: 12.9; HSP70: 14.3%. Expression of collagen-I was associated
with a shorter survival (150.898.2 vs 285.4147.2 days, p 0.029). FAK
expression was associated with a smaller tumor size (36.19.5 vs 48.214.2,
p 0.02). Finally, lack of SHH was associated with normal serum Ca19.9 levels.
CONCLUSION: Some tumor proteins expressed in unresectable PC can be
evaluated by immunohistochemistry in EUS-FNB samples to predict survival
and response to palliative chemotherapy. Expression of collagen-I is associated
with a shorter survival in patients receiving palliative therapy with gemcitabine.
Further prospective studies including a larger number of patients are required to
confirm these data.
Disclosure of Interest: None declared
P0686 CLINICAL IMPACT OF KL-6 MEASUREMENT OF PANCREATIC
JUICE FOR DIAGNOSING PANCREATIC MASSES
K. Matsumoto1,*, K. Harada1, Y. Takeda1, T. Onoyama1, S. Kawata1, M. Ueki2,
Y. Murawaki1
1
Gastroenterology, 2Promoting next-generation highly advanced medicine, Tottori
University Hospital, Yonago, Japan
Contact E-mail Address: ayano0620@hotmail.co.jp
INTRODUCTION: Pancreatic juice cytology (PJC) is considered optimal for the
differential diagnosis of pancreatic masses and is thought to be the most exact
diagnostic modality for intraductal papillary mucinous carcinoma (IPMC).
However, the accuracy of PJC has been unsatisfactory, ranging from 46.7% to
93.0%. Therefore, to improve the accuracy of diagnosis for pancreatic malignancy, alternative modalities are needed. MUC1, a membrane-associated mucin
widely expressed in gastrointestinal tissues, has a variety of types based on different glycoforms in its extracellular domain. Many investigations have shown
that aberrant expression of MUC1 in gastrointestinal cancer tissue has clinicopathological and biological importance in cancer. KL-6 mucin, one kind of
MUC1, has also been investigated; it appears to have a significant relationship
with malignant tumor behavior, especially cancer cell invasion and metastasis in
various gastrointestinal cancers.
AIMS & METHODS: The aim of this study was to evaluate the clinical impact
of the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses.
This study comprised 70 consecutive patients with pancreatic masses (34 pancreatic ductal adenocarcinomas [PDACs], 5 intraductal papillary mucinous carcinomas [IPMCs], 12 pancreatic inflammatory lesions and benign stricture of the
main pancreatic ducts [MPDs] and 19 intraductal papillary mucinous adenomas
[IPMAs]). All patients underwent PJC and measurement of the KL-6 concentration of pancreatic juice, which was obtained from the pancreatic duct. After
pancreatic juice was centrifuged at 1000 rpm for 5 minutes, cytological examination of the cell pellet was performed. The supernatant (10 L) was used to
measure the KL-6 concentration. Human KL-6 levels were assayed in duplicate
using a PICOLUMI KL-6 kit (EIDIA, Tokyo, Japan) an electrochemiluminescence immunoassay (ECLIA) specific for human KL-6.
RESULTS: The average KL-6 concentration of pancreatic juice was significantly
higher for PDACs (167.7  396.1 U/mL) than for pancreatic inflammatory
lesions and benign MPD strictures (17.5  15.7 U/mL P 0.034).
Furthermore, KL-6 was significantly higher in IPMCs (86.9  21.1 U/mL)
than in IPMNs (14.4  2.0 U/mL P 0.026). The cut-off level of KL-6 concentration was 16 U/mL for differentiating PDACs and IPMCs from pancreatic
inflammatory lesions and IPMNs. The sensitivity, specificity, positive predictive
value, negative predictive valu, and accuracy of KL-6 concentration alone were
79.5%, 64.5%, 73.8%, 71.4% and 72.9%, respectively, whereas those of PJC
alone were 82.1%, 96.8%, 97.0%, 81.1% and 88.6%, respectively. Adding the
KL-6 concentration to PJC diagnosis increased the sensitivity and accuracy of
PJC by 15.3% (P 0.025) and 8.5% (P 0.048), respectively.
CONCLUSION: The KL-6 concentration of pancreatic juice may be useful for
diagnosing PDAC, as well as PJC.
Disclosure of Interest: None declared
P0687 NEW DIAGNOSTIC STRATEGIES FOR THE EARLY DIAGNOSIS
OF PANCREATIC CANCER
K. Hanada1,*, A. Okazaki1, M. Shinzato1, Y. Izumi1, Y. Teraoka1,
K. Kanemitsu1, J. Ikemoto1, N. Hirano1
1
Gastroenterology, Onomichi General Hospital, Onomichi, Japan
Contact E-mail Address: kh-ajpbd@nifty.com
INTRODUCTION: Detection of pancreatic cancer (PC) at an early stage with
curative surgery is the approach with the potential to significantly improve longterm patient outcome. However, the rate of tumor detection of computed tomography (CT) in the case with small pancreatic cancer was not satisfied. For the
diagnoses of PC less than 10mm, the rate of tumor detection was higher for
endoscopic ultrasonography (EUS) than for CT or other modalities, and the
histologic diagnosis with EUS guided fine needle aspiration (EUS-FNA) was
helpful in confirming the diagnosis. For the diagnosis of PC in situ, EUS and
magnetic resonance pancreatocholangiography (MRCP) played important roles
in detecting of the local irregular stenosis of the pancreatic duct. Endoscopic
retrograde pancreatography (ERP) and sequential cytodiagnosis of pancreatic
juice using endoscopic nasopancreatic drainage (ENPD) multiple times were
useful in the diagnosis of PC in situ.
AIMS & METHODS: In 2007, Onomichi Medical Association tried to start a
social program for diagnosis of the small pancreatic cancer. Specialized doctors
for pancreatic cancer (SDPC) in medical centers enlightened practicing doctors
about risk factors of PC, abnormal findings of US, or elevated serum pancreatic
enzymes. Simultaneously, if practicing doctors experienced the patient with these
previous problems, they actively consulted SDPC.

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United European Gastroenterology Journal 2(1S)


RESULTS: From January 2007 to June 2013, a total of 4969 cases were consulted with SDPC in Onomichi General Hospital. Methods of image diagnosis of
CT, MRI, and EUS were performed in 4157, 2303, and 1692 cases. Among these
cases, ERP was performed in 550 cases. ENPD and the repeated cytology using
pancreatic juice were performed in 59. EUS-FNA was performed in 257. As a
result, 338 cases were proved as adenocarcinoma histocytologically. There were
13 cases with stage 0, and 28 cases with stage Ia and Ib histopathologically.
CONCLUSION: To detect of early stage of PC, the relationship between SDPC
in medical centers and practicing doctors is very important. ENPD and repeated
cytology using pancreatic juice also may play important roles in diagnosis of the
early stage of PC.
Disclosure of Interest: None declared
P0688 A COMPARATIVE STUDY BETWEEN A 22-GAUGE ASPIRATION
NEEDLE AND A 25-GAUGE BIOPSY NEEDLE FOR EUS-GUIDED
SAMPLING OF PANCREATIC MASS LESIONS
Y.S. Moon1,*, J.H. Kim2, M.J. Yang2, J.C. Hwang2
1
Gastroenterology, Haeundae Paik Hospital, Busan, 2Gastroenterology, Ajou
Unversity School of Medicine, Suwon, Korea, Republic Of
INTRODUCTION: EUS biopsy needles have recently been developed in order to
obtain both histologic and cytologic specimens.
AIMS & METHODS: We conducted this study to compare 22-gauge (G) aspiration needles (FNA) and 25G biopsy needles (FNB) for EUS-guided sampling of
solid pancreatic masses. Thirty-four patients with solid pancreatic masses underwent EUS-guided sampling with a 25G FNB from June 2012 to April 2013, and
thirty-four patients with solid pancreatic masses, who underwent EUS-guided
sampling with a 22G FNA from June 2011 to May 2012, served as the historical
control group. EUS-guided sampling was performed using the standard technique without an on-site cytopathologist.
RESULTS: The diagnostic rates of cytology were 97.1% (33/34) with 22G FNA
needles and 85.3% (29/34) with 25G FNB needles (P 0.197). The diagnostic
rates of histology were 23.5% (8/34) with 22G FNA needles and 41.2% (14/34)
with 25G FNB needles (P 0.194). There was no significant difference in the
mean number of needle passes (5.09 vs 5.76, P 0.089) or needle malfunctions
(2.9% vs 11.8%, P 0.356) between 22G FNA and 25G FNB needles, respectively. No complications were identified in either group.
CONCLUSION: The 25G FNB needle was not superior to the 22G FNA needle
in the diagnostic yield of histology for EUS-guided sampling of pancreatic mass
lesions, as the diagnostic yield, technical performance, and safety profiles were
comparable between both of them.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


ENDOSCOPY AND IMAGING
XL_____________________

II

POSTER

EXHIBITION

9:0017:00
HALL

P0689 EFFECTIVENESS OF ENDOSCOPIC MANAGEMENT FOR


ANASTOMOTIC LEAKAGE AFTER GASTRECTOMY IN GASTRIC
CANCER
J.Y. Lee1,*, Y.-W. Kim1, I.J. Choi1, C.G. Kim1, S.-J. Cho1, K.W. Ryu1,
H.M. Yoon1, B.W. Eom1, S.J. Kim1
1
Center for Gastric Cancer, National Cancer Center, Goyang, Korea, Republic Of
Contact E-mail Address: jylee@ncc.re.kr
INTRODUCTION: Anastomotic leakage after gastrectomy is an important
determinant of early and late morbidity and mortality. Various methods for
postoperative leakage are used including conservative, endoscopic or surgical
treatment.
AIMS & METHODS: We aimed to evaluate the effectiveness and safety of
endoscopic intervention for the management of leakage after gastrectomy. We
retrospectively reviewed 57 patients with anastomotic leakage after gastrectomy
for gastric cancer that was treated with endoscopic interventions between
December 2007 and March 2014. Clinical aspects of leakages and endoscopic
managements, closure rates and treatment related complications were evaluated.
RESULTS: Anastomotic leakages were found at esophagojejunostomy (n 26),
duodenal stump (n 14), gastroduodenostomy/gastrojejunostomy (n 10),
wedge resection (n 3), esophagogastrostomy (n 2) or jejunal stump (n 2).
Median size of leak was 8mm (range, 2 - 40mm). The leakages were treated by
endoclips (n 13), endoclips with detachable snare (n 31) or stent (n 13).
Simultaneously, abscess around the leak was drained by external drains
(n 32). After endoscopic treatment, complete closure was achieved in 42
patients (73.7%) and partial closure in 13 patients (22.8%). In all patients with
partial closure, final closure of leak was achieved by continuing conservative
treatment. Among remaining two patients, one with failed endoscopic treatment
went on to receive surgery and the other died due to septic shock during endoscopic treatment. Treatment related complication (esophageal fistula) occurred in
one patient who was treated with stent. The complete closure rate of the leaks at
duodenal or jejunal stump was significantly lower than that of leaks at other sites
(P 0.027), whereas the size of leak and the method of endoscopic management
were not associated with the complete closure rate.
CONCLUSION: Endoscopic management using clips or stent represents an
effective and safe method for anastomotic leakage after gastrectomy in gastric
cancer and it can be an easily available minimally-invasive option which may
reduce leakage related mortality and morbidity.
Disclosure of Interest: None declared

P0691 RISK FACTORS OF DELAYED ULCER HEALING AFTER


GASTRIC ENDOSCOPIC SUBMUCOSAL DISSECTION
J.H. Lim1,*, S.G. Kim1, J. Choi1, J.P. Im1, J.S. Kim1, H.C. Jung1
1
Departement of Internal Medicine and Liver Research Institute, Seoul National
University College of Medicine, Seoul, Korea, Republic Of
INTRODUCTION: Post-endoscopic submucosal dissection (ESD) iatrogenic
ulcer is known to have specific histologic features and heal faster than peptic
ulcer. However, some iatrogenic ulcers show delayed healing.
AIMS & METHODS: The aim of this study is to clarify risk factors of delayed
ulcer healing after gastric ESD. For this, we reviewed medical records of patients
who had ESD for gastric high-grade adenoma or early gastric cancer between
January 2005 and February 2012. Delayed ulcer healing was defined as sustaining unhealed iatrogenic ulcer at 3 months after the ESD. To find potential risk
factors we reviewed following parameters: age, sex, comorbidity that might influence mucosal healing, history of peptic ulcer, laboratory abnormalities, antiplatelet or NSAID usage, size of the specimen, location and histologic type of lesion,
Helicobacter pylori status, and hot biopsy.
RESULTS: Among 2040 subjects, 11 were excluded because of anticoagulation,
3 because of embolization for post-ESD bleeding, and 346 were excluded because
of loss of 3 month follow-up endoscopy. Out of the total 1680 patients enrolled,
95 had delayed ulcer healing. In multivariate analysis, diabetes (OR 1.743; 95%
CI: 1.017-2.989, p 0.043), coagulation abnormality (OR 3.195; 95% CI: 1.5356.650, p 0.002), specimen size greater than 4cm (OR 2.999; 95% CI 1.603-5.611,
p 0.001), and hot biopsy (OR 7.149; 95% CI 1.738-29.411, p 0.006) were
revealed to be independent risk factors of delayed ulcer healing. Meanwhile,
persistent Helicobacter pylori infection was not shown to be related to the delayed
ulcer healing.
CONCLUSION: Patients those who undergo ESD for large gastric lesions and
massive hemostasis, especially with diabetes or coagulation abnormalities, tend
to have delayed healing of iatrogenic ulcer. For such patients initial dosage
increment of PPI or addition of other anti-ulcer agents after ESD should be
considered.
Disclosure of Interest: None declared

n
w
a
ithdr

P0692 CHARACTERISTIC
ENDOSCOPIC
FINDINGS
HELICOBACTER PYLORI-NEGATIVE EARLY GASTRIC
UNDIFFERENTIATED ADENOCARCINOMA

OF

J. Fujisaki1,*, Y. Horiuchi1, H. Osumi1, T. Hirasawa1, T. Yoshio1,


Y. Yamamoto1
1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation
for Cancer Research, Tokyo, Japan
Contact E-mail Address: junko.fujisaki@jfcr.or.jp
INTRODUCTION: Helicobacter Pylori (HP) negative gastric cancer is rare.
Recently, we experienced HP negative early gastric cancer.
AIMS & METHODS: The purpose of this study is to evaluate the clinical characteristics of HP-negative Early Gastric Undifferentiated adenocarcinoma. We
examined 35 cases (19 males and 16 females) with 36 lesions of Helicobacter
Pylori (H.pylori)-negative Early gastric undifferentiated adenocarcinoma. All
cases were treated by Endoscopic Submucosal Dissection. All cases had no history of H.pylori eradication, no inflammatory changes on the resected specimen,
and no sign of atrophy on endoscopy, with negative results for pepsinogen and
urea creath tests.
RESULTS: Of the 36 lesions, 35 were diagnosed as signet-ring cell carcinoma,
with only 1 case of poorly differentiated adenocarcinoma. The mean lesion size
was 7.4mm. The macroscopic type was 0-IIc in 30 (83%) lesions and 0-IIb in 6
lesions. 33 (92%) lesions showed pale lesion in color. The depth classification was
intramucosal in 36 lesions. Of the 36 intramucosal lesions, 3 (8%) were limited to
the proliferative of the mucosa, 22 (61) invaded from the proliferative zone to the
upper side, and only 1 (2%) case invaded the lower mucosa. With respect to the
background mucosa, 25 (69%) lesion originated from the fundic gland area, 5
(14%) originated from the intermediated zone, and 6 (17%) originated from the
pyloric glands. The inciddent of HP-N-UEG was 2.3% of all ESD cases.
CONCLUSION: HP negative early gatric cancer was rare. However, we experienced HP negative early gastric undifferentiated adenocarcinoma. These cases
may have considerable relevance in the near future.
Disclosure of Interest: None declared
P0693 CHROMOENDOSCOPY WITH INDIGO CARMINE DYE ADDED
TO ACETIC ACID FOR DELINEATING EARLY GASTRIC CANCERS
IS USEFUL AND EASIER THAN MAGNIFYING ENDOSCOPY WITH
NARROW BAND IMAGING
K. Nagao1,*, H. Noda1,1, N. Ogasawara1, T. Shimura2, M. Ebi2, S. Izawa1,
Y. Kondo1, Y. Ito1, Y. Tamura1, M. Sasaki1, K. Kasugai1
1
Gastroenterology, Aichi Medical University School of Medicine, Nagakute,
2
Gastroenterology and Metabolism, Nagoya City University Graduate School of
Medical Sciences, Nagoya, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) was developed to
improve the rate of en bloc resection for early gastric cancer (EGC). Although a
clear diagnosis of EGC demarcation is important for proper treatment, demarcations are often obscure. To achieve a successful ESD outcome, it is very important to accurately determine the lateral extent of the tumor. The determination of
EGC demarcation has traditionally been performed with conventional endoscopy and chromoendoscopy (CE) using indigo carmine dye. However, it is
sometimes difficult to identify the margins of the tumors, especially those of
superficial or flat-type tumors. Various techniques using magnifying endoscopy

A322
(ME) have been developed to enhance images of EGC demarcations. Magnifying
endoscopy with narrow band imaging (ME-NBI) has reportedly been useful in
overcoming this problem but the use of MENBI is limited by the technical
difficulties in manipulating the scopes. Therefore, easier methods are required
that make it possible to accurately determine the lateral extent of these tumors.
Chromoendoscopy with indigo carmine dye added to acetic acid (CE-IA) has
recently been reported to improve the diagnostic yield in terms of recognizing the
tumor borders in patients with EGC. Our purpose was to compare the diagnostic
performance of CE-IA with that of ME-NBI and conventional ME (CME). We
investigated three methods to determine which is more effective in enhancing the
recognition of EGC demarcations.
AIMS & METHODS: The study group included 266 lesions of consecutive 259
patients with differentiated EGC who underwent ESD at Aichi Medical
University Hospital between January 2006 and March 2014. The recognition
of demarcations were evaluated using CME (n 193), ME-NBI (n 43) and
CE-IA (n 30). All observations were made on optimal foci and at the highest
magnification ratios possible. For CE-IA, 2030 mL of 1.5% acetic acid was
sprinkled onto the lesion and 10-20 mL of 0.2% indigo carmine dye was similarly
sprinkled 30-60 seconds later using a washing pipe. The recognition of demarcations between the lesion and the normal mucosa were classified as distinct or
indistinct by observation of CME, ME-NBI and CE-IA.
RESULTS: The demarcations of the lesions were distinct in 64.8% (125/193)
with CME, in 81.4% (35/43) with ME-NBI and in 90.0% (27/30) with CE-IA.
ME-NBI and CE-IA clarified the demarcation in a significantly higher percentage compared with CME (P50.05). However, the determination rate of EGC
demarcation did not differ between ME-NBI and CE-IA. The mean duration of
determination procedure for demarcation with CE-IA was significantly shorter
than that with ME-NBI (6.973.75 min vs. 8.57 4.33 min, P50.05).
CONCLUSION: CE-IA and ME-NBI are useful in determining the lateral extent
of EGCs. The mean duration of determination procedure for EGC demarcation
was significantly reduced using CE-IA compared with ME-NBI. The demarcations of EGDs were recognized most easily using CE-IA.
Disclosure of Interest: None declared
P0694 CLINICOPATHOLOGICAL FACTORS INFLUENCE ACCURATE
ASSESSMENT OF ENDOSCOPIC ULTRASONOGRAPHY FOR
EARLY GASTRIC CANCER
K. Yanamoto1,*, N. Ogasawara1, T. Shimura2, A. Shimozato1, Y. Kondo1,
H. Noda1, Y. Ito1, M. Sasaki1, K. Kasugai1
1
Aichi Medical University School of Medicine, Nagakute, 2Department of
Gastroenterology and Metabolism, Nagoya City University Graduate School of
Medical Sciences, Nagoya, Japan
INTRODUCTION: The advent of endoscopic ultrasonography (EUS) has significantly improved the preoperative diagnosis and staging of gastric cancers.
EUS is the most reliable nonsurgical method available for assessing primary
tumor with a high diagnostic rate of accuracy in staging gastric cancer. This
assessment is an important factor in choosing a proper treatment such as endoscopic resection or surgery. Especially in early gastric cancers (EGC), the size,
gross appearance, histologic diagnosis, degree of differentiation, and depth of
invasion are very important factors to be considered for therapeutic decision
making. Endoscopic submucosal dissection (ESD) currently is widely accepted
as a standard treatment strategy for EGC without any risk of lymph node
metastasis because the ESD procedure facilitates en bloc resection even in
patients with large or ulcerous lesions. Therefore, it has become more important
in treatment planning to determine the depth of invasion accurately before treatment. The aim of this study was to evaluate the clinicopathological factors affecting the diagnostic accuracy of EUS and to compare the diagnostic accuracy
evaluated by endoscopic findings with that by EUS in EGCs.
AIMS & METHODS: During the period from April 2009 to January 2014, 136
patients (94 men and 42 women; age range, 44-88 years; mean age, 72.1 years)
with an endoscopic diagnosis of EGCs underwent EUS to define pretreatment
staging. Diagnoses of invasion depth by EUS or endoscopic findings were
divided into intramucosal (M) and submucosal invasion (SM). All patients
underwent curative treatment by either ESD or standard surgical intervention,
and all lesions were evaluated by histopathological examination. Both EUSdetermined diagnosis and conventional endoscopy-determined diagnosis were
compared with the final histopathological evaluation of resected specimens,
and the impact of various clinicopathological parameters on diagnostic accuracy
was analyzed.
RESULTS: The accuracy of invasion depth were 83.0 % for EUS and 74.5 % for
conventional endoscopy, respectively. There was significant difference related
with the accuracy of invasion depth between EUS and endoscopic findings
(p50.01). The diagnostic accuracy of EUS for predicting tumor invasion depth
was significantly affected by the tumor location and the tumor size. Lesions
located in the posterior wall of the stomach larger than 3 cm were significantly
associated with lower diagnostic accuracy in predicting the tumor invasion. These
lesions had higher probability of overstaging estimated by EUS. However, no
significant differences were found in histopathological differentiation, tumor
gross appearance and ulceration. Unexpectedly, the observation time for EUS
was the same as that for conventional endoscopy (6.83.1 minutes vs. 6.14.2
minutes).
CONCLUSION: EGCs larger than 3 cm located in the posterior wall of the
stomach should be cautiously considered in the decision on treatment modality
by pretreatment EUS staging. Moreover, observation time for EUS was so short
that a sedation was not considered to be required during EUS investigation.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0695 ADDITORY RISK FACTORS FOR PYLORIC STENOSIS AFTER
ENDOSCOPIC SUBMUCOSAL DISSECTION, AND VARIOUS
MANAGEMENTS
K.S. Lee1,*, M.J. Yang1, S.J. Ahn1, S.J. Shin1
1
Department of Gastroenterology, Ajou University School of Medicine, Suwon,
Korea, Republic Of
Contact E-mail Address: kiseong@hotmail.com
INTRODUCTION: Endoscopic mucosal dissection (ESD) is useful method for
local resection of early gastric neoplasia. 1,2 But, ESD can cause early and late
complications commonly known as bleeding, perforation, and stricture formation. 3 In previous study, Coda S, et al., circumferential extent of a mucosal
defect 4 3/4 and longitudinal extent 45 cm were each significantly related to
the occurrence of post-ESD stenosis in both cardiac and pyloric resections. And
endoscopic balloon dilatation can be an effective treatment of them. 4
AIMS & METHODS: The aim of this study is to clarify the previous risk factors
and determine the additory risk factor. And we report another management
methods for pyloric stenosis after ESD. Retrospectively a total of 1621 early
gastric neoplasia resected by ESD at a single institution between 2005 and
2012. Pyloric stenosis is defined when a 1 cm diameter endoscope could not
passed through the pyloric ring.
RESULTS: Among 126 cases which resected from the pylorus, stenosis occurred
in six cases. Significant differences were found between longitudinal diameter
of resected specimen (5cm) and the others (55cm) (odd ratio 15.362,
p 0.037), circumferential mucosal defect over the half (270 ) and the others
(5270 ) (odd ratio 23.840, p 0.015). Also the number of repeated ESD was
significant different between the single lesion and the others (2 times) (odd
ratio 26.169, p 0.040). Six patients of pyloric stenosis received endoscopic
balloon dilatation for treatment of post-endoscopic resection stricture and 4
patients has improved symptoms. But two patients received an additional procedure for treatment of pyloric stenosis. One of them underwent subtotal gastrectomy and other was treated with metallic pyloric stent.
CONCLUSION: The risk factors of pyloric stenosis were the longitudinal diameter of resected specimen (45cm) and circumferential mucosal defect over 75%
of pyloric ring in this study. In addition, repeated ESD limited pylorus also
caused pyloric stenosis. We thought the diameter of specimen and circumferential
defect are important factors as previous study. 4 And this study revealed another
risk factor: repeated procedure is additional risk factor of pyloric stenosis after
ESD. In treatment of post-endoscopic resection stricture, balloon dilatation is
effective treatment. But, according Coda S, et al., procedure is needed more than
nine times on average. 4 Frequent the procedures decrease quality of life.
Therefore more confident short-term treatment is needed. Pyloric stent is
useful management of pyloric stricture. But it is too expensive and has complications like stent-migration. This is must be resolved first.
REFERENCES
1. Rembacken BJ, Gotoda T, Fujii T, et al. Endoscopic mucosal resection.
Endoscopy 2001; 33: 709-718.
2. Soetikno RM, Gotoda T, Nakanishi Y, et al. Endoscopic mucosal resection.
Gastrointest Endosc 2003; 57: 567-579.
3. Oda I, Suzuki H, Nonaka S, et al. Complications of gastric endoscopic submucosal dissection. Dig Endosc 2013; 25(Suppl. 1): 71-78.
4. Coda S, Oda I, Gotoda T, et al. Risk factors for cardiac and pyloric stenosis
after endoscopic submucosal dissection, and efficacy of endoscopic balloon dilation treatment. Endoscopy 2009; 41: 421-426.
Disclosure of Interest: None declared
P0696 ULTRA THIN ENDOSCOPE WITH NARROW BAND IMAGING
(NBI) IN DIAGNOSTIC OF GLUTEN DEPENDENT AND
INDEPENDENT SMALL INTESTINAL ATROPHY IN INFANT AND
UP TO 36 MONTHS AGE CHILDREN
K. Marakhouski1,*
1
Endoscopy, RSPC "Mother and child", Minsk, Belarus
INTRODUCTION: Using high-resolution endoscopy is sharply limited at this
age. It remains unclear whether there are differences in the high-resolution endoscopic assessment of the small intestinal mucosal pit pattern at congenital intestinal atrophy (non gluten) and atrophy at a gluten sensitivity enteropathy.
AIMS & METHODS: Inclusion criteria were: child wasnt older 36 month and
has low weight gain (WHO criteria) and non bloody diarrhea. Investigation
performed with permission and control of the local ethic committee. We analyzed
endoscopy results of 32 cases (13 girls).
Endoscopy: the EXERA III with an endoscope GIF - N180 4.9 mm in diameter
was used Evaluation of duodenal mucosa was done with narrow band imaging
(NBI, more brightly than in EXERA II light source) and for additional sign of
atrophy water flow with addtion of semethicon was done too. Two biopsy specimens were taken minimally. The description of a biopsy was carried out by a
standard technique with special orientation biopsies specimens, by two independent pathology experts. Four criteria were used for endoscopic and histological
(HYS) intestinal atrophy assessment: definitely yes, probably yes, probably no,
definitely no. The main group was divided on two subgroups: A - age up to 6
months (group of strictly non gluten enteropathy) and B - 6 - 36 months (probably gluten dependent enteropaty).
RESULTS: Age in group A (N 17) was: mean 2.9 (CI 95% 2-4), median 3.0 (CI 95% 1-4). Frequency of the HYS definitely yes atrophy was in 5,
probably yes- 1. Atrophy rate was 35% (Exact 95% C. I. (Fishers) 14.261.7). Frequency of the endoscopic definitely yes atrophy was in 6, probably
yes- 2. Endoscopy sensitivity 0.67(CI 95% 0.35 - 0,88, specificity 1,00 (CI
95% 0.68 - 1,0), odds ratio (Fleiss)- 33(CI 95% 1,6 - 151,23). If endoscopy
negative, expected HYS negative will definitely to no atrophy.

A323

United European Gastroenterology Journal 2(1S)


Age in group B (N 15) was: mean 23,5 (CI 95% 18,5-28,4), median - 21,0
(CI 95% 17-33). Frequency of the HYS definitely yes atrophy was in 4, probably yes- 0. Atrophy rate was- 26,7% (Exact 95% C. I. (Fishers) 7,8-55,1), and
not different significant from group A. Frequency of the endoscopic definitely
yes - atrophy was in 4, probably yes - 1case. Sensitivity 0.8 (CI95% 0.38 - 0,96;
specificity 1,00 (CI95% 0.72 - 1,00), odds ratio (Fleiss) 63 (2,22 - 313,23), and
LR (Test Negative) 0.2.
CONCLUSION: In infant and up to 36 months age children with low weight
gain and non bloody diarrhea small intestinal atrophy rates are from 14.2% to 61.7%. We found no difference in the two groups (gluten associated or not) used
to assess ultra thin with NBI endoscopy sensitivity, specificity, and it has value as
a good standard for visual endoscopic evaluation of duodenal villi changes as a
method for exclusive intestinal atrophy.
Disclosure of Interest: K. Marakhouski Other: "Olympus" CIS expert
P0697 PROSPECTIVE ASSESSMENT OF THE LEVEL OF TEMPORAL
AROUSAL AND SAFETY OF NURSE-ADMINISTERED PROPOFOL
SEDATION FOR ESOPHAGOGASTRODUODENOSCOPY
K. Kusumoto1,*, A. Hamada1, Y. Mizumoto2
Tango central hospital, Kyotango, 2National Hospital Organization Kyoto
Medical Center, Kyoto, Japan
Contact E-mail Address: kusumoto1024@gmail.com
1

INTRODUCTION: Propofol sedation is widely used, mainly in Europe and the


US, not only as an induction agent for general anesthesia but also in the field of
gastroenterological endoscopy. Especially in the US, the certified registered nurse
anesthetists perform general and local anesthesia for many endoscopic procedures under anesthesia management, independently from doctors. However,
quite a few states prohibit individuals other than anesthetists from performing
propofol sedation from the safety aspect. Propofol sedation, which is easy to
give and wean off, by nurse-administered propofol sedation (NAPS) is quite
meaningful, and could thereby reduce labor costs and charges for recovery rooms
and curb medical expenses.
AIMS & METHODS: We prospectively examined the safety of propofol sedation at the time of esophagogastrodudenoscopy (EGD). Between July 2013 and
January 2014, EGD was performed under NAPS in outpatients, and time to
arousal and safety were prospectively assessed. Propofol was administered manually in a prespecified regimen, and, before the test and at 10 and 60 min after the
test, the mean blood pressure, Sp02, grasping power of both hands, visual acuity
of both eyes, Mini Mental State Examination (MMSE) score, and reflex nerve
test were assessed and compared.
We hypothesized that MMSE score recovers to the pretest value 60 min after
the completion of EGD under propofol sedation. To prove this hypothesis, we
tested non-inferiority of MMSE at 60 min after the test against that before the
test. We calculated that 87 eligible patients were needed to obtain a significant
difference, and estimated the number of patients to be included at 104, expecting
20% of the patients to be ineligible. Quantitive variables were evaluated by t-test,
and the significance level of 50.05 was considered statistically significant.
RESULTS: 95 patients (mean age: 55.5  14.9 years; male/female ratio: 37/58
cases; mean examination time: 315.6  115.8 s; mean induction dose of propofol:
0.097  0.019 mL/kg; and mean total dose: 0.129  0.027 mL/kg) were included
for analysis. All patients could be successfully sedated and opened their eyes
immediately after the test. Before the test vs. 10 min after the test, the mean
blood pressure (mmHg) was 95.19  13.20 vs. 90.13  12.34 (p 5 0.01); grasping
power of right hand (kg) was 27.7  8.08 vs. 26.2  8.49 (p 5 0.01); grasping
power of left hand (kg) was 26.4  8.08 vs. 25.3  8.22 (p 5 0.01); and MMSE
(points) was 27.3  2.2 vs. 26.8  2.4 (p 5 0.05); all of which showed significant
differences. Before the test vs. 60 min after the test, the mean blood pressure
(mmHg) was 95.19  13.20 vs. 91.80  11.88 (p 5 0.01), showing a significant
decline. No occasional symptoms were observed in all patients.
CONCLUSION: EGD under NAPS was performed safely and all factors other
than mean blood pressure returned to the pretest condition 60 min after the test.
Blood pressure was also in an acceptable range as per discharge criteria, and the
patients were considered to be allowed to be safely discharged from hospital after
60 min.
REFERENCES
Dumonceau JM, Riphaus A, Aparicio JR, et al. European society of gastrointestinal endoscopy, european society of gastroenterology and endoscopy nurses
and associates, and the european society of anaesthesiology guideline: nonanesthesuiologist administration of propofol for GI endoscopy. Endoscopy
2010; 42: 960-974.
Disclosure of Interest: None declared

P0698 DEVELOPMENT
OF
PROPOFOL
SEDATION
THERAPEUTIC ENDOSCOPY UNDER DEEP SEDATION WITH
SPONTANEOUS RESPIRATION

FOR

K. Matsumoto1,*, K. Matsumoto1, A. Nagahara1, Y. Nakagawa1, H. Ueyama1,


Y. Shimada1, D. Asaoka1, M. Hojo1, S. Watanabe1
1
gastroenterology, juntendo univ., bunkyo-ku, Japan
INTRODUCTION: In recent years, propofol sedation has attracted attention for
use during therapeutic endoscopy under deep sedation with spontaneous respiration. However, a standard protocol for propofol sedation has not yet been
established.
AIMS & METHODS: Our aim was to establish a simple and safe protocol for
propofol sedation during therapeutic endoscopy. This study retrospectively
investigated 89 patients (67 male, 22 female; mean age 71.2 years) who underwent
endoscopic submucosal dissection (ESD) or endoscopic mucosal resection
(EMR) of the esophagus and stomach under anaesthesia with 1.0% propofol.
Patients were assigned to 1 of 5 groups (phases 1 5) each corresponding to a
different dosing protocol. After beginning phase 1, when it was deemed that the
dose of propofol was insufficient or excessive, the dose was adjusted and the next
phase was begun in a different group of patients. In all phases, the initial dose of
1.0% propofol was administered after bolus injection of pethidine hydrochloride
(0.5 mg/kg), and 1.0 mL of propofol was added every minute until anaesthesia to
level 6 on the Ramsey Sedation Scale was achieved. Subsequently, continuous
drip infusion was performed to maintain the depth of sedation. Induction and
maintenance doses in each phase are shown in the table below. When the patient
showed movement, a bolus injection of 1.0 mL propofol was repeated every
minute until suitable sedation was obtained, and continuous drip infusion was
increased to a dose of 5 mL/h. Oxygen saturation and blood pressure were
monitored during all procedures. A BIS monitor was used at phase 5.
Continuous drip infusion was stopped temporarily under the following conditions: SpO2 590%, BP 580 mm Hg, or BIS score 560 (5 seconds or more).
Following recovery, the rate of continuous drip infusion was decreased to 5 mL/
h. We calculated the dose of propofol at the time of induction and during the
maintenance phase, the number of additional bolus injections, and the average
total dose of propofol. The incidence of cardiorespiratory suppression was evaluated for each phase. The incidence of BIS below 60 was also evaluated in phase
5.
RESULTS: During induction, no cardiorespiratory suppression occurred in any
of the phases. During the maintenance phase, circulatory suppression occurred
more frequently in phases 1-4 than in phase 5. In contrast, no respiratory suppression occurred in any of the phases.
Table: Propofol dosing and the incidence of adverse events during each phase of
study
CONCLUSION: This newly developed propofol anesthesia protocol (phase 5)
could be safe for therapeutic endoscopy under deep sedation with spontaneous
respiration.
Disclosure of Interest: None declared
P0699 MAGNIFICATION
ENDOSCOPY
WITH
ACETIC
ENHANCEMENT AND NARROW-BAND IMAGING FOR
PREDICTING HISTOLOGIC CHARACTERISTICS OF GASTRIC
MUCOSAL NEOPLASMS

ACID-

K. Shibagaki1,*, Y. Amano2, N. Ishimura3, H. Taniguchi4, H. Fujita1,


K. Kobayashi5, Y. Kinoshita3
1
Gastroenterology, Tottori Municipal Hospital, Tottori, 2Gastroenterology, Kaken
Hospital, International University of Health and Welfare, Ichikawa,
3
Gastroenterology, Faculty of Medicine, Shimane University, Izumo, 4Tottori
Municipal Hospital, Tottori, Japan, 5Pathology, Tottori Municipal Hospital,
Tottori, Japan
INTRODUCTION: Magnification endoscopy with narrow-band imaging
(NBIME) that visualizes the capillary patterns of gastric surface structure is
useful for predicting the histologic characteristics of superficial gastric neoplasms. NBIME with acetic acid-enhancement (A-NBIME) clearly visualize the
microstructure pattern of gastric mucosal surface.
AIMS & METHODS: We performed a prospective study to compare the diagnostic reliability of white light endoscopy (WLE), NBIME, and A-NBIME for
the histologic characteristics of gastric mucosal neoplasms. Consecutive 220 gastric neoplasms (49 adenomas, 144 differentiated adenocarcinomas, and 27 undifferentiated adenocarcinomas) were photographed with WLE, NBIME and ANBIME.
Macroscopic patterns by WLE, capillary patterns by NBIME and microstructure
patterns by A-NBIME were respectively classified into type M1/M2/M3, type
C1/C2/C3/C4 and type S1/S2/S3, by referring to the previously reported

Table to abstract P0698

Dose of initial bolus injection (mg/kg)


Dose of continuous drip infusion (mg/kg/h)
Average number of additional bolus injections at introductory phase
Average number of increasing maintenance dose
Average total dose (mL)
SpO2 5 90%
Blood pressure 5 80 mm Hg
BIS score 5 60 (45 seconds)

Phase1 (n27)

Phase 2 (n11)

Phase 3 (n7)

Phase 4 (n14)

Phase 5 n30)

0.5
5
1.07 (06)
0.7 (05)
48.5(17109)
0
11 (40.7%)
NA

0.33
3.3
4.0 (113)
1.5 (02)
60.1 (24135)
0
3 (27.3%)
NA

0.5
3.3
1.6 (05)
1.3 (05)
49.6 (16133)
0
3 (42.9%)
NA

0.5
2.5
3.8 (07)
2.6 (15)
44.4 (1295)
0
4 (28.6%)
NA

0.5
2.5
3.6 (017)
1.9 (07)
52.1 (7.5170)
0
3 (4.8%)
1 (1.6%)

A324
classifications as described below. Macroscopic pattern; Type M1: the protruded
and whitish lesions with roundish edge and smooth or often nodular surface.
Type M2: the irregular-shaped and depressed, flat, or elevated lesion in red or
similar color to the surrounding mucosa. Type M3: the depressed and whitish
lesions often with variously sized nodules on the lesion. Capillary pattern; Type
C1: capillaries with homogenous diameters and distributions. Type C2: capillaries with heterogeneous diameters and irregular distributions. Type C3: capillaries grow in disorder with unclear mucosal microstructure. Type C4: capillaries
are invisible or obviously decreased. Microstructure pattern; Type S1: glandular
crypts present, homogeneously sized, shaped and arranged foveolae or grooves.
Type S2: glandular crypts present, heterogeneous. Type S3: glandular crypts are
absent or severely decreased.
Endoscopic images were independently reviewed by three expert endoscopists.
Type M1/M2/M3 in WLE, type C1/C2/C3 in NBIME, and type S1/S2/S3 in ANBIME were used as the indicator of adenoma/differentiated adenocarcinoma/
undifferentiated adenocarcinoma, respectively. Type C4 in NBIME was excluded
from the analysis of histologic diagnostic accuracy. The histologic diagnostic
accuracy and interobserver diagnostic agreement was compared among
modalities.
RESULTS: The kappa values of interobserver agreement for WLE, NBIME, and
A-NBIME diagnosis were 0.33(0.31-0.36), 0.58(0.55-0.61), and 0.61(0.54-0.67),
showing an insufficient diagnostic agreement for WLE and a statistically good
diagnostic agreement for both NBIME and A-NBIME. Adenomas/differentiated
adenocarcinomas/undifferentiated adenocarcinomas were statistically related to
type M1/M2/M3 in WLE, type C1/C2/C3 in NBIME and type S1/S2/S3 in ANBIME, respectively (P50.01). Type C4 of capillary pattern by NBIME did not
show a statistical correlation to the specific histologic characteristics. The diagnostic accuracy of WLE, NBIME, and A-NBIME were 79.0%, 74.1%, and
90.5%, showing statistical superiority of A-NBIME (P50.01). No additional
effect of NBIME to WLE.
CONCLUSION: A-NBIME is superior to WLE and NBIME in the predictive
histological diagnosis of gastric mucosal neoplasms with good clinical feasibility.
Disclosure of Interest: None declared
P0700 HIGHEST POWER MAGNIFICATION IS SUPERIOR TO LOW
POWER MAGNIFICATION FOR DELINEATION OF EARLY
GASTRIC CANCERS USING NARROW BAND IMAGING
K. Uchita1,*, K. Yao2, N. Uedo3, T. Iwasaki1, K. Kjima1, A. Kawada1,
M. Okazaki1, S. Iwamura1
1
Gastroenterology, Kochi Redcross Hospital, Kochi, 2Endoscopy, Fukuoka
University Chikushi Hospital, Fukuoka, 3Gastrointestinal Oncology, Osaka
Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
Contact E-mail Address: ucchy31@yahoo.co.jp
INTRODUCTION: Curative endoscopic submucosal dissection (ESD) of early
gastric cancers requires accurate determination of the horizontal extent of invasion. A number of studies have since reported superior diagnostic ability for
magnifying endoscopy with narrow-band imaging (ME-NBI) over conventional
endoscopy (CE) in delineating the lateral extent of early gastric neoplasias.
However, there are few studies that have reported the actual magnifying ratio
used when performing ME. The added benefits of ME-NBI over CE in terms of
the difference in magnification level have yet to be elucidated.
AIMS & METHODS: The aim of this study was to investigate the improvement in
diagnostic accuracy for tumor delineation obtained with different magnification
levels of ME-NBI following CE. This study comprised a series of 161 consecutive
early gastric cancers resected en bloc using ESD in 158 patients between July 2008
and June 2012. Each patient underwent sequential CE, LM-NBI and HM-NBI
examinations during the same procedure as preoperative diagnostic examinations
1 to 2 weeks prior to ESD. On the day of the ESD procedure, or the preceding day,
using HM-NBI we again identified the lesion margin, and made markings 3-5 mm
outside the DL. After ESD with reference to the pathohistological findings, we
identified the markings, and reconstructed the lateral extent of the cancer on the
each endoscopic image (CE, LM-NBI, HM-NBI). The histologically determined
cancer margins were used as the gold standard. The primary endpoint was the
added benefit, as measured using the successful delineation rate, for the delineation
of gastric cancer margins using CELM-NBI vs CE, and for CELM-NBIHMNBI vs CELM-NBI. We derived the successful delineation rate with 95% confidence intervals (CI) for early gastric cancers using each examination method, CE,
CELM-NBI, and CELM-NBIHM-NBI and used McNemars test with
Bonferronis multiple comparison correction to calculate p values.
RESULTS: The clinical characteristics were as follows: average age 71 years; 116
males and 45 females; mean lesion diameter 19.2 mm (14.4 mm, range 5-120
mm); and macroscopic type using the Paris classification type 0-I 4 lesions
(2.5%), type 0-IIa 64 lesions (39.8%), type 0-IIb 38 lesions (23.6%), and type
0-IIc 55 lesions (34.2%). The location of the lesion was the upper part of the
stomach in 46 cases (28.6%), middle part in 41 (25.5%), and lower part in 74
(46.0%). The successful delineation rates (95% CI) using CE, CELM-NBI and
CELM-NBIHM-NBI were 72.7 (68.5-79.9%), 88.9 (83.9-93.7%), and 98.1
(95.8-100%). The diagnostic accuracy improved significantly for CELM-NBI
compared with CE (P50.001) and for CELM-NBIHM-NBI compared with
CELM-NBI (P50.001).
CONCLUSION: ME-NBI is an extremely useful modality for the delineation of
the margins of early gastric cancers. HM-NBI is superior to LM-NBI in improving the successful delineation rate, following CE.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0701 GASTRIC ATROPHY WAS A RISK FACTOR
PRESENCE OF MISSED SYNCHRONOUS LESION AFTER
ENDOSCOPIC SUBMUCOSAL DISSECTION

FOR

THE

K.H. Kim1,*, S. I. Seo1, B.Y. Choi1


Department of Internal Medicine, Division of Gastroenterology & Hepatology,
Kangdong Sacred Heart Hospital of Hallym University Medical Center, Seoul,
Korea, Republic Of
Contact E-mail Address: minsoksumin@naver.com
1

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely


accepted as a minimally invasive therapy for gastric adenoma or early gastric
cancer (EGC). However, the risk of secondary gastric neoplasms developing
during the surveillance period after ESD has become a important medical problem. In particular, there is a high possibility that ESD can miss synchronous
gastric neoplasms compared with surgery.
AIMS & METHODS: In the present study, we aimed to investigate predictive
factors associated with the presence of missed synchronous gastric neoplasms
after ESD for gastric adenoma or EGC. We performed ESD in 370 patients
with EGC or gastric adenoma from January 2008 through December 2012 at
our institution. The patients with endoscopic surveillance interval less than 1
year, patients without curative resection, and patients with additional surgery
were excluded from the study. Missed synchronous gastric neoplams were
defined as any gastric neoplasms detected within one year after ESD, but initially
unidentified. We compared clinical, endoscopic, and pathological factors
between patients with missed synchronous gastric neoplasms and patients without missed synchronous gastric neoplasms.
RESULTS: Missed synchronous gastric neoplasms were found in 4.3% (16/370)
of the patients. Among the 16 missed synchronous gastric neoplasms, three
(18.8%) cases were carcinomas. In the univariate analysis, open-type gastric
atrophy, gastric atrophy and intestinal metaplasia more than moderate degree
were significantly associated with the presence of missed synchronous gastric
neoplasms. In multivariate logistic regression analysis, only gastric atrophy
more than moderate degree was the independent risk factor for the presence of
missed synchronous gastric neoplasms (Exp (B) 8.608, 95%CI: 1.03645.549).
CONCLUSION: Gastric atrophy could be an independent risk factor for the
presence of missed synchronous lesion after ESD. Careful endoscopic surveillance should be performed after ESD for patients with severe gastric atrophy.
Disclosure of Interest: None declared
P0702 EFFECT OF ELECTRICAL CURRENT MODE ON CLINICAL
COURSE AFTER GASTRIC ENDOSCOPIC SUBMUCOSAL
DISSECTION
K.H. Song1,*, S.M. Kim1, J.H. Park1, K.C. Huh1
1
Konyang University, Deajon, Korea, Republic Of
Contact E-mail Address: postit2@daum.net
INTRODUCTION: Several modes of electrical current are available for endoscopic submucosal dissection (ESD) of gastric epithelial tumor. There has been
no data regarding whether the electrical current mode effects on clinical course
after gastric ESD, including incidence of post ESD coagulation syndrome, ulcer
healing rate.
AIMS & METHODS: AIM Clinical courses were surveyed according to the
setting of two different dissecting mode: endocut or swift, to provide relating
data on optimal adoption of mode for gastric ESD.
METHODS Among 286 consecutive sessions of gastric ESD, 200 lesions were
surveyed after excluding cases: usage of endoknives other than IT2 knife, tumor
with nearby scar, synchronous tumor, subepithelial tumor. Only one of endocut
or swift mode was adopted for submucosal dissection in eaach session of ESD.
All the procedure were performed using an electrosurgical unit, VIO 300D
(ERBE, Germany). The ESD pathology, location of tumor, procedure and resection time, incidence of post ESD syndrome were assessed with demographic data.
Patients with pyrexia (body temperature 438.3_C) and upper abdominal pain or
tenderness after ESD, with or without symptoms of peritoneal irritation were
defined as having post ESD coagulation syndrome. Follow up endoscopy was
performed at 3 months after the endoscopic therapy and rated as ulhealed if the
ulcer was in A1 to H2 rated by Sakita-Miwa stage.
RESULTS: In total of 200 sessions, we applied endocut mode for 116 cases
(58%) and swift mode at for 84 cases (42%). The demographic data between
the two groups were not significantly different. Total of 16 post ESD coagulation
syndromes were notified. Multivariate analysis revealed adoption of swift mode
(OR 6.90, 95%CI: 1.83-25.92) and malignant pathology (OR 5.93, 95%CI: 1.4624.02) was related post ESD coagulation syndrome. Ulcer healing rate judged at
3 months after ESD tended to be delayed for endocut mode, even though it was
not statistically significant.
CONCLUSION: Mode of electrical current may be related to the incidence of
post ESD coagulation syndrome or ulcer healing after gastric ESD. Randomized
and controlled studies are warranted.
REFERENCES
Lee H, et al. Clinical features and predictive factors of coagulation syndrome
after endoscopic submucosal dissection for early gastric neoplasm. Gastric
Cancer 2012; 15: 83-90.
Disclosure of Interest: None declared

A325

United European Gastroenterology Journal 2(1S)


P0703 TRANASAL
VERSUS
PERORAL
PERCUTANEOUS
ENDOSCOPIC GASTROSTOMY: A PROSPECTIVE CASE
CONTROL STUDY
L.-F. Lin1,*
1
Gastroenterology, Pingtung Christian Hospital, Pingtung, Taiwan, Province of
China
Contact E-mail Address: lin.lian.feng@gmail.com

Table 1. Demographic, endoscopic procedures, propofol dose and adverse events


in both groups
Table to abstract P0704

Age

Weight

75 years 81  4

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a challenge


in patients with difficult oral intubation. Some cases of successful transnasal
insertion of PEG were reported. But no any case control study was conducted
to compare transnal and oral insertion of PEG.
AIMS & METHODS: This work is to investigate the difference between transnasal and peroral insertion of percutaneous endoscopic gastrostomy in clinical
outcome. A prospective, case-control study was conducted to compare transnasal
(T-PEG) and peroral (O-PEG) placement of a 20 Fr PEG tube in dysphagic
patients without conscious sedation. Additional spraying lidocain solution and
epinephrine solution to the nasal cavity and using ultrathin 5 mm endoscope
(Olympus GIF-N-260) were applied to the T-PEG. The other premedication
and procedure are same as conventional pull-method PEG. Neither the nasal
cavity nor the oral cavity were decolonized in all patients. The success rate,
operation time, occurrence of choking during PEG, nasal bleeding, stomal site
infection, post-PEG complication were recorded and analyzed.
RESULTS: Thirty-nine insertions of T-PEG and thirty-eight insertions of OPEG were attempted in 77 chronic dysphagic patients form home or nursing
home. Mean age is (T-PEG vs O-PEG) 76.310.3 vs 79.56.9 years, male
gender 67% vs 48%, operation time 14.6  4.0 vs 113 minutes (p: 0.028),
choking occurred in 3 vs 5 patients. One failed insertion and two nasal bleeding
occurred in T-PEG. There are nine stomal site infection (8 pseudomonas aeruginosa infection including one systemic infection) in T-PEG and 14 stomal site
infects (8 pseudomonas aeruginosa) in O-PEG (p 50.001). One systemic infection of urinary tract, one buried bumper, and one soiling of stoma were observed
respectively in T-PEG and O-PEG. No PEG related mortality occurred within 3
months after all PEG procedures.
CONCLUSION: Transnasal insertion is feasible in placing a 20 Fr PEG but it
causes rare nasal bleeding rate and needs longer operation time. Stomal site
infection is less but more dominant pseudomonas infection occurred in TPEG. In conclusion, T-PEG is an alternative for patients who had difficulty in
oral intubation. It needs more studies to concern the prophylaxis of pseudomonas infection.
Disclosure of Interest: None declared
P0704 PROPOFOL REQUIREMENTS FOR GASTROINTESTINAL
ENDOSCOPY IN PATIENTS OLDER THAN 75 YEARS OLD
L. Achecar1,*, X. Garc a Aguilera1, A. Gonzalez1, M. Del R o1, G. Arranz1,
M.Van Domselaar1
1
Endoscopy unit, Hospital Universitario de Torrejon de Ardoz, Madrid, Spain
Contact E-mail Address: xagarcia@torrejonsalud.com
INTRODUCTION: Numerous studies support the efficacy and safety of propofol in digestive endoscopy in which propofol is administered by non-anesthesiologist during endoscopic procedures. There is literature on the safety of sedation
with propofol in elderly patients. However, there are no clear guidelines regarding the dose of propofol to be used in this group of patients in which comorbidity
can make them more fragile, making the standard dose/kg of weight excessive to
achieve a safe sedation.
AIMS & METHODS: The aims of this study were to establish the dose of
propofol in patient 75 years compared with patients 575 years and to evaluate
the safety of propofol when is administered by non-anesthesiologist. Between
June 2012 and March 2014, we prospectively recorded all endoscopic procedures
and safety data. Only diagnostic procedures were included for this study. We
excluded: patients 518 years, not sedated by endoscopist, therapeutic and
incomplete procedures, and also patients with two endoscopies performed on
the same day. To reduce variability and determine whether the differences
between the doses of propofol in both groups were related to age, all patients
75 years were matched on a 1:1 basis with the 575 years group in terms of
weight, body mass index (BMI) and endoscopic procedure. All esophagogastroduodenoscopies (EGDs) and colonoscopies received an initial dose of propofol
0.5-1 mg/kg. Colonoscopies also received a fixed dose of 50 mcg of fentanyl.
Subsequently, boluses of 10-20 mg propofol were administered to maintain an
adequate level of sedation. Vital signs were recorded before, during and after the
procedure. A statistical analysis was performed with the SPSS v20.0 program.
RESULTS: There were 439 diagnostic EGDs and 307 diagnostic colonoscopies
performed in patients 75 years. When compared with patients 575 years, there
were significant differences between groups in mean propofol dose, and mild
adverse events. No serious adverse events occurred. Patients 75 years required
significantly less propofol than patients 575 years, 72.99 37.4mg vs. 120.54
4.8mg for EGDs (P 5 0.001) and 80.5934mg vs 129.12 55.9mg (P 5 0.001)
for colonoscopies (39.4% less in EGDs and 37.5% in colonoscopies). Table 1
shows the demographic, endoscopic procedures, propofol dose and adverse
events in both groups.

Propofol
ASA I/II/III
Colonoscopy dose EGD /
(%)
EGD n n (%)
Colonoscopy

AE (%)
Desaturation/
Bradycardia

68.56  12,4 17.3/70.3/12.4 439

307

72.99 37.4/
80.5934

575 years 51.3 13 68.55  12,4 62.8/34.9/2.3 439

307

120.54 4.8**/ 0.8/0.3*


129.12 55.9**

2.6/0.3

Data are presented as mean  SD (range: 95% CI of the mean). Abbreviations:


ASA
(American
Society
of
Anaesthesiology);
EGD
(Esophagogastroduodenoscopy). AE: adverse events. *P 5 .005; **P 5 .001
CONCLUSION: Propofol is safe when administered by non-anesthesiologists.
Patients 75 years globally require almost 40% less propofol than patients 575
years. These results support the use of a lower dose of propofol in the elderly.
REFERENCES
Disclosure of Interest: None declared
P0705 CHANGES
IN
GASTRIC
INTESTINAL
METAPLASIA
EXTENSION IN ANNUALLY FOLLOWED-UP PATIENTS: 1-YEAR
RESULTS OF A STUDY PERFORMED BY MEANS OF NARROW
BAND IMAGING WITH MAGNIFICATION ENDOSCOPY
L. Gemignani1, P. Dulbecco1, E. Giambruno1, G. Bodini1,*, M. Furnari1,
M. Giacchino1, F.E. Gianiorio1, L. Mastracci2, F. Grillo2, F. Sarocchi2,
V. Savarino1, E. Savarino3
1
Department of Internal Medicine, 2Department of Pathologic Anatomy,
University of Genoa, Italy, Genoa, 3Department of Surgical, Oncological and
Gastroenterological Sciences, University of Padua, Padua, Italy
Contact E-mail Address: alphaone81@gmail.com
INTRODUCTION: Gastric Intestinal Metaplasia (GIM) is a precancerous condition potentially leading to gastric cancer. However, this occurs in a limited
number of cases and, therefore, the need of endoscopic surveillance and
follow-up is controversial. Moreover, there is no universal consensus regarding
which patients should be better investigated and followed-up in the long-term
period. Most of the experts among pathologists and gastroenterologists recommend to perform an upper endoscopy with multiple biopsies every three-year
only in patients with extensive GIM, but no studies have validated the effectiveness of this protocol, so far.
AIMS & METHODS: Our aim was to investigate whether changes in extension
and/or progression of GIM occur during a strict yearly endoscopic follow-up
program. Between November 2011 and December 2013, we prospectively evaluated consecutive patients with an histologically defined diagnosis of GIM by
means of Narrow Band Imaging with Magnification Endoscopy (NBI-ME) and
multiples gastric biopsies (2 antrum 1 angulus 2 corpus). Helicabacter pylori
infection was excluded. Patients with a GIM extension higher than 20% were
offered to repeat the endoscopic examinations every year and, to date, 20 out of
121 accepted and were included in the follow-up program. Endoscopic examinations have been performed by experienced endoscopists (each of them with more
than 1000 NBI-MEs performed). Biopsies were taken at sites suggestive for GIM
based on NBI-ME appearance (i.e. presence of light blue crests on the surface of
gastric mucosa) or randomly if no evident mucosal alterations were seen. Biopsies
were assessed by two expert and blinded pathologists, who evaluated the percentage of extension of GIM at both times.
RESULTS: The median time between the two observations was 13 months
(range 11-18). As shown in the Table, patients were divided in three categories,
according to the changes in GIM extension, which was considered stable if there
were tiny variations (0-5%) between the two observations, or raised/lowered
otherwise. At 1-year, in all patients, the second evaluation confirmed the presence
of GIM. In patients with worsened extension, the mean percentage of GIM
increase was 20%, whereas the mean percentage of GIM lowering was 26%in
patients with a reduced GIM extension.
GIM
STABLE
GIM
MEDIAN AGE
EXTENSION GIM
EXTENSION
N AGE
RANGE LOWERED EXTENSION RAISED
Females
13 67
Males
7 64
OVERALL 20 64

56-71
53-85
53-85

3 (23%)
4 (57%)
7 (35%)

3 (23%)
1 (14%)
4 (20%)

7 (54%)
2 (29%)
9 (45%)

CONCLUSION: Our results demonstrate that already at 1-year the extension of


GIM and, therefore, the risk of developing a gastric cancer GIM-related, worsens
in about 45% of the patients. Thus, these data seem to support a more close
follow-up in patients with a GIM extension higher than 20% at histologic
assessment.
Disclosure of Interest: None declared

A326
P0706 DOES MAGNIFYING ENDOSCOPY WITH NARROW BAND
IMAGING IMPROVE DIAGNOSTIC ACCURACY FOR DEPTH OF
INVASION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA?
M. Imajoh1,*, T. Yano1, T. Kadota1, T. Kato1, S. Osera1, H. Morimoto1,
T. Odagaki1, Y. Oono1, H. Ikematsu1, K. Kaneko1
1
Department of Gastroenterology, Endoscopy Division, National Cancer Center
Hospital East, Kashiwa city, Japan
Contact E-mail Address: maomiimajo@gmail.com
INTRODUCTION: While accurate estimation for the depth of invasion in esophageal squamous cell carcinoma (ESCC) is essential to indicate relevant treatment methods, it is difficult to evaluate conventional endoscopy alone.
Microvascular patterns identified using magnifying narrow band imaging (MNBI) have been reported to be useful for the diagnosis in the depth of invasion
for superficial ESCC. Recently, a classification regarding the microvascular patterns of superficial ESCC using M-NBI was advocated from the Japan
Esophageal Society, however, it is not clear whether the depth of invasion can
be estimated more accurately according to this classification compared with
estimation using conventional white light endoscopy (WL) alone.
AIMS & METHODS: The aim of this study was to evaluate whether the diagnostic accuracy of in M-NBI is higher than that in WL alone. In this study, we
enrolled patients with superficial ESCC who had undergone pretreatment evaluation using both WL and M-NBI, and who received endoscopic resection or
surgery in our institution from June 2012 to December 2013. The patients who
had been previously treated with chemotherapy or chemoradiotherapy were
excluded. The microvessels of tumor surface observed by M-NBI were classified
into 3 groups; type B1 consisted of loop-like vessels with atypia, including dilatation and meandering; type B2 were non-loop vessels; and type B3 were large
vessels 3 or more times larger than type B2. Type B1, B2, and B3 vasculatures
were correlated with lesions invading to EP/LPM, MM/SM1, and SM2 or
deeper, respectively. Investigators who were blinded to the pathological diagnosis
estimated retrospectively the depth of invasion in the endoscopic pictures by WL
alone, and then using the pictures by M-NBI. We sorted the lesions into 3 groups
(EP/LPM, MM/SM1, and SM2/SM3) and the diagnoses for individual modalities were compared to the pathological results. Finally, sensitivity, specificity,
and positive predictive value (PPV) were analyzed.
RESULTS: A total of 198 lesions were examined. Sensitivity, specificity, and
PPV of WL-alone were 92%, 85%, 90% for EP/LPM; 63%, 89%, 51% for
MM/SM1; and 74%, 97%, 90% for SM2/SM3, respectively. Sensitivity, specificity, and PPV of M-NBI were 85%, 71%, 81% for EP/LPM; 50%, 75%, 28% for
MM/SM1; and 39%, 100%, 100% for SM2/SM3, respectively. The concordance
rate for diagnoses between both modalities was 87% in EP/LPM, 59% in MM/
SM1, and 45% in SM2/SM3. In cases of a concordance between WLE and NBIME, the PPV was 90% for EP/LPM, 61% for MM/SM1, and 100% for SM2/
SM3.
CONCLUSION: While the concordance rates between WL and M-NBI was
unfavorable in MM/SM1, and SM2/SM3, PPV was high in the diagnosis was
concordant cases between both modalities. However, the difficulty of evaluating
the invasion depth for MM/SM1 lesions remains unsolved.
REFERENCES
1 Oyama T and Monma K. A new classification of magnified endoscopy for
superficial esophageal squamous cell carcinoma. Esophagus 2011; 8: 247-251.
2 Muto M, Horimatsu T, Ezoe Y, et al. Improving visualization techniques by
narrow band imaging and magnification endoscopy. J Gastroenterol Hepatol
2009; 24: 13331346.
Disclosure of Interest: None declared
P0707 RJ 4 JUMBO VS. RJ 4 LARGE CAPACITY FORCEPS IN TISSUE
SAMPLING IN PATIENTS WITH BARRETTS ESOPHAGUS: FINAL
RESULTS OF A PROSPECTIVE, RANDOMIZED STUDY
M. Kollar1,*, J. Maluskova1, E. Honsova1, J. Krajciova2, J. Spicak2, J. Martinek2
1
Clinical and transplant pathology department, 2Hepatogastroenterology department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Contact E-mail Address: marek.kollar1@seznam.cz
INTRODUCTION: Good quality of biopsy specimen is required for reliable
diagnosis of early neoplasia in patients with Barretts esophagus (BE). Studies
comparing large capacity vs. jumbo forceps have shown inconsistent results.
The aim of this study was to assess the quality of biopsy specimen obtained by
2 different-sized biopsy forceps (Radial Jaw 4 large capacity (outer diameter 2.4
mm) vs Radial Jaw 4 jumbo (outer diameter 2.8 mm) in patients with BE. We
hypothesized that RJ4 jumbo forceps if used with a standard diagnostic endoscope (channel 2.8 mm) provides a better quality of biopsy specimen as compared
to the large capacity forceps.
AIMS & METHODS: A single center, randomized (forceps order), prospective
and single blind (pathologist) study. Twenty-one patients with BE (5 women, 16
men) were enrolled. All patients underwent an upper GI endoscopy with trimodal
imaging. Targeted or random biopsies with both types of forceps used in random
order were obtained from each patient during a single endoscopy with a diagnostic endoscope. Main outcome measurement was specimen adequacy (defined
as a well oriented biopsy specimen 2 mm in diameter or greater with mucosa
present).
RESULTS: A total of 288 biopsy specimen were analyzed (large capacity: 159,
jumbo forceps: 129). A significantly higher proportion of biopsy samples
obtained with jumbo forceps was adequate as compared to large capacity forceps
(54.3 % vs. 18.9 %, p50.0001).
Biopsies with jumbo forceps had a larger diameter (median 2.4 mm vs. 2 mm;
p50.001). Muscularis mucosae was detected in 67.4 % of specimen with jumbo
forceps vs. 31.4 % with large capacity forceps (p50.0001). Excellent or good

United European Gastroenterology Journal 2(1S)


specimen orientation was present in 79.8 % of samples with jumbo forceps and in
59.1 % with large capacity forceps (not significant). Intestinal metaplasia was
present in 69.8 % with jumbo forceps vs. 78.6 % of samples with large capacity
(not significant). The diagnostic yield of both types of forceps was comparable.
CONCLUSION: Radial Jaw 4 Jumbo biopsy forceps, if used with diagnostic
endoscope, provides more adequate biopsy specimen as compared to Radial Jaw
4 large capacity biopsy forceps. The diagnostic yield seems to be comparable.
Disclosure of Interest: None declared
P0708 OPTIMIZED IMPEDANCES OF INJECTION SOLUTIONS LEAD
TO IMPROVED CUTTING RESULTS IN ENDOSCOPIC RESECTION
N. Al-Dayaa1, M. Losle1,2, K.-E. Grund1,2,*
1
Surgical Endoscopy and Experimental Endoscopy, University Hospital, Tubingen,
2
supported by: Federal Ministry of Economics and Technology based on a resolution of the Bundestag, Berlin, Germany
Contact E-mail Address: chir.endo@uni-tuebingen.de
INTRODUCTION: The endoscopic resection of large ( 4 20 mm) lesions in the
gastrointestinal tract is a high challenge for interventional endoscopy and radiofrequency surgery. There is no easy, fast and safe way to remove large lesions enbloc. An important reason is the interaction between submucosal injection, tissue
and high-frequency parameters in respect to electrical impedances. This interaction is only partly understood and poorly investigated. Preliminary studies led to
the conclusion that problems in the cutting process like cutting delay, perforation
and thermal artifacts are due to unsuitable impedances.
AIMS & METHODS: Our aim was to improve the cuttings results (avoiding of
cutting delay and high thermal load of the intestinal wall) by optimizing the
impedances of the tissue. Therefore we analyzed various submucosal injection
solutions in respect to impedances (surface and tissue) and rf-cutting.
With standardized gold probes (1 mm/15 mm) and a special RF-impedancemeter (f 100 kHz, 10 V - 1 MV) the specific impedances of various solutions
and the impedances on the surface and in the tissue after submucosal injection of
3 ml were measured in a standardized bio-model (porcine stomach). Additionally
the elevations during 30 min were observed. The following solutions were injected
into the submucosa: 0.9% saline, 4% gelatin, 6% hydroxyethyl starch, 10%
glycerol/5% fructose in 0.9% saline, 10% glucose and aqua destillata.
Additionally 5% albumin, 20% albumin, human blood and blood plasma and
a new experimental substance.
RESULTS: Aqua destillata and 10% glucose showed a highly significant higher
(p  0.0001) specific impedance compared to the standard 0.9% saline (factor
360). After injection also the impedances on the surface and in the tissue were
significantly higher (p  0.01, resp. p  0.0001). The elevation showed no significant difference between the tested solutions. Cutting experiments in a standardized setting showed the expected improvements: no cutting delay, less
thermal load of the intestinal wall, smooth cut without carbonization but with
adequate zone of hemostasis.
CONCLUSION: Clinically used injection solutions show a highly significant
difference of specific impedances. After injection they lead to different impedances on the surface and in the tissue. Better cutting results (avoidance of
delayed cut, high thermal load and thermal artifacts) obviously depend on an
optimized impedance of the tissue. Therefore injection solutions with optimal (i.e.
higher) impedances should be further investigated and preferred to conventional
agents.
REFERENCES
Park YM, Cho E, Kang HY, et al. The effectiveness and safety of endoscopic
submucosal dissection compared with endoscopic mucosal resection for early
gastric cancer: a systematic review and metaanalysis. Surg Endosc 2011; 25:
2666-2677.
Kim YJ, Kim ES, Cho KB, et al. Comparison of clinical outcomes among
different endoscopic resection methods for treating colorectal neoplasia. Dig
Dis Sci 2013; 58: 1727-1736.
Farin G and Grund KE. Principles of electrosurgery, laser, and argon plasma
coagulation with particular regard to colonoscopy. In: Waye JD, Rex DK and
Williams CB (eds) Colonoscopy prociple and practice. Singapore: WileyBlackwell Verlag, 2009, pp. 328345.
Disclosure of Interest: None declared
P0709 PERCUTANEOUS
TRANSESOPHAGEAL
GASTROTUBING
WITHOUT RADIATION EXPOSURE WITH ENDOSCOPIC
ASSISTANCE
M. Murakami1,2,*, K. Nishino1, S. Murakami1, Y. Takaoka1, K. Mori1,
B. Murakami1, M. Azuma2, S. Tanabe2, M. Kida2, W. Koizumi2
1
Internal medicine, MURAKAMI MEMORIAL HOSPITAL, saijo,
2
Gastroenterology, Kitasato University East Hospital, Sagamihara, Japan
Contact E-mail Address: masato@mrakami-kinen.or.jp
INTRODUCTION: Percutaneous transesophageal gastrotubing (PTEG) was
developed as an alternative route to access the gastrointestinal tract for patients
where Percutaneous Endoscopic Gastrostomy was contraindicated with conditions such as prior gastrectomy, gastric anterior wall malignancies, or massive
ascites. PTEG was originally developed to be performed under fluoroscopy without endoscopy. However, endoscopy may enhance the safety of the procedure.
AIMS & METHODS: The aim of this study is to evaluate the clinical usefulness
of PTEG supported by endoscopy. A rupture-free balloon (RFB) catheter is
inserted into the lower esophagus. Percutaneous balloon puncture with a specialized needle is then performed from the left side of patients neck under ultrasonographic control. A guide wire is inserted through the needle into the RFB,
followed by a dilator and sheath. A placement tube is then inserted through the
sheath, and the sheath is removed. We started to perform PTEG under

United European Gastroenterology Journal 2(1S)


endoscopy without fluoroscopy in a total of 99 patients (63 men and 36 women,
mean age 74.0 years) in whom PEG was not feasible. PTEG was performed for
nutrition in 53 patients and for decompression in 46.
RESULTS: Satisfactory results were achieved in all 100 patients. Median followup was 60.5 days in patients who received decompression because of the obstruction due to malignancies and 231.0 days in those who received nutrition. Two of
the 99 patients in the endoscopic assistance required fluoroscopy because of the
tube insertion into the jejunum. There were no major complications, but one
patient had tracheal penetration, which was managed conservatively. Other complications were minor oozing bleeding in six patients that did not require blood
transfusion, subcutaneous emphysema in two patients, which were managed
conservatively. Nine accidental (four self) tube removals occurred more than 2
weeks after the procedure, without any problem in reinsertion. The overall complication rate associated with endoscopically assisted PTEG was 14.1%. No
patient required surgical treatment or died after PTEG.
CONCLUSION: PTEG supported by endoscopy is as feasible, safe, and useful
as PTEG supported by fluoroscopy, the original procedure. The use of endoscopy enhances the safety of the procedure and allows better confirmation of
each step involved.
Disclosure of Interest: None declared
P0710 ASSESSMENT OF THE SIMPLIFIED NARROW BAND IMAGING
PATTERN CLASSIFICATION IN BARRETTS OESOPHAGUS
M. Kato1,*, K. Goda2, Y. Shimizu3, A. Dobashi2, M. Takahashi3, M. Kato3
Endoscopy, The Jikei University Katsushika Medical Center, 2Endoscopy, The
Jikei University School of Medicine, Tokyo, 3Gastroenterology and Hepatology,
Hokkaido University Hospital, Sapporo, Japan
Contact E-mail Address: masakato89@gmail.com
1

INTRODUCTION: Various narrow band imaging (NBI) pattern classifications


in Barretts oesophagus (BO) have been proposed, but are not readily applied to
routine clinical practice due to their multiplicity or complexity.
AIMS & METHODS: We evaluate inter- and intra-observer agreement as well as
accuracy of a new simplified NBI pattern classification using NBI magnifying
endoscopic images.
A simplified binary classification is based upon NBI mucosal and vascular patterns: 1) regular pattern (non-neoplastic BO) 2) irregular (Barretts neoplasia,
BN). Four endoscopists consisting of 2 experts and 2 non-experts assessed 248
NBI magnifying endoscopic images (neoplasia 72, non-neoplasia 176) based on a
simplified binary NBI pattern classification. The endoscopists assessed two times
a randomly-arranged NBI magnifying endoscopic image sequence. The interval
between the 1st and the 2nd assessment was 6 weeks. Primary endpoint was interobserver agreement among endoscopists. Secondary endpoints were intra-observer agreements in each endoscopist and diagnostic accuracies of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) in
predicting BN as well as scores of diagnostic confidence level and image quality.
RESULTS: A median score for image quality was 5 (excellent) in both the 1st and
2nd assessment. Inter-observer agreement (multi-kappa value) among endoscocpists for BN prediction was calculated as 0.79 (substantial) and 0.86 (almost
perfect) for the 1st and 2nd assessment. Intra-observer agreement (kappa-value)
which were 0.95, 0.94 (experts) and 0.83, 0.83 (non-experts), respectively, were all
almost perfect. Mean sensitivity and specificity of NBI patterns for predicting
BN were 92.7% (experts, 90.3%; non-experts, 95.1%) and 95.9% (experts,
99.4%; non-experts, 92.3%) in the 1st assessment as well as 95.5% (experts,
95.8%; non-experts, 95.1%) and 95.7% (experts, 99.1%; non-experts, 92.3%)
in the 2nd assessment, respectively, with high confidence level in both assessments. NPV was 98.9% (experts, 96.2%; non-experts, 97.9%) and 99.3%
(experts, 98.3%; non-experts, 97.9%) in the 1st and 2nd assessment, respectively.
CONCLUSION: A simplified binary NBI pattern classification for BO showed
substantial to almost perfect inter- and intra-observer agreement and significantly high diagnostic accuracies in both experts and non-experts. A simplified
binary NBI pattern classification seems applicable to routine clinical practice.
Disclosure of Interest: None declared
P0711 PREDICTIVE FACTORS FOR LYMPH NODE METASTASIS
AFTER NONCURATIVE ENDOSCOPIC RESECTION FOR EARLY
GASTRIC CANCER
M. Inoue1,*, T. Omori1, R. Nakamura1, T. Takahashi1, N. Wada1,
H. Kawakubo1, H. Takeuchi1, Y. Saikawa1, Y. Kitagawa1
1
Department of Surgery, School of Medicine, Keio University, Shinjyuku-ku,
Tokyo, Japan
INTRODUCTION: Endoscopic resection (ER) is widely accepted as an appropriate treatment modality for early gastric cancer. The indication criteria for ER
is established, and additional treatment, including gastrectomy with lymph node
dissection, is recommended when pathological examination of resected specimens
do not meet the criteria. In some non-curative ER cases, pathological examination after additional surgery reveals lymph node metastasis which have not been
detected before ER. There is a possibility that the discovery of risk factors of LNmetastasis in non-curative ER case can expand the indications of endoscopic
treatment for early gastric cancer.
AIMS & METHODS: The aim of this study is to examine the predictive factors
of LN- metastasis which could not be detected before ER in non-curative ER
cases. The indication criteria for ER in Japan is as follows; the lesion clinically
diagnosed as intramucosal differentiated cancer which is 52 cm in size with no
ulceration findings. Expanded indications for some differentiated cancers (intramucosal cancers either 53 cm in size with ulceration findings or with no ulceration findings regardless of tumor size) and some undifferentiated cancers
(intramucosal cancers 52 cm in size with no ulceration findings) have been

A327
accepted by high volume ER centers like our institution. If the pathological
examination of resected specimens show that they do not meet the criteria including expanded indications, we diagnose them as non-curative. From Apr 2000 to
Jul 2013, 75 patients underwent ER as the expanded indication lesion, and were
diagnosed as non-curative by pathological examination in our hospital. They
underwent additional gastrectomy and their pathological findings in ER and
surgical specimens were retrospectively analyzed. And the cases with pathological
LN- metastasis, which have not been detected before ER, were picked up and
their characteristics were analyzed.
RESULTS: LN- metastasis was found in 9 cases (12%). 7 cases were primary
gastric cancers, and 2 cases were residual gastric cancers. In the 7 primary cases, 5
cases had no residual cancer in surgical specimen, while LN- metastases existed.
Focus on these complete endoscopic resection cases, 1 case was pathologically
undifferentiated type and 5 cases were mixed type. The depth of invasion was
SM1 in 1 case, and SM2 in 4 cases. Lymphatic-vascular capillary involvement
was found in all cases. In these cases, LN- metastases were found only in local D1
lymph node lesion. Lymph node relapse was found in 2 SM2 cases in the complete endoscopic resection cases at an early date, one case was in 5 months and
another in 6 months after surgical resection. Both of them had not only lymphatic capillary involvement but also vascular one.
CONCLUSION: Our data indicate that SM1/SM2 gastric cancer with pathologically mixed type, regardless of predominant type, have high risk of LN- metastasis even if complete endoscopic resection of local lesion has been performed.
Lymphatic-vascular capillary involvement also may be a predictive factor of LNmetastasis and risk factor of recurrence. In these cases, we should perform gastrectomy with appropriate LN- dissection keeping the risk of recurrence in mind
and consider adjuvant chemotherapy according to the risks.
Disclosure of Interest: None declared
P0712 HIGH DEFINITION (HD) ENDOSCOPY WITH I-SCAN FOR THE
DETECTION OF MARKERS OF COELIAC DISEASE: A FEASIBILITY
STUDY
P.D. Mooney1, M. Kurien1,*, S. Wong1, D.S. Sanders1
1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, United
Kingdom
Contact E-mail Address: peter.mooney@sth.nhs.uk
INTRODUCTION: Coeliac disease (CD) remains underdiagnosed. Previous studies have shown that up to 13% of patients with CD have undergone a previous
gastroscopy where the opportunity to take duodenal biopsies and make a diagnosis had been missed. Clinicians may rely on the presence of endoscopic markers
of CD to guide biopsy however these have been shown to lack the required
sensitivity. A routine duodenal biopsy approach may solve this problem but
this is time consuming and expensive. Methods to improve the macroscopic
detection of CD at endoscopy to guide biopsy would seem advantageous. A
single trial on I-Scan, a commercially available digital enhancement technique,
has shown promising results in identifying markers of villous atrophy (VA)1.
However this was an uncontrolled, unblinded trial in high prevalence population
(35% CD). We aimed to assess the utility of I-Scan in a lower prevalence population in a randomised controlled trial.
AIMS & METHODS: Patients on a single coeliac enriched endoscopy list were
randomised into 2 groups. Group 1 standard HD white light endoscopy (WLE)
and group 2 WLE plus I-Scan. The presence of endoscopic markers of CD,
scalloping, mosaic pattern, nodularity, loss of duodenal folds or increased vascularity was noted throughout the duodenum. All patients received 4 biopsies
from the second part of the duodenum and at least 1 biopsy from the bulb.
Coeliac serology was taken at the time of endoscopy. Macroscopic markers of
CD are compared VA on histology as the gold standard. 3, 10-point likert scales
for pain, discomfort and distress were used to assess tolerability.
RESULTS: 253 patients (149 female, mean age 53.3 SD 18.2) have been recruited
to date (127 into group 1 and 126 in group 2). In total 27 (prevalence 10.7%) new
diagnoses of CD have been made (14 in group 1 and 13 in group 2). I-Scan
appears to enhance the appearance of markers for CD and in 2 patients in
group 2 CD markers that were not noted to be seen on WLE became apparent.
Preliminary results show that endoscopic markers of CD across both groups
currently have a sensitivity of 78.6% (58.5 91.0), specificity 87.6% (82.4
91.5), positive and negative predictive values of 44.0% (30.3 58.7) and 97.1
(93.4 98.8). Median tolerability scores were good in both groups but better in
the I-Scan group than WLE alone (4/30 versus 8/30 p0.005)
CONCLUSION: The addition of I-Scan to standard endoscopy to aid the diagnosis of CD is well tolerated and is feasible. I-Scan appears to enhance the
markings of coeliac disease, however a larger study is required to truly evaluate
the effectiveness of I-Scan as an adjunct to standard endoscopy to increase CD
diagnosis.
REFERENCES
1. Cammarota G, Ianiro G, Sparano L, et al. Image enhanced endoscopy with IScan technology for the evaluation of duodenal villous patterns. Dig Dis Sci
2012; 58: 1287-1292.
Disclosure of Interest: None declared
P0713 EFFECT OF AGING ON COMPLICATIONS OF ENDOSCOPIC
SUBMUCOSAL DISSECTION (ESD) FOR EARLY GASTRIC
CANCER (EGC)
M. Kato1,*, T. Michida1, A. Soga1, A. Kusakabe1, M. Kato1, C. Hibino1,
Y. Shiode1, K. Murai1, Y. Matumura1, T. Kawai1, T. Saito1, Y. Nakada1,
M. Hamano1, K. Yamamoto1, M. Naito1, T. Ito1
1
Japan Community Health care Organization Osaka hospital, Osaka, Japan
Contact E-mail Address: minoru-kato-514@okn.gr.jp

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United European Gastroenterology Journal 2(1S)

INTRODUCTION: As ESD has been widely used as a minimally invasive treatment for EGC, opportunity to perform it for elderly patients is increasing.
However, there are few reports about safety and efficacy of ESD for them. We
evaluated the effect of aging on complications of ESD for EGC.
AIMS & METHODS: We perform a prospective study of the expanded indication of ESD for EGC (Soetikno, et al. J Clin Oncol. 23(20):4490-8). ESD was
performed in 891 patients from April 2006 to March 2013 according to the
indication. Patients were divided into elderly group (75 years or older; 344
cases) and non-elderly group (the rest; 547 cases). We compared the incidence
of complications such as post-ESD bleeding, perforation, pneumonia, and delirium between the groups.
RESULTS: No emergent surgery was experienced in all cases. One patient in
non-elderly group died of pneumonia. The incidence of pneumonia and delirium
were significantly higher in elderly group than in non-elderly group (7.0% in
elderly group vs 1.7% in non-elderly group; P50.01, 10.2% in elderly group
vs 1.0% in non-elderly group; P50.01, respectively). There was no significant
difference between two groups in the incidence of post-ESD bleeding and perforation (3.8% in elderly group vs 4.9% in non-elderly group; p 0.42, 7.0% in
elderly group vs 5.7% in non-elderly group; p 0.57, respectively). Among the
elderly group, the incidence of delirium was significantly higher in patients who
have dementia than in those who havent (79.2% in dementia patients vs 5% in
non-dementia patients; p50.01), and pneumonia was observed relatively more
often in patients who have a history of chronic obstructive pulmonary disease
(COPD) than in those who havent (10.9% in COPD patients vs 6.1% in nonCOPD patients; p 0.17).
CONCLUSION: ESD for EGC were safely performed even in elderly patients
without critical complications. However, pneumonia and delirium would be more
encountered after ESD in elderly patients, so we have to take care additionally
about them.
REFERENCES
Soetikno, et al. J Clin Oncol 23: 4490-4498.
Disclosure of Interest: None declared
P0714 ENDOSCOPIC INJECTION OF AUTOLOGOUS BLOOD VERSUS
DILUTED EPINEPHRINE FOR CONTROL OF ACTIVELY BLEEDING
GASTRODUODENAL ULCERS: A RANDOMIZED CONTROLLED
STUDY
M.H. Emara1,*, E. Darwiesh1, A.S. Bihery1, T. I. Zaher1
1
Tropical Medicine, ZAGAZIG UNIVERSITY, Zagazig, Egypt
Contact E-mail Address: emara_20007@yahoo.com
INTRODUCTION: A variety of endoscopic methods are available to achieve
hemostasis from an actively bleeding ulcer and reduce the risk of rebleeding e.g.
endoscopic injection of diluted epinephrine, applications of endoscopic clips and
argon plasma coagulation. Preliminary report showed that autologous blood
through tamponade effect, cellular components and its viscosity is effective
and easy applicable technique that can control bleeding from the actively bleeding gastroduodenal ulcers.
AIMS & METHODS: The aim of this study was to test if endoscopic injection of
autologous blood is superior to endoscopic injection of diluted epinephrine in
controlling bleeding from gastroduodenal ulcers. One hundred patients with
actively bleeding gastroduodenal ulcers were randomly assigned to autologous
blood injection (Group A, n 50) or diluted epinephrine (group B, n 50) along
the edges of the ulcers. Groups were compared for rates of initial hemostasis,
rebleeding and complications.
RESULTS:

Ulcer size
Small (52 cm)
Large (42 cm)
Ulcer site
Bulbar
Antral
Corporal
Ulcer type
Forest Ia (spurting)
Forest Ib (oozing)
Volume/cc
(blood/epinephrine)
MeanSD
Range

Group A
(Autologous blood)
N 50 (No & %)

Group B
(Diluted epinephrine)
N 50 (No & %)

32(64.0)
18(36.0)

35(70.0)
15(30.0)

20(40.0)
15(30.0)
15(30.0)

20(40.0)
20(40.0)
10(20.0)

30(60.0)
20(40.0)

30(60.0)
20(40.0)

P
0.523

0.424

1.0

0.022*
7.41.8
(5-10)

8.94.1
(5-21)

All patients initially achieved hemostasis (100%). Rebleeding occurred in 4 cases


of group A (8%) and 5 cases of group B (10%) but this difference was not
statstically significant. Two cases in group B developed cardiovascular complications (arrhythmia and ischemic heart attack) while none of group A developed
complications. Ulcer characteristics showed no difference regarding ulcer size,
site and Forrest classification (the table). There was a significant difference in the
amount needed for injection, little amounts of blood were needed to achieve
hemostasis in group A than the amounts of epinephrine needed in group B
(p 0.022)

CONCLUSION: Autologous blood is effective, comparable to diluted epinephrine in achieving initial hemostasis from actively bleeding gastroduodenal ulcers,
associated with 8% rebleeding rate and had no complications.
Disclosure of Interest: M. Emara: none, E. Darwiesh: none, A. Bihery: none, T.
Zaher: none
P0715 ENDOSCOPIC RESECTION AS A DIAGNOSTIC THERAPY FOR
BORDERLINE LESION OF GASTRIC CANCER; A MULTICENTRE
PROSPECTIVE OBSERVATIONAL STUDY
M. Kato1,2,*, A. Maekawa2, S. Egawa3, M. Komori4, T. Yamada2,5,
K. Yamamoto6, H. Ogiyama7, M. Nakahara8, N. Kawai9, T. Yabuta10,
A. Mukai11, Y. Hayashi2, T. Nishida6, M. Tsujii2, T. Takehara2
1
Department of Gastroenterology, National Hospital Organization, Tokyo Medical
Centre, Meguro-ku, Tokyo, 2Department of Gastroenterology and Hepatology,
Osaka University Graduate School of Medicine, Suita, 3Department of
Gastroenterology, Kansai Rosai Hospital, Amagasaki, 4Department of
Gastroenterology, Osaka Rosai Hospital, Sakai, 5Department of Gastroenterology,
National Hospital Organization Osaka National Hospital, Osaka, 6Department of
Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, 7Department of
Gastroenterology, Itami City Hospital, Itami, 8Department of Gastroenterology,
Ikeda Municipal Hospital, Ikeda, 9Department of Gastroenterology, Osaka Police
Hospital, Osaka, 10Department of Gastroenterology, Sakai Municipal Hospital,
Sakai, 11Department of Gastroenterology, Sumitomo Hospital, Osaka, Japan
INTRODUCTION: It is often difficult to discriminate between gastric adenocaricinoma and dysplasia/adenoma using endoscopic forceps biopsy. Endoscopic
resection (ER) is, therefore, applied for borderline malignant lesions for the
purpose of total biopsy in clinical practice. We have reported that about 40% of
patients with borderline lesion were diagnosed as adenocaricinoma after ER from
a multicenter retrospective analysis (M. Kato, et al. J Gastroenterol. 2010).
However, true incidence rate of adenocarcinoma is still unknown due to its
retrospective study design.
AIMS & METHODS: The aim of this study is to confirm the feasibility of ER
for gastric borderline malignant lesions.
This is a multi-centre prospective observational study from 10 hospitals (UMIN
Clinical Trials Registry: UMIN000007476). Patients were included if they were
diagnosed as Category 3.1 or 4.1 based on Vienna classification using endoscopic
forceps biopsy specimen. After inclusion, patients underwent ER in each hospital
and data was prospectively collected concerning macroscopic findings (size and
morphological type based on Paris classification), findings of magnified endoscopy with narrow band imaging (NBI-ME), outcomes of ER, and pathological
findings. Primary endpoint was cancer-bearing rate in patients diagnosed as
adenocarcinoma after ER. Secondary endpoints were the association between
final diagnosis and findings of macroscopic appearance and NBI-ME, and the
short-term outcomes of ER.
RESULTS: A total of 105 patients were included from April 2012 to February
2014. Among them, 48 patients were diagnosed as adenocarcinoma after ER and
cancer-bearing rate was 46%. Larger ( 20mm) and smaller (5 20mm) lesions
were not significantly different in cancer-bearing rates (43% vs 57%, p 0.2589).
Similarly, depressed and elevated lesions were not significantly different (50% vs
55%, p 0.7469). NBI-ME could predict accurately the pathological diagnosis
after ER in 52% of the patients. En bloc margin negative resection was achieved
in 103 patients (98.1%). Perforation and post-procedural bleeding occurred in 3
patients (2.9%) and 2 patients (1.9%), respectively. All these adverse events were
managed conservatively and no patients required emergent operation or blood
transfusion.
CONCLUSION: The present study showed that diagnostic ER for gastric borderline malignant lesion is clinically safe and useful because of acceptable complication and high cancer-bearing rate.
Disclosure of Interest: None declared
P0716 THIENOPYRIDINE DERIVATIVE CAN BE A RISK FACTOR FOR
POSTOPERATIVE BLEEDING WHEN PERFORMING GASTRIC
ENDOSCOPIC SUBMUCOSAL DISSECTION WITHOUT
DISCONTINUATION OF ASPIRIN: STRAP STUDY (SAFE
TREATMENT ON ANTIPLATELETS)
N. Yoshida1,*, S. Ono2, M. Fujishiro2,3, H. Doyama1, T. Kamoshida4, S. Hirai4,
T. Kishihara5, Y. Yamamoto5, H. Sakae6, A. Imagawa6, M. Hirano7, K. Koike2
1
Gastroenterology, Ishikawa prefectural central hospital, Ishikawa,
2
Gastroenterology, 3 Endoscopy and Endoscopic Surgery, Graduate School of
Medicine, The University of Tokyo, Tokyo, 4Internal Medicine, Hitachi General
Hospital, Ibaraki, 5Gastroenterology Center, The Cancer Institute Hospital of
JFCR, Tokyo, 6Gastroenterology, Mitoyo General Hospital, Kagawa,
7
Gastroenterology, Niigata Prefectural Central Hospital, Niigata, Japan
Contact E-mail Address: naohilow@yahoo.co.jp
INTRODUCTION: Endoscopic procedures for patients taking aspirin were
recently reported[1,2]. However, there was not enough evidence to support
these procedures. We evaluated the safety of endoscopic procedures in Asian
patients with a high risk of bleeding without perioperative discontinuation of
aspirin.
AIMS & METHODS: A multicenter prospective cohort study was conducted at
six high-volume endoscopy centres in Japan (UMIN000009176). Patients regularly taking antiplatelet agents and with a high risk of thromboembolism upon
discontinuation of administration were enrolled in this study. All patients underwent endoscopic procedures with a high risk of bleeding while continuing aspirin
including endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and endoscopic polypectomy of the upper and lower

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United European Gastroenterology Journal 2(1S)


gastrointestinal tracts. The primary endpoint was the rate of major bleeding
complications after endoscopic procedures.
RESULTS: This study was terminated in accordance with predetermined criteria
because seven of 28 consecutive patients experienced major bleeding complications (25.0%; 95% confidence interval, 10.7%44.9%). All major bleeding complications occurred after ESD (stomach n 6; colon, n 1). Univariate analysis
revealed that postoperative administration of a thienopyridine derivative was the
only significant factor associated with postoperative bleeding (p 0.04).
Subanalysis of gastric ESD of 23 lesions in 19 patients also confirmed that
administration of a thienopyridine derivative was the only significant factor
through multivariate analysis (p 0.01). All complications of postoperative
bleeding (postoperative day 11.2  3.5; range, 717) occurred after resuming
administration of thienopyridine derivatives postoperatively (postoperative day
2.3  2.4; range, 17). No patients experienced thromboembolic events during
the course of the study.
CONCLUSION: Endoscopic procedures with a high risk of bleeding require
careful consideration of the indications for Asian patients taking thienopyridine
derivatives. This especially applies to patients undergoing gastric ESD without
discontinuation of or with a switch to aspirin.
REFERENCES
1. Cho SJ, Choi IJ, Kim CG, et al. Aspirin use and bleeding risk after endoscopic
submucosal dissection in patients with gastric neoplasms. Endoscopy 2012; 44:
114-121.
2. Lim JH, Kim SG, Kim JW, et al. Do antiplatelets increase the risk of bleeding
after endoscopic submucosal dissection of gastric neoplasms? Gastrointest Endosc
2012; 75: 719-727.
Disclosure of Interest: N. Yoshida: None declared, S. Ono: None declared, M.
Fujishiro Lecture fee(s) from: Eisai Co., H. Doyama: None declared, T.
Kamoshida: None declared, S. Hirai: None declared, T. Kishihara: None
declared, Y. Yamamoto: None declared, H. Sakae: None declared, A.
Imagawa: None declared, M. Hirano: None declared, K. Koike: None declared
P0717 A
SECOND-LOOK
ENDOSCOPY
AFTER
ENDOSCOPIC SUBMUCOSAL DISSECTION MAY NOT BE
USEFUL FOR PREVENTING POSTOPERATIVE BLEEDING

GASTRIC

N. Yoshitake1,*, F. Takahashi1, T. Akima1, H. Kino1, M. Nakano1,


C. Tsuchida1, K. Tsuchida1, K. Tominaga1, T. Sasai1, H. Masuyama1,
H. Hiraishi1
1
Gastroenterology, Dokkyo Medical University, Mibu, Shimotsuga, Japan
INTRODUCTION: Gastric endoscopic submucosal dissection (ESD) has gradually come to be recommended as the optimal treatment for early gastric cancer;
however, one of the primary issues is postoperative bleeding. Although secondlook endoscopy is conventionally performed to reduce the risk of postoperative
bleeding, its benefit has not yet been clearly elucidated. The objective of this
study was to elucidate the benefit of second-look endoscopy.
AIMS & METHODS: From among 488 lesions in patients who underwent
gastric ESD between May 2004 and April 2013 at our hospital, a total of 29
lesions in patients who had a residual lesion, perforation, or concurrent aspiration pneumonitis, or in patients in whom the treatment modality had been
switched to open surgery or there was no evidence of cancer in the resected
specimen were excluded, and the remaining 459 lesions were included in the
analysis. The patients were divided into those who had bleeding within 24
hours after ESD (immediate bleeding) and those in whom bleeding occurred
24 hours or more after the procedure (delayed bleeding); the underlying disease,
age, lesion site, diameter of the resected specimen, and lesion diameter were
analyzed to identify the risk factors for postoperative bleeding after ESD.
RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459
cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%)
excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases
(53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the
210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant
difference between the two groups. Overall, the following factors were identified
as the risk factors for postoperative bleeding: young age (P 0.005), lesions in
the L segment (P 0.042), and large size of the resected specimen (P 0.005).
The risk factors identified in the immediate bleeding group were lesions in the L
segment (P 0.032), large size of the resected specimen (P 5 0.001), and large
tumor size (P 0.011), and those in the delayed bleeding group were young age
(P 0.013) and concomitant renal disease (P 0.011).
CONCLUSION: The results of this study suggest that second-look endoscopy
after gastric ESD may not be useful for preventing postoperative bleeding.
Disclosure of Interest: None declared
P0718 EARLY CLINICAL EXPERIENCE OF THE EFFECTIVENESS OF
HEMOSPRAY IN ACHIEVING HAEMOSTASIS IN PATIENTS WITH
ACUTE NON-VARICEAL BLEEDING
N. Sagar1,*, T. Iqbal1
Gastroenterology, Queen Elizabeth Hospital Birmingham, Birmingham, United
Kingdom
Contact E-mail Address: dr.nidhisagar@gmail.com
1

INTRODUCTION: Despite advances in management, mortality from acute


upper gastrointestinal bleeding remains high at 10%1. Current endoscopic modalities have found to be effective in achieving haemostasis in 85-95% of cases,
however 5-10% of patients still experience rebleeding despite combination therapy2. Bleeding may occur from sites, which are challenging to access or lesions
that are large and actively bleeding causing poor views for effective endoscopic
therapy. Hemospray is a novel powder designed to be a simple endoscopic technique in applying to large surface areas even in difficult positions.

AIMS & METHODS: This was a retrospective review of patients at the Queen
Elizabeth Hospital Birmingham where Hemospray was used for an acute nonvariceal upper gastrointestinal bleed. Eight patients (4 male and 4 female) were
identified between May 2012 and February 2013.
RESULTS: The median age was 63 years (range 37 84 years). Two patients had
a Forrest classification of 1a, 2 were 1b, 1 was 2a and 3 were 2b. Causes of
bleeding were duodenal ulcer (4), gastric ulcer (2), oesophageal cancer (1) and
Diuelafoy lesion in stomach (1). Hemospray was used as the sole endoscopic
modality in 1 patient and in combination with other modalities in 7 patients.
Other modalities used were adrenaline (3), clips (1), adrenaline and clips (1),
adrenaline and heater probe (1), adrenaline, clips and heater probe (1).
Immediate haemostasis was achieved in all 8 patients. 3 patients re-bled within
7 days. All 3 patients had a duodenal ulcer (Forrest classification 1a, 1b and 2b).
Two patients required further definitive therapy: radiological coiling of gastroduodenal branches (1) and endoscopic therapy with adrenaline and clips (1).
CONCLUSION: From the small number of patients in this study, we can conclude that Hemospray is an effective method in achieving immediate haemostasis
when combined with other endoscopic modalities. However, there is a high
rebleeding rate within 7 days in patients with duodenal ulcers, irrespective of
their Forrest classification, who mostly required further definitive management.
Larger studies are required to assess the efficacy of Hemospray in this particular
group of patients to determine whether they are truly at higher risk.
REFERENCES
1. http://www.nice.org.uk/nicemedia/live/13762/59549/59549.pdf
2. Sung JJY, Luo D, Wu JCY, et al. Early clinical experience of the safety and
effectiveness of Hemospray in achieving hemostasis in patients with acute peptic
ulcer bleeding. Endoscopy 2011; 43: 291-295.
Disclosure of Interest: None declared
P0719 USEFULNESS OF CHROMOENDOSCOPY WITH INDIGO
CARMINE AND ACETIC ACID FOR IDENTIFYING THE
DEMARCATION LINE PRIOR TO ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR EARLY GASTRIC CANCER
N. Numata1,*, S. Oka1, S. Tanaka1, Y. Yoshifuku2, T. Miwata2, Y. Sanomura1,
K. Arihiro3, F. Shimamoto4, K. Chayama2
1
Department of Endoscopy, 2Department of Gastroenterology and Metabolism,
3
Department of Pathology, Hiroshima University Hospital, 4Faculty of Human
Culture and Science, Prefectural University of Hiroshima, Hiroshima-shi, Japan
Contact E-mail Address: nnumata@hiroshima-u.ac.jp
INTRODUCTION: Identification of a precise demarcation line (DL) is indispensable for performing pathological complete en bloc endoscopic submucosal
dissection (ESD) for early gastric cancer (EGC). Recently, chromoendoscopy
with combination use of indigo carmine and acetic acid was reported as a
novel technique for identifying the DL; however, this technique is not effective
in all EGC cases.
AIMS & METHODS: The aim of this study was to evaluate the usefulness of
chromoendoscopy with indigo carmine and acetic acid for marking dots around
lesions during ESD for EGC. We examined 98 consecutive patients with 109
intramucosal EGCs (mean diameter, 17.8  12.4 mm; location, U 21/M 34/L
54; main histologic type, 96 intestinal and 13 diffuse) resected by en bloc ESD
after chromoendoscopy with indigo carmine and acetic acid at Hiroshima
University Hospital between December 2012 and February 2014. We identified
the DL by chromoendoscopy with indigo carmine and acetic acid just before
ESD (mean chromoendoscopy observation time, 71.6 s), and then marking dots
were placed around the EGC. Four physicians participated in the evaluation of
improved EGC visibility. Conventional endoscopic images were presented to
each of the physicians in random order for comparison with chromoendoscopy
images. Physicians scored each of the chromoendoscopy images for visibility of
the DL, and the four physicians scores for each image were tallied. EGCs were
classified into two groups: useful for identifying the DL or useless. The tumor
diameter, histologic type (intestinal/diffuse), macroscopic type (elevated, 0-I &
IIa & IIb; depressed, 0-IIaIIc & IIc), tumor lesion (U or M/L), tumor depth
(intramucosal/submucosal), tumor color (reddish/normal or pale), atrophic gastritis around tumor (present/absent), intestinal metaplasia around tumor (present/absent), and rate of histologically positive horizontal margin were evaluated
in each group.
RESULTS: Forty-two of the 109 cases (38.5%) were useful for chromoendoscopy with indigo carmine and acetic acid, which were compared to the other 67
cases. Univariate analysis showed that histologic type (intestinal type), macroscopic type (elevated type), and atrophic gastritis around the tumor (present)
were associated with the usefulness of chromoendoscopy using indigo carmine
and acetic acid. Multivariate analysis with logistic regression showed that macroscopic type (elevated type) and atrophic gastritis around the tumor (present) were
independently associated with the usefulness of chromoendoscopy using indigo
carmine and acetic acid for identifying the DL of EGCs (P 5 0.05). The histologically positive horizontal margin after ESD was 0% (0/42) in useful cases, and
7.5% (5/67) in useless cases.
CONCLUSION: To make precise markings around EGCs before ESD, chromoendoscopy with indigo carmine and acetic acid is useful for elevated-type
EGC or in cases of existing atrophic gastritis around EGCs.
Disclosure of Interest: None declared

A330

United European Gastroenterology Journal 2(1S)

P0720 THE DIAGNOSIS OF INVASION DEPTH IN SUPERFICIAL


ESOPHAGEAL CANCER: A COMPARISON BETWEEN A
MAGNIFYING NARROW-BAND IMAGING (NBI) OBSERVATION
AND EUS
1,*

N. Matsuura , N. Hanaoka , R. Ishihara , S. Yamamoto , T. Akasaka ,


Y. Takeuchi1, K. Higashino1, N. Uedo1, H. Iishi1
1
Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular
Diseases, Osaka-city, Japan
Contact E-mail Address: matuura-no@mc.pref.osaka.jp
INTRODUCTION: The diagnosis of cancer invasion depth is crucial for selecting the optimal treatment strategy for esophageal cancer. Endoscopic ultrasonography (EUS) is regarded as the standard modality for diagnosing invasion
esophageal cancer depth in the West. In Japan, magnifying endoscopy has
been used for diagnosis by observing the architecture of the esophageal microvasculature. This modality represents a rapid and simple diagnostic procedure
without the need for any additional equipment. However, the accuracy of magnifying endoscopy has not been compared with that of EUS for the diagnosis of
cancer invasion depth.
AIMS & METHODS: Patients with esophageal squamous cell carcinoma suspicious for muscularis mucosa or submucosal invasion in non-magnifying white
light imaging were included. All patients received magnifying narrow-band imaging (NBI) observation followed by EUS. Magnifying NBI observation was
performed by endoscope with magnification (GIF-Q240Z, or H260Z;
Olympus, Tokyo, Japan). EUS was performed using a high-resolution probe
by jelly-filled method. Before examination, several syringes (5 mL) containing
sufficient amounts of jelly (K-Y lubricating jelly, Johnson and Johnson, k. k.)
were prepared. After endoscope insertion (GIF-2TQ260M; Olympus) into the
target area within the esophagus, a 30-MHz miniature probe was then inserted
through the left channel of the endoscope and 30 to 40 mL of echo jelly was
instilled through the right channel until the esophageal lumen was filled. Cancer
invasion depth was diagnosed as T1a or T1b using both modalities. The diagnostic accuracy of magnifying NBI observation was compared with that of EUS
while the histologic diagnosis of resected specimen served as reference standard.
RESULTS: From January 2011 to February 2014, 166 patients with esophageal
squamous cell carcinoma were examined using the two modalities. Of the 166
patients, 91 treated with chemoradiotherapy or photodynamic therapy were
excluded from analysis because histologic specimens were not obtained.
Seventy-five patients treated either by esophagectomy (n 15) or endoscopic
resection (n 60) were included in the final analysis. Histologic diagnosis was
T1a in 43 lesions, T1b in 31 lesions, and T2 in one lesion. The overall accuracy of
diagnosing invasion depth was 66.7% (50/75 lesions) by magnifying NBI and
70.7% (53/75 lesions) by EUS (P 0.602). The accuracy of diagnosing invasion
depth in lesions with protrusions was 58.8% (20/34 lesions) and 76.5% (26/34
lesions) by magnifying NBI and EUS, respectively (P 0.194). The accuracy of
diagnosing invasion depth in lesions without protrusions was 73.2% (30/41
lesions) and 65.9% (27/41 lesions) by magnifying NBI and EUS, respectively
(P 0.632).
CONCLUSION: EUS and magnifying NBI exhibited high diagnostic accuracy
in lesions with and without protrusion. Furthermore, there was no significant
difference in the overall accuracy of these two modalities. Considering its simplicity of use, magnifying NBI has the potential to be the standard modality for
diagnosing invasion depth of esophageal squamous cell carcinoma.
Disclosure of Interest: None declared
P0721 ENDOSCOPIC
DIAGNOSIS
OF
VARIABILITY BETWEEN ENDOSCOPISTS

HIATUS

HERNIAS

O.S. Omer1,*, J.S. Nayagam1, J. Hayat1


1
Kingston Hospital, London, United Kingdom
Contact E-mail Address: oso04@ic.ac.uk
INTRODUCTION: There is a wider discrepancy in the diagnosis of hiatus hernias (HH) at upper gastro-intestinal endoscopy (OGD) compared to other techniques, such as manometry and barium swallow, or during surgery.1 Endoscopic
diagnosis may be affected by the method used (eg during intubation or extubation2), and variable definition of the gastro-oesophageal junction (eg proximal
margin of the gastric folds, squamo-columnar junction or distal margin of the
palisade zone).
AIMS & METHODS: Our aim was to assess variability in diagnosis of hiatus
hernias by different endoscopists.
A retrospective review of the endoscopy database at Kingston Hospital, was
performed. Consecutive OGD were analysed over a 3 month period (2/4/13 28/6/13). Complete data was obtained for 451 endoscopies, from 21 different
endoscopists. Mean age for patients was 60.1 years (range 20-98), female to
make ration of 1:1.04. Unpaired t-test and one-way ANOVA with Tukeys
Test were used for normal data, and Chi-squared for proportional differences.
RESULTS: Of the 451 OGD, HH were diagnosed in 168 (36.6%), most HH
under 5cm (81.55%). Main indications were for dyspepsia (14.2%), reflux symptoms (17.7%), abdominal pain (22%), anaemia (14%). There was a wide variability in the diagnosis of HH depending on speciality and grade (range 0-100%).
Age, indications and gender were similiar between groups of endoscopists.
Surgical Consultants were more likely to diagnose HH than Gastroenterology
Consultants (p50.002) or Registrars (p50.04), and Nurse Endoscopists more
likely than Gastroenterology Consultants (p50.0001) or Registrars (p50.0004).

Speciality & Grade

Number of
endoscopies

Number of
HH diagnosed

% HH

Gastroenterology Consultants
Gastroenterology Registrars
Surgical Consultant
Surgical Registrars
Nurse Endoscopists
GP Endoscopists

142
34
55
19
189
12

27
6
23
11
99
2

19%
17.7%
41.8%
57.9%
52.4%
16.7%

CONCLUSION: Endoscopic diagnosis of HH is highly variable and may be


affected by level of training and speciality of the endoscopist. This may lead to
under or overdiagnosis. A standardised approach to landmark measurement may
lead to a more consistent diagnosis of HH.
REFERENCES
1. Khajanchee YS, Cassera MA, Swanstrom LL, et al. Diagnosis of Type-1 hiatal
hernia: a comparison of high-resolution manometry and endoscopy. Dis
Esophagus 2013; 26: 1-6.
2. Burch NE, Saraj O, Lichfield B, et al. Study assessing landmark height alteration during endoscopic evaluation. Gut 2011; 60: A126.
Disclosure of Interest: None declared
P0722 THE EFFECT AND USEFULNESS OF CHROMOENDOSCOPY
WITH INDIGO CARMINE DYE ADDED TO ACETIC ACID IN
DIAGNOSIS OF EARLY GASTRIC CANCER DIFFERS DEPENDING
ON ITS MUCIN HISTOCHEMISTRY
O. Yoneyama1,*, K. Furukawa1, H. Hashidate2, M. Ogawa1, S. Ikarashi1,
A. Osaki1, M. Sato1, T. Aiba1, N. Waguri1, K. Igarashi1
1
Gastroenterology and Hepatology, Niigata City General Hospital, NIigata,
2
Diagnostic Pathology, Niigata City General Hospital, NIigata City, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) became a very
popular technique of therapeutic endoscopy for superficial gastrointestinal neoplasms, and it made possible to perform a reliable en bloc resection with higher
success rate and lower recurrence rate compared with conventional endoscopic
mucosal resection. For a complete en bloc resection of cancer lesions, it is indispensable to accurately delineate the margin, in other words, the lateral extent of
the cancer. Chromoendoscopy with indigo carmine dye added to acetic acid is
thought to be useful in the diagnosis of early gastric cancer. Usually this method
helps to clarify the lateral extent of gastric cancer. But in some cases, this method
can not help satisfactorily to delineate the margin between cancer and non-cancer
parts. We assumed that the difference of dyeing pattern arises from quantity and
character of mucus secreted from each lesion.
AIMS & METHODS: Subjects were 33 early gastric cancer lesions resected by
using ESD technique in our institution, and were divided in two groups. We
defined the lesions which were delineated clearly by acetic acid-indigo carmine
method as group A (n 17), and lesions which were not delineated clearly
enough as group B (n 16). We evaluated the mucin histochemistry of the specimens about stain levels of d-PAS and immunohistochemistry of MUC2,
MUC5AC and CD10, and compared between the two groups.
RESULTS: Both group showed lower level of d-PAS stain in its cancer tissue
than its non-cancer parts, suggesting that mucin productivity is decreased in the
cancer tissue compared with non-cancer parts. Classification grouping using
immunohistochemistry of MUC2, MUC5AC and CD10 showed that many
cases of group A have intestinal type mucin (68.8%), and group B tends to
have gastro-intestinal type mucin (64.7%).
CONCLUSION: Chromoendoscopy with indigo carmine dye added acetic to
acid is generally useful and effective in case of early gastric cancer which has
intestinal type mucin histochemistry. But on the other hand, cancer lesions
having gastro-intestinal type mucin often show unclear margin even if using
this technique.
Disclosure of Interest: None declared
P0723 FULL SPECTRUM ENDOSCOPY VS. TRADITIONAL FORWARDVIEWING COLONOSCOPY WITH AND WITHOUT RIGHT-COLON
RETROFLEXION: A RANDOMIZED, BICENTRIC BACK-TO-BACK
STUDY
I.S. Papanikolaou1,*, P. Apostolopoulos2, I. Beintaris1, A.D. Sioulas1,
D. Polymeros1, C. Malli1, E. Vlachou2, G. Vlachonikolou1, G. Alexandrakis1,
G. Dimitriadis1, K. Triantafyllou1
1
Department of Hepatogastroenterology, ATTIKON UNIVERSITY HOSPITAL,
2
Department of Gastroenterology, Army Veterans (NIMTS) Hospital, Athens,
Greece
Contact E-mail Address: ispapn@hotmail.com
INTRODUCTION: Colonoscopy can reduce colorectal cancer (CRC) incidence
and mortality through early detection and removal of adenomas, but estimates
suggest that up to 24% of adenomas are missed; various colonoscopic techniques
are evolving to improve its diagnostic yield and avoid interval CRC. Recently a
new colonoscopy platform (FUSETM system, EndoChoice Inc., Atlanta, GA,
USA) was introduced with promising initial results. FUSE-colonoscopy (F-C)
provides a 330 -field of view instead of the 170 of standard colonoscopy (S-C);
this allows polyps hidden behind folds or flexures to be seen easier.

A331

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: The aim of this study is to evaluate F-C additive contribution to detection of polyps/adenomas, compared to S-C, with and without
the addition of right-colon retroflexion (R-C), in a series of patients undergoing
same-day, back-to-back randomized (1:1) tandem colonoscopies in 2 tertiary
endoscopy centres. ClinicalTrials.gov Identifier: NCT02117674
RESULTS: Of 150 totally planned, 84 pts have been enrolled until now; 40
(47.6%) of them were randomized to undergo F-C first. There were 7 incomplete
cases for both F-C and S-C (including 1 failed case for both F-S and S-C and 1
case where F-C was not performed due to technical failure). Thus, 83 (46 screening/surveillance, 32 symptomatic and 5(6%) with polyps) were included in the
per-protocol analyses. R-C was attempted in 57/83 cases; successful in 37.
Insertion time did not differ between F-C and S-C (5min, IQR:4-10.25 vs.
5min, IQR: 4-8, respectively, p 0.4), whereas, withdrawal was marginally
longer for F-C (8min, IQR:6-10 vs. 7min, IQR:6-9, respectively, p 0.05).
Overall, 133 polyps were found (53 right colon); of these 61 were adenomas,
32 in the right colon (histology available for 24/28 pts with polyps).
By per-lesion anlaysis, F-C detected significantly more missed polyps compared
to S-C overall (26 vs. 4, p 0.033) and right-sided ones (14 vs. 2, p 0.038) and
detected more adenomas (9 vs. 3, p 0.162) overall and right-sided ones (7 vs. 2,
p 0.184). R-C offered no additional gain in polyp or adenoma detection in the
right colon.
CONCLUSION: Our initial results show that F-C could be an advancement in
colonoscopy by detecting more polyps. However, if this improvement actually
represents detection of more adenomas requires further investigation.
REFERENCES
Gralnek IM, et al. A prospective cohort study evaluating a novel colonoscopy
platform featuring full-spectrum endoscopy. Endoscopy 2013; 45: 697-702.
Gralnek IM, et al. Standard forward-viewing colonoscopy versus full-spectrum
endoscopy: an international, multicentre, randomised, tandem colonoscopy trial.
Lancet Oncol 2014; 15: 353-360.
Disclosure of Interest: None declared
P0724 ORALLY ADMINISTRATION OF OTILONIM BROMIDE BEFORE
COLONOSCOPY IMPROVES ADENOMA DETECTION RATES
S. GULITER1, F. SAPMAZ1, I.H. KALKAN1,*, P. ATASOY2
1
Gastroenterology, 2Pathology, Krkkale University Faculty of Medicine, Ankara,
Turkey
Contact E-mail Address: drismailster@gmail.com
INTRODUCTION: We aimed in this randomized prospective controlled trial to
evaluate the effect of orally administration of Otilonium bromide over the quality
of the colonoscopy in the meanings of adenoma detection rate, caecal intubation
time, and the tolerability.
AIMS & METHODS: Two-hundred consecutive volunteer outpatients were randomized to Otilonium Bromide group (100 patients) and the control group (100
patients). The patients in the Otilonium Bromide group received 30 mg
Otilonium Bromide 3 times a day for five days with the last dose given two
hours before colonoscopy. The bowel preparation quality was graded according
to the Boston bowel preparation scale. For each colon area, a distension scale
was awarded by using a previously validated 5-point scale. The pain experienced
during colonoscopy was determined by using a 1-10 visual analog pain scale.
RESULTS: Twenty-one patients in Otilonium bromide group and 22 patients in
control group were excluded from the study because of uncompleted colonoscopy. Caecum intubation time was comparable between groups (p 0.4).
There was no statistically difference between groups in the terms of mean
bowel preparation quality scores (p 0.4), while mean distension score was
greater in Otilonium bromide group (p 0.007). Polyp detection rate (26
polyps in 22 patients vs. 14 polyps in 12 patients) (32.9% vs. 17.9%, p 0.03)
was significantly higher in OB group. Also, adenoma detection rate (22 adenomas in 21 patients vs. 11 adenomas in 11 patients) (27.8% vs. 14.1%, p 0.03)
was significantly higher in OB group. The visual analog pain scale scores were
comparable between groups (p 0.07)
CONCLUSION: Otilonium bromide administration before colonoscopy
increases colonic distension, polyp detection and adenoma detection rates.
Further clinical investigations are required to determine the utility of relieving
colonic spasm with oral antispasmodics to improve adenoma detection rates.
Disclosure of Interest: None declared
P0725 NEW GENERATION FLEXIBLE SPECTRAL IMAGING COLOR
ENHANCEMENT IS USEFUL TO PREDICT HISTOLOGY OF
SMALL COLORECTAL POLYPS
J. Weigt1,*, A. Kandulski1, P. Malfertheiner1
1
Gastroenterology, Hepatology & Infectious Diseases, UNIVERSTITY
MAGDEBURG, Magdeburg, Germany
Contact E-mail Address: jochen.weigt@med.ovgu.de
INTRODUCTION: Prediction of colon polyp histology is decisive as small non
advanced adenoma may be discarded after resection and hyperplastic lesions may
be left in place. The NICE classification system for NBI endoscopy and magnification has been shown to be effective in prediction of histology. There is only
little data for the flexible spectral imaging color enhancement (FICE). Newest
generation of endoscopes have over mega pixel CMOS sensors that allow FICE
aligned with electronic zoom without loss of image quality. With this new technology, histology prediction may easily be possible during standard colonoscopy
without using optical zoom endoscopes.
AIMS & METHODS: To assess the accuracy of endoscopic prediction of histology of small colorectal polyps using white light (WLE) and FICE and CMOS
endoscope
Methods:

We randomly assigned patients for colonoscopy using a CMOS colonoscope


(EC-600 WM, Fujifilm Europe Dusseldorf). All detected polyps were assigned
to Types 1-3 according to the NICE classification system criteria using WLE and
FICE (modes 1,8,9) with and without electronic zoom. Classification was
assessed during the examination. Before starting the study, the endoscopist
underwent endoscopic training using NBI. All detected polyps were removed
for histopathology. The concordance of endoscopic classification and histology
was calculated.
RESULTS: We investigated 27 polyps in 11 patients. Median polyp size was 4
mm (range 3-20 mm) Polyps location were in the rectum and sigmoid colon
(n 15) in the right colon (n 10) and in the left colon (n 2). According to
the endoscopic classification 18 polyps were hyperplastic (Type 1) and 9 polyps
were adenomas (Type 2). No colorectal cancer or high grade adenoma were
identified. Histology proofed that 100 % of polyps were classified correctly.
One polyp classified as adenoma revealed serrated adenoma in histology.
CONCLUSION: The NICE classification system criteria can successfully be
applied for colorectal polyps being investigated with FICE and electronic
zoom using a CMOS colonoscope.
Disclosure of Interest: J. Weigt Lecture fee(s) from: Fujifilm, A. Kandulski: None
declared, P. Malfertheiner: None declared
P0726 MEASUREMENT OF
ESTIMATION ACCURATE?

COLONIC

POLYPS.

IS

VISUAL

J. Woo1,*, H. Rozati1, K. Besherdas1


1
Gastroenterology, Barnet and Chase Farm Hospitals NHS trust, London, United
Kingdom
Contact E-mail Address: jwoo@nhs.net
INTRODUCTION: Colon polyp size is a critical biomarker for clinical management of colonic polyps. Larger polyps have a greater malignant potential. During
colonoscopy, it is important to correctly measure the size of the polyps because of
the direct correlation of size with colon cancer.1 During polypectomy, size of the
colonic polyps encountered are often gauged by visual estimation or the open
forceps method.2 However, some data exists on the questionable reliability of a
visual estimate even amongst expert colonoscopists. We aim to compare the
estimation of polyp size using the visual estimation of colon polyp with or without the open biopsy forceps technique against actual polyp size measurement by
our histopathology department for all polyps 41cm in size.
AIMS & METHODS: A single centre, retrospective analysis using the Unisoft
GI auditors software was used to identify patients who have had polypectomies
done for polyps 41cm in size from October 2005 till September 2013. The size of
the polyps documented in the endoscopy report was then compared to the lab
measured actual polyp size.
RESULTS: A total of 39 patients were identified with polyps 41cm in size who
has had polypectomy done. Results are as below:
Visual estimated
size (mm)

39
1014
1519
2024
2529
430

Actual lab measured size (mm)


39

1014

1519

2024

XXXXXXX
XXXX

XXXX
X
XXX
X

XXXX
X
X
XXX
X

X
X
XX

X
X

2529

430

X
X
X

CONCLUSION: From this study we can conclude that visual estimation with or
without the open biopsy forceps technique is completely inaccurate with wide
variations between the reported size and the actual size of the polyps when
measured in our laboratory. Accurate measurement of colonic polyps is important as inaccuracies can lead to potentially larger polyps not being tattooed and
subsequent difficulty in identification during surgery and surveillance. We advocate that the gold standard practice of direct measurement of the polyp once
excised and outside the body be adopted and the actual size should be documented according to direct measurement.
REFERENCES
1) Gopalswamy N, Shenoy V, Choudhry U, et al. Is in vivo measurement of size
of polyps during colonoscopy accurate? Gastrointest Endosc 1997; 46: 497-502.
2) Rex D and Rabinovitz R. Variable interpretation of polyp size by using open
forceps by experienced colonoscopists. Gastrointest Endosc 2013: pii: S00165107(13)02317-1.
Disclosure of Interest: None declared
P0727 THE VALUE OF ENDOSCOPIC INVESTIGATION IN PATIENTS
WITH BOWEL THICKENING ON COMPUTED TOMOGRAPHY
IMAGING. A 4 MONTH RETROSPECTIVE STUDY BASED IN A
DISTRICT GENERAL HOSPITAL IN THE UK
J. Digby-Bell1,2,*, S. Powles2, A. Gunasekera2
Gastroenterology, Frimley Park Hospital, Farnborough, 2Gastroenterology, St
Peters Hospital, Chertsey, United Kingdom
Contact E-mail Address: jdigbybell@doctors.org.uk
1

A332
INTRODUCTION: Bowel wall thickening is a common and often unexpected
finding on abdominal computed tomography (CT) scans, and yet its significance
and further investigation is unclear from the literature. This study aims to clarify
the incidence of bowel wall thickening, and its investigation and outcomes in a
District General setting.
AIMS & METHODS: In this retrospective observational study, all in-patients
who underwent abdominal CT imaging were included over a 4 month period
regardless of indication. Radiology reports were analysed, and patients with
gastrointestinal wall thickening were identified for further analysis.
RESULTS: 1227 patients underwent abdominal CT imaging over the 4 month
period, of which 116 (9.5%) were found to have bowel wall thickening. 53
patients subsequently had an endoscopic examination and in 49 cases the area
of interest was visualised. 33 patients had positive endoscopic findings at the site
of bowel thickening, of which 16 had mucosal inflammation, 8 had malignancy, 6
had diverticulosis and 3 had polyps.
In the remaining 63 patients who did not have endoscopic examination, 42 were
investigated by other means including surgery or other imagining modalities, or
further investigation was not appropriate. In 21 patients, it was unclear as to why
further investigation did not take place.
CONCLUSION: Endoscopic evaluation of gastrointestinal wall thickening
found on CT imaging led to a positive diagnosis in 62.3% (33/53) patients of
which 15% (8/53) were found to have malignancy. This highlights both the
importance of further investigating GI wall thickening and the value of endoscopic visualisation.
Disclosure of Interest: None declared
P0728 THE
COMPARATIVE
STUDY
OF
SPLIT-DOSE
OF
POLYETHYLENE GLYCOL (PEG) BETWEEN LOW VOLUME PEG
PLUS ASCORBIC ACID FOCUSING ON THE BOWEL CLEANSING
EFFICACY, PATIENTS AFFINITY TO PREPARATION SOLUTION
AND MUCOSAL INJURY: A PROSPECTIVE RANDOMIZED TRIAL
J. Park1,*
1
Department of Internal Medicine, Haeundae Paik Hospital, Inje University School
of Medicine, Busan, Korea, Republic Of
Contact E-mail Address: mechant79@hanmail.net
INTRODUCTION: Adequate bowel cleansing is essential for a high-quality,
effective, and safe colonoscopy. The aims of this study were to compare the
efficacy and patients affinity to preparation solution and mucosal injury of
split dose of polyethylene glycol (PEG) solution with low volume PEG plus
ascorbic acid for outpatients who underwent scheduled colonoscopy.
AIMS & METHODS: This study was prospective randomized investigatorblinded. Overall, 160 patients were enrolled for split-dose of PEG and 159 for
the low volume PEG plus ascorbic acid, respectively. The bowel cleansing efficacy of preparation was rated according to the Ottawa bowel preparation scale
and patients affinity to preparation solution was assessed using a questionnaire.
All mucosal abnormalities observed during colonoscopy were noted and biopsied. These biopsy specimens were reviewed by pathologists.
RESULTS: Of the 319 patients, 308(96%) ingested more than 75% of the bowel
preparation. There was no significant difference between the two groups for the
mean total score using the Ottawa bowel preparation scale (p 0.376).
Significantly greater residual colonic fluid was observed in the low volume
PEG plus ascorbic acid group (0.81  0.54) than in the split-dose PEG group
(0.66  0.62) (p 0.023). There was significant difference in the Ottawa bowel
preparation score for the middle colon (split-dose PEG vs. low volume PEG plus
ascorbic acid: 1.19  0.94 vs. 1.42  0.73; p 0.014). In patients preference and
acceptance, low volume PEG plus ascorbic acid group showed better results
(p 0.001). The overall incidence of adverse events was not significantly different
between the two groups (69/160 [43.1%], 69/159 [43.4%], p 0.972); however,
the split-dose PEG group tended to had less headache and dizziness (p 0.056).
Endoscopically, mucosal lesions, possibly associated with two preparation regimen, were observed in total 11 patients (split-dose PEG: 5, low volume PEG plus
ascorbic acid: 6, respectively). Mucosal ulceration occurred in 1 patient taking
split-dose PEG compared with 2 patients receiving low volume PEG plus ascorbic acid.
CONCLUSION: Low volume PEG solution plus ascorbic acid, compared with
split-dose PEG, was associated with more residual fluid, but showed equivalent
colon cleansing efficacy and resulted in more patient preference, and acceptance.
There was no significant difference in mucosal injury.
REFERENCES
1) Lawrance IC, Willert RP and Murray K. Bowel cleansing for colonoscopy:
prospective randomized assessment of efficacy and of induced mucosal abnormality with three preparation agents. Endoscopy 2011; 43: 412-418.
2) Valiante F, Pontone S, Hassan C, et al. A randomized controlled trial evaluating a new 2-L PEG solution plus ascorbic acid vs 4-L PEG for bowel cleansing
prior to colonoscopy. Dig Liver Dis 2012; 44: 224-227.
Disclosure of Interest: None declared
P0729 COLON STENTING: CAN WE PREDICT PERFORATION?
CONSIDERING FACTORS BEFORE PLACING A COLON STENT
J.R. Umana Mejia1,*, A. Alvarez Delgado1, A. Velasco Guardado1, C. Pinero
Perez1, A. Fernandez Pordomingo1, A. Mora Soler1, V. Prieto Vicente1
1
servicio de aparato digestivo, hospital clinico universitario de salamanca, salamanca, Spain
Contact E-mail Address: josueum1@hotmail.com
INTRODUCTION: In the last decade, Colon Stenting has become a well
accepted technique for use as bridge to surgery or as palliative treatment in
cases of malignant colon strictures. None the less, recent meta-analysis had

United European Gastroenterology Journal 2(1S)


suggested that there is a high rate of complication due to this procedure carrying
an increase in morbidity in these patients that in some cases must be treated with
emergency surgery due to Peritonitis in relation to colon perforation secondary
to the procedure. In that matter we focused our study on identifying factors,
before the procedure, that can predict colon perforation.
AIMS & METHODS: Data from 213 (n 213) patients admitted in our hospital
between January 2004 to November 2012 were analyzed. All of the items
reviewed were before the procedure. Demographic factors were age and sex.
Clinical factors include length of symptoms, presence of peritoneal irritation,
cardiac frequency, temperature and blood pressure. Laboratory tests were
CRP, LDH, WBC, pH and lactate. Radiologic features included the presence
of colon dilatation, measurement in centimeters of the cecum and the most
dilatated area, function of the ileo-cecal valve and the presence of metastasis in
CT scan. Factors analyzed from the procedure include timing (urgent or elective)
(548 hrs or 448 hrs), length of the procedure, level of expertise of the endoscopist, location of the tumor, angulations of the tumor, length of the Stent and
the visualization of feces coming through the Stent after released.
RESULTS: We review data from 213 cases, after statistical analysis, rate of colon
perforation found was 12% (21 patients); factors with statistic significance
related to patients demonstrated that the presence of colonic dilatation in the
radiologic study was associated with a higher risk of perforation compared with
patients that did not have dilatation (18.1% vs 2.3%, p 0.009), being the risk of
perforation increased almost eight times [R 7.9 (IC 95%: 1.1-57.1)]. The mean
in centimeters of colon dilatation in patients that had perforation was significantly longer (8.75 cm vs 6.79 cm, p 0.012). In the other hand, factors related to
the procedure with statistic significance, revealed that seeing feces coming
through the stent after released was associated with a lower risk of perforation
(10.3% vs 31,3%, p 0.004), there was an increased risk of three times, for colon
perforation, in patients that did not present the pass of feces through the stent
after liberation [R 3.04 (IC 95%: 1.5-6.1)].
CONCLUSION: Colon dilatation and the length of dilatation before procedure
is an important factor to take in consideration when deciding to place a colon
stent, in our study we saw an important increase in colon perforation when the
length of the cecum was more than 8 cms. In the other side, seeing feces passing
through the stent when it is released, reveals an adequate function of the stent,
and demonstrated a less number of perforations. In the future, predictive models
taking these factors into consideration might be developed with the objective to
select better the patients for this procedure reducing the rate of complications.
Disclosure of Interest: None declared
P0730 THE OFFER OF ADVANCED ENDOSCOPIC IMAGING
TECHNIQUES LEADS TO HIGHER ACCEPTANCE RATES FOR
COLONOSCOPY A PROSPECTIVE STUDY
J. Gallitz1,*, M. Vieth2, G.E. Tontini1,3, M.F. Neurath1, H. Neumann1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, 2Klinikum
Bayreuth, Bayreuth, Germany, 3IRCCS Policlinico San Donato, San Donato
Milanese, Italy
INTRODUCTION: In Germany patients over the age of 55 years should
undergo colonoscopy for colorectal cancer screening. The acceptance rate of
patients undergoing screening colonoscopy is still low.
AIMS & METHODS: Aim was to evaluate whether the offer of advanced endoscopic imaging techniques including chromoendoscopy, magnification endoscopy, spectroscopy, confocal laser endomicroscopy, endocytoscopy, capsule
endoscopy, CT-colonography or device-assisted enteroscopy may lead to an
increased awareness and improved acceptance rates of patients to undergo
colonoscopy.
Prospectively, 372 patients were randomly included (168 female, 204 male). At
baseline, a standardized questionnaire was developed. Afterwards, knowledge of
advanced imaging techniques was inquired and if the patient was motivated by
the specific offer of these imaging techniques to undergo colonoscopy. In the
second phase, several media campaigns through press, internet, TV coverage, and
information events were organized reporting about advanced imaging techniques, followed by repeat evaluation of the patients. This sequence (media campaign and patients evaluation) was repeated every 3 months over a period of 12
months.
RESULTS: At baseline, 64% of the patients reported that knowledge about new
endoscopic methods is completely unknown. After the evaluation period this was
reported by only 34% of patients (P 50.05). Despite general information about
all advanced imaging techniques was given in the media campaigns, patients were
most interested in chromoendoscopy (baseline: 5% - after 12 months: 22%),
endomicroscopy (5% vs. 17%), CT colonography (16% vs. 37%) and capsule
endoscopy (12% vs. 47%). The overall grade of information increased significantly from 14% at baseline to 35% after 12 months (P 50.05). The percentage
of patients who decided to undergo colonoscopy because of the offer of new
imaging methods increased significantly from 12% at baseline to 42% after 12
months (P 50.05).
CONCLUSION: Patients were highly interested in advanced endoscopic imaging
techniques and patients knowledge about new imaging methods increased significantly over the study period. The offer of advanced imaging techniques lead
to higher acceptance rate for screening or surveillance colonoscopies.
Disclosure of Interest: None declared

A333

United European Gastroenterology Journal 2(1S)


P0731 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR HUGE COLORECTAL NEOPLASMS:
COMPARISON BETWEEN SESSILE TUMORS AND LATERALLY
SPREADING TUMORS
J.H. Bae1,*, D.-H. Yang1, J.-S. Byeon1, J.S. Soh1, S. Lee1, H.-S. Lee1, H.J. Lee1,
S.H. Park1, K.-J. Kim1, B.D. Ye1, S.-J. Myung1, S.-K. Yang1, J.-H. Kim1
1
Department of Gastroenterology, University of Ulsan College of Medicine, Asan
Medical Center, Seoul, Korea, Republic Of
INTRODUCTION: Although endoscopic submucosal dissection (ESD) is
thought as an effective treatment for large laterally spreading tumors (LSTs)
of the colorectum, the therapeutic effectiveness of ESD for large sessile colorectal
tumors has not been evaluated.
AIMS & METHODS: We aimed to evaluate the outcomes of ESD for the huge
colorectal tumors (30 mm or larger in diameter) and compare therapeutic outcomes between sessile tumors and LSTs. We retrospectively reviewed medical
records of the patients who underwent ESD for huge sessile tumors and LSTs
of the colorectum from July 2007 to November 2013. En-bloc resection rate,
complete resection rate, procedure time and procedure-related complications
were evaluated in the sessile tumor and LST groups. Multivariate analysis was
performed to identify independent factors for incomplete resection.
RESULTS: ESD was attempted for a total of 191 patients with huge colorectal
tumors (48 with sessile colorectal tumors and 143 with LSTs) by two endoscopists. The mean ( SD) time required for ESD was 82.5  4.4 minutes (range, 17392), and mean size and height of the lesions were 43.2  1.1 mm (range, 30-135)
and 9.6  0.5 mm (range, 1-33). The rate of en bloc resection and complete
resection were 85.9% and 75.9%. With regard to complications, 11.0% (21/
191) cases of intra-procedural bleeding and 15.7% (30/191) cases of perforation
were observed in total; none of the complications required surgical intervention.
In the sessile colorectal tumors, the endoscopic en bloc resection and complete
resection rate were 72.9% (35/48) and 62.5% (30/48) respectively. In the LSTs,
they were 90.2% (129/143) and 80.4% (115/143) respectively. Although endoscopic findings suggesting submucosal (sm) invasion such as Vi or Vn pit pattern
were not different between the two groups, higher sm invasion rate was noted in
the sessile tumors than the LSTs (39.6% vs 23.1%, p 0.026). Intra-procedural
bleeding was more frequent in sessile tumors than LSTs (22.9% vs 7.0%,
p 0.002). There was no significant difference in procedure time and perforation
between the two groups. The rate of operation, caused by non-curative resection,
was higher in sessile tumors (14.6% vs 5.6%, p 0.045). There was no mortality
associated with procedure or operation. On multivariate analysis, sessile morphology (OR 2.125; 95% confidence interval (CI) 1.006-4.488; p 0.048) and
presence of fibrosis (OR 2.290; 95% CI 1.216-5.251; p 0.013) were independent
risk factors of incomplete resection in ESD of huge colorectal neoplasia.
CONCLUSION: The complete resection rate of ESD for sessile tumors was
relatively lower than that of ESD for LSTs. Presence of fibrosis was another
independent risk factor of incomplete resection in ESD of huge colorectal
neoplasia.
REFERENCES
1. Zhou PH, Yao LQ and Qin XY. Endoscopic submucosal dissection for colorectal epithelial neoplasm. Surg Endosc 2009; 23: 1546-1551.
2. Fujishiro M, Yahagi N, Kakushima N, et al. Outcome of endoscopic submucosal dissection for colorectal epithelial neoplasms in 200 consecutive cases. Clin
Gastroenterol Hepatol 2007; 5: 678-683.
Disclosure of Interest: None declared
P0732 THE
FEASIBILITY
OF
ENDOSCOPIC
SUBMUCOSAL
DISSECTION FOR EARLY COLORECTAL NEOPLASM WITH
HIGHLY TECHNICAL DIFFICULTY
K. Sasajima1,*, R. Chinzei1, M. Takahashi1, Y. Koushima1
1
Gastroenterology, SAITAMA RED CROSS HOSPITAL, Saitama, Japan
Contact E-mail Address: qqfa98m9@mist.ocn.ne.jp
INTRODUCTION: Colorectal endoscopic submucosal dissection (ESD), has not
been widely spread because of technical difficulty and high incidence of perforation. Before ESD, we need to recognize whether a lesion can be removed with or
without technical difficulty. The aim of study is to assess the feasibility of colorectal ESD for lesions accompanied by highly techinical difficulty.
AIMS & METHODS: We established the indication of colorectal ESD as follows: LST-NG, LST-G (mixed nodular type), local recurrent lesion after previous
endoscopic piecemeal mucosal resection (EPMR)=20mm, and Is/Isp=30mm. 330
colorectal consecutive lesions were enrolled in this study. Flush knife was used in
all cases. From the viewpoint of morphological type and tumor size, we defined
(1) LST-NG=40mm, (2) LST-G (mixed nodular type)=50mm, (3) Is/Isp=40mm,
and (4) local recurrent lesion after EPMR=20mm, as highly difficult lesion. A
lesion except for these four groups was defined as an ordinary lesion (5). We
investigated {tumor size(mm), en bloc resection rate(%), operative time(min),
perforation/delayed bleeding rate(%), moderate/severe fibrosis rate(%)}, respectively. Each highly difficult group was respectively compared to the group (5) for
all factors. A P value 5 .05 was considered statistically significant.
RESULTS: The total average diameter of lesions was 33.8mm. For morphological type, 153 lesions were LST-NG, 110 LST-G, 37 protruded, 15 depressed
and 15 recurrent lesions. By histological examination, 226 intramucosal cancers,
49 slightly invasive submucosal cancers, 19 massively submucosal invasive cancers, and 36 tubular adenomas. The average operative time was 85.8 minutes, and
the en bloc resection rate was 97.9% (323/330). With regard to complications,
postoperative bleeding was observed 0.9% (3/330). Microperforation which
occurred in only 1 case was conservatively repaired with endoscopic clipping.
The clinical outcome of each group is as follows: (1) LST-NG=40mm, n 31
{44.4mm, 93.5%, 149.8min, 0%/0%, 25.8%/6.5%} (2) LST-G(mix)=50mm,

n 29 {62.9mm, 93.1%, 169.7min, 3.4%/6.9%, 25.8%/6.5%} (3) Is/


Isp=40mm, n 12 {51.3mm, 100%, 121.3min, 0%/0%, 25.0%/41.7%} (4)
local recurrent lesion after EPMR=20mm, n 15 {29.9mm, 100%, 118.3min,
0%/0%, 0%/100%} (5) ordinary lesion, n 243 {28.7mm, 99.2%, 63.3min,
0%/0.4%, 24.7%/2.1%}. The tumor size was significantly larger for the group
(1) (2) (3) than the group (5), respectively. Operative time was significantly longer
for these four groups than the group (5). En bloc resection rates didnt significantly differ respectively between the two groups. Except for local recurrent
lesion, moderate severe fibrosis rates were respectively similar between the two
groups. Furthermore, all recurrent lesions had severe fibrosis and the severe
fibrosis rate was significantly higher for the group (3) than the group (5). The
perforation rates were respectively similar between the two groups. The delayed
bleeding rate was significantly higher only for the group (2) than the group (5).
CONCLUSION: It is confirmed that we should regard both LST-NG and Is/
Isp=40mm as lesions with highly technical difficulty. We acquired the high curability and safety even for highly difficult lesions irrespective of longer operative
time.
Disclosure of Interest: None declared
P0733 DISTINCT
MOLECULAR
FEATURES
OF
DIFFERENT
MACROSCOPIC SUBTYPES OF COLORECTAL NEOPLASMS
K. Konda1,*, K. Konishi1, T. Yamochi1, Y.M. Ito2, H. Nozawa1, M. Tojo1,
K. Shinmura1, M. Kogo1, A. Katagiri1, Y. Kubota1, Y. Yano1, Y. Kobayashi1,
T. Kihara1, T. Tagawa1, R. Makino1, M. Takimoto1, M. Imawari1, H. Yoshida1
1
1-5-8 hatanodai shinagawa-ku, 142-8666 - Tokyo, Japan, Tokyo, 2Kita 8, Nishi 5,
Kita-ku, Sapporo city, Hokkaido, Japan
Contact E-mail Address: kenichi_konda@yahoo.co.jp
INTRODUCTION: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular
and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs).
AIMS & METHODS: We evaluated both genetic (mutations of KRAS, BRAF,
TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator
phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid
neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48
non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10
small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance.
RESULTS: S-FNs showed few molecular changes except SFRP1 methylation.
Significant differences in the frequency of KRAS mutations were observed
among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for
LST-NGs) (P 5 0.001). By contrast, the frequency of TP53 mutation was higher
in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P 5 0.007). We
also observed significant differences in the frequency of CIMP between LST-Gs
and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P 5 0.005). Moreover,
the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than
in PNs (58.3% or 60.5% vs. 63.2%, P 5 0.05). PIK3CA mutations were detected
only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes
(PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for
TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or
DN for LINE-1 hypomethylation, OR 3.41).
CONCLUSION: We demonstrated that CRNs could be classified into five
macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of
colorectal tumorigenesis.
Disclosure of Interest: None declared
P0734 ENDOCYTOSCOPY CAN PREDICT THE VENOUS
LYMPHATIC VESSEL PERMEATION OF EARLY COLORECTAL
ADENOCARCINOMA

AND

K. Takeda1,*, S.-E. Kudo1, K. Wakamura1, K. Ichimasa1, M. Kutsukawa1,


M. Misawa1, Y. Mori1, T. Kudo1, T. Hayashi1, H. Miyachi1, E. Hidaka1,
F. Ishida1
1
Digestive Disease Center, Showa University Northern Yokohama Hospital,
Yokohama city, Japan
INTRODUCTION: Endocytoscopy (EC), which enables observation of in vivo
cells and nuclei at about 380-fold magnification, provides more detailed information about the lesions.
AIMS & METHODS: The aim of our study is to evaluate the possibility of EC
with regard to prediction of venous and lymphatic vessel permeation.
The subjects were 117 colorectal differentiated adenocarcinomas (53 Tis, 41 T1
carcinomas, 12 T2 carcinomas, 11 T3 carcinomas) from 115 patients treated by
endoscopic or surgical resection after observation with EC at Showa University
Northern Yokohama Hospital from February 2009 to March 2014. In observing
EC images, we defined the average scale of four vessels as vessel diameter and
proportion between maximum portion and minimum portion of the vessel as
vessel caliber variation. We analyzed the correlationship between these parameters (vessel diameter and vessel caliber variation) and venous or lymphatic vessel permeation.
RESULTS: The mean vessel diameter of venous permeation positive tumors was
41.0mm, and that of negative tumors was 31.4mm. The mean vessel caliber variation of venous permeation positive tumors was 0.45, and that of negative tumors
was 0.38 (P 5 0.05). In lymphatic vessel permeation, the mean vessel diameter of
lymphatic vessel permeation positive tumors was 39.1mm, and that of negative
tumors was 34.4mm. The mean vessel caliber variation of venous permeation
positive tumors was 0.45, and that of negative tumor was 0.40 (P 5 0.05).

A334
There were differences in vessel diameter and vessel caliber variation between
venous permeation positive tumors and that of negative tumors especially in
T1carcinomas (p 5 0.05).
CONCLUSION: EC has the possibility to evaluate the venous and lymphatic
vessel permeation by observing the vessel formation, especially in T1 carcinoma.
Disclosure of Interest: None declared
P0736 NATURE OF WHITE OPAQUE SUBSTANCE WITHIN
COLORECTAL NEOPLASTIC EPITHELIUM AS VISUALIZED BY
MAGNIFYING ENDOSCOPY WITH NARROW-BAND IMAGING: A
NOVEL BIO-MARKER FOR COLORECTAL NEOPLASIA
K. Imamura1,2,*, K. Yao3, T. Hisabe1, K. Otsu1, H. Ishihara1, T. Nagahama1,
T. Kanemitsu1, T. Matsui1, M. Nambu2, A. Ota2, A. Iwashita2
1
Gastroenterology, 2Pathology, 3Endoscopy, Fukuoka University Chikushi
Hospital, Chikushino, Japan
Contact E-mail Address: kentaro2316@live.jp
INTRODUCTION: Background: We previously reported the presence of a white
opaque substance (WOS), opaque to the endoscope light, inside the epithelium
when we use magnifying endoscopy (ME) to examine gastric epithelial neoplasia
(adenomas and carcinomas) and chronic gastritis (intestinal metaplasia)1).
Through further pathohistological study we elucidated that this substance is
comprised of minute lipid droplets (LDs) accumulated within the mucosal epithelium of gastric epithelial neoplasia or intestinal metaplasia.2) These minute LDs
strongly backscatter the projected light, and are visualized as a white substance.
When we examined colorectal neoplastic lesions (adenomas and carcinomas)
using ME, we observed WOS as in the stomach. However, it is unclear whether
WOS in colorectal epithelial tumors is in fact an accumulation of LDs as in the
stomach.
AIMS & METHODS: Aims: To elucidate whether WOS observed in colorectal
epithelial tumors (adenomas and carcinomas) is composed of LDs.
Methods: We analyzed a continuous series of both 40 WOS-positive and 40
WOS-negative colorectal epithelial tumors. We examined colorectal neoplastic
lesions (adenomas and carcinomas), prior to planned treatment, using ME with
narrow-band imaging (NBI), determining whether WOS was present in the surface layers of the most anal part of the colorectal epithelial tumor. We took
targeted biopsies from this part of the tumor. Biopsy specimens were immediately
frozen, slices taken, and the slides were stained for lipids using oil-red O. Slides
were examined using light microscopy immediately after staining for the presence
of LDs within the neoplastic epithelium. We investigated the correlation between
the presence of WOS as visualized by ME with NBI and the presence of LDs in
the histological specimens.
RESULTS: The prevalence of LDs in WOS-positive vs WOS-negative lesions
was 47.5% (19/40) and 5% (2/40), respectively (P 5 0.001, Fishers exact test).
CONCLUSION: Conclusion: LDs do not accumulate in the normal colorectal
epithelium. However, this study elucidated for the first time that endoscopically
visualized WOS may be composed of LDs accumulated in colorectal epithelium.
This phenomenon has the potential to be a new biomarker for the pathology and
diagnosis of colorectal neoplasia.
REFERENCES
1. Yao K, Iwashita A, Tanabe H, et al. White opaque substance within superficial elevated gastric neoplasia as visualized by magnification endoscopy with
narrow-band imaging: a new optical sign for differentiating between adenoma
and carcinoma. Gastrointest Endosc 2008; 68: 574-580.
2. Yao K, Iwashita A, Nambu M, et al. Nature of white opaque substance in
gastric epithelial neoplasia as visualized by magnifying endoscopy with narrowband imaging. Dig Endosc 2012; 24: 419-425.
Disclosure of Interest: None declared
P0737 QUANTITATIVE AUTOFLUORESCENCE IMAGING IS USEFUL
FOR ASSESSING THE SEVERITY OF ULCERATIVE COLITIS
K. Moriichi1,*, M. Fujiya1, M. Ijiri1, K. Tanaka1, A. Sakatani1, T. Doukoshi1,
K. Ando1, N. Ueno1, S. Kashima1, Y. Inaba1, T. Ito1, Y. Kohgo1
1
Division of Gastroenterology and Hematology/Oncology, Department of
Medicine, Asahikawa Medical University, Asahikawa, Japan
Contact E-mail Address: morimori@asahikawa-med.ac.jp
INTRODUCTION: Maintaining remission in patients with ulcerative colitis
(UC) is the most important achievement for the present treatments. Although
precise evaluation of the mucosal inflammation is necessary to keep the remission
status as long as possible, the procedures have been inadequate to detect this
inflammation. Autofluorescence imaging (AFI) is a novel technology that can
capture the fluorescence emitted from living tissues. While AFI has been demonstrated to be useful for diagnosing colorectal neoplasms, it is unclear whether
AFI can assess the severity of ulcerative colitis (UC).
AIMS & METHODS: The aim of this prospective study was to evaluate the
efficacy of AFI and its quantification for detecting mucosal inflammation in
patients with UC. Forty-three patients diagnosed with UC who underwent
AFI at Asahikawa Medical University Hospital between 2007 and 2010 were
enrolled in this study. One hundred and thirty-five areas of the colon in the
enrolled patients were first photographed using conventional endoscopy, followed by AFI. Eleven endoscopists separately evaluated the photographs captured with WLE and AFI, and quantified the intensities of fluorescence. Biopsy
specimens were evaluated according to Matts criteria, and active inflammation
was defined when Matts grade was 2 or higher. 1) When the WLE image corresponded to a Mayo endoscopic subscore 0 or 1, the inflammation was categorized as inactive. AFI images were visually categorized into two groups, greendominant (G) and magenta-dominant (M) (vAFI). 2) AFI images were quantified using an image-analytical software program. The ratio of the reverse gamma

United European Gastroenterology Journal 2(1S)


value of green (fluorescence) divided by that of red (reflex) was defined as the
fluorescence index (F index). These endoscopic assessments and the F index were
compared with the histological findings. A cutoff value for the F index of active
inflammation was determined using an ROC analysis. 3) The inter-observer
consistency of WLE, vAFI and the quantified AFI for eleven endoscopists was
calculated.
RESULTS: 1) The average diagnostic accuracy of WLE and vAFI for the histological activity was 78.5% and 78.6%, respectively. No significant difference
was observed between these modalities. 2) The correlation coefficient between the
F index and the histological findings was closely associated with the inflammatory grade (r -0.558, p50.0001). The ROC analysis showed that active inflammation was defined when the F index was less than 0.906. The average diagnostic
accuracy of the F index (84.7%) was higher than that of WLE and AFI (p50.01,
p50.05). 3) The kappa value for inter-observer agreement of WLE, vAFI and
the F index by the overall observers, residents and experts were 0.58, 0.56 and
0.95, 0.53, 0.49 and 0.97 and 0.67, 0.64 and 0.93, respectively.
CONCLUSION: The quantified AFI is therefore considered to be a useful and
objective modality for assessing the activity of ulcerative colitis, particularly by
residents.
Disclosure of Interest: None declared
P0738 EFFICACY OF COLORECTAL ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR THE TREATMENT OF RESIDUAL OR
LOCALLY RECURRENT TUMOR OCCURRING IN THERAPEUTIC
SCAR
K. Hirasawa1,*, R. KOBAYASHI1, H. KANEKO1, M. MAKAZU1, C. SATO1,
S. MAEDA2
1
Division of Endoscopy, Yokohama City University Medical Center, 2Department
of Gastroenterology, Yokohama City University Graduate School of Medicine,
Yokohama-City, Japan
Contact E-mail Address: kingo-h@urahp.yokohama-cu.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widespread as a treatment of superficial gastric neoplasm even for ulcerative scar
cases. This technique has been recently introduced as a treatment option for
colorectal tumor; however, the efficacy of ESD for residual or locally recurrent
colorectal tumor occurring in therapeutic scar has not been fully evaluated.
AIMS & METHODS: To clarify the clinical outcomes of colorectal ESD for
residual or locally recurrent tumor occurring in therapeutic scar.
Between April 2008 and March 2014, 285 consecutive superficial colorectal
tumors in 267 patients were treated using ESD. Of these, 17 lesions in 17 patients
were treated as residual or locally recurrent tumor with therapeutic scar. These
contained 12 that recurred after endoscopic mucosal resection (EMR) and 5 after
transanal endoscopic microsurgery (TEM) (scar group). The others were defined
as non-scar group and treatment outcomes and complications were evaluated
between two groups.
RESULTS: In all patients, the rates of en bloc resection, R0 resection and
curative resection were 98.9% (282/285), 90.2% (257/285) and 82.5% (235/285)
respectively, and mean tumor size was 33.3 mm, mean treatment time was 67.2
minutes, and perforation rate was 9.5%. All patients with perforation were managed with conservative medical treatment after endoscopic closure with clipping
and did not need emergent surgery.
No significant differences were observed between the two groups with respect to
the rate of en bloc resection, R0 resection and curative resection; however, univariate analysis showed that perforation rate and treatment time were significantly higher and longer in the scar group compared with the non-scar group.
In addition, we evaluated age, sex, tumor location, tumor depth, tumor size,
tumor morphology and the presence of therapeutic scar by multivariate analysis,
and found that large tumor size and the presence of therapeutic scar were an
independent risk factor for both perforation and long treatment time.
CONCLUSION: This finding implies that colorectal ESD may be used as a
treatment choice for residual or locally recurrent tumor occurring in therapeutic
scar. However, we need to perform ESD in consideration of the risk for perforation, and it will require cooperation with surgery when treating those cases.
Disclosure of Interest: None declared
P0739 EDUCATION FOR WARD NURSES INFLUENCES ON THE
QUALITY OF INPATIENTS BOWEL PREPARATION FOR
COLONOSCOPY
K.B. Cho1,*, E.S. Kim1, K.S. Park1, E.S. Choi1, S.M. Lee1, C.H. Yang2
1
Internal Medicine, KEIMYUNG UNIVERSITY SCHOOL OF MEDICINE,
Daegu, 2Internal Medicine, Dongguk University School of Medicine, Gyeongju,
Korea, Republic Of
Contact E-mail Address: dandy813@hanmail.net
INTRODUCTION: Although adequate bowel preparation is prerequisite to
colonoscopy, preparation for inpatients is often suboptimal.
AIMS & METHODS: This study aimed to evaluate the impact of education for
ward nurses on the quality of inpatients bowel preparation. A prospective,
endoscopist-blinded, non-randomized, controlled study was performed.
Gastroenterology experts provided the education to nurses who belonged to
educated ward and this education was repeated every week for 1 month. 103
inpatients in educated ward and 102 inpatients in control ward of gastroenterology department who were scheduled for colonoscopy were enrolled. The primary
outcome was the quality of the bowel preparation using the Ottawa Bowel
Preparation Scale (OBPS). The secondary outcomes were polyp detection rate
(PDR), patient compliance and subjective feelings.
RESULTS: Baseline data including patient characteristics, indication of procedure, and preparation quality before the study were comparable between 2

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United European Gastroenterology Journal 2(1S)


Table to abstract P0740
Ileoscopy abnormal

Ileoscopy normal

Indication (n)

Diarrhoea (67)
Abdo pain (39)
IBD assessment (29)
Other* (18)
Total6 (129)

P value (all / clinically relevant)


Number

Biopsy abnormal

Clinically relevant

Number

Biopsy abnormal

Clinically relevant

15
12
12
2
34

11
9
10
2
25

9
8
9
1
21

52
27
17
16
95

7
3
3
3
14

3
2
3
1
1

wards. Mean scores of OBPS were 4.422.23 and 6.152.38 in educated and
control ward, respectively (p50.001). Rate of poor preparation (OBPS 56) in
educated ward was significantly lower than that of control (31.1% vs. 58.8%,
p50.001). PDR of educated ward was significantly higher than that of control
ward (74.8% vs. 52.0%, p 0.001). Compliance with preparation and diet
instructions in education group was superior to that in control (p50.001).
Control group was more likely to be anxious before colonoscopy (p50.001)
while education group showed a higher level of satisfaction with better sleep
quality (p50.001). In multivariate analysis, no ward nurse education (OR 2.36,
p 0.025), constipation (OR 6.52, p50.001) and no additional water ingestion
(OR 2.05, p 0.042) were factors associated with poor bowel preparation.
CONCLUSION: Ward nurse education is effective to improve the quality of
inpatient bowel preparation, PDR, and compliance. Additional effort is needed
to control constipation and to encourage additional water ingestion for better
inpatient bowel preparation.
Disclosure of Interest: None declared
P0740 WHEN SHOULD I TAKE TERMINAL
EXPERIENCE FROM A SINGLE UNIT

ILEAL

BIOPSIES?

L.J. Neilson1,2,*, R. Bevan1,2, C.J. Rees1,2


1
South Tyneside District Hospital, South Shields, 2Northern Region Endoscopy
Group, Newcastle, United Kingdom
Contact E-mail Address: neilson.laurajane@hotmail.co.uk
INTRODUCTION: Terminal ileum (TI) intubation at colonoscopy may be
useful in the investigation of patients with diarrhoea or possible inflammatory
bowel disease.1,2 The yield of TI biopsies has been shown to be variable and there
are no standards for current practice.2,3 Furthermore, in the UK, concerns
remain regarding the potential for prion transmission.
AIMS & METHODS: We aim to establish the yield of TI biopsies in a single
unit.
All TI biopsies recorded on the pathology system in a 3-year period were
reviewed. Colonoscopy reports for these cases were reviewed, as well as case
records to establish if biopsy results were clinically relevant (defined as leading
to a change in management). Statistical analysis was performed using SPSS. P
values were calculated using the Fishers exact test to show any difference in
biopsy yield between normal and abnormal looking mucosa for each indication.
The values were calculated for all abnormal biopsy results, and for clinically
relevant biopsy results.
RESULTS: 129 TI biopsies were taken between September 2010 and September
2013, 49 (38%) male and 80 (62%) female. Mean age 44 years (s.d. 17.2). There
were 29 (22.5%) cases of known inflammatory bowel disease (IBD). 5 (3.9%)
cases were completion colonoscopies after colorectal cancer surgery, where TI
biopsies are taken to prove a complete examination.
CONCLUSION: We demonstrate that when investigating patients with diarrhoea, abdominal pain, or IBD, if the terminal ileum is visually normal, biopsies
do not add to the clinical picture. There is a higher yield of relevant biopsy
abnormalities when the TI appears abnormal. We can recommend within our
practice that a visual assessment of a normal terminal biopsy is adequate, thereby
reducing unnecessary biopsies. This reduces the workload for pathology laboratories, reduces risk from biopsies, and improves patient care as normal results can
be communicated sooner to the patient.

50.001 / 50.001
50.001 / 50.001
50.001 / 0.006
0.194 / 0.284
50.001 / 50.001

REFERENCES
1. Geboes K, Ectors N, DHaens G, et al. Is ileoscopy with biopsy worthwhile in
patients presenting with symptoms of inflammatory bowel disease? Am J
Gastroenterol 1998; 93: 201-206.
2. Morini S, Lorenzetti R, Stella F, et al. Retrograde ileoscopy in chronic nonbloody diarrhea: A porspective, case-control study. Am J Gastroenterol 2003; 98:
1512-1515.
3. Melton SD, Feagins LA, Saboorian MH, et al. Ileal biopsy: Clinical indications, endoscopic and histopathologic findings in 10.000 patients. Dig Liver Dis
2011; 43: 199-203.
Disclosure of Interest: None declared
P0741 PHARMACODYNAMIC AND CLINICAL EVALUATION OF LOWVOLUME POLYETHYLENE GLYCOL (PEG)-BASED BOWEL
CLEANSING SOLUTIONS (NER1006) USING SPLIT DOSING IN
HEALTHY AND SCREENING COLONOSCOPY SUBJECTS
M. Halphen1,*, B. Tayo1, S. Flanagan1, L. Clayton1, R. Kornberger2
1
Norgine Ltd, Uxbridge, United Kingdom, 2PAREXEL International, Berlin,
Germany
Contact E-mail Address: MHalphen@norgine.com
INTRODUCTION: The effectiveness of PEG3350electrolytes based solutions
for bowel cleansing prior to endoscopy is well established but require patients to
drink 3L of fluid. Reducing this volume without compromising efficacy/safety
is the next challenge.
AIMS & METHODS: This open-label, randomised, 2-part (Part A: healthy
subjects; Part B: screening colonoscopy subjects), phase II study investigated
the pharmacodynamics (stool weight), tolerability, and clinical efficacy of doseand taste-optimised low-volume PEG-based formulations (NER1006) after split
dosing compared with MOVIPREP. Subjects (4070y) were randomised to 1 of
4 treatment arms in Parts A and B (1:1:1:1): 3 formulation arms for NER1006; 1
for MOVIPREP. NER1006 consisted of different PEG3350 formulations,
mineral salts (including ascorbate), electrolytes and flavouring, reconstituted
with water plus additional intake of specified volumes of water (Table).
Treatment was administered on Day 1 (evening dose) and Day 2 (morning
dose). The primary endpoint in Parts A and B was 24h stool weight (desired
target 2750g). Cleansing success rate (Harefield Cleansing Scale) was a coprimary endpoint in Part B. Secondary endpoints included time and volume of
study drug to reach clear effluent, safety and tolerability (vomiting rate).
RESULTS: 120 subjects were included in each part (n 30/arm). 24h stool
weight was significantly 42750g for NER1006 formulations OPT002 and
OPT003 in Part A, and OPT003 and OPT007 in Part B. Reversed order of
administration of the split dose (i.e., TF043 morning/TF048 evening) in
OPT002 was as efficacious, with a similar safety profile. Most subjects in the
NER1006 arms reached clear effluent. Mean volume of study drug required and
time to reach clear effluent are shown in the Table. In Part B, cleansing success
rate was: 100% for OPT003 and OPT007; 90% for OPT006 and OPT004. For
subjects who completed dosing, vomiting rates were 57.0% and 53.5% for all
treatments in Parts A and B, respectively, with no significant differences between
arms in either part.
CONCLUSION: In healthy and screening-colonoscopy subjects, the new lowvolume, split-dose bowel preparation NER1006 achieved high quality bowel
cleansing comparable with MOVIPREP. Stool output was consistently higher
with NER1006 treatments, and safety/tolerability profiles between treatments
were comparable.

Table to abstract P0741


Table Pharmacodynamics of different technical formulations (TF)/administration volumes of NER1006

Arm
(formulation)
Part A:
1 (OPT001)
2 (OPT002)
3 (OPT003)
4 (OPT004)
2491 (0.8764)
Part B:
1 (OPT003)
2 (OPT007)
3 (OPT006)
4 (OPT004)

Evening dose
formulation
(reconstitution
voladditional vol, mL)

Morning dose
formulation
(reconstitution
voladditional vol, mL)

TF048 (750875)
TF043 (500875)
TF047 (5001000)
MOVIPREP (1000500)
17.7

TF043 (500875)
TF048 (750875)
TF043 (5001000)
MOVIPREP (1000500)
1929

TF047 (5001000)
TF047 (500500)
TF047 (5001000)
MOVIPREP (1000500)

TF043 (5001000)
TF043 (500500)
TF044 (5001000)
MOVIPREP (1000500)

Mean time to
clear effluent, h

Mean volume of
drug required to reach
clear effluent, mL

2951 (0.2176)
3219 (0.0042)
3399
(50.0001)

15.8
12.3
17.8

1139
900
944

3050
3215
2675
2487

14.9
16.9
17.7
16.3

860
956
935
1790

Mean stool
weight, g
(p-value vs target)

(0.0268)
(0.0004)
(0.4907)
(0.9691)

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United European Gastroenterology Journal 2(1S)

Disclosure of Interest: M. Halphen Consultancy for: Norgine, B. Tayo Other:


Norgine, S. Flanagan Other: Norgine, L. Clayton Other: Norgine, R.
Kornberger Financial support for research from: Norgine
P0742 OLYMPUS NEAR FOCUS NARROW BAND IMAGING (NBI) VS
CONVENTIONAL NBI FOR IN VIVO ENDOSCOPIC HISTOLOGY OF
COLONIC POLYPS: A RANDOMIZED CONTROLLED TRIAL
M. Bustamante1,*, L. Puchades1, M. Ponce1, L. Arguello1, V. Pons1
1
Gastrointestinal Endoscopy Unit, Hospital Universitari i Polite`cnic La Fe,
Valencia, Spain
Contact E-mail Address: bustamante_mar@gva.es
INTRODUCTION: A lower diagnostic accuracy of pathologic in vivo diagnosis
with NBI has been described in nonacademic settings compared to expert centers.
Recently, Olympus has launched the 190 series, which has a pushbutton-controlled optical magnification system (near focus).
AIMS & METHODS: Aims: to assess the reliability of the near focus system
compared to conventional NBI in the histologic prediction (adenoma vs hyperplastic) of small (6-9 mm) and diminutive (1-5 mm) colonic polyps. Secondary
objective was to assess the fulfillment of PIVI criteria.1
Patients and methods: Patients scheduled for colonoscopy were consecutively
included. Patients were assigned to 190 series (group 1) or 180 series (group 2)
endoscopes using a computer-generated random number sequence. A sample size
calculation was performed, and a minimum of 136 lesions per group was programmed. All examinations were performed by the same endoscopist (MBB) with
expertise in NBI analysis. NICE classification criteria2 were used for in vivo
histological diagnosis.
RESULTS: 98 patients were included (49 women, 50%), median age 63 yr. CRC
screening was the most frequent indication (51%). Group 1 was comprised of 51
patients (52%). Finally 333 lesions were included, 82.6% from 1 to 5 mm of
diameter, and 231 (69.4%) adenomas. Under NBI examination, the histology of
277 lesions (83.2%) was predicted with high confidence. The 51 patients from
group 1 harbored 171 lesions (142 predicted with high confidence) and the 48
patients from group 2 harbored 162 lesions (135 predicted with high confidence).
Sensitivity, specificity and diagnostic accuracy for lesions diagnosed with high
confidence in both groups are summarized in table 1. There were no differences
in diagnostic accuracy between both groups (92.2% vs 89.6%, p 0.5).
(%)
(CI 95%)

Group 1

High
confidence

Group 2

High confidence
Diminutive
High
lesions
confidence

Sensitivity 91.8 (85.9-97.7) 90.0 (82.8-97.2)


Specificity 93.2 (84.6-100) 94.1 (84.7-100)
Accuracy 92.2 (87.5-97.0) 91.2 (85.6-96.9)

High
confidence
Diminutive
lesions

91.2 (84.8-97.6) 87.7 (78.9-96.5)


86.4 (75.1-97.6) 86.4 (75.1-97.6)
89.6 (84.1-95.1) 87.2 (80.4-93.9)

Six (10.3%) of the 54 diminutive lesions located in rectum and sigmoid colon and
diagnosed as hyperplastic with NBI were finally categorized as adenomas. The
overall NPV for the diagnosis of adenoma was 89.7%. In 61 (95.3%) out of the
64 patients in whom a colonoscopy control was scheduled, there was an agreement between NBI and the final pathological diagnosis (kappa 0.9), without
differences between groups.
CONCLUSION: The near focus technology does not increase the diagnostic
accuracy of conventional NBI at least for an expert examinator. NBI achieves
a good accuracy for in vivo pathological diagnosis, fulfilling PIVI criteria; therefore it may represent an alternative to pathological diagnosis in a near future.
REFERENCES
1 ASGE PIVI on real-time endoscopic assessment of the histology of diminutive
colorectal polyps. Gastrointest Endosc 2011; 73: 419-422.
2 Hewett DG, et al. Validation of a simple classification system for endoscopic
diagnosis of small colorectal polyps using narrow-band imaging.
Gastroenterology 2012; 143: 599-607.
Disclosure of Interest: None declared
P0743 CONFOCAL LASER ENDOMICROSCOPY FINDINGS
PRIMARY SCLEROSING CHOLANGITIS (PSC) -IBD PATIENTS

IN

describe the white light findings in CD. CLE findings were classified using the 4
grade classification system of inflammation, describing crypt architecture, infiltration of the cells, microvasculature alteration and leakage of fluorescein. CLE
images were collected for each segment of the colon, and targeted biopsies were
taken for histologic analysis.
RESULTS: Of the 24 PSC patients, 20 had co-existent IBD (10UC, & 10CD).
Absence of rectal inflammation based on CLE findings was seen in 20/24
patients. 10/24 had moderate to severe inflammation present in the right colon
with irregular, decreased or necrotic crypts. Two patterns of fluorescein leakage
were observed. A) In 10 patients leakage of fluorescein were observed in spaces
amongst epithelial cells, or non-uniform abundant leakage in the lumen of the
crypts associated with moderate to severe inflammation; B) In 12 patients we
observed uniform leakage of the fluorescein into the lumen of crypts in the left
side of the colon, associated with normal crypt architecture and micro-vasculature - the absence of active inflammation was confirmed by histology. The
remaining 2 patients did not showed leakage of fluorescein. Four patients did
not have a diagnosis of IBD but 3 of these patients had subtle inflammation on
CLE characterized by cellular infiltration within the lamina propria in the sigmoid colon and rectum (by histology). One had a new diagnosis of UC after
examination by CLE and colonoscopy.
CONCLUSION: CLE effectively characterizes the inflammation of PSC IBD
patients, confirming that these patients are likely have a different phenotype with
inflammation in the right side of the colon and rectal sparing. The finding of
uniform leakage of fluorescein into the lumen of the crypts, in the absence of
active inflammation, may represent a defect in the intestinal barrier. Even
patients not known to have IBD associated with PSC may demonstrate subtle
infiltration of mononuclear cells into the lamina propria as demonstrated at
CLE.
Disclosure of Interest: None declared
P0744 ANALYSIS OF THE ENDOCYTOSCOPIC IMAGE
COLORECTAL LESION FROM THE ASPECT OF MICRO
VASCULAR PATTERN

OF

M. Misawa1,*, S.-E. Kudo1, H. Nakamura1, S. Kataoka1, S. Hayashi1,


H. Oikawa1, N. Toyoshima1, Y. Mori1, T. Kudo1, N. Ogata1, T. Hayashi1,
K. Wakamura1, Y. Wada1, H. Miyachi1, F. Ishida1
1
Digestive disease center, Showa University Northern Yokohama Hospital,
Yokohama-shi, Japan
INTRODUCTION: Endocytoscopy (EC) is an ultra-magnification technique,
which can be performed to evaluate structural and cellular atypia with observation of lumens and nuclei in the surface layer of the mucosa. EC has made it
possible to diagnose living tumor cells in vivo and to obtain an ultra-magnification pathological image simply by applying the scope to the target mucosa during
an endoscopic examination. On the other hand, analysis of the surface microvessels of colorectal lesions using magnifying narrow-band imaging is useful for
identifying the appropriate treatment method for colorectal lesions. In addition,
the surface microvessels can be analyzed using EC.
AIMS & METHODS: The aim of this study was to investigate whether the
observation of surface microvessels using EC was useful in predicting the histopathology of colorectal lesions.
The study included 273 patients who underwent complete colonoscopy and endoscopic or surgical treatment between April 2006 and December 2013. A total of
337 lesions (10 normal mucosae, 23 hyperplastic polyps, 210 adenomas, and 94
submucosally invasive cancers) were retrospectively evaluated. The colonic surface micro-vascular patterns observed using EC were classified into the following
3 groups: EC-V1, the surface microvessels were obscure; EC-V2, the surface
microvessels were clearly observed, and their caliber and arrangement were uniform; and EC-V3, the surface microvessels were thick, and their caliber and
arrangement were non-homogeneous.
RESULTS: The sensitivity, specificity and accuracy of EC-V1 for diagnosis of
hyperplastic polyp were 97.0%, 99.0% and 98.8%, respectively. As regards the
sensitivity, specificity and accuracy of EC-V3 for diagnosis of invasive cancer
were 84.7%, 97.7% and 94.1%, respectively.
CONCLUSION: Vascular patterns of colorectal cancers observed by endocytoscopy were useful in predicting the histopathology of colorectal lesions.
Disclosure of Interest: None declared
P0745 EXCELLENT PROGNOSIS OF ENDOSCOPICALLY RESECTED
RECTAL NEUROENDOCRINE TUMORS DESPITE THE FREQUENT
PRESENCE OF LYMPHOVASCULAR INVASION

M. Iacucci1,*, X. Gui2, R. Panaccione 1, S. Ghosh3, B. Eksteen4


1
Inflammatory Bowel disease clinic, 2pathology departement, 3Departement of
Medicine, 4Division of Gastroenterology&Hepatology, University of Calgary,
Calgary, Canada
Contact E-mail Address: miacucci@ucalgary.ca

M. Sekiguchi1,*, S. Sekine2, T. Sakamoto1, Y. Otake1, T. Nakajima1,


T. Matsuda1, H. Taniguchi1, R. Kushima2, Y. Saito1
1
Endoscopy Division, 2Pathology DIvision, National Cancer Center Hospital,
Tokyo, Japan
Contact E-mail Address: masekigu@ncc.go.jp

INTRODUCTION: Controversy exists as to whether the colitis seen in patients


with primary sclerosing cholangitis (PSC) represents a different entity than that
classically observed in patients with Crohns disease (CD) or ulcerative colitis
(UC). Specific differences have been described in the nature of the endoscopic
and histological findings. Confocal laser endomicroscopy (CLE) is a new technology which enables real time endoscopy and histological investigation. PSC
colitis has not been investigated by CLE.
AIMS & METHODS: To describe the CLE appearance in the colon in patients
with PSC, with or without associated IBD. Patients and Methods 24 patients (16
male: median age 43y, range 20-71y) with PSC underwent colonoscopy with CLE
(Pentax, Tokyo) between 02/12 and 12/13. The Mayo endoscopy sub-score was
used to grade endoscopic findings in UC, and the SES-CD score was used to

INTRODUCTION: Endoscopic resection (ER) is increasingly used to treat small


rectal neuroendocrine tumors (NETs). Currently, several guidelines recommend
ER as a treatment of rectal NETs less than 10 mm without muscularis invasion.
However, limited data are available on the long-term outcomes of rectal NETs
treated by ER. In addition, the significance of known risk factors for metastasis
of rectal NETs, including lymphovascular invasion, remains elusive.
AIMS & METHODS: The aim of this study was to clarify the prognosis of rectal
NET patients treated by ER and to characterize the known risk factors for
metastasis of these lesions. Ninety-eight patients underwent ER for rectal
NETs at our institution between 1997 and 2011. Among them, 3 patients who
underwent colectomy for colorectal cancers after ER of rectal NETs and 8
patients with a follow-up period shorter than 1 year were excluded. Thus, a

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United European Gastroenterology Journal 2(1S)


total of 87 patients with 91 lesions were included in this study. The patients
records were retrospectively analyzed for clinical outcomes and pathological
findings including size, invasion depth, and lymphovascular invasion. Also, we
additionally evaluated tumor proliferation by Ki-67 immunohistochemistry and
lymphovascular invasion using elastic staining and double staining immunohistochemistry (CD31/synatophysin and D2-40/synaptophysin).
RESULTS: ER procedures included endoscopic submucosal resection with a
ligation device (ESMR-L) (n 82), EMR (n 5), and ESD (n 4), with an R0
resection rate of 90.1% (ESMR-L 76/82, EMR 3/5, and ESD 3/4, respectively).
No major complications were observed. All cases were followed up without
surgery after ER; with the median follow-up period of 68 months (range, 12
167), no metastasis or recurrence was detected and the 5-year overall survival rate
was 95.9%. The median tumor size of these cases was 5 mm (range, 213) and no
lesion showed invasion beyond the submucosal layer. Based on the results of Ki67 immunohistochemistry, all 91 lesions were classified as NET G1 (WHO 2010
classification). The original diagnoses based on haematoxylin and eosin staining
identified no case with lymphatic invasion and only one case with positive venous
involvement. However, additional analysis using elastic staining and double
staining immunohistochemistry revealed lymphovascular invasions in 33 lesions
(36.3%) by elastic staining, 9 lesions (9.9%) by CD31/synaptophysin double
staining, and 23 lesions (25.3%) by D2-40/synaptophysin double staining.
Collectively, lymphovascular invasion was identified in a total of 42 lesions
(46.2%) with at least one of these staining procedures. Size of NETs with lymphovascular invasion (median, 5 mm; range, 313) was significantly but only
slightly larger than that of NETs without lymphovascular invasion (median, 4
mm; range, 210; p 0.02, MannWhitney U test).
CONCLUSION: Long-term clinical outcomes of rectal NETs following ER were
favorable. While lymphovascular invasion was believed to be a strong risk factor
for metastasis, a detailed analysis revealed that it was frequently present even in
minute rectal NETs. The present results raise a question on the clinical significance of lymphovasucalar invasion in small rectal NETs.
Disclosure of Interest: None declared
P0746 HIGH PRESSURE JET INJECTION OF VISCOUS SOLUTIONS
FOR ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD): ABOUT
THE 45 FIRST HUMAN CASES IN 4 EXPERT CENTERS
M. Pioche1,2,*, V. Lepilliez3,4, P. Deprez5, M. Giovannini6, F. Caillol6,
H. Piessevaux7, J. Rivory4, O. Guillaud4, M. Ciocirlan8, D. Salmon9,
I. Lienhart4, C. Lafon2, J.-C. Saurin4, T. Ponchon4
1
Gastroenterology and endoscopy, Edouard Herriot Hospital, 2Inserm U1032,
3
Gastroenterology and endoscopy, Hopital Prive Jean Mermoz, 4Gastroenterology
and endoscopy, Hopital Edouard Herriot, Lyon, France, 5Gastroenterology and
endoscopy, Hopital Saint-Luc, Louvain, Belgium, 6Gastroenterology and endoscopy, Institut Paoli Calmette, Marseille, France, 7Gastroenterology and endoscopy, Hopital Saint Luc, Louvain, Belgium, 8Carol Davila institute, Bucharest,
Romania, 9Pharmacy, Hopital Edouard Herriot, Lyon, France
Contact E-mail Address: mathieupioche@free.fr
INTRODUCTION: Long lasting lifting is a key factor during ESD and can be
obtained by water-jet injection of saline solution or by injection of viscous
macromolecular solutions. In a previous animal study, we assessed the ability
of the Nestis Enki II system to combine jet injection and macromolecular viscous
solutions. In the present work, we used this combination in humans in the different sites of the digestive tract.
AIMS & METHODS: To assess the effectiveness and safety of Nestis system
using viscous solutions. We report retrospectively all the consecutive cases of
ESD procedures made with Nestis Enki II system with injection of viscous solutions. Information was collected about: the lesion (site, histology), the procedure
(time, perforations, bleedings, monobloc or piece meal resection), the piece (size,
R0, Rx or R1 resection) and the outcomes for the patient (curative treatment,
surgery, recurrence, delayed complications).
RESULTS: 45 resections were complete macroscopically. Procedures were performed by 6 operators: 5 experts and one beginner with only one previous
experience in human ESD (11). The lesions were: 22 lateral spreading tumors
of the rectum 11 gastric lesions, 10 esophageal lesions, 1 of the right colon and 1
of the second duodenum. The average maximal lesion diameter was 4.8 cm (SD
2.4, range 2-11 cm), the average surface was 19.8 cm2 (SD 17.7, range 2.2-72
cm2) and the average time of procedure was 79.9 min (SD /- 50.3, range 19-225
min). Three adverse events occurred with two diminutive perforations (and two
delayed bleedings treated conservatively. R0 resection rate was 91.1%.
Obstruction of the catheter occurred in 6 cases in bloody situations.
CONCLUSION: This is the first multicenter report on a new water jet system
allowing injection of viscous solutions. This system is safe and effective and
allows working in retroflexed position with different viscous solutions.
Disclosure of Interest: M. Pioche Financial support for research from: Nestis, V.
Lepilliez: None declared, P. Deprez: None declared, M. Giovannini: None
declared, F. Caillol: None declared, H. Piessevaux: None declared, J. Rivory:
None declared, O. Guillaud: None declared, M. Ciocirlan: None declared, D.
Salmon: None declared, I. Lienhart: None declared, C. Lafon: None declared, J.C. Saurin: None declared, T. Ponchon: None declared

P0747 OPTIMISATION OF ENDOSCOPIC FOLLOW-UP WAITING


LISTS IN A NEW ZEALAND DISTRICT HEALTH BOARD
N. Bhala1,*, H. Myint1, J. Lewis1, C. Virtue1, A. Simpson1, R. Cameron1
Department of Gastroenterology, Capital & Coast District Health Board,
Wellington Hospital, New Zealand
Contact E-mail Address: neeraj.bhala@ccdhb.org.nz
1

INTRODUCTION: New Zealand (NZ) has the one of the highest bowel cancer
death rates in the Western world, so prompt access to lower GI endoscopy for
new referrals is of importance in diagnosis, treatment and prevention. However,
partly as a result of follow-up colonoscopy demands, waiting lists have increased
substantially, and so the NZ Ministry of Health has funded initatives to ensure
appropriate clinical investiagtions are being done for the right indication at the
right time.
AIMS & METHODS: We sought to evaluate an optimisation exercise of followup lower GI endoscopy lists in a single District Health Board covering a population of around 300.000 people in the lower North Island of North New Zealand.
Evidence-based criteria were agreed by the endoscopy user multi-disciplinary
group for recall criteria for repeat colonoscopy for a number of conditions,
including: colorectal cancer resections; colorectal adenoma follow-up; family
history of colorectal cancer; and inflammatory bowel disease surveillance.
These were then applied to those patients on the waiting list for repeat endoscopic appearances in 2014 by a single consultant gastroenterologist.
RESULTS: Of 511 patients on the waiting list, 497% were for repeat colonoscopies. 164 procedures (32.1%) did not meet the criteria for repeat procedures,
and were cancelled. Within 2 months of this exercise, only four primary care
practitioners (2.5%) sent queries regarding cancellation, which were dealt with.
183 (35.8%) did meet the criteria, but were not being done at the appropriate
time interval, so were deferred (range 6 months - 3 years). 165 (32.3%) did meet
the indication for repeat procedure in the appropriate time interval, and were
approved and duly listed.
CONCLUSION: Initiatives to apply evidence-based criteria for repeat endoscopic procedures can improve quality, productivity and prevent unnecessary
procedures. In this real-life application in NZ, a third of repeat endoscopy workload were removed from waiting lists, and more than an additional third were
deferred to a clinically appropriate time, allowing new referrals to be seen sooner.
Centrally funded initiatives to apply evidence-based guidelines to help manage
waiting lists may be relevant to other populations.
Disclosure of Interest: None declared
P0748 PICOSALAX PROVIDES SUPERIOR BOWEL CLEANSING TO
TRADITIONAL POLYETHYLENE GLYCOL IN THE ELDERLY
POPULATION
R. Gingold-Belfer1,*, A. Geller1, A. Vilkin1, Y. kelner1, Y. Niv1, Z. Levi1
1
Gastroenterology Department, Rabin Medical Center, Petah Tikva, Israel
Contact E-mail Address: rachelgingoldbelfer@gmail.com
INTRODUCTION: Lately, life expectancy was prolonged. Therefore, endoscopic procedures are performed in an elderly population too. The level of
bowel cleansing during colonoscopy is one of the quality indicators that were
determined in order to improve the procedures efficacy. An elder age is one of
the factors for poor preparation.
AIMS & METHODS: Aims: We aimed to evaluate the level of bowel cleansing
of the elderly population, by assessing the bowel preparation with Picosalax as
compared to polyethylene glycol (PEG).
Methods: Included 6,844 patients aged 75y (mean 81.1y4.6) who underwent
colonoscopy at our endoscopy unit during 2003-2013. 3,659 (53.5%) patients
were men. 1,258 patients had preparation with Picosalax and 5,444 with PEG.
The quality of bowel cleansing was assessed according to the Aronchick scale.
Multivariable logistic regression analysis for good preparation were used and
included: the patients age, gender and bowel preparation type.
RESULTS: Total, good preparation was achieved in 1,024 (79.8%) patients who
used Picosalax as compared to 3,528 (63.4%) with PEG (p50.001). Fair preparation was achieved in 183 (14.5%) patients by Picosalax as compared to 1,322
(24.3%) by PEG. Bad and poor preparations were reported in 44 (3.5%) and 7
(0.6%) patients who used Picosalax as compared to 544(10%) and 50 (0.9%),
respectively. By using multivariable logistic regression analysis, good preparation, was significantly associated with female gender [OR: 1.38 95% confidence
interval (CI) 1.24-1.52, p50.001] and Picosalax preparation [OR: 2.15 95% CI
1.85-2.5, p50.001, PEG- ref]. An increased age, was negatively associated with
good preparation [OR: 0.9595% CI 0.97-0.99, p 0.009].
CONCLUSION: Female gender is significantly associated with good preparation
in patients aged 75y. The usage of Picosalax was associated with a 2.15 odds
ratio for predicting good bowel preparation. Despite lack of conventional guidelines of bowel preparations regimens for the elderly population, the usage of
Picosalax is indicated as an effective preparation for this age group, too.
REFERENCES
1. Jang JY and Chan HJ. Bowel preparations as quality indicators for colonoscopy. World J Gastroenterol 2014; 20: 2746-2750.
2. Romero VR and Mahadeva S. Factors influencing quality of bowel preparation for colonoscopy. World J Gastroenterol 2013; 5(2): 39-46.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)

P0749 MULTIPURPOSE USE OF THE OVER-THE-SCOPE-CLIP


SYSTEM: SWISS EXPERIENCE IN A TERTIARY CENTER
M.C. Sulz1, R. Bertolini1, R. Frei1,*, G.-M. Semadeni1, C. Meyenberger1
1
Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen,
Switzerland
Contact E-mail Address: michael.sulz@kssg.ch
INTRODUCTION: The Over-the-scope-clip (OTSC) system (Ovesco Endoscopy
AG, Tubingen, Germany) is a fairly new endoscopic device suitable to close
gastrointestinal (GI) perforations, post-surgical fistulae or to resect submucosal
tumors. It can also be used as hemostatic tool in GI bleeding and for esophageal
stent fixation. To the best of our knowledge, in literature there are only case
reports or small case series regarding the efficacy and safety, so far human
clinical randomized controlled trials are not available. The available case series
and reports are inhomogeneous concerning indication, study design, site of application and definition of success.
We present a prospective case series reflecting our all-day clinical experience with
OTSC in a tertiary endoscopy center in Switzerland. This case series illustrates
the primary successful closure in over 80% of GI lesions, mainly fistulae or
anastomotic leakages and adds data to the increasing experience with this tool.
AIMS & METHODS: Aim: To evaluate the outcome of the over-the-scope-clip
system (OTSC) regarding various indications in all-day clinical practice in
Switzerland.
Methods: This is a prospective, consecutive case series conducted at a hospital
with tertiary care endoscopy from September 2010 until January 2014.
Indications were fistulae, anastomotic leakages, perforations, deroofed submucosal lesions for biopsy, refractory bleeding and stent fixation in the gastrointestinal (GI) tract. Primary technical success was defined as an adequate
deployment of the OTSC on the target lesion. Clinical success was defined as
resolution of the problem, for instance no need for surgery or further endoscopic
intervention. In case of recurrence retreatment of a lesion with a second intervention was possible. Complications were classified into those related to sedation, endoscopy or deployment of the clip.
RESULTS: A total of 28 OTSC system applications were carried out in 21
patients (median age 64 years [range 42-85], 33% females). Main indications
were fistulae (52%), most of them after percutaneous endoscopic gastrostomy
(PEG) tube removal and anastomotic leakage after GI surgery (29%). Further
indications were unroofed submucosal lesions after biopsy, upper gastrointestinal
bleeding or esophageal stent fixation. 48% of the OTSC were applied in the
upper and 52% in the lower GI tract. The range of lesion size was 2-20 mm
(mean 8 mm). Primary technical success and clinical success were achieved in
85% and 67%, respectively. In 53% of cases the suction method was used without accessories like Twin grasper or Tissue anchor. No endoscopy-related or
OTSC-related complications were described.
CONCLUSION: OTSC is a useful tool for endoscopic closure of various GI
lesions like fistulae or leakages. Future randomized prospective multicenter trials
are needed.
Disclosure of Interest: None declared
P0750 INVESTIGATING THE INVESTIGATION
COLONIC HOTSPOTS ON PET-CT SCANS

INCIDENTAL

R. Sinha1,*, W.S. Ngu2, A. Ramadas1, A. Reddy2, R. Anandavelu1, D. Aitken2,


M. Jha2
1
Gastroenterology, 2Colorectal surgery, South Tees NHS Foundation Trust,
Middlesbrough, United Kingdom
Contact E-mail Address: rohits78@gmail.com
INTRODUCTION: Positron emission tomography (PET) measures metabolic
changes at a cellular level enabling detection of early stage disease. Incidental
2-deoxy-[18FF]fluoro-2-D-glucose (FDG) colonic uptake is detected in 1.3-3% of
patients with up to a third resulting in false positive results 1. Follow-up endoscopy is recommended to further distinguish these FDG avid lesions 2. Cancer
detection rates of 7.8-18.9% have been quoted in various studies 1,3
AIMS & METHODS: Our aim was to evaluate incidental colonic FDG avid
lesions on PET-CT by endoscopy.
An analysis of retrospectively collected database of all patients (n 1564) who
had PET-CT for extra-colonic malignancy between January 2011 to September
2013 was performed.
RESULTS: Fifty-nine (3.77%) patients had focal colonic FDG uptake and 44
(2.87%) patients went on to have colonoscopy.
Indications for PET CT for those undergoing endoscopy was lung carcinoma
(22), oesophageal carcinoma (5), gastric carcinoma (3), head and neck carcinoma
(7), lymphoma (6) and unknown primary (1).
Median age was 68 with a male preponderance (2.4:1).
Location on PET CT was categorized to sigmoid (22), rectal (9), anorectal (4),
caecal (3), hepatic flexure (2), transverse (1), splenic flexure (1), ascending (1) and
descending (1).
Findings on endoscopy ranged from polyps (21), normal (9), diverticulosis (8),
sigmoid cancer (4), caecal cancer (1) and colitis (1).
In total, out of the all patients who had endoscopy, 19 (43.2%) were found to
have low-grade tubullovillous adenomas, 5 (11.1%) had cancer, whilst 2 (4.4%)
had hyperplastic polyps on histology.
CONCLUSION: These findings are in keeping with other series and suggests to
carry on with current practice of following up these "hot-spots" with endoscopic
investigations.
REFERENCES
1. Israel O, Yefremov N, Bar-Shalom R, et al. PET/CT detection of unexpected
gastrointestinal foci of 18F-FDG uptake: incidence, localization patterns, and
clinical significance. J Nucl Med 2005; 46: 758762.

2. Tatlidil R, Jadvar H, Bading JR, et al. Incidental colonic fluorodeoxyglucose


uptake: correlation with colonoscopic and histopathologic findings. Radiology
2002; 224: 783787.
3. Putora PM, Muller J, Borovicka J, et al. Relevance of incidental colorectal
FDG-PET/CT-enhanced lesions. Onkologie 2013; 36: 200-204.
Disclosure of Interest: None declared
P0751 VARIATIONS IN ADENOMA DETECTION RATES IN THE
ENGLISH FLEXIBLE SIGMOIDOSCOPY SCREENING
PROGRAMME
R. Bevan1,2,*, C. Nickerson3, R. Blanks4, J. Patnick3, R. Loke5, B. Saunders6,
J. Stebbing7, R. Tighe8, A. Veitch9, J. Painter1, C. Rees1,2
1
South of Tyne Bowel Cancer Screening Centre (BCSC), Gateshead, 2Northern
Region Endoscopy Group, Newcastle, 3NHS Cancer Screening Programmes,
Sheffield, 4Cancer Epidemiology Unit, Oxford, 5West Kent & Medway BCSC,
Tunbridge Wells, 6St Marks BCSC, London, 7Surrey BCSC, Guilford, 8Norwich
BCSC, Norwich, 9Wolverhampton BCSC, Wolverhampton, United Kingdom
Contact E-mail Address: roisinbevan@hotmail.com
INTRODUCTION: The English Bowel Cancer Screening Programme has been
expanded to include a one-off flexible sigmoidoscopy offered to all 55 year olds,
called BowelScope Screening. Screening commenced in May 2013, with 6 pilot
sites performing flexible sigmoidoscopies in the first 8 months of screening.
AIMS & METHODS: We aim to describe ADR in BowelScope Screening. The
NHS Bowel Cancer Screening System database was interrogated and ADRs
reviewed for each screening centre and screening endoscopist. ADR was reviewed
graphically, with a funnel plot, constructed using the log odds method.
RESULTS: 49 endoscopists have performed 4444 sigmoidoscopies at 6 screening
centres. Endoscopists had performed 2-330 procedures (median 66, mean 91). 29
endoscopists had performed 50 procedures; of these, 17 had performed 100
procedures.
Centre 2 has a higher ADR than the other centres. When considering all procedures, this difference reaches statistical significance when compared to centres 3,
5, and 6 (p50.05), and approaches significance when compared to centre 1
(p 0.0687) and centre 4 (p 0.0548). When considering only the procedures
done by endoscopists who have performed 50 or 100 sigmoidoscopies, there
remains a significant difference (p50.05) between centre 2 compared to centres 5
and 6, but not to the other centres. A funnel plot of individual endoscopist ADRs
demonstrates one endoscopist below the 99.8% control limit.
Overall BowelScope ADR is 8.6%. ADR by centre is shown in Table 1.
Table 1 - ADR by centre and endoscopist volume
All Centres
Centre 1 Centre 2 Centre 3 Centre 4 Centre 5 Centre 6
Endoscopist
procedure
ADR
counts
%

ADR
%

ADR
%

ADR
%

ADR
%

ADR
%

ADR ADR
%
range %

All
50
100

11.7
11.3
11.3

8.9
8.1
8.9

7.6
8.6
8.6

6.5
6.4
3.1

7.3
6.4
5.2

8.6
8.6
8.7

8.8
8.9
9.0

0.0-60.0
3.1-14.0
3.1-13.0

CONCLUSION: Adenoma detection rates within BowelScope screening show


variation between centres. There is also variation between endoscopists in terms
of individual ADRs, although all but 1 endoscopist are above the 99.8% lower
control level on funnel plot. These variations require further exploration at both
centre and individual level, and feedback and education methods will be used to
improve ADRs.
Disclosure of Interest: None declared
P0752 FLEXIBLE SIGMOIDOSCOPY SCREENING IN THE ENGLISH
BOWEL CANCER SCREENING PROGRAMME - EARLY RESULTS
FROM THE BOWELSCOPE PILOT SITES
R. Bevan1,2,*, C. Nickerson3, J. Patnick3, R. Loke4, B. Saunders5, J. Stebbing6,
R. Tighe7, A. Veitch8, J. Painter1, C. Rees1,2
1
South of Tyne Bowel Cancer Screening Centre, Gateshead, 2Northern Region
Endoscopy Group, Newcastle, 3NHS Cancer Screening Programmes, Sheffield,
4
West Kent & Medway Bowel Cancer Screening Centre, Tunbridge Wells, 5St
Marks Bowel Cancer Screening Centre, London, 6Surrey Bowel Cancer Screening
Centre, Guilford, 7Norwich Bowel Cancer Screening Centre, Norwich,
8
Wolverhampton Bowel Cancer Screening Centre, Wolverhampton, United
Kingdom
Contact E-mail Address: roisinbevan@hotmail.com
INTRODUCTION: UK population colorectal cancer (CRC) screening has been
successfully implemented with Bowel Cancer Screening Programme (BCSP)
faecal occult blood testing biannually from age 60-75.
A large UK study of once-only flexible sigmoidoscopy (FSIG) demonstrated a
reductions in CRC incidence of 33% & death rates of 43%1. This, with the
screening centre infrastructure developed for the FOB programme, allowed provision of a new arm of BCSP, offering FSIG to 55 year olds in England, known
as BowelScope screening.
BowelScope screening began May 2013, with 6 pilot sites performing FSIGs in
the first 7 months.
AIMS & METHODS: We aim to describe procedural data from the early
months of BowelScope screening. Data were obtained from The Bowel Cancer
Screening System (BCSS) database for all participants invited and participating
in BowelScope FSIGs May-Dec 2013. Procedural data were recorded, including

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United European Gastroenterology Journal 2(1S)


insertion depth, adenoma detection rates (ADR), cancer detection, discomfort
levels, entonox usage & colonoscopy conversion rates.
RESULTS: 13927 people have been invited to or opted into BowelScope screening at 6 screening centres. Overall uptake is 43.5% (range 37.0-51.9%). 4 cancers
have been detected. Polyps were detected in 16.4-23.8% of procedures (mean
20.7%). Mean ADR was 8.4%. One centre has a significantly higher ADR
than the other 5 sites (p50.05). (see Table 1).
Table 1 BowelScope outcomes by anonymised centre
Screening
Centre

Invitees

Attended
(%)

B/S with
adenoma(s)

ADR
%

Cancer

Colonoscopy
required (%)

Entonox
used

1
2

3125
1866

1128 (51.9)
524 (37.0)

100
64

8.9%
12.1%

1
0

39 (3.5)
23 (4.4)

121
94

3
4
5
6
TOTAL

3779
986
1970
2181
13927

1070 (40.9)
311 (46.6)
625 (47.4)
479 (37.2)
4135

90
25
38
30
347

8.4%
8.0%
6.1%
6.2%
8.4%

0
0
2
1
4

50 (4.7)
12 (3.9)
21 (3.4)
18 (3.8)
163 (3.9)

60
15
28
25
343

Most (52.7%) procedures were completed in 6-10 minutes. 78.6% of procedures


were reported as causing no or minimal pain only, with only 34 procedures
(0.8%) reporting severe pain.
CONCLUSION: Uptake has varied between centres, but is lower than for the
FOB arm of the BCSP. The average ADR is 8.4% (range 6.1-12.1%), lower than
in the UK flexible sigmoidoscopy screening trial (12.1%, range 8.6-15.9%1)
although the age range studied in the trial differs from this cohort.
Further work will be required to investigate the variation in uptake rates and to
improve these rates. ADR variations may also need to be addressed in future
work.
REFERENCES
1. Atkin W, et al. Once-only flexible sigmoidoscopy screening in prevention of
colorectal cancer: a multicentre randomised controlled trial. Lancet 2010; 375:
1624-1633.
Disclosure of Interest: None declared
P0753 PATIENT-REPORTED EXPERIENCE OF COMFORT AND
DIGNITY IN FLEXIBLE SIGMOIDOSCOPY: DATA FROM THE NHS
BOWEL SCOPE SCREENING PILOT
C.Von Wagner1, H. Bowyer1, R. Bevan2,3,*, C. Rees3,4, W. Atkin5, J. Wardle1
1
Epidemiology and Public Health, UCL, London, 2Northern Region Endoscopy
Group, Newcastle, 3South of Tyne Bowel Cancer Screening Centre, Gateshead,
4
School of Pharmacy and Health, Durham University, Stockton on Tees,
5
Department of Surgery and Cancer, Imperial College, London, United Kingdom
INTRODUCTION: The NHS Bowel Cancer Screening Programme started flexible sigmoidoscopy (FS) screening (also known as Bowel Scope Screening, BSS)
at six centres across England (Gateshead, Guildford, London, Medway,
Norwich, Wolverhampton) in March 2013. The aim of this analysis was to
investigate the extent to which high levels of patient satisfaction recorded in
previous UK trials can be replicated in the early stages of a routine screening
programme.
AIMS & METHODS: We used data from an ongoing study monitoring patientreported experience in the pilot phase of the BSS Programme. We report data
from the post-AM questionnaire which is given to patients at the end of their FS
appointment and supposed to be completed on the following day.
RESULTS: As of January 2014, we had received 2,324 questionnaires.
Satisfaction with the test was high with 98.8% of patients being either satisfied
(21.1%) or very satisfied (77.7%). Nonetheless, 43% of patients reported moderate (34%) or severe pain (9%) which was high compared with the St Marks
demonstration programme1 and the UK Flexible Sigmoidoscopy Trial2. Women
were three times as likely to report severe pain during the test than men (14.3% vs
4.6%), and twice as likely to find the test as more painful than they had expected
(39.9% vs 20.1% respectively). Only about 1 in 10 patients reported being moderately (9.8%) or severely (1.4%) embarrassed during the test, with women being
slightly more likely than men to fall into these categories (13.4 vs. 8.9%). Women
also had a much stronger preference for the test to be carried out by a female
practitioner than men (41.2% vs 7.1% respectively).
CONCLUSION: The vast majority of patients were satisfied with their experience of FS screening. However, levels of pain appear high when compared with
previous trials. Emphasis should be placed on ensuring that patients have as
comfortable a procedure as possible. Additional consideration should be given
to women being able to choose the sex of the practitioner performing the test.
REFERENCES
1 Robb K, Lo S, Power E, et al. Patient-reported outcomes following flexible
sigmoidoscopy screening for colorectal cancer in a demonstration screening programme in the UK. J Med Screen 2012; 19: 171-176.
2 Taylor T, Williamson S, Wardle J, et al Acceptability of flexible sigmoidoscopy
screening in older adults in the United Kingdom. J Med Screen 2000; 7: 38-45.
Disclosure of Interest: None declared

P0754 PATIENTS EXPERIENCE OF COLONOSCOPY IN THE ENGLISH


BOWEL CANCER SCREENING PROGRAMME
A. Ghanouni1, A. Plumb2, C. Rees3,4, P. Hewitson5, H. Miller3, R. Bevan3,6,*,
C.Von Wagner1
1
Epidemiology and Public Health, 2Centre for Medical Imaging, UCL, London,
3
South of Tyne Bowel Cancer Screening Centre, Gateshead, 4School of Medicine,
Pharmacy and Health, Durham University, Stockton on Tees, 5Nuffield
Department of Population Health, University of Oxford, Oxford, 6Northern Region
Endoscopy Group, Newcastle, United Kingdom
INTRODUCTION: In the English Bowel Cancer Screening Programme, colonoscopy is the standard investigation to exclude cancer in participants who receive a
positive faecal occult blood test result. A questionnaire is sent to all patients 30
days post-test. These data were used to assess patients experience of
colonoscopy.
AIMS & METHODS: Anonymised data were extracted from the Bowel Cancer
Screening System. These included all patients who had colonoscopy between 01/
01/11 and 31/12/12. Questionnaire items on the pre-test experience (whether
patients understood the risks/benefits), the hospital experience (the test itself,
issues of dignity/privacy) and post-test complications (bleeding/pain) were analysed. Pearson chi-square tests were used to compare experiences by gender, high
vs. low levels of socioeconomic deprivation (using Index of Multiple Deprivation
scores), and whether patients reported receiving sedation or not.
RESULTS: After excluding patients outside the target date range and those who
did not have colonoscopy, 76,717 patients were eligible for analysis, of whom
60,581 (79.0%) responded to the questionnaire. Nearly all patients felt they
understood the risks (95.7%) and benefits (98.2%) of the test, and 97.8% felt
the preparation instructions were clear. Comparison by gender and deprivation
did not yield clinically meaningful (3%) differences. In terms of the hospital
experience, virtually all patients felt they were treated with respect (98.5%) and
had privacy (98.0%), but 20.8% experienced more discomfort than expected
(although only 5.2% asked for the test to be stopped/paused). Procedural discomfort was moderated by gender, with more women than men reporting higherthan-expected discomfort (25.4% vs. 17.9%; p5.0005), and requesting that the
test be stopped/paused (7.1% vs. 3.9%; p5.0005). Use of sedation showed only a
weak association with patient experience: 22.2% of sedated vs. 20.2% of nonsedated patients reported unexpected discomfort; 6.4% vs. 4.8% asked for the
test to be stopped/paused; both p-values 5.0005). Post-test, 14.3% of patients
reported pain and 6.9% reported rectal bleeding. Pain was more common in
women (18.0% vs. 11.9%; p5.0005) but there were no other clinically meaningful differences post-test related to gender or deprivation level.
CONCLUSION: Most patients referred for colonoscopy as part of the Bowel
Cancer Screening Programme have a positive colonoscopy experience. The most
negative aspect of the experience was the test being unexpectedly uncomfortable.
Patients are extensively counselled pre-procedure but more emphasis on managing expectations, along with continued measures to reduce discomfort and pain
are required, particularly for women.
Disclosure of Interest: None declared
P0755 ENDOSCOPIC RESECTION OF GIANT COLONIC POLYPS
SIZE MATTERS!
R. Bhattacharyya1,*, G. Longcroft-Wheaton1, P. Bhandari1 on behalf of
Portsmouth, UK
1
Gastroenterology, Portsmouth Hospitals NHS Trust, Portsmouth, United
Kingdom
INTRODUCTION: Colonic polyps sized 50mm and above are traditionally
treated by surgical resection. Endoscopic resection has now become increasingly
common as the expertise of western endoscopists improves. There is very little
published literature on endoscopic resection of these giant polyps.
AIMS & METHODS: The aim of the study was to evaluate the feasibility, safety
and efficacy of endoscopic resection of giant polyps 50mm in size.
This was a prospective cohort study. All patients who underwent endoscopic
resection of colonic polyps 50mm from 2007-2013 were prospectively entered
into a database. We excluded all polyps with fibrosis related to previous intervention. All patients were tertiary referrals from experienced gastroenterologists.
All procedures were performed by a single experienced endoscopist.
RESULTS: N 124 polyps in 122 patients. Mean polyp size 71mm. Range 50170mm. 27(22%) in right colon and 97 (78%) in left colon. M:F ratio 1.1:1. All
polyps were resected in a piecemeal fashion. The mean procedure time was 120
minutes (range 90 to 240).
The complication rate was 11/124(8.9%). All these patients required inpatient
stay. There were 9 bleeds (3 immediate and 6 delayed), 1 post polypectomy
syndrome and 1 case of split muscle fibres (clipped endoscopically). 1 case of
immediate bleeding required surgery to control the bleeding. All the others were
managed conservatively. 4 of the 9 bleeds required blood transfusion. The complication rate was independent of polyp size, resection technique or site of the
lesion.
Follow up data was available for 90 polyps. The recurrence rate was 21/
90(23.3%). Of the 21 recurrences, 16/21(76%) patients achieved complete clearance with a further 1 to 2 endoscopic procedures. The recurrence rate was significantly dependent on polyp size and was not dependent on the resection
technique or the site of the lesion. Recurrence gradually increased with an
increase in polyp size up to 70mm. Recurrence was seen in 3/34(8.8%) polyps
55mm, in 7/54(12.9%) polyps 60mm and in 9/63(14.2%) polyps 70mm.
However, in polyps 470mm, the recurrence rate greatly increased to 12/
27(44%) (p 0.002).

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United European Gastroenterology Journal 2(1S)

CONCLUSION: 1) It is safe and feasible to endoscopically resect polyps 50170mm in size.


2) Recurrence is significantly dependent on polyp size.
3) Giant polyps resected endoscopically have a significant recurrence rate. The
majority of these can be cleared by further endoscopic procedures. However, we
believe that the recurrence rate in polyps above 70mm is very high and surgery
should be considered in these cases.
4) Complication rates are independent of size.
Disclosure of Interest: None declared

histologic excision, polyp fly away, retrieval rate, early bleeding (48 hours),
delayed bleeding (2 weeks) and perforation.
RESULTS: A total of 157 polyps were removed. Median (range) polyp size was
4.0mm (3-7mm). There was no significant difference in the patients demographic
details or polyp characteristics between the two groups. Endoscopic completeness
of excision was significantly higher with the Exacto snare compared to the
Olympus snare (90.2% vs. 73.3%, p 5 0.05). There was also a trend towards a
higher complete histological excision rate with the Exacto snare (71.9% vs. 64.4%),
but this did not reach statistical significance (p 0.4). Polyp fly away occurred
less often with the Exacto snare (14.6% vs. 35.3%, p50.05), but there was no
significant difference in the polyp retrieval rate (84.3% vs. 83.8%, p 0.9). There
were no significant complications with either snare. Where the completeness of
excision was assessable (complete or incomplete), there was a fair level of agreement (kappa 0.36) between endoscopic and histological assessment.
CONCLUSION: This is the first study we are aware of that compares completeness of excision with different snares. Our findings suggest that snare type may be
an important factor determining completeness of excision when removing small
polyps by the cold snare techniques.
Disclosure of Interest: None declared

P0756 ADVISABILITY
OF
COLORECTAL
ENDOSCOPIC
SUBMUCOSAL DISSECTION IN ELDERLY: TREATMENT AND
LONG-TERM OUTCOMES

P0758 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE


MANAGEMENT OF PATIENTS WITH COLORECTAL LESIONS: A
CONSENSUS REPORT BASED ON CLINICAL EVIDENCE

R. Kobayashi1,*, K. HIRASAWA1, H. KANEKO1, M. MAKAZU1, C. SATO1,


A. KOKAWA1, S. MAEDA2
1
Division of Endoscopy, Yokohama City University Medical Center, 2Department
of gastroenterology, Yokohama City University Graduate School of Medicine,
Yokohama city, Japan
Contact E-mail Address: ryo_1001@yokohama-cu.ac.jp

S.K. Singh1,*, R. Arsenescu2, H. Bertani3, F. Caillol4, D. Carr-Locke5,


K. Chang6, A. Dlugosz7, J.-P. Galmiche8, S.-I. Gan9, K.Y. Ho10, V. Konda11,
H. Neumann12, F. Prat13, P. Sharma14, K. Wang15, A. Zfass16
1
Gastroenterology / Endoscopy, Boston University / VA Boston, Boston, MA, 2The
Ohio State University, Columbus, United States, 3Nuovo Ospedale Civile
SantAgostino Estense, Modena, Italy, 4CLCC Institut Paoli-Calmettes, Marseille,
France, 5Beth Israel Medical Center, New York, 6University of California Irvine
Medical Center, Orange, United States, 7Karolinska University Hospital
Huddinge, Stockholm, Sweden, 8CHU Nantes, Nantes, France, 9Virginia Mason
Medical Center, Seattle, United States, 10National University Hospital, Singapore,
Singapore, 11University of Chicago Medical Center, Chicago, United States,
12
Universitaetsklinikum Erlangen, Erlangen, Germany, 13Hopital Cochin, Paris,
France, 14VA Kansas City Medical Center, Kansas City, 15Mayo Clinic Rochester,
Rochester, 16VA Richmond Medical Center, Richmond, United States
Contact E-mail Address: singhsk@bu.edu

Size
Recurrence
21/90 (23.3%)

55mm
3/34 (8.8%)

60mm
7/54 (12.9%)

70mm
9/63 (14.2%)
p 0.002

470mm
12/27 (44.4%)

INTRODUCTION: Endoscopic submucosal dissection (ESD) is becoming widespread as a treatment of superficial colorectal neoplasm; however, the efficacy
and safety of colorectal ESD in elderly patients has not been fully evaluated.
AIMS & METHODS: In the present study, we assessed the treatment and longterm outcomes of colorectal ESD in elderly patients.
Between April 2008 and March 2014, 285 consecutive superficial colorectal
tumors in 267 patients were treated using ESD. Patients were divided into two
groups; elderly (75 years of age or older) and non-elderly (less than 75 years of
age), then were retrospectively compared to patient and tumor characteristics
and treatment outcome.
Long-term outcomes in elderly patients were also evaluated.
RESULTS: The elderly group comprised 93 lesions in 83 patients and nonelderly group comprised 192 lesions in 184 patients.
No significant differences were observed between the two groups with respect to
patient and tumor characteristics as the following factors: sex, tumor location,
tumor depth, tumor size, tumor morphology.
In all patients, the rates of en bloc resection, R0 resection and curative resection
were 98.9% (282/285), 90.2% (257/285) and 82.5% (235/285) respectively. Mean
procedure time was 67.2 minutes (range 10-273 minutes), the rate of delayed
bleeding was 3.9% (11/285) and the rate of perforation was 9.5% (27/285).
There were no significant differences between the two groups in the rates of en
bloc resection, R0 resection, curative resection, delayed bleeding, perforation,
and procedure time.
In 83 elderly patients, during a median follow-up period of 20.2 months (range
1.4-63 months), 6 patients were excluded from the long-term prognosis analysis
because of missing follow-up. Four of 16 patients who judged as non-curative
resection underwent additional surgery, and the others requested only observation. Two of 77 patients (2.6%) died of infection of unknown cause (n 1) and
heart failure (n 1). The 3- and 5-year overall survival rates were 96.4% and
87.7%, respectively. However, we did not observe local or distant recurrences in
any of the patients were followed up. Therefore, the 3- and 5-year disease-specific
survival rates were 100%.
CONCLUSION: Because there was no significant difference in treatment outcome between in elderly and non-elderly group, colorectal ESD could be used as
a treatment choice for superficial colorectal tumors in elderly patients. However,
many of the elderly non-curative cases were observed without additional surgical
treatment, implying that such patients are necessary for careful follow-up by
computed tomography (CT) or measuring tumor markers.
Disclosure of Interest: None declared
P0757 A COMPARATIVE STUDY OF TWO DIFFERENT SNARES FOR
THE COMPLETENESS OF POLYP EXCISION
S. Din1,*, A. Ball1, S. Riley1, P. Kitsanta2, S. Johal1
1
Gastroenterology, 2Histopathology, Sheffield Teaching Hospitals NHS
Foundation Trust, Sheffield, United Kingdom
INTRODUCTION: Polypectomy with cold snare is a frequently used technique
for the removal of small colorectal polyps. The influence of snare type on completeness of excision is unknown. We have therefore compared the effectiveness
of two different snares.
AIMS & METHODS: Patients attending for colonoscopy at Sheffield Teaching
Hospitals, England were prospectively included in the study. We assessed the
endoscopic and histological completeness of excision following cold snare of 37mm polyps using the Exacto mini-snare (diameter 0.30mm) and Olympus minisnare (diameter 0.47mm). Prior to the study, consensus regarding the endoscopic
completeness of excision was standardised to complete, incomplete or uncertain
using the Delphi method. Completeness of excision was aided by chromoendoscopy (indigo carmine 0.1%). The primary outcome was endoscopic completeness of excision. Secondary outcome measures included: completeness of

INTRODUCTION: Recent studies have highlighted the role of Confocal Laser


Endomicroscopy (CLE) for the characterization of colorectal lesions in vivo,
specifically for the real time characterization of polyps and endoscopic mucosal
resection (EMR) sites.
AIMS & METHODS: We sought to develop consensus recommendations for the
role of CLE in the management of patients with colorectal lesions. To this end, a
single CLE expert developed a series of preliminary statements on the use of CLE
for the characterization of colorectal lesions based on the available clinical evidence. Twenty statements were submitted for external review by a group of 16
gastrointestinal CLE experts using a modified Delphi approach. After two
rounds of votes to assess the quality of evidence and strength of recommendations based on relevant studies, statements were adopted if the threshold of
agreement exceeded 75%.
RESULTS: 15 of 20 statements achieved consensus and were adopted: CLE has
been shown to be highly accurate for real-time histopathological classification of
colonic neoplasia in situ. CLE criteria can be used to accurately and reliably
identify normal, hyperplastic, adenomatous (dysplastic), and cancerous
mucosa; criteria for serrated neoplasia require further validation. CLE criteria
characterize colonic tissue accurately both in real time during endoscopy as well
as off-line. CLE can be used to define the extent of flat lesions. The combination
of CLE and virtual chromoendoscopy (VCE) is highly accurate for classifying
colonic polyps 55 mm both in real time and offline and should undergo further
study toward enabling a resect-and-discard approach. A diagnosis of intramucosal carcinoma and/or high-grade dysplasia by CLE alone is sufficient to trigger
an appropriate therapeutic resection. CLE can be used to classify lesions and
define margins for EMR/ESD. CLE has a role in resurveillance 3-12 months
following EMR/ESD of advanced colonic neoplasia. Absence of residual neoplasia by CLE and VCE at 3-12 months obviates the need for re-EMR/ablation.
The extent of therapy for residual neoplasia post-EMR can be guided in real time
by the combination of CLE and VCE.
CONCLUSION: According to a panel of 16 gastrointestinal endoscopy experts
in Confocal Laser Endomicroscopy, CLE is an important adjunct to current
endoscopic practice for the management of colorectal lesions. Standardized
guidelines are in development to serve as an educational resource for physicians
to provide increasingly personalized, state-of-the-art care for their patients.
Disclosure of Interest: None declared
P0759 IMMEDIATE AND DELAYED BLEEDING AFTER ERCP:
RESULTS FROM SINGLE CENTRE EXPERIENCE AT A DISTRICT
GENERAL HOSPITAL IN JAPAN
H. Hisai1,*, T. Hirako1, Y. Ikeda1, S. Miura1, Y. Koshiba1, E. Miyazaki1
Department of Gastroenterology, Japanese Red Cross Date General Hospital,
Date, Japan
1

INTRODUCTION: Bleeding following endoscopic retrograde cholangiopancreatography (ERCP) including endoscopic sphincterotomy (ES) is one of the
most frequent complications, and has been reported in 1-10% of patients.
Haemorrhage that cannot be controlled by conservative management needs to
be controlled endoscopically, radiologically, or surgically. However, there are few
reports about the incidence and the outcomes at a district hospital.

A341

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: The aim of this study was to assess the incidence of
ERCP-related haemorrhage and the clinical outcomes in the district general
hospital setting. A review of all patients undergoing ERCP at our institution
from April 1996 and March 2014 was performed to assess the ERCP-related
haemorrhage. ERCP-related haemorrhage was classified according to the
timing of bleeding. Immediate bleeding was defined as any haemorrhage
during ERCP and warranting endoscopic haemostasis within the procedure following epinephrine spray. A diagnosis and severity of delayed bleeding was made
according to Cottons classification (GIE 1991).
RESULTS: Out of 6002 ERCPs, we performed ES in 975 patients, needle knife
sphincterotomy (NKS) in 195 patients, NKS followed by ES in 22 patients,
endoscopic papillectomy in 12 patients and endoscopic large balloon dilatation
in 47 patients. No patients were taking anticoagulants at the time of ERCP.
During ERCP, 48 patients (0.80%) experienced immediate bleeding. All patients
underwent endoscopic haemostatic method including balloon tanponade, dilute
epinephrine (1:10000), heater probe, clipping, covered metallic stent and combined hemostatic procedures. Initial haemostasis was achieved in all patients.
However, delayed bleeding occurred in 3 patients (6%). By definition, delayed
bleeding occurred in 26 patients (0.43%). There were 14, 5 and 7 cases of mild,
moderate and severe bleeding, respectively. The time period between ERCP and
haemorrhage ranged from 1 d to 14 d (median 4 d). The time to onset of delayed
bleeding was not significantly different between patients with or without immediate bleeding. Seventeen out of 26 (65%) were managed endoscopically with
various haemostatic methods including dilute epinephrine, heater probe, argon
plasma coagulation, clipping, fibrin glue, covered metallic stent and combined
procedures. Initial haemostasis was successfully attained in all patients. The rebleeding rate was 15% (4 of 26). The treatment for the 4 patients with re-bleeding
was as follows: 1 underwent 1 session, 1 underwent 2 sessions and 2 underwent 3
sessions of endoscopic combined procedures (2 patients required fibrin glue) and
the bleeding was finally controlled. No patients required angiographic embolisation and surgery. No complications of the hemostatic procedure occurred in any
patients. There was no bleeding-related death.
CONCLUSION: Early recognition and appropriate management of ERCPrelated haemorrhage is crucial for optimal results.
Disclosure of Interest: None declared
P0760 USEFULNESS OF CAP-ASSISTED ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY IN PATIENTS WITH
DIFFICULT CANNULATION DUE TO PERIAMPULLARY
DIVERTICULUM
H. Yoon1,*, J.H. Cho1, H.M. Kim2, Y.J. Kim1, Y.S. Kim1
1
Internal Medicine, Gachon University Gil Medical Center, Incheon, 2Internal
Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea, Republic
Of
Contact E-mail Address: hwa9620@naver.com
INTRODUCTION: Successful biliary cannulation is an essential for therapeutic
retrograde cholangiopancreatography (ERCP). In special cases of difficult cannulation due to anatomy, diverticulum, lack of space or bulky papilla other
methods are needed. Various methods depending on the practices of the endoscopist have been developed to overcome difficult cannulation.
AIMS & METHODS: We report a retrospective case series of patients with
difficult cannulation due to periampullary diverticulum and assess the utility
and safety of cap-assisted ERCP for biliary cannulation.
From November 2013 to March 2014, inclusion criteria were: (a) documented
periampullary diverticulum; and (b) use of cap-assisted ERCP as a rescue method
on the first endoscopic encounter after failed attempts to perform ERCP with a
standard side-viewing endoscope. Among 73 patients with periampullary diverticulum, 5 consecutive patients (6.8%) underwent therapeutic ERCP using a capfitted forward-viewing endoscope as a rescue method due to difficult biliary
cannulation.
RESULTS: There were three men and two women, with median age of 69 years
(range 5390 years). The indications for ERCP were bile duct stones (n 4) and
common bile duct stricture (n 1). All of the ampulla is located at 6 oclock. The
causes of difficult biliary cannulation were tangential approach in two patients and
hidden papilla in three patients. A selective biliary cannulation was achieved with
needle knife fistulotomy in four patients. The mean number of ERCP sessions was
1.8 per patient and the mean procedure time was thirty eight minutes. Therapeutic
ERCP was successfully performed in all patients. In four patients, the therapeutic
ERCP was completed with a cap-fitted forward-viewing endoscope. But in the only
one patient who had a pyloric stenosis with bulbar deformity due to duodenal ulcer
scar, CBD stones were successfully removed by percutaneous procedure combined
with rendezvous method although we performed endoscopic balloon dilation of
the stenosis. The one patient undergoing biopsy was pathologically confirmed to
carcinoma of ampulla of Vater. This patient was managed previously with biliary
stent insertion due to biliary stricture.
Two patients experienced complications; post-ERCP pancreatitis and hyperamylasemia. But their complications were not clinically significant and self limitied.
CONCLUSION: As a rescue method, cap-assisted ERCP is effective and safe
technique in patients with difficult cannulation due to periampullary
diverticulum.
REFERENCES
1. Myung DS, Park CH, Koh HR, et al. Cap-assisted ERCP in patients with
difficult cannulation due to periampullary diverticulum. Endoscopy 2014; 46:
352355.
2. Park CH, Lee WS, Joo YE, et al. Cap-assisted ERCP in patients with a
Billroth II gastrectomy. Gastrointest Endosc 2007; 66: 612615.
3. Udd M, Kylanpaa L and Halttunen J. Management of difficult bile duct
cannulation in ERCP. World J Gastrointest Endosc 2010; 2: 97103.
Disclosure of Interest: None declared

P0761 SEQUENTIAL PERFORMANCE OF DOUBLE GUIDEWIRE


TECHNIQUE AND TRANSPANCREATIC PRECUT
SPHINCTEROTOMY IN DIFFICULT BILIARY CANNULATION
J. Park 1,*, J.H. Chang1,2, C.W. Kim1, S.W. Han1
The Catholic University of Korea, Seoul, 2Internal Medicine, The Catholic
University of Korea, Bucheon, Korea, Republic Of
1

INTRODUCTION: Double guidewire technique (DTG) and transpancreatic


precut sphincterotomy (TPS) are alternative techniques in failed standard biliary
cannulation during endoscopic retrograde cholangiopancreatography (ERCP)
when a guidewire proceeds into the pancreatic duct. However, the sequential
performance of TPS after DTG has not been evaluated.
AIMS & METHODS: We aimed to investigate the usefulness and complications
of seqeuntial DTG-TPS in comparison with needle knife precut (NK). We consecutively enrolled 612 patients with na ve papilla undergoing ERCP for biliary
cannulation between March 2010 and April 2014. In cases of unsuccessful standard technique, DTG or NK was performed according to the guidewire passage
through the pancreatic duct. TPS was sequentially performed when DTG had
failed. Patients demographics, laboratory, and procedure-related data were analyzed retrospectively.
RESULTS: During 612 ERCPs, DTG and NK was attempted in 67 and 58
patients, respectively. Sequential DTG-TPS were performed in 38 patients.
Successful biliary cannulation was performed in 42%, 74%, and 66% of the
DTG, TPS, and NK group, respectively (P 0.002). The cannulation rate was
higher in the sequential DTG-TPS group (85%) than in the NK group
(P 0.014). Post-ERCP pancreatitis (PEP) occurred in 37% of the sequential
DTG-TPS group and in 10% of the NK group (P 0.002). In the sequential
DTG-TPS group, PEP developed in 24% patients with pancreatic duct (PD)
stent, but in 62% patients without PD stent (P 0.023). Among them, one
patient without PD stent expired due to severe pancreatitis.
CONCLUSION: The sequential DTG-TPS is a useful alternative technique for
biliary cannulation compared with NK in patients who have failed standard
technique. Their rate of PEP was higher than that in the NK group, but PD
stent had a protective role over PEP.
Disclosure of Interest: None declared
P0762 ENDOSCOPIC
RETROGRADE
CHOLANGIOPANCREATOGRAPHY FOR SUSPECTED
CHOLEDOCHOLITHIASIS FROM GUIDELINES TO CLINICAL
PRACTICE
J. Magalhaes1,*, B. Rosa1, J. Cotter1,2
1
Gastroenterology Department, Centro Hospitalar do Alto Ave, Guimaraes, 2Life
and Health Sciences Research Institute (ICVS), School of Health Sciences,
University of Minho, Braga/Guimaraes, Portugal
Contact E-mail Address: joanaltmagalhaes@gmail.com
INTRODUCTION: Patients suspected of having choledocholithiasis are diagnosed with a combination of laboratory tests and/or imaging studies. The
American Society for Gastrointestinal Endoscopy (ASGE) proposes a stratification of patients according to the risk for choledocholithiasis, influencing subsequent management.
AIMS & METHODS: The aim of this study was to assess the practical applicability and to validate the current ASGE guidelines in our population. This was a
retrospective single center study, covering a 4-year period, from January 2010 to
December 2013. All patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis were included. Based
on the presence or absence of predictors of choledocholithiasis (clinical ascending
cholangitis, common bile duct (CBD) stones on ultrasonography (US), total
bilirubin 44mg/dL, dilated CBD on US, total bilirubin 1,8-4mg/dL, abnormal
liver function test, age 455 years and gallstone pancreatitis), patients were stratified in low, intermediate or high risk for choledocholithiasis. For each predictor
and risk group we used the Chi-square to evaluate the statistical associations with
the presence of choledocolithiasis at ERCP. Statistical analysis was performed
using SPSS version 21.0. A p value of less than 0.05 was considered statistically
significant.
RESULTS: A total of 268 ERCPs were performed for suspected choledocholithiasis. Except for gallstone pancreatitis (p 0.063), all other predictors of
choledocholitiasis (clinical ascending cholangitis, p 0.001; CBD stones on
US, p50.001; total bilirubin 44mg/dL, p 0.035; total bilirubin 1,8-4mg/dL,
p 0.001; dilated CBD on US, p50.001; abnormal liver function test, p 0.012;
age 455 years, p 0.002) showed a statistically significant association with the
presence of choledocholithiasis at ERCP. Approximately four fifths of patients in
the high risk group (79.8%, 154/193) had confirmed choledocholithiasis on
ERCP, versus 34.2% (25/73) and 0 (0/2) in the intermediate and low risk
groups, respectively. The definition of high risk group had a sensitivity of
86%, positive predictive value 79,8% and specificity 56.2% for the presence of
choledocholithiasis at ERCP.
CONCLUSION: The use of clinical, analytical and imaging predictors, as well as
risk stratification according to ASGE guidelines, may improve risk estimation of
choledocholithiasis and should be considered to optimize patients selection for
ERCP. However, even in the high risk group the specificity was low (56.2%),
meaning that a significant proportion of patients (20%) will still perform ERCP
unnecessarily. Thus, at this point, it seems advisable that also high risk
patients undergo further testing before being submitted to ERCP, similarly to
those patients with intermediate risk, while for patients with low-risk of
choledocholithiasis a watchful waiting strategy seems adequate.
Disclosure of Interest: None declared

A342
P0763 THE EFFECT OF RECTAL KETOPROFEN IN THE PREVENTION
OF POST ERCP ACUTE PANCREATITIS
J. Amara1,*, C. Cellier 1, E. Samaha1, G. Rahmi1, M. Barret 1, J.M. Canard 1,
A. Vienne1, B. Hotayt2
1
Hopital Europeen Georges Pompidou, Paris, France, 2Belle Vue Medical Center,
Beyrouth, Lebanon
Contact E-mail Address: jph.amara@gmail.com
INTRODUCTION: Acute pancreatitis is the most common and the most fearful
complication of endoscopic retrograde cholangiopancreatography (ERCP). A
recently published meta-analysis reported that a single dose of indomethacin
or diclofenac (100 mg) administred rectally before or immediately after ERCP
decreases the incidence of post ERCP pancreatitis (PEP).
AIMS & METHODS: A retrospective single-center non randomized study was
conducted with 304 patients who underwent a primary ERCP. Patients were
divided into 2 groups. The patients in the first group had a single dose of ketoprofen 100mg administred rectally immediately after ERCP. The 2nd group was a
control group.
The aim of this study was to determine whether prophylactic rectal ketoprofen
will reduce the incidence of PEP and to determine the risk factors of this
complication.
RESULTS: Three hundred and four patients (M/F 197/107, Mean age 62.4
y.o) were included. 107 patients (35.2%) were in the first group. The groups were
similar with regard to patient demographics and to patient and procedure risk
factors for PEP. The overall incidence of PEP was 6.9%: 4.6% (5/107) in the
group 1 versus 8.1% (16/197) in the placebo group (p 0.34, IC 95%). The
pancreatitis was graded as severe in 33% of the patients. There was no significant
difference between the groups in the frequency or severity of PEP. Two risk
factors were associated with a higher incidence of PEP:a difficult cannulation
of the common bile duct (52.4 vs 16%, p 0.0004. IC 95%) and contrast
injection into the pancreatic duct (47.62 vs 24.38 %, p 0.008, IC 95%).
CONCLUSION: Prophylactic rectally administered ketoprofen (100mg) did not
affect the frequency or severity of PEP. Prospective randomized studies with a
higher number of patients are needed.
REFERENCES
1-Dumonceau JM, Andriulli A, Deviere J, et al. European Society of
Gastrointestinal Endoscopy (ESGE) Guideline: Prophylaxis of post-ERCP pancreatitis. Endoscopy 2010; 42: 503515.
2-Feurer ME and Adler DG. Post ERCP pancreatitis: Review of current preventive strategies. Curr Opin Gastroenterol 2012; 28: 280-286.
3- Elmunzer BJ, Waljee AK, Elta GH, et al. A metaanalysis of rectal NSAIDS in
the prevention of post-ERCP pancreatitis. Gut 2008; 57: 12621267.
4- Cheon YK, Cho KB, Watkins JL, et al. Efficacy of diclofenac in the prevention of post-ERCP pancreatitis in predominantly high-risk patients: a randomized double-blind prospective trial. Gastrointest Endosc 2007; 66: 1126-1132.
5- Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal
indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012; 366: 1414
1422.
6- Elmunzer BJ, Higgins PDR, Saini SD, et al. Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing
high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective
clinical trial data. Am J Gastroenterol 2013; 108: 410415.
Disclosure of Interest: None declared
P0764 ANALYSIS OF THE ROLE OF PANCREATIC DUCTAL FUSION
ANOMALIES AS A RISK FACTOR FOR DEVELOPMENT OF POSTERCP PANCREATITIS
J.J. Vila1,2,*, G.D. L. H. Belen1, D. Ruiz-Clavijo1, C. Prieto1, F. Bolado1,
J. Urman1, M.A. Casi1, I. Fernandez-Urien2, F.J. Jimenez2
1
Biliary and Pancreatic Diseases Unit., 2Endoscopy Unit., Complejo Hospitalario
de Navarra, Pamplona, Spain
Contact E-mail Address: juanjvila@gmail.com
INTRODUCTION: Pancreatic ductal fusion occurs in the early weeks of gestation. It has been suggested the possible association between pancreatic ductal
morphology and the incidence of post-ERCP pancreatitis.
AIMS & METHODS: Our aim was to evaluate the possible association between
abnormal fusion of the pancreatic duct and the development of post- ERCP
pancreatitis. We reviewed the pancreatic ERCPs (PERCP) performed in our
center from June 2009 to June 2013. The wirsungrafies were blindly reviewed
by one ERCPist who classified the pancreatic ductal fusion unaware of the
identity and evolution of patients after PERCP. The ductal fusion was classified
into four groups: Normal (Group I), when the dorsal duct joined the upper
branch of the ventral duct and Santorini duct; Ansa Pancreatica (Group II),
when the dorsal duct was fused to the upper branch of the ventral duct but
the Santorini duct was fused to the lower branch of the ventral duct;
Pancreatic Loop (Group III), when the dorsal duct was fused to the lower
branch of the ventral duct; and Pancreas Divisum (Group IV), when there was
no fusion between dorsal and ventral duct. Incomplete wirsungrafies which could
not be classified in either group were considered indeterminate and not analyzed.
Groups II, III and IV were considered together as Fusion Anomalies Group
(FA). We compared the incidence of post-ERCP pancreatitis in each of the
groups with respect to the rest and the AF group with Group I.
RESULTS: We performed 134 PERCPs in 68 patients during the inclusion
period. We were able to determine with certainty the type of ductal fusion in
56 patients (40 men). Twenty-seven patients suffered a previous acute pancreatitis
bout and 28 had chronic pancreatitis. Women had significantly more FA (69 %
vs 37 %, p 0.04). Thirty patients were included in Group I; 10 in Group II; 3 in
Group III and 13 in Group IV. Thus, 26 patients were included in FA Group.

United European Gastroenterology Journal 2(1S)


Complications occurred in 8 patients (14 %), pancreatitis in 5 of them (8.9%).
Only Group III was significantly associated with a higher rate of post-ERCP
pancreatitis (67%vs11.3%,p 0.019). The incidence of post-ERCP pancreatitis
in Group II and IV was 10 % and 15.4 % respectively. FA Group showed a
significantly higher incidence of post-ERCP pancreatitis compared with Group I
(19.2%vs0%,p 0.017) and this comparison remained significant after adjusting
for sex (p 0.017). Variables such previous acute or chronic pancreatitis, sex and
placement of pancreatic stent did not influenced post-ERCP pancreatitis incidence (p40.05).
CONCLUSION: Pancreatic ductal fusion anomalies are a risk factor for development of post-ERCP pancreatitis. This association should be confirmed by
means of prospective comparative studies.
Disclosure of Interest: None declared
P0765 RETROPERITONEAL DUODENAL PERFORATION (TYPE II)
AFTER ERCP IS A RARE BUT SEVERE COMPLICATION. A
SINGLE - CENTER REVIEW OF TEN - YEAR EXPERIENCE
K.C. Thomopoulos1,*, G. I. Theocharis1, C. Konstantakis1, V. Theopistos1,
C.K. Triantos1
1
GASTROENTEROLOGY, UNIVERSITY HOSPITAL OF PATRAS,
PATRAS, Greece
Contact E-mail Address: kxthomo@hotmail.com
INTRODUCTION: Duodenal perforation in the periampullary region due to
sphincterotomy (Type II) is a rare post - ERCP complication with significant
mortality. The aim of this study was to determine the incidence of retroperitoneal
duodenal perforations after periampullary interventions, management options,
and clinical outcome.
AIMS & METHODS: All cases of retroperitoneal duodenal perforation (Type
II) after ERCP during a ten year period (1/2004 - 12/2013) in our Department
were retrospectivelly reviewed. All patients were initially treated with broadspectrum antibiotics, nasogastric aspiration and parental nutrition and/or CTguided drainage when needed.
RESULTS: A total of 19 patients with retroperitoneal duodenal perforation
(Type II) after 3428 ERCPs (0.55%) were managed. Indications for performing
a periampullary procedure were known or suspected choledocholithiasis in 15
(79%) and biliary stricture in 4 patients. Diagnosis was made during the first 12h,
(during the procedure in 3 cases). Radiological drainage was performed in 7
patients (36%) and were successful in all patients except one who eventually
required surgery. Surgical intervention was required in 4 patients (21%). Total
parental nutrition was given to 4 patients (21%). Three patients died (two post postoperatively) giving an overall mortality of 15.8%.
CONCLUSION: Retroperitoneal duodenal perforation (Type II) is a rare complication after ERCP with high morbidity and mortality but aggressive conservative management seems effective for the majority of cases.
Disclosure of Interest: None declared
P0766 USEFULNESS OF ENDOSCOPIC PAPILLARY LARGE BALLOON
DILATION IN THE TREATMENT OF LARGE OR MULTIPLE
COMMON BILE DUCT STONES: COMPARISON WITH
ENDOSCOPIC SPHINCTEROTOMY ALONE
K. Tsuchida1,*, M. Iwasaki1, M. Tsubouchi1, C. Tsuchida1, N. Yoshitake1,
T. Koike1, K. Tominaga1, T. Sasai1, M. Iijima1, H. Hiraishi1
1
Gastroenterology, Dokkyo medical university, Simotsugagunn Mibumachi, Japan
Contact E-mail Address: tsuchida@dokkyomed.ac.jp
INTRODUCTION: Endoscopic sphincterotomy (EST) is currently recognized as
the main treatment for choledocholithiasis. However, the treatment of large
common bile duct stones (15 mm in diameter) or multiple common bile duct
stones (3 or more stones) by EST alone is difficult, and a new therapeutic procedure to supplant EST is needed. Sporadic reports have shown the usefulness of
endoscopic papillary large balloon dilation (EPLBD) in the treatment of
common bile duct stones, and this technique is anticipated to replace use of
EST alone. This study aimed to comparatively assess the therapeutic outcomes
and short-term complications of EST versus EPLBD in cases of biliary tract
stones 15 mm in diameter or multiple (3 or more) stones presumed to be
rather refractory to EST alone.
AIMS & METHODS: Data from 70 cases of choledocholithiasis (15 mm in
diameter or 3 stones) that were treated (EPLBD, n 34; EST, n 36) in our
department between April 2010 and March 2013 were comparatively reviewed
and analysed with respect to stone removal success rate, success rate of complete
stone removal in 1st session, procedure time, concomitant mechanical lithotripsy
(ML) application status, and short-term complications. Stone size and number
were checked by endoscopic cholangiography, and the patients treated using
EPLBD underwent EST before balloon dilation. EPLBD was performed using
1218-mm-diameter balloons, and stone collection was performed using a
Dormia basket or retrieval balloon. ML was added to the procedure in case of
difficulty in expelling the stones.
RESULTS: The stone removal success rate was comparable between groups
(EPLBD 100% vs. EST 89%, p 0.115). The EPLBD group exhibited a significantly higher success rate of a complete stone removal in 1st session (EPLBD
88% vs. EST 56%, p 0.03). Further, the procedure time was significantly
shorter for the EPLBD group (EPLBD 42 min vs. EST 67 min, p 0.011), and
the concomitant ML application rate was significantly lower for the EPLBD
group (EPLBD 50% vs. EST 94%, p 5 0.001). Short-term complication included
pancreatitis in 2 patients and haemorrhage in 1 patient of the EPLBD group and
pancreatitis in 8 patients and haemorrhage in 2 patients of the EST group
(EPLBD 9% vs. EST 25%, p 0.112), but there was no statistically significant
intergroup difference.

A343

United European Gastroenterology Journal 2(1S)


CONCLUSION: We successfully treated large moulded (15-mm diameter)
stone or multiple stone choledocholithiasis by EPLBD with fewer sessions and
a shorter procedure time compared to EST alone. Our findings suggest the
usefulness of EPLBD for difficult cases. However, it is necessary to accumulate
further experience of cases and examine long-term complications.
Disclosure of Interest: None declared
P0767 PER
ENDOSCOPIC
MANAGEMENT
OF
ALVEOLAR
ECHINOCCOSIS BILIARY COMPLICATIONS: A EUROPEAN
SURVEY
S. Ambregna1, L. Vuitton1,*, S. Koch1, M.C. Sulz 2, J.-B. Chevaux3,
D. Moradpour 4, P. Bichard5, F. Prat6, G. Vanbiervliet7, E. Kull8, C. Richou9,
D.A. Vuitton10, S. Bresson-Hadni10
1
gastroenterology, Besancon university hospital, Besancon, France, 2Kantonsspital,
St. Gallen, Switzerland, 3University hospital, Nancy, France, 4University hospital,
Lausanne, 5University hospital, Geneva, Switzerland, 6aphp, Paris, 7University
hospital, Nice, 8CHR, Metz, 9University hospital, 10France & WHO-Collaborating
Centre for Prevention and Treatment of Human Echinococcosis, Besancon, France
Contact E-mail Address: lvuitton@chu-besancon.fr
INTRODUCTION: Cholestasis and cholangitis are among the most common
and life-threatening complications of Alveolar Echinococcosis (AE) of the
liver, because of the liver invasion by the metacestode associated with extensive
fibro-inflammatory host reaction. Biliary complications of AE are usually treated
by surgery or radiological percutaneous biliary drainage. During the last decade
the indication of per-endoscopic biliary drainage following endoscopic retrograde cholangio-pancreatography (ERCP) has markedly increased in various
benign or malignant biliary tree obstructions, because of its less invasive
nature and better outcome. AE is an emerging indication in this field; only
little is known about its efficacy and safety.
AIMS & METHODS: Our aim was to collect and analyse the European experience in per-endoscopic management of AE biliary complications. All European
physicians practicing ERCP and/or in charge of AE patients were recruited
directly or through various professional/scientific associations to participate in
the retrospective survey. Data were collected from May, 2013 to January, 2014.
Physicians were asked to report any AE case with ERCP. Data on patients and
disease characteristics, endoscopic techniques and follow-up filled-out through
an online questionnaire were analysed. Ethical Committee of Franche-Comte
Hospitals approved this study.
RESULTS: Between 1986 and 2014, 12 centres performed ERCP for AE in
Europe. Detailed data available for 23 patients (18 men and 5 women) in 8
centres were analysed. Sixty-one ERCP were performed (median: 2 {1-9}
ERCP per patient). Patients were 55-years-old at the time of AE diagnosis and
60-years-old at the time of the first ERCP. Indications for ERCP were: biliary
pain, 14 (23%), cholangitis, 24 (39%), jaundice or chronic cholestasis, 22 (36%).
Seventy-four plastic stents and 7 fully (5) or partially (2) covered self expandable
metallic stents (SEMS) were placed in the biliary tree. The average time between
two stenting procedures was 19.5 weeks (1-98). Two patients needed surgical
intervention or radiological drainage because of endoscopic treatment failure.
There were 11 adverse events (18%): 1 perforation, 1 hepatic collection, 4
acute pancreatitis, and 5 cholangitis. Resolution of cholestasis was obtained in
42/44 therapeutic ERCP (95.4 %). Biliary duct calibration was obtained by stent
placement in 8 patients after an average of 2 procedures; definitive stent removal
was possible after a median time of 45 weeks of treatment. Among them, recurrence of stenosis led to a new stent placement 4 years later in 1 patient and
gallstones extraction in 2 patients.
CONCLUSION: Endoscopic retrograde drainage is efficient in AE with biliary
obstruction. ERCP and stenting, which are less invasive than surgery and avoid
long-term external drainage, may be proposed as a valid alternative to radiological and surgical drainage. Several procedures with stenting are usually needed
to ensure long-term efficacy and using of antibiotics are necessary during and
after the ERCP.
Disclosure of Interest: None declared
P0768 A STUDY TO INVESTIGATE RISK FACTORS FOR ASPIRATION
PNEUMONIA AFTER ERCP
M. Yamagami1,*, N. Toda1, S. Kawamura1, Y. Karasawa1, Y. Hayata1, D. Ito1,
T. Yamada1, K. Kawanishi1, K. Sato1, K. Kojima1, T. Ohki1, T. Arizumi1,
M. Seki1, K. Tagawa1
1
Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan
Contact E-mail Address: mari.umin.tjo@gmail.com
INTRODUCTION: Aspiration pneumonia is the one of complications of various
Endoscopic procedures. But there have been few reports of that complication
after Endoscopic retrograde cholangiopancreatography (ERCP).
AIMS & METHODS: The aim of this study is to identify the rate and risk
factors for aspiration pneumonia after ERCP.
978 consecutive patients who underwent ERCP between January 2011 and
December 2013 were included. The cumulative rate and potential risk factors
for aspiration pneumonia, such as patient attributes (Age, sex, underlying conditions, and medication) and ERCP procedures were retrospectively investigated.
RESULTS: Of the 978 patients 673 patients were male (68.8%). The median age
was 71.4 years (29-99y.o). 55 patients (5.62%) were diagnosed with aspiration
pneumonia after ERCP. Age over 75years (OR:5.11 P50.0001), a procedure
time of 430min (OR2.31 P50.0059), the infusion of naloxone (OR :3.68
p 0.0151), history of heart disease (OR: 2.24 p 0.0083), eGFR530 (OR
:5.45 P50.001), hemodialysis (OR :5.95 P50.0001), cancer-bearing (OR :1.96
p 0.03 ), diabetes (OR :2.08 p 0.0213), history of cerebral infarction (OR:3.68
P50.0001) and serum Alb53.5mg/dl (OR:5.76 P50.0001)were identified as the

risk factors for the pneumonia by the univariate analysis. Multivariate analysis
showed age over 75years (OR:3.26 p 0.0018), a procedure time of 430min
(OR:2.55 p 0.0062), history of cerebral infarction (OR:3.06 p 0.0063),
serum Alb53.5mg/dl (OR:3.11 p 0.00016)and hemodialysis (OR:2.59
p 0.048)were revealed to be the significant risk factors for aspiration pneumonia after ERCP.
CONCLUSION: Age over 75years, a procedure time of 430min, history of
cerebral infarction, serum Alb53.5mg/dl and hemodialysis are the independent
risk factor for the aspiration pneumonia after ERCP. Careful attention should be
taken when managing patients with these attributes.
Disclosure of Interest: None declared
P0769 EVALUATION FOR ERCP USING A BALLOON ASSISTED
ENDOSCOPY IN PATIENTS WITH ALTERED
GASTROINTESTINAL ANATOMY: COMPARISON OF A SHORT
TYPE DOUBLE BALLOON ENDOSCOPE AND A NEWLY
DEVELOPED SHORT TYPE SINGLE BALLOON ENDOSCOPE
M. Shimatani1,*, M. Takaoka1, T. Mitsuyama1, H. Miyoshi1, T. Ikeura1,
K. Okazaki1
1
The Third Department of Internal Medicine, Kansai Medical University,
Hirakata, Japan
INTRODUCTION: The advent of the short type double balloon endoscope (sDBE) and the short type single balloon endoscope (s-SBE) radically made the
endoscopic approaches feasible for pancreatobiliary diseases in patients with
altered gastrointestinal anatomy, which had been considered unpractical.
Recently many papers are published to report the efficacy of using these techniques, however, there are so far few studies regarding the comparison of s-DBE
and s-SBE.
AIMS & METHODS: This present study aimed to evaluate the usefulness of a
newly developed s-SBE for therapeutic ERCP in patients with gastrointestinal
anatomy, and also to make a comparative assessment of the respective features
and the distinctions of s-DBE and s-SBE. From March 2013 to November 2013,
ERCP using a s-SBE (s-SB-ERCP) was performed in 26 postoperative patients
who had a reconstructed intestine in our hospital. We retrospectively evaluated
the success rate of reaching the blind end, the mean time required to reach the
blind end, the diagnostic success rate, the therapeutic success rate, the mean
procedure time, and complications. Among 26 patients, the s-SB- ERCP was
applied to those 18 patients who previously had undergone s-DB-ERCP and
required the recurrent procedure. It allowed us the unique comparison of the
s-DBE and the s-SBE in the same patients analyzing the data of the mean time
required to reach the blind end and the mean procedure time.
RESULTS: The success rate of reaching the blind end was 92.3% (24/26
patients). As for 2 patients in whom s-SBE failed to reach the blind end, the
procedure was successfully accomplished after switching the scope to s-DBE. The
mean time required to reach the blind end was 28.6 min. (range, 558 min). The
diagnostic success rate was 91.7% (22/24 patients). Regarding 2 patients in whom
cholangiography failed using s-SBE, they were the cases with Roux-en-Y gastrectomy and with na ve papilla. Switching the scope to s-DBE, the procedure
was successfully accomplished subsequently in both cases. Therapeutic success
rate was 100% (24/24 patients). Complication occurred in 1 patient (3.8%; 1/26
patients). Regarding the 18 patients who had previously undergone s-DB-ERCP,
s-SB-ERCP was successfully completed in 17 patients. The mean required time of
s-SBE to reach the blind end was 24.7 min. (range, 7-50 min.), whereas that of sDBE was 13.5 min. (range, 3-31 min.). The mean procedure time of s-SB-ERCP
was 52.3 min. (range, 16-107min.), whereas that of s-DB-ERCP was 70.4min.
(range, 21-168min.).
CONCLUSION: ERCP using a newly developed s-SBE for patients with gastrointestinal anatomy is safe and effective. In comparison with s-DBE, for the
present, we conclude that a newly developed s-SBE is advantageous in the
point of efficiency of performing ERCP-related interventions.
Disclosure of Interest: None declared
P0770 IMPACT
OF
PREOPERATIVE
ENDOSCOPIC
BILIARY
DRAINAGE ON POSTOPERATIVE COMPLICATIONS AFTER
PANCREATICODUODENOSTOMY FOR PERIAMPULLARY
CANCER
M. Chiba1,*, H. Imazu1, K. Kanazawa1, N. Mori1, H. Toyoizumi1,
N. Shimamoto1, H. Tajiri2
1
Department of Endoscopy, 2Division of Gastroenterology and Hepatology,
Department of Internal Medicine, The Jikei University School of Medicine, Tokyo,
Japan
Contact E-mail Address: ccl09720@yahoo.co.jp
INTRODUCTION: The clinical impact of preoperative endoscopic biliary drainage (P-EBD) on the outcome after pancreaticoduodenostomy (PD) for periampullary cancer with obstructive jaundice is not well known.
AIMS & METHODS: The present study was aimed to investigate whether PEBD was associated with increased morbidity after PD in patients with periampullary cancer. Patients with periampullary cancer, including pancreatic carcinoma, cholangiocarcinoma, and ampullary cancer, who underwent PD from
October 2003 to September 2013 were analyzed retrospectively. At our institution, P-EBD was routinely performed with a 7 Fr or 8.5 Fr plastic stent. In
addition, endoscopic nasobiliary drainage (ENBD) or switching to a larger caliber stent was done if biliary drainage was insufficient after P-EBD.
RESULTS: One hundred and sixty-seven patients who underwent PD (85 with
pancreatic carcinoma, 47 with cholangiocarcinoma, and 35 with ampullary carcinoma) were analyzed. 98 patients received P-EBD before PD and their mean
bilirubin level before P-EBD was 7.78 mg/dl. The other 69 patients underwent

A344
PD without preoperative biliary drainage and their mean bilirubin level before
PD was 1.59 mg/dl. Complications of P-EBD occurred in 34 patients (mild postERCP pancreatitis in 10, minor bile duct perforation by the guidewire in 1, stent
occlusion in 7, and insufficient biliary drainage in 16). There was no significant
difference in the time from the diagnosis of periampullary cancer until PD
between the patients with and without complications of P-EBD. Multivariate
regression analysis was performed to clarify the influence of P-EBD on postoperative complications, including pancreatic fistula. This analysis showed that
cholangiocarcinoma and ampullary carcinoma, but not pancreatic carcinoma,
were independent risk factors for postoperative complications (p 0.002,
OR 4.9), while P-EBD had no influence on postoperative complications.
Insufficient biliary drainage was also associated with postoperative complications, but not significantly (p 0.06, OR 4.1).
CONCLUSION: P-EBD was not associated with a higher incidence of postoperative complications. However, insufficient biliary drainage after P-EBD
was associated with postoperative complications, so the development of more
effective P-EBD might be useful to prevent such complications. The present
findings showed that P-EBD is a safe and effective procedure for distal malignant
biliary stricture due to periampullary cancer.
Disclosure of Interest: None declared
P0771 TECHNICAL SUCCESS WITH WIRE-GUIDED CANNULATION
FOR CHOLANGIOGRAPHY USING EARLY PANCREATIC GUIDE
WIRE PLACEMENT WITHOUT PRECUT SPHINCTEROTOMY
M. Murata1,*, O. Inatomi1, H. Hasegawa1, H. Ban1, M. Shioya1, S. Bamba1,
A. Andoh1
1
Division of Gastroenterology, SHIGA UNIVERSITY OF MEDICAL
SCIENCE, Otsu, Japan
INTRODUCTION: Wire-guided cannulation (WGC) and pancreatic guidewire
(P-GW) placement may increase the success rate of deep cannulation of the
common bile duct (CBD) and reduce the risk of complications compared with
contrast-assisted cannulation (CC); however, the data is still unclear. Previous
studies have suggested that repeated and unintentional injections or P-GW insertions may cause post-ERCP pancreatitis due to mechanical trauma or an increase
in the hydrostatic pressure of the main pancreatic duct. Therefore, we compared
the effect of early P-GW placement on the success of deep cannulations and the
risk of post-ERCP pancreatitis with the outcomes of WGC or CC procedures.
AIMS & METHODS: We retrospectively assessed 143 patients who required
ERCP because of known or suspected biliary duct disease; we excluded patients
who had previously undergone endoscopic manipulations. Early P-GW placement was defined as placing a guidewire after one or two attempts into the main
pancreatic duct without accomplishing cannulation of CBD. We performed
ERCP with CC as the initial option for CBD cannulation in the early period
and utilized WGC during the late period. The success rate of bile duct cannulation, the frequency and risk of post-ERCP pancreatitis and the frequency of
requiring a pre-cut sphincterotomy were evaluated.
RESULTS: Conventional cannulation was attempted in 47 patients and WGC in
80 patients. The success rate of CBD cannulation was 96.0% in all cases, with
91.4% in the CC group and 97.5% in the WGC group. The frequency of early PGW placement was 20.4% in all cases, with 10.9% in the CC group and 27.5% in
the WGC group. Pre-cut sphincterotomy was performed in only one patient in
the CC group. The frequency of post-ERCP pancreatitis was 7.6% in all cases
and was 9.2% in the CC group and 7.9% in the WGC group. There were no
significant differences among the groups with regard to each cannulation, the
surgeon, actual pancreatic guide wire placement and IDUS.
CONCLUSION: Early P-GW placement can lead to a high success rate for CBD
cannulation without the use of pre-cut sphincterotomy, and it does not increase
the incidence of post-ERCP pancreatitis. In addition, WGC may be more suitable for early P-GW placement when compared with CC. WGC with early P-GW
placement may be an ideal option for CBD cannulation in difficult cases and may
involve a low rate of pre-cut sphincterotomy.
Disclosure of Interest: None declared
P0772 DOWNSTREAM REVENUE GENERATED BY PROBE-BASED
CONFOCAL LASER ENDOMICROSCOPY (PCLE) IN
UNDETERMINED PANCREATICO-BILIARY LESIONS

United European Gastroenterology Journal 2(1S)


benign disease (n 3). Major post pCLE procedures included pancreaticoduodenectomy (n 4), exploratory laparotomy (n 2) and orthotopic liver transplant (n 1). Average revenue generated from procedures was 100,512 dollars
while the average net profit was 25,592 dollars per person.
CONCLUSION: For indeterminate pancreaticobiliary lesions, PCLE has major
economic implications. Profit generated from surgical and interventional radiology procedures after pCLE is significant and negates the cost of the procedure
itself. A large scale study examining the downstream financial impact of pCLE in
otherpathologic settings may be useful for further analysis.
Disclosure of Interest: None declared
P0773 EUS-GUIDED
DRAINAGE
OF
PERI-PANCREATIC
COLLECTIONS USING A FULLY COVERED SELF EXPANDING
METAL STENT WITH DOUBLE WALLED LUMEN APPOSING
FLANGES IN AN ELECTROCAUTERY ENHANCED DELIVERY
SYSTEM
E. Rinninella1,*, M. Dollhopf 2, A.Y. Sanchez 3, U. Will4, R. Kunda 5, S. Ullrich6,
A. Meining 7, J.M. Esteban 8, J.G. Soler 9, T. Enz 10, G. Vanbiervliet 11,
F. Vleggaar 12, A. Larghi13
1
INTERNAL MEDICINE AND GASTROENTEROLOGY, CATHOLIC
UNIVERSITY OF ROME, ROME, Italy, 2Gastroenterology, Klinikum
Neuperlach, Munchen, Germany, 3Gastroenterology, Agencia Sanitaria Costa del
Sol, Marbella, Spain, 4Gastroenterology, SRH_Wald Klinkum, Gera, 5Surgical
Gastroenterology, Aarhus University Hospital, Aarhus, 6Gastroenterology,
Asklepios Klinik Altona, Hamburg, 7Gastroenterology, Technical University of
Munich, Munich, Germany, 8Gastroenterology, Hospital Clinico San Carlos,
Madrid, 9Gastroenterology, Hospital Universitario de Bellvitge, Barcelona, Spain,
10
Gastroenterology, Kliniken Nagold, Nagold, Germany, 11Gastroenterology,
Hopital LArchet, Nice, France, 12Gastroenterology, University Medical Center
Utrecht, Utrecht, Netherlands, 13Digestive endoscopy, Catholic University, Gemelli
Hospital, Rome, Italy
Contact E-mail Address: emanurinni@yahoo.it
INTRODUCTION: To analyze the safety and clinical effectiveness of EUS
guided drainage of peri-pancreatic collections (PPCs) using a fully covered selfexpanding stent incorporated in an electrocautery enhanced delivery system, the
Hot-AXIOS system (Xlumena Inc. Mountain View, Ca, USA).
AIMS & METHODS: Retrospective analysis of consecutive patients with PPCs
who underwent EUS guided drainage using the Hot-AXIOS system in 12
European Endoscopy Centers.
RESULTS: From March 2013 to April 2014, 72 patients (median age 60 yrs; 55
male) with PPCs underwent drainage using the Hot AXIOS system. Median
diameter of PPCs was 100 mm (range 38-246). 18 were pseudocysts, 35
WOPN, 15 abscesses, and 4 were acute PPCs. 41/72 PPCs were infected. In 57/
72 cases (79%) the Hot-AXIOS system was used to enter the PPCs, while in the
remaining 15 cases (21%) a 19G needle was utilized. The main approach was
transgastric (68/72), and all were technically successful with all but one procedure
described as easy to be performed. Early complications were mild fever in 2 cases
and self-limiting bleeding in 2 other cases. Late complications were: Infection (1);
self-limiting pneumoperitoneum (1); perforation (1); massive bleeding (1). Both
last two complications were related to the naso-cystic drainage placement. 3 out
of these 4 patients required surgery. Direct necrosectomy was performed in 29
cases. Overall, resolution of PPCs was achieved in 69/72 cases (95.8%). Stent
removal was done after a median of 61 days. Recurrence was seen in only two of
69 cases (2.9%), one of which was treated with repeat EUS-guided drainage while
the other did not require treatment. At the end of follow up 69 patients are alive
and asymptomatic. Complications of the PPCs was the cause of the death in two
out of the three patients who died.
CONCLUSION: EUS guided drainage with the Hot AXIOS system is a safe,
easy to use, and highly effective minimally invasive treatment modality for peripancreatic collections.
Disclosure of Interest: None declared
P0774 CRYPTOGLANDULAR ANAL FISTULA OR CROHNS ANAL
FISTULA: THE ROLE OF ULTRASONOGRAPHY IN
DIFFERENTIAL DIAGNOSIS

S. Bharmal1, R. Sharaiha1, P. Kedia1, N. Kumta1, H. Umrania1, M. Gaidhane1,


M. Kahaleh1,*
1
Gastroenterology & Hepatology, Weill Cornell Medical College, New York,
United States
Contact E-mail Address: mkahaleh@gmail.com

F. Dias De Castro1,*, P. Boal Carvalho1, J. Magalhaes1, S. Leite1, M.J. Moreira1,


J. Cotter1,2
1
Gastroenterology, Centro Hospitalar do Alto Ave Guimaraes, Portugal, 2Life
and Health Sciences Research Institute (ICVS), School of Health Sciences,
University of Minho, Guimaraes, Portugal
Contact E-mail Address: franciscadcastro@gmail.com

INTRODUCTION: Probe-based Confocal Laser Endomicroscopy (pCLE)


increases diagnostic accuracy via targeted biopsies and greatly impacts management decisions, with accuracy rates above 80%. The improved diagnostic capability of pCLE may result in high post-procedure health resource utilization
with increases in subsequent surgical and interventional procedures. Our aim
was to examine downstream revenue and profit generated from surgical and
interventional radiology procedures after pCLE.
AIMS & METHODS: A retrospective chart review was performed in a tertiary
care institution. We identified patients who underwent diagnostic pCLE between
August 2011 and December 2012 for indeterminate pancreaticobiliary lesions.
Revenue data was generated using AllScripts EPSi and billing information to
generate financial estimates.
RESULTS: 67 patients underwent diagnostic pCLE for indeterminate pancreaticobiliary lesions during the study period. Of these, 12 (18%) patients had subsequent procedures related to their diagnosis. Diagnoses included
adenocarcinoma (n 8), intraductal papillary mucinous neoplasm (n 1) and

INTRODUCTION: Endoanal ultrasonography shows good accuracy in definition of the anatomy of perianal fistulae, including those associated with Crohns
disease (CD). Several studies have been proposed ultrasonographic features to
discriminate anal fistulae associated with CD in relation to cryptoglandular
fistulae.
AIMS & METHODS: Our aim was to evaluate several ultrasonographic features
that may distinguish these two types of fistulae.
Retrospective study including fifty-eight patients who underwent endoanal ultrasonography 2D between 2008 and 2013. The perianal fistulae variables studied
were the complexity, transversal diameter, presence of secondary tracks and
fistulous debris. For patients with CD was also calculated the adapted perianal
disease activity index (PDAI excluding the influence in sexual activity).
Statistical analysis was performed using the SPSS program vs20.0 and a p value
of less than 0.05 was considered statistically significant.
RESULTS: Fifty-eight patients were included, 48% with CD with a mean PDAI
of 7.63.2. In CD patients a higher PDAI was statistically associated to more

United European Gastroenterology Journal 2(1S)


complex fistulae (8.5 vs 5.5, p 0.028). 38% of all patients had been previously
submitted to a surgery intervention for fistula resolution. The ultrasonographic
features that correlated with the presence of fistulae associated with CD were the
complexity (OR:5; IC95% 1.6-15.3; p 0.004), the presence of secondary tracks
(OR:3.2; IC95% 1.1-9.5; p 0.036) and the presence of fistulous debris (OR:5.9;
IC95% 1.6-15.3; p 0.002). There was no statistical difference between cryptoglandular fistulae and fistulae associated with CD with respect to dimensions
(4.1mm vs 4.9mm, p 0.24).
CONCLUSION: In our study, the complexity of the perianal fistulae and also
the presence of secondary tracks and debris revealed to be strong predictors of
Crohns related perianal fistulae.
Disclosure of Interest: None declared
P0776 NOVEL COMPUTER-AIDED QUANTITATIVE ANALYSIS OF
THE DISTRIBUTION OF CONTRAST IN CONTRAST-ENHANCED
EUS FOR DIFFERENTIAL DIAGNOSIS OF PANCREATIC TUMORS
H. Imazu1,*, T. Kato1, M. Chiba1, S. Koyama1, T.L. Ang2, H. Tajiri3
1
Department of Endoscopy, THE JIKEI UNIVERSITY SCHOOL OF
MEDICINE, Tokyo, Japan, 2Department of Gastroenterology and Hepatology,
Changi General Hospital, Singapore, Singapore, 3Division of Gastroenterology and
Hepatology, Department of Internal Medicine, THE JIKEI UNIVERSITY
SCHOOL OF MEDICINE, Tokyo, Japan
Contact E-mail Address: himazu21@aol.com
INTRODUCTION: Differentiating between pancreatic carcinoma (PC) and
chronic pancreatitis (CP) with pseudotumor is still challenging, even with contrast-enhanced EUS (CE-EUS) or EUS-FNA. We developed the novel computer-aided diagnostic software (Madara, Inspeedia Inc., Kariya, Japan) to
quantify the pattern of contrast distribution in CE-EUS.
AIMS & METHODS: The aim of this study was to evaluate the utility of CEEUS with Madara for differential diagnosis of PC and CP with pseudotumor.
Consecutive patients who had PC or CP with pseudotumor and underwent CEEUS from January 2011 to December 2013 were retrospectively analyzed. A
curvilinear echoendoscope (GF-UCT260), Aloka Prosound 10 processor and
intravenous administration of 0.015ml/kg of Sonazoid were used for CE-EUS.
Using our software, a region of interest (ROI) which divided into 100 cells was
placed to cover an area within pancreatic mass. Differences of grade of gray scale
levels between the adjoining cells within the ROI were detected, and the number
of adjoining cells which showed a difference of the gray scale level was automatically calculated in each frame rate of CE-EUS (heterogeneity index). A heterogeneity index curve was also automatically generated to depict the changes of the
heterogeneity index over time, and the mean heterogeneity index from start to
one minute after injection of Sonazoid was calculated. Moreover, using a conventional software to quantify the degree of enhancement, in which time intensity curve (TIC: Hitachi/Aloka Co., Ltd., Tokyo, Japan) was generated to
depict the changes in the signal intensity, maximum intensity gain (MIG: peak
intensity base intensity) was also calculated. The final diagnosis of PC was
based on the results of surgery or EUS-FNA, while CP was diagnosed from
EUS-FNA, the clinical course and other imaging tests.
RESULTS: Fifty-nine patients (39 with PC and 20 with CP) were analyzed. The
heterogeneity index curve showed bell and flat curve type in 9 patients with
CP, irregular curve type in 11 patients with CP and 37 with PC, and flat curve
type in 2 with PC. Thus, bell and flat curve type was specific to CP, while
flat curve type were specific to PC. The mean heterogeneity index in PC
patients was significantly higher than CP patients (15.6 vs. 6.1, p50.0001).
Flat curve type of heterogeneity index curve and the mean value of heterogeneity
index showed sensitivity of 92.3% and specificity of 90% for differentiating
between PC and CP with pseudotumor. On the other hand, MIG in CP patients
was significantly higher than PC patients (21.1 vs. 15.7, p 0.01), and showed
sensitivity of 71.8% and specificity of 65%. Combined assessment of heterogeneity index curve and MIG with time intensity curve, using the cut-off value of
heterogeneity index of 10.3 and MIG of 14.3, yielded sensitivity of 94.3% and
specificity of 95% to differentiate between PC and CP with pseudotumor.
CONCLUSION: CE-EUS with Madara diagnostic software to quantify the
pattern of contrast distribution might be useful for making a differential diagnosis between PC and CP with pseudotumor.
Disclosure of Interest: None declared
P0777 TRANSMURAL STENT PLACEMENT AS THE DOMINANT
STRATEGY FOR ENDOSCOPIC ULTRASOUND-GUIDED BILIARY
DRAINAGE
I. Penas Herrero1,*, N. Alcaide1, R. Sanchez-Ocana1, P. Gil-Simon1, C. De la
Serna-Higuera1, M. Perez-Miranda1
1
Gastroenterology, Hospital Universitario Ro Hortega, Valladolid, Spain
Contact E-mail Address: mpmiranda5@hotmail.com
INTRODUCTION: There are several ways to perform endoscopic ultrasoundguided biliary drainage (EUSBD): transductal (rendezvous [RV] and direct antegrade [DAG] options) or transmural (intrahepatic [hepaticogastrostomy, HGS]
and extrahepatic [choledochoduodenostomy, CDS] options). Best approach
remains contentious, while patient selection and case-volume confound evidence
from limited available comparative data.
AIMS & METHODS: To identify current dominant strategy for EUSBD at
high-volume Unit. Data from 44 patients (male 25, mean age [SD] 75 [13],
malignant/benign 77% / 33%) undergoing EUSBD from Jan-Dec 2012 at
single Unit were prospectively captured. Standardized techniques (single-puncture following comprehensive target choice, minimal needle-guidewire interplay,
graded-dilation with salvage-only 6.5F cystotome use) and algorithms for access
(intrahepatic for hilar strictures and/or altered GI anatomy; extrahepatic for the

A345
opposite when stable scope) and drainage (transductal if early guidewire passage
or if failed cannulation of native papilla in benign obstruction, transmural if
otherwise) were used. Caliber of access duct was 9.1 mm (IQR 6.3-15.6) for
extrahepatic (27%) and 5.5 mm (IQR 4.0-7.9) for intrahepatic access (73%).
Number of ERCP/PTBD over study period was 1048/5 (EUSBD 4.2% of
ERCP; PTBD 11% of EUSBD). Clinical success was defined as bilirubin 5
80% baseline values, symptom disappearance and hospital discharge. Adverse
events as per consensus. Follow-up through chart review and phone contact.
RESULTS: Technical success was achieved in 43 patients (97.7%) and clinical
success in 70%. There were adverse events in 6 patients (13.6%): 5 mild (3 mild
bleedings, 1 acute pancreatitis, 1 hypoxemia) and 1 fatal case of cholecystitis.
Transductal EUSBD was performed in 11 patients (7 DAG and 4 RV techniques), and transmural EUSBD in 36 (26 HGS/hepaticojejunostomy and 10 CDS/
choledocogastrostomy, including dual DAG-HGS in 4). Fully covered metal
stents were used in 90.6% for transmural EUS-guided biliary drainage (22
Hanaro stent, 7 Wallflex stents). A variety of stent-anchorage techniques were
employed in 65% of these patients (hemoclips, flaps, double pig-tails, balloon
expansion or more than one anchorage technique). Accurate follow-up was
obtained in 35 patients. After a mean of 146 days (SD 141), 5 dysfunctions
occurred (2 patients with plastic stents [1 migration, 1 occlusion], 3 with metal
stents [2 angulation, 1 late migration]).
CONCLUSION: After a decade-long usage, the dominant strategy for EUSBD
was transmural fully covered metal stents with ancillary anchorage. No shortterm migration, minimal late dysfunction and comparable adverse event rate to
purported less invasive RV were found. Intriguing higher rate of intrahepatic Vs
extrahepatic possibly explained by patient selection/PTBD use patterns warrants
clarification.
Disclosure of Interest: None declared
P0779 FACTORS ASSOCIATED WITH THE ACCURACY OF EUSGUIDED FINE NEEDLE ASPIRATION FOR THE DIAGNOSIS OF
SOLID PANCREATIC MASSES
J. Iglesias-Garc a1,*, D.de la Iglesia-Garc a1, N. Vallejo-Senra1, J. Larino-Noia1,
I. Abdulkader2, L. Uribarri-Gonzalez1, J.E. Dominguez-Munoz1
1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Research in Digestive Diseases, 2Pathology, University Hospital of Santiago de
Compostela, Santiago de Compostela, Spain
INTRODUCTION: Endoscopic ultrasound (EUS)-guided fine needle aspiration
(FNA) and biopsy (FNB) are accurate techniques for sampling pancreatic solid
lesions. Diagnostic yield of FNA/FNB may be influenced by different factors,
but information on this regard is lacking.
AIMS & METHODS: Aim of our study was to evaluate potential factors associated with the diagnostic accuracy of EUS-FNA/FNB for the differential diagnosis of solid pancreatic masses.
447 consecutive patients (mean age 66.4 years, range 17-92, 262 male), who
underwent EUS-FNA/FNB for the evaluation of solid pancreatic lesions over
the last 4 years were identified from a prospectively collected endoscopy database, and included in the study. EUS was performed using a convex array
echoendoscope (Pentax EG-3870UTK and EG-3270UK). FNA/FNB was performed with standard cytology and ProcoreTM histology needles (Cook Medical
Inc, Limerick Ireland). The impact of the type of scope, location and size of the
lesion, on-site cytopathological evaluation, number of needle passes and type of
needle on the diagnostic accuracy of FNA/FNB was evaluated. Overall diagnostic accuracy was calculated by using surgical histopathology in operated cases
and global clinical and radiological assessment and follow-up in non-operated
cases as gold standard. Data were analyzed by multivariate stepwise logistic
regression.
RESULTS: Mean size of solid pancreatic masses was 36.116.4 mm. 283 tumors
were located in the head of the pancreas, 124 in the body, and 40 in the tail. Final
diagnosis was pancreatic adenocarcinoma in 294 cases, inflammatory lesions in
74 cases, neuroendocrine tumor in 23 cases, pancreatic metastasis in 17 cases,
cystic lesions with solid components in 36 cases and pancreatic lymphoma in 3
cases. Overall diagnostic accuracy was 87.5% (95%CI 84.1-90.2). Size of the
lesion (OR 1.03; 95%CI 1.00-1.06; p 0.014), onsite evaluation of the FNA/
FNB sample (OR 4.36; 95%CI 1.3-14.9; p 0.019), and the use of ProcoreTM
needles (OR 3.02; 95%CI 1.4-6.5; p 0.005) were independently associated with
a correct diagnosis after FNA/FNB.
CONCLUSION: EUS-guided FNA/FNB is an accurate technique. Factors associated with a higher diagnostic yield are large lesions, onsite cytopathological
evaluation and the use of the ProcoreTM needles.
Disclosure of Interest: J. Iglesias-Garc a Lecture fee(s) from: Cook-Medical,
Consultancy for: Cook-Medical, D. de la Iglesia-Garc a: None declared, N.
Vallejo-Senra: None declared, J. Larino-Noia: None declared, I. Abdulkader:
None declared, L. Uribarri-Gonzalez: None declared, J. E. DominguezMunoz: None declared
P0780 DOES EUS-BASED CHRONIC PANCREATITIS PROGRESS TO
OBVIOUS CHRONIC PANCREATITIS? - THE FOLLOW-UP STUDY
USING EUS
K. Imbe1,*, A. Irisawa1, G. Shibukawa1, Y. Abe1, A. Saito1, K. Hoshi1,
A. Yamabe1, R. Igarashi1
1
Department of Gastroenterology, Fukushima Medical University Aizu Medical
Center, Fukushima, Japan
Contact E-mail Address: kohimbe@hotmail.com
INTRODUCTION: Endoscopic ultrasonography (EUS) has been commonly
used for diagnosis of chronic pancreatitis (CP) and assessment of its severity.
In 2009, Rosemont criteria was proposed as EUS-based criteria for CP. EUS

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United European Gastroenterology Journal 2(1S)

can detect minimal changes in the pancreatic duct and parenchyma, and may
reveal early pancreatic abnormalities. However, it is not clear whether the pathological condition revealed by EUS will progress to obvious CP or not.
AIMS & METHODS: The aim of this study is to clarify a clinical significance of
EUS-based CP.
We retrospectively reviewed all the medical records and EUS images of the
patients who had underwent EUS for pancreas from April 2010 to March
2012 in our center. The study patients were picked-up fulfilling criteria as follows;
1) the patients who had pancreatic abnormalities (Hyperechoic foci with/without
shadowing, Lobularity with/without honeycombing, Cysts, Strands, MPD calculi, Irregular MPD contour, Dilated side branches, MPD dilation, Hyperechoic
MPD margin) on the initial EUS, 2) the patients who were followed by EUS
more than twice until April 2014. These patients were classified into 4 categories
by Rosemont criteria; Consistent with CP (C-CP), Suggestive of CP (S-CP),
Indeterminate for CP (I-CP), and Normal (N). We assessed the progression of
pancreatic condition in each patient.
RESULTS: 10 of 22 patients who had pancreatic abnormalities on initial EUS
had undergone EUS more than twice (M/F:8/2, mean age: 73.5 (58-82)). Initial
diagnosis was C-CP in 1, S-CP in 2, I-CP in 3 and N in 4, respectively. In 10
patients, 5 were aggressively intervened (abstinence, taking orally protease inhibitor), and the other 5 were not taken medical intervention. In intervention
group, the number of EUS criteria increased in 2 patients. However, there was
no patient who changed the category of Rosemont classification between initial
and follow-up EUS. On the other hand, in no intervention group, the number of
EUS criteria increased in 4 patients. Moreover, 3 patients got worse the category
of Rosemont classification from N to I-CP.
CONCLUSION: It was considered that early medical intervention might be
necessary in patient with pancreatic abnormalities on EUS, even if Rosemont
classification indicated Normal.
REFERENCES
Catalano MF, Sahai A, Levy M, et al. EUS$ based criteria for the diagnosis of
chronic pancreatitis: the Rosemont classification. Gastrointest Endosc 2009; 69:
1251-1261.
Disclosure of Interest: None declared
P0781 DIFFERENT SITES OF ASPIRATION IN EUS-FNA
PANCREATIC ADENOCARCINOMA: A PROSPECTIVE,
MULTICENTER, SINGLE-BLINDED STUDY

OF

Y. Di1, K. Tanaka2, Q. Zhu3,4, S.-J. Hao1, C. Jin1, L. Zhong5,*, T.-T. Gong3, T.J. Ye6
1
Pancreatic Surgery and Pancreatic Disease Institute, Huashan Hospital, Fudan
University, Shanghai, China, 2Department of Gastroenterology, Kyoto Second Red
Cross Hospital, Kyoto, Japan, 3Department of Gastroenterology, Rui jin Hospital,
Shanghai Jiao tong University School of Medicine, 4Shanghai Gleneagles Clinic,
ParkwayHealth, 5Department of Gastroenterology and Digestive Endoscopy,
Huashan Hospital, Fudan University, 6Department of Cytopathology, Rui jin
Hospital, Shanghai Jiao tong University School of Medicine, Shanghai, China
Contact E-mail Address: zhongniping@163.com
INTRODUCTION: EUS-FNA is widely used to diagnose pancreatic malignancies. Few studies have compared different sites of aspiration when performing
EUS-FNA of pancreatic lesions.
AIMS & METHODS: to evaluate the diagnostic accuracy between center and
margin of pancreatic adenocarcinoma. 69 consecutive patients with a solid pancreatic lesion, with long axis 2cm, were included in this study between January
2012 and December 2013 in 3 hospitals. All FNA procedures were performed
using a 22G needle with 5ml suction, 7-8 uniform to-and-fro movements with
2cm depth of insertion were made within the lesion. The first puncture was
performed within the central part of the lesion and the second was along the
edge of lesion closed to unaffected tissue. A liquid-based cytologic (LBC) preparation was used to rinse the aspiration needle and fix the cytologic specimen
after every puncture and specimens were evaluated by expert cytotechnologists.
An expert cytopathologist, blinded for the sites of aspiration, reviewed the slides
for diagnosis and assessed sampling quality. The final diagnosis was based on
pathological examination of tissues obtained either surgically or by EUS-FNA,
pathological negative cases need at least 6 months follow-up to rule out benign
diseases. Data were analyzed with Students t-test and chi squared test, assuming
a significant p-value of 0.05.
RESULTS: 64 patients were confirmed with pancreatic adenocarcinoma. The
sensitivity of central site is 71.9%(46/64) and 48.4%(31/64) in marginal site
(p 0.039).
CONCLUSION: Our study shows EUS-FNA in center of tumor is more sensitive for the diagnosis of pancreatic adenocarcinoma.
Disclosure of Interest: None declared
P0782 PREDICTIVE VALUE OF PRE-OPERATIVE STAGING AND
GRADING IN PANCREATIC NEUROENDOCRINE NEOPLASMS
M.C. Petrone1,*, M.C. Mariani2, M. Manzoni2, S. Testoni1, M. Traini1,
P.A. Testoni1, P.G. Arcidiacono1
1
Gastroenterology and Digestive Endoscopy Unit, 2 Endocrine Tumors Unit, San
Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Contact E-mail Address: petrone.mariachiara@hsr.it
INTRODUCTION: Pancreatic NeuroEndocrine Tumors (P-NETs) are a heterogeneous group of neoplasms with highly variable clinical behavior. In the attempt
to assess a better prognostic description, The European Neuroendocrine Tumors
Society (ENETS) proposed a new grading and TNM-based staging system.
AIMS & METHODS: To compare pre-operative and post-operative Staging and
Grading in P-NETs and their prognostic significance; secondary to determine if a

new cut-off value of Ki-67 proliferative index for P-NETs Grading can improve
the accuracy of prognostic stratification.
Our retrospective long-term survival case study is composed of 285 patients with
P-NETs observed at San Raffaele Scientific Institute from 1988 to 2012. 274
neoplasms were classified according to ENETS classification models; out of
these, 90 and 42, respectively, were classified according to a new pre-surgical
classification, composed of pre-operative Staging (CT, MRI, EUS) and
Grading (EUS-guided fine needle aspiration and cytological Ki-67 evaluation).
Comparison between pre- and post-operative models (Pre-Stage vs. Stage e PreGrade vs. Grade) was possible for 88 and 33 neoplasms, respectively. Ki-67
proliferative index was evaluated through immunocytochemical (Pre-Grade)
and immunohistochemical (Grade) analyses. Agreement between pre-operative
and post-operative models was performed through k-statistics (Cohen). A pvalue50.05 was considered significant.
RESULTS: Among all pre-operative and post-operative models, Pre-Grade
shows the highest Harrells C (0.97), resulting the best tool for a proper prognostic stratification. When comparing pre-operative and post-operative models,
percent agreement between Pre-Stage and Stage was good (83%, k 0.74), otherwise agreement between Pre-Grade and Grade was moderate (70%, k 0.42),
when used a 2% cut-off for Grade 1 tumor definition; contrarily, when used a
5% cut-off, Pre-Grade and Grade showed a good agreement (88%, k 0.66).
The definition of a new 5% cut-off for cytological and histological Ki-67 index
improved the accuracy of patients prognostic stratification, being not significant
the difference between patients 10-year survival for Ki-67 levels within 5%
(93.75% vs. 90%).
CONCLUSION: The new proposed pre-surgical classification, based on PreStage and Pre-Grade, is comparable to post-surgical models. This system
shows a good agreement with post-surgical one, being efficient in pre-surgical
diseases biology evaluation.
Disclosure of Interest: None declared
P0783 DUPLICATION
ULTRASONOGRAPHY

CYSTS:

THE

ROLE

OF

ENDOSCOPIC

M.J. Magalhaes1,*, F. Castro-Pocas1, T. Araujo1, P. Lago1, T. Moreira1,


I. Pedroto1
1
Gastroenterology, Centro Hospitalar do Porto - Hospital de Santo Antonio, Porto,
Portugal
Contact E-mail Address: mj.magalhaes@gmail.com
INTRODUCTION: The duplication cysts are uncommon congenital anomalies
and rarely diagnosed in adults. They can be found in any part of the digestive
tract. The cysts are typically discovered incidentally on endoscopy or radiologic
imaging since they are usually asymptomatic. However complications such as
infection, bleeding, perforation, ulceration, obstruction and malignant transformation can occur. Their management can be challenging and increased availability of new diagnostic modalities such as endoscopic ultrasonography (EUS) may
change their approach.
AIMS & METHODS: To describe the experience of a center in the diagnosis of
duplication cysts by EUS.
We performed a retrospective analysis to the upper EUS performed between 2000
and 2013, with the diagnosis of duplication cyst. The patient characteristics and
the endoscopic/imaging findings were analyzed. The contribution to the diagnosis of fine needle aspiration (FNA) was also evaluated.
RESULTS: Between 2000 and 2013, 23 patients (16 men (69.6 %)) with a mean
age of 51.9  15.9 years underwent EUS, whose final diagnosis was duplication
cyst. Prior to EUS: 19 underwent gastrointestinal endoscopy (EGD), 13 of them
by symptoms such as dyspepsia (n 9) and dysphagia (n 4). Of the 19 EGD
performed, 3 had no endoscopic abnormalities and 16 had suspection of subepithelial lesions (10 esophageal); Four patients had previous imaging study by
computed tomography (CT), 2 with suspected esophageal duplication cysts. EUS
detected 16 anechoic lesions with endosonographic criteria of duplication cyst in
the esophagus (average size 24.2 x14, 2 mm; 7 with echogenic material inside) and
7 in the stomach (average size 23.6 x14, 1 mm, 2 with fluid levels and septae).
There were 8 cases where EUS FNA was performed (5 esophagus); in 75% of
cases one pass FNA was done using a 22 Gauge needle. There was cytological
confirmation in 3 cases, and in 3 other cases other entities besides cysts were
excluded. A CT scan was performed in four patients after EUS, with diagnostic
agreement in one case. Annual EUS follow up was performed in 9 patients, with
no changes in the lesions characteristics.
CONCLUSION: EUS plays a central role in the diagnosis and monitoring of an
entity which, although rare, has potential serious risks and complications
associated.
Disclosure of Interest: None declared
P0784 DECISION TREE ANALYSIS OF THE DIAGNOSTIC VALUE OF
EUS IN DETERMINING ESD INDICATION IN EGC
N. Indo1,*, A. Watanabe1, T. Fujita1
1
Digestive disease center,Department of gastroenterology, Yodogawa Christian
Hospital, Osaka, Japan
Contact E-mail Address: inchan0701@gmail.com
INTRODUCTION: In recent years, due to the spread of endoscopic submucosal
dissection (ESD) for early gastric cancer (EGC), preoperative determination of
ESD indication has become increasingly important.
AIMS & METHODS: In determining the ESD indication for EGC, we diagnose
the depth of invasion by endoscopic ultrasonography (EUS) in all cases as much
as possible in our hospital. We investigated its efficacy by decision tree analysis.
We performed EUS in 179 cases from January 2011 to March 2014. We performed EUS using 20MHz small-diameter probe. The average age was 69 years

United European Gastroenterology Journal 2(1S)


old. Male-to-female ratio was 142:37. We classified the invasion depth into M,
M-SM and SM. We evaluated the accuracy of the invasion depth by area, morphological type, histological grading and UL according to the pathology specimen after resection.
RESULTS: The accuracy of all 179 cases was 89 %. It was 91 % in the 150 cases
that ESD was performed, and 75% in the 29 cases that surgery was performed.
Total cases and accuracy according to area was 83% in 42 U area cases, 93% in
80 M area cases, and 88% in 57 L area cases. According to the macroscopic type,
accuracy was 91% in 89 0-IIc type cases, 88% in 60 0-IIa type cases, 92% in 13 0IIb type cases, 60% in 10 0-IIaIIc type cases, and 100% in 7 0-I type cases.
Accuracy was 68% in 32 UL () cases. According to histological type, accuracy
was 92% in 155 differentiated type cases, 75% in 24 undifferentiated type cases.
164 cases were diagnosed as M or M-SM, which are indications for ESD, and
correct diagnostic rate was 91%. 15 cases were diagnosed as SM, in which
surgical treatment is indicated, and accuracy was 67%. In decision tree analysis,
accuracy was 69% in UL() cases, and as low as 84% in undifferentiated UL (-)
cases, and 97% in other cases.
CONCLUSION: In ESD cases, decision tree analysis enabled differentiation
between high and low accuracy groups in diagnosis of the depth of invasion.
Disclosure of Interest: None declared
P0785 EUS-FNA OF NON MASS-FORMING CHOLANGIOCARCINOMA
WITH A 25 G PROCORE NEEDLE. A CASE SERIES
N. Pagano1,*, C. Luigiano2, L.H. Eusebi1, G. Rando3, R.M. Zagari1, F. Bazzoli1
1
Gastroenterology and Endoscopy Unit, Policlinico S. Orsola, University of
Bologna, Bologna, 2Gastroenterology Unit, ARNAS Garibaldi, Catania, 3UOC.
Chirurgia e diagnostica endoscopica, Az. ospedaliera S. Salvatore, LAquila, Italy
Contact E-mail Address: nicopagano@gmail.com
INTRODUCTION: Preoperative pathological diagnosis in patients with biliary
strictures suspected for malignancy is often difficult. The diagnostic yield of
endoscopic retrograde cholangio-pancreatography (ERCP) guided brushing is
low and endoscopic ultrasound fine needle aspiration (EUS-FNA) may be difficult to perform in non-mass forming lesions. We report a case series of patients
affected with suspected cholangiocarcinoma in which a cytological diagnosis was
attempted by EUS-FNA.
AIMS & METHODS: All the cases of EUS-FNA performed in patients with
biliary strictures suspected for malignancy from June 2012 to October 2013 were
reviewed. Patients were excluded if the EUS examination showed a mass lesion.
Only patients in whom an EUS-FNA was attempted were included in the
analysis.
RESULTS: During the study period 12 patients (8 males, mean age of 75, range
60 to 85) diagnosed with a non mass forming biliary stricture underwent EUSFNA. The stenosis was distal from the cystic duct insertion in 8 cases. Aspirates
were carried out using a 25 G core needle with the capillary suction technique.
The material was put on smears and processed in the standard fashion. The
results were definite for malignancy in 9 patients and suspected in 2 patients.
In one patient the cytological results were inconclusive. All the patients were
resected. The surgical pathology results showed a cholangiocarcinoma in all
these patients. The sensitivity of EUS-FNA was 75% considering only the positive cytology and 91% considering also the suspected ones. No complications
were reported.
CONCLUSION: Our results suggest that EUS-FNA is a safe and useful procedure for investigating biliary strictures suspected of malignancy even without a
mass. Although false-negative diagnosis can still occur, core biopsy needle seems
to improve the diagnostic yield of cytology.
Disclosure of Interest: None declared
P0786 LIMITATIONS OF CAPSULE ENDOSCOPY - A SINGLE CENTER
STUDY ON 1193 CONSECUTIVE EXAMINATIONS
E. Dulic-Lakovic1,*, M. Schleicher1, M. Dulic1, B. Blaha1, A. Halmetschleger1,
P. Ordubadi1, M. Gschwantler1
1
Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria
Contact E-mail Address: michael.gschwantler@wienkav.at
INTRODUCTION: Over the past years, capsule endoscopy (CE) has been established as an imaging technique in the diagnosis of small bowel diseases. The aim
of this study was to examine the limitations of this method by analysing a large
number of consecutive CEs.
AIMS & METHODS: This was a retrospective study, including 1193 consecutive
examinations performed at our centre in 1091 patients (male/female 517/574,
mean age  SD: 61.83  17.46a, range: 9-93a) between 2002 and 2012. In 1061
examinations the system of Given (Yoqneam, Israel) was used. In 132 examinations the capsule endoscope MiroCam (IntroMedic, Seoul, South Korea)
was used.
RESULTS: Complications requiring an endoscopic or surgical intervention
occurred in 0.34% (4/1193) of examinations: In two patients the capsule was
retained in a duodenal diverticulum or a hiatal hernia, respectively. In both
cases the capsule could be removed endoscopically. In one patient with
Crohns disease (CD) the capsule was retained in a stenosis of the terminal
ileum and was removed during colonoscopy after dilation of the stricture. One
patient underwent surgery after the capsule was retained in a stenosis caused by
CD.
Technical defects of the capsule or the data recorder occurred in 16 (1.34%) CEs:
Hence the passage through the small intestine was not completely recorded
(n 12) or the pictures could not be used for further evaluation (n 4).
Transit abnormalities: In 1017 examinations (85.25%) the cecum was reached
within the recording period.

A347
Visibility conditions were classified as very good 54.41%, as partly limited in
32.05% and as severely limited during the most part of recording in 13.54% of
examinations.
CONCLUSION: Complications of CE requiring endoscopic or surgical intervention are very rare (0.34%). However, technical defects as well as transit abnormalities and limited visibility may decrease the diagnostic yield of CE in some
cases.
Disclosure of Interest: None declared
P0787 OESOPHAGEAL CAPSULE ENDOSCOPY VERSUS STANDARD
OESOGASTRODUODENOSCOPY FOR THE SCREENING OF
OESOPHAGEAL VARICES. RESULTS OF A PROSPECTIVE TRIAL
IN PATIENTS WITH LIVER CIRRHOSIS
S. Sacher Huvelin1,*, P. cales2, C. bureau3, D. valla4, J.P. Vinel3, C. duburque5,
A. attar4, I. Archambeaud1, R. benamouzig6, M. gaudric7, D. LUET2,
P. Couzigou8, L. Planche1, J.P. galmiche1, E. Coron1
1
University Hospital, Nantes cedex 01, 2University Hospital, Angers, 3University
Hospital, toulouse, 4University Hospital, beaujon, PARIS, 5University Hospital,
lomme, 6University Hospital, Avicennes Bobigny, 7University Hospital, CochinPARIS, 8University Hospital, Bordeaux, France
Contact E-mail Address: sylvie.sacherhuvelin@chu-nantes.fr
INTRODUCTION: Oesophageal capsule endoscopy (OCE) is a non-invasive
technology that allows the investigation of the oesophagus. Our aim was to
evaluate prospectively the diagnostic yield of OCE in patients with cirrhosis
and suspected portal hypertension (PHT).
AIMS & METHODS: 330 patients with cirrhosis and without known oesophageal variz (OV) were enrolled. Patients first underwent OCE, then OGD; endoscopists who performed OGD were blind to OCE result. In case of discrepancy for
the presence of VO, a second exploration by OGD was immediately performed.
Patients satisfaction was assessed by an VAS (visual analogic scale, maximal
score 100).
RESULTS: Thirty patients were not included in the analysis because neither
OCE nor OGD were performed. Patients (216 male, mean age 56 years) had
mainly alcoholic (45%) or viral (22%) cirrhosis. The diagnostic yields of OCE
to detect, and to adequately classify, OV were as follows: sensitivity 76% [95%
CI, 69% - 83%] and 64% [95% CI, 50% - 78%], specificity 91% [95% CI, 86% 95%] and 93% [95% CI, 87% - 100%], positive predictive value 88% [95% CI,
82% - 93%] and 88% [95% CI, 77% - 99%] and negative predictive value 81%
[95% CI, 75% - 87%] and 78% [95% CI, 68% - 87%] respectively. OCE patient
satisfaction scored significantly higher than OGD (8722 vs. 5835; p50.0001).
CONCLUSION: OCE was well tolerated and safe in patients with liver cirrhosis
and suspicion of PHT. The sensitivity of OCE is not currently sufficient to
replace OGD as a first exploration in these patients. However, due to its excellent
specificity and PPV, OCE may have a role in cases of refusal or contra-indication
to OGD. OCE might also improve compliance to endoscopic follow-up and help
in making important therapeutic decisions in the prophylaxis of bleeding.
Disclosure of Interest: S. Sacher Huvelin Financial support for research from:
given imaging, Consultancy for: given imaging, P. cales Consultancy for: biolivescale, C. bureau: None declared, D. valla: None declared, J. P. Vinel: None
declared, C. duburque: None declared, A. attar: None declared, I. Archambeaud:
None declared, R. benamouzig: None declared, M. gaudric: None declared, D.
LUET: None declared, P. Couzigou: None declared, L. Planche: None declared,
J. P. galmiche: None declared, E. Coron: None declared
P0788 ARE NON-INVASIVE MARKERS OF GASTRO-INTESTINAL
DISEASE PREDICTORS OF ENTEROPATHY AT SMALL BOWEL
CAPSULE ENDOSCOPY?
R. Caccaro1, G. Lollo1,*, G. Hatem1, A. Ugoni1, A. Buda2, A. DOdorico1,
F. Galeazzi1, R. DInca`1, E. V. Savarino1, G.C. Sturniolo1
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, 2Department of Oncology, Gastroenterology Unit, Santa Maria del Prato
Hospital, Feltre, Italy
Contact E-mail Address: roberta.caccaro@gmail.com
INTRODUCTION: Small bowel capsule endoscopy (SBCE) represents the gold
standard diagnostic technique in case of obscure gastrointestinal bleeding.
Moreover, its use is gaining acceptance also as diagnostic procedure when an
organic disease of the small bowel (i.e. duodenum/jejunum/ileum) is suspected.
On the other hand, SBCE is an expensive, invasive tool and data about its cost/
effectiveness are lacking. Thus, non-invasive markers of small bowel disease are
desirable in order to increase the rate of positive SBCE examinations.
AIMS & METHODS: We aimed to evaluate the role fecal markers of inflammation (i.e. fecal calprotectin and lactoferrin) and intestinal permeability test (i.e.
lactulose-mannitol ratio, L/M) in predicting the presence of enteropathy at
SBCE. We included consecutive patients who underwent SBCE because of symptoms suggestive of small bowel disease (i.e. chronic diarrhea, chronic anemia,
signs of malabsorption) and with negative upper and lower endoscopy. Patients
dosed levels either of fecal calprotectin (normal values, n.v., 0-50 ug/g) or lactoferrin (n.v. 0-7 ug/ml) and performed L/M test (n.v.50.030) at the time of SBCE.
Erosions, aftous lesions, ulcers and vascular abnormalities at SBCE were considered positive for small bowel disease presence.
RESULTS: In this retrospective analysis of prospective collected data, 101 consecutive patients (66F/35M; mean age 40 years) with dosed levels either of fecal
calprotectin or lactoferrin were included. In 51 (50%) patients, SBCE detected
the presence of small bowel disease. Sixty-three (62%) patients had increased
levels of fecal markers, whereas in 38 (38%) patients these markers were
normal. The diagnostic accuracy of fecal markers for the detection of small
bowel disease was 62.4%, with 75% sensitivity and 46% specificity, a positive

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United European Gastroenterology Journal 2(1S)

likelihood ratio (PLR) of 1.49 and a negative likelihood ratio (NLR) of 0.51.
Sixty-seven out of 101 patients performed also L/M test. This was abnormal in 46
(69%) patients and normal in 21 (31%). In 36/67 (54%) patients, SBCE was
positive for small bowel disease. The diagnostic accuracy of L/M test for the
detection of small intestine disease was 76%, with 75% sensitivity and 56%
specificity, a PLR of 1.7 and a NLR of 0.45. The alteration of at least one
between fecal markers and L/M test has a diagnostic accuracy of 56.7%, whereas
having both fecal markers and L/M test abnormal had a diagnostic accuracy of
64.6%.

Fecal markers
L/M test
At least 1 abnormal
Both abnormal

N
Sensitivity % Specificity % PLR
patients (95%CI)
(95%CI)
(95%CI)

NLR
(95%CI)

101
67
67
48

0.57
0.45
0.65
0.49

75
75
83
79

(60-86)
(58-88)
(67-94)
(60-92)

50
56
26
42

(34-64)
(40-71)
(12-45)
(20-66)

1.36
1.70
1.12
1.37

(1.08-2.05)
(1.15-2.50)
(0.87-1.45)
(0.89-2.10)

(0.30-0.88)
(0.24-0.84)
(0.25-1.66)
(0.20-1.19)

CONCLUSION: Although fecal calprotectin and lactoferrin are established markers of colonic inflammation, their diagnostic yield in detecting small intestinal
disease through SBCE seems suboptimal. Their combination with L/M test minimally improves this diagnostic accuracy, whereas that of L/M test alone appears
the most satisfactory. It remains to establish whether performing either fecal
markers or L/M test (or both) might be cost-effective in the selection of patients
to address for SBCE when a small bowel disease is suspected.
Disclosure of Interest: None declared
P0789 A
THERAPEUTIC
WIRELESS
ROBOTIC
CONTROLLED VIA THE INTERNET REMOTELY

ENDOSCOPE

H. Ohta1,*, S. Katsuki2
1
Gastroenterology, Sapporo Orthopedics and Cardiovascular Hospital, Sapporo,
2
Gastroenterology center, Otaru Ekisaikai, Otaru, Japan
Contact E-mail Address: hideohta@true.ocn.ne.jp
INTRODUCTION: A few researchers have tried to make the paradigm shift
from diagnosis to treatment with the capsule endoscopy (CE) application.
Though technical innovation is rapidly spreading throughout the CE field,
there are still several crucial problems with both the hardware and software
which were highlighted by the system we presented at the last UEGW in
Berlin. This report presents a wirelessly controlled robotic endoscope equipped
with some newly developed tools; a syringe for injecting or spraying drugs or
contrast medium, a scalpel for cutting and a rubber band for suturing.
AIMS & METHODS: Our goal is to realize a patient-friendly, swallowable,
therapeutic and wirelessly controlled robotic endoscope. We tested three newly
developed therapeutic tools in a phantom, which had part of its inner wall
covered with a patch of porcine stomach. 1) A 0.3ml syringe for injecting or
spraying was driven by a spring and switched on electrically. The amount used
was dependent on the drug, dye or contrast medium. 2) The rubber band (similar
to a variceal ligater) was held between two cylinders and released by a spring.
When the spring was released the outer cylinder pushed the band over the
mucosa. 3) The scalpel blade was vibrated by a motor similar to a harmonic
scalpel. All the tools were triggered by signals originating from a controller in the
hospital via a smartphone next to the phantom. In addition, similar to the previous version the tools were controlled via the Internet.
RESULTS: It was possible to control all the new tools in the phantom both
locally (Bluetooth) and via the Internet. However, the cuts made by the scalpel in
the mucosa were a little bit jagged. In retrospect, it would have been better to
move the robotic endoscope slowly backwards during cutting to improve the
operators view of the lesion, so that they could have made a cleaner cut. The
tools occupied a large volume and therefore it was difficult to fit all the tools in a
single robotic endoscope. To enable the robotic endoscope to be swallowed, it
will be necessary to equip it with only one or two tools. The best approach might
be to build several specialized robotic endoscopes and the number of endoscopes
that a patient would swallow would be determined by their circumstances.
CONCLUSION: This study has built on the previous study by increasing the
number of therapeutic tools from two to five and hopefully, it has brought
treatment by a robotic endoscope, a little bit closer. However, the current prototype has a number of limitations (e.g. too large to be swallowed and the tools
could only be used once) and these will need to be addressed if treatment by
robotic endoscope is to become a reality.
Disclosure of Interest: H. Ohta: None, S. Katsuki: None
P0790 KINETICS OF COLON CAPSULE ENDOSCOPY: A NEW MODEL
OF PREPARATION
I. GUTIERREZ-DOMINGO1,*, C. GUTIERREZ-GONZALEZ1 on behalf of
Instituto de Patolog a Digestiva de Sevilla, A. GUTIERREZ-DOMINGO1,
I. MORENO-GARCIA1
1
Digestive Diseases, Instituto de Patologa Digestiva de Sevilla, Sevilla, Spain
Contact E-mail Address: ignaciogutierrezdomingo@hotmail.com
INTRODUCTION: Up until now, the use of colon capsule endoscopy (CCE)
has been limited by the inabilities to achieve a complete examination. A pilot
study was conducted to determine the efficacy of a new preparation based on
associating Prucalopride (Resolor) and polyethylene glycol plus ascorbic acid
(Moviprep). Prucalopride is a highly selective serotonin 5HT4 receptor agonist
which stimulate the release of acetylcholine necessary for smooth bowel muscle
contraction and therefore peristalsis. After observing its benefits on the treatment

for constipation, we believe that Prucalopride could be useful in the preparation


of colon capsule endoscopy, speeding up intestinal transit and therefore making
the examination shorter, increasing the excretion rate. This article presents the
results obtained in terms of transit times, total examination time and expulsion
rates.
AIMS & METHODS: Pilot study with 50 patients (cases) with the new preparation compared with 50 control patients with the standard preparation (PEG/
Fosfosoda/). Each video is read by two researchers.
Preparation protocol: - Two days of residue-free diet - Day before the test, liquid
diet - Resolor 2 mg, 1 on each day of the diet and 2 on the examination day Moviprep, 1 liter in the evening prior to the examination and 1 liter in the
morning of the examination Then 2 boosters of half a liter each in alarms 1
and 2.
RESULTS: A cohort with 41 men and 59 women, mean age of 54.6 years old
(10-90). Expulsion rate over time of 87% in the cases with respect to 55.5% in the
controls (p 0.188). The mean gastric transit time (75 vs. 49.5 minutes; p 0.12),
intestinal transit time (81.4 vs. 44 minutes; p 0.001) and colon transit time (252
vs. 232 minutes; p 0.79) were shorten.
CONCLUSION: The higher excretion rate as well as the shortened gastric and
intestinal transits, without modifying the colon transit, with the new preparation
(PrucalopridePolyethylene glycol plus ascorbic acid), allow conducting a higher
quality study of the colon over time and with less adverse effects and better
tolerance as a result of excluding sodium phosphate.
This procedure may be considered as an alternative, particularly for patients in
whom sodium phosphate-based preparations are contraindicated.
REFERENCES
1. Spada C, et al. Meta-analysis shows colon capsule endoscopy is effective in
detecting colorectal polyps. Clin Gastroenterol Hepatol 2010; 8: 516522.
2. Hansen MB. Small intestinal manometry. Physiol Res 2002; 51: 541-556.
3. Fireman Z, Paz D and Kopelman Y. Capsule endoscopy: improving transit
time and image view. World J Gastroenterol 2005; 11: 5863-5866.
4. Manabe N, et al. New-generation 5-HT4 receptor agonists: potential for treatment of gastrointestinal motility disorders. Expert Opin Investig Drugs 2010; 19:
765-775.
5. Tack, et al. Diagnosis and treatment of chronic constipation a European
perspective. Neurogastroenterol Motil 2011; 23: 697-710.
7. Quigley, et al. Clinical trial: the efficacy, impact on quality of life, and safety
and tolerability of prucalopride in severe chronic constipation a 12-week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 2009;
29: 315-328.
8. Gu a Europea Spada C, Hassan C, Galmiche JP, et al. Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Endoscopy, 2012.
Disclosure of Interest: None declared
P0791 COMPARATIVE STUDY OF SMALL BOWEL TRANSIT TIME IN
TWO SMALL-BOWEL CAPSULE ENDOSCOPY SYSTEMS
I. Ribeiro1,*, R. Pinho1, A. Rodrigues1, T. Pais1, C. Fernandes1, J. Silva1,
A. Ponte1, S. Leite1, J. Carvalho1
1
Centro Hospitalar Vila Nova Gaia, Vila Nova Gaia, Portugal
Contact E-mail Address: iolandacribeiro@gmail.com
INTRODUCTION: Some studies1 suggest that the MiroCam endoscopy capsule (CE) has a small bowel transit time (SBTT) greater than Given CE, which
may result in greater detection of positive lesions.
AIMS & METHODS: Aims: To compare the SBTT, the detection of positive
lesions and percentage of complete studies between Mirocam and Given .
Methods: retrospective study of 429 patients who underwent CE between 20052013. Lesions were considered positive according to the indication of CE:
obscure gastrointestinal bleeding (OGIB) - multiple erosions/ ulcers, typical
angiodysplasias, tumor and blood; suspected Crohns disease (CD)/ evaluation
of the extension of CD - multiple erosions/ ulcers and blood; abdominal pain tumor, multiple erosions / ulcers and blood. Statistical tests: t-student; X2
RESULTS: The mean age was 54.2 years. MiroCam CE was performed in
48.7% of patients and Given CE in 51.3% patients. Indications for performing
CE: OGIB 62.5%, suspected CD/ evaluation of the extension of CD - 21.2%,
polyposis 5%, abdominal pain 4.4% and others 6.8%.
The mean gastric transit time (GTT) in MiroCam and Given CE was
identical (38min vs 41min, p 0.52). The mean SBTT of MiroCam CE
was superior to Given CE - 5h17min vs 4h45min, p 0.004. We did not find
any differences between the two CE with respect to mean age (MiroCam - 54.9
years; Given - 53.6 years, p 0.46), sex (Mirocam - female sex 57%; Given female sex - 61.3%, p 0.35), percentage of diabetic patients (10.1% MiroCam
- 10.1%; Given - 14.5%, p 0.2), percentage of complete exams (MiroCam 90%; Given - 89%, p 0.63) and positive lesions (MiroCam - 38.2%, Given - 39.5%, p 0.78). There were also no differences regarding the indications for CE (p 0.051).
CONCLUSION: Our study suggests that the SBTT of MiroCam CE was
superior to Given CE, but it does not influence the positive findings or complete examination rate. However, a longer SBTT is associated with a longer
reading time, an important aspect in daily clinical practice.
REFERENCES
1 - Pioche M, et al. Prospective, randomized comparison of two small-bowel
capsule endoscopy systems in patients with obscure GI bleeding. Gastrointest
Endosc 2011; 73: 1181-1188.
Disclosure of Interest: None declared

A349

United European Gastroenterology Journal 2(1S)


P0792 THE USE OF SMALL BOWEL CAPSULE ENDOSCOPY IN
OCTOGENARIANS; THE EDINBURGH EXPERIENCE
L. Bartzis1, A. Koulaouzidis1,*
Centre for Liver & Digestive Disorders, The Royal Infirmary OF Edinburgh,
Edinburgh, United Kingdom
1

INTRODUCTION: Over the last 13 years, the clinical use of capsule endoscopy
(CE) has revolutionised the investigation pathways for the small-bowel.
Although (as procedure) non-invasive, there are reports of capsule aspiration
in certain patient-groups.[1] Moreover, CE video sequence review is a time-consuming process and on occasions with limited diagnostic yield (DY). There is
scarcity of data on the use of CE in octogenarians.[2-4]
AIMS & METHODS: Aim: We aim to report our centres experience in using CE
in octogenarians. Setting: University hospital & tertiary referral centre for CE for
the South East of Scotland. Retrospective study; the small-bowel CE database of
our unit was interrogated for patients480 years of age who underwent CE.
Categorical data are reported as mean SD (range). The Fischers exact, the
chi-square and the t (unpaired) tests were used to compare datasets. A twotailed P value of 50.05 was considered statistically significant.
RESULTS: 1,477 patients underwent small-bowel CE between 2005 and 2013. 93
CE were performed in 84 (35M/59F) octogenarians; mean age 84 2.9 years.
PillCamSB1/SB2 & MiroCam were used in 61 & 32 CE examinations, respectively. Ten (11.9%) patients had more than 1 CE. One patient was unable to
swallow the capsule, and in another the capsule was retained in the stomach. The
CE report was unavailable in one case. Indications for small-bowel CE were iron
deficiency anaemia (IDA): 44, obscure gastrointestinal bleeding (OGIB): 29,
OBIGIDA: 6, diarrhoea: 4,?small-bowel varices:1. Forty-five (53.6%) patients
subsequently died. The mean time from small-bowel CE to death was 23 20.9
months, (range: 0.13-83 months). The DY (all findings) of CE in our octogenarian cohort was 56.8%. Vascular lesions (any P class)/active bleeding were found
in 33, inflammatory pathology in 9, and other findings in 4 CE. No neoplastic
pathology was identified. The DY was independent to the indications for the
procedure (P 0.166), the small-bowel CE system used (P 0.068), the patient
final outcome i.e. deceased/alive (P 0.051) and/or the time from CE to death
(P 0.053).
CONCLUSION: CE in patients 480 years of age has high DY, but sinister
pathology in this cohort is rare. Furthermore, small-bowel CE has limited
impact on the final patient outcome in this patient-group.
REFERENCES
1. Koulaouzidis A, et al. Small-bowel capsule endoscopy: a ten-point contemporary review. World J Gastroenterol 2013; 19: 3726-3746.
2. Koulaouzidis A, et al. The use of small-bowel capsule endoscopy in irondeficiency anemia alone; be aware of the young anemic patient. Scand J
Gastroenterol 2012; 47: 1094-1100.
3. Tsibouris P, et al. Capsule endoscopy findings in patients with occult or overt
bleeding older than 80 years. Dig Endosc 2012; 24: 154-158.
4. Sidhu R and McAlindon ME. Age should not be a barrier to performing
capsule endoscopy in the elderly with anaemia. Dig Dis Sci 2011; 56: 2497-2498.
Disclosure of Interest: L. Bartzis Financial support for research from: Grant from
the Hellenic Society of Gastroenterology, A. Koulaouzidis Financial support for
research from: ESGE-Given Imaging research grant 2011, Lecture fee(s) from:
Dr Falk Pharma, Other: Travel support: Dr FalkPharma, Abbott,MSD
P0793 USEFULNESS OF FLEXIBLE SPECTRAL IMAGING COLOR
ENHANCEMENT (FICE) IN DIFFICULT TO INTERPRET MUCOSAL
ULCERATIVE LESIONS OF THE SMALL BOWEL
M. Rimbas1,2,*, L. Negreanu2,3, L. Ciobanu4, C. Spada5, A. Bengus2,
C.R. Baicus2,6, G. Costamagna5
1
Gastroenterology Department, Colentina Clinical Hospital, 2Internal Medicine
Department, Carol Davila University of Medicine and Pharmacy, 3Internal
Medicine Department, Emergency University Hospital, Bucharest, 4Regional
Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of
Medicine and Pharmacy, Cluj-Napoca, Romania, 5Digestive Endoscopy Unit,
Universita Cattolica del Sacro Cuore, Rome, Italy, 6Clinical Research Unit
RECIF, Reseau dEpidemiologie Clinique International Francophone, Bucharest,
Romania
Contact E-mail Address: mrimbas@gmail.com
INTRODUCTION: Identification of subtle small bowel mucosal lesions can
sometimes be challenging, as small differences in mucosal hue or pattern are
difficult to detect. To overcome this problem, chromoendoscopy virtual techniques based on narrowing the bandwidth of the conventional white light endoscopy (WLE) image were imagined, possibly allowing for contrast-enhanced
assessment of the nature of small-bowel mucosal lesions. However, data on the
already implemented FICE (Flexible spectral Imaging Color Enhancement) software application in videocapsule endoscopy (VCE) are limited.[1-3]
AIMS & METHODS: This is a multicenter study involving a selection of mixed
de-identified images of 250 difficult to interpret small bowel ulcerative lesions
(selected as the least representative visualization of an unequivocally confirmed
erosion from a succession of images, comprising small or shallow mucosal
defects, erosions lacking a clear rim of erythema or located marginally in the
field of view, or lesions with a poor image quality due to luminal content), and 50
artifacts mimicking ulcerative lesions, all selected from the 64 VCE recordings in
a prospective study (ClinicalTrials.gov ID NCT00768950). The evaluation was
performed by three blinded experienced VCE readers in two steps, initially as
white light images, then with the addition of all available FICE settings (1,2,3
and Blue), labeling them as real or faked lesions and rating each FICE setting as
useful or not. The comparison of accuracies in correctly categorizing the images
was performed between the two readings (McNemars test).

RESULTS: Between the first (WLE only) and the second (FICE aided) reading,
in terms of accuracy, there was a 19.5% [95% CI:15.7% to 23%] improvement
(from 52% to 71.5%) in the global evaluation of all images (p50.001), coming
from a 26% [95% CI: 22% to 30%] improvement (from 47% to 73%) in the
evaluation of true ulcerative images (p50.001), and a 12% [95% CI: 3.5% to
22%] decrease (from 75% to 63%) in the evaluation of faked ulcerative images
(p50.01), results reproduced for all three readers. FICE 1 and 2 settings were
rated as most useful.
CONCLUSION: This study demonstrates that FICE virtual chromoendoscopy
(mostly settings 1 and 2) applied for VCE is useful to enhance surface patterns
and color differences and to better categorize difficult to interpret small bowel
mucosal ulcerative lesions. However, care must be taken, and individual images
should only be evaluated as part of a succession in a recording, as the technology
could also misguide the interpretation of artifacts as ulcerative lesions.
REFERENCES
1. Gupta T, et al. Evaluation of Fujinon intelligent chromo endoscopy-assisted
capsule endoscopy in patients with obscure gastroenterology bleeding. World J
Gastroenterol 2011; 17: 4590-4595.
2. Imagawa H, et al. Improved detectability of small-bowel lesions via capsule
endoscopy with computed virtual chromoendoscopy: a pilot study. Scand J
Gastroenterol 2011; 46: 1133-1137.
3. Duque G, et al. Virtual chromoendoscopy can be a useful software tool in
capsule endoscopy. Rev Esp Enferm Dig 2012; 104: 231-236.
Disclosure of Interest: None declared
P0794 THE CORRELATION OF WIRELESS VIDEO CAPSULE
ENDOSCOPY AND OTHER RADIOLOGICAL IMAGING IN THE
INVESTIGATION OF SUSPECTED AND ESTABLISHED SMALL
BOWEL CROHNS DISEASE
P. Moore1,*, G. Holleran1, B. Hall1, D. McNamara1
Tallaght Hospital, Tallaght, Ireland
Contact E-mail Address: moorepe@tcd.ie
1

INTRODUCTION: Background: In recent times there have been significant


advances in both the radiological, CT and MRI Enterocolysis (CTE / MRE)
and the endoscopic, video capsule endoscopy (CE) investigation of small bowel
disease. The optimal complimentary and appropriate use of various new evolving
and standard diagnostic modalities remains to be established. In particular, their
role in identifying small bowel Crohns disease remains unclear. Early identification of ileal Crohns disease is desirable to guide treatment and impact on longterm outcome.
AIMS & METHODS: Aim: To compare the diagnostic performance of CE and
radiological imaging in detecting small bowel Crohns disease in the local population and to correlate the findings of CE with other various imaging modalities.
Method: A retrospective analysis was undertaken of a database of patients who
underwent capsule endoscopy from 2009 to 2013 at Tallaght Hospital. Those
patients who underwent CE for known histologically-confirmed or suspected
Crohns disease were identified. This cohort was cross-referenced with the
Hospital Radiology Report system Keogh for the same period. Patient demographics, radiological procedures, CE and radiology findings were recorded. The
diagnostic yield and correlation coefficient was calculated for radiological tests
compared to CE.
RESULTS: Results: In all, 263 patients, 155 female (59%), mean age 41 years,
had a CE for known (n 29, 11%) or suspected (n 234, 89%) Crohns disease.
In all 110 (42%) had active disease on CE. In only 96 (37%) patients additional
radiological tests were available for comparison, 73 (76%) and 23 (24%) in
positive and negative CE cases. Of 28 CTEs, 28 SBFTs and 17 Abdominal
CTs performed in positive CE subjects only 37 (51%) also reported evidence
of active Crohns disease, overall correlation coefficient k 0.49, 95% CI 0.370.61. SBFT was the least sensitive test, 32% (9/28), while CTE and Abdominal
CTs had similar diagnostic yields of 64% (11/17) and 61% (17/28). Correlation
was better among patients without active Crohns disease, with 20 of 23 radiological tests, 7 CTEs, 7 SBFTs and 9 Abdominal CTs also being reported as
normal, correlation coefficient k 0.87, 95% CI 0.72-1.0. The incremental diagnostic yield for CE in patients with suspected or known Crohns disease in our
cohort compared to radiological investigations was 34%, CE 76% and all
Radiology 42%. Table 1: Diagnostic yield according to test.
Number (%)

CE

CTE

CT-Abd

SBFT

Positive
Negative
Total

73 (76%)
23 (24%)
96

18 (51%)
17 (49%)
35 (36%)

11 (42%)
15 (58%)
26 (27%)

11 (31%)
24 (69%)
35 (36%)

CONCLUSION: Despite its poor diagnostic yield and the advent of new diagnostic modalities SBFT remains a frequently employed test in CD.
Notwithstanding the inherent bias in our study, the findings suggest the correlation between CE and standard and targeted small bowel radiology is at best
moderate, with CE having a higher diagnostic yield. CE should be considered
in all subjects with suspected Crohns disease.
Disclosure of Interest: None declared

A350

United European Gastroenterology Journal 2(1S)

P0795 PROSPECTIVE FOLLOW-UP OF MESENTERIC PANNICULITIS


IN A FRENCH UNIVERSITY HOSPITAL; SHOULD WE GO ON WITH
CLOSED FOLLOW UP OF PATIENTS?
1,*

Station

Cardia
(%)

Fundus
(%)

Body
(%)

Incisura
(%)

Antrum
(%)

Pylorus
(%)

Station 1 Station 3
Station 1 Station 4

87
92

99
99

99
99

100
100

100
100

45
86

C. Briquez , L. Vuitton , F. Mauny , S. Valmary , S. Koch , N. Badet ,


E. Delabrousse4
1
gastroenterology, 2centre de methodologie clinique, 3Pathology, 4Radiology,
Besancon university hospital, Besancon, France
Contact E-mail Address: lvuitton@chu-besancon.fr
INTRODUCTION: Mesenteric panniculitis (MP) is a rare, non-specific inflammatory process affecting the adipose tissue of the mesentery. Symptoms may be
absent or there may be fever, abdominal pain, vomiting or diarrhea. MP is
characterised on computed tomography (CT) scan by an increased mesenteric
fat density called misty mesentery and the presence of lymph nodes within the
fatty mass; and sometimes the presence of a hypodense halo surrounding blood
vessels and nodes called fat ring sign, and/or a hyperdense pseudocapsule
surrounding the mesenteric fat. Prior studies suggested an association of MP
with malignancy and also with acute abdominal disorders, infectious or inflammatory diseases. However data are heterogeneous and mainly retrospective and
patients care and follow-up remain unclear.
AIMS & METHODS: We aimed to evaluate the prevalence of cancer in patients
with MP on abdominopelvic CT scans, and to study clinical and radiological
course of patients. A prospective and descriptive study was performed in a
French University hospital. All CT scans performed in the Radiology department
between January 2012 and February 2013 with a diagnosis of MP were recorded.
The diagnosis of MP was defined as the presence of misty mesentery, infracentimetric nodes, and the absence of invasion of the adjacent small-bowel loops
and vascular structures. Clinical and radiological characteristics of patients with
MP were recorded, and patients with isolated MP were followed-up in the
Gastroenterology department. An initial search for associated disease, especially
for cancer, was performed and prospective 1-year follow-up was proposed.
RESULTS: MP was diagnosed based on CT findings in 100 consecutive patients
among 9027 abdominopelvic CT scans (1.1%) over the study period; 54 patients
(54%) had cancer, of which 12 (22 %) were melanomas and 11 (20 %) were
lymphomas. MP was present at the time of diagnosis (35/54), or appeared within
the subsequent months (7/54). Twenty-two patients had MP associated with
acute abdominal disorders, and 24 patients had isolated MP. Among those
patients and during the prospective follow-up only one cancer was diagnosed,
and it was a basal cell carcinoma. Regarding radiological aspects of MP: a
pseudocapsule was found in 58 % of cases, a fat ring sign in 63 % of cases
and a left-sided location in 88 % of cases. There were no significant difference
between the radiological characteristics of MP according to the associated diseases, especially cancer.
CONCLUSION: This study is one of the largest to describe MP diagnosed at CT
scan and the first to propose prospective evaluation of patients. MP is frequently
associated with cancer, mainly melanoma and lymphoma, already documented at
the time of MP diagnosis. However data from follow-up suggest that when PM is
isolated, or associated with other disease there does not appear to be underlying
or incidental cancer.
Disclosure of Interest: None declared
P0796 CT RADIOLOGICAL MODELLING OF THE UPPER GI TRACT
ANATOMY; ESSENTIAL CLUES TO PERFORMING MAGNETIC
ASSISTED CAPSULE ENDOSCOPY (MACE)
I. Rahman1,*, M. Kay1, T. Bryant1, S. Pelitari1, P. Patel1
1
University Hospital Southampton, Southampton, United Kingdom
Contact E-mail Address: imdi81@hotmail.com
INTRODUCTION: Capsule endoscopy, employed to investigate the small
bowel, is now being further developed to visualise the upper GI tract. In a pig
model, using a hand held magnet, we have demonstrated that magnetic assisted
capsule endoscopy (MACE) in the stomach is feasible. However, it is unclear
what the best methodology is to achieve complete gastric luminal views in
humans. Our aim was to utilise CT modelling of the abdomen to determine
the optimal placements of a capsule endoscope in the stomach to allow complete
mucosal visualisation and to determine the optimal placement of the hand held
magnet to aid pyloric traversing.
AIMS & METHODS: Using multiplanar reformatting, 100 good quality contrast abdominal CT scans were analysed to assess luminal visualisation by a
magnetic capsule endoscope from 5 fixed stations throughout the stomach.
From each station, we assessed the ability of a capsule endoscope to visualise
6 anatomical landmarks (cardia, fundus, body, incisura, antrum and pylorus).
Success of visualisation of an anatomical area was only accepted when 490%
mucosal visualisation was achieved from a particular station. The pyloric canal
angles were calculated to create a vector. We mapped the position of this vector
on the patients skin (pyloric canal vector surface point) to determine the optimal
placement of the magnet that would allow traversing of the capsule endoscope
through the pylorus.
RESULTS: There were 65 female and 35 male patients. Mean age of patients was
53 years (s.d/-18 years). Best mucosal visualisation of the stomach landmarks
was achieved from 3 stations; fundal dependant, antral dependent and opposite
the antral dependent points. Maximal visualisation of the whole of the stomach,
required combining 2 stations as shown in Table 1

The optimal positioning of the magnet to aid pyloric traversing was posteriorly
between vertebrae T5 to L2, in an area 10cm to the left and 18cm to the right
(83% cases). Age455yrs (p 0.03) and the ability to view the pylorus from
station 3 (p 0.04) was associated with an extreme pyloric canal vector.
CONCLUSION: CT modelling has provided important data regarding the optimal stations in the stomach to position a magnetic capsule endoscope to allow
maximal luminal mucosal visualisation and traversing the pylorus. Although
there is some extreme variation in the upper GI anatomy, the majority of cases
will allow the use of a single standard method in performing MACE which may
be very useful for screening purposes.
Disclosure of Interest: None declared
P0797 INVESTIGATION
OF
URGENT
REFERRALS
UNEXPLAINED IRON DEFICIENCY ANAEMIA: IS A CT SCAN
RELEVANT?

WITH

J. Iqbal1,*, G. Kaur1
1
Surgery, SCUNTHORPE GENERAL HOSPITAL, Scunthorpe, United
Kingdom
Contact E-mail Address: gkaur@email.com
INTRODUCTION: Anaemia is a common medical problem and can be due to
deficiency of one or more nutrients, blood loss or a variety of medical problems.
Generally, anaemia of almost any degree requires medical assessment so that the
correct cause can be ascertained and appropriate treatment given. The patients
symptoms and initial FBC findings will influence both the urgency and direction
of initial clinical investigation. Upper and lower GI investigations should be
considered in all males and post-menopausal females with iron deficiency anaemia unless there is an obvious alternative cause. NICE guidelines for referral for
suspected colorectal/ Upper GI cancer includes referral of patients with unexplained iron deficiency anaemia who are men of any age with a haemoglobin of
11 g/100 ml or below and who are non-menstruating women with a haemoglobin
of 10 g/100 ml or below. Unexplained iron deficiency anaemia does not usually
prompt a referral to chest physicians, gynaecologists nor the urologists.
AIMS & METHODS: All our urgent referral patients with iron deficiency anaemia are investigated with upper and lower GI endoscopy where possible and a
CT scan of the chest abdomen and pelvis. We aimed to evaluate our management
of these patients with respect to investigations performed, especially the cost
effectiveness of a adding on a CT scan to the upper and lower GI scopes that
are always part of this investigation.
All Urgent referrals to the Colorectal unit over a 3 month period were retrospectively analysed. CT scan, Colonoscopy and Flexible sigmoidoscopy data was
collected as well as any histology obtained from biopsies taken.
Of 73 urgent referrals, 54 were referred with Iron deficiency anaemia. Of these, 46
(85%) underwent a Lower GI scope (37 Colonoscopy and 9 Flexible sigmoidoscopy); 8 did not undergo any scope - 1 failure, 1 refusal (both underwent CT
pneumocolon) and 6 patients who were considered too frail, poor mobility etc.
43% patients undergoing colonoscopy were reported normal; of the 57% with
findings, 28% were found to have bowel cancer. 98% patients referred urgently
with unexplained iron deficiency anaemia underwent a CT scan; of these, 15
(28%) were normal. Of the remaining 38 patients, 47% had significant findings
with respect to malignancy (half of which were bowel related) and the remaining
53% had other relevant non-cancer pathology (40% of which was bowel related).
Hence, CT scans picked up non bowel related pathology that would not have
been found on colonoscopy alone in 39% patients referred urgently with iron
deficiency anaemia, 17% of which was significant with respect to malignancy.
CONCLUSION: Patients with iron deficiency anaemia are generally referred to
gastroenterology / colorectal surgery for further investigations, with appropriate
urgency. These patients are usually investigated with a gastroscopy and colonoscopy. We found our routine use of an addition of a CT scan chest, abdomen and
pelvis yielded useful results, both related to malignant and non malignant nonbowel related pathology. This helped us guide further management appropriately, with an urgency dependent on the causative pathology. We would therefore
recommend the routine use of a CT scan in the investigation of a patient referred
urgently with iron deficiency anaemia, unless contraindicated for any reason.
Disclosure of Interest: None declared
P0798 PATIENT-RELATED
FACTORS
AFFECTING
PATIENT
ACCEPTANCE FOR REDUCED-LAXATIVE CT COLONOGRAPHY:
WHO DOES PREFER TO CT COLONOGRAPHY?
K. Nagata1,2,*, A. Iyama3, H. Kanazawa2, T. Mikami3, H. Sugimoto2
1
Department of Gastroenterology, Tokyo International Clinic, Chiyoda-ku,
2
Department of Radiology, Jichi Medical University, Shimotsuke, 3Department of
Radiology, Sakakibara Sapia-tower Clinic, Chiyoda-ku, Japan
Contact E-mail Address: Nagata7@aol.com
INTRODUCTION: Although CT colonography (CTC) is minimal invasive procedure, the actual patient acceptance for CTC varies between patients.
AIMS & METHODS: The aim of this prospective study was to assess patient
tolerance and to identify the patient-related factors affecting the patient

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United European Gastroenterology Journal 2(1S)


acceptance of reduced-laxative CTC in screening purpose. A total of 1242 outpatients at average risk for colorectal cancer were consecutively enrolled in this
study. All patients underwent reduced-laxative fecal-tagging CTC with 64-detector row CT using carbon dioxide insufflation. Patients age, gender, height,
weight, and the bowel habits were recorded before the procedure. After the
procedure, acceptance and preference were evaluated using self-assessed questionnaires regarding tolerance assessment for overall procedure and preference
for future testing.
RESULTS: Percentages of patients in good tolerance category for CTC were
83.9% (897/1069). Sixty percent (641/1062) of patients were willing to accept
CTC as a future method of examination. Discomfort factors during CTC were
abdominal distention (64.8%) and abdominal pain (4.9%). Among the patient
factors, only the older age affected the degree of discomfort during CTC (over 60
vs. under 60, odds ratio 1.59, p 0.006). Patient factors of gender, BMI, constipation/laxative use, history of abdominal surgery, and previous colonoscopy
or barium enema experiences were not related to patient tolerance during CTC.
CONCLUSION: An uncomfortable CTC procedure may be expected in elder
patients. Overall, reduced-laxative CTC has excellent patient tolerance.
Disclosure of Interest: None declared
P0799 INCIDENTAL SLIDING HIATAL HERNIA: FINDINGS AND
RELATIONSHIP WITH CT WITH WATER ENEMA AND CT
COLONOGRAPHY
M. Revelli1, M. Furnari2,*, L. Bacigalupo3, F. Paparo3, D. Astengo1,
E. Savarino4, G.A. Rollandi3
1
E. O. Ospedali Galliera, Unit of Radiology, 2Di. M. I., Gastroenterology Unit,
UNIVERSITY OF GENOA, 3Unit of Radiology, E. O. Ospedali Galliera, genoa,
4
Division of Gastroenterology, Department of Surgery, Oncology and
Gastroenterology, University of Padua, Padua, Italy
Contact E-mail Address: matteorevelli@gmail.com
INTRODUCTION: Barium-contrast radiography originally constituted the first
development in diagnosing hiatal hernia (HH) and reflux disease however, conventional radiology is no more a gold standard investigation for their assessment.
We observed in clinical practice a worrisome rate of HH type I reported as extracolonic finding during CT with water enema (CT-WE) and CT colonography
(CTC), likely induced by increased intra-abdominal pressure due to colon distension. HH has been positively related with the incidence and severity of reflux
disease and with the risk of its complications. Although HH is not a life-threatening condition it is our opinion that erroneous reporting of HH may trigger
consecutive diagnostic unnecessary processes that induce unmotivated anxiety
and expensive and time-consuming for the patient and the socio-sanitary system.
AIMS & METHODS: To determine whether colonic distension at CT-WE and
CTC can induce a small incidental physiologic sliding hiatal hernia and whether
exist differences between water and gas distension achieved with the two different
techniques. We retrospectively evaluated 400 consecutive patients, 200 undergoing CT with water enema and 200 undergoing CT colonography, including
59 subjects who also underwent a routine abdominal CT evaluation at a different
time, used as internal control, while a separate group of 200 consecutive patients
who underwent abdominal CT evaluation was used as external control. Two
abdominal radiologists assessed the CT exams for the presence of a sliding
HH, grading the size as small, moderate, or large; the internal control groups
were directly compared with the corresponding CT-WE or CTC study looking
for a change in hernia size. We used the Fisher exact test applying a size-specific
correction factor, in order to account for the effect of colonic distention: these
corrected values were then individually compared with the external control
group.
RESULTS: Sliding HH was present in 51% (102/200) of the CT-WE patients and
in 48.5% (97/200) of the CTC patients. Internal control CT of the 31 patients
with a hernia at CT-WE showed resolution of the hernia in 58.1% (18/31) of
patients, including 76.5% (13/17) and 45.5% (5/11) of small and moderate HH.
Comparison CT of the 28 patients with HH at CTC showed absence of the it in
57.1% (16/28) patients, including 68.8% (11/16) and 50% (5/10) of small and
moderate HH. Its prevalence in the external control group was 22% (44/200),
lower than the CT-WE and CTC cohorts prevalence of 51% (p 5 0.0001) and
48.5% (p 5 0.0001). After applying the correction factors for the CT-WE and
the CTC groups, the estimated residual prevalences (16% and 18.5%, respectively) were much closer to that of the external control patients (p 0.160 for CTWE and p 0.455 for CTC).
CONCLUSION: Incidental findings at CT-WE and CTC should be considered
according to the clinical background. Small sliding HH should not be reported in
patients with unrelated symptoms undergoing CT-WE or CTC: when encountering these findings, accurate anamnesis and review of medical history looking for
GERD-related symptoms are essential, in order to address these patients to a
correct diagnostic iter, taking advantage from appropriate techniques such as GI
endoscopy or esophageal manometry.
Disclosure of Interest: None declared
P0800 THE POTENTIAL OF MR COLONOGRAPHY AS A SCREENING
TOOL FOR COLORECTAL CANCER: A COST-EFFECTIVENESS
ANALYSIS
M. Greuter1,*, E. Demirel1, J. Berkhof1, R. Fijneman1, J. Stoker2, G. Meijer1,
V. Coupe1
1
VU University Medical Center, 2Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: mj.greuter@vumc.nl
INTRODUCTION: For colorectal cancer (CRC), a range of screening modalities
is available. Based on diagnostic accuracy, colonoscopy is the preferred test but

there is a low risk on serious complications and, due to the burdensome procedure, the population uptake is low. MR colonography may have potential as a
CRC screening tool since it has comparable test characteristics as colonoscopy
but is less invasive. Furthermore, innovators in the field of MR technology are
striving to develop a targeted contrast agent that specifically detects adenomas at
high risk of progressing to CRC. This might even further increase the potential of
MR colonography for CRC screening.
AIMS & METHODS: To explore the potential of conventional and targeted MR
colonography in terms of (cost-)effectiveness using the Adenoma and Serrated
pathway to Colorectal CAncer (ASCCA) model.
Thirteen screening strategies were evaluated, differing in primary screening
instrument and number of screening rounds. The strategies under consideration
were conventional MR colonography, targeted MR colonography, colonoscopy
and CT colonography with two, three and four screening rounds at a ten year
screening interval. In addition, eleven rounds of biennial faecal immunochemical
test (FIT) screening were evaluated because this is the current Dutch screening
programme. For each strategy, both realistic and perfect participation rates were
taken into account. Incremental costs and effects were estimated from a societal
perspective with an ICER less than the Dutch GDP per capita in 2012, i.e.
E35,823/LYG, considered as cost-effective.
RESULTS: All screening strategies were cost-effective compared to no screening.
For conventional MR colonography, the ICER ranged between E1,271/LYG to
E3,003/LYG for two to four screening rounds at a participation rate of 34%. For
participation rates of 62% and 100%, this range was respectively E1,576/LYG to
E3,777/LYG and E1,971/LYG to E4,577/LYG. However, conventional MR
colonography screening was more expensive than other screening strategies at
comparable LYG, for all participation rates. For example, colonoscopy at two to
four screening rounds at realistic participation (22%) led to cost-savings of E71
to E87 at 0.025 to 0.035 LYG per person. The effectiveness of targeted MR
colonography was only slightly higher than of conventional MR colonography
but it was considerably more costly, even under the most favourable assumptions
regarding test characteristics and costs per test.
CONCLUSION: This is the first study to evaluate the cost-effectiveness of MR
colonography screening for CRC. Although conventional and targeted MR colonography are cost-effective compared to no screening, at the moment they cannot
compete with more established screening tests because of the high costs per test.
Disclosure of Interest: None declared
P0801 PRELIMINARY STUDY OF PHOTODYNAMIC
USING 5-AMINOLEVULINIC ACID IN GASTRIC AND
COLORECTAL TUMORS

DIAGNOSIS

M. Nakamura1,*, J. Nishikawa1, K. Hamabe1, A. Goto1, J. Nishimura1,


H. Shibata1, M. Nagao1, S. Hashimoto1, T. Okamoto1, I. Sakaida1
1
Department of Gastroenterology and Hepatology, Yamaguchi University
Graduate School of Medicine, Ube, Yamaguchi, Japan
INTRODUCTION: Photodynamic diagnosis (PDD) using 5-aminolevulinic acid
(5-ALA), has been performed to detect the accumulation of fluorescent protoporphyrin IX (PpIX) in tumors. 5-ALA is a precursor of the fluorescence-emitting PpIX, and PpIX accumulates specifically in tumor cells and emits
fluorescence when the excitation light irradiated on them. This property of 5ALA may improve the endoscopic diagnosis of gastric and colorectal tumors.
AIMS & METHODS: In this preliminary study, we investigated the utility of 5ALA using PDD in the detection of gastric and colorectal tumors. This prospective single-center study investigated inter-subject variability in patients with early
stage gastric or colorectal tumor indicated for endoscopic resection. Patient
selection criteria were age 2080 years, either sex, and provision of informed
consent. After oral administration of 5-ALA, endoscopic resection of gastric
or colorectal tumors was performed, then the resected specimens were subjected
to fluorescence endoscopy to examine for red fluorescence. Endoscopic, macroscopic, and histopathologic findings of the tumors were assessed.
RESULTS: Ten patients (7 men and 3 women) with a total of 13 lesions (10
gastric and 3 colorectal tumors) were enrolled in this study. Fluorescence was
detected in 7 (53.8%) of the 13 lesions. No significant differences were observed
in sex, age, color of the tumor, tumor diameter, macroscopic type, histological
type, invasion depth, lymph node metastasis, or procedure time between the cases
with and without fluorescence. The detection rate of fluorescence tended to be
high for elevated lesions. Liver dysfunction developed in 4 (40.0%) of the 10
patients.
CONCLUSION: The results of this preliminary study suggest the utility of PDD
using 5-ALA for screening gastric and colorectal cancers.
Disclosure of Interest: None declared
P0802 INCREASED VISCERAL TO SUBCUTANEOUS FAT RATIO IS
ASSOCIATED WITH LOWER RISK OF IBD RELATED SURGERY
IN PATIENTS WITH CROHNS DISEASE ON INFLIXIMAB
P. Brown1,*, D. Tolan2, L. Warren3, T. Clark3, G. Dowson3, J. Hamlin3,
V. Subramanian1
1
Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, St James
University hopsital, Universityof Leeds, 2Radiology, 3Gastroenterology, St James
University Hospital, Leeds Teaching Hospital NHS Trust, Leeds, Leeds, United
Kingdom
Contact E-mail Address: v.subramanian@leeds.ac.uk
INTRODUCTION: Fat wrapping and mesenteric hypertrophy are characteristics of Crohns disease (CD). In patients with CD, mesenteric adipose tissue
releases higher levels of adiponectin, which could up-regulate production of
tumor necrosis factor- and increase the risk for aggressive disease. We have

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United European Gastroenterology Journal 2(1S)

previously shown that a higher visceral to subcutaneous fat ratio was associated
with complicated (stricturing or fistuling) CD (reference).
AIMS & METHODS: The aim of this study was to investigate the effect of
visceral fat accumulation on clinical outcomes in patients with CD on
Infliximab. We identified patients with a confirmed diagnosis of CD on
Infiximab who had computed tomography or magnetic resonance imaging
scans of their abdomens within 12 weeks of starting infliximab, from the biologics database of Leeds Teaching Hospital NHS Trust. Areas of subcutaneous and
visceral fat were measured in 1 cross-sectional scan, taken at the level of the
umbilicus using a previously validated method. All measurements were made
using AdodeTM CS3 with magic wand function. The outcomes of interest were
1) IBD related flare (defined as increase in dose or steroid use or need for IBD
related hospitalization or surgery), 2. Any IBD related surgery and 3) IBD
related resectional surgery.
RESULTS: 150 patients with CD on Infliximab met our predefined inclusion
criteria. The mean age of the patients was 37.2  13.9 years. On multivariate
analysis a higher visceral to subcutaneous fat ratio was associated with a lower
risk of all IBD related surgery (HR 0.125 and 95% CI 0.02 0 0.81) and a lower
risk of an IBD related flare that almost reached significance (HR 0.39, 95% CI
0.13-1.14). Females were less likely to need IBD related surgery (p 0.03) and
ileal and ileo-colonic disease was associated with a higher risk of surgery compared to colonic disease (p 0.03). Only structuring and fistulating disease phenotype was significantly associated with a higher risk of resectional surgery
(p 0.0.2).
CONCLUSION: Higher visceral to subcutaneous fat on cross sectional imaging
at baseline is associated with better clinical outcomes in patients with CD on
Infliximab. This could imply that mesenteric fat hypertrophy has a protective
role in CD.
REFERENCES
Erhayiem B, Dhingsa R, Hawkey CJ, et al. The ratio of visceral to subcutaneous
fat area is a biomarker of complicated Crohns disease. Clin Gastroenterol
Hepatol 2011; 9: 684-687.
Disclosure of Interest: None declared
P0803 "DOUBLE-DUCT"
SIGNIFICANCE?

SIGN

WHAT

IS

THE

CLINICAL

K. Padala1,*, T. Gardner1, R. Sinha2, O. Elneima1, S. Niaz1, J.R. Greenaway2,


D. Joy2
1
Gastroenterology, 2Endoscopy, South Tees NHS Foundation Trust,
Middlesbrough, United Kingdom
Contact E-mail Address: rohits78@gmail.com
INTRODUCTION: Double-duct sign on endoscopic retrograde cholangiopancreatography (ERCP) is considered suggestive of pancreatic or biliary malignancy [1]. This sign is frequently encountered in radiological imaging. We wish to
investigate the prognostic value of the double-duct sign in patients who undergo
magnetic resonance cholangio-pancreatogram (MRCP), attempting to define the
associated features, which would predict underlying malignant disease [1,2].
AIMS & METHODS: An analysis of retrospectively collected database of all
patients (n 2,741) who had MRCP over a four-year period; January 2010 to
December 2013 was performed. All the radiological reports showing both a
dilated common bile duct (CBD) and pancreatic duct (PD) or the doubleduct sign were included. These were all interpreted and reported by specialist
gastrointestinal radiologist. The demographics, liver biochemistry, final diagnosis
and outcome for all patients with the double duct sign were accessed using the
radiology PACS system, biochemical results WebICE, hospital letters and
case notes. Follow up information was available for a mean of 36 months
(range 12-48 months).
RESULTS: 81 patients (annual incidence 2.2% - 3.3% incidence) had doubleduct sign with a mean age of 71 years. The ratio of male to female patients was
(F: M) 1.2:1. The commonest cause of double duct sign was choledo-cholithiasis
(27.2%) followed by malignancy (20%). Patients with jaundice in the context of
double-duct sign had a higher incidence of malignancy (48%). More than half
of the patients, (48/81; 59%) with double-duct sign were anicteric. None of the
anicteric patients were found to have malignancy (p 0.002). Of the anicteric
patients, 25% (12/48) had completely normal liver test and the remaining 75%
(36/48) had some abnormality of the liver enzymes (raised GGT and/or Alkaline
phosphatase). Four patients in the anicteric group had benign tumours (1 case of
benign IPMN [Intra-ductal papillary mucinous neoplasm] and 3 cases of benign
ampullary tumour, histology confirming low grade and high grade dysplasia
without evidence of invasive malignancy on resection specimens). The benign
nature was confirmed on clinical, pathological and radiological follow-up. All
four patients remained anicteric over the period of follow-up (mean 24 months;
and one unrelated death at 18 months). Our results show that double duct sign
in the absence of jaundice makes a malignant aetiology unlikely.
CONCLUSION: In patients with cross-sectional imaging evidence of doubleduct sign, the absence of jaundice makes a malignant aetiology unlikely.
Conversely, in jaundiced patient a malignant cause is much more likely.
REFERENCES
1. Baillie J, et al. Biliary imaging: a review. Gastroenterology 2003; 125: 1565.
2. Ahualli J. The double duct sign. Radiology 2007; 244: 314-315.
Disclosure of Interest: None declared

P0804 QUANTITATIVE ASSESSMENT OF GLOBAL SMALL BOWEL


MOTILITY IN CHRONIC INTESTINAL PSEUDO-OBSTRUCTION
AND CONTROLS: A PRELIMINARY STUDY
S.K. Butt1,*, A. Menys2, D. Atkinson2, A. Plumb2, S.A. Taylor2, N. ZarateLopez1, A. Emmanuel1
1
Gastroenterology, 2Centre for medical imaging, UCLH, London, United Kingdom
Contact E-mail Address: s.butt@ucl.ac.uk
INTRODUCTION: In this preliminary report, we present the initial results of a
prospective investigation comparing MRI quantified global small bowel motility in
healthy controls and patients with proven clinical and radiological Chronic Intestinal
pseudo-obstruction (CIPO). Diagnosis is initially difficult and often delayed, many
patients undergoing unnecessary surgical intervention prior to final diagnosis. MRI
offers a potential non-invasive modality of diagnosis and monitoring, employing
post-processing quantitation of global metrics describing small bowel motility1.
AIMS & METHODS: Subject selection: 11 healthy non-smoking volunteers (7
Male, mean age 33[22 to 48]) and 5 CIPO patients (3 Male, mean age 53[32 to 82])
were recruited. CIPO patients stopped any medications that influenced small bowel
motility for one week prior to scan including opioids, anti-emetics & anti-diarrhoeals.
Study overview: Participants underwent a single MRI motility scan before and
immediately after an injection of 0.5mg IV neostigmine, a cholinomimetic with
potent prokinetic action.
MR Protocol: The motility scan protocol used a 3D Balanced Turbo Field Echo
(BTFE) motility sequence capturing one coronal volume through the abdomen
and pelvis per second over a 20 second breath hold (2.5x2.5x10 in mm resolution,
FA 20, TE 1.7ms, TR 3.5ms, 15cm thickness in 15 reconstructed slices)
Motility Analysis: Dynamic time-series data was registered using a modified 2D
optic-flow technique for each slice through the abdominal volume2. The deformation fields generated by the registration process were used to provide a motility
metric (arbitrary unit, AU) expressed as the standard deviation of pixels Jacobian
(a measure of local area change) and averaged across a user defined ROI.
ROI Placement: A radiologist, with 5 years experience reading MRE, placed
regions of interest (ROIs) around the small bowel in each coronal slice over
the 15-slice volume. The radiologist was blinded both to subject group and
whether the scan was preRESULTS: 1) Mean baseline small bowel motility scores in CIPO patients was
0.19AU (range 0.1 to 0.25) and in controls 0.35AU (range 0.275 to 0.37) with a
statistically significant difference of 0.17AU, p 0.0026 (CI 0.09 to 0.23).
2) The mean percent increase in small bowel motility scores in CIPO patients
following noestigmine was 29% (95% CI from 19 to 50%) and in controls 10%
(range 0 to 34) with a statistically significant difference in groups response to
neostigmine of 19%, p 0.029 (95% CI from 4 to 40%).
CONCLUSION: This study demonstrated significant differences in both resting
and cholinomimetic-induced global motility between CIPO patients and healthy
controls. Despite marked bowel distension in the CIPO patients, motility
appeared present but reduced compared to controls, and responded to provocation with neostigmine suggesting the bowel still exhibits the expected pro-kinetic
effects following pharmacological stimulation. With just five patients this is a
preliminary study, nevertheless initial results appear promising and support our
ongoing investigation program.
REFERENCES
1) Menys, et al. Radiol 2013; 269: 443-450.
2) Odille, et al. MRM 2012; 68: 783-793.
Disclosure of Interest: None declared
P0805 MALIGNANT
GASTRODUODENAL
OBSTRUCTION
TREATMENT WITH SELF-EXPANDABLE METALLIC STENTS IN A
SINGLE REFERRAL CENTRE

L.C. R. Freitas1,*, L. Meireles1, P. Sousa1, J. Lopes1, L.C. Ribeiro1, J. Velosa1


1
Gastrenterology and Hepatology Department, Hospital de Santa Maria, Lisbon,
Portugal
Contact E-mail Address: luisfreitas29@gmail.com
INTRODUCTION: Endoscopic treatment is a valid choice in treating malignant
gastroduodenal obstruction, when patients are not candidates to surgery. Selfexpandable metallic stents (SEMS) have been increasingly used in this context.
AIMS & METHODS: To retrospectively analyze the use of SEMS in malignant
gastroduodenal obstructions, in one referral centre, over a period of 8 consecutive
years.
RESULTS: SEMS were successfully inserted in 43 patients in this period (male sex
21 (48.8%); mean age 70.67/-13.46 years), all of them complaining with stasis
symptoms. Primary tumor was gastric adenocarcinoma in 26 patients (60.5%),
pancreatic adenocarcinoma in 12 patients (27.9%), and cholangiocarcinoma, gallbladder and colon cancer in 5 patients (11.6%). The median time between tumor
diagnosis and stent placement was 27.5 days (range 0-980). Complications to the
procedure occurred in 3 patients (7%): hypovolemic shock, perforation and aspiration pneumonia. Clear clinical improvement (tolerance to oral intake) was seen in
26 patients (60.5%). In 10 patients (23.3%), reintervention due to stent occlusion
was necessary, including stent-in-stent placement in 6 patients, balloon dilation in 2
and argon plasma coagulation in 2. Median survival after sent insertion was 42
days (range 1-420), with 15 patients (34.9%) dying within less than 30 days after
the procedure, with no statistical significant differences between different ages and
different types of primary tumor.
CONCLUSION: When feasible, SEMS placement is a safe and efficient therapy
for malignant gastroduodenal obstruction. The relatively high percentage of
patients that were dead one month after stent placement, in our series, may
reflect an over-selection of patients that had too advanced a disease to benefit
from this technique.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0806 SELF EXPANDIBLE METAL STENTS IN VARICEAL BLEEDING
AS THE BLAKEMORE-SENGSTAKEN TUBE OF NOWADAYS? A
SINGLE INSTITUTION EXPERIENCE
M. Muller1,*, T. Seufferlein1, M. Wagner1, A. Kleger1
1
Department of Gastroenterology, Universitatsklinikum Ulm, Ulm, Germany
Contact E-mail Address: martin.mueller@uniklinik-ulm.de
INTRODUCTION: Despite a dramatic reduction of lethality rates due to upper
gastrointestinal bleeding, esophageal variceal bleeding remains a challenge and
still accounts for a mortality rate of up to 50 % within the first 6 weeks. Rapid
and efficient varical ligations in combination with vasoactive terlipressin are key
requirements for the initial patients stabilization. However, a relevant proportion
of esophageal varical bleeding remains refractory, thus, making a call for additional tools to achieve hemostasis. Self expandible metal stents (SEMS) incorporate such a tool.
AIMS & METHODS: We report 12 cases of stent application in patients with
variceal bleeding between 2011 and 2014. A retrospective analysis reporting a
series of clinically relevant parameters in combination with bleeding control rates
and adverse events was performed.
RESULTS: The initial bleeding control rate was 100 %. Despite this success, we
observed a 30% mortality within the first 42 days due to non-hemorrhage associated reasons in the cirrhotic patients. Interestingly, we found in 7 out of 12
patients stent dislocation even after a proven correct position 24 h after hemostasis. The stent removal procedure appeared to be safe with slight reactivation of
bleeding in only one of our patients. Of note, our study cohort required an
extensive amount of hospital care.
CONCLUSION: Self expandible metal stents seem to be safe and efficient in
patients with therapy refractory variceal bleeding. Despite high rates of stent
migration no serious adverse events were observed in short term observation.
This contrasts strongly with the formerly used Blakemore-Sengstaken tubes.
Thus, SEMS should be considered as the new Gold standard in case of refractory
esophageal bleeding.
Disclosure of Interest: None declared
P0807 SAFETY AND EFFICACY OF COLONIC STENTING: 7 YEAR
EXPERIENCE FROM A DISTRICT GENERAL HOSPITAL IN THE UK
M. Hu1,*, V. Mitra1, V. Krishnan1, D. Majumdar1, B. Chaudhury1, J. Hancock1,
D. Dwarakanath1
1
Department of Gastroenterology, University Hospital of North Tees, Stockton-onTees, United Kingdom
Contact E-mail Address: deepak.dwarakanath@nth.nhs.uk
INTRODUCTION: A significant proportion of patients with colon cancer present with partial or complete bowel obstruction. Emergency decompression surgery may be associated with up to 25% mortality1. Self expandable metal stents
(SEMS) provide an alternative low-risk option for managing these patients2 and
have been routinely used as the first line of treatment of these patients in our
hospital. The aim of this study was to assess the safety and efficacy of SEMS in
malignant colonic obstruction (MCO) in a district general hospital (DGH)
setting.
AIMS & METHODS: A retrospective study of patients presenting with MCO
and treated with uncovered SEMS between 2007 and 2013 was carried out. All
stents were deployed by experienced gastroenterologists. Data including patient
demographics, indication and treatment intent, site of lesion, stent type, procedure outcome, adverse events, and outcome at six months were obtained using
the endoscopy reporting software and hospital patient record.
RESULTS: 78 patients were included. 53 (68%) had elective and 25 (32%) had
emergency stenting. Median age was 77 years (range 47-96 years). 53 (68%)
patients were male. 4 (16%) out of 25 patients who underwent emergency stenting subsequently had curative surgery. 6 (11.3%) patients in the elective stenting
group (n 53) had curative surgery. Overall, SEMS was used as a bridge to
surgery in 10 (12.8%) patients while 68 (87.2%) underwent palliative stenting.
The sites of malignancy were as follows: sigmoid colon 40 (51.3%), descending
colon 15 (19.2%), rectum 14 (17.9%), transverse colon 7 (9.0%) and anastomotic
recurrence post left hemicolectomy 2 (2.6%). Procedure related serious complications included one case of stent related perforation (proceeded to palliative
rescue Hartmanns procedure) and one of contrast extravasation (successfully
managed conservatively). 3 patients presented with early stent failure from
blocked stent patency was restored in one with endoscopy, one underwent
Hartmanns procedure and the third patient chose to be palliated. The stents
did not adequately restore luminal patency in 2 patients despite optimal positioning. Stent migration was discovered in 2 patients who represented with partial
obstruction. 2 patients with rectal stents complained of discomfort and were
managed conservatively. The technical success rate was 98.7% (n 77) and the
clinical success rate (functional stent without complication) was 88.5%. The 30day all-cause mortality was 10.3% (n 8) with none being attributable to the
procedure.
CONCLUSION: Our study shows that a safe and effective colonic stenting
service can be delivered in a DGH setting. There was no procedure related
mortality compared to emergency decompression surgery which has a higher
mortality rate1. This relates to service delivery by experienced operators. We
suggest that all DGH with acute surgical admissions should provide this service
to reduce the morbidity and mortality related to emergency decompression
surgery.
REFERENCES
1 Tekkis PP, et al. The Association of Coloproctology of Great Britain and
Ireland study of large bowel obstruction caused by colorectal cancer. Ann Surg
2004; 240: 76-81.

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2 Small AJ, et al. Endoscopic placement of self-expandable metal stents for
malignant colonic obstruction: long-term outcomes and complication factors.
Gastrointest Endosc 2010; 71: 560-572.
Disclosure of Interest: None declared
P0808 ENDOSCOPIC
STENT
PLACEMENT
OR
SURGICAL
GASTROJEJUNOSTOMY FOR THE PALLIATION OF MALIGNANT
GASTRIC OUTLET OBSTRUCTION CAUSED BY UNRESECTABLE
OR METASTATIC GASTRIC CANCER
M. Murakami1,*, R. Takenaka1, C. Sakaguchi1, S. Oka1, Y. Baba1, N. Okazaki1,
D. Kawai1, H. Tsugeno1, K. Takemoto1, S. Fujiki1
1
Gastroenterology, Tsuyama, Japan
INTRODUCTION: Malignant gastric outlet obstruction (GOO) is traditionally
treated with gastrojejunostomy (GJJ). Recently, endoscopic placement of a selfexpanding metal stent (SEMS) to the GOO was covered by insurance and spread
widely in Japan because it was a minimally invasive and effective method. The
aim of this study was to verify the usefulness of SEMS compared with GJJ.
AIMS & METHODS: We conducted a retrospective study comparing the
patients treated with endoscopic SEMS placement from April in 2010 to
December 2013 with those treated with GJJ from April in 2000 to December
2013 in the management of malignant GOO caused by gastric cancer. Endoscopic
SEMS placement was performed by using WallFlex duodenal stent (Boston
Scientific, Tokyo, Japan). Following variables were evaluated between the
SEMS group and the GJJ group; age, gender, clinical stage of gastric cancer,
procedure time, Gastric Outlet Obstruction Scoring System (GOOSS) score,
fasting period after placement, period of hospitalization after placement, survival
period after placement, and complications.
RESULTS: The study subjects consisted of 16 patients in the SEMS group and
28 patients in the GJJ group. Between the 2 groups, there were no significant
differences in median age (70 years vs. 72 years), percentage of women (31% vs.
18%), percentage of clinical stage at IV (81% vs. 89%), median GOOSS score (1
vs. 1). The technical success rates were 100% both in the SEMS group and the
GJJ group. Median procedure time for SEMS stent placement was shorter than
that for GJJ (25 minutes vs. 128 minutes; P 5 0.0001). The clinical success rates
were 88% in the SEMS group and 71% in the GJJ group (p 0.28). The median
GOOSS score after SEMS placement was similar to that after GJJ (3 vs. 3).
However, the time to oral intake was significantly less in the SEMS group
than in the GJJ group (2 days vs. 7 days; p 5 0.0001). Early adverse event
(occurring 5 1 week) rates did not differ significantly between the 2 groups:
(6% in the SEMS vs. 7% in the GJJ group). The median postprocedure length
of hospital stay was shorter in the SEMS group than in the GJJ group, but not
significant (17 days vs. 26 days; p 0.13). Median postprocedure survival periods
was similar in 2 treatment groups (68 days vs. 109 days; p 0.85). Late adverse
event (occurring  1 week) occurred in 2 patient in the SEMS group and 3
patients in GJJ group.
CONCLUSION: Endoscopic stent placement is preferable to GJJ in terms of
shorter treatment time and more rapid improvement of food intake. Endoscopic
stent placement seems to contribute to improve quality of life for the palliation of
malignant GOO cause by gastric cancer.
Disclosure of Interest: None declared
P0809 ESOPHAGEAL
COVERED
STENTS
FIXATION
USING
ENDOSCOPIC OVER-THE SCOPE CLIPS VERSUS ENDOSCOPIC
SUTURING SYSTEM (WITH VIDEO)
M. Diana1,2,*, L. Swanstrom2, P. Halvax2, A. Le`gner2, Y.-Y. Liu2, S. Cho2,
A. Alzaga2, N. Demartines1, J. Marescaux2
1
Visceral Surgery, University Hospital of Lausanne, Lausanne, Switzerland,
2
General, Digestive and Endocrine Surgery, IRCAD/IHU UNIVERSITY
HOSPITAL STRASBOURG, Strasbourg, France
Contact E-mail Address: michele.diana@ircad.fr
INTRODUCTION: Endoscopic prosthesis migration from the originally stented
area occurs in up to 40% of cases and may lead to serious life-threatening
complications. Endoscopic suture fixation of the stent using the OverStitchTM
Suturing System (Apollo Endosurgery, Inc.) significantly reduces migration.
However, suturing with the OverStitchTM has a steep learning curve and is
time-consuming. A novel memory shape over-the-scope endoscopic clip, the
PadlockTM clip, has been developed recently by Aponos Medical. The device is
a preloaded point & shoot single-use instrument.
AIMS & METHODS: The aim of this study was to demonstrate that the anchoring of a covered Self-Expandable Metallic Stent using the PadlockTM clip is as
effective as endoscopic suturing by means of the OverStitchTM and that
PadlockTM fixation can be faster and user-friendly. Eleven pigs were involved
in this experimental study. A fully covered esophageal stent (Wall-Flex, Boston
Scientific) of 12.3cm in length, 18mm in diameter, was placed under endoscopic
guidance at the esophagogastric junction. Five pigs underwent stent fixation with
1 figure-of-eight suture using the OverStitchTM. In 4 pigs, the stent was fixed by
firing the Aponos Clip over a loop of Vicryl 0, which was attached to the upper
edge of the stent. In two pigs, the stent was placed but not fixed and was used as a
control. A laparotomy was performed and a specifically designed pulling device
made of 4 fishing hooks attached to a plastic ring was anchored to the distal part
of the stent at 4 cardinal points after performing a gastrotomy. A suture attached
to the plastic ring was passed over the holding hook of a Digital Dynamometer
(Chatillon II, Ametek, Inc.). Constant traction was applied on the sutures until
full stent mobilization was achieved. The force required to remove the stent was
recorded.
RESULTS: Mean force to mobilize the stent was higher in the OverStitchTM
group when compared to the PadlockTM group (23.99N; SD 14.91 vs. 19.97N;

A354
SD 7.62), but the difference was not statistically significant. In the 2 control pigs,
the force required was 7 and 11 Newtons respectively. Mean suturing time was
statistically significantly higher when compared to the time required to apply the
PadlockTM clip (455.4sec; SD 144.83 vs. 155sec; SD 12.9; p 0.002).
CONCLUSION: Full-thickness PadlockTM clip application is faster and may
achieve a comparable stent fixation when compared to endoscopic suturing
with the OverStitchTM.
Disclosure of Interest: M. Diana: None declared, L. Swanstrom Consultancy for:
Unpaid consultant for Apollo Endosurgery and Aponos, P. Halvax: None
declared, A. Le`gner: None declared, Y.-Y. Liu: None declared, S. Cho: None
declared, A. Alzaga: None declared, N. Demartines: None declared, J.
Marescaux: None declared
P0810 ENDOSCOPIC DILATATION OF BENIGN PYLORIC STENOSIS:
IS IT A GOOD ALTERNATIVE TO SURGERY?
M. Acharki1,*, M. Bakkar2, N. Kabbaj2
EFD hepato gastro enterology, 2EFD hepato gastro enterology, Ibn Sina Hospital,
Rabat, Morocco

INTRODUCTION: Pyloric stenosis is a common complication of ulcerative


disease which requires surgery. The endoscopic dilatation is now a good
alternative.
AIMS & METHODS: Aim: evaluate the efficiency of the endoscopic dilatation
in the managment of benign pyloric stenosis due to ulcer diseases.
It is a prospective study from January 2009 to January 2014 including 21
patients. The dilatation was performed using a hydrostatic balloon.
RESULTS: There were 13 men and 8 women. Mean age was 48 years (35-70
years). 58 dilations were performed. In 11 cases (52 %), patients had ulcer disease
and in 6 cases (29 %) non steroidal anti -inflammatory medication. The duration
of symptoms was 13 months (3 months - 3 years). Vomiting and epigastric pain
were the predominant clinical signs (90%). All patients underwent an upper
endoscopy and had pyloric stenosis and / or pyloro - bulbar stenosis. 12 cases
(57%) had impassable strictures. The average number of dilatations was three per
patient (1-5). 17 patients (81%) had favorable response. The average follow-up
time was 30 months (3-60 months).
CONCLUSION: Through this prospective study, we identified factors of success
and failure of endoscopic dilation in benign pyloro-bulbar stenosis: the passable
nature of the stenosis, the extent of the stenosis, the distance between the pylorus
and the dental arches reflecting gastric distension and food stasis.
Disclosure of Interest: None declared
P0811 PREVIOUS BILIARY STENTING IS NOT REQUIRED BEFORE
ENDOSCOPIC PLACEMENT OF DUODENAL COVERED SELF
EXPANDABLE METAL STENTS
F. Goutorbe1, O. Rouquette1,*, A. Mulliez2, M. Goutte1, A. Abergel1,
M. Dapoigny1, G. Bommelaer1, L. Poincloux1
1
Gastroenterology and Hepatology department, 2Clinical research and innovation
department, CHU ESTAING, Clermont Ferrand, France
Contact E-mail Address: fgoutorbe@chu-clermontferrand.fr
INTRODUCTION: Gastroduodenal uncovered Self Expandable Metal Stent
(SEMS) placement is the first line treatment in advanced malignant gastroduodenal obstruction. The main disadvantage of uncovered stents is recurrent
obstruction, mainly due to tumor ingrowth. Covered SEMS (cSEMS) reduce
the re-obstruction rate. As cSEMS are removable they could represent an alternative to surgery or endoscopic dilation in benign stricture. However, cSEMS
placement covering the major papilla has been suspected to be responsible of
mechanical occlusion the ampullary of Vater, which could lead to cholangitis or
pancreatitis. Despite the lack of data, some authors recommend concomitant
biliary stenting to guarantee the adequate bile outflow before duodenal cSEMS
placement. Nevertheless, the need for biliary stenting in patient without concomitant biliary stricture before cSEMS placement remains unknown.
AIMS & METHODS: The aim of our study is to compare the occurrence of
jaundice or pancreatitis after duodenal cSEMS placement in patients with biliary
stenting vs patients with no biliary stenting.
All consecutive patients who underwent endoscopic duodenal cSEMS placement
in the second duodenum area between June 2005 and March 2014, because of
obstructive symptoms were assessed. Biliary stenting was performed when
patients presented with associated biliary stricture. Patients with previous or
concomitant biliary stenting (cSEMSBS group) were compared to patients
with no biliary stent (cSEMS group). The primary end point was the occurrence
of jaundice during an observation period of 90 days. Secondary end points were
bilirubinemia at baseline compared to day 10, technical success, clinical effectivenes and complications rates, during a follow-up period of 90 days.
RESULTS: 106 patients were included: 53 patients in the cSEMS group (58%
male, mean 66.4/-13.3 y/o) and 53 patients in cSEMSBS group (60% male,
mean 70.4/-11.6y/o). The obstruction was due to cancer in 45% in cSEMS
group and 87% in cSEMSBS group. No case of jaundice was reported in the
cSEMS group or in the cSEMSBS group. We report one case (2%) of edematous pancreatitis after stent removal 90 days after stent placement in the cSEMS
group (p 1). In cSEMS group the mean bilirubin level (mmol/L  SD) was 9.3
5.8 at baseline and 8.4 4.5 at day 10, while in the cSEMS-BS group it was
90.3106.9 at baseline and 34.7 39 at day 10. No significant difference was
observed between the two groups in term of technical success, clinical effectiveness, migration and other complications. In all patients, endoscopic duodenal
stenting was successful. The global clinical effectiveness was 90%. The overall
migration rate was 25% and the symptomatic migration rate, defined as obstructive symptoms recurrence, was 16%. Other reported complications were gastrointestinal bleeding (2% in cSEMS group vs 4 % in cSEMS-BS group), Duodenal

United European Gastroenterology Journal 2(1S)


perforation (0% in cSEMS group vs 4% in cSEMS-BS group), death from all
causes (13% in cSEms group vs 28% in cSEMS-BS group, p 0.06). We report
3% of stent obstruction due tumor ingrowth.
CONCLUSION: Concomitant biliary stenting is not recommended before covered duodenal SEMS placement in patients with no concomitant biliary
obstruction.
Disclosure of Interest: None declared
P0812 ENDOSCOPIC THERAPY OF ESOPHAGEAL LEAKS WITH
STENTS: EXPERIENCE IN A REFERRAL CENTER
P. Sousa1,1,*, L. Meireles1, L.C. Freitas1, J. Lopes1, C. Noronha Ferreira1,
R. Palma1, L. Carrilho Ribeiro1, J. Velosa1
1
Gastrenterologia, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria,
Lisboa, Portugal
Contact E-mail Address: patlizbms@gmail.com
INTRODUCTION: Esophageal leaks have an important morbi-mortality. The
best approach is still unclear; some studies show a potential benefit of stents.
Randomized controlled trials are difficult in this area.
AIMS & METHODS: The aim of this study was to evaluate the efficacy of
esophageal stents for the treatment of esophageal leaks.
Retrospective analysis of stent use for esophageal leaks. In a period of 60 months
demographic data, leak etiology, endoscopic procedures, time until closure and
fistulas relapse were analyzed.
RESULTS: 45 consecutive patients were included (29 males; mean age 63 years).
42% had post-operative leaks (10 after gastric sleeve, 6 after Y-Roux and 3 after
subtotal esophagectomy), 42% had malignant esophagopulmonary fistulas (16
esophageal and 3 bronchogenic), 7% had boerhaave syndrome and 9% had
iatrogenic perforation (2 foreign body and 2 after esophageal dilation). The
median time for post-operative fistula detection was 16 days (4-145).
In 36 of the 45 patients the initial approach was using a stent. Of these, in 16
patients this was the only endoscopic therapy done. Metallic stents were inserted
in 40 (13 partially covered, 27 fully covered) and plastic in 5. The rest of patients
had another therapeutic endoscopic procedure - another stent (n 10), throughthe-scope (TTS) clip (n 3), nasoenteric tube (n 10), over-the-scope clip (n 2)
and argon-plasma coagulation (n 6).
The median time for leak closure was 48.5 days (13-308). In 6 cases the fistulas
closure wasnt documented.
In 4 patients there was relapse of the leak in a median of 125 days after the initial
closure. All cases were managed endoscopically - metallic stent (n 3), argonplasma coagulation (n 6), nasoenteric tube (n 3) and TTS clip (n 1). In 3
cases there was closure in a median of 27 days after the diagnosis.
In 12 patients the overall endoscopic approach failed and surgery was needed in 8
patients and percutaneous drainage in 4.
The observed complications were: stent migration (n 10), upper GI bleeding
(n 2). There was no need for surgery in any case or death for a procedure
related complication.
CONCLUSION: The use of esophageal stents seems to be a safe and effective
therapy for esophageal leaks.
Disclosure of Interest: None declared
P0813 TREATMENT OF POSTOPERATIVE LEAKS OF THE UPPER
GASTROINTESTINAL TRACT WITH COLONIC SELFEXPANDABLE METAL STENTS: SINGLE CENTRE EXPERIENCE
P.R. Sousa1,*, A. Castanheira1, P. Ministro1, R. Araujo1, E. Cancela1,
L.F. Pinheiro2, R. Simao2, J. Castro3, A. Silva1
1
Gastroenterology, 2Surgery 1, 3Surgery 2, Centro Hospitalar Tondela-Viseu,
Viseu, Portugal
Contact E-mail Address: paulacrfsousa@gmail.com
INTRODUCTION: The use of self-expandable metal stents (SEMS) for the
treatment of postoperative leaks of the upper gastrointestinal tract is already
established. However, there are discrepancies between the relatively small caliber
of the esophageal stents available in our center and the post-surgical luminal size,
which may determine an inadequate juxtaposition. As colonic stents have a
bigger diameter, they might be more adequate. Additionally, stents with a
larger diameter might have a lower risk of migration.
AIMS & METHODS: The aim of this study was to evaluate the efficacy and
complications associated with the use of colonic SEMS in the treatment of postoperative leaks in critical patients. All patients with postoperative leaks of the
upper gastrointestinal tract treated with colonic stents (Hanarostent CCI)
between 2010 and 2013 were retrospectively included.
RESULTS: Four patients with postoperative leaks treated with colonic SEMS
were identified (3 men, 1 woman) with a mean age of 63. The underlying surgeries
were a gastric bypass, an esophagogastrectomy for Boerhaave syndrome, a primary repair of esophagopleural fistula due to Boerhaave syndrome and an esophagectomy due to squamous cell cancer of esophagus. The leaks were detected
on average 17 days after the initial surgery, and surgical resolution wasnt possible. In this way, the four cases were of difficult management, and in need of
urgent care. They were all admitted to the intensive care unit.
Stent placement was technically feasible in all patients. There were no cases of
stent dislocation. The median residence time of the stent was 7 weeks, and no
complications were verified when they were removed. The treatment was successful in all patients, with complete healing of the leaks. On follow-up, one of the
patients needs periodic endoscopic dilation due to esophagogastric stenosis.
Another patient died 15 days after stent removal, due to septic shock not related
to the procedure.
CONCLUSION: The placement of colonic SEMS seems to be successful and safe
in the treatment of postoperative leaks of the upper gastrointestinal tract.

A355

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: P. Sousa: None declared, A. Castanheira: None declared, P.
Ministro Consultancy for: MSD, Abbott, Abbvie, Hospira, Ferring Portugal, R.
Araujo: None declared, E. Cancela: None declared, L. Pinheiro: None declared, R.
Simao: None declared, J. Castro: None declared, A. Silva: None declared
P0814 TIPS BEYOND THE CLASSICALLY
SEVERE HYPERTENSIVE GASTROPATHY

RECOMMENDED:

IN

S. Campos1,*, A. Oliveira1, A. Agostinho2, V. Carvalheira2, D. Gomes1, C. Sofia1


1
Gastroenterology, 2Imagiology, Centro Hospitalar Universitario de Coimbra,
Coimbra, Portugal
Contact E-mail Address: saratcampos@gmail.com
INTRODUCTION: In addition to variceal hemorrhage, upper gastrointestinal
bleeding due to hypertensive gastropathy may also occur in liver cirrhosis with
portal hypertension, contributing to the poor prognosis of these patients. The
portal decompression achieved by transjugular intrahepatic portosystemic shunts
(TIPS) has shown positive results in the treatment/secondary prophylaxis of
variceal hemorrhage, and in that sense, the analysis of their value in other complications of portal hypertension becomes relevant.
AIMS & METHODS: The aim of this study was to evaluate the efficacy and
safety of TIPS in patients with severe hypertensive gastropathy.
Retrospective study including patients undergoing TIPS for severe hypertensive
gastropathy in a hospital in the period between 2000 and 2013, evaluating: demographic characteristics (age, gender), liver disease (cirrhosis etiology, prior therapy, Child-Pugh, MELD), episode of decompensation (clinical and analytical
parameters) and outcome (effectiveness, complications after TIPS, liver transplantation, death at 30 days and at 1 year).
RESULTS: Of the 8 patients with severe hypertensive gastropathy with recurrent
medical therapy undergoing TIPS, 62.5% were male with a mean age of 53  15
years. In terms of the underlying liver disease: 37.5 % had alcoholic cirrhosis,
average MELD of 17 and Child-Pugh stage C in 50%. TIPS has proved effective
in only 28.6% of the patients. Portosystemic encephalopathy was recorded in
57.4% of the cases. Mortality: 1 case at 30 days and 28.6% at year, both ChildPugh C. No other feature was implicated in the prognosis of patients after TIPS
placement. Two patients underwent liver transplantation. The mean follow-up
was 773 days (0-3534 days).
CONCLUSION: Given the low rates of efficacy and high morbidity and mortality rates, TIPS should be carefully weighed in patients with severe hypertensive
gastropathy, especially in those with more advanced liver disease.
Disclosure of Interest: None declared
P0815 TIPS IN REFRACTORY HYDROTHORAX A CONTRIBUTION
TO AN INCREASED RELEVANCE
S. Campos1,*, A. Oliveira1, A. Agostinho2, V. Carvalheira2, D. Gomes1, C. Sofia1
1
Gastroenterology, 2Imagiology, Centro Hospitalar Universitario de Coimbra,
Coimbra, Portugal
Contact E-mail Address: saratcampos@gmail.com
INTRODUCTION: Hepatic hydrothorax (HHT) is a relatively rare complication
of portal hypertension, but potentially severe. Although conservative therapy
may be effective, it is not without risk and refractory cases are not rare. The
portal decompression achieved by transjugular intrahepatic portosystemic shunts
(TIPS) have shown positive results in the treatment of refractory ascites, and in
that sense, the analysis of their value in other complications of portal hypertension becomes relevant.
AIMS & METHODS: The aim of this study was to evaluate the efficacy and
safety of TIPS in patients with HHT.
Retrospective study including patients with HHT undergoing TIPS in a hospital
in the period between 2000 and 2013, evaluating: demographic characteristics
(age, gender), liver disease (cirrhosis etiology, prior therapy, Child-Pugh,
MELD) episode of decompensation (clinical and analytical parameters) and outcome (effectiveness, complications after TIPS, liver transplantation, death at 30
days and 1 year).
RESULTS: 15 patients with HHT underwent TIPS, most previously underwent
multiple thoracenteses and all with hypoalbuminemia, 60%4male, mean age 63 
9years, 73% with cirrhosis of alcoholic etiology, mean MELD-16 and 53% with
Child-Pugh B. TIPS was effective in 50% of cases. Portosystemic encephalopathy
was recorded in 66.6% of the cases. Mortality: 20% at 30 days and 40% at year
with septic complications or progression of liver disease. Two cases underwent
liver transplantation. In the univariate analysis, only the hematocrit value had
prognostic value (p 0.016). The mean follow-up was 443 days (1-2250 days).
CONCLUSION: TIPS appears to be a relatively efficient method of control
HHT, making it a valid option in refractory cases despite the high risk of portosystemic encephalopathy and mortality. Low hematocrit levels seem to imply a
worse prognosis of patients to be considered for TIPS for refractory HHT.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
SURGERY II POSTER EXHIBITION HALL XL_____________________
P0816 DIFFERENCES IN MORTALITY BETWEEN ARTERIAL, VENOUS
AND NON-OCCLUSIVE MESENTERIC INFARCTION. A
SYSTEMATIC REVIEW AND META-ANALYSIS OF
OBSERVATIONAL STUDIES
F. Adaba1,*, A. Askari2, S. Gabe2, C. Vaizey2, J. Nightingale2, J. Warusavitarne2
1
Intestinal Failure, 2St Marks Hospital, Harrow, United Kingdom, London, United
Kingdom
Contact E-mail Address: f.adaba@nhs.net
INTRODUCTION: Acute mesenteric infarction is a rare but often lethal event.
Primary vascular aetiology can be of arterial, venous or a Non-occlusive mechanism. Mortality from acute mesenteric infarction may vary with aetiology. The
aim of this study is to determine whether there are differences in mortality
between arterial, venous and non-occlusive mesenteric infarction.
AIMS & METHODS: A literature search was performed via PubMed, Ovid and
Google Scholar. Studies that had reported comparative mortality between arterial, venous and Non-occlusive mesenteric infarction (NOMI) were included.
Odds ratios of mortality were calculated using a Mantel-Haenszel, random
effect model. Meta-regression was attempted, however due to lack of adequate
information in studies, it was not possible.
RESULTS: A total of 1,207 articles were screened. Of which, 20 were suitable for
data synthesis for arterial vs. venous infarction, 16 for NOMI vs. venous infarction and 15 for Arterial vs. NOMI. When compared with venous infarction,
patients who had arterial infarction were significantly more likely to die during
primary hospital admission (OR 3.47, CI 2.43-4.96, p 50.001). Similarly,
patients with NOMI were over three times more likely to die during hospital
admission compared with those with venous infarction (OR 3.2, CI 1.83-5.6,
p 50.001). There was no difference in mortality rates between arterial infarction and NOMI (OR 1.08, CI 0.57-2.03, p 0.82)
CONCLUSION: Patients with arterial infarction or NOMI are over three times
more likely to die from mesenteric infarction during primary hospital admission.
Disclosure of Interest: None declared
P0817 A SCORING SYSTEM TO DISTINGUISH SIMPLE FROM
PERFORATED APPENDICITIS BASED ON CLINICAL PLUS
IMAGING FEATURES
J. Atema1,*, M. Leeuwenburgh1, C.Van Rossem2, J. Stoker3, M. Boermeester1 on
behalf of On behalf of the OPTIMA and OPTIMAP study groups
1
Surgery, Academic Medical Center, Amsterdam, 2Surgery, Tergooi Hospital,
Hilversum, 3Radiology, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: j.j.atema@amc.nl
INTRODUCTION: During the last decade, conservative management is suggested to be a safe and effective alternative to appendectomy for selected patients
with non-perforated (simple) appendicitis. However, preoperative selection of
patients with uncomplicated appendicitis is proven to be a challenge.
Computed tomography (CT) is generally accepted as the most accurate test for
the diagnosis of acute appendicitis, but the performance of CT in distinguishing
simple from perforated appendicitis is by far not accurate enough.
AIMS & METHODS: The aim of this study was to analyse clinical and CT
features associated with perforation and to develop a scoring system for the
selection of patients with simple appendicitis.
All patients with a final diagnosis of acute appendicitis were selected from a
prospective database including adult patients with acute abdominal pain. The
final diagnosis was assigned by an expert panel based on perioperative data,
histopathology and at least 3-months of follow-up. Predefined clinical and imaging features were recorded in a structured online case record form. Only patients
in whom CT was performed were included in the present analysis. Medical
literature was searched and several clinical and imaging features suggested to
be associated with perforated appendicitis were selected. Stepwise backward
elimination (p50.05) was used to construct a multivariable regression model
with independent predictors of perforation. The discriminatory capacity of the
model was expressed as the area under the curve (AUC). The model was transformed into a clinically applicable scoring system and a cut-off analysis was
performed to illustrate the consequences in our cohort.
RESULTS: A total of 333 patients with a final diagnosis of acute appendicitis
were identified. A CT was performed in 281 patients of whom 65 (23%) had
perforated appendicitis. The final model for clinical and CT features included;
age 4 45 years (OR 2.726; 95%CI 1.363-5.452), temperature 437.2 (OR 6.066;
95%CI 2.632-13.978), white blood cell count 4 10 x 109/L (OR 4.786; 95%CI
1.532-14.952), c-reactive protein 45 4 mg/L (OR 4.761; 95%CI 2.263-10.016),
appendicolith on CT (OR 2.309; 95%CI 1.142-4.661), destruction of appendiceal
wall on CT (OR 2.370; 95%CI 1.028-5.467) and free extraluminal air on CT (OR
4.026; 95%CI 1.172-13.829). The model had a discriminative value of 0.850
(95%CI 0.801-0.898). A scoring system was constructed and points were assigned
for every variable, with a maximum score of 27 points. Using this score in the
study cohort, 134 (48%) patients were identified with a score of 12 or less of
whom 7 (5%) had perforated appendicitis, resulting in a negative predictive value
of 95%.
CONCLUSION: Using this simple scoring system, a subgroup of patients with
simple appendicitis can be identified based on clinical and CT features with a low
percentage (5%) of false negatives (i.e. patients with perforated appendicitis).
These patients can be considered for treatment options other than
appendectomy.
Disclosure of Interest: None declared

A356
P0818 SURGICAL
CHALLENGES

United European Gastroenterology Journal 2(1S)


META-EVIDENCE

AND

ITS

CURRENT

J. Delaney1,*, P. Laws2, Y. Salama3, J. Evans3, A. Engel3


Northern Clinical School, University of Sydney, 2Prince of Wales Hospital,
3
Department of Colorectal Surgery, Royal North Shore Hospital, Sydney,
Australia
Contact E-mail Address: jdel2642@uni.sydney.edu.au
1

INTRODUCTION: The aim of this study was to compare the methodological


quality and input paper characteristics of systematic reviews and meta-analyses
done in the medical and surgical literature by performing a systematic "overview
of reviews". Ulcerative colitis (UC) and Crohns disease (CD) were used as the
framework for this comparison as they are relatively common, serious conditions
with medical and surgical therapy options.
AIMS & METHODS: MEDLINE, Embase, CINHAL and the Cochrane
Database were searched to November 2013. Eligible papers were systematic
reviews or meta-analyses that considered a question of therapy in either CD or
UC. Two independent reviewers selected the papers, extracted the data and
scored their methodology using the AMSTAR scoring system. The papers
were categorized into medical therapy (M), surgical therapy (S), or surgical
and medical therapy (MS) groups.
Following retrieval of the sample of meta-evidence papers, the original input
studies used in their creation were identified and a search of MEDLINE,
Embase, CINHAL and the Cochrane Database was performed. A team of
researchers then examined this collection of papers for bibliographic and financial information.
RESULTS: 500 papers were identified in the meta-evidence search. 114 were
deemed eligible. There was a significant difference in the AMSTAR-rated average quality of the papers (S 7.36, M 8.87, MS 8.11, ANOVA p 0.016). On
average S papers were published in journals with a lower impact factor (S
3.26, M 5.13, MS 5.32, p50.001). S papers also showed more heterogeneity
(I2: S 37%, M 24%, MS 10%, p50.001). Some 25% of S meta-analyses used
data-sets with significant heterogeneity (I2 4 75%), compared to 8% of M metaanalyses and 3% of the MS group. Some 5% of S papers were done on data sets
that had I2 values 4 90%.
There was no significant difference in the average number of papers assessed in
each group (S 15.5, M 12.33, MS 15.2, p 0.38), the average number of patients per
meta-paper (S 1,304, M 1,757, MS 2,576, p 0.2), the average time over which
the reviews covered (S 16.1yrs, M 15.2yrs, MS 14.8yrs, p 0.93), the average
number of papers considered within each meta-analysis (S 5.7, M 5, MS 3.8,
p 0.45), or the average number of patients considered within each meta-analysis
(S 632, M 689, MS 473, p 0.12). Considering the conclusions of each metaanalysis, S meta-evidence was 50% more likely than M meta-evidence to be
unable to make recommendations for practice.
1,443 original input papers were identified, of which 469 were duplicates. Within
the non-duplicate papers (n 974) the average impact factor within the S group
was lower than that of the M and the MS groups (3.805 vs 10.241 & 7.062,
ANOVA p50.001). When compared with S papers, M papers had higher rates
of pharmaceutical sponsorship (M 51% vs S 1%) and twice the level of government support (M 14% vs S 7%). Of note, 21% of M papers had corporate
sponsorship but did not list any conflict of interest.
CONCLUSION: Compared to medical meta-analyses, surgical meta-analyses, in
the UC and CD domain, are more likely to be of poorer methodological quality,
are of a greater degree of heterogeneity, and less often offer a positive conclusion.
The input papers used to generate meta-evidence in medical papers have a greater
degree of corporate and government sponsorship, and are more likely to come
from journals with higher impact factors.
Disclosure of Interest: None declared
P0819 ALTERED CORTICAL PROCESSING IN RESPONSE TO RECTAL
STIMULI IN PATIENTS SUFFERING FROM IDIOPATHIC FECAL
INCONTINENCE
S. Haas1,*, C. Brock2,3, K. Krogh4, M. Gram3, L. Lundby1, A.M. Drewes2,3,
S. Laurberg1
1
Department of Surgery P, Aarhus University Hospital, Aarhus C, 2Center for
Sensory-Motor Interaction (SMI), Department of Health Science and Technology,
Aalborg University Hospital, 3Department of Gastroenterology and hepatology,
Mech-Sense, Aalborg University Hospital, Aalborg, 4Neurogastroenterology Unit,
Department of Hepatology and Gastroenterology, Aarhus University Hospital,
Aarhus C, Denmark
Contact E-mail Address: susahaas@rm.dk
INTRODUCTION: The role of intact sensory function of both the rectum and
the anal canal has been recognized to be essential for fecal continence. We
hypothesized that a cause of idiopathic fecal incontinence is related to changes
in the afferent sensory pathways and that this would be reflected in cortical
potentials evoked by mechanical stimulation of the rectum.
AIMS & METHODS: Nineteen healthy women (mean age 5412, mean Wexner
score 1.5) and 20 women suffering from ideopathic fecal incontinence (mean
6113, mean Wexner score 14.5) underwent repeated rapid balloon distensions
of the rectum at the level of discomfort/ urge to defecate under simultaneous
recording of cortical evoked potentials. Single sweep spectral band analysis was
conducted to obtain the relative EEG amplitude within each frequency band.
RESULTS: The latency of the cortical evoked potentials generated in the vertex
electrode of idiopathic fecal incontinence patients was longer than in healthy
subjects (p50.001), but there were no differences in location or strength of
electrical sources in areas involved in the cerebral processing (insula, secondary
somatosensory cortex and mid-cingulate gyrus bilaterally).

Analysing spectral contents of single sweeps, we found a significant increase in


the alpha (8 - 12 Hz) and beta (12-32 Hz) bands (p50.001) and a significant
decrease in the gamma (32-70 Hz) band (p50.0001) whereas low frequency
bands did not differ. The changes in the gamma band were negatively correlated
to the anal resting- and squeeze pressure as well as the first urge to defecate.
CONCLUSION: Our study indicates that idiopathic fecal incontinence is associated with abnormal rectal sensory perception and cortical processing of the
afferent activity.
Disclosure of Interest: None declared
P0820 ENDOSCOPIC INTERNAL DRAINAGE FOR TREATMENT OF
LEAKS FOLLOWING SLEEVE GASTRECTOMY
G. Donatelli1,*, B.M. Vergeau1, J.-L. Dumont1, T. Tuszynski1, P. Dhumane2,
B. Meduri1
1
Unite dEndoscopie Interventionnelle, Hopital Prive des Peupliers, Generale de
Sante, Paris, France, 2General and Laparoscopic Surgery, Lilavati Hospital and
Research Center, Mumbai, India
Contact E-mail Address: donatelligianfranco@gmail.com
INTRODUCTION: The most common complications of sleeve gastrectomy (SG)
are gastric line leaks (GLL). Standard management protocol for GLL is not yet
established. We report our experience about endoscopic internal drainage (EID)
using double plastic pigtails stent changed between 4 and 6 weeks until healing.
AIMS & METHODS: 34 pts (26 F), 43.6 y (23 70) presented GLL 12.8 days (1
97) from surgery. 8 patients underwent single port and 26 laparoscopic SG. 25
patients underwent a second surgery at 10.6 (0 97) days from SG. 9 out 34
patients presented peri-gastric collections and fever. One, two or three plastic
pigtail stents (AdvanixO`, Boston Scientific), according to orifices size and
collection, were delivered with the one end in the collection and the other one
in the stomach. In 26 patients a naso-jejunal feeding tube was inserted and kept
NPO. 2 presented jejunostomy, and 4 kept to eat normal. Endoscopic control
was performed systematically between 4 - 6 weeks, with either re-stenting (if the
leak was still present), or removal (if no extravasation of contrast medium in the
peritoneal cavity was detected), or closure with an OTSC (if contrast material
passed through the crossing stent without concomitant detection in the peritoneal
cavity).
RESULTS: EID was possible in 97% (33/34) of patient. 1 (3%) was perforated
during stenting deliver. 13 patients were healed at first control, 32.3 days (26 54)
from stenting, 2 needed OTSC. At a second control, 61.6 days (48 87) by first
EID, 10 patients respected criteria of good outcome, 4 presented a sealed fistula,
6 needed OTSC. Three patients healed as follows: three changes at 84 days,
fourth change at 135 days, and at 180 days follows 7 changes respectively. 1
patient died, 24h later EID for pulmonary embolism. Overall, 6 out 32 patients
(18.8 %) are still under treatment, and 26/32 (81.2 %) were healed with an
average time of EID treatment of 57.4 days (26 180), they are now symptom-free, on a normal diet at a median follow up of 129 days (2 276).
CONCLUSION: EID is a promising therapeutic mini invasive approach for the
treatment of leaks following SG, well tolerated by patients, despite the need of
multiple endoscopic sessions. It allows draining peri-gastric collections and promotes tissue regrow, permitting to avoid re-surgery.
Disclosure of Interest: None declared
P0821 PERINEAL WOUND PROBLEMS AFTER ABDOMINOPERINEAL
RESECTION FOR RECTAL CANCER; A TWO-INSTITUTIONAL
EXPERIENCE IN THE ERA OF INTENSIFIED ONCOLOGICAL
TREATMENT
G.D. Musters1,*, D.A. Sloothaak1, S. Roodbeen1, A.A. van Geloven2,
W.A. Bemelman1, P.J. Tanis1
1
Surgery, Academic Medical Center, Amsterdam, 2Surgery, Tergooi ziekenhuizen,
Hilversum, Netherlands
Contact E-mail Address: G. D. Musters@amc.nl
INTRODUCTION: Intensified treatment for distal rectal cancer has improved
oncological outcome but at the cost of more perineal wound problems in patients
undergoing an abdominoperineal resection (APR). The aim of this study was to
analyse perineal wound healing after APR with primary perineal wound closure
over time.
AIMS & METHODS: All patients undergoing APR for primary rectal cancer
with primary wound closure between 2000 and 2013 were included and analysed
in three consecutive time periods. Both early (530 days postoperatively) and late
perineal wound complications were determined. Independent risk factors of perineal wound complications were identified using multivariable analysis.
RESULTS: In total 136 patients were identified, of whom 129 patients underwent primary perineal wound closure. The use of neo-adjuvant (chemo)radiotherapy increased from 58% to 91% and the use of an extralevator
approach increased from 9% to 19%. The rate of complicated perineal wound
healing increased from 18% to 31%. An extralevator approach (OR 3.17; 95%
CI 1.16-8.66) and intra-operative perforation (OR 3.35; 95% CI 1.06-10.57) were
independent predictors for perineal wound complications. No differences in
oncological outcome were found in patients with and without perineal wound
complications. During a median follow-up of 28 months (IQR 14-56), 3% developed a perineal fistula, in 8% a persistent presacral sinus was diagnosed, and in
8% of the patients a perineal hernia occurred.
CONCLUSION: The increased use of an extralevator approach significantly
increased the perineal wound complication rate over time. Intra-operative perforation was also an independent predictor of perineal wound problems.
Disclosure of Interest: None declared

A357

United European Gastroenterology Journal 2(1S)


P0822 SEALING BOWEL DEFECTS WITH TISSUE ADHESIVES: A
COMPARATIVE ANALYSIS OF THE CLINICAL, MECHANICAL
AND HISTOPATHOLOGICAL EFFECTS OF 7 SURGICAL
ADHESIVES
K. Vakalopoulos1,*, Z. Wu1, L. Kroese1, K. Lam2, G.-J. Kleinrensink3,
H. Jeekel1, J. Lange1
1
Surgery, 2Pathology, 3Neurosciences, Erasmus MC, Rotterdam, Netherlands
Contact E-mail Address: k.a.vakalopoulos@gmail.com
INTRODUCTION: The use of tissue adhesives (TA) in bowel surgery is gaining
popularity. Sealing bowel defects with TA may be a quick and safe alternative to
suture closure. This study provides information on the sealing capability of
several TA, as well as their histopathological effects on colonic tissue, providing
a tool for the selection of the optimal TA.
AIMS & METHODS: 160 rats received a 0.5 cm incision in the proximal and
distal colon which was then sealed with 1 of the following TA: Histoacryl Flex,
Bioglue, Dermabond, Evicel, Duraseal Xact, Gelatin-Resorcinol-Formaldehyde
and Glubran 2. A control group without TA was also included. Follow-up was 3
or 10 days. Leakage related complications were noted, bursting pressure (BP) and
histopathological analysis were performed.
RESULTS: At 3 days leakage rates were highest in the control group and for
Bioglue, Duraseal Xact and Tissucol. Glubran 2 and Tissucol showed the lowest
Leakage rates. BP was highest in Duraseal Xact, Tissucol and Omnex.
Histopathologically Tissucol, Omnex and the control group showed highest
inflammation scores. At day 10 Controls, Bioglue and Duraseal showed the
highest leakage rates and Tissucol and Omnex the lowest. BP was highest in
Tissucol, Glubran 2 and Histoacryl Flex. Histopathological analysis showed
highest inflammation for Bioglue, Omnex and Tissucol.
CONCLUSION: Sealing of colonic defects with TA is a safe and effective way to
prevent leakage-related complications while maintaining high mechanical
strength. However, large differences exist between the safety and effectiveness
of the available TA. In this study, the cyanoacrylates Histoacryl Flex, Omnex
and Glubran 2 as well as the fibrin glue Tissucol showed lowest leakage rates and
the most inert histopathological profile while maintaining sufficient mechanical
strength.
REFERENCES
1. Vakalopoulos KA, Daams F, Wu Z, et al. Tissue adhesives in gastrointestinal
anastomosis: a systematic review. J Surg Res 2013; 180: 290-300.
2. Vakalopoulos KA, Wu Z, Kroese L, et al. Mechanical strength and rheological
properties of tissue adhesives with regard to colorectal anastomosis: an ex vivo
study. Ann Surg. Epub ahead of print 25 March 2014.
3. Kingham TP and Pachter HL. Colonic anastomotic leak: risk factors, diagnosis, and treatment. J Am Coll Surg 2009; 208: 269-278.
4. Pommergaard HC, Achiam MP and Rosenberg J. External coating of colonic
anastomoses: a systematic review. Int J Colorectal Dis 2012; 27: 1247-1258.
5. Spotnitz WD and Burks S. State-of-the-art review: Hemostats, sealants, and
adhesives II: Update as well as how and when to use the components of the
surgical toolbox. Clin Appl Thromb Hemost 2010; 16: 497-514.
6. Reece TB, Maxey TS and Kron IL. A prospectus on tissue adhesives. Am J
Surg 2001; 182(Suppl.): 40S-44S.
Disclosure of Interest: None declared
P0823 CASE CONTROL STUDY OF USEFULNESS OF INTRA-GASTRIC
BALLOON BEFORE BARIATRIC SURGERY IN MORBID OBESITY
A. Ortega1, L.R. Rabago1,*, C. Vicente2, A. Olivares1, M.L. Arias1, A. Castillo1,
A. Alonso1, J. Vazquez Echarri3, N. Herrera3
1
gastroenterology, 2internal Medicine, 3Surgical Department, HOSPITAL
SEVERO OCHOA, Leganes, Spain
Contact E-mail Address: lrabagot@gmail.com
INTRODUCTION: Bariatric surgery has an important morbidity with a scarce
number of reports using intragastric- balloons (IGB-BIB) before surgery trying
to lose weight and subsequently to reduce postoperative complications.
AIMS & METHODS: In the setting of an on-going randomized study of (IGBBIB for 6 months before Bariatric surgery [sleeve resection (SR) or gastric
bypass (GB)]) to reduce postoperative complications. We present an interim
case-control study comparing with patients came from our historic surgical
group "gr2" and operated by the same surgical team. We matched cases, by
gender, age ( 5 years) and type of surgery (1:1). The study protocol was
approved by the H. Ethical Committee. All patients provided their informed
consent OBJECTIVE: to evaluate if morbidity (medical and surgical) and hospital stay will decrease after IGB-BIB treatment, and to check if there was any
relationship between patient (pt) weight before surgery and morbidity
RESULTS: The historic group included 47 pts, 21.7% were male, with a mean
age of 45.9 y-o (SD 10.33), a weight before surgery of 125.05 kg (SD 21.25) and
BMI of 47.42 (SD 6.77). 50% of pts were ASA III. 61% of these pts were
operated with GB. All in all the surgical complications rate was 32.6% (57.1%
of them severe,15pts). The hospital stay was 8 days (P25-75: 6-9). The case-control study included 48 pts, 24 in each group matched by sex (58.3% women), type
of surgery (66.7% GB and 33.3% SR) and age (gr1, 41.5 y-o, SD 10.04, gr2, 44.4
y-o,SD 10.04, p 0.261). When we compared the age, sex, weight before surgery,
surgical morbidity, hospital stay and ASA score between gr2 and the pts left in
the historic group, we did not find statistical differences. The rate of IGB-BIB
failure was 20,9% in gr1. The gr1 had a lower ASA score than the gr2 (ASA III,
25% vs. 54.2%, p 0.04). The mean weight loss before surgery was greater in gr1
than gr2: 16.7 kg (SD 9.7) vs. 1.6 (SD 6.1), p 0.0001. the morbidity related to the
balloon was 8,3% in gr1. Surgical complications rate was 29.2% in gr1 (38,5% of
them severe) vs 33.3% in gr2(58.8% severe). The reoperation rate was 8,3% in
both groups. The hospital stay was 7 days (p25-75: 5.2-8) in gr1 and 8 d (p25-75:

7-9.2) in gr2, p 0.061. One patient died in gr2 representing a 2.1% rate of mortality in the historic group. We did not find any significative differences either in
surgical morbidity (p 0.781) or in total morbidity [surgical plus balloon morbidity
(p 1)] in the case-control analysis. There was also not difference in morbidity
classified as severe (p 1) in this case control-study. Multivariable logistic
Regression Analysis in all the cohort patients of the study (gr1historic group)
did not find that weight before surgery,type of surgical procedure, age of sex were
predictors of morbidity.
CONCLUSION: 20.9% of pt with IGB-BIB failed to lose weight. It has not been
found yet a decrease in morbidity or hospital stay in the IGB-BIB group
compared with their matched control group in spite of the fact that that the
case group had a lower ASA score. Case control and Multivariate analysis
have not proven any relationship between patient weight before surgery and
morbidity.
Disclosure of Interest: None declared
P0824 ROUTINELY CRP QUANTIFICATION AFTER APPENDECTOMY
DUE TO ACUTE APPENDICITIS A WASTE OF MONEY?
M. Tachezy1,*, I. Anusic1, F. Gebauer1, J.R. Izbicki1, M. Bockhorn1
General, Visceral and Thoracic Surgery, University Medical Center HamburgEppendorf, Hamburg, Germany
Contact E-mail Address: m.tachezy@uke.de
1

INTRODUCTION: Appendectomy is the most frequent non elective surgical


procedure in general surgery. Until now, indication is generally based on clinical
findings. However, laboratory results such as leukocyte count and C-related
Protein (CrP) are usually determined before and after the surgical procedure,
and clinicians are not infrequently confronted with the question, if a patient can
be discharged with an increasing inflammatory laboratory parameter. A clear
evidence for a prospective value of the parameters and their trend regarding
complications is missing.
AIMS & METHODS: Between November 2004 and April 2010, nine hundred
sixty-nine patients underwent a surgical procedure due to clinically suspected
acute appendicitis. All clinical, laboratory and histopathological data were
obtained from the clinical and pathological records and a quality control data
base containing information 0 (n 243). Laboratory results were correlated with
clinical and histopathological data (t-test, Chi-square test, regression analysis,
ROC curve, respectively).
RESULTS: Eight hundred ninety-two (92%) patients had a histological confirmed acute appendicitis; median hospitalisation was 3 days (range 1-38 days).
Overall morbidity was 6.2%; 60 (5.7%) patients suffered from infectious complications. Strongest predictive parameter for complications was a CrP value of
more than 108 mg/l on the first postoperative day with an odds ratio of 16.6
(96% CI 6.4/42.8, p50.001). ROC analysis revealed an AUC of 0.821 with a
Specificity of 88% and Sensitivity of 69%. Patients with below the threshold
suffered from complications in 1.1% in contrast to the patients above with
16.8% (p50.001). In patients without acute appendicitis Operative trauma
causes a CrP increase from less than 5 mg/l up to a median of 30 mg/l (25th
percentile: 8mg/l and 75th percentile 100mg/l) on POD 1 to 47 mg/dl (25th percentile: 23mg/l and 75th percentile 125mg/l) on POD 2.
CONCLUSION: Operative trauma due to a non-acute inflamed appendectomy
causes a significant increase of serum CrP, which must be taken into account for
clinical assessment after appendectomy. Therefore, a moderate elevation of CrP
values postoperatively is no general contraindication for discharge. However,
postoperative determination of CrP serum values after appendectomy seems to
be an effective predictor for complications and should therefore be measured in
the clinical routine.
Disclosure of Interest: None declared
P0825 ENDOSCOPIC ELECTROCAUTERY
IMPLANTABLE CARDIAC DEVICES

IN

PATIENTS

WITH

M.K. Baeg1,*, S.-W. Kim1, S.H. Ko1, C.-H. Lim1, H.H. Kim1, J.S. Kim1,
Y.K. Cho1, J.M. Park1, B.-I. Lee1, I.-S. Lee1, M.-G. Choi1
1
Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul,
Korea, Republic Of
Contact E-mail Address: baegmk@catholic.ac.kr
INTRODUCTION: Patients with implantable cardiac devices who undergo
endoscopic electrosurgery are at risk of potentially harmful electromagnetic
interference (EMI). However, few reports on the association between the two
exist.
AIMS & METHODS: We aimed to analyze the effects of endoscopic electrosurgery in patients with implantable cardiac devices. The medical records of
patients who underwent endoscopic procedures requiring the use of electrosurgery, such as snare polypectomy, endoscopic submucosal dissection (ESD), and
endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic
sphincterotomy (EST), were analyzed retrospectively. Patients with implantable
cardiac devices had their medical records reviewed, which included postprocedural patient symptoms, demographic data, and outpatient follow-up data.
Electrical data, including preprocedural and postprocedural arrhythmia records,
such as pacemaker interrogation, 24 h Holter monitoring, and electrocardiogram, were also reviewed.
RESULTS: Forty-nine patients who underwent 59 procedures were analyzed.
Fifty procedures were performed in 43 patients with pacemakers, and nine procedures were performed in six patients with implantable cardioverter-defibrillators. There were 44 colon snare polypectomies, one colon ESD, one gastric snare
polypectomy, five gastric ESDs, and eight ERCPs with EST. Fifty-five cases of
electrical follow-up were observed, with two postprocedure changes noted that
were not caused by electrosurgical EMI. Thirty-one pacemaker interrogations

A358

United European Gastroenterology Journal 2(1S)

had recordings of the procedure, with two cases of asymptomatic tachycardia


events. All patients were asymptomatic, and no adverse events after the procedure were reported.
CONCLUSION: Our study reported no adverse events from endoscopic electrosurgery in patients with implantable cardiac devices, which suggests that this
procedure is safe. However, because of the possibility of EMI, recommendations
regarding endoscopic electrosurgery should be followed.
Disclosure of Interest: None declared
P0826 RISE IN TROPONIN T AFTER MAJOR GASTROINTESTINAL
SURGERY IS ASSOCIATED WITH OCCURRENCE OF NEW
MAJOR CARDIOVASCULAR EVENTS
P.W. Chiu1,*, M.T. Chan2, S.S. Ng1, A.Y. Teoh1, S.K. Wong1, E.K. Ng1
1
Department of Surgery, 2Department of Anesthesia and Intensive Care, THE
CHINESE UNIVERSITY OF HONG KONG, Hong Kong, China
Contact E-mail Address: philipchiu@surgery.cuhk.edu.hk
INTRODUCTION: A risk in Troponin T is associated with myocardial infarction, cardiovascular death and heart failure. Recently, an international prospective cohort study recently suggested a significant association between peak
postoperative Troponin T (TnT) within three days after surgery and 30-day
mortality. However, there is no study to investigate the long term risk of cardiovascular events among those with elevated troponin T level after surgery. This
study aimed to investigate elevated Troponin after gastrointestinal surgery and 3
year outcomes.
AIMS & METHODS: This is a prospective cohort study including patients age
above 45 years who underwent either elective or emergency upper or lower GI
surgery under general anesthesia. Those recruited had measurement of peak
troponin T (TnT) levels by fourth generation TnT assay. The data for assessing
perioperative mortality and cardiovascular diseases were collected, including
baseline demographics, smoking status, history of cardiovascular disease, type
of surgery performed as well as clinical outcomes. The primary outcome was 3
year mortality after surgery. Secondary outcomes included new major cardiovascular events (which were defined as myocardial infarction, stroke, deep vein
thrombosis and pulmonary embolism), new use of anti-platelet medication (e.g.
aspirin, clopidogrel) and new use of anti-coagulation drugs (e.g. warfarin) within
3 years after surgery.
RESULTS: A total of 213 patients were recruited including 128 male and 85
female. 53 patients underwent upper gastrointestinal surgery and 152 underwent
lower gastrointestinal surgery. 28 patients (13.1%) had elevated peak troponin T
level (40.01ng/mL) in at least one measurement within 3 days after surgery. 5
out of 213 patients drop out of the study with 97.7% of patients completed 3-year
follow-up. There was no difference in 3 year mortality between those with and
without elevation of TnT after surgery. Those in the elevated TnT group sustained significantly higher rate of cardiovascular events (57.1% vs 10.4%; p 5
0.001) and also higher use of anti-platelets agents (30% vs8.2%; p 0.009) within
3 years after surgery when compared to the normal TnT group. There was no
difference in 3 year cancer recurrence between the two groups.

Age
BMI
Gender M:F
Upper GI Surgery
Lower GI Surgery
History of coronary
artery disease
History of Diabetes
Occurrence of new
cardiovascular
events in 3 years
New use of aspirin /
Clopidogrel in 3 years

Elevated Troponin
T group (TnT)
(n 28)

Non-elevated
Troponin T
group (non-TnT)
(n 185)

75 (51-99)
22.70 (15.36-30.03)
15/13
6 (22.2%)
21 (77.8%)
8 (28.6%)

68 (45-90)
22.10 (14.91-29.29)
113/72
47 (26.4%)
131 (73.6%)
7 (3.8%)

0.002y
0.426
0.450
0.644

8 (28.6%)
16 (57.1%)

41 (22.2%)
19 (10.4%)

0.453
50.001y

6 (30%)

14 (8.2%)

0.009y

P value

50.001y

CONCLUSION: Patients with elevated TnT after major gastrointestinal surgery


had significantly higher risk of cardiovascular events in 3 years after surgery.
Disclosure of Interest: None declared
P0827 DEFUNCTIONING ILEOSTOMY DOES NOT PREVENT
ANASTOMOTIC LEAKS AFTER RESTORATIVE
PROCTOCOLECTOMY; A MULTICENTER EVALUATION OF
CLINICAL AND SURGICAL RISK FACTORS
S. Sahami1,*, C. Buskens1, P. Tanis1, T. Young Fadok2, A. De Buck van
Overstraeten3, A. DHoore3, W. Bemelman1
1
Surgery, AMC, Amsterdam, Netherlands, 2Surgery, Mayo Clinic, Phoenix,
United States, 3Surgery, UZ Leuven, Leuven, Belgium
Contact E-mail Address: s.sahami@amc.uva.nl
INTRODUCTION: Anastomotic leakage (AL) is a serious complication after
restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) that
could lead to pelvic sepsis and ultimately to pouch failure. Previous studies

have shown significantly decreased leak rates in diverted patients with less
severe clinical consequences. The last decade, a trend has been seen towards
more extensive medical treatment in IBD patients, leaving refractory patients
in a worse condition when it comes to surgery. Since timely identification of
high-risk patients could influence surgical decision-making and diminish the
risk for complications, the aim of our study is to identify clinical and surgical
parameters associated with AL and to analyse whether a defunctioning ileostomy
should be considered as standard care in patients undergoing IPAA.
AIMS & METHODS: In a retrospective study, 691 patients undergoing IPAA
for IBD, dysplasia, or FAP were identified from prospectively maintained databases of three large IBD centres. The creation of an ileostomy was left at the
discretion of the surgeon. AL was defined as any leak confirmed by either contrast extravasation on imaging or by re-laparotomy. Multivariable regression
models were developed to identify risk factors for AL.
RESULTS: In 305 IBD patients (49.1%), an ileostomy was created during IPAA.
A comparable overall leak rate was found in the stoma group when compared to
non-diverted patients (16.7% vs 17.1%, p 0.92). This unexpected finding of
high leak rates despite stoma formation could probably be explained by the
increased use of anti-TNF (12.6% versus 4.6%, p50.001), steroids (33.0% vs
12.1%, p50.001), and weightloss (45% of bodyweight) (14.6% vs 8.5%,
p 0.02) when compared to non-diverted patients. Despite having a stoma, a
high leak rate (40.0% vs 15.1%, p 0.02) was found in patients treated with a
combination of anti-TNF and steroids. This was also emphasized by the fact that
patients undergoing subtotal colectomy with IPAA at a later stage (weaned of
medication) had a significantly decreased leak rate when compared to patients
undergoing primary IPAA (11.6% vs 20.7%, p 0.003). Multivariable regression
models demonstrated, long-term disease course (OR 2.01, 95%CI 1.273.19),
high ASA score (OR 1.94, 95%CI 1.093.47) and a combination of anti-TNF
and steroid treatment (OR 5.61, 95%CI 1.7118.48) as independent risk factors
for AL.
CONCLUSION: These results imply that in daily practice surgeons perform
ileostomy in more fragile and disease affected patients. This strategy seems ineffective in the prevention of AL in these series implicating that a staged procedure,
that is subtotal colectomy followed by completion proctectomy and IPAA after
weaning of the medication, is more appropriate when preoperative risk factors
are identified. Long-term disease course, high ASA score, and a combination of
anti-TNF and steroid treatment within 3 months before IPAA were all independent risk factors for AL.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


IBD II POSTER EXHIBITION HALL XL_____________________

9:0017:00

P0828 DIFFERENTIAL EXPRESSION OF TRPM6 AND TRPM7


FOLLOWING INTESTINAL INFLAMMATION EMERGING NEW
PATHWAYS OF CHRONIC INFLAMMATION AND DIARRHEA
F. Scaldaferri1,*, V. Petito1, V. Trapani2, L. Lopetuso1, D. Scannone2,
A. Boninsegna2, A. Sgambato2, F. Wolf2, A. Gasbarrini1
1
Internal Medicine Department, Gastroenterology division, 2Pathology
Department, Catholic University of Sacred Heart of Rome, Rome, Italy
INTRODUCTION: IBD patients display a variety of nutritional deficiencies
because of decreased nutrient intake or absorption and/or increased losses.
Magnesium (Mg) is a critical cofactor for numerous enzyme systems and its
deficiency may result in several clinical manifestations. Recent evidence
showed that Mg participates in immune system regulation. Intestinal mucosa
and kidneys, are the natural access routes for magnesium into the blood
stream which involves cation channels and transporters, like TRPM-6 and -7.
Few information exist on Mg in IBD pathogenesis.
AIMS & METHODS: The aim of the study is to assess whether Mg receptors
TRPM-6 and -7 are involved in an experimental model of colitis. DSS colitis was
induced in C57BL/6 mice. 5 Mice received 2.5% DSS in tap water for 5 days and
then sacrificed, while controls received only water. 5 further mice received 2.5%
DSS for 5 days and then exposed to water for further 7 days to observe recovery.
At the sacrifice plasma was collected from each animal, stored at -80 C and then
assessed for Mg content by atomic absorption spectroscopy; a first section of
liver, kidney and bowel were snap frozen and then analized by Real Time (RT)PCR for TRPM-6 and -7; a second section of each was fixed in 4% formalin and
embedded in paraffin for immunohistochemistry (IHC).
RESULTS: As expected mice exposed to DSS for 5 days developed a mild colitis,
which was associated to lower Mg plasma concentration (mean value 0.64mM)
compared to healthy controls (mean value 0.77 mM). At IHC and RT-PCR
analysis TRPM-6 and -7 expression did not differ in liver and kidney among
healthy and colitic mice. On the contrary, their expression in bowel decreased
drastically in colitic mice. By IHC, we observed a decrease of TRPM6 expression
and a change of localization of TRPM7 within enterocytes from apical to basolateral position. In recovered mice, the intestinal expression of
TRPM-6 and -7 was restored.
CONCLUSION: Mg plasma concentration decrease during active colitis. This
observation paralleled the decrease of intestinal TRPM-6 and -7 expression.
Further experiments are required to show the immunological consequences of
this observation.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)


P0829 HIRSUTENONE
AMELIORATES
EPITHELIAL
BARRIER
DISRUPTION THROUGH CONVERGENCE OF EGFR/AKT AND
ERK1/2 PATHWAYS ON HEME OXIDASE-1 INDUCTION IN HUMAN
INTESTINAL EPITHELIAL CELLS
W.-Y. Jiang1,2, H. Jin1,2, G.S. Seo3, S.H. Lee1,2,*
1
College of Pharmacy, Wonkwang University, 2BK21plus program & Department
of Smart Life-Care Convergence, Wonkwang University, Graduate School,
3
Digestive Disease Research Institute, Wonkwang University College of Medicine,
Iksan, Korea, Republic Of
Contact E-mail Address: gsseo@wku.ac.kr
INTRODUCTION: Oxidative stress-induced disruption of epithelial tight junctions (TJ) plays a critical role in the pathogenesis of intestinal disorders, including inflammatory bowel disease (IBD).
AIMS & METHODS: The current study investigated the protective effect of
diarylheptanoid hirsutenone against disruption of the intestinal barrier in vitro
and in a mouse model of colitis. Caco-2 cells were stimulated with tert-butyl
hydroperoxide (t-BH). Monolayer permeability was assessed by measuring the
transepithelial electrical resistance and inulin flux. Colitis was induced in mice by
intrarectal administration of trinitrobenzene sulfonic acid (TNBS). The mRNA
and protein levels were analyzed by real-time polymerase chain reaction (PCR)
and immunoblotting, respectively.
RESULTS: Hirsutenone prevented the t-BH-induced increase in permeability by
inhibiting the reduction in zonula occludens-1 (ZO-1) expression, and rapidly
stimulated tyrosine phosphorylation of the epidermal growth factor receptor
(EGFR). Hirsutenone-mediated protection against the loss of ZO-1 depends
on the activation of both ERK1/2 and Akt signaling pathways. Interestingly,
hirsutenone-mediated activation of Akt, but not ERK1/2, signaling was EGFRdependent. Hirsutenone increased heme oxygenase-1 (HO-1) expression through
both EGFR/Akt- and ERK1/2-dependent pathways, contributing to the protective effects against TJ dysfunction. Hirsutenone administration improved the
clinical parameters and tissue histological appearance, stimulated HO-1 expression, attenuated reduction of ZO-1 and occludin mRNA, and promoted BrdU
incorporation in the colonic epithelium of TNBS-treated mice.
CONCLUSION: Hirsutenone reversed disordered intestinal permeability by activating EGFR/Akt and ERK1/2 pathways, which are involved in HO-1 expression regulation. These findings highlight the potential of hirsutenone for clinical
applications in the treatment of IBD.
Disclosure of Interest: None declared
P0830 DIFFERENTIAL EXPRESSION IN ALPHA7 NICOTINIC
RECEPTOR IN MUCOSAL MACROPHAGES OF IBD PATIENTS: A
ROLE FOR NICOTINE MODULATION OF INFLAMMATION?
L. Spagnol1,2, G. Girardin1,*, P. Brun2, M. Scarpa2,3, M. Scarpa3, R. DInca`1,
G.C. Sturniolo1, I. Castagliuolo2, F. Galeazzi1
1
Dpt of Surgical, Oncologicall and Gastroenterological Science, Section of
Gastroenterology, Padova University-Hospital, 2Dpt of molecular medicine,
Microbiology and clinical microbiology, 3Dpt of Surgical, Oncologicall and
Gastroenterological Science, Surgical Oncology Unit, Veneto Institute of
Oncology, Padova, Italy
Contact E-mail Address: giulia.girardin@gmail.com
INTRODUCTION: It is well accepted that in animal models of intestinal inflammation nicotine activates a cholinergic counter-inflammatory mechanism
through the alpha7 nicotinic acetylcholine receptors (7nAChR). However in
inflammatory bowel diseases (IBD) nicotine shows opposing effects on intestinal
inflammation: its beneficial in ulcerative colitis (UC) while it increases risk of
surgery and relapse in Crohns disease (CD).
AIMS & METHODS: In this study we measured 7nACh expression on peripheral and intestinal mucosa-derived macrophages from patients with UC, CD and
healthy controls (HV) and evaluated the effect of nicotine on LPS-induced cytokines production in macrophages. Peripheral blood derived macrophages (Mc)
were obtained by supplementing blood monocytes from UC and CD patients (in
clinical remission) and HV with M-CSF (7 days). 7nAChR mRNA and protein
levels were evaluated by qRT-PCR and FACS analysis using -bungarotoxin
(Bgt)-FITC. Mc were pre-incubated with nicotine (1mg/ml 30min) and then
stimulated with LPS (1mg/ml 24 hrs). TNF levels were measured on supernatant
using ELISA. Colonic mucosa macrophages (Mi) were isolated from biopsies
of UC (n 12), CD (n 11) and HV (n 17) and 7nAchR expression was
evaluated by FACS analysis using Bgt-FITC. Macrophages were incubated
for 24 hrs with LPS (1mg/ml) in presence or absence of nicotine (1mg/ml) and
TNF and IFN assessed by staining with specific antibodies and cytofluorimetric analysis.
RESULTS: Mc from UC showed greater 7nAchR mRNA levels then cells
from CD (p 0.006), while no differences were found with HV. FACS analysis
confirmed greater 7AChR expression in UC patients than in CD (90.75 Gmean
in UC Vs 15.62 Gmean in CD, p 0.031) but not in HV. Although nicotine
significantly decreased LPS-stimulated TNF release in Mc from HV, CD
and UC, no differences were observed among groups. Indeed, in UC derived
Mi 7nAChR levels were significantly higher than in CD and HV cells
(p50.01 vs both). Furthermore, nicotine significantly specifically reduced LPSinduced TNF upregulation in Mi from UC patients (from 18.912.57 to
10.811.99 %fluorescence, p 0.013) but not in CD and HV whereas nicotine
had no effect on LPS-induced IFN upregulation in Mi in the different experimental groups.
CONCLUSION: The selective 7nAchR upregulation in Mi from UC patients
and their responsiveness to the anti-inflammatory effects of nicotine may explain
nicotines protective effects in UC but not in CD patients.
Disclosure of Interest: None declared

P0831 NOTCH
SIGNALING
AND
TNF-A
SYNERGISTICALLY
PROMOTES INTRACELLULAR PROTEIN ACCUMULATION OF
OLFM4 IN THE INFLAMED MUCOSA OF ULCERATIVE COLITIS
G. Ito1,*, R. Okamoto1,2, H. Shimizu1, S. Fujii1, T. Nakata1, K. Suzuki1,
K. Tsuchiya1, T. Nakamura1, M. Watanabe1
1
Gastroenterology and Hepatology, 2Center for Stem Cell and Regenerative
Medicine, Tokyo medical and dental university, Tokyo, Japan
Contact E-mail Address: rokamed2@tmd.ac.jp
INTRODUCTION: The intestinal epithelium is maintained by the stem cell
residing at the bottom of the crypt. Olfactomedin-4 (OLFM4) is one of the
specific marker genes of the human intestinal stem cell. The gene encodes secretory-type, as well as intracellular-type, OLFM4 proteins. Reports have shown
that secretory-type OLFM4 facilitates cell adhesion and may take part in mucosal defense, whereas intracellular-type OLFM4 can exhibit anti-apoptotic property. Also, it has been shown that the expression and secretion of OLFM4 is
upregulated in the inflamed mucosa of ulcerative colitis (UC), where Notch
signaling is highly activated. However, the expression of the intracellular-type
OLFM4 protein in the inflamed mucosa, or the mechanism regulating its expression, remains unclear.
AIMS & METHODS: We aimed to identify the expression of intracellular-type
OLFM4 in the normal and inflamed mucosa of the human colonic tissue, and
also to clarify the molecular mechanism regulating its expression in the inflamed
mucosa. Expression of intracellular-type OLFM4 in colonic tissues of normal
and UC patients was analyzed by immunohistochemistry (IHC). Human colonic
epithelial cell lines, Ls174T and DLD1, were employed to analyze the expression
of OLFM4 in response to various inflammatory stimuli. Involvement of Notch
signaling in OLFM4 protein expression was examined by using a sub-line of
Ls174T cells (Ls174T-NICD cells) in which Doxycycline-dependent activation
of Notch signaling can be induced. Using those cell-lines, the expression of
secretory-type OLFM4 protein was quantified by ELISA, whereas that of intracellular-type OLFM4 protein was examined either by immunoblot analysis or by
immunocytochemistry.
RESULTS: IHC analysis of the normal human colon tissues showed that
OLFM4 is expressed mostly at the apical surface of epithelial cells residing at
the lower crypt, indicating dominant expression of secretory-type OLFM4.
However, in the inflamed mucosa of UC patients, an increased number of colonic
epithelial cells clearly expressed OLFM4 in their cytoplasm, indicating high-level
expression of intracellular-type OLFM4. In vitro analysis using human colonic
epithelial cell-lines showed that, among various pro-inflammatory cytokines,
TNF- significantly upregulates secretion of OLFM4, but do not promote accumulation of the intracellular-type OLFM4. In contrast, forced activation of
Notch signaling never induced secretion of OLFM4, but induced accumulation
of intracellular-type OLFM4. Upon addition of TNF- under forced activation
of Notch signaling, those stimuli synergistically up-regulated the accumulation of
intracellular-type OLFM4 protein to a remarkably high-level, but did not give
any additional change to secretion of the OLFM4 protein.
Immunocytochemistry clearly confirmed the cytoplasmic accumulation of
OLFM4 protein by the synergistic effect of TNF- and Notch activation.
CONCLUSION: Notch signaling and TNF- synergistically promotes accumulation of intracellular-type OLFM4 protein in human colonic epithelial cells. As
it has been suggested that those type of OLFM4 protein can exhibit anti-apoptotic function, such an accumulation may contribute to protect human colonic
epithelial cells in the inflammatory environment.
Disclosure of Interest: None declared
P0832 PPAR-GAMMA EXPRESSION IN THE COLON IS REGULATED
BY THE MIR27A UNDER HYPOXEMIC CONDITION
G. Bouguen1,2,*, J.-B. Delobel1, C. Rauch1, B. Clement1, L. Dubuquoy3,
A. Corlu1, L. Siproudhis1,2
1
INSERM U991, Universite de Rennes 1, 2Service des maladies de lAppareil
Digestif, CHU Pontchaillou, Rennes, 3INSERM U995, Universite de Lille 2, Lille,
France
Contact E-mail Address: guillaume.bouguen@chu-rennes.fr
INTRODUCTION: The peroxisome proliferator-activated receptor- (PPAR)
is a key factor of mucosal homeostasis and the pharmaceutical target of 5-aminosalycilates. Thus, understanding of the primarily decrease expression of
PPAR during UC remains challenging and of therapeutic interest. Mucosal
hypoxemia has been well described during UC. The aim of the study was to
assess and to study the link between hypoxia and PPAR expression in intesintal
epithelial cell during UC.
AIMS & METHODS: In Vitro, PPAR mRNA and protein were quantified in
various epithelial cell lines 1) during exposure to hypoxia (1%O2) at several time
points 2) after chemical induction of HIF-1 3) after transfection of miR-27a or
knockout of miR-27a (a microRNA induced by hypoxia and with high affinity to
PPAR in silico) and 4) after stimulation by sildenafil (a phosphodiesterase type
5 inhibitor used for blood vessel dysfunction). Ex vivo, PPAR and miR27a
expressions were quantified from mucosal biopsies of surgical specimens from
controls or patients with UC.
RESULTS: In vitro, exposure of Caco-2 and HT29 cells to hypoxia (1% O2)
decreased significantly mRNA and protein expression of PPAR (at least 50%)
as compared to normoxic condition (21% O2) at days 2. To assess the link
between hypoxia and the decreased expression of PPAR, we first induced
HIF-1 expression, a key factor of cells response under hypoxic condition, by
chemical treatment of cultured cells lineages (deferoxamine, cobalt chloride and
dimethyloxaloylglycine). No effect was observed either on PPAR expression
neither on miR27a expression. Regarding this result suggesting an independent
HIF-1 way that controls PPAR expression during hypoxia, we focused on

A360
miR-27a. MiR-27a was induced by hypoxia in epithelial cells. When miR-27a
was overexpressed by transfection in caco-2 cells during normoxic condition,
PPAR expression was decreased. Conversely, PPAR was not affected by
hypoxia after knockout for miR27a of caco-2 cells by transfection of miR-27a
inhibitors. Ex vivo, we confirmed a decreased of PPAR expression in colonic
mucosa of patients with UC and higher miR-27a expression as compared to
controls. In order to affect the variation of PPAR expression during hypoxia
we used the sildenafil. The sildenafil raised PPAR expression in caco-2 cells
exposed to hypoxia. Furthermore the use of sildenafil resulted in the absence of
overeexpression of miR-27a expression during hypoxia.
CONCLUSION: A direct relationship was observed between hypoxia and
PPAR expression. Mir-27a which is overexpressed during hypoxia and in
patients with UC might be the key factor involved during hypoxia to control
PPAR expression. These results open new insight into the pathophysiology of
UC and the role of hypoxia as well as new therapeutic strategy such as the use of
sildenafil.
Disclosure of Interest: None declared
P0833 MECHANISMS UNDERLYING THE EFFECTS OF CALCITONIN
GENE-RELATED PEPTIDE IN A RAT COLITIS MODEL
H. Yamasaki1,*, R. Yamauchi1, K. Kuwaki1, S. Yoshioka1, H. Takedatsu1,
K. Mitsuyma1,2, T. Torimura1
1
Department of Medicine, 2Infllamatory Bowel Disease Center, KURUME
UNIVERSITY SCHOOL OF MEDICINE, Kurume, Japan
INTRODUCTION: Calcitonin gene-related peptide (CGRP), a vasodilative neuropeptide, is involved in potent tissue repair and anti-inflammatory actions.
Previous studies have shown that the administration of CGRP prevents colonic
injury. However, the mechanism of action responsible for the effect of CGRP on
colitis remains unknown.
AIMS & METHODS: Colitis was induced by the oral feeding of 3% dextran
sulfate sodium to rats for up to 7 days. After the induction of colitis, CGRP (200
g/L/day) was administered via the tail vein twice a day for 7 consecutive days.
Disease severity was assessed by clinical and endoscopic evaluation, and histologic scoring. The tissue levels of pro-inflammatory cytokines (interleukin [IL]1, IL-6, and tumor necrosis factor [TNF]-) and CGRP receptors (receptor
activity-modifying protein-1 [RAMP1] and calcitonin receptor-like receptor)
were determined using real time-PCR. Bone marrow cell induction and colonic
blood flow were also investigated. Additionally, the cytokine response in peripheral blood mononuclear cells stimulated by lipopolysaccharide with or without
CGRP was examined in vitro.
RESULTS: The administration of CGRP, but not a control vehicle, improved
the clinical disease activity (P 0.009) and the endoscopic disease activity
(P 0.009). CGRP decreased the mRNA levels of IL-1 (P 0.032), IL-6
(P 0.032) and TNF- (P 0.016) and increased the mRNA level of RAMP1
(P 0.001). CGRP increased the colonies of CFU-GM in the bone marrow
(P 0.016) and the number of endothelial progenitor cells in the peripheral
blood (P 0.040) and enhanced the colonic blood flow (P 0.032). The
mRNA and protein levels of the inflammatory cytokines in lipopolysaccharidestimulated peripheral blood mononuclear cells were significantly reduced after
the addition of CGRP in vitro.
CONCLUSION: The administration of CGRP effectively suppresses colonic
injury through the down-regulation of pro-inflammatory cytokines and the upregulation of protective events, including bone marrow-derived cell induction, in
addition to promoting colonic blood flow. Consequently, CGRP is an attractive
and novel therapeutic target for the treatment of inflammatory bowel disease.
Disclosure of Interest: None declared
P0834 SERUM IL-23 DIFFERENTLY CORRELATES WITH COLONIC
MMP-9/TIMP-1 AND MMP-9/TIMP-2 IN CROHNS DISEASE, BUT
NOT ULCERATIVE COLITIS PATIENTS
A. Piechota-Polanczyk1, M. Jonakowski1, A. Pilarczyk1, M. Wlodarczyk2,
A. Sobolewska2, M. Wis niewska-Jarosinska2, J. Fichna1,*
1
Department of Biochemistry, 2Department of Gastroenterology, MEDICAL
UNIVERSITY OF LODZ, Lodz, Poland
Contact E-mail Address: jakub.fichna@umed.lodz.pl
INTRODUCTION: Intestinal alterations in IBD are triggered and sustained by
over-expression of pro-inflammatory cytokines. Cytokine quantification may
become a non-invasive tool to monitor the disease progression and effectiveness
of therapy, or assist in understanding disease etiology. Currently, there are limited non-invasive biomarkers for monitoring IBD progression; however, the role
of selected cytokines like IL-23 and IL-17, or proteolytic proteins like matrix
metaloproteinases (MMP) or their tissue inhibitors (TIMP), is under
consideration.
AIMS & METHODS: The aim of this study was to evaluate if IL-17 and IL-23
correlate with MMP-9/TIMP complexes in IBD and if those parameters differ in
affected and unaffected colon mucosa.
Serum and biopsy specimens from affected and unaffected colonic mucosa of 19
patients with IBD (9 with ulcerative colitis, UC and 10 with Crohns disease, CD)
and 8 controls were included in our study. Serum and tissue cytokines, and tissue
MMP-9/TIMP-1 and MMP-9/TIMP-2 were quantified at the protein level by
ELISA.
RESULTS: The UC subjects had significantly lower serum IL-23 (p 0.002) and
slightly higher serum IL-17 level (p 0.09) compared with control. In unaffected
tissues, there was a significant decrease in IL-23 content (p 0.002 vs. control).
In CD patients no difference in serum IL-23 or IL-17 content was measured;
however, both IL-23 and IL-17 were significantly decreased in unaffected colon

United European Gastroenterology Journal 2(1S)


tissues (p 0.00003 and p 000002 vs. control). The levels of IL-23 or IL-17 in
affected tissues from UC and CD groups were comparable.
As IL-17/IL-23 axis directly influences MMP-9 activity, we measured the concentration of MMP-9 in complex with TIMP-1 or TIMP-2. The UC group had
significantly higher MMP-9/TIMP-1 level in unaffected tissue compared with
control (p 0.001), while in CD an opposite tendency was observed.
Regarding MMP-9/TIMP-2, there was a decrease in unaffected tissue in both
UC and CD groups compared with control (p 0.07 and p 0.08, respectively).
Further analysis revealed that IL-23 correlates with MMP-9/TIMP-1 in UC and
with MMP-9/TIMP-2 in CD. In the UC group serum IL-23 negatively correlated
with MMP-9/TIMP-1 in unaffected tissue (r -0.903), but positively in affected
colon sections (r 0.72). In CD subjects, there was a strong negative correlation
between serum IL-23 and MMP-9/TIMP-2 in unaffected tissue (r -0.94); and
positive correlations between tissue IL-23 and MMP-9/TIMP-2 in both unaffected and affected areas (r 0.66 and r 0.62, respectively).
CONCLUSION: It is believed that higher IL-23 levels decrease the content of
MMP-9/TIMP complexes, which in turn may lead to elevated MMP-9 levels and
MMP-9-induced tissue damage. The correlations between serum and tissue IL-23
and MMP-9/TIMP-1 in UC or MMP-9/TIMP-2 in CD, in particular in unaffected mucosa, may therefore be an indicator of an ongoing inflammatory process. However, further studies are necessary to explain the interaction between
cytokines, especially IL-23 and pro- and anti-proteolytic proteins in inflamed and
non-inflamed areas in IBD subjects.
Disclosure of Interest: None declared
P0835 CROHNS DISEASE-ASSOCIATED ADHERENT-INVASIVE E.
COLI INDUCE SECRETION OF EXOSOMES WITH PROINFLAMMATORY ACTIVITY BY INTESTINAL EPITHELIAL CELLS
J. Carriere1,*, H. Nguyen1, A. Darfeuille-Michaud1
1
UMR 1071 Inserm, University of Auvergne, Clermont-Ferrand, France
INTRODUCTION: Crohns disease (CD) is a chronic inflammatory bowel disease of which the etiology involves environmental, genetic and microbial factors.
Our group and others have shown a high prevalence of the invasive E. coli
strains, designated adherent-invasive E. coli (AIEC), in the intestinal mucosa
of CD patients. Exosomes are small endosomal-derived vesicles involved in cell
to cell communication and have been implicated in various diseases including
cancer and infectious disorders. It has been reported that mammalian cells
infected with pathogens can release exosomes containing microbial compounds.
AIMS & METHODS: Here, we investigated the capacity of CD-associated
AIEC bacteria to induce secretion of exosomes by intestinal epithelial cells and
to determine the inflammatory characteristics of the released exosomes. Human
intestinal epithelial T84 cells cultured on transwell filters were infected with an
AIEC reference strain LF82. Exosomes were purified using the ExoQuick exosome precipitation reagent. Exosomes released into the apical or basolateral
compartments of LF82-infected T84 cells were tested for their ability to promote
a pro-inflammatory response in na ve macrophagic cells.
RESULTS: Electron microscopy and immunogold-labeling for an exosomal
marker, CD63, analyses showed that differentiated T84 cells infected with
AIEC LF82 secreted an increased amount of exosome compared to uninfected
cells. This was confirmed by increased levels of four exosomal markers (CD63,
CD81, CD9 and Hsp70) as assessed by Western blot. Exosomes apically secreted
by infected T84 cells but not from uninfected cells significantly induced production of the pro-inflammatory cytokines TNF- and IL-6 in human macrophages,
and this was not due to the presence of lipopolysaccharide, known to induce a
pro-inflammatory response.
CONCLUSION: In conclusion, our study shows that upon infection with CDassociated AIEC bacteria, differentiated intestinal epithelial cells release exosomes that can trigger pro-inflammatory responses in na ve macrophagic recipient cells.
Disclosure of Interest: None declared
P0836 DIAGNOSIS AND PERSISTENCE OF HISTOLOGICAL CHANGES
IN LYMPHOCYTIC COLITIS
J. Rasmussen1,*, P. Engel2, L.K. Munck3,4
1
Department of medicin, Kge Sygehus, Kge, 2Department of pathology, Roskilde
Hospital, Roskilde, 3Department of medicin, Kge Hospital, Kge, 4Faculty of
Health and medical sciences, University of copenhagen, copenhagen, Denmark
Contact E-mail Address: jul.rasmussen@gmail.com
INTRODUCTION: The topographic distribution of histological changes in
microscopic colitis (MC) remains controversial. The main conception has been
that in order to detect or rule out MC, biopsies from the right colon is necessary.
However this has to some extent been proposed on the basis of a selected population of patients included in randomised trials with collagenous colitis (CC). A
sigmoideoscopy is more gentle with the patient, cheaper and often more accessible and thus would be preferred if sufficient in detecting MC.
AIMS & METHODS: Aims: To access the topography of histological changes in
the colon diagnostic of lymphocytic colitis (LC) in a complete series of consecutive, non-selected patients and to provide the sensitivity of left- and right-side
biopsies respectively. Furthermore to analyse the persistence of changes in
repeated endoscopies.
Methods: Retrospective review of the pathologic descriptions in the Danish
National Pathology Database in patients diagnosed with lymphocytic colitis in
the coverage area of Kge Hospital from 2000 through March 2014. Biopsies
from the rectum were excluded.
RESULTS: LC was diagnosed in 238 patients; in 81 (34%) by sigmoideosopy
and in 136 (57%) by colonoscopy. A medical history of watery diarrhoea could
be retrieved in 196, 1 did not have diarrhoea. The median number of biopsies

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United European Gastroenterology Journal 2(1S)


taken was 6 (mean 7.6). Biopsies were taken from both right and left colon in 122
(51%) and showed LC in both left and right colon of 119 (98%). At the diagnostic endoscopy 3 patients (2%) had changes in the left colon only and no one
had changes in the right colon only. The histological diagnosis in the right colon
were: normal (1), chronic inflammation (1) and incomplete LC (1). The sensitivity of left sided biopsies for the primary diagnosis of LC were 100% (95% CI: 97100%) and right sided 98% (94-100%). A second endoscopy following the diagnostic one was performed in 50 (21%) of the 238 patients after a median of 13.5
months (mean 27.2) with a median of 6.5 biopsies (mean 7.1). LC was reconfirmed in 28 (56%). Other histological changes found were: normal (4), chronic
inflammation (2), incomplete LC (2), CC (2) and non specific changes (10). In 3
patients histological changes diagnostic of collagenous colitis were found in one
or more of the endoscopies following the diagnostic one. Looking at the total
number (161) of colonoscopies diagnostic of LC (with biopsies from both right
and left colon) done in the population, 1 patient (1%) had changes in the right
colon only and 3 patients (2%) had changes in the left colon only. Prior nondiagnostic endoscopies were performed in 22 patients (9%) with a median of 4
(mean 5) biopsies. In these histological changes were: normal (4), chronic inflammation (10), incomplete LC (4) and non specific changes (4).
CONCLUSION: While a full colonoscopy can be necessary in order to exclude
other diagnoses, biopsies from the left colon are suffice for diagnosing or excluding LC in patients with chronic watery diarrhoea. The histological findings are
not permanent and can change from one type of microscopic colitis to another
suggesting that the different types of microscopic colitis are closely related.
Disclosure of Interest: None declared
P0837 METABOLIC PROFILING OF FECAL VOLATILE ORGANIC
COMPOUNDS IN ULCERATIVE COLITIS PATIENTS
L. Boesmans1,*, K. Windey1, G. Vandermeulen1, V. De Preter1, K. Verbeke1
1
Translational Research for Gastrointestinal Disorders, Leuven Food Science and
Nutrition Research Centre, KU Leuven, Leuven, Belgium
Contact E-mail Address: leen.boesmans@med.kuleuven.be
INTRODUCTION: Ulcerative colitis (UC) is an inflammatory bowel disease
characterized by chronic inflammation of the colonic epithelium. The exact etiology of the disease is not fully understood, but the microbiota is implicated in the
initiation and the propagation of the disease. Through bacterial fermentation of
carbohydrates and proteins a plethora of luminal compounds is produced in the
colon, which might interact with the hosts physiology. In the present study, the
metabolic activity of the microbiota was compared between healthy controls and
UC patients with both active and quiescent disease.
AIMS & METHODS: Fecal samples were collected from healthy control subjects
(HC; n 19, 11 female/8 male, age range 20-61 years) and UC patients with active
disease (UC-A; n 45, 14 female/31 male, age range 20-84 years) and during
remission (UC-R; n 40, 15 female/25 male, age range 19-78 years). Active disease
was defined as a partial Mayo score 3. Fecal water (FW) was derived from these
samples by ultracentrifugation at 50.000 x g at 4 C for 2h and was sterile filtered.
Profiles of volatile organic compounds (VOCs) were determined in the FW samples using GC-MS (single quadrupole), coupled on line to a purge-and-trap sample
preparation system. All VOCs were relatively quantified versus an internal standard and classified according to chemical class. Partial least squares (PLS) analysis
was applied to cluster samples with similar metabolite profiles and to identify
VOCs accounting for discrimination between HC and UC patients.
RESULTS: A total of 201 different VOCs were identified in the FW samples,
with an average of 618 VOCs per sample. Cluster analysis of the metabolite
profiles revealed complete separate clustering between HC and UC patients.
Samples from UC-A and UC-R patients were not completely separated. FW
samples from UC patients were associated with a higher prevalence of alcohols,
phenols and benzene-like VOCs. The two latter groups are suggested to arise
from protein fermentation. UC-A patient samples were associated with the presence of primary alcohols (ethanol, 1-propanol and 1-butanol) and low levels of
short and medium chain fatty acids (SCFA and MCFA) and other acids. SCFA
(acetate, propionate and butyrate) are generally recognized to be beneficial for
the hosts health and mainly originate from carbohydrate fermentation. Similar
reductions of SCFA in UC patients were previously observed by the use of
proton NMR [1]. These carboxylic acids are the oxidized counterparts of the
primary alcohols, which suggests an imbalance in reduction-oxidation (redox)
reactions in the colonic lumen.
CONCLUSION: The metabolite profiles of fecal samples allowed to differentiate
HC from UC patients, partly due to the increased presence of alcohols, phenols
and benzene-derivatives in UC patient samples. We identified primary alcohols,
SCFA and MCFA as the most discriminatory metabolites in UC-A patients
compared to HC and UC-R patients. The role of the observed shift in intestinal
redox balance in UC-A patients (more primary alcohols, less SCFA) needs to be
further investigated.
REFERENCES
[1] Marchesi JR, et al. J Proteome Res 2007; 6: 546-551.
Disclosure of Interest: None declared
P0838 THE ASM MUCINASE IS INVOLVED IN ILEAL COLONIZATION
BY CROHNS DISEASE-ASSOCIATED ADHERENT-INVASIVE
ESCHERICHIA COLI
L. GIBOLD1,2,*, C. GALLUCCI1, G. DALMASSO2, D. CIA3, N. BARNICH2,
R. BONNET1,2, J. DELMAS1,2
1
Laboratoire de Bacteriologie, CHU Gabriel Montpied, 2Laboratoire M2iSH,
UMR 1071 Inserm/UdA USC INRA 2018, 3Equipe Biophysique neurosensorielle,
UMR INSERM 1107, Clermont-Ferrand, France
Contact E-mail Address: llyonne@chu-clermontferrand.fr

INTRODUCTION: Mucins are secreted by the intestinal epithelium and constitute an efficient component of innate immune defenses to promote homeostasis
and protect against bacteria. Enteric pathogens, such as Shigella and Vibrio
cholerae, can produce proteases designated mucinases that are capable of cleaving mucins. Ileal lesions of patients with Crohns disease (CD) are abnormally
colonized by adherent-invasive Escherichia coli (AIEC).
AIMS & METHODS: Genome analysis of the AIEC strain LF82 revealed the
presence of a chromosomal gene, designated asm, similar to the Hbp gene of the
avian pathogenic E. coli strains (79% of homology). Hbp has a mucinolytic
activity. To determine whether the Asm protein cleaves mucins, we generated
the LF82asm isogenic mutant and transcomplemented this mutant with the
cloned asm gene.
RESULTS: Concentrated supernatants from LF82 strain and transcomplemented LF82Dasm/asm yielded zones of clearing on mucin gels, whereas LFDasm
did not exhibit mucinolytic activity. We showed, by using a simple column penetration assay, that Asm promoted mucus penetration of LF82. No difference in
adhesion and invasion between LF82 and LF82asm was found in the colonic
epithelial HT29 cells, which are not mucin hyperproducing. However, a significant difference between these strains was observed in the mucin hyperproducing
cell line HT29-16E, suggesting a role for Asm in mucus penetration. These results
were also obtained by confocal and electronic microscopy. To evaluate the involvement of Asm in LF82 colonization in vivo, CEABAC10 transgenic mice were
orally challenged with LF82 or LF82Dasm strains. The numbers of bacteria
counted in the feces and of intestinal mucosal-associated bacteria were increased
in mice infected with LF82 compared to those infected with LF82Dasm.
Quantification of asm mRNA levels showed that bile salts act as an activator
of Asm transcription as well as ileal pH.
CONCLUSION: In conclusion, Asm has a mucinolytic activity that promotes
mucus penetration of AIEC strains and enhances adhesion and invasion to
epithelial cells. Asm contributes to gut colonization of AIEC in murine model.
Thus, mucinases could be one of the key factors of AIEC implantation in CD
patients.
Disclosure of Interest: None declared
P0839 HYPERBARIC OXYGEN THERAPY AMELIORATES
INDUCED ACUTE DISTAL COLITIS IN RATS

TNBS-

R.S. Parra1, L.R. R. Camperoni1,*, A. Lopes2, E.U. Carreira2, F.Q. Cunha2,


S.B. Garcia3, T.M. Cunha2, J.J. R. Rocha1, O. Feres1
1
Surgery and Anatomy, 2Pharmacology, 3Pathology, University of Sao Paulo,
Ribeirao Preto, Brazil
Contact E-mail Address: rsparra@yahoo.com.br
INTRODUCTION: This study investigated the therapeutic effects of hyperbaric
oxygen (HBO) in experimental acute distal colitis focusing on its effect on cytokines and HIF-1.
AIMS & METHODS: Twenty-eight Wistar rats were divided into four groups
(each group had 7 rats): I (Saline); II (Saline/HBO); III (TNBS); and IV
(TNBSHBO). Colitis was induced with a rectal infusion of 150 mg/kg of trinitrobenzenesulfonic acidethanol (TNBS) under anesthesia with Ketamine (50
mg/kg) and Xylazine (10 mg/kg). Control animals received only rectal saline.
After induction, the colitis animals were subjected to two sessions of HBO and
were then euthanized. The distal intestine was resected for macroscopic analysis,
myeloperoxidase activity (MPO) measurements, Western-blot analyses of nitric
oxide synthase activity (iNOS) and Cicloxygenase-2 (COX-2) and immunohistochemical analysis of HIF-1 and COX-2. Cytokines levels (IL-1, CINC-1, IL-10
and TNF-) in the distal intestine were measured using an enzyme-linked immunosorbent assay (ELISA).
RESULTS: HBO therapy attenuated the severity of acute distal colitis, with
reduced macroscopic damage score and reduced cytokine expression. HBO therapy inhibited the acute distal colitis-induced up-regulation of HIF-1 and its
downstream iNOS and myeloperoxidase activity, as well as producing diminished
COX-2 levels
CONCLUSION: The results indicate that HBO therapy attenuates the severity
of acute distal colitis through the down-regulation of the expression of HIF-1
and pro-inflammatory cytokines
REFERENCES
Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417-429.
Iezzi LE, Feitosa MR, Medeiros BA, et al. Crohns disease and hyperbaric
oxygen therapy. Acta Cir Bras 2001; 26(Suppl. 2): 129-132.
Eltzschig HK and Carmeliet P. Hypoxia and inflammation. N Engl J Med 2011;
364: 656-665.
Disclosure of Interest: None declared
P0840 DIFFERENCES IN EXPRESSION OF G PROTEIN-COUPLED
RECEPTOR 55 IN PATIENTS WITH CROHNS DISEASE AND
ULCERATIVE COLITIS
M. Wlodarczyk1,*, A. Sobolewska1, A. I. Cygankiewicz2, P.K. Zakrzewski2,
W.M. Krajewska2, K. Stec-Michalska1, A. Piechota-Polanczyk3, J. Fichna3,
M. Wis niewska-Jarosinska1
1
Department of Gastroenterology, Medical Univeristy of Lodz, 2Department of
Cytobiochemistry, University of Lodz, 3Department of Biochemistry, Medical
Univeristy of Lodz, Lodz, Poland
Contact E-mail Address: dr.mwlodarczyk@gmail.com
INTRODUCTION: G protein-coupled receptor 55 (GPR55) is a newly discovered cannabinoid (CB) receptor, which has been qualified as a part of the endogenous CB system along with classical receptors CB1 and CB2. There is a
growing interest in the possible use of CB receptor agonists in the treatment of
inflammation and abdominal pain. Here we attempted at establishing the levels

A362
of GPR55 expression in inflammatory bowel disease (IBD) patients and healthy
controls and potential implication in IBD treatment.
AIMS & METHODS: The study aimed at identifying whether GPR55 is
expressed in colonic tissue of IBD patients and if so, whether the GPR55 levels
differ between Crohns disease (CD) and ulcerative colitis (UC) patients and
between IBD patients and controls. Twenty five adult patients with IBD (UC:
n 11; CD: n 14) were enrolled in the study. The control group consisted of 6
healthy subjects. The GPR55 mRNA and protein expression were measured
using RT-PCR and immunoenzymatic (Western blot) assay, respectively. Each
assay was performed in triplicate.
RESULTS: GPR55 mRNA was detected in all samples tested. The level of
GPR55 mRNA was strongly (2.7 fold) increased in CD, but only moderately
in UC patients vs. controls. In CD, GPR55 mRNA expression was 3.5 fold
higher in biopsies from inflamed compared to non-inflamed tissues. In contrast,
GPR55 mRNA level in inflamed and non-inflamed tissues in UC was comparable. Similar results were observed for GPR55 expression at protein level. The
changes in GPR55 expression were unrelated to patient age or gender.
CONCLUSION: Different patterns of expression of GPR55 at mRNA and protein levels were observed in IBD patients. We speculate that GPR55 is crucial for
the inflammatory processes in IBD, in particular in CD and may affect disease
severity, as well as response to treatment depending on disease type. The GPR55
receptors may become an attractive target for novel therapeutic strategies in the
treatment of IBD.
Disclosure of Interest: None declared
P0841 HYPERACTIVITY OF THE ENDOGENOUS OPIOID SYSTEM
PROTECTS AGAINST ACUTE, BUT NOT CHRONIC STRESSINDUCED EXACERBATION OF COLITIS IN MICE
M. Sobczak1,*, M. Salaga1, A. Wasilewski1, H. Zatorski1, M. Sacharczuk2,3,
J. Fichna1,3
1
Department of Biochemistry, Medical Univesity of Lodz, Lodz, 2Department of
Molecular Cytogenetics, Institute of Genetics and Animal Breeding, Polish
Academy of Sciences, Jastrzebiec, 3Mossakowski Medical Research Center, Polish
Academy of Sciences, Warsaw, Poland
Contact E-mail Address: sobczak.mart@gmail.com
INTRODUCTION: The endogenous opioid system plays an important role in
the maintenance of homeostasis in the gastrointestinal tract. Recent studies suggest that the impairment of EOS function may be crucial in the pathogenesis and
progression of inflammatory bowel diseases (IBD). However, this has not been
confirmed due to the lack of relevant models.
Recently, two mouse lines - with high (HA) and low (LA) opioid system activity
were developed based on the expression of swim stress-induced analgesia. The
aim of our study was to characterize the role of the endogenous opioid system
and stress in the development of IBD symptoms in HA and LA mouse lines.
AIMS & METHODS: Mice were bred using bidirectional selection and classified
as HA or LA line based on the measurement of analgesia with the hotplate and
tail-flick tests. Colitis was induced by instillation of trinitrobenzenesulfonic acid
(TNBS) in 30% EtOH/saline. After 3 days, the macroscopic score was assessed
and the samples for biochemical, molecular and histological studies were collected. To evaluate the influence of stress on development of colitis, we used
chronic mild stress (exposure to stress stimuli for 2 and 5 weeks) and acute
stress (short restraint over 3 days) models.
RESULTS: We observed a significant difference in the development of colitis
between non-stressed HA and LA mice, as indicated by the macroscopic score
(3.080.06 vs. 6.500.79 for HA and LA, respectively) and ulcer score
(0.300.31 vs. 2.100.31 for HA and LA, respectively). Chronic mild stress
had no influence on colitis in both mouse lines. Colitis was improved in HA
mice exposed to acute stress in comparison with non-stressed animals (1.770.12
vs. 4.601.60), but did not change the inflammation score in LA line.
CONCLUSION: Our studies strongly support the hypothesis that the activity of
the endogenous opioid system may be crucial in IBD development and affect the
success rate in IBD treatment. We also evidence that acute, but not chronic stress
influence significantly the exacerbation of IBD symptoms depending on the
endogenous opioid system activity.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


(ZO1 immunostaining) and IEC proliferation (DAPI cell counting). EGCderived soluble factors (IL6, TGF, proEGF, GSH) and thirty polyunsaturated
fatty acid (PUFA) metabolites were quantified in EGC supernatants. 15dPGJ2,
PPAR agonist (Rosiglitazone) and PPAR antagonist (GW9662) functional
impacts were then measured on IEC spreading and IEB resistance.
RESULTS: EGC isolated from CD and cancer patients (considered as control
EGC) expressed the same level of glial markers (GFAP, S100beta, Sox10).
Whereas control EGC increased significantly IEC transepithelial resistance,
IEC spreading and decreased IEC proliferation, CD EGC had no significant
effect. EGC supernatants showed a severe decrease in 15dPGJ2 and
11betaPGF1alpha production but no change in others EGC-derived soluble
factor expression. 15dPGJ2 also induced a decrease in IEC proliferation but
also an increase in IEC spreading and IEB resistance. In addition, PPAR agonist reproduced these effects and PPAR antagonist abrogated them.
CONCLUSION: All together, these results show that human EGC from Crohns
disease patients have lost their protective properties on IEB integrity among the
regulation of IEB resistance, IEC spreading and proliferation. This could be due
to a defect in the 15dPGJ2 pathway in CD EGC.
Disclosure of Interest: None declared
P0843 HOMOCYSTEINE EXACERBATED DSS-INDUCED COLITIS BY
ACTIVATION OF TH17 CELLS VIA P38 SIGNALING PATHWAY
S. Zhu1, J. Li1, W. Yan1, M. Chen1,*, B. Xia1
1
Department of gastroenterology, Zhongnan hospital, Wuhan, China
Contact E-mail Address: chenmin8106@aliyun.com
INTRODUCTION: It is well knownz that homosysteine is a pro-inflammatory
molecule and contributes to the chronic inflammation of cardiovascular and
cerebral disorders. Hyperhomocysteinemia (HHcy) is a common phenomenon
observed in patients with inflammatory bowel disease (IBD). The influence of
HHcy on the colonic inflammation of IBD has never been explored.
AIMS & METHODS: The aim of this study is to investigate the effect of HHcy
on Dextran sulfate sodium (DSS) induced-colitis. Rats were randomly divided
into 5 groups (n 6 per group): control, HHcy, DSS, HHcyDSS and
HHcyDSSp38 inhibitor. HHcy was induced by giving rats rodent food containing 1.7% methionine for three weeks. Colitis was induced by giving water
containing 5% DSS. The p38 inhibitor (5mmol SB203508/kg) was given twice
daily beginning 60h after DSS treatment. The plasmatic concentration of IL-17
was measured by ELISA. The mRNA and protein expressions of inflammatory
mediators were detected by RT-PCR and Western-blot, respectively.
RESULTS: The rats of HHcyDSS group had scientifically higher body weight
loss, MPO activity, DAI score, and histological score compared to the rats of
DSS group. HHcy significantly increased the plasmatic concentration, the colonic mRNA and protein levels of IL-17, as well as the protein levels of phosphorylated-p38
MAP
kinase,
phosphorylated
cytosolic
phospolipaseA2,
cyclooxygenases 2 and RORt. The increased protein expressions of these
inflammatory mediators were suppressed by p38 inhibitor.
CONCLUSION: HHcy aggravated DSS-induced colitis by the activation of
Th17 cells via p38 signaling pathway. The p38 inhibitor may represent a novel
approach to treatment the chronic intestinal inflammation exacerbated by HHcy
in patients with IBD.
REFERENCES
1. Oussalah A, Gueant JL and Peyrin-Biroulet L. Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases. Aliment Pharmacol Ther 2011; 34:
1173-1184.
2. Peyrin-Biroulet L, Rodriguez-Gueant RM, Chamaillard M, et al. Vascular and
cellular stress in inflammatory bowel disease: revisiting the role of homocysteine.
Am J Gastroenterol 2007; 102: 1108-1115.
3. Chen M, Peyrin-Biroulet L, George A, et al. Methyl deficient diet aggravates
experimental colitis in rats. J Cell Mol Med 2011; 15: 2486-2497.
4. Danese S, Sgambato A, Papa A, et al. Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. Am J Gastroenterol 2005; 100:
886-895.
Disclosure of Interest: None declared
P0844 MICRORNA-612 REGULATES AQUAPORIN 8 EXPRESSION AND
IS UP-REGULATED IN PATIENTS WITH ULCERATIVE COLITIS

P0842 ENTERIC GLIAL CELLS FROM CROHNS DISEASE PATIENTS


MISPRODUCE 15-DEOXY-12,14-PROSTAGLANDIN J2: DEFECT IN
INTESTINAL EPITHELIAL BARRIER RESISTANCE
S. Coquenlorge1, N. Cenac2, M. Biraud1, J. Jaulin1, N. Vergnolle2, M. neunlist1,*,
M. Rolli-Derkinderen1
1
Inserm UMR913, Nantes, 2INSERM UMR-1043 CNRS UMR-5282, Toulouse,
France
Contact E-mail Address: malvyne.derkinderen@univ-nantes.fr
INTRODUCTION: Enteric glia, the major constituent of the enteric nervous
system, plays a key role in the control of intestinal epithelial barrier (IEB) functions. Under physiological conditions, enteric glial cells (EGC) inhibit intestinal
epithelial cells (IEC) proliferation, enhance IEB repair and increase its resistance
to pathogens. All these mechanisms are altered during inflammatory bowel disease (IBD), such as Crohns Disease (CD). EGC lesions have also been observed
in this pathological context, and we investigated here the possible link between
CD EGC and IEB dysfunctions.
AIMS & METHODS: First, we have characterised EGC isolated from CD and
cancer patients (considered as control EGC) by real time Q-PCR and immunostaining. Next, we studied EGC functional impact on IEB using an indirect coculture model with human intestinal epithelial cell (IEC; Caco-2) cell line seeded
on Transwell filters, measuring transepithelial resistance (EVOM), IEC spreading

M. Min1,*, Y. Yang2, Y. Liu1


1
Dept. of Gastroenterology and Hepatology, Affiliated Hospital of Academy of
Military Medical Sciences, 2Dept. of Gastroenterology and Hepatology, Chinese
PLA general hospital, Beijing, China
INTRODUCTION: MicroRNA (miRNA) plays an important role in the pathogenesis of many diseases by regulating the gene expression at the post-transcriptional level and control crucial physiological processes. Altered levels and
functions of miRNAs have been associated with ulcerative colitis (UC), although
little is known about their roles in UC.
AIMS & METHODS: We screened different genes from UC tissues and healthy
subjects by using genome-wide and miRNA microarray in colon samples from 20
patients with UC and 16 healthy subjects undergoing diagnostic colonoscopy.
AQP8 expression and miR-612 were measured by real-time polymerase chain
reaction analysis. Regulation of gene expression by miRNAs was assessed by
luciferase reporter construct assays and transfection of specific miRNA mimics
and inhibitor.
RESULTS: We identified that 1596 genes and 33 miRNAs were increased, 1301
genes and 35 miRNAs were decreased in UC patients compared to healthy subjects. Among them, aquaporin 8 (AQP8) was decreased in patients with UC
compared with control tissues (P 50.01). We searched candidate target
miRNAs of AQP8 through bioformatics and the luciferase report assay analysis

A363

United European Gastroenterology Journal 2(1S)


indicated that miR-612 which has complementary site in the 3-untranslated
region (UTR) of AQP8 could decrease the relative luciferase activities by 45%
and transfection of HT29 cells with the miR-612 mimic resulted in inhibition of
the basal AQP8 protein.
CONCLUSION: miR-612 appears to regulate the expression of AQP8. Increased
levels of miR-612 in colon tissues of active UC appear to decrease expression of
AQP8, which could involved in the pathogenesis of UC.
Disclosure of Interest: None declared
P0845 HEPATOBILIARY,
PANCREATIC
AND
MANIFESTATIONS IN GREEK INFLAMMATORY BOWEL
DISEASE PATIENTS

RENAL

K. Karmiris1,1, A. Avgerinos2, A. Tavernaraki1, C. Zeglinas3, P. Karatzas4,


T. Koukouratos4, K. Oikonomou5, A. Kostas6, E. Zampeli7, V. Papadopoulos8,
A. Theodoropoulou1,*, N. Viazis4, D. Polymeros8, S. Michopoulos7, G. Bamias6,
A. Kapsoritakis5, D.G. Karamanolis4, G. Mantzaris4, C. Tzathas3,
I.E. Koutroubakis2
1
Gastroenterology, Venizeleio General Hospital, 2Gastroenterology, University
Hospital, Heraklion, Crete, 3Gastroenterology, Tzaneio General Hospital, Pireus,
4
Gastroenterology, Evangelismos Hospital, Athens, 5Gastroenterology, University
Hospital, Larissa, 6Gastroenterology, Laiko Hospital, 7Gastroenterology,
Alexandra General Hospital, 8Gastroenterology, Attikon University Hospital,
Athens, Greece
Contact E-mail Address: kkarmiris@gmail.com
INTRODUCTION: Inflammatory bowel disease (IBD) patients often exhibit
common manifestations, which are not characterized as classic extra-intestinal
manifestations, posing clinical dilemmas.
AIMS & METHODS: The aim of our study was to investigate the prevalence
and characteristics of certain common manifestations from the liver, biliary tree,
pancreas and kidneys in IBD patients followed-up in tertiary centers. Data from
1741 IBD patients (females: 43.5%, Crohns disease: 53.9%, median [IQR] age at
IBD diagnosis: 32.9 [23.0-48.4] and IBD duration until 1st EIM diagnosis: 3.0
[0.2-8.0] years) have been retrospectively retrieved and registered according to a
pre-defined protocol. Positive results were based on imaging findings and/or preexisting compatible clinical diagnosis. The impact of certain demographic and
IBD characteristics on results was studied.
RESULTS: Cholelithiasis was present in 113/1489 (7.6%) patients mainly in
females (p50.0001) with Crohns disease ileitis or extensive ulcerative colitis
(p 0.042), concomitant nephrolithiasis (p50.0001) and those having undergone
a major IBD surgery (p 0.031), appendectomy or tonsillectomy (p50.0001).
Non-alcoholic fatty liver disease was detected in 159/1489 (10.7%) patients
mainly in females (p50.0001) with ulcerative colitis (p 0.014) and concomitant
nephrolithiasis (p50.0001). Pancreatitis was diagnosed in 46/1656 (2.8%)
patients. In particular, autoimmune IgG4-related pancreatitis was observed in
5/46 (10.9%), drug-induced in 34/46 (73.9%) and lithiasic in 6/46 (13%) patients.
Pancreatitis was more frequent in smokers (p 0.004) with concomitant nephrolithiasis (p 0.002) and in patients with an ileal-anal pouch anastomosis
(p 0.049). Nephrolithiasis was present in 140/1592 (8.8%) patients less frequently in those with perianal Crohns disease (p 0.019).
CONCLUSION: One tenth or less of our IBD patients exhibited at least one
hepatobiliary, pancreatic or renal manifestation. A different pattern of appearance was observed between Crohns disease and ulcerative colitis patients.
Nephrolithiasis often accompanies the other manifestations.
Disclosure of Interest: None declared
P0846 RENAL CELL CARCINOMA PATIENTS HAVE A BETTER
SURVIVAL IN A NATIONWIDE INFLAMMATORY BOWEL
DISEASE COHORT COMPARED WITH THE GENERAL
POPULATION
L.A. Derikx1,*, C.M. van Herpen2, J.P. Drenth1, W. Kievit3, L. Nissen1,
P.F. Mulders4, I.D. Nagtegaal5, F. Hoentjen1 on behalf of Dutch Initiative on
Crohn and Colitis
1
Department of Gastroenterology and Hepatology, 2Department of Oncology,
3
Department for Health Evidence, 4Department of Urology, 5Department of
Pathology, Radboud university medical centre, Nijmegen, Netherlands
Contact E-mail Address: Lauranne. Derikx@radboudumc.nl
INTRODUCTION: Patients with inflammatory bowel disease (IBD) frequently
undergo abdominal imaging. This may result in an increased number of incidentalomas including renal cell carcinoma (RCC). A high percentage of incidentally
found RCCs might improve cancer outcome; however, immunomodulators and
biological agents, as used in the treatment of IBD, may also impact cancer outcome. In this study we aimed to compare the outcome of RCC between IBD
patients and the general population. Next we evaluated the impact of IBD therapy on RCC outcome.
AIMS & METHODS: Using the Dutch National Pathology Registry (PALGA)
we identified all IBD patients diagnosed with RCC in The Netherlands from
January 1991 until May 2013. Cases were confirmed using anonymized medical
records and clinical and demographic variables were collected. The control group
was derived from the Eindhoven Cancer Registry (1991-2010) which provided the
cancer registration for approximately 2.3 million people in The Netherlands.
RCC characteristics like TNM stage, age at RCC diagnosis and treatment
were compared univariately between cases and controls. Survival analyses were
made with Kaplan Meier curves and confounder correction was performed with
Cox regression.
RESULTS: We included 160 patients from 69 academic and non-academic hospitals with a confirmed IBD diagnosis who developed RCC. 64/160 (45.1%) IBD
patients used thiopurines or biologicals during their disease course of IBD. 73/

160 (51.8%) RCC cases in IBD patients concerned incidentalomas. The control
group consisted of 4388 patients with RCC. Upon comparison, IBD patients had
a statistically significant lower age at RCC diagnosis (median 62.0 versus 66.0;
p50.005), lower N-stage (5.8% N versus 11.4% N; p 0.030) and lower Mstage (10.7% M1 versus 20.0% M1; p50.005). Furthermore IBD patients underwent more frequently surgical treatment for RCC (96.2% versus 75.6%;
p50.005). A Kaplan Meier curve showed better overall survival in IBD patients
(log rank p50.005). Age at RCC diagnosis, T, and M-stage, and surgical treatment emerged as confounders. Adjusted for these confounders, a protective effect
of IBD on overall survival was still present (p 0.015; hazard ratio 0.690; 95%
CI 0.512-0.932). Comparing IBD patients with and without thiopurines and/or
biologicals, overall survival was significantly better in the group who did use
immunosuppression (log rank p 0.012). However, a Cox model adjusted for
TNM stage and age at RCC diagnosis completely abolished the protective effect
of immunosuppression (p 0.949).
CONCLUSION: Patients with IBD who develop RCC have a significantly better
overall survival compared to the general population with RCC, which may partially be explained by an earlier diagnosis of RCC with a subsequent lower
disease stage. Immunosuppression does not adversely affect overall survival.
Disclosure of Interest: None declared
P0847 INFLUENCE OF COPING ON THE CLINICAL COURSE OF
PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A
PROSPECTIVE COHORT STUDY
M. Barreiro-de Acosta1,*, R. Ferreiro-Iglesias2, A. Lorenzo-Gonzalez3,
J.E. Dominguez-Munoz2
1
University Hospital of Santiago de Compostela. Foundation for Research in
Digestive Diseases, Santiago de Compostela, Spain, 2Gastroenterology, University
Hospital of Santiago de Compostela. Foundation for Research in Digestive
Diseases, 3Gastroenterology, University Hospital of Santiago de Compostela,
Santiago de Compostela, Spain
INTRODUCTION: Coping strategies are used to manage conflicts and illnesses,
and may have both adaptative or maladaptative effects on health status. Coping
strategies have not been well studied in patients with Inflammatory Bowel
Disease (IBD), and their influence on the clinical course of the disease and the
use of health resources is unknown
AIMS & METHODS: The aim of the study was to evaluate the influence of the
use of different coping strategies on the number of emergency or unscheduled
visits and hospitalisations in IBD patients.
Methods: A prospective observational cohort study was designed. The cohort
consisted of consecutive out-patients with IBD (Crohns disease (CD) and ulcerative colitis (UC)) who attended our monographic IBD Unit. A basal demographic and clinical questionnaire was completed by all patients. Coping
strategies were assessed with the Spanish version of the COPE scale. It consists
of 60 items that participants rated themselves using the dispositional response
format, and indicating how frequently they engaged in each coping behaviour on
a 4-point Likert scale. The scale had 3 different global strategies: Problemfocused coping, avoidance coping and emotion-focused coping. All emergency
and unscheduled visits and hospitalisations related to IBD over a follow-up
period of 18 months were recorded. The influence of coping on clinical course
was analysed by Multiple Regression analysis.
RESULTS: 776 patients were included (364 male (46.9%), mean age 45 years,
age ranging from 18 to 86 years). 317 (40.9%) patients had CD and 459 (59.1%)
UC. At the baseline evaluation, the most frequently used coping strategies by
IBD patients were problem-focused coping (mean: 2.72 standard deviation, SD:
0.45) and avoidance coping (mean: 2.60, SD: 0.37), and the least frequently used
was emotion-focused coping (mean: 2.36, SD: 0.57). The mean number of
unscheduled or emergency visits was 1.05 (SD: 1.68, range 0-14) and the mean
number of hospitalizations was 0.35 (SD: 0.94, range 0-9). After a follow up of 18
months, the use of avoidance coping strategies was a risk factor for a higher
number of emergency or unscheduled visits in the multivariate analysis
(B 0.027, CI95%: 0.009-0.045; p50.005). However, coping strategies did not
influence the need of hospitalisations.
CONCLUSION: The coping strategies mostly used by IBD patients are the
problem-focused coping and avoidance coping. A frequent use of avoidance
coping strategies appears to be a risk factor for requiring a higher number of
emergency visits in the following months. Therefore, these patients would probably benefit from psychological support.
Disclosure of Interest: None declared
P0848 SEXUAL DYSFUNCTION IN INFLAMMATORY BOWEL
DISEASE: DO GASTROENTEROLOGISTS OVERLOOK THIS ISSUE?
M.J. Arguero1,*, M.J. Etchevers1, M.J. Sobrero1, N.S. Causada Calo1,
M. Mahler1, P.R. Daffra1, R.C. Gonzalez Sueyro1, D.C. Madrid1,
D. Manazzoni1, J.A. De Paula1
1
Gastroenterology, Hospital Italiano de Buenos de Aires, Ciudad Autonoma de
Buenos Aires, Argentina
Contact E-mail Address: maria.arguero@hiba.org.ar
INTRODUCTION: Inflammatory bowel disease (IBD) is a condition associated
with high morbidity and poor quality of life (QoL). This population is usually
young and sexually active. Studies addressing sexual dysfunction (SD) in IBD
patients are scarce and their results are controversial. Moreover, little is known
about how often gastroenterologists discuss this matter with IBD patients.
AIMS & METHODS: Our primary objective was to estimate SD frequency
among IBD patients in the ambulatory setting. Secondary objective was to estimate how often SD is addressed by gastroenterologists. A self-administered
anonymous questionnaire was delivered to adult ( 18 years) IBD patients

A364
who assisted the IBD ambulatory clinic between August and September 2013.
The survey had two parts. The first one assessed QoL by the EuroQol scale and
SD by the Female Sexual Function Index (FSFI) and the International Index of
Erectile Function (IIEF-15) in women and men, respectively. Patients were asked
about whether gastroenterologists inquiry about their sexual function and if they
considered this to be relevant. The second part was filled out by the gastroenterologist who was blinded to the first one. It included the Mayo and HarveyBradshaw Scores, IBD treatment in the previous month and IBD phenotype
according to the Montreal Classification.
RESULTS: Response rate was 74.5%. Seventy five patients were recruited, 61%
(n 46) had ulcerative colitis, 37% (n 28) had Crohns disease and one had
undetermined colitis. Median age was 37 years (IQR 30-55) and 56% (n 42)
were women. SD prevalence in women was 69.7% (n 30). In men, the most
affected domains were overall satisfaction 64.5% (n 20), sexual desire 38%
(n 12) and intercourse satisfaction 35% (n 11). SD was not addressed in
84% (n 63) of IBD patients. In this subgroup, 57% (n 36) answered that
the main reason was that the gastroenterologist did not ask them and 41%
(n 26) answered that it would had been important to be asked about it. QoL
was good or very good in 97% (n 73) of the subjects. None of the patients was
consuming antidepressants.
CONCLUSION: SD was very frequent in both genders. Above 50% of our IBD
patients had impaired sexuality, whereas in the general population SD is considered to be lower, around 35%. Notably, men had lower overall satisfaction and
sexual desire rather than orgasmic and erectile dysfunction. Gastroenterologists
did not assess SD in the majority of IBD patients, while a considerable proportion
of them found discussing this topic with their physician to be relevant. Therefore,
this issue should be addressed. Even though QoL was satisfactory in the vast
majority, SD was prevalent and it should be included in the assessment of QoL
in this population. The small sample size did not allow us to estimate associations.
This is the first study in Latin America that addresses SD in IBD patients.
REFERENCES
Gut 2005; 54: 364-368./Inflamm Bowel Dis 2006; 12(Suppl. 1): S3-S9./
Gastroenterology 2009; 136: 361-362./J Gastroenterol 2013; 48: 713-720./
Gastroenterol Hepatol 2009; 32: 50-54./Clin Gastroenterol Hepatol 2007; 5: 8794./Sexualidad y Salud Mental, ed. Glosa 2003./Gu a GETECCU 2012./
Gastroenterology 2009; 136: A-361-A-362.
Disclosure of Interest: None declared
P0849 INCREASED RISK OF WORK DISABILITY IN INFLAMMATORY
BOWEL DISEASE PATIENTS AFTER SEVEN YEARS OF FOLLOWUP A POPULATION-BASED COHORT STUDY
M.K. Vester-Andersen1, M. V. Prosberg1, I. Vind1, M. Andersson2, T. Jess2,*,
F. Bendtsen1
1
Gastro unit, medical section, Hvidovre Hospital, University of Copenhagen,
Hvidovre, 2Department of Epidemiological Research, National Health Surveillance
and Research, Copenhagen, Denmark
Contact E-mail Address: marianne@kajbaek.dk
INTRODUCTION: Inflammatory bowel disease (IBD) often affects younger
persons and may have considerable impact on the ability to maintain connected
to the labour market.
AIMS & METHODS: We aimed to evaluate the occurrence and risk of sick leave
(SL) and work disability (WD) in incident patients with IBD after 7 years of
follow-up compared to a population-based control group and look for associations of social, phenotypic and clinical characteristics.
A subgroup of 379 IBD patients aged 18-67 years from an IBD-inception cohort
(513 patients) registered Jan 1 2003 to Dec 31 2004 in a well-defined Copenhagen
area were our IBD study population. Clinical data were collected from the medical records. Data on eucational level, sick leave and work disability was retrieved
from national registers. A random subset of the general population (n 1435)
were matched on sex, age and residency to IBD cases. Survival curves displaying
the cumulative probabilities of work disability and sick leave were derived with
the Kaplan-Meier method. Cox proportional hazard regression analyses were
performed to identify possible independently associated predictive factors.
RESULTS: After 7 years of follow-up the cumulative risk of SL and WD was
47.8% and 5.8% in UC respectively and 55.8% and 6.3% in CD respectively.
The overall hazard of SL was 2.01 (95% CI 1.66-2.43) and 2.03 (95% CI 1.183.49) of WD in IBD patients. Male IBD patients (HR 2.38 (95% CI 1.10-5.14))
and patients aged 55-67 years at diagnosis (HR 4.36 (1.65-11.53)) were at
increased risk of receiving WD compared to the general population. Both
women (HR 1.83 (1.43-2.35)) and men (HR 2.29 (1.71-3.08)) were at increased
risk of SL as well as patients aged 18 to 55 had a significantly higher risk of SL
compared to the background population. Age above 55 years increased the risk
of WD in patients with CD (HR 17.49 (95% CI 1.92-159.01) but WD in CD was
not explained by sex, educational level, behaviour and localisation of disease,
smoking or surgery after mutually adjustment. Educational level (HR4 13 years of
schooling 1.79 (95% CI 1.02-3.15)), stricturing disease behaviour (HRB2 0.33 (95%
CI 0.14-0.83) and surgery (HR1 resection 4.09 (95% CI 2.17-7.71), HR2 resections
8.96 (95% CI 2.86-28.03)) were predictors of SL in CD. Smoking ((former (HR
0.22 (95% CI 0.02-2.16) or current (HR 6.02 (95% CI 0.95-37.99)) compared to
never (p .04)) was a predictor of WD in UC and female gender (HR 1.73 (95%
CI 1.10-2.72)) and surgery (HR 4.19 (95% CI 2.09-8.38)) were predictors of SL in
UC.
CONCLUSION: In this population-based study of incident Danish IBD patients
we found that after 7 years of follow-up IBD patients are at increased risk of WD
and SL compared to the background population and that educational level, disease behaviour and surgery were predictors of SL in CD, while high age was a
predictor of WD in CD. Female gender and surgery were predictors of SL in UC,
while smoking status was a predictor of WD in UC. Continuous attention early
after diagnosis should be made on reducing the risk of WD in IBD patients.

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: M. Vester-Andersen: None declared, M. Prosberg: None
declared, I. Vind: None declared, M. Andersson: None declared, T. Jess: None
declared, F. Bendtsen Financial support for research from: MSD, Ferring
Pharmaceuticals, The Research Council of Hvidovre Hospital and The
Research Council of the Capital Region of Denmark.
P0850 PHENOTYPIC
CHARACTERISTICS
AND
USE
THERAPEUTIC RESOURCES IN ELDERLY-ONSET
INFLAMMATORY BOWEL DISEASE: A MULTICENTRE, CASECONTROL STUDY

OF

M. Manosa1,2,*, M. Calafat2, R.de Francisco3, C. Garcia4, M.J. Casanova5,6,


P. Huelin7, M. Calvo8, J. Tosca9, A. Ruiz-Cerulla10, Y. Zabana1,11 on behalf of
on behalf of GETECCU
1
CIBEREHD, Barcelona, 2Gastroenterology, Hospital Universitari Germans Trias
i Pujol, Badalona, 3Gastroenterology, Hospital Central de Asturias, Oviedo,
4
Gastroenterology, Hospital reina Sofa, Cordoba, 5CIBEREHD,
6
Gastroenterology, Hospital La Princesa, Madrid, 7Hospital Santa Creu i Sant
Pau, Barcelona, 8Hospital Puerta de Hierro, Madrid, 9Hospital Clnic de Valencia,
Vale`ncia, 10Hospital de Bellvitge, LHospitalet de Llobregat, 11Gastroenterology,
Hospital Mutua de Terrassa, Terrassa, Spain
Contact E-mail Address: mmanosa.germanstrias@gencat.cat
INTRODUCTION: It has been reported that IBD onset occurs at old age in up
to 10% of cases. Elderly patients have more comorbidities and, therefore, a
potential increased risk of drug adverse effects, increased likelihood of hospital
admissions and postoperative complications.
AIMS & METHODS: To evaluate the phenotypic characteristics and use of
therapeutic resources in patients with elderlyonset IBD.
Methods: Retrospective, case-control, multicentre study. All those patients diagnosed with IBD over the age of 60 years (cases) since 2000 and with a follow-up
412 months were identified from the IBD databases of each centre. Cases were
compared with controls, who were diagnosed with IBD between 18 and 40 years
of age, and matched by year of diagnosis, gender, and type of IBD.
RESULTS: A total of 1,374 cases and 1,374 matched controls were included, of
whom 43% women, 62% ulcerative colitis (UC), 36% Crohns disease (CD) and
2% unclassified IBD. The mean age at diagnosis was 68 years (range, 60-87) within
cases and 28 years (range, 18-45) within controls. 59% of the cases (but only 3% of
controls) had at least one cardiovascular risk factor (arterial hypertension, dyslipidemia or diabetes). The proportion of active smokers at the time of IBD diagnosis was 25% among controls and 13% among cases. Phenotypically, elderlyonset patients had a lower proportion of extensive UC (p50.0001), and a higher
proportion of stenosing and a lower proportion of penetrating pattern (p50.0001)
and exclusive colonic location (p50.0001). Elderly-onset patients had a lower rate
of IBD-related complications (p 0.009) but a higher prevalence of thrombotic
events (p50.0001). Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (p50.0001), immunomodulators
(p50.0001) and biological agents (p50.0001) in elderly-onset patients as compared to controls, but a similar rate of surgeries. Finally, elderly-onset patients had
a higher rate of hospitalizations (p50.0001), neoplasms (p50.0001) and deaths
(p50.0001). In the multivariate analysis, elderly-onset of IBD was independently
associated to a decreased need of immunomodulators and biological agents, and
an increased need of hospital admissions.
CONCLUSION: Elderly-onset IBD is associated to a less severe/complicated
phenotype and the lesser use of immunosuppressive therapies, which probably
accounts for a non-increased IBD-related morbidity. Age at diagnosis might
explain the increase in the rate of hospitalizations among elderly patients.
Disclosure of Interest: None declared
P0851 C. DIFFICILE COLONISATION AND INFECTION RATES ARE
NO LONGER RAISED IN INFLAMMATORY BOWEL DISEASE
N.M. Joshi1,*, M. Adelson1, D. Ball2, D.S. Rampton1
1
Centre for Digestive Diseases, Blizard Instuite, Barts and The London School of
Medicine and Dentistry, 2Department of Medical Microbiology, Barts Health NHS
Trust, London, United Kingdom
Contact E-mail Address: n.m.joshi@qmul.ac.uk
INTRODUCTION: While several studies in the last 10 years have reported
higher rates of C. difficile colonisation (CDC) and C. difficile infection (CDI)
in IBD than in non-IBD patients, the overall incidence of CDI in the UK is now
falling. We have therefore reassessed the incidence of CDC and CDI in diarrhoeal patients with and without IBD.
AIMS & METHODS: All stool samples tested for C. difficile by our laboratory
in the 3-month period ending October 2012 were identified using the microbiology database (Barts Health NHS Trust). A 2-step, ELISA algorithm for
C. difficile testing was applied to liquid stools only: the first was a test for
CDC (presence of glutamate dehydrogenase[GDH] a C. difficile-specific
enzyme); if GDH was positive, a second step was performed to look for CDI
(presence of toxin in stool). Electronic patient records (EPR) were then reviewed
to see if patients whose stool was tested had a known diagnosis of IBD (Crohns
or ulcerative colitis) when the sample was sent.
RESULTS: 927 stool samples were tested, EPR data was not available for 22
(2%) cases (excluded from analysis). 88 (10%) patients had IBD. Mean age
(SEM) in years was 42.1 (2.1) for IBD and 58.2 (0.8) for non-IBD patients,
respectively (p50.0001). With the groups combined: 109 (11%) patients had
CDC and 27 (3%) had CDI. CDC was found in 4 (5%) IBD and 105 (12%)
non-IBD patients (p 0.02). There were no CDI cases in IBD patients and 27
(3%) in non-IBD samples (p 0.1). None of the non-IBD CDC patients went on
to develop IBD (EPR review to March 2014) after their samples were analysed.

A365

United European Gastroenterology Journal 2(1S)


CONCLUSION: In our diarrhoeal patients, CDC is now less common in IBD
than in non-IBD patients. We also found no CDI in our 88 IBD samples.
Although the period studied was short and the numbers of samples limited,
our results suggest that the recent epidemic of CDI in IBD patients may now
be on the wane.
Disclosure of Interest: None declared
P0852 RECENTLY-DIAGNOSED
CROHNS
DISEASE
PATIENTS
DEMONSTRATE MIXED COPING SKILLS TO CONTROL THEIR
PSYCHOLOGICAL DISTRESS
O. Sarid1,*, V. Slonim-Nevo1, D. Schwartz2, V. Dizengof2, N. Abu Freha2,
L. Eidelman2, N. Gaspar2, A. Moshkelo2, A. Rozental2, G. Ben Yaakov2,
D. Munteau2, P. Krugliak2, A. Fich2, M. Friger3, H. Vardi3, D. Greenberg4,
S. Odes5 on behalf of Israel IBD Research Nucleus
1
Social Work, Ben Gurion University of the Negev, 2Gastroenterology and
Hepatology, Soroka University Hospital, 3Public Health, 4Health Systems
Management, Ben Gurion University of the Negev, Beer Sheva, 5Gastroenterology
and Hepatology, Ben Gurion University of the Negev, Metar, Israel
Contact E-mail Address: odes@bgu.ac.il
INTRODUCTION: The general psychopathology and coping processes of
Crohns disease (CD) patients are incompletely understood. Since these elements
are expected to impact on quality of life, it is necessary to define their relationships precisely. The social constructionist perspective has become a useful framework for understanding coping strategies of men and women. This study
examines emotional distress and coping strategies between the genders.
AIMS & METHODS: 158 consecutive CD patients undergoing clinical assessment at the IBD Clinic completed a series of questionnaires: Brief Symptom
Inventory (BSI) which measures psychological distress (range: 0 "not at all"
to 4 "extremely distressed"), Ways of Coping (WAYS) that measures thoughts
and actions that people use to handle stressful encounters (range: 1-8, greater
value higher use), and IBDQ (disease-specific quality of life). Appropriate univariate analysis was performed. Data given as mean  SD.
RESULTS: 135 patients (85%) completed the questionnaires, 62 men (age 39.1 
14.9 years, Harvey-Bradshaw Index (HBI) 7.1  3.7, disease duration 2.2  0.3
years) and 73 women (age 43.5  17.2, HBI 7.9  4.4, disease duration 2.4  0.8).
BSI scores for somatization (1.15), obsessive-compulsive behavior (1.10), interpersonal sensitivity (0.83), depression (0.81), anxiety (1.08), hostility (0.79),
phobic anxiety (0.65), paranoid ideation (0.81) and psychoticism (0.59) revealed
low levels of psychological distress and did not differ significantly between men
and women. WAYS scores without gender differences were: range 46: acceptance, self-blame, active coping; range 5-6: self-distraction, planning, positive
reframing; range 2-4.9: humor, religion, denial, behavioral disengagement, substance use. WAYS scores with gender differences were: use of emotional support
(men 4.03, women 4.80, p50.02), use of instrumental support (3.92, 4.64,
p50.03), venting (3.48, 4.32, p50.005). BSI depression correlated with WAYS
instrumental support (p 0.01), behavioral disengagement (p50.03), and selfblame (p50.02). IBDQ scores were men 49.2  14.9; women 48.6  12.6.
Significant correlations were found between IBDQ and the WAYS scores of
self-distraction, denial, behavioral disengagement, venting, self-blame and religion; and HBI with the BSI scores of somatization, positive symptom total and
positive symptom distress index. IBDQ correlated with HBI (p50.001).
CONCLUSION: In this recently-diagnosed CD cohort, men and women had
similar levels of disease activity and psychological distress. The most prominent
positive coping mechanisms were acceptance and active coping, and negative
trends of self-blame and self-distraction. Women practiced more emotional support, instrumental support and venting. These findings need attention in clinical
practice. [Supported by a generous grant from the Leona M. and Harry B.
Helmsley Charitable Trust].
Disclosure of Interest: None declared
P0853 PREVALENCE OF ALCOHOL CONSUMPTION AND
INFLUENCE ON DISEASE COURSE IN SWISS IBD PATIENTS

ITS

F. Brunner1, R.von Kanel2, S. Begre3, C. Clair4, A. Macpherson1, P. Juillerat1,*


1
Visceral Surgery and Medicine, Gastroenterology, 2Department of General
Internal Medicine, Division Psychosomatic Medicine, Inselspital Bern, Bern,
3
Psychiatric Service, Spital Burgdorf, Burgdorf, 4Policlinique medicale universitaire, University Hospital Lausanne, Lausanne, Switzerland
INTRODUCTION: Little is known about the prevalence and influence of alcohol consumption on the disease course in patients with IBD.
Pathophysiologically alcohol might have an impact on disease course by increasing intestinal permeability, disrupting gut barrier function, inhibiting intestinal
immune system and favouring bacterial overgrowth. Otherwise, low to moderate
alcohol consumption might have an anti-inflammatory effect by lowering IL-6
and TNF- levels.
AIMS & METHODS: We aimed to estimate the prevalence of alcohol consumption and its influence on disease course within the Swiss IBD cohort. Frequency
of alcohol consumption was assessed in a screening question provided in the
enrolment questionnaire of the Swiss IBD cohort. According to the given
answers patients were distributed in 3 categories: non-drinkers (abstainers or
rarely), light-to-moderate drinkers (1-2x per week to daily alcohol consumption),
heavy drinkers (4 2x daily). At enrolment socio-demographic variables and
disease characteristics were compared cross-sectionally to identify risk factors for
increased alcohol consumption and to evaluate a possible influence of alcohol
consumption on disease course. During follow-up need for surgeries and occurrence of abscesses and fistulas were compared prospectively between the 3
groups.

RESULTS: 2019 patients, who had answered the question about alcohol consumption at enrolment in the Swiss IBD cohort between July 2006 and May
2013, were included in the analysis. 870 patients (43%) drank regularly alcohol:
818 low-to-moderately, 52 heavily. Drinkers were older, by the majority male,
had a higher body mass index and smoked more often. The proportion of
Crohns disease patients was lower in non-drinkers (59%) compared to low-tomoderate drinkers (52%). Drinkers reported less extraintestinal manifestations
than non-drinkers (32% vs. 39%, P50.01). Low-to moderate drinkers (31%)
with ulcerative colitis have a lower (p 0.03) proportion of pancolitis than nondrinkers (41%). However heavy drinkers with ulcerative colitis had to be hospitalized less often before enrolment,which, after stratification, seems to be due to
the known protective effect of smoking. Generally heavy drinkers received significantly less immunomodulators (AZA, MTX) and anti-TNF-inhibitors.
During follow-up (6925 patient-years) the need for surgery was similar among
non-drinkers and low-to-moderate drinkers. However heavy drinkers with
Crohns disease had to undergo less surgeries and developed fewer abscesses
and fistulas.
CONCLUSION: The prevalence of regular alcohol consumption within the
Swiss IBD cohort was 43%, whereof 94% drank low-to-moderately. Patients
with higher alcohol consumption were older, preferably males with a higher
body mass index and more often smokers. Heavy drinkers received less treatment
with immunosupressants. In ulcerative colitis low-to-moderate drinking seemed
to favour a shorter extent and heavy drinkers were less hospitalized. In Crohns
disease heavy drinking seemed to reduce the development of abscesses and fistulas and the need for surgeries during follow-up. A prospective project nested
within the Swiss IBD cohort for a better understanding of alcohol on disease
course is ongoing.
Disclosure of Interest: F. Brunner: None declared, R. von Kanel: None declared,
S. Begre: None declared, C. Clair: None declared, A. Macpherson: None
declared, P. Juillerat Lecture fee(s) from: AbbVie, UCB, MSD and Vifor
P0854 IS HOSPITALIZATION PREDICTING THE DISEASE COURSE IN
UC? PREVALENCE AND PREDICTORS OF HOSPITALIZATION
AND RE-HOSPITALIZATION IN ULCERATIVE COLITIS IN A
POPULATION-BASED INCEPTION COHORT BETWEEN 2000-2012
P.L. Lakatos1,*, P.A. Golovics1, M. Mandel1, Z. Kurti1, I. Szita2, Z. Vegh1,
L.S. Kiss1, A. Horvath3, T. Pandur2, M. Balogh4, A. Mohas1, B.D. Lovasz1,
L. Lakatos2
1
1st Department of Medicine, Semmelweis University, Budapest, 2Department of
Medicine, 3Department of Pediatrics, Csolnoky F. Province Hospital, Veszprem,
4
Department of Medicine, Grof Eszterhazy Hospital, Papa, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: Limited data are available on the hospitalization rates in
population-based studies. This is a very important outcome measure.
AIMS & METHODS: The aim of this study was to analyze prospectively if early
hospitalization is associated with the later disease course as well as to determine
the prevalence and predictors of hospitalization and re-hospitalization in the
population-based UC inception cohort in the Veszprem province database
between 2000 and 2012. Data of 347 incident UC patients diagnosed between
January 1, 2000 and December 31, 2010 were analyzed (m/f: 200/147, median age
at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR 4-10 years). Both in- and
outpatient records were collected and comprehensively reviewed.
RESULTS: Probabilities of first UC-related hospitalization and first re-hospitalization were 28.6%, 53.7%, 66.2% and 23.7%, 55.8% and 74.6% after 1, 5 and
10 years of follow-up in Kaplan-Meier analysis. Main reasons for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC
related surgery (4.8%), but the majority of the hospitalizations were unrelated
to UC (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at
diagnosis (HR: 1.35, p 0.018, HRextensive: 1.79, p 0.02 vs. proctitis) or at last
follow-up (HR: 1.56, p 0.001), need for steroids (HR: 1.98, p50.001),
azathioprine (HR: 1.55, p 0.038) and anti-TNF (HR: 2.28, p50.001) were
associated with the risk of UC-related hospitalization. Early hospitalization
was not associated with a specific disease phenotype, however 46.2% of all
colectomies were performed in the year of diagnosis.
CONCLUSION: Hospitalization and re-hospitalization rates are relatively high
in this population-based UC cohort. Early hospitalization was not predictive for
the later disease course.
Disclosure of Interest: None declared
P0855 FAECAL CALPROTECTIN IS AN ACCURATE PREDICTOR OF
ENDOSCOPIC AND HISTOLOGICAL DISEASE ACTIVITY IN IBD
G. Chung-Faye1,*, A. Rahman2, J. Tumova2, B. Hayee2, R. Sherwood2
1
Gastroenterology, Kings College Hospital, 2Kings College Hospital, London,
United Kingdom
Contact E-mail Address: guycf1@gmail.com
INTRODUCTION: Assessment of disease activity in Inflammatory Bowel
Disease (IBD) is challenging as the gold standards of endoscopy and histology
are invasive, expensive and impractical for regular use. Faecal calprotectin (FC)
is increasingly being used as a biomarker of intestinal inflammation but its role in
predicting endoscopic and histological changes in IBD is limited. We explore the
role of FC to assess histological disease in IBD patients, in comparison to Creactive protein (CRP), in the largest series of IBD patients to date.
AIMS & METHODS: Retrospective analyses of 407 IBD patients who had a
colonoscopy with FC (mg/g) and CRP (mg/L) measurements. The most severe
histological inflammation found was graded according to the simplified histology
score (0-normal, 1-mild, 2-moderate, 3-severe). Spearmans correlation coefficient (r) was used to measure correlation between the groups. Receiver operating

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United European Gastroenterology Journal 2(1S)

characteristic (ROC) curves were used to differentiate patients with normal/mild


disease (histology scores 0-1) from patients with moderate/severe disease (histology scores 2-3).
RESULTS: In 203 Crohns disease (CD) patients, the median FC values for the
histology scores; 0, 1, 2, 3 were; 113, 238, 645 and 3075, respectively (graph). The
corresponding medians for CRP were; 2.5, 9.8, 14.6 and 54.6. Both FC ( 0.59,
p50.0001) and CRP ( 0.30, p50.0001) showed very strong correlations to
histology scores. Using a cut-off value of 250g/g, FC showed an 88% sensitivity
and 62% specificity for predicting moderate / severe disease (AUC 0.82). CRP
46 mg/L was less sensitive and specific (70%, 44%, respectively, AUC 0.64).
In 204 ulcerative colitis (UC) patients, the median FC values for the histology
scores; 0, 1, 2, 3 were; 38, 296, 520 and 1468, respectively (graph). The corresponding values for CRP were; 2.5, 5.4, 8.2 and 9.7. There was a very strong
correlation between the FC values to histology scores ( 0.37, p50.0001), compared to CRP ( 0.21, p 0.003). Using a cut off value of 222 g/g, FC had a
71% sensitivity and 51% specificity (AUC 0.66) for predicting moderate / severe
histological disease. The corresponding figures for CRP46 mg/L were 54% and
59%, respectively (AUC 0.59).
Histology n
CD - Calpro 95%
score
(CD) (Median)
CI
0
1
2
3

42
87
65
9

113.0
238.0
645.0
3075.0

53.0 to
175.0 to
517.0 to
452.0 to

n
UC - Calpro
(UC) (Median)
95% CI
161.0 25
330.0 94
955.0 73
5575.0 12

38.0
295.5
520.0
1468.0

25.0
205.0
280.0
122.0

to
to
to
to

66.0
481.0
770.0
4655.0

CONCLUSION: In the largest IBD series to date, FC was strongly predictive of


histological disease activity in both CD and UC patients, and with a cut off level
of 220-250g/g gave high sensitivity and moderate specificity for predicting
moderate to severe disease activity. FC showed greater accuracy in CD than in
UC and also performed better than CRP. This study highlights the importance of
FC as a valuable, non-invasive biomarker of disease activity in IBD, which can
help direct treatment and reduce the need for invasive endoscopic procedures.
Disclosure of Interest: None declared
P0856 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE
MANAGEMENT OF PATIENTS WITH INFLAMMATORY BOWEL
DISEASES: A CONSENSUS REPORT BASED ON LITERATURE
H. Neumann1,*, R. Arsenescu2, H. Bertani3, E. Coron4, A. Dlugosz5,
J. Galmiche4, K. Ho6, S. Singh7
1
Universitatsklinikum Erlangen, Erlangen, Germany, 2Ohio State University
Medical Center, Columbus, United States, 3Nuovo Ospedale Civile SantAgostino
Estense, Modena, Italy, 4CHU Nantes, Nantes, France, 5Karolinska University
Hospital Huddinge, Stockholm, Sweden, 6National University Hospital, Singapore,
Singapore, 7VA Boston Healthcare System- West Roxbury, Jamaica Plain, United
States
Contact E-mail Address: helmut.neumann@uk-erlangen.de
INTRODUCTION: Confocal Laser Endomicroscopy (CLE) allows microscopic
imaging of the colonic mucosal layer during endoscopy. Clinical studies published during the past years have enhanced the potential of this technique to
accurately assess the mucosa at the microscopic level and to provide accurate
information either for the assessment of inflammation or for the detection of
neoplasia. Those findings have the potential to improve patient management by
tailoring both diagnostic and treatment approaches.
AIMS & METHODS: The aim of this study is to develop evidence-based consensus statements for the assessment of the role of CLE in the management of
patients with IBD.
Initial statements on the use of CLE in the assessment of IBD were developed by
a single CLE expert based on the available clinical literature. Those preliminary
statements were edited and submitted by an external group of 8 GI physicians
experts in CLE, using a modified Delphi approach. After two rounds of votes
based on current literature and strength of recommendation, statements were
adopted if the threshold of agreement was higher than 75%.
RESULTS: Out of 17 proposed statements, 11 were adopted and 6 rejected. CLE
can identify Crohns disease (CD) and ulcerative colitis (UC) associated histological changes in vivo. CLE can be used to acquire targeted biopsies for surveillance of IBD patients. Targeted biopsies should be preferably used instead of
random four quadrant biopsies for surveillance in IBD. CLE can identify IBD
associated histological changes in macroscopically non-inflamed mucosa. CLE
provides dynamic in vivo live information about intestinal barrier function and
vascular permeability. CLE provides dynamic in vivo live information about
intestinal barrier function and vascular permeability. Surveillance in IBD by
using CLE should be performed in macroscopically non-inflamed mucosa.
CLE can redefine the term mucosal healing in vivo. The ultimate goal of
CLE for IBD patients is to predict response to anti-tumour Necrosis Factor
(anti-TNF) antibody therapy and may help to initiate an individualised therapy
of IBD patients to reduce drug associated side effects, morbidity and costs for the
health care system. Step-down and step-up approaches should be replaced by an
individualized, adapted approach, including microscopic evaluation of the
mucosa.
CONCLUSION: 11 consensus statements on the use of Confocal Laser
Endomicroscopy for the management of IBD were adopted by a panel of 8
clinical experts. These statements were established based on published literature
and consensus opinions, suggesting that Confocal Laser Endomicroscopy has the
potential to play an important role in the management of IBD patients by

assessing mucosal healing and individualizing approach with biologics. Further


clinical studies are necessary to support these ideas.
Disclosure of Interest: H. Neumann: None declared, R. Arsenescu: None
declared, H. Bertani: None declared, E. Coron Consultancy for: Has been a
consultancy for Mauna Kea Technologies, A. Dlugosz: None declared, J.
Galmiche Consultancy for: Mauna Kea Technologies, K. Ho: None declared,
S. Singh: None declared
P0857 NEGATIVE PREDICTIVE VALUE OF TRANSABDOMINAL
ULTRASOUND FOR SHORT-TERM OUTCOMES OF
INFLAMMATORY BOWEL DISEASE
I. Sturdik1,*, J. Toth1, T. Hlavaty1, T. Koller1, M. Huorka1, Z. Zelinkova1
1
5th internal medicine department, University hospital Bratislava, Bratislava,
Slovakia
Contact E-mail Address: igor.sturdik@gmail.com
INTRODUCTION: Transabdominal ultrasound is considered a useful tool for
the assessment of inflammatory bowel disease (IBD) activity but its negative
predictive value for gold standards diagnostic methods, such as endoscopy, is
limited. Therefore, usefulness of transabdominal ultrasound in monitoring of
disease activity has been questioned. However, the diagnostic value of ultrasound
has not been tested with regards to short or long-term outcomes of IBD.
AIMS & METHODS: The aim of our study was to assess the negative predictive
value of transabdominal ultrasound in IBD for short term disease complications. We retrospectively evaluated all IBD patients with clinical suspicion of
disease flare who underwent an intestinal ultrasound performed by one sonographist at a single tertiary IBD Center. Disease activity and the presence of
disease complications were evaluated according to standard parameters for
intestinal ultrasound. Findings of colonoscopy performed within 2 months of
the ultrasound were compared to the ultrasound findings for each respective
bowel segment. For correlation of categorical findings at ultrasound and colonoscopy a chi-square test was used. The changes in therapy were noted as well as
clinical remission and surgical intervention at respective month 3 and 6 following
the ultrasound and negative predictive value of ultrasound was calculated for
each of the outcomes.
RESULTS: In total, sixty five ultrasounds were performed in 61 IBD patients
(mean age 39, range 18 to 94 years; 41% of males; 45/16 Crohns disease/ ulcerative colitis) were evaluated. Overall, there were 45 cases (70%) of disease activity
detected by ultrasound, in 18 cases (28%) no abnormalities were found and 2
cases (3%) were inconclusive. Complications of IBD, such as abscess and fistulas
were found in 10 cases (15%). Colonoscopy was performed in 39 cases.
Ultrasound correlated well with endoscopy in assessment of disease activity in
terminal ileum (p 0.049) as well as in colonic disease (p50.0001). The positive
and negative predictive values (NPV) of ultrasound for disease activity as
assessed by endoscopy were 90% and 78%, respectively, for terminal ileum disease localisation; and 100% and 75%, respectively, for colonic disease. None out
of 18 cases with no abnormalities found on ultrasound needed a therapy adjustement nor surgery during the six months following the ultrasound; all these
patients were in remission at respective months 3 and 6 (NPV of relapse 100%).
CONCLUSION: Transabdominal intestinal ultrasound has a high negative predictive value for short-term complications of inflammatory bowel disease.
Disclosure of Interest: None declared
P0858 HERPES
FAMILY
VIRUSES
IN
PATIENTS
WITH
INFLAMMATORY BOWEL DISEASE AND IMMUNOSUPPRESSION
P. Tsibouris1,1, I. Koumoutsos1, P. Apostolopoulos1, C. Kalantzis1, E. Chounta1,
E. Vlachou1,*, G. Alexandrakis1
1
GASTROENTEROLOGY, NIMTS GENERAL HOSPITAL, Athens, Greece
Contact E-mail Address: tsibofam@yahoo.com
INTRODUCTION: Herpes family viruses (herpes simplex virus 1 and 2 (HSV1
and HSV 2), Epstein Barr Virus (EBV), cytomegalovirus (CMV)) are prevalent in
the adult population.
AIMS & METHODS: Aim: Study the primary infection in an adult population
with inflammatory bowel disease and infection reactivation under
immunesuppression.
Patients-Methods: 56 patients (40 with Crohns disease, 13 with ulcerative colitis,
3 with indetermined inflammatory bowel disease) were evaluated before immunosuppression initiation (infliximab 36 patients, immunosuppressant 9, infliximabimmunosuppressant: 11). Serology was evaluated before treatment (antiHSV IgG/IgM antibodies, anti-CMV IgG/IgM antibodies, IgG/IgM antibodies
against EBV viral capsid antigens and nuclear antigen). Patients were follow-up
for 3 years with serologic evaluation every 3 months and tissue sampling in case
of disease flare ups for PCR.
RESULTS: In patients aged 17-20 years 3/3 (100%) were HSV 1,2 (), 3/3
(100%) EBV (), 2/3 (66%) CMV (); in those aged 21-25: 6/8 (75%) were
HSV 1 (), 5/8 (63%) HSV2 (), 8/8 (100%) EBV (), 7/8 (88%) CMV ();
in patients aged 26-30 years: 6/7 (86%) were HSV1 (), 5/7 (71%) HSV2 (), 4/7
(58%) EBV (), 6/7 (84%) CMV (); in patients aged 31-40: 9/11 (81%) were
HSV 1,2 (), 9/11 (81%) EBV (), 9/11 (81%) CMV (); in patients aged 41-50:
11/11 (100%) were HSV 1 (), 10/11 (91%) 10/11 (91%) EBV (), 7/11 (64%)
CMV (); in patients aged over 60: 10/12 (84%) were HSV 1,2 (), 12/12 (100%)
EBV (), 9/12 CMV (). During follow-up 3 patients presented HSV2 seroconversion, while HSV1 was positive, 3 EBV seroconversion and 3 CMV seroconversion. All of them were reported to be asymptomatic. 3 patients presented HSV
flare-ups treated with topical and systematic treatment, while immunosuppression was temporally withheld. No flare-ups reported for EBV and CMV.

A367

United European Gastroenterology Journal 2(1S)


CONCLUSION: Herpes family viruses are prevalent in patients with inflammatory bowel disease. Flare-ups under immunosuppression are rare while seroconversions are rather asymptomatic.
Disclosure of Interest: None declared

1. NICE. Faecal calprotectin diagnostic tests for inflammatory diseases of the


bowel, http://www.nice.org.uk/nicemedia/live/14285/65337/65337.pdf (accessed
14 April 2014).
Disclosure of Interest: None declared

P0859 ACIDITY OF INTESTINAL CONTENTS IN THE DISTAL PARTS


OF THE COLON IN PATIENTS WITH ULCERATIVE COLITIS

P0861 INFLAMMATORY LOAD MEASURED BY SPECT-CT RELIABLY


CORRELATES WITH HISTOLOGY AND FECAL CALPROTECTIN IN
ULCERATIVE COLITIS

I. Gubonina1,*, V. Grinevich1, V. Ekimov1, N. Sherstneva2


2nd Therapy Department, 2Military Medical Academy, Saint-Petersburg, Russian
Federation
Contact E-mail Address: giv70@bk.ru

INTRODUCTION: It is nececcary to determine the possibility of using mesalazine-delivering drugs with different release mechanisms depending on the pH
value in patients with UC relapse.
AIMS & METHODS: To evaluate the acidity of intestinal contents in the distal
parts of the colon in patients with ulcerative colitis (UC) relapse. 43 patients with
left-sided UC and 24 patients with extensive UC having mild or moderate relapse
were evaluated. The evaluation of the pH of the chymus with use of a universal
indicator test strip, as well as analysis of changes in the oM of intestinal contents
depending on clinical, laboratory and endoscopic indicators of ulcerative colitis
activity, were carried out in all these patients. The control group consisted of 16
healthy volunteers.
RESULTS: On the whole, there was a trend towards acidification of chymus in
patients with left-sided UC as compared to healthy volunteers (oM 6.760.21
vs. oM 6.940.2, respectively); however, this difference was not statistically
significant. In the group of patients with extensive UC, a decrease in pH to
below 6.0 (20.8%) was noted significantly more often as compared to the patients
with left-sided UC (4.7%, o50.05) or control group subjects (0%, o50.05).
Statistically significant correlation between the pH of the intestinal contents
with ulcerative colitis activity index (correlation coefficient (CC) -0.23), fecal
calprotectin value (CC -0.25), UC duration (CC -0.21) or duration of UC
treatment (CC 0.35) was not revealed.
CONCLUSION: In patients with left-sided UC, acidity of the intestinal contents
in the distal parts of the colon did not differ from that in the healthy volunteers
and did not depend on disease activity or duration of ulcerative colitis. Decrease
in the pH of the intestinal contents to below 6.0 was noted significantly more
often in patients with extensive UC as compared to patients with left-sided UC or
healthy volunteers. In the treatment of patients with decreased intraluminal pH
levels, preference should be given to drugs with oM-independent release of active
ingredient.
Disclosure of Interest: None declared
P0860 ITS ALL IN THE STOOL. FAECAL CALPROTECTIN TO HELP
GUIDE ANTI-TNF THERAPY; A RETROSPECTIVE STUDY
J. Gulliver1,*, G. Baker1, K. Millington 1, K. Zacchariah1, R. Makins1
Gastroenterology, Cheltenham General Hospital, Gloucestershire Hospitals NHS
Foundation Trust, Cheltenham, United Kingdom
Contact E-mail Address: james.gulliver@glos.nhs.uk
1

INTRODUCTION: Faecal calprotectin (FC), a protein derived mainly from


neutrophils and monocytes, is detected in increased quantities in the stool of
patients with inflammatory bowel disease (IBD). Recently, the National
Institute of Clinical Excellence (NICE) in the United Kingdom (UK) has recommended its use as a biochemical test to differentiate between IBD and functional
bowel disease; furthermore, it can also be used to evaluate disease activity or
response to treatment. We routinely assess patients symptoms and biological
markers including FC at least annually once established on anti-TNF therapy.
This assessment is brought forward if there is a suspicion of ongoing disease
activity.
AIMS & METHODS: We sought to assess the impact of FC testing on our
clinical management, specifically for our patients with Crohns disease receiving
anti-TNF therapy. We interrogated our pathology database to collect FC results
from all patients at Gloucestershire Hospitals NHS Foundation Trust who were
established on anti-TNF therapy for Crohns disease. FC samples had been
obtained either as part of annual assessment or earlier due to ongoing symptoms.
We then reviewed the patients notes to determine what actions, if any, had been
taken as a consequence of the FC results.
RESULTS: FC results were available from 28 of 31 patients collected during
2011 and 2012. Results were subdivided based on the FC level into four groups.
1) 5 50ug/g (n 9, 32.1%); 2) 50-100ug/g (n 7, 25%); 3) 100-200ug/g (n 5,
17.9%) and 4) 4200ug/g (n 7, 25%).
Across all four groups anti-TNF therapy was unaltered in 14 patients (50%) and
stopped in 3 (11%). The dose was increased but frequency of treatment maintained in 2 (7%), and frequency increased in a further 2 (7%). Frequency was
reduced in one patient from 8 weekly to 10 weekly (3.5%). Two patients were lost
to local follow up.
More specifically, in group 1, 34% had their anti-TNF therapy unaltered and
22% had their therapy stopped with consequent significant cost savings. In contrast; 43% of patients in group 4 had their anti-TNF therapy altered, either by
increasing dose or frequency of administration. Regarding further investigations
no patient with a FC result 4100ug/g went on to have a colonoscopy compared
with 33% of patients with an FC 550ug/g.
CONCLUSION: FC is a useful tool when judging clinical response to anti-TNF
therapy in patients with Crohns disease. Once treatment is established it allows
identification of patients for whom anti-TNF therapy can be further optimised or
stopped. It also helps guide the need for further investigation, if either to re-stage
disease extent and severity or if considering alternative diagnoses.
REFERENCES

J.F. Brandse1,*, R. Bennink2, S.van Eeden3, P.A. Baars4, M. Lowenberg1,


C.Y. Ponsioen1, G.R. van den Brink5, G.R. DHaens1
1
Department of Gastroenterology & Hepatology, 2Nuclear Medicine, 3Pathology,
4
Experimental Immunology, Academic Medical Center, Amsterdam, 5Department
of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: j.f.brandse@amc.uva.nl
INTRODUCTION: Assessing inflammatory activity is essential in therapeutic
decision making in Ulcerative Colitis (UC). Novel scintigraphy techniques
including SPECT-CT are promising to measure inflammatory load in chronic
inflammatory conditions such as UC. Leukocyte scintigraphy therefore needs to
be validated using other established markers of inflammation.
AIMS & METHODS: We aimed to prospectively validate leukocyte SPECT-CT
as a tool to measure and quantify inflammatory load in patients with different
extent and severity of UC.
UC patients with an indication for full colonoscopy were included. Within 1
week and without any changes in therapy both colonoscopy (Mayo score,
UCEIS) with biopsies (Geboes score) and leukocyte scintigraphy were performed. In addition, serum CRP and fecal calprotectin (Buhlmann ELISA)
were measured and clinical questionnaires (CCAI, Mayo) were collected.
Patients peripheral blood leukocytes were isolated and labelled with 200 MBq
technetium-99m HMPAO. SPECT combined with a low-dose CT was performed
60 min after reinjection of labelled cells. To quantify inflammation in each colon
segment the uptake of leukocytes was calculated as a ratio to the mean uptake in
bone marrow of 4 lumbar vertebrae and expressed as SPECT inflammation score
in each colon segment and a Summed Activity Score (SAS) for the inflammatory
activity in all 5 colonic segments together.
RESULTS: Twenty-six UC patients were studied. 3/26 were using anti-TNF, 4/
26 thiopurines, 3/26 prednisone and 20/26 5-ASA at inclusion. At endoscopy 6/
26 (23%) of patients had proctitis, 8/26 (31%) left-sided and 12/26 (46%) pancolitis. According to endoscopic Mayo score, 1/26 (4%) of patients had inactive,
5/26 (19%) mild, 8/26 (31%) moderate and 12/26 (46%) severe disease. The
median (IQR) full Mayo score was 7 (5-10), CCAI: 6 (2-9), serum CRP 4.1
mg/L (1.7-12.5) and fecal calprotectin 449 ug/g (245-1142). According to
SPECT-CT patients were classified as having 9/26 mild, 12/26 moderate and 5/
26 severe disease in their most affected segment. At the level of individual segments, significant correlations (Spearman) were observed between the SPECT
inflammation score and endoscopic Mayo: r 0.54 (P50.01), UCEIS r 0.56
(P50.01) and histologic Geboes score r 0.59 (P50.01). The Summed Activity
Score correlated much better with fecal calprotectin r 0.55 (P50.01) than with
CRP: r 0.24 (p 0.24), CCAI: r 0.43 (P50.05) or clinical Mayo: r 0.54 (P50.01).
CONCLUSION: SPECT-CT assessment of UC disease severity in the most
inflamed colon segment is correlated with both endoscopic and histologic
scores. The total inflammatory load in UC at SPECT-CT is better reflected by
fecal calprotectin than by serum CRP.
Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie and Takeda,
R. Bennink: None declared, S. van Eeden: None declared, P. Baars: None
declared, M. Lowenberg: None declared, C. Ponsioen: None declared, G. van
den Brink: None declared, G. DHaens Financial support for research from:
Abbott Inc, Jansen Biologics, Given Imaging, MSD, DrFalk Pharma,
Photopill, Lecture fee(s) from: Abbott Inc, Tillotts, Tramedico, Ferring, MSD,
UCB, Norgine, Shire, Consultancy for: Abbott Laboratories, Actogenix,
Centocor, Cosmo, Engene, Ferring Pharmaceuticals, GlaxoSmithKline, Jansen
Biologics, Millenium Pharmaceuticals, MSD, Novonordisk, PDL Biopharma,
Pfizer, SetPoint, Shire, Takeda, Teva, UCB
P0862 A
COCOON
IMMUNISATION
STRATEGY
HOUSEHOLD CHILDREN OF ADULTS PATIENTS WITH
INFLAMMATORY BOWEL DISEASE

AMONG

K. Waszczuk1,*, E. Waszczuk2, A. Mulak2, L. Szenborn1, L. Paradowski2


Department of Pediatric Infectious Diseases, 2Department of Gastroenterology
and Hepatology, Wroclaw Medical University, Wroclaw, Poland
Contact E-mail Address: karolkap@gmail.com
1

INTRODUCTION: In order to protect patients with inflammatory bowel disease


(IBD) against serious infections, vaccination of their household children is
recommended.
AIMS & METHODS: The aim of our study was to assess the not mandatory and
not reimbursed vaccination coverage including pneumococcal, rotavirus, influenza, and varicella vaccines among household children of adult patients with
IBD as the Cocoon Strategy. A self-designed survey was conducted in 138
IBD patients hospitalised in the Department of Gastroenterology and
Hepatology at Wroclaw Medical University from November 2013 to March
2014. The survey comprised questions about household children vaccination
coverage and the reasons of its refusal as well as the history of infectious diseases
in the patients. Randomly, patients completed the survey with a physician present to determine questions comprehension. In order to provide test-retest reliability a group of ten patients completed it twice. Fisher exact test was used for
cross-classification tables.

A368
RESULTS: The survey data from 52 IBD patients having household children (25
women, 27 men, mean age: 36 years) were analysed. Two patients declared
refusing one obligatory vaccination of their children, while 40% of the patients
reported at least one not reimbursed vaccine administration. Most frequently,
children obtained pneumococcal (31%), rotavirus (23%), varicella (14%), and
influenza (10%) vaccines. The most common reasons for non-immunisation was
unawareness of the existing recommendations (46%), fear of adverse effects of
the vaccines (18%) and not believing in vaccines efficacy (10%). In one case a
medical health care worker discouraged from immunisation. There was statistically significant association between not reimbursed vaccines coverage and educational level of the patients (p50.001). Despite the fact that 28% of IBD
patients could not definitively recall varicella infection, none of their household
children nor they were vaccinated against chickenpox.
CONCLUSION: The use of not mandatory vaccines recommended in Poland in
IBD patients family members is insufficient. Frequently, patients have serious
doubts concerning safety and efficacy of vaccinations. Therefore, further vaccines promotion and education of patients as well as their health care providers
are needed. A particular concern is associated with not vaccinating against influenza and varicella, which pose a high risk of infection. Non-immunised and VZV
seronegative IBD patients should be vaccinated, and in case of their immunosupression, vaccination of household children is required.
Disclosure of Interest: None declared
P0863 THE ROLE OF PET-CT IN THE CHARACTERIZATION OF THE
ACTIVITY OF CROHNS DISEASE
K. Palatka1,*, L. Szilvia1, L. Davida1, I. Altorjay1, L. Galuska2
1
Gastroenterology, 2Department Of Nuclear Medicine, University Of Debrecen,
Debrecen, Hungary
Contact E-mail Address: palatka@med.unideb.hu
INTRODUCTION: Crohns disease is an immune-mediated disorder with
unknown etiology, characterized by segmental, transmural inflammation of the
gastrointestinal tract and extraintestinal inflammatory symptoms. The diagnosis
is based on endoscopy, imaging examinations, the disease activity is characterized
by Crohns disease activity index (CDAI), which includes subjective, objective
sympthoms and laboratory parameters. PET-CT is a global, non-invasive, highly
sensitive method to determine the location and activity of some malignant and
inflammatory lesions. Former studies showed 85% sensitivity and 87% specifity
of 18F-FDG-PET-CT in IBD.
AIMS & METHODS: The aim of the study was to evaluate the role of PET-CT
in patients with active Crohns disease (CDAI 4300) before and after biological
therapy and comparing with endoscopic index (SES-CD), CDAI and biochemical
parameters. Twelve patient were examined: 5M/6F, age between 18 and 39,
average age: 25 years. The evaluation of the PET-CT activity was determined
considering the activity of the small intestine and the four colon segments. The
SUVmax (Standardized Uptake Value) of the intestinal segment was correlated
to the SUVmax of the liver, which was chosen as a reference for normal tissue
activity. To get the global PET-score, the activity scores of the five intestinal
segments were summed.
RESULTS: The PET-score showed correlation with CDAI (R2 0.1441) and
CRP (R2 0.0512), but not with SES-CD (R2 0.0041). After one year biologic
therapy CDAI (R2 0.1622), CRP (R2 0.0815) and SES-CD (R2 0.1699) correlated well with the PET-score. In active disease, the PET-CT was more sensitive
than the endoscopy to indicate the extent of the inflammation. Examining new
patients, PET-CT was the most informative on the activity and extent of the
disease (small intestine involvement). In one case, the terminal ileum stenosis
with high CDAI score associated with negative PET-CT score, which was a
fibrotic stenosis as it turned out after the surgery. Patients with negative PETCT score after biological treatment remained in remission during a two year
follow-up period.
CONCLUSION: The PET-CT results correlated well with the activity of the
Crohns disease. In the future, this should be a promising, non-invasive
method in the diagnosis of Crohns disease and in the planning the treatment
and follow-up. Negative PET-CT proved to be a good indicator of deep
remission.
Disclosure of Interest: None declared
P0864 THE ROLE OF DOUBLE BALLOON ENDOSCOPY FOR CROHNS
DISEASE
K. Mitsui1,*, S. Fujimori1, A. Ehara1, J. Omori1, N. Akimoto1, K. Maki1,
M. Suzuki1, Y. Kosugi1, Y. Ensaka1, Y. Kasuga1, M. Yonezawa1, S. Tanaka1,
A. Tatsuguchi1, C. Sakamoto1
1
Gastroenterology, NIPPON MEDICAL SCHOOL, Graduate School of
Medicine, Tokyo, Japan
Contact E-mail Address: k5mitsui@gmail.com
INTRODUCTION: Deep enteroscopy has been widely used for various small
bowel diseases. One of the most common diseases that affected the small bowel is
Crohns disease. The idea is being accepted that the mucosal healing is important
parameter for the better outcome of Crohns disease. However the efficacy and
safety of the DBE is not fully understood.
AIMS & METHODS: We conducted a retrospective case series study to elucidate the efficacy of DBE in Crohns disease. We enrolled the consecutive 40
patient who underwent the 95 DBE examinations since 2003. Patients characteristics, indications of the deep enteroscopy, duration of procedures, therapeutic
interventions and complications were assessed.
RESULTS: Subjects were 7 females and 33 males, mean age was 3813 years
old. The indications of DBE were mucosal evaluation for known Crohns disease,
obscure gastrointestinal bleeding, small bowel obstruction, removal of the

United European Gastroenterology Journal 2(1S)


retained small bowel capsule endoscopy (SBCE), suspicious of Crohns disease
and further evaluation of protein-losing enteropathy in 17, 10, 7, 3, 2, 1 case,
respectively. The mean number of DBE examination per patient was 2.41.4.
Types of scope were type T, type P (thin type), and type B (short type) in 49, 41
and 5 cases. The choice of the scope had depended on the therapeutic capability
or the facility of deeper insertion. The insertion roots were antegrade (from
mouth) in 31 patients and retrograde (from anus) in 64 patients. The mean
insertion time was 6531 minute. The antegrade vs. retrograde was 4525 vs.
3440 minutes (p 0.005). The mean total examination time was 8334 min.
The antegrade vs. retrograde was 8334 vs. 5626 min. (p50.0001). The mean
insertion depth was 9593 cm. The antegrade vs. retrograde was 17875 vs.
5570 minutes (p50.0001). Balloon dilation therapies were performed in 18
procedures in 8 patients. In 10 patients, the prior SBCE had been done and 6
patients were retained. All the retained SBCE were removed by double balloon
endoscopy. In only one out of 10 patients, DBE had not shown any severe
stricture and SBCE was used for the mucosal evaluation repeatedly. No complication was encountered in diagnostic and therapeutic DBE.
CONCLUSION: DBE showed that ileal lesions were more common and oral
DBE was time-consuming in Crohns disease. The evaluation with DBE also can
pick out the patient who can undergo the SBCE. The dilation therapy may delay
the timing of the surgical interventions. DBE, especially the retrograde DBE,
have a potential to improve the outcome of Crohns disease.
Disclosure of Interest: None declared
P0865 USE OF INTERVAL ULTRASOUND TO PROSPECTIVELY
MONITOR PATIENTS WITH CROHNS DISEASE ON ADALIMUMAB
K. Novak1,*, G. Kaplan1, R. Panaccione1, S. Ghosh1, E. Ehteshami Afshar1,
A. Wilson1, S. Wilson2
1
Medicine, 2Diagnostic Imaging, University of Calgary, Calgary, Canada
Contact E-mail Address: knovak@ucalgary.ca
INTRODUCTION: Accurate, non-invasive methods of evaluating treatment
response in patients with Crohns disease (CD) are important in a treat to
target paradigm. The aim of this study is to prospectively evaluate the ability
of sonography to monitor patients on adalimumab (ADA), correlated with endoscopy as a gold standard.
AIMS & METHODS: This is an IRB-approved, single-center, prospective study,
evaluating patients with CD treated with adalimumab for at least 6 months.
Baseline clinical score (Harvey Bradshaw/HBI), C-reactive protein (CRP), ileocolonoscopy and transabdominal ultrasound were completed within 2 weeks at
time zero and 12 months (if clinically indicated), with intervening scans at 4 and 8
months. Standard sonographic assessment included bowel wall thickness, color
Doppler signal, presence of inflammatory fat and lymph nodes. Endoscopy was
scored using validated simple endoscopic score (SES) and/or Rutgeerts score
(Ri) in post-operative patients. Endoscopic responsiveness was defined as mucosal healing (SES-CD5 and/or Ri1) and sonographic responsiveness as bowel
wall thickness (6mm) with minimal inflammatory fat and Doppler signal. The
aim of this study is to prospectively evaluate sonographic and endoscopic maintenance of remission in patients on adalimumab.
RESULTS: 50 patients have been recruited to date with n 34 included in this
analysis (n 16 excluded given drop out, missing data or in progress). At time
zero, 34 patients had endoscopy and 19/34 (56%) patients underwent follow-up
endoscopy at 1 year, those who did not were deemed in clinical and serologic
remission without indication for endoscopy. There were (3/34) strictures limiting
endoscopic visualization of disease at time zero, and one had proximal disease.
The agreement between the remaining US and endoscopy (n 30) at time zero
was excellent (complete agreement in 26/30), as was the correlation at twelve
months. Table 1 shows endoscopy and US findings for 17/19 at 12 months.
Final endoscopies were limited given proximal disease in 2/19 and thus were
not included. Patients with endoscopically active disease at 12 months showed
active sonographic disease as early as 4 months.

Absence of US disease
Presence of US Disease

Mucosal Healing
(SES-CD3
and/or Ri1)

Endoscopically Active
(SES-CD43
and/or RI41)

11
1

0
4 (1 pouch case)

CONCLUSION: US is an accurate, non-invasive modality useful in evaluating


maintenance of response to therapy, which correlates with mucosal healing on
endoscopy. Thus, US may be a surrogate for endoscopy and a repeatable, objective target for treatment.
Disclosure of Interest: None declared
P0866 QUALITY OF LIFE IN ULCERATIVE COLITIS ASSOCIATION
BETWEEN THE SHORT INFLAMMATORY BOWEL DISEASE
QUESTIONNAIRE (SIBDQ) AND THE SHORT HEALTH SCALE
(SHS) AND THEIR RELATIONSHIPS WITH CLINICAL AND
ENDOSCOPIC DISEASE ACTIVITY
K. Theede1,*, M. Kiszka-Kanowitz1, I. Nordgaard-Lassen1, A.M. Nielsen1
1
Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre,
Hvidovre, Denmark
INTRODUCTION: Health Related Quality of Life (HRQoL) is an important
part of Inflammatory Bowel Disease (IBD) assessment, and is affected by both
disease activity, psychological, and social factors. Several HRQoL questionnaires

United European Gastroenterology Journal 2(1S)


have been developed, but are primarily used in the setting of clinical trials. Little
is known about the relationship between HRQoL and disease activity and
between the different HRQoL questionnaires. We aimed to assess the association
between the SIBDQ and the SHS and their associations with clinical and endoscopic disease activity.
AIMS & METHODS: Prospectively, 110 patients with ulcerative colitis underwent sigmoidoscopy and completed the SIBDQ and the SHS. The SIBDQ is a
validated 10-question tool measuring physical, social, and emotional status (score
10-70, poor-good). The SHS is a four-part visual analogue scale questionnaire
measuring bowel symptoms, activities of daily life, worry, and general well-being
(score 0-40, good-poor). Clinical disease activity was assessed using the Mayo
score (0-12) and was divided into remission (2), mild (3-5), moderate (6-9), and
severe (10-12) activities. The endoscopic grade of inflammation was assessed
using Mayo Endoscopic Score (MES, 0-3).
RESULTS: The median age was 37 years (19-80), and 56 % were female. The
median disease duration was 4.5 years. 29 % had mucosal healing, 20 % active
proctitis, 16 % active proctosigmoiditis, 18 % active left-sided colitis and 18 %
pancolitis. According to the MES, 29 % had mucosal healing, 26 % had mild, 31
% moderate and 14 % severe inflammation. According to the Mayo score, 37 %
were in clinical remission, 21 % had mild, 31 % moderate and 11 % severe
disease activity.
HRQoL significantly decreased with increasing clinical disease activity (Mayo
score) when assessed with both SIBDQ (2 51.9, p50.0001) and SHS
(2 56.2, p50.0001). HRQoL also significantly decreased with increasing endoscopic disease severity (MES) when assessed by both SIBDQ (2 33.1,
p50.0001) and SHS (2 40.3, p50.0001). Overall, we found a significant difference in HRQoL between patients with mucosal healing (MES 0) and active
inflammation (SIBDQ, inactive/active, 59.1/45.6, p50.0001 and SHS, inactive/
active, 6.8/19.7, p50.0001). Moreover, we found a strong association between
SIBDQ and SHS using linear regression (SHS -0.73SIBDQ52.1,
p50.0001).
CONCLUSION: In this study we demonstrate that HRQoL is not only strongly
associated with clinical disease activity, but also with the endoscopic disease
severity. We also demonstrate that SIBDQ and SHS are strongly associated
with each other.
Both SIBDQ and SHS show significantly decreasing HRQoL with increasing
clinical disease activity as well as with increasing endoscopic disease severity.
The study also shows significant difference in HRQoL between patients with
mucosal healing and endoscopic active disease. Both questionnaires seem equally
adequate in determining the disease impact on HRQoL.
HRQoL is from the patients perspective one of the most important parts of IBD
management. SIBDQ and especially SHS can be completed quickly during regular visits, and can be used as an easy tool for HRQoL monitoring. Significant
changes must be followed by exploration of the possible causes including assessment of disease activity.
Disclosure of Interest: K. Theede Financial support for research from: Research
grant from AbbVie Inc. and Ferring Pharmaceuticals, M. Kiszka-Kanowitz:
None declared, I. Nordgaard-Lassen Financial support for research from:
Research grant from AbbVie Inc. and Ferring Pharmaceuticals, Consultancy
for: Advisory Board AbbVie Inc., A. Nielsen Financial support for research
from: Research grant from AbbVie Inc. and Ferring Pharmaceuticals,
Consultancy for: Advisory Board AbbVie Inc.
P0867 IS THE TUBERCULIN SKIN TEST ALONE ACCURATE IN
MODEATE-TO-SEVERE BCG VACCINATED PATIENTS WITH
INFLAMMATORY BOWEL DISEASE TREATED WITH
IMMUNOSUPPRESSIVES TO TEST FOR LATENT TUBERCULOSIS?
K.B. Gecse1,*, Z. Kurti1, A. Balint2, K. Farkas2, B.D. Lovasz1, A. Szabo1,
M. Mandel1, A. Gyurcsanyi1, Z. Vegh1, A. Mohas1, T. Molnar2, L.S. Kiss1,
P.A. Golovics1, P.L. Lakatos1
1
1st Department of Medicine, Semmelweis University, Budapest, 21st Department
of Medicine, University of Szeged, Szeged, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: There are few data available on effect of immunomodulator/
biological therapy on the accuracy of tuberculin skin test (TST, Mantoux skin
test) and interferon-gamma release assay (IGRA) in BCG vaccinated immunosuppressed IBD patients.
AIMS & METHODS: Our aim was to define the accuracy of the TST and IGRA
tests in a BCG vaccinated referral IBD cohort treated with immunosuppressives
and/or biologicals. Data of 135 consecutive moderate-to-severe IBD (98 CD, 37
UC) patients were analyzed (male/female: 64/71, median age at diagnosis: 24.0;
IQR: 18-31 years, duration: 7.0; IQR: 4-13 years). Patients were treated with
immunosuppressives (azathioprine, steroids) and/or anti-TNF therapy. Blood
samples for IGRA were collected during routine laboratory testing parallel
with TST. The result of TST was determined according to international guidelines. Both in- and outpatient records were collected and comprehensively
reviewed.
RESULTS: TST positivity rate was 21.6%, 20.1%, 13.4% or 12.7% with cut-off
values of 5, 10, 15 and 20mm. IGRA positivity rate was 7.7% with indeterminate
result in 1.2%. The correlation between TST and IGRA was significant, with
moderate-to-good kappa values if TST results were 415mm (kappa: 0.32-0.34,
p50.001). In addition, a TST of 14 and 17mm was also identified as best cut-off
value in a ROC analysis (AUC: 0.70, p 0.04). There was no association between
the type and number of immunomodulators used or any disease phenotype characteristics and the TST or IGRA results. Importantly, smoking was identified as
a risk factors for TST but not IGRA positivity (OR: 3.80, 4.88, 9.87 and 8.98,
p50.002, for TSTcut-off 5, 10, 15 and 20mm).
CONCLUSION: The TST and IGRA are partly complimentary methods and
accuracy is acceptable also in BCG vaccinated and immunosuppressed IBD

A369
patients. A TST of 415mm should be used as a cut-off to identify patients at
risk for latent TB in these patients. Smoking is a risk factor for TST positivity.
Disclosure of Interest: None declared
P0868 INCREASED EXTRACELLULAR MATRIX PROTEINS TURNOVER IN PATIENTS WITH CROHNS DISEASE
L.E. Godskesen1, M.D. Jensen1,*, L. Klinge1, J. Mortensen2, A.-C. Bay-Jensen2,
A. Krag1, J. Kjeldsen1
1
Department of Gastroenterology, Odense University Hospital, Odense C, 2Nordic
Bioscience A/S, Herlev, Denmark
Contact E-mail Address: line@napoleon.dk
INTRODUCTION: Ongoing inflammation in Crohns disease (CD) may lead to
development of intestinal fibrosis and patients may present with stenosis.
Inflammation is a dynamic process with a permanent remodeling of the extracellular matrix (ECM). Small fragments of the ECM generated during this process, so called neoepitopes, are released into the circulation and could be used as
biochemical markers of disease activity or markers of fibrosis.
AIMS & METHODS: This study investigates a panel of these novel developed
markers in patients with suspected or known CD.
106 patients referred for evaluation of CD had serum samples drawn. Patients
were evaluated with colonoscopy, small-bowel imaging (capsule endoscopy, MR
enterography, and CT enterography), fecal calprotectin, and C-reactive protein.
35 patients had newly diagnosed CD, 26 had CD with active inflammation or
stenosis, 11 had known CD without inflammation or complication, and 34 had
no evidence of Crohns disease. The following neoepitopes were measured by
competitive ELISAs; MMP-mediated of type I, III, IV collagen (C1M, C3M,
C4M), N-terminus pro-collagen type I (P1NP), and MMP-degraded, citrullinated vimentin (VICM).
Data were not normally distributed and Kruskal-Wallis one-way analysis of
variance was used for comparison. ROC-curve analysis were used to test the
biomarkers ability to discriminate CD from non-CD.
RESULTS: Serum levels of C3M were significantly elevated in patients with CD
compared to patients without CD (median 24.4 and 19.1, respectively; P 0.01).
C3M discriminated CD from non-CD with an AUC of 0.66. Concentrations of
C1M and C4M were also elevated but statistical significance was not reached
(C1M: median 68.9 and 62.9; P 0.12. C4M: median 70.5 and 67.2; P 0.15). In
patients with CD, C1M and C3M concentrations were higher in clinically active
disease (CDAI 4 150) compared to quiescent disease (C1M: median 75.0 and
63.2; P 0.02. C3M: median 24.5 and 22.7; P 0.10), and C3M concentrations
were higher in CD involving the colon compared to small bowel CD (median 26.2
and 22.1; P 0.05). C1M, C3M and C4M correlated with CRP (Spearmans rho
0.76, 0.40, and 0.45, respectively; P 5 0.001) but not with fecal calprotectin.
Concentrations of ECM degradation markers were not significantly increased in
patients with stricturing CD compared to patients without CD. In subgroup
analysis of patients with diagnosed CD and elevated CRP compared to nonCD and normal CRP C1M, C3M and C4M discriminated CD from non-CD
(AUC of 0.95, 0.88 and 0.90).
CONCLUSION: Turnover of ECM proteins is increased in patients with CD.
These neoepitopes may distinguish between patients with CD and patients without CD and between active CD and disease in remission. Further studies of these
promising markers of the ECM are warranted.
Disclosure of Interest: L. E. Godskesen: None declared, M. Jensen: None
declared, L. Klinge: None declared, J. Mortensen Other: Employee at Nordic
Bioscience, A.-C. Bay-Jensen Other: Employee at Nordic Bioscience, A. Krag:
None declared, J. Kjeldsen: None declared
P0869 INTESTINAL EPSTEIN- BARR VIRUS IS ASSOCIATED WITH
MUCOSAL LYMPHOPROLIFERATION AND SUBSEQUENT
INTESTINAL SURGERY IN INFLAMMATORY BOWEL DISEASE
PATIENTS
L. Nissen1,2,*, I. Nagtegaal2, D.de Jong1, W. Kievit1, L. Derikx1, M. Lynch2,
H.van Krieken2, F. Hoentjen1
1
Gastroenterology and Hepatology, 2Pathology, RadboudUMC Nijmegen, The
Netherlands, Nijmegen, Netherlands
Contact E-mail Address: loes.nissen@radboudumc.nl
INTRODUCTION: Thiopurine therapy increases the risk of (Epstein- Barr virus
associated) lymphomas for Inflammatory Bowel Disease (IBD) patients up to
four times. Epstein- Barr virus (EBV) can cause a wide spectrum of lymphoproliferative reactions, ranging from morphologically benign with normal B lymphocytes (BL) and lymphoplasmacytic infiltrate in the lamina propria (LI) to
aggressive lymphomas with atypical BL and LI.
EBV can be detected in colonic mucosa in up to 60 % of the IBD patients, but
there is no consensus on when to perform EBV testing on intestinal mucosa. We
hypothesized that EBV testing can be guided by histological features including
morphology of BL and LI.
AIMS & METHODS: The aim of this study was to determine the value of the
histology of the inflammation in predicting EBV presence in intestinal mucosa
and to correlate EBV positivity with clinical endpoints such as intestinal surgery
and development of lymphoma.
All IBD patients who underwent EBV testing by EBV-encoded RNA in situ
hybridization (EBER) in intestinal biopsies between January 2005 and October
2013 in our centre were identified. All biopsies were revised by a blinded, expert
gastro-intestinal pathologist and scored on three histological features: number of
EBV positive cells per high power field (HPF); normal or atypical LI and normal
or atypical BL. Demographic and clinical data were collected from patient charts.
Adverse events that were registered included intestinal surgery and lymphoma.

A370

United European Gastroenterology Journal 2(1S)

We used the Chi square test or Fishers exact test to identify an association with
EBV positivity.
RESULTS: 58 IBD patients were included, 28 were EBV positive and 30 were
EBV negative. Ulcerative colitis was more frequent in the EBV positive group
(82,1 % versus 56,7 %; p 0.052)
EBV positive patients had significantly more frequent atypical LI (57.1 % versus
3.3 %; p 50.001). The specificity for predicting EBV presence of the atypical
LI is high (96.7 %), just as its positive predictive value (94.1 %). At time of
biopsy, EBV positive patients used more often combinations of two or more antiinflammatory drugs (5-aminosalicytes excluded; 50 % versus 16.7 %; p 0.007)
Eighteen EBV positive patients (64.29 %) had 20 pre-defined complications (18
colectomies, 2 lymphomas). Within the group of EBV positive patients, those
who developed complications had a significantly higher EBV load (50 % versus
10 %; p 0.048), expressed as the frequency of  10 EBV positive cells per HPF.
11 patients had atypical LI and BL, including 2 lymphomas: those were treated
with chemotherapy. In the other 9 patients at least one immunosuppressive drug
was stopped. In all patients the atypical LI showed resolution. 8 of the 9 patients
became EBV negative and 1 patient had reduction of EBV positive cells.
CONCLUSION: In the present study, atypical LI was associated with mucosal
EBV in IBD patients. A high EBV load is correlated with adverse events.
Reduction of immunosuppression may decrease intestinal EBV associated
lymphoproliferation.
Disclosure of Interest: None declared

and 9% had inactive disease (64% mild, 20% moderate and 7% severe disease).
Mean MEGS was 2018, with 82% having active disease and 18% inactive
disease (p50.01 in comparison to endoscopy, sensibility 88%, specificity 75%,
VPP 97%, VPN 38%). MEGS, was significantly higher in penetrating than in
non-penetrating and non-stricturing disease (respectively 359 vs 711, p5
0.001). MEGS was significantly correlated with SES-CD (p50.01), in particular
for the ileal (p50.01) and ceacum-ascending colon subscores (p 50.05). Severity
of the disease at endoscopy did not correlate to severity at MEGS (p 0.7). Both
MEGS and SES-CD show significant correlations with CDAI (p50.01) and
CRP (p50.05), yet SES-CD only correlated significantly with FC (p50.001).
The extramural involvement subscore, observed in half of patients, regardless of
the behavior and severity at endoscopy, was associated to CRP positivity
(p50.05), not with fecal calprotectin (p 0.67). Increasing staging of grading
at endoscopy was significantly correlated to the risk of extramural involvement
(p 0.008)
CONCLUSION: MRI is capable of identifying disease activity, although it
results less accurate in the assessment of severity as measured at endoscopy.
The presence of positive CPR suggests the need of MRI for the staging of
patients with active luminal disease.
REFERENCES
1 Makanyanga J, et al. Eur Radiol 2014.
2 Daperno M, et al. Gastrointest Endosc 2004.
Disclosure of Interest: None declared

P0870 SCREENING OF NOVEL PLASMA MICRORNAS ASSOCIATED


WITH DISEASE PROGRESSION IN ULCERATIVE COLITIS

P0872 ASSAY SPECIFIC DIFFERENCES IN CONSECUTIVELY


MEASURED F-CALPROTECTIN IN PATIENTS WITH IBD
FOLLOWED OVER TIME

M. Patel1,2,*, A.M. Verma1,2, M. I. Aslam1,2, K. West2, J. Jameson2,


J.H. Pringle1, B. Singh2
1
Cancer Studies & Molecular Medicine, University of Leicester, 2University
Hospitals of Leicester, Leicester, United Kingdom
Contact E-mail Address: maleene@doctors.org.uk
INTRODUCTION: New biomarkers are required to monitor patients with
Ulcerative Colitis (UC) and predict complications such as dysplasia and colitis
associated cancer (CAC). Accurate plasma based biomarkers would allow physicians to make clinical decisions, thereby avoiding unnecessary invasive tests.
AIMS & METHODS: This feasibility study aimed to identify novel microRNAs
(miRNAs) in the plasma of patients with Ulcerative Colitis related to disease
progression.
RESULTS: Primary analysis of the array data identified the differential expression of several miRNAs from which the following miRNAs 122,125b, 139-3p,
331-5p, 375, 383-3p, 409-3p, 720, 1274B were chosen for validation. Analysis of
variance was used to assess differences between groups. MiR-375 was shown to
be significantly up-regulated in the CAC cohort (p 0.002) when compared to
UC and PSC. MiR-375 was found to be an effective biomarker of disease progression over disease duration, with Cox-regression analysis showing a Cox
hazard ratio of 1.91 (p 0.01).
CONCLUSION: Peripheral plasma miRNAs have the potential to act as biomarkers of disease progression in Ulcerative colitis. This study provides the first
evidence that miRNA-375 is up regulated in cases of CAC. This finding needs to
be extended to a larger validation cohort.
Disclosure of Interest: None declared
P0871 THE INS AND OUTS OF MRI AND ENDOSCOPY IN THE
EVALUATION OF DISEASE ACTIVITY AND SEVERITY IN
CROHNS DISEASE
M. Serio1,*, A. Pierro2, G. Maselli2, K. Efthymakis1, A. Milano1, F. Laterza1,
A. Bonitatibus1, G. Sallustio2, M. Neri1
1
Medicine and Aging Sciences and CESI, Universita` "G. DAnnunzio", Chieti,
2
Radiology Department, Fondazione di Ricerca e Cura Giovanni Paolo II,
Universita` Cattolica del Sacro Cuore, Campobasso, Italy
Contact E-mail Address: mneri@unich.it
INTRODUCTION: Endoscopy is the gold standard for activity assessment in
luminal Crohns disease (CD) but, due to the full thickness involvement of the
bowel wall, or presence of complications, CD activity is the result of an integration of endoscopic, clinical, laboratory, and imaging data. Recently, a radiological score which integrates both mural and extramural involvement has been
validated for a global disease evaluation (1).
AIMS & METHODS: to examine the relationships among MRI, laboratory
inflammatory markers, clinical activity scores and endoscopy in a series of CD
patients.
45 consecutive patients with endoscopically proven CD underwent at the time of
enrollment MRI enterography, performed utilizing a 1.5 T system, for the staging
of disease at diagnosis and activity assessment. Endoscopic activity was measured
by a quantitative score (Simple Endoscopic Score for Crohns Disease, SES-CD
(2), range 0-40) with active disease being present for a 43 score and mild,
moderate ad severe disease for ranges of respectively 4-10, 11-19 and 420.
MRI activity was measured by a previously validated quantitative score
(Magnetic Resonance Enterography global score, MEGS, range 0-296), with
active disease being present for a 40 score. For all participants the Crohns
Disease Activity Index (CDAI) was completed and CRP and fecal calprotectin
(FC) were measured (positivity cut-off respectively 4 0.50 mg/dl and 4150 g/
gr).
RESULTS: We enrolled 19 males and 26 females, mean age 3714 years, mean
disease duration 5 years. According to Montreal disease classification the phenotype was L1 in 47%, L2 in 6% and L3 in 47%; the behavior was B1 in 24%, B2
in 56%, B3 in 20% and perianal disease in 2%; resectional surgery related to CD
was observed in 20%. According to SES-CD, 91% of patient had active disease

K. Amcoff1, M. Lampinen2, M. Stridsberg3, J. Halfvarson1,4, M. Carlson2,*


1
School of Health and Medical Sciences, Orebro University, Orebro, 2Department
of Medical Sciences, Gastroenterology Research Group, Uppsala University,
3
Department of Clinical Chemistry and Pharmacology, Uppsala, 4Dep of Internal
Medicine, Div of Gastroenterology, Orebro University Hospital, Orebro, Sweden
Contact E-mail Address: jonas.halfvarson@orebroll.se
INTRODUCTION: Faecal calprotectin (FC), an abundant neutrophil protein,
has recently been introduced as a non-invasive marker for monitoring of disease
activity in inflammatory bowel disease (IBD). However, it has been difficult to
define a definite threshold to discriminate between remission and active disease.
AIMS & METHODS: We, aimed to compare the results of different FC-assays
in a well-characterized cohort of patients with IBD, followed over time. Patients
(n 13) with established IBD provided faecal samples and reported clinical activity every third months prospectively for a two year period. Relapse was defined
as increasing symptoms and intensified treatment. FC was measured with three
different assays; Calprotectin Elisa Buhlmann Laboratories AG, Basel,
Switzerland; Phadia Elia Calprotectin, ThermoFischer Scientific, Freiburg,
Germany; and PhiCal Calprotectin Elisa, Immundiagnostik AG, Bensheim,
Germany. Disease status, defined as clinical remission or relapse, i.e. active disease, was determined at the time of collection of each fecal sample in each
patient. Samples were grouped as corresponding to clinical remission or active
disease. However, samples collected three months after a relapse were excluded to
reduce possible bias due to prolonged intensified therapy, steroid dependent
disease or ongoing subclinical inflammation.
RESULTS: In total, the 13 patients prospectively provided 91 faecal samples
during the two year period. The median (IQR) concentration of FC was 187
(57 582) mg/g, 52 (15 415) mg/g and 55 (9 158) mg/g using the Buhlmann-,
Phadia- and Immundiagnostik assay, respectively (p50.0001). Based on the cutoff provided by the manufactures, i.e. 450 mg/g, the FC assay was positive in 74
(81 %), 47 (52 %) and 50 (55 %) of the 91 samples when analyzed by the
Buhlman-, Phadia- and Immundiagnostik assay, respectively. Modest to fairly
good correlations were observed between the Buhlmann- and the Phadia assay,
the Buhlmann- and the Immundiagnostik assay and the Phadia- and the
Immundiagnostik assay (R2 0.70, R2 0.80 and R2 0.86, respectively).
However, Bland-Altman plots revealed overall poor agreement between the
assays. Assay specific sensitivity, specificity and predictive values for defining
clinical remission vs. active disease for each assay based on different cut-offs
are shown in table 1.
Table 1. Assay specific sensitivity, specificity and predictive values for defining
clinical remission vs. active disease for each assay based on different cut-offs
FC cut-off
(mg/g)
Bu 50 Ph 50 Im 50 Bu 100 Ph 100 Im 100 Bu 150 Ph 150 Im 150
Sensitivity
Specificity
NPV
PPV

86%
26%
87%
24%

71%
66%
89%
37%

86%
62%
94%
39%

86%
50%
93%
32%

64%
72%
88%
39%

36%
78%
81%
31%

79%
56%
90%
33%

50%
76%
84%
37%

14%
80%
77%
17%

Bu; Buhlmann assay, Ph; Phadia assay, Im; Immundiagnostik assay, NPV; negative predictive value, PPV; positive predictive value
CONCLUSION: By cross-comparisons pronounced inter-assay differences were
revealed. Although moderate to fairly good correlations between the FC assays
were observed, Bland-Altman plots showed overall poor agreement.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0873 RESIDUAL ABNORMALITIES AFTER MAYO ENDOSCOPIC
SUBSCORE DEFINED COMPLETE MUCOSAL HEALING
DEMONSTRATED BY NOVEL ISCAN ENDOSCOPIC AND REFINED
HISTOLOGICAL GRADINGS
M. Iacucci1,*, M. Fort Gasia1, R. Panaccione1, S. Ghosh1, X. Gui2
1
IBD clinic. Division of Gastroenterology, 2Department of Pathology, University of
Calgary, Calgary, Canada
Contact E-mail Address: miacucci@ucalgary.ca
INTRODUCTION: High definition(HD)- iSCAN endoscopy can characterize in
details the mucosa in patients with ulcerative colitis (UC) and may provide more
information about inflammation and mucosal healing (MH). However, the gold
standard of mucosal healing is still histological diagnosis. More refined histologic
and high definition iSCAN endoscopic criteria may redefine mucosal healing.
AIMS & METHODS: 78 patients (40 male, median age 42y, range 19-90y)
with UC were assessed by HDiSCAN colonoscopy (Pentax EC-3490Fi; Pentax,
Japan) as well as by white light endoscopy (WLE). Mayo endoscopic subscore
and UC endoscopic index of severity (UCEIS) score were assigned to patients
according WLE findings. Mucosal pattern on iSCAN was graded as 1 normal,
2 mosaic pattern, 3 tubular-gyrus, 4 nodular rosette. The vascular pattern
was graded as 1 normal, 2 spiral isolated vessels, 3 crowded tortuous vessels, 4 Irregular vessels. A histological grading and scoring system that assesses
all changes possibly seen in IBD was developed for a detailed and comprehensive
evaluation. This system (GUI-ECAP system) was designed to reflect all histologic
changes in IBD categorized as 1) Extent of inflammation (focal, multifocal,
diffuse), 2) Chronicity (crypt architectural alteration, Paneth cell metaplasia),
3) Activity (surface epithelium changes, neutrophilic cryptitis, crypt abscess,
crypt destruction, lamina propria mononuclear cellularity, lamina propria neutrophil infiltration, and basal plasmacytosis), and 4) Plus additional findings,
including eosinophilia and lymphoid follicles/aggregates. An established histologic grading system, New York Mount Sinai score was used to validate the grading of inflammation.
RESULTS: In this cohort of 78 patients with UC, 23 (29%) patients had Mayo
endoscopic subscore of 0. Of these 23 patients with complete MH, 18 patients
(78%) had abnormal vascular pattern on iSCAN and 7 (30%) had abnormal
mucosal pattern on iSCAN. By using ECAP histologic scoring all 23 patients
(100%) showed various histologic abnormalities including crypt architectural
alteration [19, (83%)], surface epithelium abnormality [16, (70%)], crypt destruction [3, (13%)], increase in lamina propria mononuclear cells [15, (65%)], basal
plasmacytosis [11, (48%)], lamina propria neutrophilic infiltration [5, (21%)] and
other additional findings [19, (83%)].
CONCLUSION: The subtle histologic abnormalities underlying the apparently
healed mucosa with Mayo endoscopic subscore of 0 can be detected by using
refined histological scoring system (GUI-ECAP) in combination with iSCAN.
Sensitive endoscopic techniques such as iSCAN and histologic scoring such as
ECAP can detect residual abnormalities in the majority of patients with seemingly complete MH in UC.
Disclosure of Interest: None declared
P0874 COLORECTAL CANCER IN IBD PATIENTS TREATED OR
UNTREATED WITH ANTI-TNFS: A RETROSPECTIVE MATCHEDPAIR STUDY IN A 13 YEARS FOLLOW UP
M. Ascolani1,*, G. Condino1, C. Petruzziello1, S. Onali1, E. Calabrese1, E. Lolli1,
A. Ruffa1, F. Pallone1, L. Biancone1
1
Universita` Tor Vergata, Rome, Italy
Contact E-mail Address: biancone@med.uniroma2.it
INTRODUCTION: In murine models, blocking TNF-alpha showed efficacy in
colitis-associated colon cancer. Chronic inflammation in Inflammatory Bowel
Disease (IBD) colitis has been associated with colorectal cancer (CCR).
AIMS & METHODS: In a monocentric retrospective matched-pair study, the
frequency of colon cancer was compared in a cohort of IBD patients treated or
untreated with anti-TNFs. In a matched-pair study, the role played by clinical
characteristics of IBD in determining the frequency of colon cancer was also
evaluated. Clinical records of all IBD patients in follow up from 2000 to 2013
at our tertiary IBD referral center developing cancer of the lower GI tract (IBDK)(small intestine, appendix, CCR, anal canal) were reviewed. Each IBD-K
patient was retrospectively matched with 2 IBD patients with no cancer of the
lower GI tract (IBD-C), for IBD type (MDC/RCU), gender, age (5yrs). AntiTNFs (Infliximab or Adalimumab1 dose) and IMM (6mos) use was reported.
Data expressed as median (range). Students T test and Chi squared test used as
appropriate.
RESULTS: From 2000 to 2013, the study population included 2387 IBD
patients: anti-TFNs use in 384 (16%). Cancer of the lower GI tract developed
in 15/2387 (0.62%) patients (9CD,6UC), including 12 CCR, (6UC,6CD), 1 ileal
adenocarcinoma (1CD), 1 carcinoid of the appendix (1CD), 1 anal canal carcinoma (1CD). In the 15 IBD-K patients, age at diagnosis of cancer was 51 (28-73)
yrs, IBD duration 19yrs (1-47): there were 9 CD of the ileum (I) (n 4), colon (C)
(n 2), ileum-colon (IC) (n 3) and 6 UC distal (n 3), left-sided (n 1) or total
(n 2). Among the 15 IBD-K patients, 3 (20%) received anti-TNFs and/or IMM
(combined in all 3). In these 3 patients, cancer included CCR (n 2) or carcinoid
(n 1) in 2CD (2F,age 40 and 54yrs, CD duration 28 and 26 yrs; I-C, fistulizing)
and 1UC (1F, CCR, age 30, duration 19yrs; pancolitis). Among the 384/2387
(16%) IBD patients treated with anti-TNFs, CCR developed in 3 (0.78%)(combined IMM in 3). Among the 2003/2387 (84%) patients anti-TNFs na ve,
12(0.6%) developed cancer of the lower GI tract,including CCR in 10 (0.5%)
(p ns vs anti-TNFs treated patients). IBD-C included 30 patients
(18CD,12UC;14 M/16 F, age 54,range 37-75), with CD (13 I;2 C;3 I-C) or UC
(distal 11, left-sided 1). Anti-TNFs use was reported in a comparable proportion

A371
of IBD patients developing or not cancer (IBD-C n 6/30; 20% vs IBD-K n 3/
15; 20%). In IBD-C, IMM were used in 10 (33%)(combined anti-TNFs in 2;6.
7%).
CONCLUSION: In a retrospective matched-pair study, a comparable low frequency of colon cancer was observed in IBD patients treated or untreated with
anti-TNFs.
Disclosure of Interest: None declared
P0875 IS THERE A ROLE FOR THE NEW SEROLOGICAL MARKERS IN
PREDICTING DISEASE COURSE IN AN IBD POPULATION
COHORT? LESSONS LEARNT FROM A PROSPECTIVE IRISH
POPULATION
M.N. Shuhaibar1,*, C. OMorain1
1
Department of Gastroenterology/ Clinical Medicine, AMNCH/Trinity College
Dublin, DUBLIN, Ireland
Contact E-mail Address: mnshuh@gmail.com
INTRODUCTION: Crohns disease and Ulcerative colitis are the two main
forms of inflammatory bowel disease. There are different disease phenotypes
within those groups and yet another 10-17% of patients may not have either
diagnosis and can be then be classified as indeterminate colitis until later on in
their disease course when they are reclassified into either main group as symptoms progress. Furthermore, some patient with gastrointestinal symptoms may
not have IBD initially, but develop it in future. Several antibodies have been
linked to CD and different IBD subtypes.
AIMS & METHODS: The aim of our study was to determine the prevalence of
the new anti-glycans antibody panel in a prospective homogenous IBD cohort to
help differentiating those with IBD from healthy controls. We aimed to assess
panels role in discriminating between CD and UC with their different phenotype
and their predictive value for disease course and treatment stratification in the
future.
Antibodies against a mannan epitope of Saccharomyces cerevisiae (gASCA),
laminaribioside (ALCA), Chitobioside (ACCA), mannobioside (AMCA) were
tested in serum samples of 103 IBD patients, 199 healthy matched controls.
Antibody response was matched to disease type and course. A backward step
multiple-regression analysis was performed along with 2- sample t-test for univariate biomarker analysis.
RESULTS: The anti-glycans antibody panel was useful in differentiating IBD
patients from healthy matched controls. Overall, 72% of IBD patients tested
positive for anti-glycans antibodies and of those 64% were positive for
gASCA, compared to 49% for ACCA antibody. gASCA was highly sensitive
and specific in CD patients.
CONCLUSION: From applying the anti-glycans antibody panel, combination of
gASCA IgA, Anti-L and Anti-C antibodies were statistically very significant in
differentiating CD from UC (with a p 50.0001). gASCA was very specific to CD
and correlated with severe disease course requiring surgery or fistulas, requiring
anti -TNF therapy in the lateral years.
Disclosure of Interest: None declared
P0876 CLINICAL OUTCOMES IN PATIENTS WITH INTERMEDIATE
RAISED FAECAL CALPROTECTIN LEVELS
M. Mcfarlane1, A. Dhaliwal1, S. Chambers1,*, C. Nwokolo1, A. Patel1,
R. Arasaradnam1,2
1
Gastroenterology, UHCW, Coventry, 2CSRI, University of Warwick, Warwick,
United Kingdom
Contact E-mail Address: r.arasaradnam@warwick.ac.uk
INTRODUCTION: Calprotectin is a calcium binding protein of the S100 family
associated with inflammation. A recent systematic review has confirmed its value
in distinguishing between organic (inflammatory bowel disease - IBD) and nonorganic gastrointestinal disease (irritable bowel syndrome - IBS). Those with FC
levels below 50 mcg/g have a negative predictive value of 492% to exclude
organic gastrointestinal disease. Conversely, FC levels greater than 250mcg/g,
correlates with endoscopic disease activity in those with IBD; sensitivity of 90%.
The aim of our study was to determine the clinical outcome in patients presenting
with an intermediate raised level of FC between 50-250 mcg/g.
AIMS & METHODS: FC test results from July 2012 to October 2013 were
reviewed. FC testing was performed using the PhiCal ELISA method. 482
patients were identified from the UHCW pathology database: 390 normal
(550mcg/g), 51 intermediate (50-250mcg/g) and 41 high (4250mcg/g).
Excluding paediatric patients (under 16), left 47 intermediate and 35 high results.
Where possible clinical information was obtained from the UHCW Clinical
results and reporting system. If no information was found then general practitioners (GPs) were contacted for further details (long term clinical data could not
be found for 5 intermediate and 9 high patients).
RESULTS: We studied a subset of 50 of the 390 normal FC values (550mcg/g)
which served as a comparator group. Of these, 9 (18%) were referred to secondary care gastroenterology, with 3 (6%) still in secondary care 6 months post FC.
None were diagnosed with IBD.
Of the 26 patients with high FC (4250mcg/g), 8 did not have details provided by
their GPs, 8 (31%) were known IBD patients and 3 (12%) were not investigated declining referral or patient mortality. 6 (23%) had a new diagnosis of IBD and 1
(4%) with post infective IBS. 15 (58%) were still in secondary care 6 months after
FC testing.
Of the 42 intermediate (50-250mcg/g) patients, 17 did not have information
provided by their GPs and 2 (5%) were known IBD patients. 8 patients (19%)
were diagnosed with colon cancer or were still under investigation. 3 (7%) had a
new diagnosis of IBD and 12 (29%) with non IBD conditions (e.g. BAM,

A372

United European Gastroenterology Journal 2(1S)

Diverticular disease and IBS). 13 (31%) patients were still in secondary care 6
months after initial FC see table 1.
Within the intermediate group, 10 patients had FC 5 100mcg/g, none were
diagnosed with IBD and 20% remained in secondary care 6 months post FCP.
Of the 16 available patients with FC of 100-250, 3 (23%) had a new diagnosis of
IBD and 7 (54%) were still in secondary care 6 months after FC.

Groups
Managed in primary care
Undergoing investigations
New diagnosis of IBD
Existing diagnosis of IBD
Still under follow-up at 6 months
(from FC testing)

550mcg/g
(subset n 50)

50-250mcg/g
(n 42)

4250mcg/g
(n 26)

41(82%)
9 (18%)
0
0
3 (6%)

5 (12%)
17 (40%)
3 (7%)
2 (5%)
13 (31%)

3 (12%)
6 (23%)
6 (23%)
8 (31%)
15 (58%)

CONCLUSION: 1) The majority (81%) of FC requested were normal with a


similar proportion managed in primary care without any new diagnosis of IBD.
2) New diagnosis of IBD is three times more common in those with FC values 4
250mcg/g and 3) A third (31%) with intermediate FC levels remain under secondary/tertiary care at 6 months but still half compared with those having high
FC levels.
Disclosure of Interest: None declared
P0877 LONG-TERM EFFECTIVENESS, PATIENT SATISFACTION &
COST-BENEFIT ANALYSIS OF A SELF-MANAGEMENT
PROGRAMME FOR PATIENTS WITH INFLAMMATORY BOWEL
DISEASE: A FIVE YEAR FOLLOW-UP STUDY
S. Gethins1, M.S. Hanna1,*, B. Robinson1, T. Duckett1, P. Hunt1,
R.J. Robinson1
1
Department of Gastroenterology, Leicester General Hospital, Leicester, United
Kingdom
Contact E-mail Address: minahanna@yahoo.com
INTRODUCTION: Self management programmes enable patients with
Inflammatory Bowel Disease to play a greater role in monitoring and treating
their illness, allowing them to be discharged from hospital follow up. Short-term
studies have shown reduced health service utilization, without compromising
health outcomes1.
AIMS & METHODS: The aim of our study was to evaluate the long-term
effectiveness of a self-management programme for patients with IBD and
assess patient satisfaction and health care cost benefits. Over a 12 month
period in 2007, 157 patients with IBD (122 with Ulcerative colitis (UC), 31
Crohns disease (CD) and 4 indeterminate colitis were recruited to our IBD
self management programme. Stable patients on first line therapy met with a
specialist IBD nurse and were provided with specific information about their
diagnosis, relapse recognition and medication. A personalised written self management programme was provided with an escalation plan in the event of symptoms. The first 70 patients recruited to the study were sent a patient satisfaction
questionnaire 1 year post-recruitment. A cost-saving analysis over the 5 year
period was performed based on the premise of avoiding 2 hospital follow-up
appointments per year and the local tariff (103). After 5 years, the case notes
of all patients re-referred were reviewed to establish the reason for re-referral and
interval between discharge & re-referral.
RESULTS: Over the 5 year period 22 (14.0%) patients (22 UC, 2 CD) had
been re-referred to our service with a flare of their IBD. Five patients required
azathioprine & one patient with Crohns disease was started on biologics. One
patient was admitted as an emergency, initially responding to cyclosporine but
required a colectomy 1 year later. The remainder were treated with increased 5ASA, topical therapy or oral steroids. Median time from discharge to re-referral
was 31 months (range 11-60 months). 62/70 (88.6%) patients completed their
patient satisfaction surveys; 58 (93.5%) being satisfied with the programme and
58 (93.5%) feeling involved in their treatment decisions. Over the 5 year period,
there was an estimated health-care cost saving of 147290. (Table 1)

Year
Year 1
Year 2
Year 3
Year 4
Year 5
Overall savings

No. of patients in
self-management
programme at
start of year No. of
patients re-referred
to service in each year

Local follow-up
appointment
tariff x estimated
appointments
per year

157155149142136-

103
103
103
103
103

2 155
6 149
7 142
6 136
3 133

x
x
x
x
x

2
2
2
2
2

Estimated
Cost-savings
31930
30694
29252
28016
27398
147290

CONCLUSION: This study shows that self-management is an effective long


term strategy for selected stable patients with IBD and is acceptable to patients.
Few patients are re-referred and the substantial 5-year cost savings could be reinvested in developing specialist IBD services.

REFERENCES
Robinson A. Review article: inflammatory bowel diseaseempowering the
patient and improving outcome. Aliment Pharmacol Ther 2004; 20(Suppl. 4):
84-87.
Disclosure of Interest: None declared
P0878 SERUM HEPCIDIN LEVELS PREDICT INTESTINAL IRON
ABSORPTION IN IBD PATIENTS
M. Wiesenthal1,*, F. Hartmann1, T. Iqbal2, A. Dignass1,3, J. Stein1,4
1
Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany, 2Birmingham
University Hospital, Birmingham, United Kingdom, 3Agaplesion Markus
Krankenhaus, 4Krankenhaus Sachsenhausen, Frankfurt/Main, Germany
Contact E-mail Address: j.stein@em.uni-frankfurt.de
INTRODUCTION: Circulating hepcidin is proposed to regulate iron absorption
by modulating iron export by ferroportin at the basolateral membrane of the
duodenal mucosal cells and/or uptake into the cells at the apical membrane by
DMT1. To date, no data have shown a relationship between plasma hepcidin
concentrations and iron absorption in IBD patients.
AIMS & METHODS: We used stored samples from a human iron absorption
study to further test the hypothesis that plasma hepcidin may explain interindividual variation in iron absorption in IBD patients. Serum ferritin (SF) and
serum markers of inflammation [high-sensitivity C-reactive protein (hsCRP)
and IL-6] were measured in stored samples from a human iron absorption
study using commercially available immune-assays. Hepcidin-25 concentrations
were determined in fasting samples from 71 adult subjects with IBD (31 UC, 40
CD) and 26 healthy controls. Hepcidin was measured by LC-MS.
RESULTS: There was a positive correlation between hepcidin (mean: 2.3; range:
0.17.8nmol/L) and hsCRP (p50.005), but not between hepcidin and serum
ferritin (p40.05). Whereas iron absorption was negatively correlated with
serum ferritin only in patients with inactive disease (hsCRP55md/dl; p5
0.001), a negative correlation was observed with serum hepcidin in both active
and inactive disease (p 0.006), independent of IBD phenotype. Multiple linear
regression models showed that serum hepcidin in isolation significantly predicted
the interindividual variation in iron absorption.
CONCLUSION: Concentration of serum hepcidin, but not serum ferritin, was
highly correlated with intestinal iron absorption in IBD patients.
Disclosure of Interest: None declared
P0879 LONG TERM OUTCOME OF CROHNS DISEASE ACTIVITY A
PROSPECTIVE STUDYN. Bounab1,*, L. Kecili1, A. Balamane1, K. Belhocine1, K. Layaida1, L. Gamar1,
T. Boucekkine1
1
Faculty of Medicine, Algiers, Algeria
INTRODUCTION: Crohns Disease (CD) is a chronic and heterogeneous
inflammatory bowel disease affecting the gastrointestinal tract; its etiology is
unknown and its outcome is unpredictable
AIMS & METHODS: To analyze the long term outcome of the disease activity,
we studied a cohort of 226 consecutive cases of CD hospitalized from 01/01/2000
to 31/12/2004. These patients, enrolled at diagnosis, underwent initial complete
investigation. CD diagnosis was based on international criteria. All patients were
included in a prospective study and followed-up from 01/01/2005 to 31/12/2009
during at least 5 years or until the first surgical resection. A systematic clinical
control was performed every 6 or 12 months and on demand; complete investigation comprising endoscopy was done when needed. Statistical study: Student
Fishers t test and Mann Withney U test.
RESULTS: The cohort included 103 males and 123 females (mean age was 30, 3
years at diagnosis); 41 patients were smokers (18.1%). At the end of follow-up: 1/
The overall annual activity which was defined as the percentage of active disease
per year has showed a progressive decrease (from 59.3 % the first year to 46.5%
the last year p50.05) associated with a decrease of the number of severe flares
(from 34.7% to 15% p50.05). 2/the age at onset of the disease didnt influence
the disease activity: 62%; 59.3%; 59.7% at diagnosis and 50%; 45.3%; 45.4% at
the end of follow- up in patients aged 520 years, 20-40 years, 440 years respectively (p 40.05).3/ the rate of activity tends to decrease over time when lesions
were located in both small intestine and colon (59.5% to 46.5% p50.05) whereas
it remained stable when lesions were located exclusively in the colon (from 48.8%
to 44.1%;p40.05). 4/decrease of activity was more often observed in inflammatory type lesions (from 50% to 41.3% p 5 0.05). 5/smoker (S), non smoker (NS)
and previous smoker (PS) statutes didnt influence activity outcome
(from:S 60%;PS 60%; NS 57.6% to S 45.4%; PS 43.4%; NS 47%:
p40.05).6/ however, the need for surgery increased progressively over the time
(from 4% the first year to 7% the last year).
CONCLUSION: This prospective study showed that the overall Crohns Disease
activity decreased and became less severe over time, which probably expresses a
slight tendency to a disease extinction. The course of disease hasnt been significantly influenced neitherby the age at onset of disease, nor by tobacco consumption. The outcome of initial inflammatory type lesions was more favourable than
stricturing or penetrating lesions.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0880 PREVALENCE OF ANAEMIA IN A COHORT OF PATIENTS
WITH IBD AND ITS RELATIONSHIP TO FAECAL AND SERUM
BIO-MARKERS OF INFLAMMATORY BURDEN, AND MARKERS OF
IRON STATUS
N.S. Taylor1,*, D.A. Lloyd1, S. Cotton1, L.-A. McCabe1, J.N. Gordon1
1
Gastroenterology, Hampshire Hospitals NHS Foundation Trust, Winchester,
United Kingdom
Contact E-mail Address: john.gordon@hhft.nhs.uk
INTRODUCTION: Anaemia is common in IBD and usually due to either irondeficiency or anaemia of chronic disease. Serum ferritin is a frequently used
marker of iron status in patients with IBD. It is influenced by inflammatory
status with CRP commonly used in clinical practice to aid in determining the
presence or absence of iron deficiency. However, the correlation of ferritin with
markers of mucosal disease activity such as faecal calprotectin (FC) is unknown
and may have important implications in determining the effect of inflammation
on the diagnosis of iron deficiency. The aim of this study was to investigate the
prevalence of anaemia and its relationship to markers of iron stores and faecal
and serum markers of inflammation in IBD.
AIMS & METHODS: We performed a computer database search of all IBD
clinic patients who had paired blood tests (including Hb, mean cell volume, CRP,
ferritin) and FC in the last 12 months. Blood and faecal samples were accepted as
paired if taken within 7 days of each other. Anaemia was defined using WHO
criteria, with a ferritin of 530ng/ml taken to indicate iron-deficiency. An FC of
550 ug/g was taken to indicate inactive disease, an FC of 50-200 ug/g a borderline result and an FC 4200 ug/g as active disease. Results were analysed to assess
for prevalence of anaemia and iron deficiency and their correlation with faecal
and biochemical markers of disease activity.
RESULTS: 124 patients (79 Crohns disease, 45 Ulcerative Colitis) with a diagnosis of IBD and paired blood tests and faecal inflammatory markers were
identified and their data analysed. 30/124 (21%) of the whole cohort were anaemia, and 34% were iron-deficient. There was a clear negative correlation between
disease activity and both haemoglobin and ferritin levels. 20/30 (66%) of the
anaemic patients had a ferritin of 530 and could clearly be classified as irondeficient. The average CRP in this group was 11.4mg/l and calprotectin 686ug/g.
9/30 (30%) of patients had a ferritin of 430 with one patient having a ferritin of
4100. The average CRP in this group was 17.8 and calprotectin 832ug/g. 40% of
anaemic patients with a ferritin 430 had a CRP 55 and would not be classified
as iron deficient. All these patients had a raised calprotectin (av 1030). Use of a
raised Calprotectin of 4500ug/g as a marker of inflammatory burden rather
than CRP would have resulted in half these patients being classified as iron
deficient which was supported by other markers of iron stores.
CONCLUSION: Anaemia (21%) and iron deficiency (34%) were common in
this cohort of patients with IBD. There was a clear negative correlation between
markers of anaemia and iron deficiency and faecal calprotectin. There was a
closer correlation between calprotectin and anaemia than CRP and anaemia.
Calprotectin may be a more effective marker of inflammatory burden than
CRP in the assessment of IDA in patients with active IBD.
Disclosure of Interest: None declared
P0881 UTILITY OF FAECAL CALPROTECTIN IN PREDICTING
RELAPSE IN INFLAMMATORY BOWEL DISEASE: A METAANALYSIS
N. Mohammed1,*, E. Telakis2, V. Subramanian1
1
Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, St Jamess
University Hospital, University of Leeds, Leeds, United Kingdom,
2
Gastroenterology, Bioclinic of Piraeus, Piraeus, Greece
Contact E-mail Address: v.subramanian@leeds.ac.uk
INTRODUCTION: Faecal calprotectin (FCP) is a non-invasive marker of gastrointestinal inflammation. Its utility in the clinical management of inflammatory
bowel disease (IBD) is still under evaluation. We aimed to perform a metaanalysis of prospective studies in assessing the ability of baseline FCP for predicting disease relapse with 12 months in patients with Crohns disease (CD) and
ulcerative colitis (UC) in clinical remission.
AIMS & METHODS: Multiple electronic databases were searched including
Pubmed, Embase and Ovid looking for studies providing data on relapse prediction in IBD using FCP. Pooled sensitivity, specificity, negative (LR-) and positive
(LR) predictive value diagnostic odds ratio (DOR) and pooled area under the
receiver operating characteristic (AUROC) was calculated using MetaDiSc
ver1.4 software. A random effects model was used and publication bias was
assessed using Funnel plots and Eggers test and heterogeneity was assessed
using Cochrans Q and the I2 test.
RESULTS: 8 studies involving 507 patients with CD and 8 studies involving 587
patients with UC were included. The predictive value for a relapse within 12
months for baseline FCP in patients with CD was sensitivity 73%(64-80), specificity 78% (74-82), LR 2.9 (1.9-4.5), LR- 0.4 (0.2-0.6), DOR 10.1 (4.5-22.6) and
AUROC 0.83 (0.04). The cut off for baseline FCP used for the CD studies
ranged from 130-340 mg/g. The predictive value for a relapse within 12 months
for baseline FCP in patients with UC was sensitivity 72%(65-77), specificity 78%
(74-83), LR 3.0 (2.3-4.0), LR- 0.4 (0.2-0.6), DOR 9.2 (5.4-15.7) and AUROC
0.82 (0.03). The cut off for baseline FCP used for the UC studies ranged from
130-250 mg/g. There was significant heterogeneity (I2 4 50%) for all the analysis
likely because of the differences in relapse rates and FCP cut off values used.
CONCLUSION: FCP is a simple non-invasive marker with the potential to
predict relapse in CD and UC. With pooled sensitivity and specificity under
80% for both CD and UC but with a likelihood ratio of a negative test being
0.4, its value may be mainly to identify low risk patients. However wide variations in the cut off values for FCP used in these studies makes it difficult to apply

A373
this to routine clinical practice. Serial measurements of FCP to check for a rise
from baseline may be the way forward for future studies.
Disclosure of Interest: None declared
P0882 IS THERE ANY RELATION BETWEEN RED BLOOD CELL
DISTRIBUTION WIDTH AND MUCOSAL REMISSION IN
ULCERATIVE COLITIS?
O. Kocaman1,*, A. Danalioglu1, A.T. Ince1, K. Turkdogan1, H. Senturk1,
B. Baysal1, M. Tozlu1, Y. Kayar1
1
Department of Gastroenterology, Bezmialem Vakif University, Istanbul, Turkey
Contact E-mail Address: drokocaman@hotmail.com
INTRODUCTION: A higher red blood cell distribution width (RDW) has been
shown as an indicator of disease activity in ulcerative colitis (UC). However, the
relation of mucosal remission with RDW has not been investigated. We aimed to
determine if RDW level as a categorical variable (high or normal) could be used
as a parameter for predicting mucosal remission in UC.
AIMS & METHODS: This study was conducted prospectively at a university
hospital with high volume of inflammatory bowel disease patients. C-reactive
protein (CRP), RDW value and colonoscopic findings were analyzed in UC
patients. The endoscopic procedures were performed by a dedicated IBD endoscopist. Mucosal remission was defined as a Mayo score of 0 for UC. The groups
were compared using chi-square test. SPSS version 16 was used for statistics.
RESULTS: A total of 178 patients (102 male, 76 female; age range: 19 to 82
years) were included in the study. The number of patients with mucosal-remission
was 57 (normal or inactive disease). No correlation between CRP levels and
mucosal remission was found. Of the patients in mucosal remission, 46 had
normal RDW level. Of the 121 patients with no mucosal remission, 75 had
normal RDW level. RDW was found as a significantly useful parameter for
identifying mucosally active UC patients (p50.005).
CONCLUSION: This study shows that categorical RDW value is a useful parameter for identifying mucosally active UC patients and could be used as a marker
for non-invasive monitoring of mucosal activity in UC patients.
Disclosure of Interest: None declared
P0883 PREVENTION OF OPPORTUNISTIC INFECTIONS IN PATIENTS
ON BIOLOGICAL AGENTS FOR MANAGEMENT OF
INFLAMMATORY BOWEL DISEASE
H. Gordon1,*, A. Steel1
1
Gastroenterology, Chelsea and Westminster Hospital, London, United Kingdom
Contact E-mail Address: hannah.gordon@chelwest.nhs.uk
INTRODUCTION: Patients with inflammatory bowel disease are at increased
risk of infection; this is especially true of the 20% on biological agents. ECCO
guidelines recommend the following vaccines: Influenza (annual), Pneumococcal,
Hepatitis B, Varicella, HPV (women under 26). The guidelines also highlight the
need to exclude latent TB; local policy is to perform an interferon gamma release
assay. Within the UK vaccination services are provided by primary care.
AIMS & METHODS: The measures taken to prevent opportunistic infection in
patients prescribed anti-TNFs for IBD at Chelsea and Westminster Hospital in
2013 were audited against the ECCO OI Guidelines. The following were retrieved
from electronic records: age, sex, anti TNF prescribed, pneumococcal antibodies,
hepatitis B core and surface antibodies, varicella IgG, Elispot. Attempts were
made to retrieve vaccination history from General Practice.
RESULTS: 60 patients were prescribed infliximab and 15 patients were prescribed adalimumab. 46 GPs were able to provide vaccination history.
Influenza: 50% (23/46) patients received vaccination against influenza within the
past year.
Pneumococcus: 55% (47/85) patients demonstrated immunity. 6% (5/85) were
not immune and the remainder were not tested. The vaccination history of 26
patients who were not immune or not tested was retrieved. 27% (7/26) had since
been vaccinated.
Hepatitis B: No patients were core Ab positive. Surface Ab levels demonstrated
immunity in 7% (6/85). 53% (45/85) were not immune, and the remainder were
not tested. Vaccination history of 44 patients who were not immune or not tested
was retrieved. Of these, 25% (11/44) had since been vaccinated.
HPV: 4 patients were women under 26 years old. 25% (1/4) had confirmed HPV
vaccination.
Varicella: 21% (18/85) patients demonstrated immunity to varicella. 2% 2/85
were not immune.
Elispot: 65% (55/85) patients had a nonreactive assay. 1% (1/85) had a positive
result and the remainder were not tested.
CONCLUSION: The standards set out by ECCO to protect patients from
opportunistic infection are not being met.
Problems obtaining accurate vaccination history from GP records include incorrect surgery details, lack of availability of staff able to review records and incomplete records. HPV vaccination usually takes place at school and is not routinely
recorded by primary care.
Potential service improvements include provision of vaccines at clinic, improved
patient education regarding the importance of vaccination and a check list to
review bloods at first anti-TNF prescription.
REFERENCES
1. Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based
Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009; 3: 4791.
Disclosure of Interest: None declared

A374
P0884 EFFICACY, SAFETY, AND DEMOGRAPHICS FACTOR OF ORAL
TACROLIMUS THERAPY IN 666 JAPANESE PATIENTS WITH
REFRACTORY ULCERATIVE COLITIS
H. Ogata1,*, T. Yamamoto2, R. Kunisaki3, K. Ishida4, T. Hibi5
1
School of Medicine, Keio University, Tokyo, 2Yokkaichi Hazu Medical Center,
Yokkaichi, 3Yokohama City University Medical Center, Yokohama, 4Astellas
Pharma Inc., 5Kitasato University Kitasato Institute Hospital, Tokyo, Japan
Contact E-mail Address: kota.ishida@astellas.com
INTRODUCTION: Ulcerative colitis (UC) is a form of chronic inflammatory
bowel disease and is characterized by periods of remission and episodes of
relapse. The pathogenesis of UC remains unclear. This study aims to evaluate
the efficacy and safety of tacrolimus (TAC).
AIMS & METHODS: Aims: To evaluate the safety and efficacy of oral TAC in
Japanese patients with refractory (corticosteroid-resistant or -dependent) active
UC in a real clinical setting.
Methods: The observation period of this study was 6 months. Six hundred and
sixty-six UC patients were enrolled between 2009 and 2011 in 145 medical institutions. Efficacy was evaluated using the Disease Activity Index (DAI) score (1),
clinical remission and endoscopic remission. DAI score improvement was defined
as either a reduction in DAI of more than 4 points with improvement of all
categories (Stool frequency, Rectal bleeding, Mucosal appearance, Physicians
global assessment) or complete resolution of all categories (2). Clinical remission
was defined as stool frequency  3 per day and no rectal bleeding. Endoscopic
remission was defined as mucosal appearance  1.
RESULTS: Mean DAI score was 8.9  1.97 at baseline. Adverse drug reactions
(ADRs) occurred in 39% of the patients. The most frequent ADRs were Nervous
system disorders (serious: 2 patients, non-serious: 71 patients) such as finger
tremor (50 patients), and the most frequent serious ADRs were infections and
infestations (20 patients) such as cytomegalovirus-related events (7 patients) and
pneumonia-related events (5 patients). In 18 out of 20 patients, serious infections
and infestations were resolved or became mild during the observation period.
When serious infections and infestations occurred, 6 patients discontinued the
TAC treatment and 11 patients continued after they occurred. One patient had
discontinued before the event. In another 2 patients, one patient (age 81) developed sepsis and died 2 days after it occurred. One patient (age 56) developed
herpes zoster and didnt improve during the observation period. TAC treatment
was continued after it occurred. Serious renal and urinary disorders were
reported in 8 patients. Seven out of 8 patients were resolved or became mild
during the observation period. One patient (age 62) developed renal impairment
and didnt improve during the observation period. All of the 8 patients discontinued the TAC treatment when serious renal and urinary disorders occurred.
DAI score improvement was observed in 63% of the patients during the observation period. Sixty-seven percent of the patients had clinical remission during
the observation period. The endoscopic remission rate increased with time during
the observation period (17% after 3 months, 31% after 6 months).
CONCLUSION: Oral TAC therapy, with monitoring of blood trough concentration was well tolerated and induced clinical and endoscopic remission with
time in Japanese patients with refractory active UC.
REFERENCES
1. Schroeder KW, Tremaine WJ and Ilstrup DM. Coated oral 5-aminosalicylic
acid therapy for mildly to moderately active ulcerative colitis, a randomized
study. N Engl J Med 1987; 317: 16251629.
2. Ogata H, Matsui T, Nakamura M, et al. A randomised dose finding study of
oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006; 55:
1255-1262.
Disclosure of Interest: H. Ogata Financial support for research from: Astellas
Pharma Inc., Zeria Pharmaceutical Co., Ltd., AstraZeneca, Boston Scientific
Corporation, Otsuka Pharma, Kyorin Pharmaceutical Co.,Ltd., Lecture fee(s)
from: Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Dainippon
Sumitomo Pharma Co. Ltd., Given Imaging Ltd., Takeda Pharmaceutical
Company Ltd, Kyorin Pharmaceutical Co.,Ltd., Consultancy for: AbbVie Inc.
Mochida Pharmaceutical Plant Co., Ltd., Johnson & Johnson, T. Yamamoto:
None, R. Kunisaki Lecture fee(s) from: Astellas Pharma Inc., Shareholder of:
Astellas Pharma Inc., K. Ishida: Employee of: Astellas Pharma Inc., T. Hibi
Financial support for research from: JIMRO Co. Ltd., AbbVie Inc. Zeria
Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Lecture
fee(s) from: Astellas Pharma Inc., Yoshida Pharmaceutical, Zeria
Pharmaceutical Co., Ltd., Eisai Co. Ltd., JIMRO Co. Ltd., Kyorin
Pharmaceutical Co.,Ltd. AbbVie Inc. Mitsubishi Tanabe Pharma Corporation,
Nippon Kayaku Co. Ltd., Consultancy for: Astellas Pharma Inc., Nippon
Kayaku Co. Ltd. Eisai Co. Ltd., AbbVie Inc. Ajinomoto Pharmaceuticals Co.,
Ltd.
P0885 WITHDRAWAL OF AZATHIOPRINE IN PATIENTS WITH
CROHNS DISEASE IN STABLE CLINICAL REMISSION: A
DOUBLE-BLIND, PLACEBO-CONTROLLED 2 YEARS TRIAL
H.H. Wenzl1,*, C. Primas2, G. Novacek2, A. Teml2, A. Offerlbauer-Ernst2,
C. Hogenauer1, H. Vogelsang2, W. Petritsch1, W. Reinisch2
1
Internal Medicine, Medical University of Graz, Graz, 2Internal Medicine, Medical
University of Vienna, Vienna, Austria
INTRODUCTION: Many patients with quiescent Crohns disease are maintained on long-term treatment with azathioprine (AZA), but controlled data
are limited. The aim of the present study was to evaluate the efficacy of AZA
therapy for more than 4 years to maintain clinical remission.
AIMS & METHODS: We performed a randomized double-blind placebo-controlled AZA withdrawal trial with a follow-up period of 24 months. Patients had
to have continuous AZA therapy for a minimum of 4 years without exacerbation

United European Gastroenterology Journal 2(1S)


of disease during the previous 12 months before enrollment, and a Crohns
disease activity index 5150 at baseline. Patients were randomized to continue
on AZA (n 26) or switch to placebo (n 26). The primary endpoint was time to
clinical relapse during follow-up.
RESULTS: During the 2-year follow-up clinical relapse occurred in 4 patients on
continued AZA and in 8 patients on placebo. Time to clinical relapse averaged
22.3 months (95% CI 20.6-24.0) in the AZA group, and 19.2 months (95% CI
16.4-22.1) in the placebo group (p 0.20). According to life-table analysis, the
proportion of patients in remission after 12 and 24 months was 964% and
867% in patients receiving AZA versus 768% and 689% in patients receiving placebo (month 12, p 0.035; month 24, p 0.30). A higher AZA dose at
enrollment was an independent predictive factor for relapse (p50.05).
CONCLUSION: In patients with clinically inactive Crohns disease on maintenance therapy with AZA for 4 4 years discontinuation of AZA resulted in a
numerically higher relapse rate compared to further AZA treatment. Our results
are in line with previous observations.
Disclosure of Interest: H. Wenzl Lecture fee(s) from: Abbvie, MSD, and SHIRE,
C. Primas Lecture fee(s) from: MSD, G. Novacek Lecture fee(s) from: MSD,
AbbVie, and Ferring, Consultancy for: MSD, AbbVie, and Astro Pharma, A.
Teml: None declared, A. Offerlbauer-Ernst: None declared, C. Hogenauer
Lecture fee(s) from: MSD, AbbVie, Signatis Pharma and Astro Pharma, H.
Vogelsang Lecture fee(s) from: MSD, AbbVie, Astro Pharma, Johnson &
Johnson and Ferring, W. Petritsch Lecture fee(s) from: Abbott Laboratories,
AbbVie, Aesca, Ferring, Merck and MSD, Consultancy for: Abbvie and MSD,
W. Reinisch Financial support for research from: Abbott Laboratories, Abbvie,
AESCA, and MSD, Lecture fee(s) from: Abbott Laboratories, Abbvie, Aesca,
Aptalis Centocor, Ferring, Janssen Millenium, Mitsubishi Tanabe Pharma
Corporation, MSD, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda,
and Therakos, Consultancy for: Abbott Laboratories, AbbVie, Aesca, Amgen,
AM Pharma, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb,
Cellerix, Chemocentryx, Celgene, Centocor, Danone Austria, Elan, Ferring,
Galapagos, Genentech, Grunenthal, Janssen, Johnson & Johnson, Kyowa
Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe
Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos,
Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, ScheringPlough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor,
Yakult, Zyngenia, and 4SC, Other: Lipid Therapeutics, Pharmacos and Pfizer
P0886 COST-EFFECTIVENESS OF ADALIMUMAB IN MODERATELY
TO SEVERELY ACTIVE ULCERATIVE COLITIS (SUB-ACUTE) IN
THE UK
H. Yang1, A. Curry2, S. Wang3,*, M. Yang1, M. Skup3, J. Chao3, Y. Bao3
1
Analysis Group, Inc., Boston, United States, 2AbbVie Ltd, Berkshire, United
Kingdom, 3AbbVie Inc., North Chicago, United States
Contact E-mail Address: song.wang2@abbvie.com
INTRODUCTION: The objective was to compare the cost-effectiveness of adalimumab (ADA) versus standard of care (SOC) for the treatment of patients with
moderately to severely active ulcerative colitis (UC) (sub-acute) who have an
inadequate response to SOC in the UK. The base case was conducted for a
UC patient population including patients who are na ve to the cytokine inhibitors affecting tumour necrosis factor alpha (anti-TNF-) and patients who have
previously been exposed to anti-TNF- agents other than ADA.
AIMS & METHODS: A Markov model was constructed to simulate the treatments and disease course of adults with moderately to severely active UC
(including both anti-TNF- na ve and experienced patients) who had an inadequate response to conventional therapies receiving ADA therapy, or receiving
SOC. SOC refers to conventional treatments including anti-inflammatory drugs
or immunosuppressants. The model estimated the direct health care costs and
quality-adjusted life years (QALYs) over a 10-year time horizon. The model was
conducted from the perspective of the U. K. National Health Service. Only direct
costs were considered. Eight health states were defined in the Markov model,
including three pre-surgery states (i.e. remission, mild, and moderate-to-severe),
surgery state, and four post-surgery states (i.e. post-surgery without complication, transient complication, chronic complication, and surgery-related death).
The transitional probabilities of the pre-surgery states were primarily derived
from the randomized, controlled clinical trials of ADA in the treatment of moderately to severely active UC patients [the Ulcerative Colitis Long-term
Remission and Maintenance with Adalimumab M06-827 (ULTRA 2) trial and
M10-223 (the ULTRA 1/2 extension trial)]. The transitional probabilities for the
surgery and post-surgery states were derived based on published literature.
Utility values were specified for each disease state, and were based on published
literature. The model considered drug costs, disease states costs, hospitalization
costs, surgery costs, surgery-related complication costs, and costs associated with
surgery-related death. These costs inputs were derived from published literature.
Results were expressed in the incremental cost-effectiveness ratio (ICER) per
QALY gained. The impact of uncertainty of model parameters was examined
using deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA).
RESULTS: The ICER per QALY gained for ADA vs. SOC was 34,417 over a
10-year time horizon in the base case (in 2013 GBP pounds). DSA varying key
model inputs produced ICER per QALY gained in the range of 29,437 to
38,073. The probability for ADA to be cost-effective at the willingness-to-pay
threshold of 30.000 was 30%.
CONCLUSION: With no NICE recommended biologic options, there is currently a high unmet need for patients in England and Wales with moderately
to severely active UC (sub-acute) who have failed on standard of care. This
economic evaluation demonstrated that when compared to SOC, the ADA therapy has a reasonable cost-effectiveness ratio. The cost-effectiveness result of the
ADA strategy was shown to be robust in a range of sensitivity analyses.

A375

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: H. Yang Other: Employee: Analysis Group, Inc, under
contract with AbbVie, A. Curry Shareholder of: AbbVie, Other: Employee:
AbbVie, S. Wang Shareholder of: AbbVie, Other: Employee: AbbVie, M.
Yang Other: Employee: Analysis Group, Inc, under contract with AbbVie, M.
Skup Shareholder of: AbbVie, Other: Employee: AbbVie, J. Chao Shareholder
of: AbbVie, Other: Employee: AbbVie, Y. Bao Shareholder of: AbbVie, Other:
Employee: AbbVie
P0887 MAINTENANCE OF REMISSION OF ULCERATIVE COLITIS:
PREBIOTICS AND DIETARY FIBER
I. Copaci1,*, G. Chiriac1
Center of Internal Medicine, FUNDENI CLINICAL INSTITUTE, Bucharest,
Romania
Contact E-mail Address: laurentiumicu2000@yahoo.com
1

INTRODUCTION: Butyrate enemas may be effective in the treatment of active


distal ulcerative colitis (UC). Colonic fermentation of Plantago Ovata seeds
(dietary fiber) yields butyrate. UC patients have an altered intestinal flora
which can be modified by administration of prebiotics such as fructo-oligosaccharides, and probiotics like bifidobacterium longum w11, which promote selective growth of saccharolytic bacteria with low inflammatory potential.
AIMS & METHODS: We conducted an open-label, parallel group, randomized
clinical trial. A total of 36 patients with ulcerative colitis who were in remission
for over 3 months (45C. A. I. Rachimilewitz) were randomized into 3 groups to
receive oral treatment with mesalamine (group A), Plantago Ovata (Colon help)
mesalamine (group B) and fructo-oligosaccharides/bifidobacterium longum
w11 mesalamine (group C). All patients were 18-65 years old. At day 0 and
weeks 12 and 24 we determined the clinical activity index (C. A. I.) and the
endoscopic index. Clinical safety was monitored using the Gastrointestinal
Symptom Rating Scale (GSRS) questionnaire every 4 weeks.
RESULTS: After 6 months, treatment failure was 35% in group A, 28% in
group B (p 0.02) and 30% in group C (p 0.05). Probability of continued
remission was similar (Mantel Cox test, p 0.76; Breslow test, p 0.52). Mean
times to treatment failure were 4.340.44, 4.570.76 and 4.620.81 months,
respectively for groups A, B and C. It was shown that patients with total colitis
as compared to those with left-sided colitis had an increased probability of
relapse during the 1 year follow-up. Patients of group B experienced more asymptomatic nights (90% vs 77% in group C vs 58% in group A, p 0.0011) during
the first 3 months. Fecal calprotectin was lower in group C vs A and B (p50.05).
CONCLUSION: Plantago Ovata seeds and the combination of fructo-oligosaccharides/bifidobacterium longum w11 maintain UC remission and increase the
response to mesalamine.
Disclosure of Interest: None declared

MSD and Abbvie., M. Arredondo: None declared, M. Chaparro Other: Dra. M


Chaparro has served as a speaker and has received research funding from MSD
and Abbvie, I. Canamares: None declared, E. Dauden: None declared, G.
Fernandez-Jimenez: None declared, V. Meca: None declared, A. Morell: None
declared, J. Aspa: None declared, L. Carmona: None declared, J. M. AlvaroGracia: None declared
P0889 CLINICAL BENEFIT OF ADALIMUMAB DOSE ADJUSTMENT
FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE
CROHNS DISEASE IN EXTEND
J.-F. Colombel1,*, P. Rutgeerts2, W.J. Sandborn3, D. Wolf4, W. Reinisch5,
G.Van Assche2, S. Eichner6, Q. Zhou6, J. Petersson6, A.M. Robinson6,
R.B. Thakkar6
1
Icahn School of Medicine at Mount Sinai, New York, United States, 2University
of Leuven, Leuven, Belgium, 3UCSD, La Jolla, 4Atlanta Gastroenterology
Associates, Atlanta, United States, 5McMaster University, Hamilton, Canada,
6
AbbVie Inc, North Chicago, United States
INTRODUCTION: Weekly dosing was shown to have a clinical benefit for
adalimumab (ADA)-treated patients with Crohns disease enrolled in the clinical
trial CHARM who had flares or lost response to every other week (EOW) ADA
dosing1. The clinical outcomes of dose escalation in patients enrolled in the
EXTEND2 trial are evaluated.
AIMS & METHODS: EXTEND was a 52-week double-blind (DB) trial in which
patients received open-label (OL) ADA 160/80 mg at weeks 0/2. At week 4,
patients were randomized to placebo or ADA 40 mg EOW. Patients with
flares/non-response could move to OL ADA 40 mg EOW beginning at week 8,
followed by escalation to 40 mg weekly (EW) for continued flare/non-response.
Week 52 clinical remission (CDAI5150), clinical response (decrease in CDAI 
70 from baseline), and mucosal healing (absence of mucosal ulceration) were
assessed in patients who moved to and remained on OL ADA EOW and in
those who moved to OL ADA EW. Endpoints are reported using non-responder
imputation (NRI) for patients with missing data and as observed for patients
remaining in the study at week 52. Logistic regression analysis was used to
determine predictors of moving to OL EW ADA.
RESULTS: In EXTEND, 42.2% (27/64) of patients randomized to DB ADA
moved to OL ADA, and 23.4% (15/64) escalated to EW dosing. The only significant predictor of dose escalation was week 4 non-response (odds ratio 24.2,
95% CI 1.6, 365.2, p 0.021). Week 52 outcomes for patients who completed the
study on OL ADA (EOW or EW) are shown in the table. Increased adverse event
rates were not observed with OL EW dosing.
Table. Week 52 efficacy in patients randomized to ADA who completed the
study on OL EOW or EW ADA dosing
NRI

P0888 DRUG SURVIVAL AND REASONS FOR DISCONTINUATION OF


ANTI-TNF THERAPY IN INFLAMMATORY BOWEL DISEASE (IBD)
IN CLINICAL PRACTICE
J.P. Gisbert1,2,*, M. Arredondo2,3, M. Chaparro1,2, I. Canamares2,4,
E. Dauden2,5, G. Fernandez-Jimenez2,3, V. Meca2,6, A. Morell2,4, J. Aspa2,7,
L. Carmona2,8, J.M. Alvaro-Gracia2,9
1
Gastroenterology Unit, Hospital de La Princesa, CIBERehd and IP, 2Biologic
Therapies Unit, 3Documentation Service, 4Pharmacy service, 5Dermatology
Service, 6Neurology Service, 7Medical Director, Hospital de La Princesa, 8Institute
for Musculoskeletal Health, 9Reumatology Service, Hospital de La Princesa,
Madrid, Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: Since its introduction, anti-TNF therapy has shown to be
effective for the treatment of IBD in several clinical trials. However, its long-term
effectiveness and reasons for discontinuation in clinical practice might be different from those observed in clinical trials
AIMS & METHODS: Aims: To evaluate the drug survival and reasons for
discontinuation of the first anti-TNF therapy in IBD patients in clinical practice.
Methods: IBD patients under anti-TNF therapy from 2000 to 2012 in our center
were included. Data regarding the first anti-TNF treatment were extracted from
clinical records fulfilled prospectively. Kaplan-Meier method was used to estimate the long-term drug survival of the treatment.
RESULTS: 160 IBD patients were included: 130 with Crohns disease (mean age
4214 years; 47% male) and 30 with ulcerative colitis (mean age 4517 years;
63% male). The distribution of first biologic in Crohns disease was 76 (58%)
adalimumab and 54 (42%) infliximab, while in ulcerative colitis it was 1 (3%)
adalimumab and 29 (97%) infliximab. Time to a probability of 50% discontinuation was 3.94 years in Crohns disease compared with 0.97 years in ulcerative
colitis (p50.001). The reasons for discontinuation of the drug, respectively in
Crohns disease and ulcerative colitis, were: intolerance (20% and 19%), lack of
response (30% and 24%), loss of response (22% and 19%), remission achievement (17% and 29%), and others (11% and 10%). The probability of maintaining (retention rate) the anti-TNF treatment in Crohns disease was 69% at 1 year,
59% at 2 years, 52% at 3 years, 50% at 4 years, 45% at 5 years, and 41% at 10
years. The corresponding figures for ulcerative colitis were 48% at 1 year, 41% at
2 years, 36% at 3 years, 31% at 4 years, and 15% at 5, 6 and 7 years
CONCLUSION: The probability of maintaining the first anti-TNF drug in
Crohns disease patients is around 50% after 5 years of treatment.
Discontinuation rate was even higher in ulcerative colitis, with only 15% of
patients maintaining anti-TNF therapy at 5 years. The most frequent reasons
for discontinuation of anti-TNF therapy were lack of response, loss of response,
remission achievement and intolerance
Disclosure of Interest: J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker,
a consultant and advisory member for, and has received research funding from

Remission
Response
Mucosal healing

Observed

OL EOW
n/N (%)

OL EW
n/N (%)

OL EOW
n/N (%)

OL EW
n/N (%)

3/12 (25.0)
6/12 (50.0)
1/12 (8.3)

3/15 (20.0)
6/15 (40.0)
2/15 (13.3)

3/6 (50.0)
6/6 (100)
1/7 (14.3)

3/9 (33.3)
6/9 (66.7)
2/7 (28.6)

CONCLUSION: Escalation to weekly ADA dosing demonstrated clinical benefit


in patients who met protocol criteria for dose escalation. No new safety risks
were observed with EW ADA dosing.
REFERENCES
1. Sandborn WJ, et al. Inflamm Bowel Dis 2011; 17: 141-151.
2. Rutgeerts P, et al. Gastroenterology 2012; 142: 1102-1111.
Disclosure of Interest: J.-F. Colombel Consultancy for: AbbVie, Bristol Meyers
Squibb, Ferring, Genentech, Giuliani SPA, Given Imaging, Merck & Co.,
Millenium Pharmaceuticals Inc., Pfizer Inc. Prometheus Laboratories, Sanofi,
Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma
(previously named Celltech Therapeutics, Ltd)., P. Rutgeerts Financial support
for research from: AbbVie, Centocor, Merck and UCB Pharma, Lecture fee(s)
from: AbbVie, Centocor, Merck and UCB Pharma, Consultancy for: AbbVie,
Bristol-Myers Squibb, Centocor, Merck, Millennium Pharmaceuticals Inc. (now
Takeda) and UCB Pharma, W. Sandborn Financial support for research from:
AbbVie, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen,
Millennium, Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire
Pharmaceuticals, and UCB Pharma., Lecture fee(s) from: AbbVie, BristolMyers Squibb, and Janssen, Consultancy for: AbbVie, ActoGeniX NV, AGI
Therapeutics, Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman,
Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic
Healthcare Limited, Aptalis, BioBalance Corporation, Boehringer-Ingelheim
Inc, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL,
Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies,
Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai
Medical Research Inc, Elan Pharmaceuticals, EnGene, Inc., Eli Lilly,
Enteromedics, Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion
Therapeutics, Inc., Funxional Therapeutics Limited, Genzyme Corporation,
Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human
Genome
Sciences,
Ironwood
Pharmaceuticals,
Janssen,
KaloBios
Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda
Pharmaceuticals, Merck Research Laboratories, MerckSerono, Merck & Co.,
Millennium, Nisshin Kyorin Pharmaceuticals Co., Ltd., Novo Nordisk A/S,
NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc.,
PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories,

A376
ProtAb Limited, Purgenesis Technologies, Inc., Receptos, Relypsa, Inc., Salient
Pharmaceuticals, Salix Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals,
Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L.
A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts
Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular
Biogenics Limited (VBL), Warner Chilcott UK Limited, D. Wolf Financial support for research from: AbbVie, Elan Pharmaceuticals, Given Imaging,
GlaxoSmithKline, Genentech, Janssen, Millennium Pharmaceutical, Pfizer,
Prometheus Laboratories, Receptos, Shire Pharmaceutical, Tsumura, and UCB
Pharma., Consultancy for: AbbVie, Elan Pharmaceuticals, Genentech, Given
Imaging, Janssen, Prometheus Laboratories, Salix Pharmaceuticals, UCB
Pharma, and Warner Chilcott. He has received lectures fees from AbbVie,
Janssen, Prometheus Laboratories, Santarus, Salix Pharmaceutical, Shire
Pharmaceutical, and UCB Pharma., W. Reinisch Consultancy for: AbbVie,
Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb,
Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Ferring,
Genentech, Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma,
Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation,
MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter &
Gamble,
Prometheus,
Robarts
Clinical
Trial,
Schering-Plough,
Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult,
Zyngenia, Austria and 4SC., G. Van Assche Financial support for research
from: AbbVie, Janssen Biologicals, MSD, Pfizer, Lecture fee(s) from: AbbVie,
Ferring, MSD, Janssen, UCB Pharma, Shire, Consultancy for: AbbVie, Biogen,
BMS, MSD, Janssen Biologicals, Novartis, S. Eichner Shareholder of: AbbVie,
Other: Employee: AbbVie, Q. Zhou Shareholder of: AbbVie, Other: Employee:
AbbVie, J. Petersson Shareholder of: AbbVie, Other: Employee: AbbVie, A.
Robinson Shareholder of: AbbVie, Other: Employee: AbbVie, R. Thakkar
Shareholder of: AbbVie, Other: Employee: AbbVie
P0890 CLINICAL
OUTCOMES
IN
CONTINUOUS
CLINICAL
RESPONDERS WITH MODERATELY TO SEVERELY ACTIVE
ULCERATIVE COLITIS: SUB-ANALYSES FROM THE PURSUIT-SC
MAINTENANCE STUDY
J. Colombel1,*, W. Reinisch2, P. Gibson3, W.J. Sandborn4, B.G. Feagan5,
C. Marano6, R. Strauss6, J. Johanns6, H. Zhang6, H. Weng7, R. Yao7,
D. Tarabar8, Z. Hebzda9, P. Rutgeerts10
1
Hopital Claude Huriez, Lille Cedex, France, 2Universitatsklinik fur Innere
Medizin III/McMaster University, Vienna/Hamilton, Austria, 3Alfred Hospital,
Melbourne, Australia, 4University of California San Diego, La Jolla, United
States, 5Robarts Research Institute, University of Western Ontario, London,
Canada, 6Janssen Research & Development, LLC., Spring House, 7Merck Sharp &
Dohme, Kenilworth, United States, 8Military Medical Academy, Belgrade, Serbia,
9
Klinika Chorob Wewnetrznych, Krakow, Poland, 10University Hospital,
Gathuisburg, Belgium
AIMS & METHODS: The objective was to evaluate long-term clinical outcomes
in patients with moderately to severely active UC who achieved complete continuous response (CCR) compared with patients who did not achieve CCR (nonCCR) through Wk54 of SC golimumab (GLM) maintenance therapy. During
PURSUIT-Maintenance, GLM induction responders (464 patients) were randomized to receive PBO, SC GLM 50mg, or SC GLM 100mg at baseline (Wk0) and
q4wks through Wk52. The primary endpoint was clinical response through Wk54
(CCR). Clinical remission, mucosal healing, corticosteroid use, and IBDQ outcomes and fecal markers at Wk54 among CCR versus non-CCR were assessed.
All sub-analyses are based on patients randomized at Wk0 of maintenance
(n 456).
RESULTS: On all of the selected endpoints evaluated, CCR patients had better
results when compared with non-CCR patients (Table). Among patients receiving corticosteroids at baseline, a greater proportion of CCR patients were not
receiving corticosteroids at Wk54 versus non-CCR patients. Greater proportions
of CCR patients were also in clinical remission versus non-CCR patients.
Additionally, mean decreases in fecal lactoferrin and fecal calprotectin at
Wk54 from Wk0 of maintenance were greater for CCR patients compared
with non-CCR patients. Data between the GLM groups were similar and thus
were pooled in the table.

United European Gastroenterology Journal 2(1S)


Table: Clinical outcomes based on continuous clinical response at Wk54 in the
PURSUIT-SC maintenance study*
Table to abstract P0890

Clinical endpoints
Randomized pts receiving concomitant steroids at Wk 0
(n)
Pts not receiving corticosteroids
at Wk54(%)
Remission: Randomized pts(n)
Pts in clinical remission at
Wk54(%)
Mucosal healing:Randomized
pts(n)
Pts with mucosal healing at
Wk54 (%)
IBDQ score:Randomized pts
(n)
Change from Wk0 through
Wk54 [mean(SD)]
Pts with IBDQ score 4170 at
Wk54 (%)

Non-CCR:
Non-CCR: Combined CCR:
GLM
PBO
PBO

CCR:
Combined
GLM

60

87

27

73

1.7

4.6

66.7

75.3

106
0.9

156
1.9

48
68.8

146
67.1

106

156

48

146

1.9

2.6

87.5

90.4

105

156

48

144

-38.9(32.1) -36.9(37.6) 10.6(18.2) 11.3(28.1)


18.1

24.4

81.2

75.0

CONCLUSION: These data continue to support that patients induced into clinical response who maintain a clinical response through Wk54 are more likely to
have better clinical outcomes.
Disclosure of Interest: J. Colombel Financial support for research from: Janssen
Research & Development, LLC, W. Reinisch Financial support for research
from: Janssen Research & Development, LLC, P. Gibson Financial support
for research from: Janssen Research & Development, LLC, W. Sandborn
Financial support for research from: Janssen Research & Development, LLC,
B. Feagan Financial support for research from: Janssen Research &
Development, LLC, C. Marano Other: Employee of Janssen Research &
Development, LLC, R. Strauss Other: Employee of Janssen Research &
Development, LLC, J. Johanns Other: Employee of Janssen Research &
Development, LLC, H. Zhang Other: Employee of Janssen Research &
Development, LLC, H. Weng Other: Employee of Merck Sharp & Dohme, R.
Yao Other: Employee of Merck Sharp & Dohme, D. Tarabar Financial support
for research from: Janssen Research & Development, LLC, Z. Hebzda Financial
support for research from: Janssen Research & Development, LLC, P. Rutgeerts
Financial support for research from: Janssen Research & Development, LLC
P0892 INTRA-ABDOMINAL ABSCESSES IN CROHNS
OUTCOMES FOLLOWING INFLIXIMAB THERAPY

DISEASE:

J. Ruel1,*, J.-F. Colombel2, B. Cohen2


1
Gastroenterology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke,
Canada, 2Gastroenterology, Icahn School of Medicine at Mount Sinai, New York,
United States
Contact E-mail Address: benjamin.cohen@mssm.edu
INTRODUCTION: Crohns disease (CD) may be complicated by a sealed-off
perforation that results in the development of an abscess typically located next to
adjacent loops of bowel. Traditional treatment has been antibiotics, surgical or
CT-guided drainage of drainable collections, bowel rest, and, ultimately, in some
patients, resection of the affected bowel segment. Most gastroenterologists avoid
immune suppression in this setting because of the potential for disseminated and
systemic infection. Data regarding use of anti-tumor necrosis factor (TNF) in this
situation are scarce. The aim of this study was to examine outcomes for patients
with CD who developed an abdominal abscess that was subsequently treated
with infliximab without initial drainage in order to evaluate its safety and efficacy
in a larger number of patients than previously reported.
AIMS & METHODS: We retrospectively reviewed the records of all CD patients
attending the Mount Sinai Medical Center in New York City, between 2000 and
2013, with an intra-abdominal abscess who were treated with infliximab in order
to evaluate its safety and efficacy.
RESULTS: There were 18 patients with CD complicated by an intra-abdominal
collection treated with antibiotics and infliximab at our center between 2000 and
2013. The median age was 25.5 (18-46) years and eleven patients were males.
Seventeen patients had ileal disease. Fourteen patients developed an intraabdominal abscess (size ranging from 1.1 cm to 7.9 cm) and four had a phlegmon
only. In addition to anti-TNF therapy, all patients were treated with broadspectrum antibiotics. No complications following infliximab therapy were
reported including sustained fever or sepsis. None required a surgical drainage
but four patients required abscess drainage by interventional radiology. Eight
patients underwent surgery within 6 months after initiating anti-TNF therapy.
CONCLUSION: Penetrating CD complicated by intra-abdominal abscess formation may be safely and effectively managed with a combination of antibiotics
and infliximab therapy without drainage. Prospective trials are required to confirm these findings.
Disclosure of Interest: J. Ruel: None declared, J.-F. Colombel Consultancy for:
Janssen and Abbvie, B. Cohen Lecture fee(s) from: Abbvie

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P0893 HIGH SERUM CRP PREDICTS FASTER CLEARANCE OF
INFLIXIMAB AND POOR OUTCOME IN MODERATE-SEVERE
ULCERATIVE COLITIS
J.F. Brandse1,*, G.R. van den Brink1, D.van der Kleij2, T. Rispens3, K. Bloem3,
Y. Ashruf1, J.M. Jansen4, M. Lowenberg1, C. Ponsioen1, R.A. Mathot5,
G.R. DHaens1
1
Department of Gastroenterology & Hepatology, Academic Medical Center,
2
Sanquin Diagnostic Services, 3Sanquin Research, Sanquin Laboratories,
4
Department of Gastroenterology & Hepatology, Onze Lieve Vrouwe Gasthuis,
5
Pharmacy, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: j.f.brandse@amc.uva.nl
INTRODUCTION: Insufficient serum concentrations have been suggested as a
cause of lack of response to infliximab (IFX) in Ulcerative Colitis (UC) and may
be associated with a high inflammatory load. Early pharmacokinetics (PK) of
IFX related to inflammatory markers and response to induction therapy have
been poorly studied.
AIMS & METHODS: We studied the PK of IFX induction therapy and markers/predictors for response in patients with moderate-to-severe UC (endoscopy
Mayo 2 or 3) in a multicenter prospective study. Serum IFX concentrations and
antibodies to IFX (Radioimmunoassay, Sanquin Laboratories, Amsterdam),
serum CRP and albumin and fecal samples (for calprotectin and IFX concentrations) were collected at 10 serial time points during the first 6 weeks of therapy.
Endoscopic response was defined as improvement by at least 1 Mayo point at
week 6-8.
RESULTS: Twenty patients were included, all but one receiving IFX according
to standard induction regime (5mg/kg at week 0.2,6). 11/19 patients showed
endoscopic improvement. The median IFX serum concentration at week 6 was
2.9 (0.01-5.8) ug/ml for endoscopic non-responders versus 8.1 (3.0-13.7) ug/ml for
responders (p 0.03). Serum IFX7ug/ml at week 6 was defined as a predictive
cut-off (OR:18.67, 95%CI 1.56-223.1, p 0.02) for endoscopic non-response.
The presence of antibodies to IFX at week 6 (n 4) was associated with a 2.93
fold increased clearance of the drug. Fecal IFX concentrations at day 1 were 4.1
(1.3-20.1) ug/ml in non-responders compared to 1.3 (0-5.8) ug/ml for responders
(P[GD1] 0.10). Median area under the curve (AUC), IFX concentration versus
time, was 1229 mg/L/day in the endoscopic non-responders compared to 1352
mg/L/day for the responders (p 0.65). Patients with a baseline CRP450mg/l
had a significantly smaller AUC than those below 50mg/l (578 vs. 1361 mg/L/
day, p 0.001), with IFX clearance 1.63 fold increased (P50.001, multivariate
analysis).
CONCLUSION: Ulcerative Colitis patients with a high baseline serum CRP
have increased clearance and lower serum IFX concentrations during IFX induction therapy, predicting poor outcome as early as week 6. These patients can be
selected for more intensive induction regimens.
Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie, Takeda, G.
van den Brink Financial support for research from: Abbott laboratories, Crucell
and Ferring Pharmaceuticals, Lecture fee(s) from: Abbott laboratories, Merck
Sharp & Dohme and Ferring Pharmaceuticals, Consultancy for: Abbott laboratories, D. van der Kleij: None declared, T. Rispens: None declared, K. Bloem:
None declared, Y. Ashruf: None declared, J. Jansen Lecture fee(s) from: MSD en
Abbott, Consultancy for: Ferring Pharmaceuticals, Schering Plough, Abbvie,
and Pfizer, M. Lowenberg Lecture fee(s) from: Abbott, Dr. Falk, Ferring,
MSD and Tramedico, C. Ponsioen Financial support for research from:
Schering Plough, Falk Pharma, Tramedico, Abbott Inc., and Glaxo Smith
Klin, Lecture fee(s) from: Schering Plough, Falk Pharma, Tramedico, Abbott
Inc., and Glaxo Smith Kline, Consultancy for: Schering Plough, Falk Pharma,
Tramedico, Abbott Inc., and Glaxo Smith Kline, R. Mathot: None declared, G.
DHaens Financial support for research from: Abbott Inc, Jansen Biologics,
Given Imaging, MSD, DrFalk Pharma, Photopill, Lecture fee(s) from: Abbott
Inc, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire, Consultancy for:
Abbott Laboratories, Actogenix, Centocor, Cosmo, Engene, Ferring
Pharmaceuticals,
GlaxoSmithKline,
Jansen
Biologics,
Millenium
Pharmaceuticals, MSD, Novonordisk, PDL Biopharma, Pfizer, SetPoint,
Shire, Takeda, Teva, UCB
P0894 PULMONARY INVOLVEMENT AND THE EFFECT OF TNFALPHA-INHIBITORS ON PULMONARY FUNCTION IN IBDPATIENTS
J. Bethge1,*, M. Ellrichmann1, C. Conrad1, S. Nikolaus1, R. Noth2, D. Schuldt1,
S. Zeissig1, S. Schreiber1,2
1
Medical Department I, Gastroenterology, 2Medical Department I, Pulmonology,
University Medical Center, Schleswig Holstein, Campus Kiel, Kiel, Germany
Contact E-mail Address: jbethge@1med.uni-kiel.de
INTRODUCTION: Extraintestinal manifestations are a frequent complication
in patients with Inflammatory-Bowel-Disease (IBD). Pulmonary involvement is
commonly recognized but describe as a rare manifestation. Of note, increased
mortality from respiratory diseases was observed in patients with ulcerative colitis. This may be due to an overlap between genetic causes in IBD and various
chronic inflammatory lung diseases. Therefore, pulmonary involvement may be
overlooked in IBD patients.
AIMS & METHODS: The aim of this prospective study was to assess pulmonary-function-abnormalities in IBD patients in comparison to healthy controls
and investigate the effect of TNF-a-inhibitors on pulmonary-function-test
(PFT). 90 consecutive patients with IBD (51 Crohns disease (CD), 39 UC)
were included. 47 patients were in remission and 43 had active disease. Out of
these, 25 patients were seen for initiating anti-TNF therapy. 40 matched healthy
controls were included. Pulmonary function was evaluated using the Medical
Research Council (MRC) dyspnea index and a standardized spirometry. IBD

activity was assessed using Harvey-Bradshaw index for CD and partial-Mayoscore for UC. In patients treated with anti-TNF all parameters were reevaluated
6 weeks later. Data are presented as Median/25thpercentile/75thpercentile.
RESULTS: Patients with active IBD showed significantly reduced parameters in
their PFT. Tiffeneau index-values (FEV1%) were significantly reduced in IBD
patients with active disease (78,9/73,7/85,1) compared to controls (86/81,8/88,3;
p 0.001) and IBD patients in remission (84,5/81,2/89,4; p 0.0002). No difference was found between IBD patients in remission and controls (p40.05).
Parameters of peripheral airway obstruction (MEF 75-25%) showed comparable
changes (MEF75: IBDactive vs. controls p 0.01; IBDactive vs. IBDremission
p 0.002). Clinically significant peripheral airway obstruction was seen in
19.1%, obstructive dysfunction in 12.8% and restrictive dysfunction in 2.1%
of IBD patients with an active disease (IBDremission: 4.6%/2.3%/6.9%;
Control: 5%/0%/0%). Patients treated with anti-TNF showed a significant
improvement of obstructive parameters (p 0.003 FEV1%) compared to baseline levels.
CONCLUSION: IBD patients with active disease showed significant abnormalities in their obstructive PFT-parameters in comparison to healthy controls and
IBD patients in remission. Anti-inflammatory therapy with anti-TNF improves
obstructive abnormalities. Pulmonary obstruction and chronic broncho-pulmonary inflammation might be the cause of reduced exercise levels during active
disease and may be overlooked in the majority of patients. Further studies are
necessary to determine whether chronic obstruction should be treated and
whether it contributes to the observed mortality from lung problems in IBD.
Disclosure of Interest: None declared
P0895 THE EFFECT OF ANTI-TNF TREATMENT ON FISTULAS IN
CROHNS DISEASE: A SYSTEMATIC REVIEW AND METAANALYSIS
J. De Groof1,*, S. Sahami2, C. Lucas3, C. Ponsioen4, W. Bemelman2, C. Buskens2
1
Department of Surgery and Gastroenterology & Hepatology, 2Department of
Surgery, 3Department of Epidemiology, Biostatistics & Bioinformatics,
4
Department of Gastroenterology & Hepatology, Academic Medical Centre,
Amsterdam, Netherlands
Contact E-mail Address: e.j.degroof@amc.uva.nl
INTRODUCTION: Peri-anal fistulas are an incapacitating complication of
Crohns disease affecting approximately 25% of patients in population-based
estimates. Since the introduction of anti-TNF agents (infliximab and adalimumab), the treatment for Crohns fistulas has changed from almost exclusively
surgical to placing a much larger emphasis on medical therapy.
AIMS & METHODS: The purpose of this systematic review is to provide an
overview of the literature evaluating the success rate of perianal fistula treatment
with anti-TNF. PubMed, Embase and Biosis were searched. Randomized controlled trials on the effect of anti-TNF treatment on Crohns perianal fistulas
were included. Studies assessing perianal fistulas in children, rectovaginal fistulas
and costs were excluded. The primary outcome of interest was complete fistula
closure with partial closure as a secondary outcome parameter. A subgroup
analysis for complete fistula closure was performed based on studies with a
follow-up longer than 4 weeks.
RESULTS: Four studies comparing placebo with anti-TNF therapy regimens
were included in the meta-analysis: one study on infliximab (ACCENT study)
and three studies analysing adalimumab (CLASSIC, CHARM and GAIN trial).
All patients with fistulising disease were included in the trials (peri-anal, enterocutaneous and entero-enteral fistulas). In total, 179 patients were treated with
anti-TNF medication whereas 109 patients received placebo. All studies assessed
complete closures rates and three studies reported partial closure rates. The mean
follow-up time was 13 weeks (range 4-26). In the anti-TNF group, 54 of 179
(30%) patients responded to treatment with complete fistula closure, whereas
complete healing was seen in 13 of 109 (12%) patients in the placebo group.
Partial fistula closure was seen in 48 of 109 (44%) patients in the anti-TNF
treatment group and in 15 of 62 (24%) patients in the placebo group. There
was no significant difference in complete or partial closure rates between the
two groups (RD 0.12, -0.06-0.30, I2 74% and 0.09, 95% CI -0.23-0.41, I2 78%,
respectively). The subgroup analysis showed a significant advantage for complete
fistula closure with anti-TNF in the two trials with follow-up longer than 4 weeks
(ACCENT: 46% versus 13%, p 0.003 and CHARM: 30% versus 13%,
p 0.03) when compared to the placebo group.
CONCLUSION: Meta-analysis of 4 randomized controlled trials did not show a
significant advantage for (partial) fistula closure with anti-TNF treatment as
compared to placebo. However, subgroup analysis showed an advantage of
anti-TNF treatment on complete fistula closure rates in the two trials with a
follow-up longer than 4 weeks.
Disclosure of Interest: None declared
P0896 SAFETY AND EFFICACY OF BUDESONIDE MMX
REMISSION OF ULCERATIVE COLITIS: A META ANALYSIS

n
w
a
r
d
h
t
i
W
1,*

IN

J.A. D. M. Jalandoon , I.H. Y. cua


Gastroenterology, Institute of digestive and liver disease, St. lukes medical centre,
gastroenterology, st lukes medical center, quezon city, Philippines
Contact E-mail Address: doyangelie@yahoo.com
1

INTRODUCTION: Significance.
Budesonide MMX, a novel drug developed for the treatment of ulcerative colitis
using multi-matrix system. The effects on remission of disease would help to form
recommendations for efficacy and safety profile. Most of these trials conducted
have relatively small size, limited data and a meta-analysis for this drug could
have stronger conclusion.

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United European Gastroenterology Journal 2(1S)

AIMS & METHODS: Manual search through MEDLINE & PUBMED using
ulcerative colitis and Budesonide MMX were merged yielding 9 studies. Six
studies were shown which was limited to human. Excluded were two reviews and
a comment. Three multicenter, randomized, placebo-controlled trials were
included & Cochrane Review Manager Software Version 5 was used.
RESULTS: There was a significant remission of symptoms in patients using the
combined Budesonide MMX 9 & 6 mg with a p-value of 0.02. Sensitivity analysis
using Budesonide MMX 9 mg is effective in the remission compared to
Budesonide 6 mg alone and placebo with p-value 0.0005 at 95% confidence
interval. Adverse effects showed no significant difference between Budesonide
MMX group and the placebo group with a p value of 0.71.
CONCLUSION: Budesonide MMX, on clinical improvement, is beneficial in
assessing the response to treatment in remission of symptoms. The adverse effects
have no significant difference with placebo thus further study is needed to assess
the safety profile of the drug.
REFERENCES
DHaens GR, et al. Clinical trial: preliminary efficacy and safety study of a new
budesonide-MMX 9 mg extended-release tablets in patients with active left-sided
ulcerative colitis. J Crohns Colitis 2010; 4: 153-160.
Sandborn WJ, et al. Once-daily budesonide MMX extended-release tablets
induce remission in patients with mild to moderate ulcerative colitis: results
from the CORE I study. Gastroenterology 2012; 143: 1218-1226.
Travis SPL, et al. Once-daily budesonide MMX in active, mild-to-moderate
ulcerative colitis: results from the randomised CORE II study. Gut Br J Med
2013; 0: 1-9.
Sandborn WJ, et al. MMX multi matrix system mesalazine for the induction of
remission in patients with mild-to-moderate ulcerative colitis: a combined analysis of two randomized, double-blind, placebo-controlled trials. Aliment
Pharmacol Ther 2007; 26: 205215.
Disclosure of Interest: None declared

n
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P0897 PHLEGMONOUS CROHNS DISEASE:


OUTCOMES AT A TERTIARY CENTRE

REVIEW

OF

K. V. Patel1,*, N. Griffin2, R. Goel1, E. Westcott3, A.B. Williams3,


A. Darakhshan3, S.H. Anderson1, P.M. Irving1, J.D. Sanderson1
1
Gastroenterology, 2Radiology, 3Colorectal Surgery, Guys and St Thomas NHS
Foundation Trust, London, United Kingdom
Contact E-mail Address: kamal0079@hotmail.com
INTRODUCTION: Penetrating Crohns disease (CD) can be complicated by
sealed-off perforation resulting in the development of an inFammatory mass or
phlegmon. This typically involves the mesentery and adjacent bowel loops, and
can be further complicated by an abscess or a Estula. The optimal management
strategy and long-term outcomes of phlegmons in CD remains unknown.
AIMS & METHODS: Patients with CD and confirmed phlegmons on MRI/CT
between January 2009 and December 2012 were identified retrospectively.
Radiographic evidence of co-existing strictures, abscess, fistula and/or perforation was recorded. Medical records were reviewed and demographic data, CD
phenotype, CD therapy prior to and following presentation, requirement for
abscess drainage or surgical resection, and clinical status at most recent followup were recorded. Clinical remission was defined as a Harvey -Bradshaw index of
55. Repeat imaging was evaluated to assess phlegmon resolution.
RESULTS: 13 patients (7 male) were identified with median follow up of 40
months (range 33-61 months). 3 had ileal and 10 had ileocolonic CD. 11 had
co-existing strictures, 5 had co-existing abscess, and 4 had co-existing enteroenteric fistula. 4 patients were receiving a thiopurine at presentation with phlegmon.
12 patients reported significant abdominal pain with 8 requiring admission. In 4
of these, imaging studies confirmed perforation. 2 patients required short-term
parenteral nutrition and 6 were managed with exclusive liquid diet.
7 patients were treated primarily with medical management (2 with prolonged
courses of antibiotics, 5 with thiopurine and corticosteroids, and subsequently 2
escalated to an anti-TNF agent) and this led to phlegmon resolution in 4 patients,
and clinical remission in 3 patients. 2 patients have subsequently required surgery, and 2 persist with low grade obstructive symptoms treated conservatively.
6 patients were managed with primary surgery. All received a thiopurine as postoperative prophylaxis, of whom 3 escalated to an anti-TNF agent for significant
post-operative recurrence. Repeat surgical resection or abscess drainage was not
required subsequently.
2 of 4 patients presenting with perforation and phlegmon at presentation were
treated surgically, 2 of 4 patients with enteroenteric fistula and phlegmon at
presentation were treated surgically, and 3 of 5 patients with abscess and phlegmon at presentation were treated surgically. All 4 patients on thiopurine at
presentation required surgery.
CONCLUSION: Phlegmonous disease remains challenging to treat. Medical and
surgical management are both viable options, however phlegmon resolution was
more likely in the surgically treated group. Medically treated patients remain at
risk of need for future surgery. Surgically treated patients require aggressive
medical treatment post-operatively, to limit recurrence of CD.
Disclosure of Interest: None declared
P0898 COMBINED USE OF AZATHIOPRINE/6-MERCAPTOPURINE
ARE ASSOCIATED WITH DECREASED RISK OF ANTI-TNF
INDUCED SKIN LESIONS
K.-J. Kim1,*, J.S. Soe1, S. Hyun1
1
Gastroenterology, Asan Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: capsulendos@gmail.com
INTRODUCTION: Anti-tumor necrosis factors (anti-TNF) agents are given for
treating patients with moderate to severe active inflammatory bowel disease

(IBD). Among various adverse events during anti-TNF therapy, skin lesions
such as psoriasis or eczema could be a reason for discontinuation of anti-TNF
therapy.
AIMS & METHODS: We aimed to identify the risk factors for skin lesion
occurrence and compared the cumulative incidence of skin lesions in relation
to concomitant use of azathioprine/6-mercaptopurine during being treated with
anti-TNF agents in IBD patients. Methods: Between June 2002 and July 2013,
500 patients (404 Crohns disease and 96 ulcerative colitis) were treated with antiTNF at Asan Medical Center. Among them, new skin lesions occurred in 47 IBD
patients at the department of dermatology. We retrospectively reviewed the
medical records. To identify risk factors for skin lesions, we compared 47 patients
with skin lesions to 443 patients without any skin disease or history.
RESULTS: The incidence of skin lesions during anti TNF therapy was 9.4%.
The skin lesions were listed in Table 1. Face was the most common involved site
(n 21, 45%), followed by trunk (n 18, 38%) and upper extremities (n 18,
38%). Thirty three (70%) patients were treated with topical steroids with or
without antihistamine and showed good response. Four subjects (9%) discontinued anti-TNF because of eczematiform (n 2), psoriasiform (n 1), linear
IgA dermatosis (n 1). On univariate analysis, skin lesion occurred more in
female (HR: 1.794, 95% CI: 1.011-3.181, p 0.046) than in male. Also, combined
use of azathioprine/6-mecaptopurine was associated with decreased risk of the
occurrence of skin lesions (HR: 0.452, 95% CI: 0.251-0.814, p 0.008). However,
only combined use of azathioprine/6-mercaptopurine (HR: 0.437, 95% CI: 0.2420.790, p 0.006) decreased the risk of occurrence for skin lesions on multivariate
analysis. Thus, we compared the cumulative incidence of skin lesions according
to the use of azathioprine/6-mercaptopurine. Combined use of azathioprine/6mercaptopurine at the time of starting anti-TNF agents tended to be lower
cumulative incidence of skin lesions (p 0.009 by log rank test) during followup period.
Multivariate analysis of factors associated with skin lesion occurred during treatment of anti-TNF agents in patients with inflammatory bowel disease
Variables
Sex
Age
Concomitant use with IMM
(azathioprine / 6mecaptopurine)

IBD group

HR
Male
Female
No concomitant use

95% CI

p-value

1
1.741 0.978-3.105 0.059
0.129
1
0.941-1.008

Continue to concomitant
use during follow-up
period

0.441 0.215-0.905 0.025

Stop IMM during followup period


CD
UC

0.433 0.214-0.879 0.020


1
0.672 0.230-1.961 0.467

HR, hazard ratio; CI, confidence interval; IMM, immunomodulator; IBD,


inflammatory bowel disease
CONCLUSION: Combined use of azathioprine/6-mercaptopurine may reduce
the occurrence of skin lesions on anti-TNF therapy at the time of starting antiTNF agents.
Disclosure of Interest: None declared
P0899 COSTS DRUG SAVINGS USING A TEST-BASED STRATEGY
VERSUS AN EMPIRIC DOSE ESCALATION IN PATIENTS WITH
CROHNS DISEASE LOOSING RESPONSE TO ANTI-TNF THERAPY
X. Roblin1, M. Lamure2, A. Attar3, B. Savarieau4, P. brunel1, G. Duru5,
L. Peyrin Biroulet6,*
1
university hospital, saint etienne, 2university hospital, Lyon, 3hopital beaujon,
4
Nukleus, Paris, 5universite claude bernard, Lyon, 6university hospital, Nancy,
France
Contact E-mail Address: xavier.roblin@chu-st-etienne.fr
INTRODUCTION: Pharmacokinetics of anti-TNF therapy is increasingly used
to treat inflammatory bowel disease (IBD). Whether this approach is associated
with significant cost savings beyond one year in a large cohort of patients with
IBD has yet to be determined (1,2).
AIMS & METHODS: We compared two cohorts of patients with Crohns disease
treated with anti-TNF therapy (infliximab and then adalimumab in case of infliximab failure) and presenting loss of response. The first cohort followed a process
management based on current practice, with drug optimization (increasing dose
and/or shortening the interval) not taking into account pharmacokinetics of antiTNF. In the second cohort, results of trough levels and antibodies against anti
TNF were integrated when patient was not responding for the first time to an anti
TNF agent. We used a selected mathematical model to describe the trajectories of
Crohns disease patients in the management of their disease based on a discrete
event system. This allows tracking over a given period (1, 3 or 5 years) a double
cohort of patients (10.000 patients) who move randomly and asynchronously from
one state to another while keeping the whole information on their entire trajectory.
Both cohorts were modeled by a state diagram parameters where transition probabilities from one state to another are derived from literature data. A stochastic
sensitivity analysis on the transition probabilities was conducted in order to assess
the stability of results. In the second analysis, we used the cost of an Elisa test from
Theradiag (France, 100 euros) and no other indirect costs were included in this test
based strategy. The costs of anti TNF therapy integrated in this model were
reported by the French healthcare system.

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United European Gastroenterology Journal 2(1S)


RESULTS: There was a dramatic decrease in overall costs within the cohort of
Crohns disease patients benefiting from a test-based strategy (table 1)

One year
Three years
Five years

Decrease in total
costs (n 10.000)

Percentage of
decrease in
direct costs

Decrease in
costs per patient

23 847 619 E
88 588 892 E
131 300 293 E

14.1%
22.4%
24.6%

2 385 E
8 859 E
13 130 E

For this simulation, the mean decrease in costs was similar when testing a population of 3 000 or 10 000 patients. At 5 years the mean decreased costs were 12
899 (95% CI:11820 - 13977) for 3 000 patients and 13 130 euros (95% CI:12535 13725) for 10 000 patients. After a stochastic sensitivity analysis (30 simulations
with random choice of transition probabilities and a bootstrap analysis), these
results were comparable with a decreased costs at 5 years for each patient using
tests with a 95CI [13 251,74 E - 13 565,05 E]. The impact of the direct cost of test
is not significant and our results were similar using cost of test of 2.000 euros.
CONCLUSION: A test-based strategy is associated with major cost savings
among Crohns disease patients treated with anti-TNF strategy. These findings
should be taken into account to guide decision making in clinical practice and
also by French healthcare system.
REFERENCES
Velayos T, et al. Clinical Gastroenterol Hepatol 2013; 11: 654-666.
Steenholdt C, et al. Gut in press.
Disclosure of Interest: X. Roblin Lecture fee(s) from: Theradiag, MSD, Abbvie,
M. Lamure: None declared, A. Attar: None declared, B. Savarieau: None
declared, P. brunel: None declared, G. Duru: None declared, L. Peyrin
Biroulet Financial support for research from: MSD, Lecture fee(s) from: Abbvie
P0900 LONG-TERM OUTCOME IN PATIENTS WITH CHRONIC
ACTIVE ULCERATIVE COLITIS STARTED ON INFLIXIMAB: A
RETROSPECTIVE SWEDISH MULTICENTER STUDY
L. Angelison1,*, S. Almer2, A. Bajor3, J. Bjork2, M. Eberhardsson2, A. Eriksson3,
O. Grip4, P. Hammarlund5, U. Hindorf4, P. Karling6, M. Thorn7, J. Torp8,
E. Hertervig4
1
Department of Medicine, Helsingborg Hospital, Helsingborg, 2Department of
Gastroenterology, Stockholm University Hospital, Stockholm, 3Department of
Gastroenterology, Sahlgrenska University Hospital, Gothenburg, 4Department of
Gastroenterology, Skane university Hospital, Lund/Malmo, 5Department of
Medicine, Angelholm Hospital, Angelholm, 6Department of Gastroenterology,
Umea University Hospital, Umea, 7Department of Gastroenterology, Uppsala
University Hospital, Uppsala, 8Department of Medicine, Kristianstad Hospital,
Kristianstad, Sweden
Contact E-mail Address: leif.angelison@skane.se
INTRODUCTION: Infliximab has been shown to be effective in acute severe
ulcerative colitis (UC) reducing the risk of colectomy. The ACT studies proved
efficacy for IFX in patients with a more chronic type of UC, However, long-term
data on clinical outcome of anti-TNF therapy are scarce. We assessed long-term
outcome in patients with chronic UC started on IFX.
AIMS & METHODS: METHODS: Retrospective data capture from local registries at 9 Swedish IBD centers from November 2004 to December 2011. Inclusion
criteria were: a) IFX treatment on an ambulatory basis. b) age 18 years, c) 8
weeks or more on continuous steroid use or more than 12 weeks during the last 6
months, d) steroid intolerance, e) insufficient response to, or intolerance to thiopurine therapy. Patients were eligible if followed at least 12 months or until
colectomy.
RESULTS: 243 patients (145 males, 98 females) were included; median age 26.3
years (8-71.7) at diagnosis and a median disease duration of 5.0 years (0.2-39.5
years). 114/243 patients (47%) were on steroids and 116/243 (48%) were on
concomitant thiopurines, 25/243 (10%) started a thiopurine together with IFX
at inclusion and 90/243 (37%) patients had a previous thiopurine exposure.
Median follow-up was 3.3 years (0.1 8.9 years) during which a median of 6
(1-41) infusions were given. At 12 months 114/243 (46.9%) patients were in
steroid-free remission and 46/243 (18.9%) had a steroid-free response. Lack of
response was noted in 39/243 (16%) and 32/243 (13.2%) underwent colectomy.
The corresponding figures at a median follow-up of 3.3 years were steroid-free
remission: 114/243 (46.9%), steroid-free response 31/243 (12.8%), no response
14/243 (5.8%) while 75/243 (30.9%) had undergone colectomy. Of non-responders at 1 year, 21/39 (53.8%) had a colectomy during follow-up compared to 22/
172 (13%) patients with response or remission at 12 months. At last follow-up, 44
patients were on IFX maintenance treatment with a median of 24 (11-54) infusions. The remaining 199 patients had a first course of IFX treatment with a
median of 4 (1-41) infusions, 41 patients had a second course with a median of 5
(1-29) infusions, 9 patients a third course with a median of 5 (1-14) infusions and
one patient a fourth course with 4 infusions. The main reasons for stopping IFX
at the first course was remission in 32%, loss of response 28%, non-response
18% and adverse events 10%. Overall 62 (25,5%) patients were switched to
adalimumab.
CONCLUSION: Anti-TNF is an efficacious long-term treatment in chronic
active UC with 47% of patients in steroid-free remission at 12 months and
sustained at 3.3 years. 66% had at least a clinically significant steroid-free
response at 12 months with a slight decrease to 60% at 3.3 years. In contrast,
non-response at 12 months was associated with a high risk of subsequent
colectomy.
Disclosure of Interest: None declared

P0901 INFLIXIMAB POPULATION PHARMACOKINETIC MODELLING


IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE:
ESTIMATION OF INDIVIDUAL PHARMACOKINETIC
PARAMETERS AND TROUGH LEVELS PREDICTION
L. Rodr guez-Alonso1,*, E. Santacana2, N. Padulles2, H. Colom3, A. Padulles2,
C. Arajol1, S. Cobo2, A. Ruiz1, F. Rodr guez1, J. Bas4, J. Climent4,
F. Morandeira4, J. Guardiola1
1
Gastroenterology, 2Pharmacy, Hospital Universitari Bellvitge. Idibell,
3
Pharmacokinetics, School of Pharmacy (Universitat de Barcelona),
4
Immunology, Hospital Universitari Bellvitge. Idibell, Barcelona, Spain
Contact E-mail Address: eugenia.santacana@bellvitgehospital.cat
INTRODUCTION: Infliximab (IFX) trough levels (TLI) vary greatly between
inflammatory bowel disease (IBD) patients. This variability is relevant because
there is a relationship between IFX concentration and clinical response.
AIMS & METHODS: Main objective: estimate individual pharmacokinetic
parameters and predict trough IFX levels. Secondary objective: evaluate the
association between IFX exposure and covariates that could modify trough
levels.
(a) Observational and prospective study of patients on IFX treatment from July
2013 to March 2014. TLI and antibodies toward infliximab (ATI) were measured
by ELISA at steady-state. Variables recorded: demographic, disease location Creactive protein levels (CRP), serum albumin concentrations (SAC), immunomodulatory treatment (IMM) and smoking. Individual pharmacokinetic parameters
were estimated and TLI were predicted using population PK modelling
(Nonmem 7.2).
RESULTS: 55 patients (49% women) were included. 93 TLI and ATI were
measured. Mean age: 43 yr (18-75); weight: 74 kg (IC95%: 71-77.5). Diagnose:
58.5% CD and 41.5% UC. 70 % received IMM. 27% patients were under
intensified IFX doses. Mean CRP: 6.45 mg/L (IC95%: 4.56-8.35), mean SAC:
4.70 g/dL (IC95% 2.55-6.84).
Mean TLI: 3.34 mg/L (CD: 3.62. UC: 2.49) (IC95%:2.66-4.02). TLI: 53: 56 %
and 3-7: 31.2%. ATI status: 4.3% of patients tested positive. All patients who
developed ATI had undetectable trough levels. 68.5% of patients with trough
levels53 were in remission. Mean estimated peak levels: 114.35 mg/L (IC95%:
107.37-121.305); mean estimated AUC: 27105.77 mg/h/L (IC95%: 2483529376.54).
Fasanmade et al (2011) population PK model for CD was used in both CD and
UC patients. Mean predicted TLI: 3.1 mg/L (IC 95%: 2.49-3.69). Bias 5.55%
(IC95 %: -7.98-(-3.129)) and precision 10.4% (IC95 %: 8.85-11.95). Fasanmade
et al (2009) population PK model for UC was not precise enough.
Individual estimated PK parameters (mean): central clearance (Cl) 5.65 ml/kg/
day (IC95%: 5.13-6.16), volume of distribution (central) (Vd) 50.59 ml/kg
(IC95%: 49.97-51.21), half-life (t1/2): 11.7 days (IC95%: 10.7 -12.7). Population
PK parameters: Cl 5.42 ml/kg/day, Vd 52.4 ml/kg. Difference between individual
and population PK parameters: 4% in Cl and 3.4% in Vd. Comparison of
exposures achieved showed that patients with positive ATI, SAC5 3.9 g/dL,
non receiving IMM and smokers had significant lower trough IFX levels,
higher Cl and lower t1/2. Patients with PCR46 mg/L and ileo-colonic CD had
lower IFX levels.
CONCLUSION: High interindividual variability in IFX PK and trough levels
exists in IBD patients. The influence of IMM, SAC, smoking and inflammation
on infliximab clearance suggests that individual adjustment of infliximab doses
according to disease activity may be useful in IBD.
REFERENCES
Fasanmade AA, Adedokun OJ, Blank M, et al. Pharmacokinetic properties of
infliximab in children and adults with Crohns disesase: a retrospective analysis
of data from 2 phase III clinical trials. Clin Ther 2011; 33: 946-964.
Disclosure of Interest: None declared
P0902 MESENCHYMAL STEM CELL TREATMENT DOES
INCREASE COLITIS-ASSOCIATED COLON CANCER RISK

NOT

L.R. Lopetuso1,*, F. Scaldaferri1, V. Petito1, A. Puglisi1, S. Vetrano2,


M.E. Caristo3, V. Arena4, V. Cufino4, A. Sgambato4, A. Gasbarrini1
1
INTERNAL MEDICINE, GASTROENTEROLOGY DIVISION, CATHOLIC
UNIVERSITY OF ROME, Rome, 2Division of Gastroenterology, Humanitas
Clinical and Research Center, Rozzano, Milan, 3Experimental Center,
CATHOLIC UNIVERSITY OF ROME, 4Pathology, CATHOLIC
UNIVERSITY OF ROME, Rome, Italy, Rome, Italy
Contact E-mail Address: lopetusoloris@libero.it
INTRODUCTION: Mesenchymal stem cells (MSCs) are potent immune regulators, proposed for local and systemic use in human IBD. Recent studies reported
that MSCs can promote tumorigenesis, warning their use in clinical condition
associated to increased cancer risk, such as IBD.
AIMS & METHODS: To evaluate the cancer risk associated to the therapeutic
effect of MSCs in murine model of colon cancer associated to chronic colitis.
MSCs were isolated from adipose tissue of C57BL/6 mice, and analyzed for
MSCs markers and for adipocyte and osteogenic differentiation. An MTT
assay was used to explore the direct effects of MSCs on tumor intestinal epithelial
cells proliferation and vitality. CT26 cells were incubated with TNF-a for 48 h
and then exposed to the surnatant of TNF-alfa pre- treated AMSC. C57BL/6
mice were injected intraperitoneally with azoxymethane (AOM) and exposed to 3
weekly cycles of 2.5% DSS.1 million of MSCs were injected intra-peritoneally at
day 3 of each DSS cycle, control (CT) mice received saline. Body weight, occult
blood test and stool consistency were used to calculate the Disease Activity Index
(DAI). Mice were sacrificed at week 10 and colon was analyzed macroscopically
and microscopically for number of cancer and degree of inflammation. Nude
mice were subcutaneously engrafted respectively with murine (CT26) or human

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United European Gastroenterology Journal 2(1S)

(HCT116) tumor cells lines alone or in combination with MSCs to evaluate their
role in tumor cell growth. CT nude mice received MSCs alone.
RESULTS: MSCs differentiated into adipocytes and osteocytes, and expressed
low levels of CD31, CD34, LIN and cKIT markers, and highlevels of SCA-1,
CD44 and CD106. MSCs proliferation was increased when stimulated with TNF.
Their surnatant leaded to a not significant reduction of CT26 growth. MSCs
injection significantly reduced DAI in treated mice vs. CT. MSCs treated mice
showed lower body weight loss and better survival rate. Treated mice had a not
significant reduced rate of colon cancer development vs. CT. In nude mice, there
was no significant difference in tumor size between groups. No lesions were
found in CT mice.
CONCLUSION: MSCs did not increase cancer risk in this colitis model and did
not affect the progression of pre-existing tumor lesions. MSCs exerted an
immune-modulatory effect in vivo, by decreasing the severity of colitis in
mouse, suggesting that their anti-inflammatory effects may contra-balance
their pro-carcinogenetic potential, even in pre-cancer condition such as chronic
colitis. Further analyses are required to define mechanisms of action underlying
these findings.
Disclosure of Interest: None declared
P0903 INCREASED FREQUENCY OF ENDOSCOPIC MUCOSAL
HEALING AND REDUCED INTESTINAL RESECTION IN
PATIENTS WITH SEVERE IBD BY LONGTERM AZATHIOPRINE
THERAPY, BUT NEGATIVELY AFFECTED BY MALE GENDER
M. Basaranoglu1, M. Yuksel1,*, M. Kaplan1, N. Suna1, A.E. Demirbag1,
O. Coskun1, Y. Akpinar1, M. Yalinkilic1, Y. Ozin1, F. Saygili1, E. Kayacetin1
1
Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey
Contact E-mail Address: metin_basaranoglu@yahoo.com
INTRODUCTION: Currently, safety and economic issues have increasingly
raised concerns about the long term use of biologics as maintenance therapies.
AIMS & METHODS: To evaluate the role of azathioprine (AZA) on mucosal
healing in patients with inflammatory bowel disease (IBD). Two thousand seven
hundred patients with IBD were evaluated from January 1995 to April 2014. The
searching criteria were as follows: (1) endoscopic records before the AZA and
during the AZA therapy; (2) AZA na ve patients with severe IBD. The data
included patients and disease demographics and the efEcacy of AZA. Patients
with a minimum duration of 4 months of AZA were included in this study.
RESULTS: A total of 120 patients treated with AZA for IBD were enrolled.
AZA therapy reduced the number of the surgical interventions in patients with
IBD* (*: p50.05). Male gender had a negative impact on the efficacy of AZA
therapy*. IBD patients with responce were older than the nonresponder*. There
was no difference between the operated CD patients and nonoperated for the
AZA responce rates (32% vs 34%, p4 0.05 respectively). Then, 33 AZA nonresponder patients with CD were put on biologics. Responce rate was 30%. Of
the nonresponders, intestinal resection performed in 35% .

number

mucosal
healing
by AZA

Nonresponce %

Patients with IBD


120
37 %
63%
UC
38%(45p)
42%
58%
CD
62%(75p)
33%
67%
Male
60%
25%
67%*
Operated after AZA 13%
4.5%
18.4*
AZA used (months)
31.524.7 (4-113) 31.225.7 (4-90) 31.624.3 (4-113)
Age at IBD
36.812.3 (11-72) 38.112.3 (17-58) 36.112.3 (11-72) *
diagnose (years)
Period (AZA
39.852.5 (0-264) 5669 (0-264)
3037 (0-204)
started-IBD
diagnosed (months)

CONCLUSION: In this study, we showed that AZA therapy increased endoscopic mucosal healing rates and decreased the frequency of the surgical interventions in AZA na ve patients with severe IBD. We believe that there is still
room for the AZA therapy in the management of severe IBD patients. Of the 33
CD patients with no previous AZA responce, biologics failed in 70%.
REFERENCES
Treton X, Bouhnik Y, Mary JY, et al. Azathioprine withdrawal in patients with
Crohns disease maintained on prolonged remission: a high risk of relapse. Clin
Gastroenterol Hepatol 2009; 7: 8085.
Disclosure of Interest: None declared
P0904 EFFICACY OF ADALIMUMAB TREATMENT IN STEROIDDEPENDENT ULCERATIVE COLITIS PATIENTS
M. Barreiro-De Acosta1,*, F. Munoz2, M. Sierra2, M. Garc a Alvarado3,
A. Lorenzo1, J.E. Dominguez-Munoz1
1
University Hospital, Santiago, 2Hospital de Leon, Leon, 3Hospital de Zamora,
Zamora, Spain
INTRODUCTION: Steroid dependency develops frequently (more than 30%)
with regards to ulcerative colitis (UC) patients. Limited data exists concerning
adalimumab (ADA) administration in steroid-dependent UC patients.

AIMS & METHODS: Our aim was to evaluate the clinical efficacy of ADA in
steroid-dependent UC patients.
We designed an open-label, retrospective, consecutive, and multicentre study.
Inclusion criteria were patients over 18 years old with UC and ECCO criteria
of steroid-dependency: Patients who are either unable to reduce corticosteroids
below the equivalent of prednisolone 10 mg/day within three months of starting
corticosteroids, without recurrent active disease or who have a relapse within
three months of stopping corticosteroids. All patients received ADA treatment
for induction (160/80 mg) at weeks 0 and 2 and 40 mg every 2 weeks thereafter. In
the event of loss of response patients received higher doses of ADA. The main
endpoint evaluated was clinical remission without steroids during all the treatment. Clinical response, mucosal healing and varying levels of C-reactive protein
(CRP) and calprotectine were also evaluated. Results are shown in percentages;
associations were analyzed by Cox regression whenever appropriate.
RESULTS: 37 steroid-dependent UC patients were treated with ADA: 67%
female, mean years since UC diagnosis being 11 years, 40% presenting extraintestinal manifestations and 65% with extensive colitis (E3). 12 patients (32%)
were na ve to anti-TNF and 25 (68%) had previously received infliximab. Mean
follow-up was 25.9 months. 83% received concomitant treatment with immunosuppressive drugs. 43% needed higher doses of ADA treatment due to loss of
response. After induction 35% of patients were in remission and after 12 months.
40% of patients were in remission without steroids. The mean partial mayo score
was 6.89 basal, 3.13 at month 6 and 2.33 at month 12 (p50.001). Mucosal
healing was achieved in 48% of patients. Mean calprotectine decreased from
563 basal to 218 at month 6 (p50.05) and to 61 at month 12. CRP decreased
from 19.13 to 6.13 at month 12 (p50.001). Only 3 patients (8%) needed a
colectomy during the first year. We did not observe any association between
concomitant treatment with immunosuppressive drugs and response to ADA,
but after Cox regression patients with need of intensification with ADA
(HR 48.1 95%IC:1.46-1589.1; p 0.03) and with previous IFX (HR 12.8;
95%CI: 2.24-73.54, p 0.004) had a lower remission rates.
CONCLUSION: Adalimumab can be effective for clinical remission without
steroids and mucosal healing in steroid-dependent UC. Previous IFX or need
of intensification are predictive factors of poorer efficacy.
Disclosure of Interest: None declared
P0905 ONE HOUR INFLIXIMAB INFUSIONS DO NOT AFFECT
ANTIBODIES ANTI-INFLIXIMAB AND TROUGH LEVELS IN IBD
PATIENTS
M. Marzo1,*, A. Armuzzi1, B. Tolusso2, D. Pugliese1, C. Felice1, G. Andrisani1,
O. Nardone1, F. Pizzolante1, G. Mocci1, S. Canestri2, E. Gremese2,
G. Ferraccioli2, A. Papa1, G. Rapaccini1, L. Guidi1
1
IBD Unit, 2Reumatology Unit, Complesso Integrato Columbus, Catholic
University, Rome, Italy
Contact E-mail Address: manuelamarzo@gmail.com
INTRODUCTION: Infliximab therapy in patients with inflammatory bowel disease (IBD) requires intravenous administration in over 2 hours, with a further 1
hour of post-infusion observation. Recent studies demonstrated the safety and
the tolerance of a shortened 1-hour infusion in IBD patients under scheduled
maintenance infliximab treatment. We report our experience in order to evaluate
if repeated 1-hour infliximab infusions could affect the antibodies to infliximab
(ATI) and the infliximab trough levels (TL).
AIMS & METHODS: This was a prospective cohort study on patients with IBD
receiving infliximab with shortened 1-hour infusions. All patients were treated
with scheduled maintenance infliximab therapy, after at least 5 well tolerated 2hours infusions before enrolment. For each patient we recorded diagnosis, vital
signs. All patients were routinely premedicated with 20 mg i.v. methylprednisolone and oral antihistaminics. We analyzed serum samples collected before starting the first shortened infusion and after one year of maintenance scheduled
infliximab treatment for ATI and TL by a commercial ELISA kit according to
the manufacturer instructions (DRG Diagnostics GmbH, Marburg, Germany).
All samples were analyzed simultaneously at the end of the collection period.
Statistical analysis was performed by Wilcoxon test for paired samples and
Fishers exact test.
RESULTS: Fifty-seven IBD patients (28 Crohns Disease, 29 Ulcerative Colitis)
were treated at our IBD Outpatient clinic with 1-hour infliximab infusion protocol: out of them 24 (42%) at the dose of 10 mg/kg and 18 (31.6%) with a
shortened interval of 6 weeks. Eleven patients (19.3%) were on concomitant
immunosuppressants. In total, 396 maintenance 1-hour infliximab infusions
were administered. Adverse reactions were reported in 2 out of 396 (0.5%) 1hour infusions: these reactions were considered as severe, resulting in infliximab
discontinuation. Both patients had elevated ATI at the time of the first 1-hour
infusion. No significant difference was found between median ATI (17.5 AU/ml
versus 17.7 AU/ml) and TL (3.1 mcg/ml versus 2.26 mcg/ml) measured before
and after 1 year of shortened infliximab infusions. The percentage of patients
with ATI positive (scoring higher than 10 AU/ml) and of patients with undetectable TL were unchanged after one year of 1-hour infusions. We found no correlations of ATI positivity and detectable TL measured after one year of shortened
infusions with the infliximab dose (5 mg/kg or double dose 10 mg/kg), the dose
interval (every 8 or 6 weeks) and the concurrent immunosuppressive therapy.
Five out of 55 patients (9%) changed their ATI status from negative to positive,
while 10/55 (18%) from positive to negative, at the end of the study period
(p n.s.).
CONCLUSION: In our experience, shortened 1-hour infliximab infusions were
safe and well tolerated in IBD patients under scheduled maintenance therapy also
with dose and interval optimisation and did not affect ATI and TL.
Disclosure of Interest: M. Marzo: None declared, A. Armuzzi Lecture fee(s) from:
AbbVie, MSD, Chiesi, Ferring, Nycomed, Takeda and Otsuka, Consultancy for:
AbbVie, Lilly, MSD and Takeda, B. Tolusso: None declared, D. Pugliese: None

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United European Gastroenterology Journal 2(1S)


declared, C. Felice: None declared, G. Andrisani: None declared, O. Nardone:
None declared, F. Pizzolante: None declared, G. Mocci: None declared, S.
Canestri: None declared, E. Gremese: None declared, G. Ferraccioli: None
declared, A. Papa: None declared, G. Rapaccini: None declared, L. Guidi
Financial support for research from: AbbVie, MSD
P0906 TUBERCULOSIS INFECTION IN INFLAMMATORY BOWEL
DISEASE PATIENTS AFTER ANTI-TNF THERAPY IN A HIGH
TUBERCULOSIS PREVALENCE RATE AREA
M.L. De Castro1,*, V. Rodil2, V. Hernandez1, J.R. Pineda1, L. Sanroman1,
S. Pereira1, J. Mart nez-Cadilla1, J. I. Rodr guez-Prada1
1
Gastroenterology, 2Internal Medicine, Universitary Hospital of Vigo-CHUVI,
Vigo, Spain
Contact E-mail Address: maria.luisa.decastro.parga@sergas.es

and ratio between MeMP and 6TGN decreased from 31 to 0, 55 upon changing
from thiopurine mono-therapy to combination-therapy.
Four (11 %) patients had no or poor response to combination therapy, 2 had a
colectomy and 2 started treatment with anti-TNFa.
Twenty-six (70 %) patients responded to combination treatment and have since
start of treatment been in steroid and anti-TNFa free clinical remission.
CONCLUSION: Combination therapy with low dose thiopurine and allopurinol
is well tolerated, cheap and a highly effective treatment in patients with CU and a
high MeMP/6-TGN ratio experience intolerance or having poor or no response
to thiopurine mono-therapy.
Disclosure of Interest: None declared
P0908 CAN MINDFULNESS-BASED COGNITIVE THERAPY IMPROVE
THE QUALITY OF LIFE FOR PATIENTS WITH INFLAMMATORY
BOWEL DISEASE (IBD)?

INTRODUCTION: Galicia is a region located in the north west of Spain. It has


an estimated incidence of 27 new cases of tuberculosis per 100000 population,
that is higher than the Spanish average rate of 15.5/100000. On the other hand
cases of active tuberculosis have been reported worldwide with the use of therapeutic agents that inhibit tumor necrosis factor (TNF) alpha. Our aim was to
study the prevalence of latent tuberculosis infection and active tuberculosis in
inflammatory bowel disease (IBD) patients before and during TNF therapy in
this geographical area.
AIMS & METHODS: We conducted a retrospective study collecting clinica data
of IBD patients on anti TNF therapy from January 2000 to December 2012,
identifying the cases with latent tuberculosis and active tuberculosis infection.
Latent tuberculosis was defined as a positive tuberculin cutaneous test (TCT) or
Booster re-test (4 5 mms). Active tuberculosis infection was confirmed by positive culture to Mycobacterium tuberculosis.
RESULTS: 225 patients received TNF alpha drugs: 136 male (60.4%), 173
(76.9%) Crohns disease. No patient had suffered from previous lung diseases.
Tuberculin cutaneous test was documented in 190 patients, and Booster re-test in
100. Latent tuberculosis was diagnosed in 20 and 1 patients whether TCT or
Booster were 45 mms respectvely and all of them received oral isoniacide prophylaxis (9.3%). Seven patients suffered from active tuberculosis infection
(3.1%): 4 male (57.1%) mean age 49.6 years 57.1% ulcerative colitis. Four of
them had negative TCT and Booster but they were on inmunosuppresant but no
corticosteroids when these tests were performed, and the other 3 patients had
received oral quimioprofilaxis (3-6 months) because TCT was positive. Time
from last TNF dose to symptoms and from symptoms to tuberculosis diagnose
were and days respectively. Active tuberculosis were generally disseminated
(85.5%) and required hospitalization until diagnose and clinical stabilization.
Multidrug therapy was continued for 6-8 months but one patient eventually
died. Anti TNF-alpha was no restarted in these patients.
CONCLUSION: Active tuberculosis in IBD patients on antiTNF therapy in a
high prevalence area was 3.1%. The infection was generally disseminated,
required hospitalizations and even caused death.
TCT test and previous oral quimioprofilaxis failed to eliminate risk of active
infection in these patients, so any other tests or preventive measures should be
develop.
Disclosure of Interest: None declared

M. Schoultz1,*, I. Atherton1, R. Kyle1, A. Watson1


1
University of Stirling, Inverness, United Kingdom
Contact E-mail Address: ms84@stir.ac.uk

P0907 COMBINATION THERAPY WITH LOW DOSE THIOPURINE


AND ALLOPURINOL IN PATIENTS WITH ULCERATIVE COLITIS

P0909 ARE HIGH INFLIXIMAB TROUGH LEVELS ASSOCIATED WITH


IMPAIRED QUALITY OF LIFE IN IBD PATIENTS IN CLINICAL AND
BIOCHEMICAL REMISSION ON INFLIXIMAB MAINTENANCE
THERAPY?

n
w
a
r
d
h
t
i
W

M. Kiszka-Kanowitz1,*, K. Theede1, A.M. Nielsen1


1
Hvidovre Hospital, Hvidovre, Denmark
Contact E-mail Address: marianne.kiszka-kanowitz@regionh.dk
INTRODUCTION: Thiopuine is used as a second line therapy in patients with
ulcerative colitis (UC) failing 5-ASA treatment. However up to 50 % of patients
treated with thiopurine fail this treatment due to intolerance or to lack of efficacy. A high ratio between Methylmercaptopurine (MeMP) and the active metabolite 6-Thioguanine-nucleotide (6-TGN) can be the explanation for intolerance
and thiopurine-faliure in some patients.
Adding Allopurinol to a low dose of thiopurine changes the ratio between MeMP
and 6-TGN, thereby decreasing the risk of some adverse events and at the same
time increasing the efficacy.
AIMS & METHODS: To determine the tolerance and efficacy of combination
therapy with low dose of thiopurine and allopurinol in patient with UC.
A retrospective analysis of patient with CU starting combination therapy
between October 1th 2010 and October 1th. 2013 in a single IBD-center in
Denmark.
36 UC patients were identified. 21 males and 15 females. Disease duration was
mean 7 years (range 2 28 years). 2 patients had proctitis, 22 patients had leftsides colitis and 12 patients had pancolits.
The reason for starting combination therapy was: abnormal liver test in 8
patients, high MeMP/6-TGN ratio in 24 (14 were proven to fail mono-treatment
with thiopurine), 3 other adverse events and 2 patient failing thiopurine treatments, but without a high MeMP/6-TGN ratio.
When starting combination therapy 20 patients had active disease despite of
treatment with systemic steroid in 2 patient, anti-TNFa treatment in 5, steroid
and anti-TNFa treatment in 3 patients. 16 patients had inactive disease, but 3
patients were receiving steroid and 7 anti-TNFa treatment.
RESULTS: Six (17 %) patients were intolerant to combination therapy and had
to stop treatment. 5 patients had the same adverse event as in mono-therapy and
1 patient had an unspecific event not thought to be related to treatment.
The active metabolite increased from mean 130 pmol/nmol Hgb (range 62-220) to
mean 243 pmol/nmol Hgb (range 115-434) and MeMP decreased from 4158
pmol/nmol Hgb (range 487-12150) to mean 134 pmol/nmol Hgb (range: 0-419)

INTRODUCTION: Around 30% of patients with IBD report depression and


anxiety and require psychological support. A prolonged effect of such comorbidities has been associated with poorer quality of life (QoL) and exacerbation of
IBD symptoms. Mindfulness-Based Cognitive Therapy (MBCT) is a psychological intervention successful in improving depression and anxiety scores in
depressed patients, but no previous randomised controlled trial has tested its
possible effects on IBD patients.
AIMS & METHODS: The aim of this study was to evaluate the feasibility and
acceptability of MBCT with IBD patients and assess its possible effect on QoL,
depression, anxiety, disease activity and dispositional mindfulness.
IBD patients (n 44) recruited from outpatient gastroenterology clinics in two
Scottish NHS Boards were randomised to receive MBCT (intervention group
n 22) or allocated to a wait-list (control group n 22). The intervention was
16 hours of structured group MBCT training over 8 consecutive weeks plus
guided home practice and an hour of monthly follow up session for four
months. Primary outcome was feasibility and acceptability of MBCT assessed
by a self-complete questionnaire. Secondary outcomes included: QoL, depression, anxiety, disease activity and dispositional mindfulness assessed at three
points: baseline, post intervention and six month follow up.
RESULTS: 24 patients completed the trial. All patients described the MBCT
program as a feasible and useful method and 100% would recommend MBCT to
other IBD patients. Dispositional mindfulness significantly improved (p .03) in
the intervention group at post intervention and follow up. QoL, depression,
anxiety and disease activity scores also showed promising improvement in the
intervention group.
CONCLUSION: A larger randomised controlled trial of MBCT for patients
with IBD is feasible and pilot data suggests that MBCT significantly improved
dispositional mindfulness in IBD patients and also has the potential to improve
QoL, depression, anxiety and disease activity scores. MBCT offered in combination to standard care holds a potential to benefit IBD patients.
Disclosure of Interest: M. Schoultz: none, I. Atherton: none, R. Kyle: none, A.
Watson: none

M. Lowenberg1,*, J.F. Brandse1, L.M. Vos1, C. I. Ponsioen1, G.R. Van den


Brink1, G.R. DHaens1 on behalf of IBD group AMC Amsterdam
1
Department of Gastroenterology and Hepatology, AMC Amsterdam, Amsterdam,
Netherlands
Contact E-mail Address: m.lowenberg@amc.uva.nl
INTRODUCTION: Preliminary evidence suggests a therapeutic window for
infliximab (IFX) trough levels (TLs) in patients with inflammatory bowel disease
(IBD). It remains unknown if higher or presumably supra-therapeutic TLs are
associated with adverse effects. The aim of this study was to identify a possible
association between high TLs, side effects of IFX treatment and quality of life.
AIMS & METHODS: We performed a cross-sectional study in IBD patients in
clinical and biochemical remission whilst receiving IFX maintenance therapy.
Clinical remission was defined as HBI55 for Crohns disease (CD) and
CCAI55 for ulcerative colitis (UC). Biochemical remission was defined as a
fecal calprotectin 5 250 ug/g. IFX TLs and biochemical markers (Hb, Ht,
TSH, CRP and vitamin D) were assessed to rule out alternative diagnoses for
fatigue. Patients were excluded in case of pregnancy or diseases such as cancer,
infections or rheumatologic disorders. Quality of life was assessed by IBDQ and
SF-36. Fatigue and joint pain were measured by visual analogue scores (VAS)
and for skin lesions a skin questionnaire was completed. The patient cohort was
separated in groups consisting of patients with therapeutic (IFX TL 3-7 ug/ml)
and supra-therapeutic (IFX TL 47 ug/ml) TLs. Patients and investigators were
unaware of TL results when completing the questionnaires and during the assessment of clinical and biochemical remission. In total 115 patients on IFX maintenance treatment (5 or 10 mg/kg) were approached of which 46 patients (CD
n 33, UC n 13) were deemed fit for inclusion.
RESULTS: We did not find a significant correlation between the severity of sideeffects and IFX TLs. Moreover, no correlation was observed between quality of
life and IFX TLs. Patients with supra-therapeutic TLs had lower median scores
(although not significant) compared to the therapeutic TL group on several SF36 domains: e.g. SFphysical, SFsocial, SFpain, SFrole-physical and
SFperception. The supra-therapeutic group scored lower on the physical

A382
component score (PCS) (43.9 vs. 49.7; p 0.18) while both groups scored equally
on the mental component score (MCS) (47.2 vs. 48.3; p 0.98). The supra-therapeutic TL group had lower scores on the IBDQ (178 vs. 183; p 0.35) and joint
pain VAS (10 vs. 6; p 0.67) compared to the therapeutic TL group. Skin problems were more often seen in the therapeutic group versus patients in the supratherapeutic TL group, but this difference did also not reach statistical significance, Skin score (4 vs. 6; p 0.097).
CONCLUSION: CD and UC patients who were in clinical and biochemical
remission with supra-therapeutic IFX TLs did not show an increase in sideeffects nor impaired quality of life compared to patients with therapeutic IFX
TLs.
Disclosure of Interest: None declared
P0910 THE RELATIONSHIP BETWEEN REMISSION STATUS AND
HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH MILDTO-MODERATE ULCERATIVE COLITIS RECEIVING SHORT-TERM
AND LONG-TERM DAILY THERAPY WITH MULTIMATRIX
MESALAZINE
M.K. Willian1,*, A. Yarlas2, A. V. Joshi1
Shire, Wayne, PA, 2Optum, Lincoln, RI, United States
Contact E-mail Address: MWillian@shire.com

INTRODUCTION: Studies of patients with ulcerative colitis (UC) have found


an inverse relationship between disease activity and health-related quality of life
(HRQL): Decreases in disease severity predict improvement in HRQL. The current analysis examines whether this association holds at various levels of disease
activity by testing whether HRQL differs among patients in complete clinical and
endoscopic remission, in partial remission, or not in remission after treatment
with multimatrix mesalazine.
AIMS & METHODS: Data were from a multinational, open-label, prospective
trial of multimatrix mesalazine (ClinicalTrials.gov ID: NCT01124149). In the
initial (acute) treatment phase, patients with active mild-to-moderate UC
received 4.8 g/day of multimatrix mesalazine once daily (QD) for 8 weeks.
Patients in complete or partial remission at Week 8 were eligible to receive 12
months of maintenance treatment with 2.4 g/day of multimatrix mesalazine QD.
Remission status at Week 8 and Month 12 was determined using a modified UCDisease Activity Index (UC-DAI). Complete remission was defined as UC-DAI
1 with scores of 0 on both rectal bleeding (RB) and stool frequency (SF)
components and 1-point reduction from Baseline in the endoscopy component.
Partial remission was defined as UC-DAI 3, RBSF 1, and not in complete
remission. At Baseline, Week 8, and Month 12, patients completed measures of
generic HRQL (12-item Short-Form survey [SF-12v2]) and disease-specific
HRQL (Shortened Inflammatory Bowel Disease Questionnaire [SIBDQ]).
Analysis of variance models tested whether HRQL scores at Week 8 and
Month 12 differed by remission status. Repeated-measures mixed-effects
models (RMMM) tested if changes in HRQL scores across Baseline, Week 8,
and Month 12 visits varied by remission status. Analyses of each phase included
only patients who fully completed treatment during that phase.
RESULTS: The numbers of patients in complete, partial, and no remission,
respectively, were 186 (30.0%), 282 (45.4%) and 153 (24.6%) at Week 8 for
acute phase completers, and 159 (50.6%), 103 (32.8%) and 52 (16.6%) at
Month 12 for maintenance phase completers. At both Week 8 and Month 12
visits, patients in complete or partial remission scored better on all SF-12v2 and
SIBDQ domains than those not in remission (all Bonferroni-adjusted P 50.001).
At Week 8, scores on most HRQL domains (all but the SF-12v2 pain domain,
and social functioning domains on both instruments) did not statistically differ
between patients in complete vs. partial remission. HRQL scores also did not
differ between complete and partial remission groups at Month 12 (all
Bonferroni-adjusted P 0.130). Estimated parameters and means from
RMMM models indicated that patients who achieved or maintained complete
or partial remission showed similarly larger improvements and better maintenance of HRQL than patients not in remission.
CONCLUSION: Patients with UC in complete or partial remission who completed short-term and long-term daily treatment with multimatrix mesalazine had
similar HRQL. Both groups had better HRQL than completers not in remission.
These results indicate that achievement of partial remission of UC provides
advantages comparable to those of complete remission with respect to improvement and maintenance of HRQL.
Disclosure of Interest: M. K. Willian Shareholder of: Shire, Other: Employee of
Shire, A. Yarlas Other: Employee of Optum, which received funds from Shire
Development LLC to conduct these analyses, A. Joshi Shareholder of: Shire,
Other: Employee of Shire
P0911 DISEASE BURDEN AND TREATMENT IMPACT IN PATIENTS
WITH MILD-TO-MODERATE ULCERATIVE COLITIS: A
COMPARISON OF RESULTS FROM TWO OPEN-LABEL TRIALS
M.K. Willian1,*, A. Yarlas2, A. V. Joshi1
Shire, Wayne, PA, 2Optum, Lincoln, RI, United States
Contact E-mail Address: MWillian@shire.com

INTRODUCTION: Data addressing the burden of ulcerative colitis (UC) on


health-related quality of life (HRQL) and the impact of multimatrix mesalamine
treatment on HRQL and work-related outcomes (WRO) of patients with UC
were compared across 2 similarly-designed clinical trials. The objective of this
comparison was to examine the robustness and relative magnitudes of these
effects among multiple samples.
AIMS & METHODS: Trials 409 (ClinicalTrials.gov ID: NCT01124149) and 404
(NCT00446849) were each multicenter, open-label, prospective studies of multimatrix mesalazine treatment for adults with active mild-to-moderate UC. Both

United European Gastroenterology Journal 2(1S)


trials included an 8-week acute treatment phase followed by a 12-month maintenance treatment phase. This analysis includes acute phase data only. Patients
received 4.8 g/day (Trial 409) or 2.4 to 4.8 g/day (Trial 404) of multimatrix
mesalazine once daily for 8 weeks. At Baseline and Week 8 visits, all patients
completed 3 patient-reported outcomes (PRO) instruments, measuring HRQL
(the 12-item Short-Form survey [SF-12v2] and the Short Inflammatory Bowel
Disease Questionnaire [SIBDQ]) and WRO (Work Productivity and Activity
Impairment Questionnaire: UC [WPAI:UC]). Within each trial, burden of UC
on HRQL was estimated as the deficits in patients SF-12v2 scores relative to
scores from a US general population sample (USGPS). Analysis of variance
(ANOVA) models compared the magnitude of pre-treatment disease burden,
and differences in Baseline PRO scores, between trials. ANOVA models also
tested between-trial differences in burden at Week 8 for patients who completed
treatment. Analysis of covariance (ANCOVA) models tested for between-trial
differences in PRO scores at Week 8, controlling for Baseline scores for treatment
completers.
RESULTS: In Trial 404, 42.4% (56/132) of patients completed treatment at 8
weeks, compared to 89.1% (639/717) in Trial 409. Patients in Trial 409, compared to Trial 404, showed greater burden on several SF-12v2 domains (general
health, limitations due to emotional problems, social functioning, and mental
health; P 50.05 for differences). Comparisons of Baseline PRO scores between
trials found worse scores for Trial 409 than Trial 404 on several domains of the
SF-12v2 (general health, limitations due to emotional problems, and mental
health), SIBDQ (social and emotional function), and WPAI:UC (presenteeism
and overall work impairment); P 50.05 for differences. Comparison of burden at
Week 8 for treatment completers found no trial differences for any SF-12v2
domains (all P 40.05); burden at Week 8 was similarly small for each trial,
with most domain scores at least equivalent to those scores of the USGPS.
Direct comparisons of Week 8 post-treatment scores between trials found no
significant differences for any PRO measure (all P 40.05).
CONCLUSION: Patients in Trial 409 entered treatment with a larger disease
burden on HRQL and with generally worse HRQL and WRO than patients in
Trial 404. At Week 8, there were no between-trial differences in burden on
HRQL or for direct comparisons of all HRQL and WRO measures for treatment
completers. Further, for patients in both trials, Week 8 scores on most SF-12v2
domains were not below scores from the USGPS, indicating that patients with
UC achieved near-normal levels of most aspects of HRQL following 8 weeks of
daily multimatrix mesalazine treatment.
Disclosure of Interest: M. K. Willian Shareholder of: Shire, Other: Employee of
Shire, A. Yarlas Other: Employee of Optum, which received funds from Shire
Development LLC to conduct these analyses, A. Joshi Shareholder of: Shire,
Other: Employee of Shire
P0912 EFFICACY AND SAFETY OF INFLIXIMAB SALVAGE THERAPY
IN PATIENTS WITH ULCAERATIVE COLITIS AFTER FAILURE OF
TACROLIMUS INDUCTION THERAPY
M. Sugimura1,*, M. Iwabuchi1, H. Takahashi1, K. Shishikura1, K. Ukai1,
K. Tadokoro1
1
Gastroenterology, Sendai medical center, Sendai, Japan
Contact E-mail Address: msugimura@snh.go.jp
INTRODUCTION: Tacrolimus and anti-TNF therapy like infliximab have
been shown to be effective for the treatment of patients with moderate to
severe corticosteroid-refractory/dependent ulcerative colitis. However, currently,
there are no guidelines pertained to the order or the timing of these medications.
AIMS & METHODS: In our hospital, tacrolimus precedes infliximab as a
second-line therapy for patients of ulcerative colitis. This study was to investigate
the efficacy and safety of infliximab in patients with moderate to severe corticosteroid-refractory/dependent ulcerative colitis who failed to respond to tacrolimus induction therapy. We enrolled twenty-nine patients (16 male, 13 female;
mean age 43.9) treated with tacrolimus between January 2010 and January 2014,
and 11 (4 male, 7 female; mean age 47.6) out of these patients were treated with
infliximab because of refractoriness or loss of response to tacrolimus, or no
tolerance. We assessed therapeutic outcomes at baseline, 8, and 30 weeks for
11 patients treated with infliximab using Lichtiger index, a score of which less
than or equal to 4 was defined as clinical remission.
RESULTS: Mean Lichtiger index was significantly decreased to 11.6, 6.7, and 5.1
at baseline, 8, and 30 weeks, respectively (P50.05). Five patients (45%) showed
clinical remission at 8 weeks and six (54%) showed clinical remission at 30 weeks.
Three patients who did not respond to infliximab were all over 60 years old, and
finally underwent colectomy. Rates of clinical remission at 8 and 30 weeks were
42.4% and 53.1% in tacrolimus responders (2 loss of response; 4 no tolerance),
46.3% and 56.4% even in tacrolimus nonresponders (4 patients). There was no
significant difference in clinical remission rate between tacrolimus responders and
nonresponders. No serious adverse events were encountered.
CONCLUSION: Infliximab salvage therapy following tacrolimus appeared to be
efficacious in both tacrolimus responders (loss of response or no tolerance) and
in nonresponders (refractoriness), and 8 (72.7%) of 11 patients could avoid
colectomy. Infliximab salvage therapy is considered to be useful and well
tolerated.
Disclosure of Interest: None declared

A383

United European Gastroenterology Journal 2(1S)


P0913 PATIENT PERCEPTION TOWARDS FAECAL MICROBIOTA
TRANSPLANTATION FOR TREATMENT OF INFLAMMATORY
BOWEL DISEASE
N. Quraishi1, M. McMillan1, M. Widlak1,*, L. Nell1, K. Quraishi2,
S. Pathmakanthan1, N. Sharma2, T. Iqbal1
1
Gastroenterology, Queen Elizabeth Hospital, University Hospitals Birmingham
NHS Foundation Trust, 2Gastroenterology, Heartlands Hospital, Heart of England
NHS Foundation Trust, Birmingham, United Kingdom
Contact E-mail Address: T. H. IQBAL@bham.ac.uk
INTRODUCTION: Faecal microbiota transplant (FMT) is a novel highly effective treatment for Clostridium difficile infection (CDI).* Initial clinical trials and
case reports suggest that this may be a promising therapy for patients with
inflammatory bowel disease (IBD).** As part of a patient audit regarding our
FMT treatment for CDI we performed a survey to evaluate patient attitudes to
potentially receiving FMT as treatment for IBD and gauged attitudes towards
participation in a future clinical trial evaluating the effectiveness of FMT in IBD.
AIMS & METHODS: We conducted a structured survey on patients attending
gastroenterology clinics to assess perceptions of effectiveness, tolerability, safety
and thresholds for considering FMT as a treatment.
RESULTS: We collected 105 responses (M:F 46:59, Median age 36 years) including 80 (76%) from patients with IBD. 91% (96/105) felt that this treatment would
be effective and 56% (59/105) did not consider it unpleasant. 96% (101/105)
patients perceived it to be safe. 72% (76/105) and 82% (86/105) would be comfortable with having FMT via an NG tube or rectal enema route respectively.
78% (82/105) did not have any concerns regarding the faecal transplant being
obtained from a screened unrelated donor. 74% (78/105) of the patients would be
willing to have FMT as a first line treatment of CDI. 50% (40/80) of IBD
patients surveyed would consider FMT as a first line treatment of their IBD,
85% (68/80) if steroid resistant or dependant, 89% (71/80) if failing on biologics
and 94% (75/80) as a salvage treatment option prior to surgery. Importantly
75% (60/80) would consider taking part in a clinical trial evaluating faecal microbiota transplantation for treatment of their IBD.
CONCLUSION: In this survey of patient attitudes to FMT amongst patients
from the UK, we found that patients perceived FMT as a potentially effective,
safe, tolerable treatment and were inclined to consider this as part of conventional medical therapy for IBD. In our cohort we did not discover reluctance to
take part in a trial of FMT for treatment of IBD.
REFERENCES
Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces
for recurrent Clostridium difficile. New Eng J Med 2013; 368: 407-415.
Angelberger S, Reinisch W, Makristathis A, et al. Temporal bacterial community
dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol 2013; 108: 1620-1630.
Disclosure of Interest: None declared
P0914 ADALILMUMAB SERUM CONCENTRATION AS A PREDICTOR
FOR CLINICAL EFFICACY - ROC ANALYSES
N.M. Mostafa1,*, A.M. Robinson1, S. Sharma1, W.J. Sandborn2, S. Ghosh3,
S.B. Hanauer4, J.-F. Colombel5, R.B. Thakkar1, W.M. Awni1
1
AbbVie Inc., North Chicago, 2Inflammatory Bowel Disease Center, Division of
Gastroenterology, University of California San Diego Health System, La Jolla,
United States, 3Department of Medicine, University of Calgary, Calgary, Canada,
4
Feinberg School of Medicine, Northwestern University, Chicago, 5Icahn School of
Medicine at Mount Sinai, New York, United States
INTRODUCTION: The relationship between adalimumab trough concentration
and efficacy (clinical remission and response) in patients with ulcerative colitis
has been previously characterized1. The purpose of this analysis was to explore
whether an adalimumab concentration threshold is predictive of adalimumab
efficacy in ulcerative colitis.
AIMS & METHODS: Data from 242 patients with moderate to severe ulcerative
colitis enrolled in the adalimumab treatment arm in ULTRA2 were included in
the analysis. Patients received 160/80 mg adalimumab at Week 0/ 2 and 40 mg
eow thereafter. Adalimumab trough concentration at Week 8 was used to predict
clinical remission and response per Full Mayo scores at Week 8, 32 or 52. In case
of dropouts or missing Week 8 concentrations, values were imputed using lastobservation-carried-forward method. For Week 8, 32 and 52, efficacy, nonresponder imputation was implemented such that subjects were considered not
in remission/response if they were discontinued or moved to open-label prior to
the time point of efficacy assessment or if they had a missing Mayo score at the
time point of efficacy assessment. Receiver operating characteristic (ROC) curves
were constructed and area-under the ROC curves (AUC) were calculated using R
Ver 3.0.3. Determination of predictive adalimumab trough concentration thresholds was based on the choice of corresponding specificity and sensitivity pair
determined from the ROC curves.
RESULTS: Mean (range) adalimumab trough concentrations at Week 8 were 8.7
(0-22.8 mcg/mL). ROC curves showed AUC values ranging from 0.64 to 0.67 for
remission and 0.55 to 0.63 for response at Week 8, 32 and 52. No concentration
threshold exhibited a combination of specificity and sensitivity that was highly
predictive of remission or response at Week 8, 32 or 52. The highest value for
AUC (0.67) was associated with Week 52 remission, for which the algorithmdetermined threshold showed a specificity and sensitivity of 0.52and 0.78,
respectively.
CONCLUSION: ROC analyses were conducted and did not identify an adalimumab trough concentration threshold that predicts clinical remission or
response at Week 8, 32 or 52 in UC.

REFERENCES
1. Mostafa NM, Eckert D, Pradhan RS, et al. Exposure-Efficacy Relationship
(ER) for adalimumab during induction phase of treatment of adult patients with
moderate to severe ulcerative colitis. Gastroenterology 2013; 144: S-225.
Disclosure of Interest: N. Mostafa Shareholder of: AbbVie, Other: AbbVie
employee, A. Robinson Shareholder of: AbbVie, Other: AbbVie employee, S.
Sharma Shareholder of: AbbVie, Other: AbbVie employee, W. Sandborn
Consultancy for: AbbVie, S. Ghosh Consultancy for: AbbVie, S. Hanauer
Consultancy for: AbbVie, J.-F. Colombel Consultancy for: Abbvie, ABScience,
Amgen, Bristol Meyers Squibb, Celltrion, Danone, Ferring, Genentech, Giuliani
SPA, Given Imaging, Janssen, Immune Pharmaceuticals, Merck & Co.,
Millenium Pharmaceuticals Inc., Nutrition Science Partners Ltd., Pfizer Inc.
Prometheus Laboratories, Protagonsit, Receptos, Sanofi, Schering Plough
Corporation, Second Genome, Takeda, Teva Pharmaceuticals, UCB Pharma,
Vertex, Dr. August Wolff GmbH & Co., R. Thakkar Shareholder of: AbbVie,
Other: AbbVie employee, W. Awni Shareholder of: AbbVie, Other: AbbVie
employee
P0915 EFFICACY OF CONCOMITANT MESALAMINE SUPPOSITORY
IN PATIENTS WITH ACTIVE ULCERATIVE COLITIS WHO
SHOWED INADEQUATE RESPONSE TO ORAL 5AMINOSALICYLIC ACID PREPARATIONS: A PROSPECTIVE
STUDY
N. Yoshimura1,*, T. Kawaguchi1, M. Sako1, M. Takazoe1
1
Department of Internal Medicine, Division of IBD, Tokyo Yamate Medical
Centre, Tokyo, Japan
INTRODUCTION: Oral 5-aminosalicylic acid (5-ASA) preparations have been
widely given as first-line medications for inducing and maintaining remission in
patients with mildly to moderately active ulcerative colitis (UC). Further, for
distal UC, topical salicylate preparations as enema or suppository have been
applied. However, up to now, there is no widely accepted evidence for efficacy
of concomitant mesalamine suppository in patients with active UC who do not
respond well to oral 5-ASA preparations.
AIMS & METHODS: We were interested to evaluate the efficacy of concomitant
Pentasa suppository as remission induction therapy in patients who had active
UC while on oral mesalamine preparations for at least 4 weeks. In a single-centre
prospective setting, 114 consecutive patients with mildly to moderately active UC
with rectal inflammation who had shown inadequate response to oral 5-ASA
preparations were included. All patients received concomitant Pentasa 1g suppository rectally once a day for 4 weeks together with the ongoing oral 5-ASA
preparations. No patient received corticosteroid or immunosuppressant. At
week 4, clinical efficacy for Pentasa suppository was evaluated by the UCDisease Activity Index (UC-DAI), including the 3 sub-scores. Clinical remission
was defined as the bleeding sub-score 0.and a decrease of  3 in the UC-DAI
score, while clinical response meant a decrease of  1 in the UC-DAI score.
RESULTS: Of the 114 patients, 41 (36.0%) achieved clinical remission, 37
(32.4%) achieved response level. The UC-DAI fell from 3.20.8 at entry to
1.61.7 at week 4 (n 114, P50.001). The bleeding sub-score fell from
1.00.2 to 0.40.5 (P50.001). Regarding the response rate vs extent of UC,
the UC-DAI fell from 3.20.8 to 1.51.7 in patients with proctitis (n 101,
P50.001), and from 3.00.6 to 1.81.5 in patients with left-sided colitis
(n 12, P50.05), and one patient with pancolitis worsened. Further, by concomitant Pentasa suppository, the bleeding sub-score in patients who did not
respond well to oral 5-ASA preparations alone (n 60) fell from 1.00.1 to
0.40.5; in sulphasalazine-treated subgroup (n 21), mean dose 3.71.2g/day,
range 1.5-6.0/day fell from 1.0  0.0 to 0.40.5 (P50.01); in Pentasa (n 7)
1.70.6g/day, range 1.5-3.0/day fell from 1.0  0.0 to 0.30.5 (P50.05); in
Asacol (n 32) 3.50.3g/day, range 2.4-3.6/day fell from 1.0  0.2 to 0.40.6
(P50.001), reflecting significant efficacy for concomitant Pentasa suppository in
patients who did not respond well to high dose oral 5-ASA preparations alone.
No serious adverse events were observed.
CONCLUSION: This is the first study in Japan that has investigated the efficacy
of Pentasa suppository in patients who did not respond well to oral 5-ASA
preparations. Based on the outcomes of the present investigation, we believe
that patients with distal UC who remain with active UC while on oral 5-ASA
preparations alone should benefit from receiving concomitant Pentasa
suppository.
Disclosure of Interest: None declared
P0916 PREDICTORS AND FREQUENCY OF ANTI-TNF
ESCALATION AND DE-ESCALATION IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE

DOSE

N. Viazis1, T. Koukouratos1, J. Anastasiou1, M. Giakoumis1, C. Triantos2,


C. Tsolias2, G. Theocharis2, E. Vienna1, D.G. Karamanolis1,*
1
Department of Gastroenterology, EVANGELISMOS HOSPITAL, Athens,
2
Department of Gastroenterology, University Hospital of Patras, Patras, Greece
Contact E-mail Address: nikos.viazis@gmail.com
INTRODUCTION: The role of anti-TNF therapy in patients with Inflammatory
Bowel Disease (IBD) is well established; however in some patient dose needs to
be intensified in order to maintain remission. We aimed to determine predictors
and frequency of anti-TNF dose escalation and de-escalation in patients treated
with infliximab or adalimumab for ulcerative colitis (UC) or Crohns disease
(CD).
AIMS & METHODS: Since September 2010, all consecutive patients treated
with infliximab or adalimumab for active Crohns disease or ulcerative colitis
at the IBD clinics of the two participating centers (both tertiary referral hospitals)
were prospectively included in this cohort study. All patients were anti-TNF

A384
na ve, while concomitant azathioprine was administered for 6 months. The outcome of anti-TNF therapy was consequently evaluated every 2 months throughout the follow up period. Secondary loss of response was defined in those patients
who initially responded to anti-TNF therapy and subsequently lost clinical
response. Patients were considered to initially respond to anti-TNF therapy if
they experienced a clear improvement in symptoms and drop in CRP if elevated
at baseline at week 6 through week 14. Absence of primary response precluded
the patient from further analysis. Patients were considered to lose response if
symptoms reappeared and CRP re-elevated at any time period after the first 14
weeks of anti-TNF therapy. For patients losing response, anti-TNF dose escalation was scheduled. During the follow up period and after 1 year of intensified
administration, anti-TNF was de-escalated in patients in remission (absence of
symptoms, normal CRP).
RESULTS: During the study period 161 IBD patients (CD 133, UC 28) were
started on infliximab (n 96) or adalimumb (n 65) in the participating centers;
however 29 (18.0%) did not respond to therapy (absence of primary response)
and were excluded from further analysis. From the remaining 132 patients
(CD 113, UC 19, infliximab 77, adalimumab 5), 31 (23.5%) needed a
dose escalation for maintenance of remission (CD 30, UC 1), during the
median follow up period of 26 months (range 2 to 36 months). Factors associated
with the need for anti-TNF dose escalation were azathioprine discontinuation
earlier than 6 months in all patients and smoking in CD patients. Most patients
achieved clinical remission (n 25, 80.6%) without any other intervention and
among them, 16 (64%) were successfully de-escalated to the standard maintenance infliximab or adalimumab dose schedule, after 1 year of intensified antiTNF administration.
CONCLUSION: A substantial number of UC and CD patients (23.5%) initially
responding to anti-TNF therapy required dose escalation to maintain disease
remission. Factors associated with anti-TNF loss of response were discontinuation of azathiorpine co-administration earlier than 6 months in all patients and
smoking in Crohns disease patients. Dose escalation was successful in 80.6% of
the patients studied and among them dose de-escalation was possible in 64%,
after 12 months of intensified anti-TNF administration
Disclosure of Interest: None declared
P0917 THE IMPACT OF ANTI-TNF THERAPY AND SURGERY ON
PERIANAL CROHNS FISTULAS
N.A. Yassin1,*, A. Askari1, J. Warusavitarne1, O. Faiz1, T. Athanasiou2,
R. Phillips1, A. Hart1
1
St Marks Hospital and Academic Institute, 2St Marys Hospital, London, United
Kingdom
Contact E-mail Address: nayassin@gmail.com
INTRODUCTION: The management of perianal Crohns fistulae represents a
significant challenge. Combination medical and surgical therapy, guided by radiology is often required. The aim of this systematic review and meta-analysis is to
assess healing rates between medical treatment (anti-TNF-a therapies /- immunomodulators) or surgical treatment alone compared to combined medical and
surgical treatment in fistulating Crohns Disease (CD).
AIMS & METHODS: This review was carried out according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers searched PubMed (January 1966 to January
2014), the Cochrane Database, and EMBASE (January 1980 January 2014). All
studies investigating anti-TNF- therapy combined with surgery as a treatment
for Crohns perianal and rectovaginal fistulas were included. Meta analysis was
carried out using a random effects model. Odds ratios and confidence intervals
were generated.
RESULTS: A total of 24 articles were included. Six were amenable to quantitative data synthesis and were meta-analysed. The total population was 1138
patients; 460 (40.4%) received single treatment with either biological or surgical
therapy, and 682 (60%) received combined biological and surgical therapy. Forty
four percent of the patients were male (n 503) and 48.6% were female (n 553).
Across the studies, the mean age ranged from 28 years to 46 years of age.
Similarly the median age reported, ranged from 25 years to 43 years old. The
mean follow up ranged from 2.5 to 68.8 months whilst the median was 8 to 62.5
months.
Within the six studies, the total population was 686 patients (single therapy,
n 382, combination therapy n 304). In the single therapy group (either biologics alone or surgery), out of 382 patients, 184 patients were in complete
remission (48.2%). This was lower than the healing rate of the combined therapy
group 170/304 (56.0%). Patients who had single therapy were less likely to go
into complete remission when compared with the combination therapy group
(OR 0.69, CI 0.50-0.95, p 0.02).
CONCLUSION: Combined surgical and anti-TNF-a therapy has an additional
beneficial effect on perianal fistula healing in patients with Crohns disease,
compared with surgery or medical therapy alone. A well-designed Crohns perianal fistula clinical trial is required in a multidisciplinary medical and surgical
setting with clearly defined end points of clinical and radiological healing.
Disclosure of Interest: None declared
P0918 LONG TERM OUTCOMES OF ANTI-TNF THERAPY FOR
FISTULISING PERIANAL CROHNS DISEASE
N.A. Yassin1,*, A. Askari1, L. Ferrari1, J. Warusavitarne1, C. Vaizey1, O. Faiz1,
R. Phillips1, A. Hart1
1
St Marks Hospital and Academic Institute, London, United Kingdom
Contact E-mail Address: nayassin@gmail.com
INTRODUCTION: Fistulising perianal Crohns disease (CD) is a challenging
condition to treat and a multidisciplinary approach to treatment is required.

United European Gastroenterology Journal 2(1S)


Little is known regarding long-term efficacy of anti-TNF therapy for this
group of patients.
AIMS & METHODS: We evaluated the clinical and radiological outcomes and
the effects of biological therapy on our cohort of CD patients.
A database of 173 consecutive patients with Crohns disease treated at our institution between 2005 and 2014 was established. Data on patient demographics
and relevant outcomes were collated from medical, electronic and radiological
reports. Chi-Squared, Cox regression and binary logistic analysis were used for
statistical analyses.
RESULTS: Patients received Infliximab therapy (61%), Adalimumab therapy
(6%) or switched between the two (33%) for the treatment of perianal fistulas.
Forty-five percent of the patients were male and 55% female, with 13.5% being
current smokers and 68% previous smokers. A fistula diagnosis and treatment
occurred in 8% of patients prior to Crohns diagnosis with a 10-year gap between
a diagnosis of fistula and a diagnosis of CD in 65% of patients. Montreal
classification identified that 40% of patients had L1 disease, 76% L2, 28% L3
and 2% L4, and 3.5% had perianal disease only. Proctitis was noted in 36% of
patients.
At the start of anti-TNF therapy, 32% of patients had a simple fistula, 68% had
a complex fistula at the baseline MRI. Combined therapy with thiopurines was
observed in 58% of patients. Seton drainage was performed for 51% of patients
at the start of anti-TNF therapy.
Overall, after a median follow-up period of 52 months (range 1-163), 32% of
patients were in clinical remission, 74% of patients had a clinical response to
treatment and the recurrence rate after remission was 12%. Radiological remission was noted in 14% of patients, response in 62% of patients and recurrence of
4.7% over a median of 37 months (range 3-101) MRI follow-up.
With regards to complexity of fistula, Cox Regression analysis demonstrated that
clinical remission was seen in 47% of patients with a classification of a simple
fistula, and 22% of those with a complex fistula (p50.01). Radiological remission however was noted in 28% of patients with a simple fistula and 5% of those
with a complex fistula (p50.01). Factors influencing the time to clinical response
were fistula duration (p 0.03), and the concomitant use of immunomodulators
(p 0.02).
Multivaraite binary logistic regression revealed that patients who have a
Montreal classification of L1 disease are 64% less likely to achieve clinical remission (OR 0.36, CI 0.17-0.79 p 0.01), and those who have L3 disease are
60% less likely to achieve remission (OR 0.40, CI 0.17-0.93, p 0.03).
Having proctitis at the start of biological therapy predicts a 60% decrease in
the likelihood of clinical remission in this group of patients (OR 0.40,
CI 0.16-0.98, p 0.04).
CONCLUSION: About three-quarters of patients with fistulising perianal
Crohns disease had clinical response to biological therapy, whereas two-thirds
had a radiological response. Fistula complexity and the presence of ileal and ileocolonic disease were predictors of a worse clinical and radiological outcome.
Radiological remission is an important outcome measure to assessment in predicting sustained fistula healing.
Disclosure of Interest: None declared
P0919 ANAEMIA DEVELOPS IN PATIENTS FOLLOWING ILEOANAL
POUCH ANASTOMOSIS (IPAA): A SINGLE CENTRE STUDY
REVIEW OF IPAA PATIENTS
E.Van Blankenstein1,*, M.F. Jaboli1, T.C. Shepherd1, M. Hamilton1, E. Despott1,
G. Erian1, O. Epstein1, C. Murray1
1
Gastroenterology, Royal Free London, London, United Kingdom
Contact E-mail Address: emily.blankenstein.09@ucl.ac.uk
INTRODUCTION: Anaemia is reported in 17% of patients following IPAA[1].
However, few studies specifically report the prevalence of iron deficiency anaemia (IDA) following IPAA: One small study of 18 patients report 56% developed
IDA[2]. There are no specific guidelines on investigating IDA in IPAA.
AIMS & METHODS: Retrospective demographic and pre and post-operatively
medical data from IPAA patients at the Royal Free Hospital was collected to
analyse the frequency of anaemia, specifically IDA, and its subsequent investigation and treatment. Anaemia was defined as Haemoglobin (Hb) 5 13g/dL for
males or 512g/dL for females; iron deficiency defined using CRP adjusted
ferritin.
RESULTS: 80 patients (51% [41] male), median age 38 years (range 19 to 74)
were included. Pre-operatively all 80 had a diagnosis of ulcerative colitis (UC),
although subsequent histological analysis was most consistent with Crohns
Disease in 5% [4/80] and Indeterminate Colitis in 2.5% [2/80]. Median age at
diagnosis 17.5 years, and median age at pouch formation 28 years.
16% [13/80] were anaemic pre-operatively, while 64% [51/80] developed anaemia
within a 6 month period post-operatively. 53% [42/80] patients were iron deficient and 21% [17/80] patients had IDA post-operatively. Most (76% [13/17])
were treated with either oral or parenteral iron. 82% [14/17] were investigated
with sigmoidoscopy, 29% [5/17] with OGD, 65% [11/17] had a TTG checked and
29% [5/17] with video wireless capsule endoscopy. 94% [16/17] had pouchitis.
CONCLUSION: We report that anaemia develops many months post IPAA in a
large proportion of patients. Many patients are iron deficient and some have
IDA. IDA was well treated, but investigated predominantly with only sigmoidoscopy; invariably pouchitis was discovered and felt to be the aetiology of IDA.
We suggest that there is a need for further research into the mechanisms of
anaemia following IPAA. IDA, even when pouchitis is discovered, should still
be investigated following BSG guidelines, given 20% of patients will have dual
pathology.
REFERENCES
[1] Oikonomou IK, Fazio VW, Remzi FH, et al. Risk factors for anemia in
patients with ileal pouch-anal anastomosis. Dis Colon Rectum 2007; 50: 69-74.

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[2] Pastrana RJ, Torres EA, Arroyo JM, et al. Iron-deficiency anemia as presentation of pouchitis. J Clin Gastroenterol 2007; 41: 41-44.
Disclosure of Interest: None declared
P0920 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR DYSPLASTIC
LESIONS IN LONG-STANDING ULCERATIVE COLITIS: LESION
DEFINITION AND CURATIVE RESECTION
F. Iacopini1,*, C. Grossi1, T. Gotoda2, T. Matsuda3, Y. Saito3, G. Costamagna4,
A. Scozzarro1
1
Gastroenterology and Endoscopy Unit, Ospedale S. Giuseppe, Albano L; Rome,
Italy, 2Department of Gastroenterology and Hepatology, Tokyo Medical
University, 3Endoscopy Unit, National Cancer Center Hospital, Tokyo, Japan,
4
European Endoscopy Training Center, Catholic University, Rome, Italy
Contact E-mail Address: federico.iacopini@gmail.com
INTRODUCTION: Long-standing inflammatory bowel diseases (IBD) are associated to an increased risk of dysplasia and cancer, and proctocolectomy is
recommended for flat dysplasia and dysplastic lesions associated with dysplasia
in the surrounding flat mucosa (DALM) due to the risk of synchronous / metachronous advanced cancer. Contrary to resection by snare, endoscopic submucosal dissection (ESD) achieves curative resections with wide margins of normal
mucosa regardless lesion size and submucosal (SM) fibrosis.
AIMS & METHODS: To assess ESD feasibility of curative resection of IBD
dysplastic lesions and differentiate DALM from sporadic adenomatous-like mass
(ALM). From May 2011, consecutive patients with long-standing (48 yrs)
extended ulcerative colitis (UC) and a superficial dysplastic lesion within the
colitic mucosa were prospectively enrolled. Dysplastic lesions were characterized
by chromoendoscopy (CE) with indigo-carmine 0.4% and acetic acid 1%, and
narrow band imaging (NBI) with no magnification. ESD was performed according to the standard technique. Mucosal incision was planned at 45 mm from
lesion margins. SM fibrosis was graded from 0 to 2. Follow-up with pan-CE
colonoscopy was planned every 6 months after curative resection (low-risk for
lymph node metastasis after en bloc R0 resection).
RESULTS: Five patients with 6 lesions were included. Patient mean age was 63
(55-69), UC duration 13 yrs (9-22). Lesion morphology was LST-G homogeneous type in 3, LST-NG flat type in 3. Lesions were located in the right, left
colon, and rectum in 3, 2, and 1, respectively. Median diameter was 28 mm (2040). The rectal lesion had a wide scar from previous transanal endoscopic microsurgery. Acetic acid CE permitted to better delimitate lesion margins; peripheral
markings were used in two cases. SM fibrosis was observed in 3 cases during
dissection. ESD achieved en bloc, R0 and curative resection in 5 (83%) cases, and
failed in the rectal case. Histology showed a T1 cancer with SM-slight invasion in
1 case. Wide margins of normal mucosa were achieved in all successful ESD cases
with no flat dysplasia. No complication occurred. No advanced cancers or flat
dysplasia on random biopsies were observed within a follow-up of 20 months
(16-36).
CONCLUSION: Delineation of IBD dysplastic lesion margins is difficult and
requires a multimodal CE approach. The ESD en bloc R0 resection of IBD
dysplastic lesions with wide margins of normal mucosa is feasible and permits
to accurately differentiate DALM from ALM with important clinical
implications.
Disclosure of Interest: None declared
P0921 INTESTINAL SURGERY FOR CROHNS DISEASE: ROLE OF
PREOPERATIVE THERAPY IN POST OPERATIVE OUTCOME
M. Scarpa1, M. Martinato2, E. Bertin3, A.D. Roit3, A. Pozza4, C. Ruffolo4,
R. DInca`5, R. Bardini3, G.C. Sturniolo5, C. Castoro6, I. Angriman3,*
1
Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), 2Azienda
Ospedaliera di Padova, 3General Surgery Unit, University of Padova, Padova,
4
General Surgery Unit, Ca Foncello Hospital, Treviso, 5Gastroenterology Unit,
University of Padova, 6Surgical Oncology Unit, Veneto Institute of Oncology
(IOV-IRCCS), Padova, Italy
INTRODUCTION: Patients affected by Crohns disease (CD) require life-long
medical therapy but they can also often require abdominal surgery. The effect of
CD therapy on postoperative course is still unclear. The aim of this study was to
evaluate the effect of preoperative medical therapy on the outcome of intestinal
surgery in these patients.
AIMS & METHODS: Data from a consecutive series of 186 patients with CD
operated on at the University of Padova Hospital form 2000 to 2013 were
retrieved. Data of their preoperative therapy during the 6 months before surgery
were available for 146 patients who were enrolled in this retrospective study.
Clinical data and surgical details were retrieved and postoperative complications
and reoperation were considered outcome measures. Univariate and multivariate
analysis were performed.
RESULTS: No significant difference was observed between patients without
data about their preoperative therapy and those with them. Eight patients underwent reoperation in the first 30 postoperative days: two of them for anastomotic
leak, three for bleeding, one for obstruction and two for abdominal wound
dehiscence. At multivariate analysis preoperative adalimumab and budesonide
resulted to be an independent predictor of reoperation (OR 7,67
(95%CI 1,49-39,20), p 0.01 and OR 6,7749 (95%CI 0.98-46,48),
p 0.05, respectively). At multivariate analysis neither pharmacological nor clinical variables resulted to predict anastomotic leak.
CONCLUSION: In our series, adalimumab but not infliximab seemed to be
associated to early reoperation after intestinal surgery. This may be due to a
worst disease severity in patients who needed surgery in spite of biological therapy. Preoperative tapering of budesonide dose seems a safe option before elective
abdominal surgery for CD.

Disclosure of Interest: None declared


P0922 LONG-TERM OUTCOME OF TERMINAL ILEOSTOMY IN
CROHNS DISEASE (CD) PATIENTS AT THE ERA OF BIOLOGICS.
A RETROSPECTIVE SINGLE CENTRE STUDY
R. Akrimi-Molie`re1, V. Juif1, L. Dupont-Kazma1, N. Herraney1, J.M. Reimund1,*, B. Duclos1
1
Hepato-Gastroenterologie et Assistance Nutritive, Hopitaux Universitaires de
Strasbourg, CHU de Hautepierre, Strasbourg Cedex, France
INTRODUCTION: Anti-TNF antibodies (mAbs) significantly changed CD
treatment strategy. However, despite their efficacy, several patients failed all
available medical therapy and require surgery, in some cases coloproctectomy
with terminal ileostomy. By contrast to ileocolonic resection with ileocolonic
anastomosis where postoperative relapse risk factors are known, for terminal
ileostomy - often considered as at low risk of recurrence, such factors have not
been clearly identified.
AIMS & METHODS: We aimed to analyze the long-term outcome of CD
patients with terminal ileostomy and to try to find predictive factors of relapse,
since anti-TNF mAb were largely used.
All patients with coloproctectomy/terminal ileostomy performed between 1995
and 2010 were considered for this single center study (to ensure homogeneity of
the studied group, with a same treatment and follow-up strategy). The following
items were recorded: demographic, clinical, biological and therapeutic patients
characteristics, frequency and characteristics of disease relapse after ileostomy
(defined by the association of clinical symptoms, at least one endoscopic or
radiologic result confirming CD relapse, and the need to introduce/change a
medical treatment), factors potentially predictive of relapse (including antiTNF mAb use previous to surgery). Statistical significance was set at p50.05.
RESULTS: The charts of 1414 patients were reviewed. 51 CD patients with
terminal ileostomy were found. Nine were excluded from analysis (5 lost for
follow-up, 4 with discharge ileostomy). Among the remaining 42 patients,
23.8% relapsed. Recurrence at 5 and 10 years was of 21.7 and 30.7% respectively,
with a mean delay between ileostomy and the first recurrence of 3637 months
(mean follow-up: 85 years). 42.9% of patients needed at least one new surgical
procedure (for ileostomy complications or CD relapse). Anti-TNF mAb treatment before terminal ileostomy (n 20/42) did not change the risk to need terminal ileostomy despite ileostomy was performed at a younger age in these patients
(40.610.6 vs. 51.510.6 years; p 0.01). Multivariate analysis showed that age
at ileostomy [Hazard ratio (HR): 0.92 - 95% confidence interval (95% CI): 0.841; p 0.05), presence of granuloma at resection (HR: 6.31 - 95% CI: 1.49-26.75;
p 0.01) and ongoing smoking after ileostomy (HR: 9.11 - 95%CI: 2.19-37.83);
p 0.01) were independent factors associated to CD relapse after ileostomy.
CONCLUSION: In conclusion, despite an increasing use of anti-TNF mAb for
CD treatment, long-term CD relapse after terminal ileostomy occurred in 24% of
patients. We identified three factors being predictive of risk of recurrence.
Among those, presence of granulomas on resected tissue at the time of ileostomy
and continuing smoking after ileostomy may allow to identify patients at high
relapse risk. These patients are susceptible to need a close long-term postoperative surveillance.
Disclosure of Interest: R. Akrimi-Molie`re: None, V. Juif: None, L. DupontKazma: None, N. Herraney: None, J.-M. Reimund: None, B. Duclos: None
P0923 ENDOSCOPIC BALLOON DILATION OF STRICTURES IN
CROHNS DISEASE PATIENTS: SAFE AND EFFECTIVE
ALTERNATIVE TO REPEATED SURGERY
M. Bortl k1,2,*, D. Duricova2, M. Lukas2, N. Machkova2, V. Hruba2,
I. Romanko2, K. Mitrova2, M. Lukas2
1
Department of Internal Medicine, 1st Medical Faculty, Charles University, 2IBD
Clinical and Research Center, ISCARE and 1st Medical Faculty, Charles
University, Prague, Czech Republic
Contact E-mail Address: mbortlik@seznam.cz
INTRODUCTION: Endoscopic balloon dilation is frequently used to avoid
repetitive surgery in patients with Crohns disease.
AIMS & METHODS: The aim was to evaluate efficacy and safety of endoscopic
balloon dilations in patients with Crohns disease-related strictures. This was a
retrospective study in patients who underwent endoscopic balloon dilation
between May 2007 and December 2013 at a single tertiary IBD center. We
assessed both short- and long-term efficacy and safety of this procedure as well
as relationship between efficacy and specific disease and patients characteristics.
RESULTS: We performed 220 dilations in 108 patients with Crohns disease (49
women, median age 37 years, range 13-75), majority of procedures (85%) were
performed in anastomotic strictures. Obstructive symptoms preceded only 53%
of dilations, remaining procedures were either coincidental, or resulted from
regular endoscopic check-up. Technical success (passage with endoscope through
the stricture after dilation) was achieved in 77% of procedures, 75% of dilations
were effective clinically (relief of obstructive symptoms). Median duration of
symptomatic relief was 10 months (range 1-59). Significantly more patients
with end-to-end anastomosis lost their obstructive pain after dilation as compared to those with end-to-side anastomosis (89% vs. 61%, resp., p 0.01,
Fisher s exact test). In contrary, patients with end-to-side anastomosis had significantly longer clinical effect (median duration 17 months, range 3-55) compared to patients with end-to-end anstomosis (median duration 10 months, range
1-38, p 0.006, Mann-Whitney test). Technical success was associated with
longer duration of symptomatic relief. We have not found any relationship
between age, smoking or medical therapy at the time of procedure, and clinical
efficacy of dilation. Mild bleeding occured after 9% of dilations, it was stopped

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endoscopically in all cases. Serious complications, such as delayed bleeding or


perforation were rare (2%), and no patient died.
CONCLUSION: Endoscopic balloon dilation is highly effective and safe therapeutic modality of Crohns disease-related strictures, especially when the passage
of the scope is achieved. Effectiveness of dilation seems not to bee associated with
medical treatment.
Acknowledgement: The study was supported by IBD-COMFORT Foundation.
Disclosure of Interest: None declared
P0924 FACTORS AFFECTING THE INCIDENCE OF AN EARLY
ENDOSCOPIC RECURRENCE AFTER ILEOCOLONIC RESECTION
FOR CROHNS DISEASE: A MULTICENTRE STUDY
T. Yamamoto1,*, P. Kotze2, A. Spinelli3, Y. Suzuki4, F. Teixeir5 on behalf of the
MULTIPER Study Group
1
Inflammatory Bowel Disease Centre, YOKKAICHI HAZU MEDICAL
CENTRE, Yokkaichi, Japan, 2Colorectal Surgery Unit, Cajuru University
Hospital, Curitiba, Brazil, 3IBD Surgery Unit, Humanitas Research Hospital,
Milano, Italy, 4Internal Medicine, Toho University, Sakura, Japan, 5Colorectal
Surgery, Gastrosaude, Marilia, Brazil
INTRODUCTION: An early endoscopic recurrence is frequently observed in
patients following resection for Crohns disease (CD). However, factors affecting
the incidence of an early endoscopic recurrence have not been fully determined.
AIMS & METHODS: The aim of this study was to evaluate risk factors for an
endoscopic recurrence after ileocolonic resection for CD. This was a retrospective, international multicentre study. All consecutive patients who underwent
ileocolonic resections for CD in 7 IBD referral centres from 3 countries
(Japan, Brazil, Italy) were initially included in our MULTIPER database. In
this study, 127 patients with the first ileocolonoscopy conducted between 6 and
12 months after resection were included. The endoscopic activity score at the
proximal site of the ileocolonic anastomosis was determined according to
Rutgeerts, and an endoscopic recurrence was defined as a Rutgeerts sore of 
i2. The following variables were investigated as potential risk factors for an early
endoscopic recurrence: sex, age at surgery, location and behaviour (perforating
vs non-perforating) of CD, smoking, concomitant perianal lesions, preoperative
use of steroids, immunosuppressants and biologics, previous resection, blood
transfusion, surgical procedure (open vs laparoscopic), length of resected
bowel, type of anastomosis (side-to-side vs end-to-end), postoperative complications, granuloma, and postoperative biologic therapy. To identify risk factors for
an endoscopic recurrence, both univariate and multivariate analyses were
conducted.
RESULTS: Forty-three patients (34%) developed an endoscopic recurrence
which was confirmed at the time of ileocolonoscopy between 6 and 12 months
after resection. In the univariate analysis, only preoperative steroid use was significantly associated with a higher rate of an early endoscopic recurrence.
Twenty-one of 45 patients (47%) on steroids and 22 of 82 patients (27%) without
steroids developed an endoscopic recurrence (p 0.04). In the multivariate analysis, no factors were associated with the incidence of an endoscopic recurrence.
CONCLUSION: This study failed to find any significant factors associated with
an endoscopic recurrence after ileocolonic resection for CD. However, prospective studies are necessary to precisely evaluate the impact of perioperative medications on an early endoscopic recurrence.
Disclosure of Interest: None declared
P0925 HAND-ASSISTED
LAPAROSCOPIC
VERSUS
COLECTOMY FOR ULCERATIVE COLITIS: SAFETY AND
FEASIBILITY

OPEN

T. Yamamoto1,*, S. Nakayama1, K. Matsumoto1


1
Inflammatory Bowel Disease Centre, YOKKAICHI HAZU MEDICAL
CENTRE, Yokkaichi, Japan
INTRODUCTION: Laparoscopic surgery is now becoming widely used in the
management of colorectal cancer. However, safety and feasibility of laparoscopic
colectomy for ulcerative colitis (UC) have not been fully evaluated.
AIMS & METHODS: Since 2005, we have introduced hand-assisted laparoscopic surgery (HALS) for patients with UC and extensive Crohns colitis.
This study was to assess safety and feasibility of HALS for UC. Seventy UC
patients were treated with HALS (HALS group). The outcomes of HALS were
compared with those of open surgery conducted for 70 age-, sex- and disease
severity-matched patients (OPEN group).
RESULTS: In both groups, 37 elective patients were treated with a total proctocolectomy and ileal pouch-anal (canal) anastomosis with a loop ileostomy, and
33 emergency patients with a total colectomy (rectal closure) with an end-ileostomy. In the HALS group, intra-operative complications were experienced in two
patients (duodenal injury 1, colonic perforation 1). None of the patients required
conversion to open procedure, and laparoscopic procedure was successfully completed in all patients. In the HALS group, the mean operative time was 293
minutes, which was significantly longer than 258 minutes in the OPEN group.
The mean intra-operative blood loss was not significantly different between the
groups. Eighteen patients (26%) in the HALS group and 20 patients (29%) in the
OPEN group experienced postoperative complications (not significant). Six
patients in the HALS group and 7 patients in the OPEN group required laparotomy for postoperative complications (not significant).
CONCLUSION: Although HALS takes longer time as compared with open
surgery, it can be safely conducted without conversion to open procedure.
HALS is a feasible option in the surgical management of UC.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
OTHER LOWER GI DISORDERS II POSTER EXHIBITION HALL
XL_____________________
P0926 URGENT LOWER GASTROINTESTINAL BLEEDING: IS THERE
A PLACE FOR COLONOSCOPY WITHOUT ORAL PREPARATION
IN ELDERLY PATIENTS? A SINGLE CENTRE EXPERIENCE
A.R. Alves1,*, S. Giestas1, R. Cardoso1, S. Lopes1, P. Figueiredo1, F. Portela1,
C. Sofia1
1
Gastroenterology Department, Coimbra Hospital and University Centre,
Coimbra, Portugal
Contact E-mail Address: alvess.anarita@gmail.com
INTRODUCTION: In urgent lower gastrointestinal bleeding (LGIB), bowel
preparation for colonoscopy is highly influenced by logistic factors, patient tolerance and adverse reactions, particularly in elderly patients. In these cases a
colonoscopy can be performed without preparation (WP) or after a cleansing
enema (CE).
AIMS & METHODS: The aim of this study was to compare diagnostic accuracy
of urgent colonoscopy WP and after CE in elderly patients. It was performed a
retrospective study involving patients aged over 70 years with acute LGIB, submitted to colonoscopy WP and after CE, according to the gastroenterologist
option, for a 6-month period. Cases with known inflammatory bowel disease
or recent polipectomy were excluded. Data related with demographics, clinical
information, colonic segment reached in the exam and diagnostic findings in the
two groups were compared.
RESULTS: Seventy-four patients (mean age 81.66.6 years, 54.4% male) were
included. Chronic medication: antiaggregants - 50.0%, anticoagulants - 10.8%
and nonsteroidal anti-inflammatory drugs - 4.1%. Mean hemoglobin value at
admission was 11.12.9g/dl and red blood cell transfusion was required in 24.3%
patients. Colonoscopy was performed WP in 70.3% and after CE in 29.7%.
Colonic segment reached: cecum - 5.4%, ascending colon - 2.7%, transverse
colon - 12.2%, descending colon - 23.0%, sigmoid colon - 52.7% and rectum 4.1%. Diagnostic findings: ischemic colitis - 29.7%, diverticula - 20.3%, hemorrhoids - 10.8% and neoplasia - 6.8%. There were no statistically significant
differences between WP and CE colonoscopies regarding the colonic segment
or diagnostic findings. Globally, including the diagnosis considered as definitive
by the gastroenterologist, the diagnostic yield of colonoscopy without oral preparation, (WP and after CE) was 56.8%. Transfusion requirement at admission
was an independent risk factor for absence of diagnosis, in both groups (OR 11.5;
p50.001).
CONCLUSION: Comparing WP and post CE colonoscopy, there were no differences in the colon segment achieved or in endoscopic findings. Colonoscopy
without oral bowel preparation showed to have a limited diagnostic yield. In
more severe LGIB (with transfusion requirement) should be considered diagnostic colonoscopy after oral preparation ab initio.
Disclosure of Interest: None declared
P0927 PREDICTIVE FACTORS OF RECURRENCE AND MORTALITY IN
LONG-TERM IN PATIENTS WITH COLONIC ANGIODYSPLASIA
BLEEDING
C. Gallois1,*, D. Lorenzo1, E. Cuillerier2, R. Faroux3, B. Bour4, A.-J. Remy5,
C. Naouri6, A. Pariente7, G. Bellaiche8, B. Lesgourgues1, S. Nahon1
1
CH Montfermeil, Montfermeil, 2CH Dreux, Dreux, 3CHD Vendee, Vendee, 4CH
Le Mans, Le Mans, 5CH Perpignan, Perpignan, 6CH Macon, Macon, 7CH Pau,
Pau, 8CH Aulnay, Aulnay, France
Contact E-mail Address: claire.gallois2412@gmail.com
INTRODUCTION: Data on rates of recurrence and mortality throughout the
course of colonic angiodysplasia are limited. The aim of this study is to determine
rates and risk factors for recurrence and mortality in long-term in a cohort of
patients.
AIMS & METHODS: In 2007, data from 2462 patients with lower gastrointestinal bleeding were collected prospectively in 102 french general hospitals; 79
patients (3.2%) bled on colonic angiodysplasia. We retrospectively studied in
2013 the follow up of these patients. Collected data were: rates of death and
reccurence, taking anticoagulant and antiplatelets treatments, comorbidity
Charlsons score, ischemic and valvular diseases. Data were obtained by contacting the referent gastroenterologist, the general practitionner and sometimes the
patient. Predictive factors of recurrence and mortality were studied by univariate
analysis.
RESULTS: Data of 46 patients (58.2% of the initial population) were collected;
it was 22 women (47.8%). Six patients were excluded because of an early death,
13 patients were lost to sight and in 14 cases no data were available. The median
duration of follow up was 3.3 years (OQR 25-75% :1.5-5.4 years). The average
age of patients at the end of follow up was 76.8 /- 9 years; 8 (17.4%) had a
valvular disease. Twenty-three patients died (50%), including 4 from bleeding
recurrence. Mortality rates at 1 year, 3 years et 5 years were respectively 19.6%,
34.8% and 43.5%. Eighteen patients (39.1%) had at least a bleeding recurrence.
Reccurence rates at 1 year, 3 years and 5 years were respectively 19.6%, 34.8%
and 39.1%. These reccurences were complicated by 4 deaths. One patient has
needed an hemostatic colectomy. Seven patients (38.8% of recurrences) had to
stop anticoagulant and antiplatelet treatments because of a recurrence, and 3
have developed after that an ischemic disease (2 strokes and one myocardial
infarction). No risk factors of recurrence and mortality was found, especially
taking anticoagulant and antiplatelets treatments or a valvular disease.
Charlons score was not higher in dead patients.
CONCLUSION: Bleeding colonic angiodysplasia are a rare cause of lower gastrointestinal bleeding and concern an elderly population. In this study, after a

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median follow-up of 3.3 years, the cumulated rate of recurrence was 39.1% and
the mortality rate was 54.3%. The continuation of antiplatelet and anticoagulant
treatment is not associated with a higher risk of recurrence and conversely stopping aspirin may increase the risk of death because of ischemic diseases.
Disclosure of Interest: None declared
P0928 LONG-TERM FOLLOW-UP AND PREDICTIVE FACTORS OF
REBLEEDING AND MORTALITY IN PATIENTS WITH
DIVERTICULAR BLEEDING
D. Lorenzo1,*, P. Lahmek1, C. Gallois1, B. Lesgourgues1, C. Champion1,
R. Faroux2, B. Bour3, A. Jean Remy4, T. Morin5, C. Naouri6, A. Pariente7,
M. Picon8, E. Poncin9, G. Macaigne10, J.A. Seyrig11, S. Nahon1 on behalf of
ANGH
1
hepatogastroenterologie, hopital de montfermeil, Montfermeil , 2hepatogastroenterologie, CH vendee, La roche sur Yon, 3hepatogastroenterologie, CH Le Mans,
Le mans, 4hepatogastroenterologie, CH perpignan, Perpignan, 5hepatogastroenterologie, CH Tarbes, Tarbes, 6hepatogastroenterologie, CH Macon, Macon,
7
hepatogastroenterologie, CH Pau, Pau, 8hepatogastroenterologie, CH Aix en
provence, Aix en Provence, 9hepatogastroenterologie, CH Dax, Dax, 10hepatogastroenterologie, CH Lagny, Lagny, 11hepatogastroenterologie, CH centre
Bretagne, Pontivy, France
Contact E-mail Address: diane.lorenzo@gmail.com
INTRODUCTION: Data on rates of recurrence and mortality in patients with
diverticular bleeding (DB) are limited. The aims of this study were to determine
rates and risk factors for recurrence and mortality in a large cohort of patients
with previous DB.
AIMS & METHODS: In 2007, data from 2462 patients with lower GI bleeding
were collected prospectively in 102 French general hospitals, 789 (32%) had DB.
We retrospectively studied in 2013 the follow up of these patients. The following
data were collected: recurrence and mortality rates, drug intake (anticoagulants,
antiplatelet agents, NSAIDs), rate of surgery and comorbidities (evaluated by the
Charlsons score). These data were obtained by contacting the gastroenterologist,
the attending physician and sometimes the patient himself. Predictive factors of
recurrence and mortality were studied by univariate and multivariate analyses.
RESULTS: Data of 365 patients (47.3 % of the initial population) were collected, including 181 women (49.6 %). Mean age of patients was 84.79.7
years. Median duration of follow-up was 3.9 years. Hundred forty eight patients
died (40.5%) nine of them after bleeding. Mortality rate at 1, 3 and 5 years were
22 %, 36 % and 52 % respectively. Sixty-nine patients (19.2%) had at least one
recurrent bleeding. Recurrence rate at 1, 3 and 5 years were 11 %, 21% and 30%
respectively. Among patients with recurrence, 9 died (12.8 % mortality of recurrences) and 3 (4.3%) had surgical hemostasis procedure. Anticoagulation or
antiplatelet therapy were discontinued in 17 (19.2%) cases.
Risk factors for mortality by multivariate analysis were: age4 80 years (p
50.001) and a Charlson comorbidity score 4 2 (p 0.003). Discontinuation
of anticoagulation or antiplatelet therapies was not associated with an excess
risk of death by cardiovascular events.
No risk factors for rebleeding were identified in particular taking antiplatelet or
anticoagulant therapy. A past history of DB was almost significant (p 0.078).
CONCLUSION: In this population, cumulative recurrence rate was 19.2 % after
a median follow up of 3.9 years, and the mortality rate of 40.5 %. The majority
of deaths were not related to bleeding. Continuation of anticoagulant and antiplatelet treatment was not associated with an excess risk of rebleeding conversely
discontinuation did not significantly increased mortality from ischemic injury.
Disclosure of Interest: None declared
P0929 OUTCOMES OF URGENT COLONOSCOPY IN PATIENTS WITH
LOWER GASTROINTESTINAL BLEEDING

colonoscopy for LGIB should be individualized, taking into consideration relative importance of timing of intervention versus colonic preparation and overall
impact on Clinical management of patients.
Disclosure of Interest: None declared
P0930 ENDOSCOPIC
BAND
LIGATION
FOR
DIVERTICULAR HEMORRHAGE: A LARGE CASE SERIES

COLONIC

K. Nakano1,*, M. Ego1, Y. Shimamura1, T. Ikeya1, N. Ishii1


1
Gastroenterology, St. Lukes International Hospital, Tokyo, Japan
INTRODUCTION: Endoscopic band ligation (EBL) has been performed for
haemostasis in colonic diverticular haemorrhage1. However, the number of the
patients who have colonic diverticular haemorrhage and have been treated by
EBL is not sufficient, and the safety and efficacy of EBL in the colon have not
been fully established.
AIMS & METHODS: The aim of this study is to evaluate the safety and efficacy
of EBL for colonic diverticular haemorrhage. EBL was applied as an initial
treatment in 91 consecutive patients (67 males and 24 females; age range: 34-93
years) who presented between June 2009 and March 2014 with definitive colonic
diverticular haemorrhage. This type of haemorrhage involves the diverticula with
stigmata of recent haemorrhage (SRH) such as active bleeding (AB), non-bleeding visible vessels (NBVV), or adherent clots (AC). We retrospectively evaluated
these patients to determine the success rates of EBL and the rates of early rebleeding (re-bleeding within 30 days of the initial EBL) and to outline any complications such as perforation and abscess formation. Informed written consents
for EBL were obtained from all the patients.
RESULTS:
Location in colon (right / left), no

68 / 23

SRH (AB / NBVV / AC), no


Success rate of EBL (%)
Median procedural duration (range) (min)
Rate of early re-bleeding after EBL (%)
Median time to early re-bleeding (range) (days)
Complications (%)

33 / 22 / 36
93 (85/91)
36 (15-101)
15.3 (13/85)
2 (0-21)
0 (0/85)

The results of performing EBL for colonic diverticular haemorrhage are presented in the table. The success rate of EBL was 93% (85/91). Five lesions that
had a small orifice and large dome and one lesion with an orifice that was too
large could not be adequately suctioned into the suction cup of the endoscopic
ligator, and EBL was not successful. Endoscopic clipping or epinephrine injection was performed in these cases, and in one of the cases interventional radiology was also performed for haemostasis. The rate of early re-bleeding after
EBL was 15.3% (13/85). Re-bleeding was managed conservatively and/or endoscopically (repeat EBL or endoscopic clipping) except in one case where a right
hemicolectomy was performed because of the patients preference. There were no
complications such as perforation or abscess formation after EBL.
CONCLUSION: EBL can be considered to be a safe and effective endoscopic
treatment for colonic diverticular haemorrhage.
REFERENCES
1. Ishii N, Setoyama T, Deshpande GA, et al. Endoscopic band ligation for
colonic diverticular hemorrhage. Gastrointest Endosc 2012; 75: 382-387.
Disclosure of Interest: None declared
P0931 GI BLEEDING IN THE MODERN ERA - A 3-YEAR REVIEW AT
TALLAGHT HOSPITAL

G. Muzzaffar1,*, S.M. Gill1, A. Nawaz 1, T. Niaz 1 on behalf of


Gastroenterology, Maroof International Hospital, Islamabad
1
Gastroenterology, Maroof International Hospital, Islamabad, Pakistan
Contact E-mail Address: gill95@yahoo.com

P. Moore1,*, D. McNamara1
Tallaght Hospital, Tallaght, Ireland
Contact E-mail Address: moorepe@tcd.ie

INTRODUCTION: Early endoscopy is the standard of care in upper gastrointestinal bleeding. However most patients with lower gastrointestinal bleeding
(LGIB) have favorable outcomes and majority will stop bleeding spontaneously.
Therefore the role of urgent colonoscopy in LGIB remains controversial.
AIMS & METHODS: We wanted to study, diagnostic yield and clinical outcome
of urgent colonoscopy in patients with Lower gastrointestinal bleed. We prospectively enrolled 140 consecutive patients who presented to our facility with lower
gastrointestinal bleed. Study was conducted from January 2012 to December
2012. All patients who had malena, upper GI endoscopy was normal (was not
source of bleed) were considered eligible for this study.
RESULTS: 120 urgent colonoscopies were performed for LGIB during study
period. 70 (59%) were male. Mean age was 56.5 years and median age was 56.6
years (range 18:8 to 90.0 years). Caecal intubation rate was (60% n 70). 10% (n
12) of patients needed repeat colonoscopy due to inadequate visualization of
bowel for definite clinical decisions. (25.0% n 30) had an endoscopic therapy
done. 40% (n 12) of them altered the immediate clinical management. Causes
were found in (60%n 70) of patients. However only 40% (n - 24) of them had
endoscopic therapy and (60% n 46) had no clinical impact on immediate management of patients though the cause was identified. The causes were colorectal
ulcers (n 30, 25%), diverticular disease (n 40, 34%), hemorrhoid (n 20, 17 %),
colitis (n 20, 17 %), carcinoma (n 10, 8%).
CONCLUSION: Urgent colonoscopy for LGI bleed results in high rate of
incomplete examinations. Even when causes were found, only half of them had
an impact on the clinical management in terms of endoscopic intervention or
change in immediate clinical decision. Therefore, decision to perform urgent

INTRODUCTION: Gastrointestinal bleeding is a common clinical condition


accounting for up to 13% of Gastroenterology referrals. It frequently requires
hospitalization with subsequent intervention and is associated with significant
morbidity and mortality. Determining the origin of bleeding can be a challenge.
Newly available modalities in both gastroenterology and radiology are available
to address obscure bleeding cases.
AIMS & METHODS: a) To examine the role of endoscopic and radiological
investigations in a cohort with GI bleeding.
b) To assess the diagnostic performance of available radiological and endoscopic
techniques in cases of GI bleeding, including obscure bleeding.
Methods:
A Retrospective analysis was undertaken of patients admitted with
Gastrointestinal bleeding at Tallaght Hospital from 2010-2013 via HIPE
(Primary discharge diagnosis Malaena, Haematemesis, Gastrointestinal haemorrhage or IDA due to bleeding). Discharge summaries were reviewed and
patients were excluded if they were 518 yrs or had no evidence of bleeding.
All radiological and endoscopic investigations were identified from cross-referencing with Keogh Radiology, Capsule Endoscopy (CE) and Unisoft
Endoscopy Reporting Systems. Outpatient investigations were included if
prompted by the index admission. Patient demographics, procedures and positivity rates for the various modalities were recorded
RESULTS: In all, 418 patients were identified from HIPE, 106 (25%) were
excluded following discharge review. Of the 312 remaining cases the majority
were male 176 (56%) with a mean age of 59 years (Range 18-97). In all 294 (94%)
presented with overt bleeding vs 18 (6%) with occult bleeding. Of note 18 (6%)

A388
underwent no investigation for bleeding. Of the 294 who had tests, 163 (55%)
had either a colonoscopy or OGD and 122 (41%) had both and 39 (13%)
proceeded to have additional endoscopic tests, CE and/or Enteroscopy. In all
110 (37%) had a specialized radiological test. After any investigation, 122 (41%)
had negative tests with no etiology found. While 77 (26%) had obscure GI
bleeding defined as a negative gastroscopy and colonoscopy. In this obscure
cohort, only 26 (34%) had 2nd line GI Investigations and disregarding standard
CT, only 27 (35%) had a specialized radiological test. Overall 66 (22%) remained
obscure despite all investigations. The frequency of investigations by type and
positivity rate is illustrated in table 1. Diagnostic yield was highest for standard
endoscopy at 48% OGD and 28% Colon whilst also significant for CE (31%),
Enteroscopy (50%) and Angiography (50%).
CONCLUSION: Obscure GI bleeding remains common (26%) and the diagnosis
often remains elusive despite advanced endoscopic and radiological tests. The
diagnostic yield for many commonly employed less specific modalities is poor
and suggests changes to the diagnostic paradigm are appropriate.
Disclosure of Interest: None declared
P0932 HOW TO DETERMINE THE NEED FOR EMERGENCY
COLONOSCOPY TO ACHIEVE TIMELY HEMOSTASIS OF LOWER
GI BLEEDING
S. Umezawa1,*, S. Koyama2, T. Kato1
Division of Gastroenterology, 2Endoscopy Center, Tokyo Metropolitan Hiroo
Hospital, Tokyo, Japan
Contact E-mail Address: p0a4p7a3n1e8k4o1@yahoo.co.jp
1

INTRODUCTION: We occasionally perform endoscopic hemostasis during


emergency colonoscopy for lower gastrointestinal (GI) tract bleeding, but endoscopic hemostasis is not always necessary. Making the correct decision about the
need for emergency colonoscopy is very important from the perspective of preparation and examination time.
AIMS & METHODS: To investigate how to determine the need for endoscopic
hemostasis in cases of lower GI bleeding, 241 cases of lower GI bleeding
(excluding post polypectomy bleeding) that underwent CT and emergency colonoscopy between January 2008 and February 2014 were reviewed retrospectively.
Glasgow-Blatchford scores (usually used in upper GI bleeding) and the results of
CT and colonoscopy were analyzed. The indications for hemostasis were active
bleeding, a visible vessel, and adherent clot.
RESULTS: High-frequency colonic bleeding sources included diverticular bleeding (122 cases, 51%), ischemic colitis (52 cases, 22%), and rectal ulcer (15 cases,
6%). Hemostasis was required in 41 (17%) cases. CT findings consisted of extravasation of contrast medium showing active bleeding (group A; 23 cases) and
colonic wall thickening showing inflammation (group C; 47 cases). Group B was
defined as neither extravasation nor wall thickening (171 cases). Endoscopic
hemostasis was performed in 83% of group A (19/23), 13% of group B (22/
171), and none of group C. The Glasgow-Blatchford scores without melena
were significantly higher in hemostasis cases (7.6  3.8) than in no hemostasis
cases (4.3  4.0) (P50.01). Scores of hemostasis cases varied from 1 to 15, and 37
of 41 hemostasis cases had scores of four or more, whereas 109 of 200 of no
hemostasis cases had scores of three or less (P50.01). If one takes both group B
cases with scores of three or less and group C cases as non emergency cases, there
were 119 non-emergency cases. Of these, 116 (97%) were actually no hemostasis
cases, that is, use of this criterion would avoid emergency colonoscopy in 58% of
no hemostasis cases. The remaining three hemostasis cases all had slight bleeding.
CONCLUSION: CT findings and Glasgow-Blatchford scores are useful for
determining the need for emergency colonoscopy to achieve timely hemostasis
of lower GI bleeding.
Disclosure of Interest: None declared
P0933 LONG-TERM FOLLOW-UP STUDY ON THE RECURRENCE OF
PATIENTS HOSPITALIZED FOR ACUTE LOWER
GASTROINTESTINAL HEMORRHAGE
T. Aoki1,*, N. Nagata1, R. Niikura2, S. Moriyasu1, K. Sekine1, H. Okubo1,
K. Watanabe1, T. Sakurai1, C. Yokoi1, J. Akiyama1
1
Gastroenterology and Hepatology, National Center for Global Health and
Medicine, 2Gastroenterology and Hepatology, The University of Tokyo Hospital,
Tokyo, Japan
Contact E-mail Address: iitomo.1020@gmail.com
INTRODUCTION: Long-term recurrence in lower gastrointestinal bleeding
(LGIB), particularly benign diseases, has not been extensively studied. This
study aimed to ascertain the rate of recurrence in LGIB and associated risk
factors.
AIMS & METHODS: A cohort of 312 patients hospitalized for overt LGIB from
benign sources was analyzed. All patients underwent colonoscopy. The Charlson
comorbidity score and the use of non-steroidal anti-inflammatory drugs
(NSAIDs), low-dose aspirin, other antiplatelet drugs, and warfarin were assessed.
The KaplanMeier method was used to estimate the cumulative recurrence of
LGIB. The Cox proportional hazards model was used to estimate hazard ratios
(HR).
RESULTS: Rebleeding was identified in 84 patients with a mean (SD) follow-up
of 19 (22) months. The cumulative rebleeding rate at 1 and 5 years was 21% and
51%, respectively. Associations with recurrence by univariate analysis were as
follows: age 65 years (p50.01), Charlson comorbidity index 2 (p50.05), and
the use of NSAIDs (p 0.02), low-dose aspirin (p 0.03), non-aspirin antiplatelet drugs (p50.02) and warfarin (p 0.59). Multivariate analysis revealed age
65 years (HR, 1.9; p 0.02) and the use of NSAIDs (HR, 1.8; p 0.03) and
non-aspirin antiplatelet drugs (HR, 2.0; p 0.02) as independent risk factors for

United European Gastroenterology Journal 2(1S)


rebleeding. Dual antiplatelet therapy carried a higher risk than single therapy
(adjusted HR, 1.8; p50.05).
CONCLUSION: There is a substantial recurrence rate among patients hospitalized for LGIB. Besides advanced age, various antithrombotic drugs increased
the risk of recurrence in LGIB. Dual users of those drugs have a higher risk than
single users.
Disclosure of Interest: None declared
P0934 WHAT FACTORS ARE RELATED TO DEATH
INTESTINAL ISCHEMIA IN THE PATIENTS WITH RENAL
FAILURE UNDERGOING CONTINUOUS HEMODIALYSIS?

FROM

Y. Goto1,2,*, K. Yasuda3, H. Kasuga4, H. Seno5, S. Maruyama6, K. Wakai2


Gastroenterology, Nagoya Kyoritsu Hospital, 2Preventive Medicine, Nagoya
University Graduate School of Medicine, 3Nephrology, Masuko Memorial
Hospital, 4Nephrology, Nagoya Kyoritsu Hospital, 5Nephrology, Kaikoukai Josai
Hospital, 6Nephrology, Nagoya University Graduate School of Medicine, Nagoya,
Japan
1

INTRODUCTION: It has been reported that end-stage renal disease (ESRD)


patients on hemodialysis (HD) were at risk for intestinal ischemia (II). Some
severe cases of II die from transmural gangrenous necrosis of the intestine.
Other mild cases develop ulceration and colitis, and can be treated with conservative management. In this study, we tried to identify factors associated with
death from II in patients on HD.
AIMS & METHODS: Approximately 2,500 patients at our dialysis clinics underwent HD three times weekly from January 2009 to October 2013. The diagnosis
of II, which includes mesenteric ischemia, non-occlusion mesenteric ischemia,
and ischemic colitis, was made from endoscopy, pathology, computed tomography, ultrasound findings, and/or clinical condition. The subjects were divided
into two groups of the fatal II group and the non-fatal II group. The latter
included some who died from other causes than II. Continuous variables were
compared by t-test, while qualitative variables by Fishers exact test.
RESULTS: Twenty-six of 2,500 longterm HD patients developed II for the first
time during the study period. The fatal and the non-fatal group consisted of 7
and 19 subjects, respectively. Six of the non-fatal group died from the following
causes: cerebral hemorrhage, infective endocarditis, heart failure, pneumonia,
suicide, and unknown. The frequencies of those who had each of warfarin and
laxative were higher in the fatal group than in the non-fatal (57.1% vs 5.26%,
respectively, p 0.01). Two fatal cases used both of the drugs. Then, we needed
avoid the effect of laxative on II, to focus on the effect of warfarin only. After
removal of the two, the corresponding result still remained to be significant
(66.7% in the fatal vs 5.56% in the nonfatal, p 0.04). Three of 4 who had
warfarin suffered from atrial fibrillation (Af) in the fatal group. In the nonfatal group, 3 had Af but 1 of them took warfarin. There was no significant
difference in the frequency of Af between the two groups. The fatal group more
frequently underwent laparotomy than the non-fatal (42.9% vs 5.26%, respectively, p 0.05). Regarding the location of II, 71.4% of the fatal group developed
the ischemic colitis on the right-sided, while 5.26% of the non-fatal on the rightsided (p50.01).
CONCLUSION: This study showed that there was a possibility that warfarin
causes the fatal II regardless of Af, as well as laxative. Therefore, considering the
previous reports that warfarin provokes calciphylaxis on ESRD, warfarin could
facilitate ischemia based on calcification of the feeding-artery. In addition, the
fatal group involved the right-sided colon, and undertook laparotomy more
frequently as the previous studied reported. Further studies with larger number
of the subjects are required to confirm our results.
Disclosure of Interest: None declared
P0935 COMPARISON OF MICROWAVE COAGULATION
MONOPOLAR AND BIPOLAR COAGULATION IN A PORCINE
MODEL

WITH

Z.P. Tsiamoulos1,*, C. Hancock2, P. Sibbons3, B.P. Saunders1


1
Wolfson unit for Endoscopy, St Marks Hospital/Academic Institute, London,
2
School of Electronic Engineering, University of Bangor, Bangor, 3Division of
Surgical Science, Northwick Park Institute for Medical Research, London, United
Kingdom
INTRODUCTION: Intra-procedural bleeding is considered an immediate serious adverse event and a major concern for the endoscopist and the patient.
Current endoscopic devices utilise monopolar or bipolar energy to treat acute
bleeding vessels and/or pre-coagulate visible vessels. Monopolar/Bipolar devices
have proven safe in clinical practice to control acute arteriolar bleeding but there
are no ex vivo comparative studies assessing the safety profile with histology.
AIMS & METHODS: The optimal time of application for the microwave modality of a new endoscopic device Speedboat-RS2, Creo Medical Ltd, UK was
initially assessed compared to a standard mono-polar endoscopic device,
Coagrasper, Olympus, USA. After histological assessment of the optimal time
range, a comparison of the Speedboat RS2 to a standard bipolar endoscopic
device, Gold Probe, Boston Scientific, USA, and to standard monopolar
device, Coagrasper, was performed to assess the safety profile of coagulation
with histology and the endoscopic performance of pre-coagulation in the porcine
colon. The Speedboat-RS2 blade delivers microwave coagulation (5.8GHz) for
hemostasis, and also has an insulated hull to prevent thermal injury to the underlying muscle layer. Cold snare polypectomy (9mm) was performed to reveal the
submucosal layer and video recorded on 3 consecutive 60kg pigs. The colonic
resection sites were aligned in cranial-caudal direction. The following parameters
were measured: histological assessment and pre-coagulation endoscopic performance. All animals were recovered for 2days, 5days and 7days.

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United European Gastroenterology Journal 2(1S)


RESULTS: In animal one, microwave bursts of 5sec, 10sec and 15sec were
applied to the revealed submucosa compared to standard monopolar bursts of
a 1sec. Histology showed that 5sec and 10sec of microwave has equivalent histological appearance with standard monolopar preserving the serosal integrity
with mild muscle alteration. In animal 2 and 3, microwave was applied for 9 sec
in 6 lesions, standard monopolar was applied for 1-2sec in 6 lesions and standard
bipolar was applied for 3-4sec in 6 more lesions. Histology showed viable serosa
with no muscle alterations in microwave group, viable serosa with mild muscle
alterations in standard bipolar and viable serosa with mild/moderate muscle
alterations in standard monopolar group. In all cases muscle layer cells were
contiguous. During the pre-coagulations endoscopic assessment, all modalities
were applied to coagulate vessels with median calibre of 2mm before and after
dissection. Effective pre-coagulation was achieved in 3 out of the 6 visible vessels
(microwave group) and in 2 out of the 6 visible vessels (standard monopolar and
bipolar groups). Effective coagulation (defined when blood flow stopped) was
achieved after the dissection, in all three groups.
CONCLUSION: Compared to Coagrasper (monopolar) and Gold Probe
(bipolar), the microwave modality of Speedboat RS2 appears to be equivalent
during the pre-coagulation phase. The safety profile of coagulation phase resembles the profile of the other two modalities but with less muscle alterations in the
histological specimens.
Disclosure of Interest: Z. Tsiamoulos Consultancy for: Creo Medical Ltd, C.
Hancock Shareholder of: Creo Medical Ltd, P. Sibbons Consultancy for: Creo
Medical Ltd, B. Saunders Consultancy for: Creo Medical Ltd

per year compared with 36 per 100 000 per year in NSA (p50.05). The probability of colon cancer is higher (OR 3.84; p50.05) in NSA compared with SA
patients. Similarly patients in the 65-70 age group have the highest risk
(OR 1.60; p50.05) of colorectal cancer.

P0936 BPREDICT:
BURGENLAND
PREVENTION
TRIAL
COLORECTAL DISEASE WITH IMMUNOLOGICAL TESTING

Table: Factors predicting risk of colorectal cancer in BCSP. *denotes statistical


significance (p50.05).
CONCLUSION: The colorectal cancer risk is significantly higher in the male
NSA BCS population in this regional study. This is the first such study in the
BCS population.
REFERENCES
Hebbar S, Fuggle WJ, Nevill AM, et al. Colorectal cancer incidence and trend in
UK South Asians: a 20-year study. Colorectal Dis 2012; 14.
Disclosure of Interest: None declared

OF

G. Leeb1,*, P. Hofer2, A. Gsur2, G. Bohm3, G. Puhr1, K. Mach1


1
Hospital Oberpullendorf, Oberpullendorf, 2Department of Medicine I, Medical
University of Vienna, Institute of Cancer Research, Vienna, 3Hospital Oberwart,
Oberwart, Austria
Contact E-mail Address: gernot.leeb@gmail.com
INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer
and cause of cancer death in Europe and continues to be among the most severe
health problems in the EU. In Austria, 4,600 new cases are diagnosed per year.
Ten years ago there used to be a remarkable east west decline in CRC incidence
with the highest incidence rates in Burgenland, a province in the very east of
Austria, with about 300.000 inhabitants. Therefore, 2003 the screening project
Burgenland PREvention trial of colorectal Disease with ImmunologiCal Testing
(bPREDICT) was initiated.
AIMS & METHODS: This screening project utilizing fecal immunochemical
testing (FIT) was first implemented in the district Oberpullendorf in 2003.
Since 2006, the screening program has been expanded to the whole province
Burgenland. Between 2003 and 2010, a qualitative fecal occult blood test was
applied. Since 2010 this test was replaced by a quanitiative FIT test (OC sensor,
Mast Diagnostica Germany).
Annually, 150.000 residents aged between 40 and 80 (50% of the population)
receive a stool sample container and are invited to take part in bPREDICT. Stool
samples are processed and evaluated in a central laboratory. Individuals with
positive testing (cutoff level 50ng hemoglobin/mL) are advised to undergo
colonoscopy.
RESULTS: The target group from 2003 to 2012 was 1.2 million. In this time
period 100.000 colonoscopies were performed, 20,292 (25%) were triggered by
the screening program. The participation rate was about 35 percent, 8.3 percent
of the participants had a positive FIT. Within this group we found CRC in 314
persons, high grade intraepithelial neoplasias in 225, high risk adenomas in 2,673
and low risk adenomas in 3,379 individuals.
Age-standarized incidence rates per 100.000 decreased from 43.4 (average 19982000) to 25.7 (average 2009-2011) in Burgenland (Statistic Austria).
Within bPREDICT FIT positive participants are also invited to take part in the
Colorectal Cancer Study of Austria (CORSA), yielding a large biobank (DNA
and plasma) comprising more than 10.000 CRC patients and colonoscopy-negative controls. This biobank is the basis for several molecular epidemiology
research projects.
CONCLUSION: Most recent data of Statistic Austria show that the incidence
pattern has changed in Austria, Burgenland is now on the last but one position,
this may due to the effect of bPREDICT.
Disclosure of Interest: None declared
P0937 COLORECTAL CANCER RISK IS HIGHEST IN MALE NONSOUTH ASIAN (NSA) PATIENTS IN A REGIONAL BOWEL
CANCER SCREENING (BCS) POPULATION

95% confidence interval


Parameter

Risk odds ratio

Lower

Upper

Male
NSA
South Staffordshire
Walsall
Wolverhampton
Age 65-70
Age 70-75
Intercept (SA female aged 60-65
years living in Dudley is the
baseline and all groups are
deviations from this
estimate)

2.26021*
3.846221*
0.517331*
1.124037
1.130742
1.602908*
1.449215*
4.54E-05

1.72979
1.894585
0.318861
0.827787
0.818731
1.18412
1.051271
3.06E-05

2.953527
7.806838
0.839457
1.526534
1.562051
2.170592
1.997707
6.75E-05

P0938 OPPORTUNISTIC COLORECTAL CANCER SCREENING HOW


OFTEN DID WE FOUND PATHOLOGY IN CLINICAL PRACTICE?
O. Gradinaru Tascau1, I. Sporea1,*, A. Popescu1, S. Bat;aga2, M. Popescu1,
M. Danila1, R. Sirli1, S. Bota1 on behalf of Athena Plaian, Dorina Chisevescu,
Flavia Mot;iu
1
Department of Gastroenterology and Hepatology Timisoara, Emergency County
Hospital of Timisoara, Timisoara, 2Medical 1 Department, University of Medicine
and Pharmacy Tg Mures, Tg. Mures, Romania
Contact E-mail Address: alinamircea.popescu@gmail.com
INTRODUCTION: While a population-based colorectal cancer screening program is not implemented, probably any other method of early detection of this
disease is welcome.
AIMS & METHODS: The aim of our study was to assess which were the findings in regard to neoplastic pathology (polyps or colorectal cancer) of opportunistic colorectal cancer screening by colonoscopy (asymptomatic subjects in
whom we performed a colonoscopy for colorectal cancer screening).
We included in our study the colonoscopies performed in asymptomatic subjects
in whom the indication was screening for colorectal cancer, in 3 endoscopy
centers from Timisoara and Tg. Mures. We excluded the colonoscopies performed in patients with previous history of polyps and colorectal cancer. We
studied the prevalence of polyps, significant polyps (polyp 1cm) and colorectal
cancer, globally and in different age groups.
RESULTS: 2537 colonoscopies were performed in asymptomatic subjects in the
3 endoscopy centers between January 2008-December 2013; from these 95.9%
(2433 cases) were total colonoscopies. The statistic analysis was performed only
on total colonoscopies.
The 2433 total colonoscopies performed in asymptomatic subjects led to the
discovery of polyps in 32.1% (783/2433) of cases, of significant polyps in only
7.2% (175/2433) of cases and of colorectal cancer in 2% of cases (50/2433). Most
often we found neoplastic pathology in the 60-69 years age group: 38.5% (302/
785) polyps, 8.4% (66/785) significant polyps, 2.5% (20/785) cancers.
CONCLUSION: The detection rate of significant pathology (significant polyps
and cancer) in asymptomatic subjects colonoscopy was 9.2% in the studied
group, which confirms the need for colorectal cancer screening.
Disclosure of Interest: None declared
P0939 RADIATION
PROCTOCOLITIS
COLORECTAL NEOPLASIA

AND

THE

RISK

OF

H. Padmanabhan1,*, M. Widlak1, L. Ford1, C. Simpson1, C. Kothari1,


B. McKaig1, A. Veitch1, M. Brookes1
1
Gastroenterology, Royal Wolverhampton NHS Trust, Wolverhampton, United
Kingdom
Contact E-mail Address: Hari. Padmanabhan@nhs.net

J.S. Mcgrath , E. Randell , S. Antle , D. Pace , S. Stone , M. Borgaonkar1


1
Medicine, Memorial University, St. Johns, Canada
Contact E-mail Address: jmcgrath@mun.ca

INTRODUCTION: The literature on colorectal cancer screening and ethnic diversity is dominated by studies from the USA. There is no such published data from
the UK BCS population. 10.3% of the Black Country BCS population are of
South Asian (SA) ethnicity. We aimed to determine the effect of ethnicity and
gender on the risk of polyp or cancer detection over a 5 year period (2007-11).
AIMS & METHODS: Data was collected from the BCS cohort retrospectively.
SA patients were identified and compared to those of Non South Asian (NSA)
ethnicity and colonoscopy outcomes were determined.
RESULTS: 3552 subjects underwent BCS colonoscopy (NSA 3363; SA 189).
The incidence of colorectal cancer within the SA population was 7.4 per 100.000

INTRODUCTION: A mainstay in the treatment of prostate and some gynecological cancers is the use of external beam radiation therapy. Radiation proctocolitis is a common complication of this treatment. Little is known about the
association between external beam radiation, radiation proctocolitis, and the risk
of colonic neoplasia.
AIMS & METHODS: The current study is a prospective analysis of patients with
radiation proctocolitis referred from the Newfoundland and Labrador Bliss
Murphy Cancer Centre from Jan. 2010 to Dec. 2013. The current study investigated the relationship between radiation proctocolitis at index colonoscopy and
the detection of colorectal polyps. These results were then compared to data

1,*

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United European Gastroenterology Journal 2(1S)

collected for colonoscopies conducted on (i) average risk individuals and (ii) fecal
immunohistochemical test (FIT) positive patients. Data was recorded on a standardized data sheet and entered into SPSS version 20.0 for analysis.
RESULTS: Data was collected on 81 individuals who had radiation proctocolitis, 130 individuals who were average risk, and 109 FIT positive individuals. At
colonoscopy the adenoma detection rate (ADR) was 60.5% for patients with
radiation proctocolitis, 21.5% for individuals at average risk and 55.6% for
FIT positive individuals. The colon cancer rate was 6.2% for individuals with
radiation proctocolitis, 0% for individuals at average risk and 1.8% for FIT
positive individuals.
There was a significant difference in the ADR between the patients with radiation
proctocolitis and average risk individuals 60.5% vs. 21.3 (p50.0001) and the
corresponding colon cancer rate was 6.2% vs. 0 respectively (p50.002). There
was no significant difference in the ADR or colon cancer rate in patients with
radiation proctocolitis compared to FIT positive.
Histiopathology

ADR

Colon Cancer Rate

Patients with Radiation Proctocolitis (n 81)


Average Risk Individuals (n 130)
FIT Positive Individuals (n 109)

60.5%
21.5%
55.6%

6.2%
0%
1.8%

CONCLUSION: Pelvic radiation exposure is known to be associated with the


development of proctocolitis. This study also shows it is associated with an
extremely high prevalence of colorectal neoplasia. Patients with a history of
radiotherapy require screening for colonic neoplasia.
Disclosure of Interest: None declared
P0940 HEIGHT AND RISK OF COLORECTAL ADENOMA: A COHORT
STUDY OF A KOREAN MEN
J. Pyo1,*, Y.H. kim1, S.N. Hong1, D.K. Chang1, P.-L. Rhee1, J.J. Kim1
1
Gastroenterology, Samsung medical center, Seoul, Korea, Republic Of
Contact E-mail Address: tyoma@hanmail.net
INTRODUCTION: Increasing cancer risk with increasing adult height has been
reported for all cancers combined and for several common site specific cancers,
including colon and rectum. The underlying mechanism is unclear, but it has
been suggested that increased cell turnover mediated by insulin like growth factor
or increased cell number might increase cancer risk by increasing the amount of
tissue available to undergo malignent transformation. Evidence is limited, however, for adenomatous polyps, precursors to colorectal cancer.
AIMS & METHODS: The aim of this study was to evaluate the associations
between height and risk of colorectal adenomas at the various stages of the
adenoma-carcinoma pathway.
We conducted a retrospective study using data from who had undergone a complete colonoscopy as part of a health examination at the Health Promotion
Center of Samsung Medical Center between October 13, 2009 and December
31, 2011. A total of 1356 male subjects were included. Multivariable logistic
regression analysis was used to evaluate the association between height and
colorectal adenoma.
RESULTS: Each 5-cm increment in height was associated with 19.4% and 9.8%
higher risk of advanced colorectal adenoma and high risk colorectal adenoma,
after adjusting for age, BMI, metabolic syndrome, smoking, drinking, family
history of colorectal cancer, and regular use of aspirin. Still, there was clearly
no significant association. (p-vaule 0.4404 and 0.6852 each)
CONCLUSION: Unlike colorectal cancer, there is no clear association between
colorectal adenoma and height. The difference between the patterns associated
with cacner and adenoma could be explained as some cancers may not arise from
an adenoma, and only a limited portion of subjects with adenomas will eventually have cancer.
REFERENCES
1. Sung J, Song J-M, Lawlor D, Davey Smith G, Ebrahim S. Height and sitespecifi c cancer risk: a cohort study of a Korean adult population. Am J
Epidemiol 2009; 170: 5364. 2. Gunnell D, Okasha M, Davey Smith G, et al.
Height, leg length, and cancer risk: a systematic review. Epidemiol Rev.
2001;23(2):313342. 3. Roland B. Walter, Theodore M. Brasky, Sarah A.
Buckley, John D. Potter, Emily White Height as an Explanatory Factor for
Sex Differences in Human Cancer J Natl Cancer Inst;2013;105:860868 4.
Green J, Cairns BJ, Casabonne D, Wright FL, Reeves G, Beral V, Height and
cancer incidence in the Million Women Study: prospective cohort, and metaanalysis of prospective studies of height and total cancer risk. Lancet Oncol.
2011 Aug;12(8):785-94. 5. Albanes D, Winick M. Are cell number and cell proliferation risk factors for cancer? J Natl Cancer Inst. 1988;80(10): 772774. 6.
Height and Site-specific Cancer Risk in Korea 63 Am J Epidemiol 2009;170:53
64 7. Ma J, Pollak MN, Giovannucci E, et al. Prospective study of colorectal
cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and
IGF-binding protein-3. J Natl Cancer Inst. 1999;91(7):620625. 8. Albanes D,
Jones DY, Schatzkin A, Micozzi MS, Taylor PR. Adult stature and risk of
cancer. Cancer Res 1988; 48: 165862. 9. Pischon T, Lahmann PH, Boeing H,
et al. Body size and risk of colon and rectal cancer in the European Prospective
Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2006; 98:
92031.
Disclosure of Interest: None declared

P0941 RECTAL NEUROENDOCRINE TUMOURS: MANAGEMENT AND


SURVIVAL IN 60 PATIENTS
K. Naik1,*, R.E. Rossi1, D. Mandair1, C. Toumpanakis1, M. Caplin1
1
Neuroendocrine Tumour Unit, Centre of Gastroenterology, Royal Free Hospital,
London, United Kingdom
Contact E-mail Address: keval.naik@nhs.net
INTRODUCTION: Rectal neuroendocrine tumours (rNETs) are increasing in
incidence, with more found incidentally on routine colonoscopy.
AIMS & METHODS: To retrospectively analyse a cohort of rNETs to characterize diagnostic features and clinical behaviour. Patients (pts) with confirmed
diagnosis of rNET were identified from a database
RESULTS: 60 pts evaluated, median age 55 years (range 23-78). Most common
presentation was rectal bleeding n 29 (48%). 29/60 pts had tumour 51cm, 7/60
pts 1-2cm, 22/60 42cm, 2/60 size was unknown. Of patients with tumour size
51cm, 3/29 did not require endoscopic follow-up (pT1a) and of the other 26,
none had evidence of recurrence on endoscopic follow-up (follow-up range 6 to
88 m). 24/60 pts had metastases at presentation, 5/60 developed metastases
during follow-up (of these 29 pts 86% liver, 40% bone, 10% lung). Of 29 pts
with metastases, 24/29 had somatostatin receptor imaging with 62% avid uptake.
Chromogranin A available in 23/29 pts and was not elevated in 83%. Of 29 pts
with metastases, 19/29 had chemotherapy, 10/29 somatostatin analogues (SST),
15/29 surgery and 10/29 peptide-receptor-radionuclide-therapy (PRRT).
Chemotherapy: 1/19 pts partial response, 2/19 stable disease (SD), 12/19 progressive disease (PD) (median time to progression 4 months (m)); 4/19 no data.
PRRT: 4/10 had SD (follow-up range 24 to 53m), 4/10 PD (median time to
progression 4m, range 2-9), 2/10 no data. SST: 2 sustained SD (range 12-27m),
7/10 PD, (median time to progression 3m, range 2-5); 1/10 no data. During
median follow-up of 20m (range 3170m), 100% of pts with primary tumour
51cm, 86% with tumour size 1-2cm, and 25% with size 42cm are currently
alive. Tumour size 42cm have poorer outcome than the other 2 groups
(p50.001).
CONCLUSION: Tumours larger than 2cm are associated with poor prognosis.
Chromogranin A is mostly normal even in advanced disease. Prospective studies
are needed to determine progression free survival data for systemic therapy.
Disclosure of Interest: None declared
P0942 CANCER INVADING THE SUBMUCOSAL LAYER: SOMETHING
IS MISSING. A SINGLE CENTER EXPERIENCE
L. Peraro1,*, E. Rosa-Rizzotto1, M. Lo Mele2, E. Guido1, D. Caroli1,
F. Ancona1, F. Polato1, M. Rugge2, F. De Lazzari1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital,
2
Surgical Pathology and Cytopathology Unit, Department of Diagnostic, Medical
Sciences and Special Therapies, University of Padua, Padua, Italy
INTRODUCTION: Actually we dont know how long does it takes for a preneoplastic lesion to became a cancer invading the submucosal layer (pT1). We
dont know, also, how long a pT1 lesion rest in the submucosal layer before going
deeper to reach the muscolaris propria becoming pT2. Qualitative parameters to
determinate high metastatical risk in pT1 as showed in Europeans Guidelines in
Colorectal Cancer (CCR) screening1 and Japanese Society for Cancer of the
Colon and Rectum (JSCCR) guidelines2 are: high tumor grade, deep extent of
invasion, vascular invasion, presence of high grade budding, polipectomy resection margin 51mm. The presence of none (low risk) or one (high risk) of these
parameters involves a metstatical risk from 0.7% to 36%, and a overall average
of 13%.
AIMS & METHODS: to assess the metastatical risk in pT1 lesions diagnosed
during routine colonoscopies and in those found during the colorectal cancer
screening program. We retrospectively enrolled in the study 15.252 consecutive
patients gone for colonoscopy in our Endoscopy Unit from april 2009 to april
2014. 4.970 patients were Fecal Occult Blood Test (FOBT) positive and enrolled
in the CCR screening program. pT1 patients gone for a strict follow-up with CT
scan, CEA and colonoscopy. Fisher exact test and Students T-test for unpaired
data were used for statistical analysis.
RESULTS: in 5 yr 119 pT1 (67M, 52F) tumors were detected, 96 during screening colonoscopies (SC) and 23 during routine colonoscopies (RC). Overall pT1
prevalence was 1,9% in SC and 0.3% in RC. 60/119 (50.4%) patients underwent
for surgery because considered at high metastatic risk, of those only 3 patients
(3.3%) presented limphnode metastasis, 1/5 (20%) in RC and 2/55 (3.6%) in SC
(p ns). The mean follow-up was 132 months. During the follow-up none other
patient had metastasis. Population mean age was higher in RC 71.87 vs 61.24
(p50.0001). High risk pT1 were more frequent in SC (56.2% vs 26.1%, p 0.01).
No differences were found in the two populations for: polyp dimension, tumor
grading, deep/extent of invasion, vascular invasion, polypectomy resection
margin (p ns). The presence of tumor budding was higher in male (23.1%
15/65 vs 6.1% 3/49, p 0.01) and in RC pT1 gone for surgery (60% 3/5 vs
16% 8/50, p50.05).
CONCLUSION: The probability to find a pT1 tumor is 6 times higher during
SC. Colorectal pT1 lesions found during the screening colonoscopy program
seams to be at less metastatic risk compared to analogue pT1 lesions found
during routine colonoscopies, probably because are diagnosed at an early
stage; for this reason we must find new parameters to better predict the real
metststic risk for these kind of tumors. The controversial budding parameter is
probably affected by gender.
REFERENCES
1 Quirke P, et al. European guidelines for quality assurance in colorectal cancer
screening and diagnosis. First edition quality assurance in pathology in colorectal
cancer screening and diagnosis. Endoscopy 2012; 44: SE112-SE130.

United European Gastroenterology Journal 2(1S)


2 Watanabe T, et al. Japanese Society for Cancer of the Colon and Rectum
(JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin
Oncol 17: 129.
Disclosure of Interest: None declared
P0943 NATIONAL COLORECTAL CANCER SCREENING PROGRAME
IN CROATIA
M. Kalauz1,*, N. Antoljak2, M. Katicic3, M. Strnad Pesikan4, D. Stimac5,
M. Samija6
1
Department of Internal Medicine, Division of Gastroenterology, Clinical Hospital
Center Zagreb, Zagreb, Croatia, 2Public Health Institute, Zagreb, -, 3Clinical
Hospital Merkur, Zagreb, Croatia, 4Clinical Hospital Rijeka, Rijeka, -,
5
Department of gastroenterology, Clinical Hospital Center Rijeka, Rijeka,
6
Ministry of Health, Zagreb, Croatia
Contact E-mail Address: mirjanakalauz1@gmail.com
INTRODUCTION: In Croatia in 2012 colorectal cancer was the second leading
cause of cancer mortality in males, (1.136 or 55.0/100.000) as well as women (868
or 39.1/100.000). According to Croatian Cancer Registry in 2011 it was diagnosed in 19% of cases at the localised stage, and 61% with regional metastases or
distant metastases at time of diagnosis.
AIMS & METHODS: Faecal occult blood testing (FOBT) is an evidence based,
cost-effective screening approach in organised population-based colorectal
cancer screening programmes throughout the world. The hypersensitive guaiacbased Hemognost (Biognost, Zagreb) card test was used to screen population age
between 50-75 years in Croatia.
RESULTS: By the end of September 2012 a total of 1,419.639 persons (born
between 1933-1957) were received three FOBT test cards. Among them, 15,339
persons were ineligible for testing. 288,935 (21%) sent test packages with correctly applied specimens which is in accordance to the response rate according to
EU guidelines (17.2 to 70.8%) in the first round.
Within the program, more than 10.000 colonoscopy examinations were conducted (80% response rate) and 576 people with colon cancer were discovered
(2.3% of total number of tested persons, which is consistent with the expected:
EU guidelines 1.2-2,3/1000). In 4223 people polyps were found (39.7% of
incurred colonoscopy) and removed. The largest number of polyps were found
in the left half of the colon: 64% (19%, 37% and 8% in the rectum, sigma, and
descendens, respectively). The other 36% were detected in the proximal part
(17% in the transverse colon and 19% in ceco-ascending colon). Small polyps
in the rectum (5-10 mm in diameter), sigmoid and descending colon were histologically found to be tubular adenomas in 60% of cases, with a low degree of
dysplasia, and 40% were classified as hyperplastic. Polyps of this size in the
transverse or ceco-ascending colon in almost 20% had a histologically villous
component, but still had a low degree of dysplasia. Polyps sized 10-20 mm in
diameter were in 43% cases tubulovillous, and among them, 32% had areas with
a high degree of dysplasia, especially those polyps in the ceco-ascending or
transverse part
CONCLUSION: According to first cycle results and organisational obstacles it
was suggested a need for intervention strategies in order to improve compliance.
A number of organizational changes are performed together with educational
and promotional activities to improve awareness of CRC screening usefulness
and increase participation rates.
Disclosure of Interest: None declared
P0944 RISK FOR COLORECTAL ADENOMAS AMONG PATIENTS
WITH INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS OF
THE PANCREAS (IPMNS): A CASE-CONTROL STUDY
N. Panic1,*, G. Capurso2, F. Attili3, S. Boccia1, G. Costamagna3, G. Vitale3,
G. Delle Fave2, S. Stigliano2, A. Larghi3
1
Institute of Public Health-Section of Hygiene, Universita` Cattolica del Sacro
Cuore, 2Digestive and Liver Disease Unit, University Sapienza, 3Digestive
Endoscopy Unit, Universita` Cattolica del Sacro Cuore, Rome, Italy
Contact E-mail Address: nikola.panicmail@gmail.com
INTRODUCTION: It is well documented that patients with IPMN are at the
incresed risk of colorectal cancer.
AIMS & METHODS: Aim of the study was to investigate if risk of colorectal
cancer development in patients with IPMN may be related to an increased propensity to harbor colorectal adenomas. A two centers casecontrol study. Cases
were prevalent IPMN without history of colorectal cancer, who underwent
screening colonoscopy for the first time in their life. Matched controls were
enrolled along side between individuals who underwent colonoscopy for screening and evaluation of non specific abdominal pain.
RESULTS: During the study period, 122 IPMN cases and 246 controls were
enrolled. IPMNs were more frequently branch-duct (87.7%), multifocal (67.2%)
with a mean diameter of greater lesion of 16.1 mm  8.1. First-degree family
history of colorectal cancer was more frequently among controls (14.1% vs.
37.8%, p50.001), while 2nd degree family history of any cancer (18.2% vs.
10.3%, p 0.035), as well as pancreatic ductal adenocarcinoma (3.3% vs. 0%,
p 0.01) was more frequent among cases. Colorectal polyps were found in 52
IPMN (42.6%) and 78 controls (31.7%). In 29 cases (23.8%) and 55 controls
(22.5%) histological examination disclosed adenomatous polyps, which were
multiple in 11 cases (9%) and 20 controls (8.2%). Three cases of cancer were
found, 2 in IPMNs (1.6%) and 1 in controls (0.4%). We observed a significantly
increased risk for harboring colorectal polyps among IPMN cases than IPMNfree controls [adjusted odds ratio (OR): 1.60, 95% confidence interval (CI): 1.102.59]. However, IPMN was not significant risk factor for harboring adenomatous
polyps (OR: 1.05, 95% CI: 0.61-1.80). Due to the small number of discovered

A391
cancers it was not possible to conduct the same analysis for colorectal cancer as
an outcome.
CONCLUSION: Increased risk of colorectal cancer in patients with IPMNs do
not seem to be related to an increased propensity to harbor adenomatous polyps.
Disclosure of Interest: None declared
P0945 DIMINUTIVE POLYPS: RESECT AND DISCARD STRATEGY IS
NOT ENOUGH. A DIFFERENT FOLLOW UP IS NEEDED IF THERE
IS A CONCOMITANT PRESENCE OF LARGER POLYPS
D. Caroli1,*, L. Peraro1, E. Rosa-Rizzotto1, M. Lo Mele2, E. Guido1,
F. Ancona1, F. Polato1, M. Rugge2, F. De Lazzari1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital,
2
Surgical Pathology and Cytopathology Unit, Department of Diagnostic, Medical
Sciences and Special Therapies, University of Padua, Padua, Italy
INTRODUCTION: Oncological significance of diminutive polyps alone (DPA)
is controversial as the association of diminutive polyps with other types of larger
polypoid or non-polypoid lesions (DPP). The resect and discard strategy for
diminutive polyps appears to be cost effective but the post polypectomy follow
up, that is crucial for colonoscopy screening programs, still remain uncertain1.
Colonoscopy intervals are based on pathological assessment of all polyps
detected during colonoscopy and several elements contribute to assess the risk
to develop colon cancer: polyps dimension, colon side, histology, number of
polyps detected at the index colonoscopy and colonoscopy quality.
AIMS & METHODS: to establish the appropriateness and safety of the resect
and discard strategy in a colorectal cancer screening population undergone for
index colonoscopy in 2010 and subjected at least a survaillance colonoscopy
within 3 years. We retrospectively analyzed 585 patients positive for FOBT
undergone for colonoscopy during a Colorectal Cancer Screening Program in
Padua in 2010 and with polyps. Subsequently among this initial population were
identified 387 patients with detection of DPA or with DPP. These patients were
divided into two groups: DPA (184 pts) and DPP (203 pts). The number, dimension, colon side and histology of all the polyps were assessed at first colonoscopy
and during the follow up. Only clean colonoscopies were considered in the study.
Statistical analysis used: Fisher exact test and Students T-test for paired and
unpaired data.
RESULTS: A regular follow up was observed in 82 pts (M 60-F 22, mean age 66
y) with DPA and in 158 pts (M 113- F 45, mean age 66 y) with DPP. Quality
index of colonscopy: adenoma detection rate 57.2% and coecal intubation 98%.
1150 polyps resected at index colonoscopy, 397 (34.3%) DPA and 758 (65.7%)
DPP. 450 polyps were resected during the follow up, 125 (27.7%) in DPA and
325 (72.2%) in DPP. The total number of patients with advanced adenomas was
higher in DPP vs DPA 108-83% vs 21-17% (p50.0001) at index colonoscopy,
but in the follow up colonoscopy the difference about advanced adenomas was
not significant (p 0.342). Also the right side was predominantly in DPP at the
index colonoscopy (113-59.8% vs 76-41.2%, p50.0001). Finally the two group
as expected are different for mean number of total polyps at index DPA 2.17 vs
DPP 3.72 (p50.0001) and subsequent colonoscopy DPA 1.52  DPP 2.06
(p50.05), mean number of colonoscopies at follow up was similar 1.37 vs 1.39
(p ns). One interval cancer was found in the group of DPP in the right colon,
this event was statistically consistent with literature data2.
CONCLUSION: The resect and discard strategy appears to be safe, cost
effective and adequate in the context of colorectal screening programs against
data of follow up in patients with only diminutive polyps, in who prevails not
advanced adenomas. A closer follow up program should be performed according
to the presence of non diminutive polyps, where prevails advanced adenomas and
frequently the lesions are in the right colon with consequent high risk of interval
cancer.
REFERENCES
Hassan C, et al. Gastrointest Endosc Clin N Am 2013; 23: 663-678.
Samadder NJ, et al. Gastroenterology 2014; 146: 950-960.
Disclosure of Interest: None declared
P0946 KRAS_G12C
MUTATION:
AN
EFFECTIVE
SCREENING
BIOMARKER FOR MUTYH-ASSOCIATED POLYPOSIS DIAGNOSIS
E. Hernandez-Illan1, C. Guarinos1, M. Juarez1, A. Castillejo2, F. Balaguer3,
C. Egoavil4, M.-I. Castillejo2, L. Perez-Carbonell 1, M. Rodriguez-Soler 5, V.M. Barbera2, S. Oltra6, A.-B. Sanchez-Heras 7, J.-L. Soto2, R. Jover5,* on behalf
of EPICOLON, EPIPOLIP groups and Hereditary Cancer Program of the
Valencian Region
1
Research Unit. Alicante University Hospital, Alicante, 2Molecular Genetics
Department. Elche University Hospital, Elche, 3Institut de Malaties Digestives i
Metabo`liques. CIBERehd. Hospital Clnic., Barcelona, 4Department of Pathology.
Alicante University Hospital, 5Gastroenterology Department, Alicante University
Hospital, Alicante, 6La Fe University Hospital, Valencia, 7Genetic Counselling
Unit, Elche University Hospital, Elche, Spain
Contact E-mail Address: jover_rod@gva.es
INTRODUCTION: MUTYH-associated polyposis (MAP) is an autosomal
recessive inherited condition commonly showing an attenuated familial adenomatous polyposis phenotype. It represents about 1% of all CRC although is
thought that it might be underdiagnosed. Apparent sporadic cases not fulfilling
clinical and pathological criteria are being described, though no screening marker
is widely adopted.
AIMS & METHODS: We aimed to approach the analytical and clinical validation of KRAS_G12C somatic mutation as screening marker for MAP diagnosis.
Sensitivity, specificity, positive and negative predictive values were calculated.
A total number of 103 patients were included in this study: 75 patients with
polyposis (EPIPOLIP cohort) and 28 CRC patients (EPICOLON and

A392

United European Gastroenterology Journal 2(1S)

Hereditary Cancer Program Comunidad Valenciana, cohorts). All patients were


tested for germline mutations at MUTYH gene (Sanger sequencing of the whole
coding region and intron-exon boundaries); and KRAS_G12C mutation at
polyps or CRC microdisected tissues (Sanger sequencing).
RESULTS: MUTYH biallelic mutation was present in 13 and 19 of the polyposis
and CRC patients, respectively. No MUTYH mutation was detected in 62 and 9
of the polyposis and CRC patients, respectively. Eleven out of 13 (84.6%)
MUTYH biallelic carriers and 2 out 62 (3.2%) wildtype MUTYH polyposis
patients harboured KRAS_G12C mutation in at least one of their polyps. In
the CRC cohort, 13 out of 19 (68%) MUTYH biallelic mutation carriers and
none of the nine MUTYH wildtype patients had KRAS_G12C mutation. Taking
together these results, we found that the diagnostic value of KRAS_G12C for
screening of MAP syndrome shows a specificity and sensibility of 0.972 and 0.75
respectively, with positive and negative predictive values of 0.923 and 0.896,
respectively.
CONCLUSION: Our results suggest that KRAS_G12C mutation is an effective
screening marker for MAP syndrome in both, polyps and tumor tissues. Larger
studies are needed to confirm the clinical value of this marker for its potential use
in the universal screening for MAP-syndrome.
REFERENCES
1- Balaguer F, et al. Identification of MYH mutation carriers in colorectal
cancer: a multicenter, case-control, population-based study. Clin Gastroenterol
Hepatol 2007; 5: 379-387.
2- Guarinos C, Juarez M, Egoavil C, et al. Prevalence and characteristics of
MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps. Clin Cancer Res 2014; 20: 1158-1168.
Disclosure of Interest: None declared
P0947 SHOULD ALL BARIUM ENEMAS BE CONVERTED
COLONOSCOPY? ANALYSIS OF 300 BARIUM ENEMAS BY
INDICATION AND OUTCOME

TO

F. Rana1,*, D. Tate1, P. Hanson1


1
Gastroenterology, Great Western Hospital, Swindon, United Kingdom
Contact E-mail Address: fahdrana@outlook.com
INTRODUCTION: Historically in the UK barium enemas have played a greater
role in clinical diagnosis than in countries where colonoscopy is more available. It
is now the policy of the Department of Health and thr National Institue for
Health and Care Excellence (NICE) to improve access to colonoscopy and
phase out barium enemas[1]. At the Great Western Hospital 2,700 barium studies
were done in 2012; to switch all of these to colonoscopy would have major
implications for colonoscopy workload. Furthermore, the switch might not
always be clinically appropriate.
AIMS & METHODS: We retrospectively studied the stated indications for 300
consecutive barium enemas in patients over 45 years (older age group) and those
45 years and younger (younger age group). We looked at the outcome for each
age group and indication: a Relevant Positive examination revealed pathology
considered relevant to the stated indication; a Diagnostic Negative was a negative
result with no further colonic investigations (these 2 groups constitute Useful
Results). A Disbelieved Negative was a negative result followed up with lower
gastrointestinaI endoscopy. False Positives and False Negative results were based
on subsequent revision of findings on colonoscopy.
RESULTS: Five indications accounted for 83% of all studies in both age groups
cumulatively: altered bowel habit (ABH) 42%; Per Rectal bleed (PRB) 22%;
abdominal pain (AP) 15%; anaemia (An)14% and diarrhoea (Dia) 7%.
ABH comprised the majority of indications in both age groups when combined
together (42%). In the younger age group, this, together with abdominal pain,
yielded mostly diagnostic negatives (63% & 78% respectively) and only 12%
relevant positives, all diverticulosis. The yield of relevant positives doubled in
the older age group to 25% (mostly diverticulosis but 18% neoplasms, 5%
strictures, 5% rectocele).
PRB was more common than other indications in the younger age group (38%)
compared with older age group (20%). In the younger age group all patients with
PRB who had positive results were found to have neoplasms, whereas in the older
age group, 33% were neoplasms and 67% diverticulosis. The rectal bleeding
groups also provided the most disbelieved negatives (55%) prompting clinicians
to request a colonoscopy.
In the older age group, anaemia and diarrhoea had low yields (6% and 18%
respectively) and a significant number of disbelieved and false negatives necessitating further investigation with colonoscopy.
CONCLUSION: Colonoscopy is preferable in patients with rectal bleeding, diarrhoea or anaemia. For young patients with altered bowel habit and/or abdominal
pain a negative barium result was common and accepted as reassuring; colonic
investigation should therefore be used sparingly in these patients and where used,
should be less invasive and expensive than colonoscopy.
REFERENCES
1) National Institute for Health and Care Excellence 2013. Investigating and
diagnosing colorectal cancer; 131. London: National Institute for Health and
Care Excellence.
Disclosure of Interest: None declared

P0948 DISCORDANCE IN TUMOR GRADE BETWEEN PRIMARY AND


METASTATIC LESIONS IN PATIENTS WITH ENTEROPANCREATIC NEUROENDOCRINE TUMORS: IMPLICATIONS FOR
CLINICAL MANAGEMENT?
F. Foubert1,*, C. Dumars2, Y. Touchefeu3, N. Regenet4, H. Senellart5, M.F. Heyman2, T. Matysiak-Budnik4
1
IMAD & Hepato-Gastroenterology & Digestive Oncology, 2Service
dAnatomopathologie, CHU de Nantes, 3IMAD&Hepato-Gastroenterologie,
4
IMAD & CHU de Nantes, 5ICO, Centre Rene Gauducheau, Nantes, France
Contact E-mail Address: tamara.matysiakbudnik@chu-nantes.fr
INTRODUCTION: In neuroendocrine tumors (NET), the therapeutic strategy is
highly dependent on tumor grade assessed according to the WHO classification.
The decision is commonly based on the histological characteristics of the primary
tumor, even in the patients in whom metastatic disease developed several years
after resection of the primary tumor. It is possible, however that metastatic
lesions present characteristics different from the primary tumor which could
have important clinical implications. The aim of the present study was to compare the tumor grade between the primary tumors and their liver metastases in
patients with entero-pancreatic NETs, and to determine the consequences in
terms of survival
AIMS & METHODS: Patients with entero-pancreatic NETs treated in our institution from 1995 until 2012, for whom both the samples from the primary tumor
and from the liver metastases were available, were included. Clinical data were
collected and 3 markers of tumor cell proliferation (reflecting the tumor grade)
were evaluated: a) mitotic index (MI), measured by counting the number of
mitoses in 10 HPF presenting the highest mitotic activity, b) mitotic index measured with a new metaphase specific marker: phosphohistone 3 (PPH3), assessed
in the same conditions, and c) the Ki67 index, expressed as percentage of MIB1positive cells per 2000 tumor cells in the areas of the highest proliferation activity.
Statistical analyses were performed using the exact Mc Nemar test. Survival was
analysed using logrank test.
RESULTS: Twenty-five patients (12 males, median age 58 years, range 33-79)
were included. Primary NETs were pancreatic in 7 patients and intestinal in 18
patients. Liver metastases were synchronous in 20 patients and metachronous in
5 patients. 44% and 56% of primary lesions were of grade 1 and 2, respectively,
while 20%, 68% and 8% of the metastatic lesions were of grade 1, 2 and 3,
respectively. Tumor grade differed between the primary and the metastatic
lesion in 12 patients (48%): out of 10 patients who had a Ki672% in the
primary lesion, 8 had a Ki6742% in the metastatic lesion, out of 22 patients
who had a MI 5 2 in the primary lesion, 10 had a MI  2 in the metastatic
lesion, and out of 14 patients who had a PPH3 5 2 in the primary lesion, 9 had a
PPH3  2 in the metastatic lesion. The median Ki67 and MI in metastases were
statistically higher than in primary tumors (p 0.01). Ki67 of metastases, but not
of primary lesions, tended to correlate with mortality: 0% of mortality if Ki672
% and 66% if Ki6742% on metastases, vs 60% and 47%, respectively, on
primary lesions, for the median follow-up of 87 months. A good correlation
was found between Ki67 and PPH3 (p 0.0001), but not between Ki67 and
MI (p 0.4).
CONCLUSION: In about half of the patients with entero-pancreatic NETs,
there is a significant difference in tumor grade between the primary and the
metastatic lesions. Metastatic histology seems to better correlate with the survival. The prognostic and therapeutic impact of systematic biopsies of metastatic
lesions needs to be further investigated.
Disclosure of Interest: None declared
P0949 A STUDY OF HYPERPLASTIC POLYP AS THE PRECURSOR OF
SSA/P IN COLON AND RECTUM
H.-O. Yamano1,*, H.-O. Matsushita1, K. Yoshikawa1, E. Harada1, R. Takagi1,
Y. Tanaka1, M. Nakaoka1, R. Himori1, Y. Yoshida1, Y. Imai1, T. Sugai2,
H. Aoki3, E. Yamamoto3, H. Suzuki3
1
Department of Gastroenterology, AKITA RED CROSS HOSPITAL, Akita,
2
Department of Molecular Diagnostic Pathology, Iwate Medical University School
of Medicine, Morioka, 3Department of molecular biology, Sapporo Medical
University School of Medicine, Sapporo, Japan
Contact E-mail Address: h-yamano@h9.dion.ne.jp
INTRODUCTION: SSA/P (sessile serrated adenoma/polyp), the precursor of
MSI positive colorectal cancer proposed by serrated pathway, has recently
attracted attention. We pathologically and genetically investigated serrated
lesions including SSA/P based on the findings of magnifying endoscopy. We
have reported BRAF mutation presence in the right colon in SSA/P, CpG
island methylator phenotype (CIMP)-positive and characteristic findings of magnifying endoscopy (Kimura T, et al. Am J Gastroenterology 107:460-469, 2012).
It is essential to investigate the precursor of SSA/P.
AIMS & METHODS: According to the WHO classification, hyperplastic polyps
(HPs) were sub-classified and pathologically and genetically investigated. The
aim of this study was to investigate the precursor of SSA/P.
Subjects were 46 HPs endoscopically resected at our center. According to WHO
classification proposed in 2010, microvesicular variant (MVHP), goblet cell rich
variant (GCHP) and mucin poor variant (MPHP) were classified. We investigated genetic mutation and methylation from samples extracted from lesions by
location.
RESULTS: Classification of 46 HPs and locations was as follows; 33 MVHPs (14
lesions in the right colon and 19 in the left colon), 13 GCHPs (3 lesions in the
right and 10 lesions in the left), and absence of MPHP. In investigation of genetic
mutation, 7 MVHPs were observed in kras mutation, 22 MVHPs in BRAF
mutation and 4 MVHPs in wild type. Conversely, 8 GCHPs were observed in
kras mutation, 5 GCHPs in wild type and lesions were not observed in BRAF

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United European Gastroenterology Journal 2(1S)


mutation. Regarding investigation of methylation, CIMP-positive was confirmed
in 10 lesions out of 22 lesions indicating BRAF mutation in MVHPs and the
other lesions were CIMP-negative. In BRAF mutation, CIMP-positive was
observed in 8 lesions (66.7%) out of 12 lesions in the right colon and 2 lesions
(20.0%) out of 10 lesions in the left colon and difference between the left and
right was confirmed. On the other hand, all of the GCHPs were CIMP-negative.
CONCLUSION: The findings indicated that MVHP presence in the right colon
was considered to be similar to SSA/P by clinical pathology and generic background and may be the precursor of SSA/P.
Disclosure of Interest: None declared
P0950 SERUM SCD26 AND NDK-A IN A PREDICTIVE MODEL TO
IDENTIFY COLORECTAL ADVANCED NEOPLASIA IN A
NEGATIVE FECAL IMMUNOCHEMICAL TEST COHORT AT
FAMILIAL RISK
O. Otero Estevez1, L. De Chiara1, L. Barcia Castro1, M. Paez de la Cadena1,
F.J. Rodr guez Berrocal1, J. Cubiella Fernandez2,*, I. Castro Novo2,
V. Hernandez Ram rez3, C. Gonzalez Mao4, V.S. Mart nez Zorzano1
1
Bioqumica, Genetica e Inmunologa, Universidade de Vigo, Vigo, 2Servicio de
Aparato Digestivo, Complexo Hospitalario Universitario de Ourense, Ourense,
3
Servicio de Aparato Digestivo, 4Servicio de Analisis Clnicos, Complexo
Hospitalario Universitario de Vigo, Vigo, Spain
Contact E-mail Address: olalla.otero@uvigo.es
INTRODUCTION: First-degree relatives (FDR) of colorectal cancer (CRC)
patients have an increased CRC risk [1] and are likely to show advanced neoplasia [AN: CRC and advanced adenomas (AA)] despite a negative FIT [2].
Consequently, there is an imperative need to find new non-invasive screening
tests to identify patients with AN after a false-negative FIT result. Based on our
previous results we propose the proteins sCD26 and NDK-A as serum candidate
biomarkers [3-4].
AIMS & METHODS: To find a risk prediction model combining serum sCD26
and NDK-A proteins, and clinical variables to identify AN in FIT negative
subjects at familial risk. The studied cohort included 486 asymptomatic individuals with at least one FDR with CRC and a negative FIT result, recruited from
the Complejo Hospitalario de Ourense. All individuals underwent a colonoscopy and a blood extraction. Concentration of sCD26 and NDKA in serum was
measured with ELISA kits.
RESULTS: According to the colonoscopy findings patients were classified as:
335 with no neoplasia, 116 with non-advanced adenomas and 36 with AA. The
risk of AN associated with the molecular and clinical variables was evaluated
with a univariate analysis (see table).
Risk factors associated with the presence of AN in a FIT negative family-risk
cohort.
Variable

Odds Ratio (95% IC)

sCD26 (330ng/mL)
NDK-A (66.5 pg/mL)
Age (50 years)
Sex (male)
Number of FDR (2 or more)
Age of younger FDR (60 years)

7.38
2.78
2.90
2.00
1.20
1.03

50.001
0.003
0.020
0.047
0.679
0.055

(3.57-15.28)
(1.40-5.52)
(1.18-7.10)
(1.01-3.97)
(0.50-2.88)
(1.00-1.07)

The variables associated with an increased risk for AN (P50.1) were included in
the logistic regression model. The ROC curve obtained had an AUC of 0.820
(95% IC 0.758-0.891). The proposed risk model at a 0.122 cut-off predicts the
presence of AA with a sensitivity of 48.6% and a specificity of 89.4%.
Accordingly, 18 cases of AA originally not detected by FIT would be identified.
CONCLUSION: The risk prediction model proposed including serum sCD26
(330 ng/mL) and NDK-A (66.5 pg/mL), and the variables sex (male), age
(50 years) and age of younger FDR (60 years) has the capability to re-classify
FIT negative individuals who are at risk of having AA in a family-risk
population.
REFERENCES
1. Sulz et al. Eur J Gastroenterol Hepatol 2014; 26: 222-228.
2. Cha, et al. Digestion 2012; 86: 283-287.
3. De Chiara et al. BMC Cancer 2010; 10: 333-342.
4. Alvarez-Chaver, et al. J Proteomics 2011; 74: 874-886.
Disclosure of Interest: None declared
P0951 DIAGNOSTIC RISK FACTORS FOR THE DETECTION OF
ADVANCED SERRATED POLYPS IN ASYMPTOMATIC PATIENTS
J. Ijspeert1,*, M.van Leerdam2, I. Stegeman3, T.de Wijkerslooth1, E. Stoop4,
P. Bossuyt5, E. Kuipers4, E. Dekker1
1
Department of Gastroenterology and Hepatology, Academic Medical Centre,
2
Department of Gastroenterology and Hepatology, National Cancer Institute,
Amsterdam, 3Department of Otolaryngology, Utrecht University Medical Centre,
Utrecht, 4Department of Gastroenterology and Hepatology, Erasmus MC
University Medical Centre, Rotterdam, 5Department of Clinical Epidemiology,
Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam,
Netherlands
Contact E-mail Address: j.e.ijspeert@amc.uva.nl
INTRODUCTION: Evidence has accumulated that approximately 20% of colorectal cancer (CRC) arises from a serrated polyp (SP) precursor lesion via the

serrated neoplasia pathway. Therefore CRC population screening should not


only focus on detecting advanced adenomas and CRC, but also on detecting
advanced SPs (ASPs). Risk stratification for the detection of ASPs could contribute to target colonoscopy screening towards a population of increased risk.
AIMS & METHODS: The aim of this study was to identify diagnostic risk
factors associated with ASPs in a colonoscopy screening program for CRC.
Data were collected from the colonoscopy arm of a multicenter randomized
trial conducted in the Netherlands comparing colonoscopy with CT-colonography for primary population screening. 6600 Asymptomatic men and women
between the age of 50 and 75 years were randomly selected from a population
registry and invited to undergo a screening colonoscopy. Information on patient
risk factors was obtained before colonoscopy through an extensive and validated
risk questionnaire. A literature review was conducted to identify possible risk
factors for ASPs. For these risk factors, the diagnostic odds ratio (OR) for the
detection of ASPs during colonoscopy was calculated using multiple logistic
regression analysis. SPs were defined as hyperplastic polyps, sessile serrated
lesions or traditional serrated lesions. ASPs were defined as SPs 10mm or
SPs with dysplasia.
RESULTS: Of 6600 screening participants, 1426 underwent a colonoscopy; 1236
(86%) also completed the questionnaire. Of all participants, 636 (52%) were male
and the average age was 60.3 (SD 6.2). Colonoscopy detected an ASP in 53
(4.3%) participants.
The evaluated diagnostic risk factors are presented in table 1. The following risk
factors were significantly associated with ASPs detected at colonoscopy: current
smoking (OR: 4.36; 95% CI: 2.937.95), BMI (OR: 1.08 per kg/m2; 95% CI:
1.021.15) and fiber intake (OR: 1.02 per gram; 95% CI: 1.011.03).
Table 1. Association of risk factors and the detection of advanced serrated polyps

Risk factor

OR (95% CI)
univariate
advanced SP

Male gender
Age (years)
First degree relative with CRC
BMI (kg/m2)
Current smoking
Alcohol consumption (units/week)
Fiber intake (g/week)
Calcium intake (mg/week)
Aspirin/NSAID use

1.15 (0.66-2.00)
1.019 (0.98-1.07)
1.38 (0.68-2.79)
1.07 (1.01-1.14)
4.00 (1.95-8.22)
1.01 (0.98-1.04)
1.01 (1.00-1.02)
1.00 (0.99-1.01)
0.94 (0.48-1.86)

OR (95% CI)
multivariate
advanced SP

1.08 (1.02-1.15)
4.36 (2.93-7.95)
1.02 (1.01-1.03)

CONCLUSION: Current smoking, elevated BMI and elevated fiber intake are
diagnostic clinical risk factors for the detection of ASPs during colonoscopy in
asymptomatic patients. These risk factors could be combined with risk factors for
the detection of advanced adenomas and CRC to optimize targeting CRC population screening towards a high-risk population.
Disclosure of Interest: None declared
P0952 CIRCULATING GALECTIN-1 AND 90K/MAC-2BP CORRELATED
WITH THE TUMOR STAGES OF PATIENTS WITH COLON CANCER
K.-L. Wu1,*, E.-Y. Huang2, C.-M. Liang1
1
Division of Hepatogastroenterology, 2Department of radiooncology, Kaohsiung
Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Province of China
Contact E-mail Address: kengliang_wu@yahoo.com.tw
INTRODUCTION: The simultaneous correlation of serum galectin-1,-3, 90K/
Mac-2BP levels with clinical stages of patients with colon cancer has not yet been
clarified.
AIMS & METHODS: To measure the serum levels of galectin-1,-3 and 90K/
Mac-2BP of patients at different stages of colon cancer and analyze the correlation of these galectins with stages of colorectal cancers. One hundred ninety-eight
colorectal cancer patients (62  13 (range 31-85) years old, 43.6 % female) were
recruited for this study. Subjects were checked blood samples for serum galectin1, galectin-3, 90K/Mac-2BP and CEA by sandwich ELISAs. We determined the
correlation between plasma concentrations with pathologic TNM stages.
RESULTS: Our study found colon cancer patients with larger cancer sizes (stage
T3, 4 than T1, 2) have higher serum 90K/Mac-2BP levels (p 0.014) and patients
with lymph node metastasis have higher serum galectin-1 levels (p 0.002) but
there was not a significant correlation between galectin-3 levels and patients with
prognosis of colon cancer patients. In colon cancer patients with normal CEA
levels, serum galectin-1 levels could predict more lymph node metastasis.
CONCLUSION: We found 90K/Mac-2BP correlated with the size of colorectal
cancer. Galectin-1 but not galectin-3 was associated with lymph node metastasis.
Galectin-1 could predict more lymph node metastasis of colon cancer when colon
cancer patients had normal serum CEA levels.
Disclosure of Interest: None declared

A394
P0953 METHYLATED SEPTIN 9 DETECTION IN TISSUE AND PLASMA
OF COLORECTAL NEOPLASIA AND THE RELATIONSHIP TO THE
AMOUNT OF CIRCULATING CELL-FREE DNA
K. Toth1,*, R. Wasserkort2, F. Sipos1, A. Kalmar1,3, B. Wichmann1, K. Leiszter1,
G. Valcz1, M. Juhasz1, P. Miheller1, A. V. Patai1, Z. Tulassay1,3, B. Molnar1,3
1
2nd Department of Internal Medicine, SEMMELWEIS UNIVERSITY,
Budapest, Hungary, 2Extracorporeal Immune Modulation Unit, Fraunhofer
Institute of Cell Therapy and Immunology, Rostock, Germany, 3Molecular
Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary
INTRODUCTION: Methylated Septin 9 (SEPT9) was evaluated as a sensitive
and specific biomarker for colorectal cancer (CRC) in plasma samples. However,
it has not been investigated how methylated DNA detected in plasma relates to
the occurrence of methylated DNA in colon tissue.
AIMS & METHODS: The goal of this study was to quantitatively compare
levels of methylated SEPT9 in matched plasma and tissue samples of healthy,
adenoma and CRC cases; and to determine the amount of circulating free DNA
(cfDNA) and the expression of Septin-9 protein in tissue. Plasma and matching
biopsy samples were collected from 24 patients with no evidence of disease
(NED), 26 adenomas and 34 CRC. A commercial real-time PCR assay was
used to determine the total amount of DNA in each sample and the portion of
DNA methylated at a specific locus of SEPT9 after bisulfite conversion of DNA.
In a subset of tissue samples, Septin-9 protein expression was determined using
immunohistochemistry.
RESULTS: In tissue samples, percent of methylated reference (PMR) values of
SEPT9 above a selected PMR threshold of 1% were detected in 4.2% (1/24) of
NED, 100% (26/26) of adenoma and 97.1% (33/34) of CRC. PMR differences
were found highly significant (p50.001) between NED vs. adenoma and NED
vs. CRC comparisons.
In matching plasma samples SEPT9 PMR values, using a cut-off level of 0.01%,
were detected in 8.3% (2/24) of NED, 30.8% (8/26) of adenoma and 88.2% (30/
34) of CRC cases. Significant PMR differences were observed in comparisons
between NED vs. CRC (p50.01) and adenoma vs. CRC (p50.01).
Significant differences (p50.01) in the amount of cfDNA (circulating cell-free
DNA) were found between NED and CRC and a modest correlation was
observed between mSEPT9 concentration and cfDNA in plasma of cancer
patients (R2 0.48).
Protein expression of Septin-9 in tissues determined by IHC was inversely correlated to SEPT9 methylation levels with abundant expression in normals, and
diminished expression in adenomas and tumors.
CONCLUSION: Methylated SEPT9 was detected in healthy tissue samples only
at low levels, but significantly elevated in adenoma and CRC tissues. In plasma
samples, elevated mSEPT9 values were detected in CRC, but not in adenomas.
Tissue levels of mSEPT9 alone are not sufficient to predict mSEPT9 levels in
plasma. Parameters like degree of vascularisation of the lesions, the amount of
cfDNA in plasma and probably additional factors seem to be equally important.
Disclosure of Interest: None declared
P0954 COMPARATIVE CLINICOPATHOLOGICAL CHARACTERISTICS
OF COLON AND RECTAL T1 CARCINOMAS: A SINGLE-CENTER
RETROSPECTIVE STUDY
K. Ichimasa1,*, S.-E. Kudo1, H. Miyachi1, T. Hayashi1, T. Hisayuki1,
H. Oikawa1, S. Matsudaira1, Y. Kouyama1, N. Toyoshima1, T. Ishigaki1,
Y. Yagawa1, M. Misawa1, Y. Mori1, T. Kudo1, K. Kodama1, K. Wakamura1,
A. Katagiri1, M. Kaga1, S. Hamatani1, E. Hidaka1, F. Ishida1
1
Digestive Disease Center, Showa University Northern Yokohama Hospital,
Yokohama city, Japan
Contact E-mail Address: ichitommy14@yahoo.co.jp
INTRODUCTION: The biology of colorectal carcinomas has been reported to
differ by location. Although the investigation of clinicopathological diversities
between colon and rectal carcinomas could provide useful information for more
effective clinical treatment, there is not adequate evidence of the differences.
AIMS & METHODS: The aim was to compare the clinicopathological features
of T1 carcinomas between colon and rectum and to reveal whether these carcinomas should be considered as a single entity or two distinct entities. This study
was performed at Showa University Northern Yokohama Hospital in Japan
(UMIN Clinical Trials Registry number, UMIN000010979). A total of 21060
colorectal neoplasms were resected endoscopically or surgically at our institution
between April 2001 and September 2013. Of these, 580 surgically resected T1
carcinomas, 475 colon and 105 rectal were evaluated. Factors analyzed included
patient age, gender, tumor size, morphology, recurrence, depth of invasion, histologic type, vascular invasion, lymphatic invasion, tumor budding, and lymph
node metastasis.
RESULTS: Rectal T1 carcinomas were significantly larger (19.910.9 mm vs.
23.712.9 mm, p50.001) and were accompanied by significantly higher rates of
vascular invasion (30.7% vs. 47.6%, p50.001) and recurrence (0.4% vs. 2.9%,
p50.05) than colon T1 carcinomas. None of the other clinicopathological factors, including lymph node metastasis, differed significantly.
CONCLUSION: Rectal T1 carcinomas were significantly larger in size, with a
significantly higher rate of vascular invasion and recurrence, than colon T1
carcinomas. However, the tumor location was not a risk factor for lymph node
metastasis. These suggest that additional surgery after endoscopic resection be
recommended for rectal T1 carcinomas with high risk for lymph node metastasis
as well as colon ones even if rectal surgery is more invasive and rectal T1 carcinomas need more careful management after treatment.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P0955 CLINICAL UTILITY OF APPLYING A SIMPLE, LOW-COST
METHODIC APPROACH TO EVALUATION OF CIRCULATING
TUMOR DNA (CTDNA) IN COLORECTAL CANCER PATIENTS
UNDERGOING SURGICAL TREATMENT
L. Benesova1, B. Belsanova1, T. Halkova1, P. Minarikova2, J. Pudil3, J. Cyrany4,
F. Pazdirek5, J. Bures4, M. Oliverius6, J. Hoch5, M. Zavoral2, L. Lipska7,
V. Treska8, L. Petruzelka9, M. Ryska3, M. Minarik1,2,*
1
Center for applied genomics of solid tumors, Genomac Research Institute,
2
Internal Clinic, 1st Faculty of Medicine, Charles University and Central Military
Hospital, Military Faculty Hospital, 3Surgical Clinic, 2nd Faculty of Medicine,
Charles University in Prague and Military University Hospital, Prague, 42nd
Department of Internal Medicine, Charles University Medical Faculty and
Teaching Hospital, Hradec Kralove, 5Department of Surgery, 2nd Faculty of
Medicine, Charles University in Prague and University Hospital Motol,
6
Transplant Surgery Department, Institute for Clinical and Experimental Medicine
Prague, 7Department of Surgery, 1st Faculty of Medicine Charles University in
Prague and Thomayer Hospital, Prague, 8Surgery clinic, Faculty Hospital, Pilsen,
9
Department of oncology, 1st Faculty of Medicine of Charles University and
General University Hospital, Prague, Czech Republic
Contact E-mail Address: mminarik@email.com
INTRODUCTION: Circulating tumor DNA (ctDNA) is a very promising
marker for non-invasive management of patients with cancer (1). The main
clinical significance of ctDNA is in monitoring of patients after tumor resection,
detection of recurrence or progression of disease and predicting and monitoring
of the response to treatment. Most methods for ctDNA detection and monitoring
are based on highly dedicated technologies, mainly utilizing digital PCR with
subsequent detection by flow cytometry or next-generation sequencing (2). The
high cost of equipment as well as sample processing prevents wide application of
ctDNA testing in a clinical practice.
AIMS & METHODS: In a multicentric setting consisting of seven clinical collaborators we have optimized methodology for the collection and processing of
samples and isolation and detection of ctDNA by PCR followed by denaturing
capillary electrophoresis (DCE). In total, we have prospectively examined presence of ctDNA in 210 patients including 186 patients with colorectal cancer
(CRC) at various stages and 24 patients with colorectal adenomas. Subsequent
samplings were carried at 2-6 month intervals to monitor the ctDNA dynamics.
Results were correlated with clinical data of patients (stage R0/R2 surgery, tumor
markers, response to treatment, recurrence or progression of the disease).
RESULTS: The overall ctDNA detection rate in cancer patients was 28% (52/
186), with the highest rate of 68% (19/28) in stage IV. In subsequently monitored
patients levels of ctDNA correlated with the R0/R2 resection radicality, response
to (neo)adjuvant chemotherapy, recurrence or eventual disease progression.
Tumor markers CEA and CA19-9 correlated with ctDNA in 62% (65/104) of
cases, in 13% (13/104) of ctDNA-positive cases the markers were negative.
CONCLUSION: A routine procedure has been implemented for the ctDNA
analysis applying a simple methodology available to standard molecular laboratory. The ctDNA detection rates are ca. 20% below the rates produced by
dedicated techniques and at 10 50x lower cost per patient. Our results confirm
a significant potential of ctDNA in monitoring patients after resection of the
primary tumor / metastasis and prediction of the response to biological treatment. The work was supported by IGA Ministry of Health No. NT 13660.
REFERENCES
1. Diaz LA Jr and Bardelli A. Liquid biopsies: genotyping circulating tumor
DNA. J Clin Oncol 2014; 32: 579-586.
2. Benesova L, Belsanova B, et al. Mutation-based detection and monitoring of
cell-free tumor DNA in peripheral blood of cancer patients. Anal Biochem 2013;
433: 227-234.
Disclosure of Interest: None declared
P0956 FAMILIAL ADENOMATOUS POLYPOSIS (FAP) IN PEDIATRIC
PATIENTS. A SINGLE CENTRE EXPERIENCE
M. Rogalidou1,*, K. Katsanos2, D. Christodoulou2, M. Tzoufi1, I. Saougou1,
D. Kourou1, E. Tsianos2, A. Siamopoulou-Mavridou1
1
Pediatric Gastroenterology Unit, Pediatrics Department, University Hospital of
Ioannina, 2Division of Gastroenterology, Medical School of Ioannina, Ioannina,
Greece
Contact E-mail Address: rogalidoum@yahoo.com
INTRODUCTION: Familial Adenomatous Polyposis is an autosomal dominant
inherited disorder in 80% of cases, characterized by the early onset of hundreds
to thousands of adenomatous polyps throughout the colon. If left untreated, all
patients develop colon cancer by age 35-40 years. In children with FAP colectomy is advised at the age of 17-18 years.
AIMS & METHODS: Aim of presentation was to study the characteristics of
pediatric patients with FAP from our centre.
7 patients with Familial adenomatous polyposis, aged 7.5-17 years {5 boys (B) &
2 girls (G)} were included. All patients had positive familial history of FAP. One
patient has Turcot syndrome, while the rest of patients have no other pathological findings or associated conditions. They were asymptomatic, with normal
growth, and normal blood tests.

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United European Gastroenterology Journal 2(1S)


RESULTS: P0956
Patients

Genetic study

Endoscopy

Histological findings

B /12.5 y
B/7.5 y
G /14 y Sdr Turcot

(-)
P. Ser1213X (c3638 C4A)
P. Ser1213X (c3638 C4A)

1000-10.000 polyps
 10-100 polyps
 100 polyps

B /16 y
G/16 y
B /17 y
B/14 y

(-)
p. Ser583X (c.1748 G4A)
p. Ser583X (c.1748 G4A)
p. Ser583X (c.1748 G4A)

1000 polyps
 10-100 polyps
 100-1000 polyps
 100-1000 polyps

Adenomatous polyps with moderate grade epithelial dysplasia


Adenomatous polyps
Tubular-vilous adenoma (median grade differentiation) with high
grade dysplasia & focal signs of adenocarcinoma
Adenomatous polyps with low to moderate grade epithelial dysplasia
Adenomatous polyps with moderate grade epithelial dysplasia
Adenomatous polyps with low grade epithelial dysplasia
Adenomatous polyps with low grade epithelial dysplasia

CONCLUSION: The development of colon adenocarcinoma in patients with


FAP could occur also in pediatric age even without any previous alarming
symptom. Children with a positive family history should be checked regularly
and in the presence of FAP an intensive follow-up & eventually early intervention
should be considered.
REFERENCES
Douma KF, Bleiker EM, Aaronson NK, et al. Long-term compliance with endoscopic surveillance advice for familial adenomatous polyposis (FAP). Colorectal
Dis 2010; 12: 1198-1207.
Newton K, Mallinson E, Bowen J, et al. Genotype-phenotype correlation in
colorectal polyposis.
Disclosure of Interest: None declared
P0957 A PHASE 3 PLACEBO-CONTROLLED TRIAL OF CELECOXIB IN
GENOTYPE-POSITIVE SUBJECTS WITH FAMILIAL
ADENOMATOUS POLYPOSIS
P.M. Lynch1,*, C. Burke2, R. Phillips3, M.F. Berger4, C. Li4, M. Noyes Essex5,
D. Iorga4
1
Department of Gastroenterology, The University of Texas MD Anderson Cancer
Center, Houston, USA, Houston, 2Department of Gastroenterology and
Hepatology, Cleveland Clinic, Cleveland, USA, Cleveland, United States,
3
Department of Surgery, St Marks Hospital and Academic Institute, Middlesex,
UK, Middlesex, United Kingdom, 4Department of Clinical Affairs, 5Department of
Medical Affairs, Pfizer, Inc., New York, United States
Contact E-mail Address: dinu.iorga@pfizer.com
INTRODUCTION: This study was conducted to evaluate efficacy and safety of
celecoxib versus placebo in paediatric subjects with familial adenomatous polyposis (FAP).
AIMS & METHODS: The standard of care for FAP has long been prophylactic
colectomy, a major surgical procedure associated with up to 2% mortality.
Colonoscopic polypectomy has a role in maintaining a minimal polyp burden,
in order to delay surgery in the typically young (age 10-16 y) patient. Elevated
levels of cyclooxygenase-2 (COX-2) in colorectal adenomas suggest that COX-2
inhibitors may help maintain the polyp burden within the limits of endoscopic
management, as has been demonstrated in clinical trials.
METHODS: This was a randomised, double-blind, multicentre, placebo-controlled, 5-year study in subjects aged 10-17 years, with a confirmed diagnosis
of FAP (based on mutation testing) and no more than 30 colorectal polyps at
screening, all of which had to be removed such that no subjects initiated treatment with an adenoma 4 2 mm. Approximately 200 subjects were to be randomized in a 1:1 ratio to the 2 treatment arms: celecoxib 16 mg/kg/d or placebo.
Subjects had yearly visits, with colonoscopies at each visit. The primary end point
was the time-to-treatment failure, defined as the time from randomisation to the
earliest occurrence of  20 polyps (4 2 mm in size) at any colonoscopy during
the study or diagnosis of colorectal malignancy.
RESULTS: The study was terminated, at the recommendation of the Data
Monitoring Committee, due to lower than expected enrolment and end point
accumulation rate. At the time of study termination, 106 subjects had been
randomised. There were 7 (13%) subjects in the celecoxib group and 13 (26%)
in the placebo group who met the primary end point. Among them, the median
time to disease progression was 2.1 years in the celecoxib group and 1.1 years in
the placebo group, respectively. None of the subjects in any treatment group
developed colorectal malignancy. The proportion of subjects reporting all causality treatment-emergent adverse events (TEAE) was similar between the treatment groups: 40 (76%) subjects in the celecoxib group and 35 (73%) subjects in
the placebo group. The proportion of subjects with treatment-related TEAEs was
also similar: 18 (34%) subjects in the celecoxib group and 15 (31%) subjects in
the placebo group. The most common AEs (occurring in more than 10% of
subjects in a group) were abdominal discomfort, abdominal pain, diarrhoea,
nausea, vomiting, fatigue, seasonal allergy, influenza, nasopharyngitis, upper
respiratory tract infection, pain in extremity, headache, cough, and oropharyngeal pain.
CONCLUSION: Treatment with celecoxib in children with FAP was generally
well tolerated, with a safety and tolerability profile similar to that observed in
previous studies, and with no new or unexpected safety results. Although a trend
toward delay in progression of adenomas was seen in the celecoxib arm, it was
not statistically significant, which was likely to be related to low sample size and
event rate.
Disclosure of Interest: P. Lynch: None declared, C. Burke Financial support for
research from: Pfizer and Merk, R. Phillips: None declared, M. Berger: None
declared, C. Li: None declared, M. Noyes Essex: None declared, D. Iorga: None
declared

P0958 PROSPECTIVE MULTICENTER STUDY OF SELF-EXPANDABLE


METALLIC STENTS FOR MALIGNANT COLORECTAL
OBSTRUCTION IN JAPAN: SHORT-TERM SAFETY AND EFFICACY
IN 512 PATIENTS
S. Yoshida1,*, H. Isayama2, T. Matsuzawa3, T. Kuwai4, I. Maetani5, T. Yamada6,
S. Saito7, M. Tomita8, T. Sasaki2, Y. Saida9
1
Endoscopic Surgery, 2Gastroenterology, The University of Tokyo, Tokyo,
3
Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical
University, Kawagoe, 4Gastroenterology, National Hospital Organization Kure
Medical Center and Chugoku Cancer Center, Kure, 5Internal Medicine, Toho
University Ohashi Medical Center, Tokyo, 6Gastroenterology, Nagoya Daini Red
Cross Hospital, Nagoya, 7Surgery, National Hospital Organization Yokohama
Medical Centre, Yokohama, 8Surgery, Kishiwada Tokushukai Hospita, Osaka,
9
Surgery, Toho University Ohashi Medical Center, Tokyo, Japan
Contact E-mail Address: shungtang@hotmail.com
INTRODUCTION: Endoscopic stenting with self-expandable metallic stent
(SEMS) is a widely accepted procedure for the palliative management of malignant colonic obstruction and as a bridge to surgery, however, was not able to be
performed under Japanese insurance system. We conducted prospective feasibility study, after this procedure was covered by government medical insurance in
Jan. 2012.
AIMS & METHODS: Our objectives were to estimate safety and feasibility of
SEMS placement for malignant colorectal obstruction in general clinical practice
in Japan.
We conducted a prospective, observational, single-arm and multicenter clinical
trial from Mar. 2012 to Oct. 2013. This study was registered with UMIN Clinical
Trial Registry (UMIN000007953). Forty five facilities consisted of 12 academic
and 33 community hospitals participated this study. Ahead of the start-up of the
study, we launched a website (http://colon-stent.com/) and pronounced the standard methods based on previous published data to standardize the maneuver of
SEMS placement. Each patient was treated with an uncovered WallFlex Enteral
Colonic Stent (Boston Scientific Corporation). SEMS were placed under fluoroscopy and endoscopy. Technical success was defined as deployment of the stent
across the entire length of the stricture on the first attempt. Clinical success was
defined as a resolution of symptoms and radiological relief of the obstruction
within 24 h. Patients undergoing the stenting as a bridge to surgery (BTS) were
followed until surgery, and incurable patients undergoing palliative treatment
(PAL) were followed until death or 12, whichever came first. The following
conditions were considered to be complications: stent occlusion, stent migration,
colonic erosion or ulcer, perforation, hematochezia, tenesmus, and bacteremia.
Complications were categorized as early (within 7 days) or late (after 7 days).
RESULTS: We registered 518 patients. Six patients were excluded, because of
loose stenosis with passed by colonoscope (3), benign stricture (1), unknown
indication (1) and placement with another SEMS (1). We enrolled 512 patients
for a BTS (311) and PAL (201) indication. In an intension-to-treat analysis,
technical and clinical success was 98% (97% BTS, 99% PAL) and 96% (96%
BTS, 95% PAL). The overall early complication rate was 8% (7% BTS, 9%
PAL), including stent occlusion 1.2% (0.3% BTS, 2.5% PAL), stent migration in
1.5% (0.5% BTS, 2.3% PAL), perforation in 1.9% (2.3% BTS, 1.5% PAL).
CONCLUSION: This large multicenter, prospective study demonstrates the feasibility of SEMS placement for malignant colorectal obstruction within 7 days
after SEMS placement. Despite of short period experience of this procedure in
Japan, the incidence of complications including perforation was relatively low.
Disclosure of Interest: S. Yoshida: None declared, H. Isayama Financial support
for research from: Boston Scientific Japan, Lecture fee(s) from: Boston Scientific
Japan, T. Matsuzawa: None declared, T. Kuwai: None declared, I. Maetani:
None declared, T. Yamada: None declared, S. Saito: None declared, M.
Tomita: None declared, T. Sasaki: None declared, Y. Saida Consultancy for:
Boston Scientific Japan
P0959 EICOSAPENTAENOIC ACID (EPA) SUPPRESSES COLORECTAL
ABERRANT CRYPT FOCI (ACF) AND CELL PROLIFERATION IN
COLORECTAL EPITHELIUM VIA GPR120
T. Higurashi1,*, S. Uchiyama1, S. Umezawa1, E. Sakai1, H. Ohkubo1, H. Endo1,
H. Takahashi1, A. Nakajima1
1
Department of Gastroenterology and Hepatology, Yokohama City University,
Yokohama, Japan
INTRODUCTION: Eicosapentaenoic acid (EPA), the omega-3 polyunsaturated
fatty acid (!3PUFA) that is widely used in the treatment of hyperlipidemia and

A396
prevention of cardiovascular disease, has recently been suggested to have a suppressive effect on tumorigenesis and cancer cell growth. However, the mechanism
of EPA chemopreventive effect was still unclear. Recently, G-protein coupled
receptor 120 (GPR120) functions as a receptor for!3PUFA and has a critical role
in various physiological homeostasis mechanisms. It is known that GPR120 is
expressed abundantly in the intestinal tract and in adipocytes. However, it is
unclear that the role of GPR120 in intestinal tract, especially in anti-carcinogenesis effect against EPA. In the present study, we explore the colon chemopreventive effect of EPA focused on via GPR120 pathway using GPR120 deficient mice.
AIMS & METHODS: We produced and used GPR120 deficient mice and the
littermate wild type mice. Both mice were fed with normal diet or EPA containing chow. Then we investigated carcinogen-induced formation of aberrant crypt
foci ACF and tumors in the colon.
RESULTS: In WT, mice fed with EPA were significantly suppressed ACF formation. On the other hand, in GPR deficient, both mice fed with normal diet and
EPA containing chow were present similar ACF formation.
CONCLUSION: We demonstrated the importance of EPA/GPR120 signaling in
the colon in colorectal carcinogenesis.
Disclosure of Interest: None declared
P0960 DOES THE UBIQUITIN PROTEASOME SYSTEM IS INVOLVED
IN THE EFFECTS OF PAR2 RECEPTORS ACTIVATION IN THE
INTESTINE?
I. Ghouzali1,2,*, S. Azhar1, C. Bole-feysot1, P. Dechelotte1,3, M. Coeffier1,3
1
UMR 1073 nutrition, inflamation, brain gut axis dysfunction, 2Institute for
Research and Innovation in Biomedicine, University of Rouen, 3Department of
Nutrition, University Hospital, Rouen, France
INTRODUCTION: The irritable bowel syndrome (IBS) is a functional disorder
in which chronic digestive discomfort or abdominal pain are the primary symptoms. Dysfunction of the intestinal barrier has been observed leading to changes
in the immune system and visceral hypersensitivity. Protease-activated receptor
type 2 (PAR2) and ubiquitin-proteasome system might play contribute to the
pathophysiology of IBS. Thus, we aimed to investigate whether ubiquitin proteasome system might be involved in the effects of PAR2 activation in human
intestinal epithelial Caco-2 cells and in C57BL/6 mice.
AIMS & METHODS: Caco-2 cells were grown on microporous filters to obtain
a monolayer of polarized cells and were then incubated with the agonist peptide
PAR2 (PAR2-AP, 100M) and/or IL-1 (1ng/ml) and/or a proteasome inhibitor, MG132 (10 M). Production of proinflammatory IL-8 chemokine was measured by ELISA in apical and basolateral culture media. Proteolytic activities of
proteasome, paracellular permeability and the expression of subunits of proteasome have been evaluated. C57BL/6 Mice also received intraperitoneal injection
of a proteasome inhibitor MG132 (15mol/kg) or "vehicle". After one hour,
under anesthesia, mice received intracolic injection of a solution of 100l of
PAR2-AP (1mg/ml) or saline. After 4 hours, production of proinflammatory
CXCL1/KC chemokine was measured by ELISA in colonic washes and in
portal serum.
RESULTS: Addition of PAR2-AP alone did not influence the ubiquitin-proteasome system, both in its activity and in its composition. However, when PAR2AP was combined with IL-1, chymotrypsin-like and caspase-like proteasome
activities were increased (2.85 and 1.37 fold changes, respectively) as well as the
composition of proteasome. Indeed, the ratio 5i / 5 was significantly decreased.
Production of IL-8 and its mRNA level was increased in presence of PAR2-AP (p
5 0.05). In Caco-2 cells polarized model, production of IL -8 was apical or
basolateral differentially modulated when PAR2-AP was applied in apical or
basolateral media. Proteasome inhibitor, MG132, exacerbated effects of PAR2AP on production of IL-8 and barrier function. In mice, intracolonic injection of
PAR2-AP decreased production of CXCL1/KC in both luminal and portal sides.
This effect was blocked by injection of MG132.
CONCLUSION: In conclusion, we have shown in a cell model that PAR2 agonist peptide alone did not affect the ubiquitin-proteasome system under basal
conditions but can modify proteasome activities in presence of an inflammatory
stimulus (IL-1). Furthermore, complete inhibition of proteasome enhances
effects of PAR2 activation on inflammatory response and intestinal barrier. In
contrast, in mice, inhibition of proteasome blocks effects of agonist peptide
PAR2 on production CXCL1/KC. Further studies are needed to explain these
results.
Disclosure of Interest: None declared
P0961 LACTIC ACID BACTERIA DIFFERENTIALLY MODULATES
UROCORTIN 2 MRNA EXPRESSION IN HUMAN COLON
EPITHELIAL CELLS
C. Gonzalez-Arancibia1, M. Gotteland2, M. Julio-Pieper1, J.A. Bravo1,*
1
Grupo de NeuroGastroBioqumica, Laboratorio de Qumica Biologica. Instituto de
Qumica, Facultad de Ciencias, Pontificia Universidad Catolica de Valparaso,
Valparaso, 2Departamento de Nutricion, Facultad de Medicina, Universidad de
Chile, Santiago, Chile
Contact E-mail Address: javier.bravo@ucv.cl
INTRODUCTION: It has been shown that interventions on the gut microbiota
affect behaviour in rodents and healthy human volunteers. This has led to establish what is now recognized as the microbiota-gut-brain axis. However, the
mechanisms of communication between microbes and nerve cells or nerve endings in the gastrointestinal tract (GIT) remain largely unknown.
The intestinal microbiota is composed by a large number of microorganisms,
including gram-positive lactic acid bacteria, which are able to interact with several cell types within GIT, including epithelial cells. Due to their ability to express
neuropeptides, epithelial cells might act as intermediaries capable of transducing

United European Gastroenterology Journal 2(1S)


signals from luminal bacteria to nerve cells or sensory nerve endings in the GIT
wall. One candidate neuropeptide is urocortin 2 (UCN2), which is known to
regulate visceral nociception and gastric emptying.
AIMS & METHODS: We aimed to evaluate whether human colonic epithelial
cells (Caco-2 cell line) are able to increase UCN2 mRNA expression upon stimulation with three types of Lactobacillus species: L. rhamnosus GG, L. casei
L54-2-33 and L. plantarum L46-1-12. For this, Caco-2 cells were stimulated with
103, 105 and 107 colony forming units (cfu) per millilitre (cfu/mL) of each
Lactobacillus strain for 3 hours. Control Caco-2 cells were exposed to broth
alone. Then, total mRNA was extracted and UCN2 mRNA expression was
analyzed using RT-PCR.
RESULTS: Caco-2 cells stimulated with 105 and 107cfu/mL of L. casei L54-2-33
displayed increased levels of UCN2 mRNA in comparison to control Caco-2
cells. On the other hand, stimulation of Caco-2 cells with 107cfu/mL of L. plantarum L46-1-12 reduced UCN2 mRNA expression in comparison to controls,
while L. rhamnosus GG was not able to affect UCN2 expression at any of the
analyzed doses.
CONCLUSION: These findings show that lactic acid bacteria are able to modulate neuropeptide expression (i.e.: UCN2) in intestinal epithelial cells, suggesting
a potential pathway of communication with the nervous system. Modulation of
UCN2 expression was strain specific suggesting that alterations in the intestinal
microbiota and/or interventions through the use of antibiotics or probiotic bacteria would differentially affect this communication and potentially have differential effects on the gut-brain axis.
Funding: PUCV DI 37.386/2014 and FONDECYT1140776
Disclosure of Interest: None declared
P0962 ACUTE
PSYCHOLOGICAL
STRESS
INCREASES
PARACELLULAR PERMEABILITY IN THE SIGMOID COLON OF
HEALTHY VOLUNTEERS
L. Gerdin1,2,*, M. Persborn3, Y. Braaf1,2, C.D. Ley Magana1, M. Olsson4, A.C. Ericson1, S. Walter5, J. Dabrosin Soderholm1
1
IKE, Linkoping University, Linkoping, 2Surgery, Eksjo Hospital, 3IKE,
Linkopings universitet, Eksjo, 4Surgery, 5Gastroenterology, Linkoping University
Hospital, Linkoping, Sweden
Contact E-mail Address: linda.gerdin@liu.se
INTRODUCTION: Psychological stress (PS) has been shown to have an effect
on the course of both irritable bowel syndrome (IBS) and ulcerative colitis (UC).
The mechanisms behind these effects are as yet unknown. Animal studies have
shown that PS increases the intestinal barrier function. Our group has previous
preliminary data showing that in vivo PS increases paracellular permeability in
the rectum of healthy volunteers (HV). Whether or not the same is true for the
sigmoid colon is unknown.
AIMS & METHODS: 18 HV (11 women and 7 men) were stressed using the
method modified dichotomous stress for 60 minutes. Stress was monitored as
blood pressure (BP), pulse (HF) and subjectively using a visual analogue scale
(VAS). The control session was 60 min listening to calm music and the same HV
were their own controls. Immediately following the stress/control sessions biopsies were taken from the sigmoid colon. The biopsies were mounted in modified
Ussing chambers and passage of the paracellular permeability marker CrEDTA
was measured for 120 min.
RESULTS: VAS, BP and HF were significantly higher at the stress than at the
control session. There was a significant increase in passage of CrEDTA (6.2E-06
(5.3 E-06 -8.3 E-06)cm/s vs 4.4 E-06 (3.3-6.2) cm/s (median(IQR) (p(50.05).
CONCLUSION: Vanuytsel et al have recently shown that PS increases paracelluar premability in the small intestine in HV. Our results show similar permeability results in the colon. The mechanisms should be further investigated.
REFERENCES
Vanuytsel T, van Wanrooy S, Vanheel H, et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast
cell-dependent mechanism. Gut. Epub ahead of print 23 October 2013. DOI:
10.1136/gutjnl-2013-305690
Disclosure of Interest: None declared
P0963 ROLE
OF
INSULAR
CORTEX
IN
VISCERAL
HYPERSENSITIVITY RAT INDUCED BY CHRONIC STRESS
H. Sun1,*, L. Yi1, C. Ge1, Y. Chen1, Y. Jiang1, P. Wu2, S. Xu1
1
Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji
Hospital, Tongji University School of Medicine, 2Clinical Nutrition, Tongji
Hospital, Tongji University School of Medicine, shanghai, China
Contact E-mail Address: s-haijie@163.com
INTRODUCTION: Visceral hypersensitivity is an important pathophysiological
mechanism of stress-related FGIDs. In recent years, abnormalities of brain activity are thought to play important roles in the pathogenesis of visceral hypersensitivity. The insula as one important center processing visceral sensory and
regulating emotion is inferred to be closely related with the pathogenesis of
visceral hypersensitivity induced by chronic stress. However, the role of insula
in visceral hypersensitivity has not been clearly defined.
AIMS & METHODS: We aimed to determine if insular neuron activation plays
an important role in visceral hypersensitivity induced by chronic stress. Chronic
water avoidance stress (WAS) was used to establish visceral hypersensitivity rat
models. Visceral sensitivity was determined by measuring visceromotor response
(VMR) amplitude to graded colorectal distention (20mmHg, 40mmHg, 60mmHg
CRD). The bilateral insula was stimulated electrically, and insular lesions were
generated with n-methyl-d-aspartate (NMDA).
RESULTS: Compared with sham WAS (2.070.61) and normal rats
(2.150.46), the VMR to graded CRD in WAS rats (4.220.35) significantly

A397

United European Gastroenterology Journal 2(1S)


increased (p 0.000). Bilateral insular lesions caused a significant decrease of the
VMR in WAS rats (2.170.56) comparing with that in sham-lesion (4.020.84)
and non-lesion WAS (4.350.87) rats (p 0.000). The VMR to 60mmHg in
insular lesion WAS rats have no significant differences with that in normal
rats (p 0.691). Electrically stimulating (ES) the left or right insula all enhanced
the VMR of WAS rats (left: ES-before 4.621.51, ES-after 13.594.27 p 0.000;
right: ES-before 4.540.62, ES-after 13.954.77 p 0.000) and the increase level
of VMR amplitude had no significant differences between bilateral insula electrically stimulated (p40.05)
CONCLUSION: Insula plays a critical role in the modulation of visceral hypersensitivity induced by chronic stress, without unilateral advantage phenomenon
in modulating process. After insular lesions, the pathological hypersensitivity
symptoms in visceral hypersensitivity rats disappearance, but it keeps natural
state visceral sensitivity.
Disclosure of Interest: None declared
P0964 IN IBS PATIENTS WITH SEVERE POSTPRANDIAL BLOATING
AND ABDOMINAL DISTENTION, COLONIC TONE IS REDUCED IN
POSTPRANDIAL PERIOD
M. Di Stefano1, M. Bergonzi1,*, C. Mengoli1, E. Pagani1, E. Miceli1,
G.R. Corazza1
1
1st Department of Internal Medicine, IRCCC Policlinico S. Matteo, University of
Pavia, Pavia, Italy
Contact E-mail Address: m.distefano@unipv.it
INTRODUCTION: Bloating is a very frequent complaint, is frequently associated to IBS and, in a subgroup of patients, is accompanied by a severe, visible
abdominal distention. These subgroup of patients is characterized by different
clinical presentations: bloating and abdominal distention onset may be related or
not to food ingestion, they may be absent on waking and progressively worsen
during the day, they may occur immediately after meal ingestion. The characteristics of the onset suggest a different pathophysiology.
AIMS & METHODS: Accordingly, we studied colonic tone in fasting condition
and after a meal in a group of IBS patients with bloating and abdominal distention and we compared the results of patients with a meal-related and a meal
unrelated occurrence of symptoms.
A group of 38 consecutive IBS patients (mean age 38.49.4 years, range 21-60,
IBS-C 20; IBS-D 5 IBS-M 13) with severe bloating and abdominal distension, diagnosed according to Rome III criteria was enrolled. Twenty-one patients
suffered from postprandial onset of bloating and severe abdominal distention
and 17 had meal-unrelated symptoms. In all subjects, recto-sigmoid tone was
monitored with barostat, during a 30-min fasting period and a 60-min period
after meal consumption (200 Kcal, 200 ml liquid meal). Every ten minutes, the
occurrence of abdominal distention was monitored by abdominal girth
measurement.
RESULTS: In the subgroup of patients with postprandial occurrence of bloating
and abdominal distention, meal intake induced a significant decrease of rectosigmoid tone as mean postprandial recto-sigmoid volume modification was
26.64,4% in these patients; on the contrary and as expected, in the subgroup
with meal unrelated symptoms, mean recto-sigmoid volume modification was 4,14.0% (p 0.001). Moreover, in patients with postprandial symptoms a
meal-induced increase of the balloon volume higher than 10% of the fasting
value was present in 14/21 (66.7%) vs 2/17 (11.7%) of the other subgroup
(p 0.0009) and postprandial abdominal girth significantly increased (85.0 cm
 7.7 cm) vs the other subgroup (83.4 cm  7.2; p50.01).
CONCLUSION: A reduction of intestinal tone in the postprandial period may
represent an important pathophysiological mechanism for the occurrence of
abdominal distention in functional patients with bloating. An inappropriate,
diffuse activation of a nitrergic pathway might be responsible for this alteration.
REFERENCES
1. Azpiroz Gastroenterol 2005; 129: 1060-1078.
Disclosure of Interest: None declared
P0965 DIFFERENTIAL EFFECTS OF EXTRACELLULAR CYCLIC GMP
(CGMP) AND THE GUANYLATE CYCLASE-C (GC-C) AGONIST,
LINACLOTIDE, ON MOUSE GASTRIC VAGAL AFFERENT
MECHANOSENSITIVITY
S.J. Kentish1, T.A. ODonnell1, S.M. Brierley1, C. Kurtz2, A. Silos-Santiago2,
A. Page1,*
1
University of Adelaide, Adelaide, Australia, 2Ironwood Pharmaceuticals Inc.,
Cambridge, United States
Contact E-mail Address: amanda.page@adelaide.edu.au
INTRODUCTION: cGMP is a second messenger produced in intestinal epithelial cells in response to GC-C activation. GC-C is expressed in the epithelium of
the stomach (1). In addition, the endogenous peptide ligand for GC-C, uroguanylin, is located in enterochromaffin-like cells within the stomach (2). These
findings suggest the stomach mucosa may be capable of producing cGMP in
response to a GC-C agonist. In mouse colon both extracellular cGMP and
linaclotide inhibit colonic nociceptor mechanosensitivity. Vagal afferents are
associated with reflexes commonly altered in diseases such as functional dyspepsia. However, little is known about the effects of GC-C receptor activation and
cGMP on these afferents.
AIMS & METHODS: We aimed to determine the effect of extracellular cGMP
and linaclotide on gastric vagal afferent mechanosensitivity. Single fibre in vitro
recordings of gastric vagal mechanoreceptors from 8wk old female C57BL/6 mice
were recorded (3). The response of mucosal receptors to mucosal stroking with
von Frey hairs (10-1000mg) and tension receptors to circular stretch (1-5g) in the
absence and presence of cGMP (30-1000mM) or linaclotide (10-300nM) was

determined. An increase or decrease in response to mucosal stroking (50mg)/


circular tension (3g) of  20% in the presence of cGMP or linaclotide was
considered to be potentiation or inhibition, respectively.
RESULTS: The effect of cGMP and linaclotide on gastric vagal afferent mucosal
and tension receptor mechanosensitivity is illustrated in the table below:
cGMP (30-1000mM)

Linaclotide (10-300nM)

Inhibit Potentiate No effect Inhibit Potentiate No effect


% gastric mucosal 27%
receptors
(n 7)
% gastric tension 0%
receptors

31%
(n 8)
44%
(n 7)

42%
(n 11)
56%
(n 9)

36%
(n 5)
18%
(n 6)

41%
(n 9)
55%
(n 12)

23%
(n 8)
27%
(n 4)

The inhibitory and excitatory effects of linaclotide occurred close to the limiting
ridge in the corpus and along the lower curvature of the stomach respectively. In
contrast, there was no relationship between cGMP effects on vagal afferents and
the location of these afferents in the stomach.
CONCLUSION: Linaclotide and extracellular cGMP can both inhibit and
enhance responses of gastric vagal afferents to mechanical stimulation. The functional significance of these effects on gastric sensory signalling remains to be
determined.
REFERENCES
1) London RM et al. Am J Physiol 1997; 273: G93-G105.
2) Date Y et al. Endocrinology 1999; 140: 2398-2404.
3) Page et al. J Neurophysiol 2002; 87: 2095-2103.
Supported by Ironwood Pharmaceuticals, Inc., Forest Laboratories, Inc.
Disclosure of Interest: S. Kentish Financial support for research from: Ironwood
Pharmaceuticals, Inc.; Forest Laboratories, Inc., T. ODonnell: None declared,
S. Brierley Financial support for research from: Ironwood Pharmaceuticals, Inc.;
Forest Laboratories, Inc.; Tioga Pharmaceuticals, Inc., Consultancy for:
Ironwood Pharmaceuticals, Inc.; Forest Laboratories, Inc., C. Kurtz Financial
support for research from: Ironwood Pharmaceuticals, Inc., Shareholder of:
Ironwood Pharmaceuticals, Inc., A. Silos-Santiago Financial support for
research from: Ironwood Pharmaceuticals, Inc., Shareholder of: Ironwood
Pharmaceuticals, Inc., A. Page Financial support for research from: Ironwood
Pharmaceuticals, Inc.; Forest Laboratories, Inc.
P0966 DIFFERENT SUBTYPES OF PATIENTS WITH IRRITABLE
BOWEL SYNDROME HAVE DISTINCT ALTERATIONS IN THE
GUANYLATE CYCLASE-C/CYCLIC GMP PATHWAY
A.M. Harrington1,2, J. Castro1,2, R.L. Young1,2, C. Kurtz3, I. Silos-Santiago3,*,
N. Nguyen2, J. Andrews2, S.M. Brierley1,2
1
Nerve-Gut Research Laboratory, Discipline of Medicine, Faculty of Health
Science, University of Adelaide, 2Department of Gastroenterology & Hepatology,
Royal Adelaide Hospital, Adelaide, Australia, 3Ironwood Pharmaceuticals,
Cambridge, MA, United States
INTRODUCTION: Linaclotide, a guanylate cyclase C (GC-C) agonist, reduces
abdominal pain and improves constipation in patients with irritable bowel syndrome with constipation (IBS-C).1 We recently showed that linaclotide activates
GC-C expressed on intestinal epithelial cells, resulting in the production and
release of cyclic GMP (cGMP), which accelerates gastrointestinal transit and
inhibits colonic nociceptors.1 We have also shown that key components of the
GC-C/cGMP signalling pathway are expressed within human colonic mucosa.
AIMS & METHODS: We investigated whether components of the GC-C/cGMP
signalling pathway are differentially expressed in different IBS patient subtypes.
Recto-sigmoid mucosal biopsies were obtained from healthy subjects (N 10)
and IBS patients (N 14), as per Rome II criteria. We compared IBS patients
with mixed (constipation and diarrhoea) bowel habits (IBS-M; N 7) and
patients with IBS-C (N 7). RNA was extracted from biopsies and Taqman
qRT-PCR used to assess mRNA expression of: GC-C (GUCY2C); the endogenous GC-C agonists, guanylin (GUCA2A) and uroguanylin (GUCA2B); and the
cGMP transporters, MRP4 (ABCC4) and MRP5 (ABCC5). Expression of these
targets was determined relative to the housekeeping genes 18S RNA and
GAPDH. In separate biopsies, immunohistochemistry determined localisation
of GC-C/cGMP signalling pathway components to cellular structures.
RESULTS: In mucosal biopsies from healthy controls, guanylin was the most
abundantly expressed component of the GC-C/cGMP signalling pathway, followed sequentially by uroguanylin (P50.01), GC-C (P50.001), MRP5
(P50.001) and MRP4 (P50.001), respectively. In IBS-M biopsies, both of the
endogenous GC-C agonists (guanylin and uroguanylin) were significantly
reduced compared with healthy controls (P50.05). By contrast, in IBS-C patient
biopsies, MRP4 was significantly down-regulated compared with expression in
biopsies from healthy controls (P50.001). No significant change in either MRP5
or GC-C expression was observed between IBS patient subtypes and healthy
controls. Immunohistochemistry revealed MRP4 expression on the apical side
of colonic epithelial cells, whilst MRP5 displayed basolateral expression.
CONCLUSION: Distinct alterations in the GC-C/cGMP pathway are evident
between different subtypes of IBS patients and may contribute to the pathophysiology of IBS. In IBS-M, reduced expression of the endogenous hormones guanylin and uroguanylin may contribute to alternating bowel habits. In IBS-C, a
reduction in apically expressed MRP4 may result in reduced release of cGMP
into the colonic lumen. Overall, these changes may help to explain some aspects
of the pathophysiology associated with IBS and the differential stool frequency
and symptom patterns between IBS subtypes, which are under further
investigation.

A398
REFERENCES
1. Castro J, et al. Gastroenterology 2013; 145: 1334-1346.
Supported by Ironwood Pharmaceuticals, Inc., and NHMRC Australia.
Disclosure of Interest: A. Harrington Financial support for research from:
Ironwood Pharmaceuticals, Consultancy for: Ironwood Pharmaceuticals, J.
Castro Financial support for research from: Ironwood Pharmaceuticals,
Consultancy for: Ironwood Pharmaceuticals, R. Young Financial support for
research from: Ironwood Pharmaceuticals, Consultancy for: Ironwood
Pharmaceuticals, C. Kurtz Shareholder of: Ironwood Pharmaceuticals, Other:
Employee Ironwood Pharmaceuticals, I. Silos-Santiago Shareholder of:
Ironwood Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals, N.
Nguyen Financial support for research from: Ironwood Pharmaceuticals,
Consultancy for: Ironwood Pharmaceuticals, J. Andrews Financial support for
research from: Ironwood Pharmaceuticals, Consultancy for: Ironwood
Pharmaceuticals, S. Brierley Financial support for research from: Ironwood
Pharmaceuticals, Consultancy for: Ironwood Pharmaceuticals
P0967 EXTRACELLULAR CYCLIC GMP, THE DOWNSTREAM
MEDIATOR RELEASED IN RESPONSE TO LINACLOTIDEINDUCED ACTIVATION OF GUANYLATE CYCLASE C, REDUCES
EXCITABILITY OF MURINE AND HUMAN DORSAL ROOT
GANGLION NEURONS
J. Castro1,2, G.Y. Rychkov3, A. Ghetti4, A.M. Harrington1,2, C. Kurtz5, I. SilosSantiago5,*, S.M. Brierley1,2
1
Nerve-Gut Research Laboratory, Discipline of Medicine, University of Adelaide,
2
Department of Gastroenterology & Hepatology, Royal Adelaide Hospital,
3
Discipline of Physiology, Faculty of Health Science, University of Adelaide,
Adelaide, Australia, 4Anabios Inc, San Diego, CA, 5Ironwood Pharmaceuticals,
Cambridge, MA, United States
INTRODUCTION: Linaclotide, a guanylate cyclase C (GC-C) agonist, reduces
abdominal pain and improves constipation in patients with irritable bowel syndrome with constipation (IBS-C).1 Cyclic GMP (cGMP) is a second messenger
produced in intestinal epithelial cells in response to GC-C activation. We have
recently shown that both linaclotide and exogenous extracellular cGMP inhibit
colonic nociceptor mechanosensitivity with greater efficacy during chronic visceral hypersensitivity (CVH) compared with healthy nociceptors.1 However, the
effects of exogenous cGMP on sensory neuron function remain to be determined
in isolation.
AIMS & METHODS: We investigated the effects of exogenous extracellular
cGMP on dorsal route ganglion (DRG) neurons isolated from both mice and
humans. For mouse DRG studies we performed whole-cell patch-clamp recordings in current-clamp mode from retrogradely traced colonic DRG neurons. We
compared the effect of cGMP (100 nM-50 M) on the rheobase, or threshold for
action potential firing, of DRG neurons from healthy C57BL/6 mice and mice
with CVH, 28 days post-trinitrobenzene sulphonic acid administration.1 For
human DRG studies we performed calcium-imaging studies and compared the
effects of cGMP (10 M-300 M) on Ca2 influx in response to hypo-osmotic
stimuli of DRG neurons from healthy donors.
RESULTS: Colonic DRG neurons from CVH mice displayed a significantly
reduced rheobase (P50.001, n 13-23) and fired significantly more action
potentials (P50.05, n 13-23) compared with healthy mice. In a subpopulation
of colonic DRG neurons, cGMP inhibited the neuronal excitability of putative
nociceptors, significantly increasing the rheobase (P50.01) and reducing action
potential discharge (P50.01). This effect was evident in both healthy and CVH
DRG neurons, was most apparent in CVH DRG neurons, and occurred at
concentrations as low as 100 nM cGMP. In human DRG neurons, cGMP
induced an overall reduction in the number of cells responding to hypo-osmotic
stimulation. In addition, in human DRG neurons cGMP caused, in a concentration-dependent manner, up to 60% inhibition of the Ca2 influx induced by
hypo-osmotic stimulation.
CONCLUSION: Exogenous cGMP directly decreases the excitability of sensory
DRG neurons isolated from both mice and humans. These results complement
our previous findings in mice, which demonstrated that cGMP inhibited the
peripheral endings of nociceptors within the wall of the colon. These current
findings also provide further mechanistic insight into how linaclotide, through
GC-C agonism and the release of cGMP from mucosal epithelial cells, reduces
nociceptive signalling from the colon.
REFERENCES
1. Castro J, et al. Gastroenterology 2013; 145: 1334-1346.
Supported by Ironwood Pharmaceuticals, Inc., Forest Laboratories, Inc., and
NHMRC Australia.
Disclosure of Interest: J. Castro Financial support for research from: Ironwood
Pharmaceuticals, Consultancy for: Ironwood Pharmaceuticals, G. Rychkov
Financial support for research from: Ironwood Pharmaceuticals, A. Ghetti
Financial support for research from: Ironwood Pharmaceuticals, A.
Harrington Financial support for research from: Ironwood Pharmaceuticals,
Consultancy for: Ironwood Pharmaceuticals, C. Kurtz Shareholder of:
Ironwood Pharmaceuticals, Other: Employee of Ironwood Pharmaceuticals, I.
Silos-Santiago Shareholder of: Ironwood Pharmaceuticals, Other: Employee of
Ironwood Pharmaceuticals, S. Brierley Financial support for research from:
Ironwood Pharmaceuticals, Consultancy for: Ironwood Pharmaceuticals /
Forest laboratories

United European Gastroenterology Journal 2(1S)


P0968 EFFECT OF TOLL LIKE RECEPTORS 2 AND 4 ON THE
SEROTONIN INDUCED MOTOR RESPONSE MEDIATED BY 5-HT2
AND 5-HT3 RECEPTORS IN MOUSE ILEUM
R. Forcen1,*, E. Latorre1, J. Pardo2, A. I. Alcalde1, M.D. Murillo1, L. Grasa1
1
Pharmacology and Physiology / Physiology, 2Biochemistry and Molecular and
Cellular Biology, University of Zaragoza, Zaragoza, Spain
Contact E-mail Address: lgralo@unizar.es
INTRODUCTION: The recognition of intestinal microbiota is in part carried
out by toll-like receptors (TLR), which are responsible for initiating the innate
immune response. Alterations in the intestinal microbiota may contribute to the
development of intestinal inflammatory pathologies. Moreover, it has been
described that the serotonergic system may result also altered in situations of
intestinal inflammation. Serotonin (5-HT) has been shown to regulate gastrointestinal motility by binding to several receptors (5-HT1-7). However, the influence
of TLRs in 5-HT intestinal motor response mediated by 5-HT receptors in the
intestine remains unknown.
AIMS & METHODS: The aim of this study was to investigate the role of 5-HT2
and 5-HT3 receptors in the motor response induced by 5-HT in the mouse ileum,
and the involvement of TLR2 and TLR4 in this response.
Segments of ileum from male C57/BL10 wild-type (WT), TLR2 -/- and TLR4 -/mice of 8-12 weeks old were suspended in an organ bath in the direction of
longitudinal smooth muscle fibres. The effects of ritanserin (5-HT2 receptor
antagonist) or ondansetron (5-HT3 receptor antagonist) on motor responses
induced by 5-HT in the WT, TLR2 -/- and TLR4 -/- mice were studied. The
gene expression (mRNA) of 5-HT2 and 5-HT3 receptors was determined in
ileum from WT, TLR2 -/- and TLR4 -/- mice by quantitative RT-PCR.
RESULTS: Expression of 5-HT2A, 5-HT2B and 5-HT3 receptors was found in
ileum from WT mice. The contractile response induced by 5-HT 100 mM in ileum
from WT mice was partially reverted by ritanserin 1 nM and ondansetron 10 nM,
suggesting that 5-HT2 and 5-HT3 may be involved in this response. Expression of
5-HT2A, 5-HT2B and 5-HT3 in ileum from TLR2 -/- mice, was not modified
compared with WT mice. 5-HT-induced contractile response in TLR2-/- mice
was partially reverted by ritanserin but not by ondansetron, indicating that 5HT2 but not 5-HT3 may be involved in this response. In TLR4 -/- mice ileum, the
expression of 5-HT2A, 5-HT2B and 5-HT3 resulted increased compared with WT
mice. The 5-HT-induced contractile response in TLR4-/- was blocked by ritanserin and ondansetron, suggesting that 5-HT2 and 5-HT3 may be involved in this
response.
CONCLUSION: These results suggest that 5-HT2 and 5-HT3 receptors are
involved in the contractile response evoked by serotonin in mouse ileum.
Furthermore, TLR2 and TLR4 seem to interact with 5-HT2 and 5-HT3 receptors.
Funding by Gobierno de Aragon (B61/2013) and University of Zaragoza (JIUZ2013-BIO-08). E. Latorre has a personal grant (B105/11).
Disclosure of Interest: None declared
P0969 ELECTROPHYSIOLOGICAL
PROPERTIES
OF
BIOPSIES FROM PATIENTS WITH IRRITABLE BOWEL
SYNDROME ARE ALTERED BY EXPOSURE TO E. COLI

COLON

S.M. P. Bennet1,*, M. Sapnara1, H. Sjovall1, J.K. Gustafsson2, H. Eutamene3,


B.L. Neve4, H. Tornblom1, L. Ohman1, M. Simren1
1
Dept. of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at
University of Gothenburg, 2Dept. Biocheimcal chemistry, University of Gothenburg,
Gothenburg, Sweden, 3Neuro-Gastroenterology & Nutrition Group, NRA, UMR
1331 Toxalim, Toulouse, 4Dept. of Life Science, Danone Research, Palaiseau,
France
Contact E-mail Address: sean.bennet@gu.se
INTRODUCTION: Prior research indicates altered basal bowel permeability in
IBS patients and aberrations in the expression of tight junction proteins (TJP).
We therefore studied the electrophysiological characteristics of colon biopsies
using square wave current analysis in vitro.
AIMS & METHODS: Sigmoidal colonic biopsies (unprepared colon) from 35
IBS patients (female 27, median age 29 years (27-37)), (Rome III; IBS-C 4,
IBS-D 6, IBS-M 25) and 20 healthy controls (female 14, median age 36
years (27-47)) were mounted in miniaturized Ussing chambers and a solution
with or without E. coli (1x108 CFU/ml) was added to the luminal side. The
electrical properties of the mucosa were assessed by square wave current analysis
that enables quantification of epithelial/tight junction resistance, net current
generated by the membrane, and membrane capacitance reflecting the process
of exocytosis. To induce epithelial chloride secretion and/or release of mucin
from goblet cells, carbachol (Cch, 1mM) was added on the serosal side. In addition, TJP, claudin and occludin expression in 114 IBS patients (female 72,
median age 32 years (27-39)) (Rome III; IBS-C 14, IBS-D 26, IBS-M 74)
and 37 healthy controls (female 25, median age 27 years (23-35)) was analysed
using qRT-PCR. Immunohistochemistry was used to determine the tight junction
protein ZO-1 (TJP1) in 56 IBS patients (female 38, median age 30 years (24-36))
and 19 healthy controls (female 12, age median age 33 years (26-48)). Data is
shown as median, range 25-75 percentile.
RESULTS: Carbachol addition evoked similar changes in electrophysiological
parameters in IBS patients and healthy controls, with no differences seen between
IBS subgroups. However, IBS biopsies exposed to E. coli had an increased basal
membrane resistance (10.4 Ohm *cm2(9.2-12.5) vs. 8.3 Ohm*cm2 (7.5-10);
p 0.01) and net membrane current (-203.7 uA/cm2 (-311.9 -115.9) vs. -121
uA/cm2 (-210.3 -79.7); p 0.005) compared to unexposed IBS biopsies. E. coli
exposed IBS biopsies also had an increased response to CCh compared to unexposed IBS biopsies (-321.5 uA/cm2 (-411.3 -216.5) vs. -236.8 uA/cm2 (-335.8 102.3); p 0.01) and a reduced capacitance response (4.3 uF/cm2 (2.5-8.2) vs. 7.8
uF/cm2 (6.2-11.7); p 0.04). qRT-PCR analyses, demonstrated a tendency

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United European Gastroenterology Journal 2(1S)


towards lower expression of claudin (p 0.07) and TJP1 (p 0.06) in IBS
patients compared to healthy controls. Occludin expression was similar in IBS
patients and healthy controls, but was higher in IBS-C compared to IBS-M
(p 0.004). No significant difference was seen in levels of TJP1 ZO-1 protein
expression between IBS patients and healthy controls (p 0.4).
CONCLUSION: Colon mucosa from IBS patients reacts differently to mucosal
exposure to E. coli, with increased basal membrane resistance and net membrane
current as well as an increased reactivity to the muscarinic agonist CCh. The
exact mechanisms behind these phenomena remain unknown but may reflect
altered reactivity of epithelial ion channels and/or tight junctions.
Disclosure of Interest: None declared
P0971 MICROANGIOPATHY IS COMMON IN SUBMUCOSAL VESSELS
THROUGHOUT THE LARGE INTESTINE
B. Ohlsson1,*, A. Sasor2
1
Department of Clinical Sciences, Lund University, Division of Internal Medicine,
Skane University Hospital, Malmo, 2Department of Clinical Sciences, Division of
Pathology, Lund Universty, Lund, Sweden
Contact E-mail Address: bodil.ohlsson@med.lu.se
INTRODUCTION: The pathophysiology behind gastrointestinal dysmotility in
diabetes mellitus is unknown. Both esophageal dysmotility and gastroparesis
have been shown to be associated with retinopathy, suggesting microangiopathy
as important also for dysmotility.
AIMS & METHODS: The aim of the present study was to examine whether
patients with diabetes mellitus exhibit microangiopathy in the large intestine, and
if present, to correlate this to the clinical picture.
Consecutive patients subjected to surgery of the large intestine at any of the
Departments of Surgery in the southernmost districts of Skane between
January 2011 and May 2013 were identified. All medical records were scrutinized,
and patients with a history of diabetes mellitus were reconsidered for histopathologic reevaluation, according established criteria (1, 2). Morphometric examination of the vessels was compared with biopsies from non-diabetic patients.
Gender, age, type of diabetes, diabetic complications, type of diabetes treatment,
and other concomitant diseases were registered from the medical records.
RESULTS: Of 1135 identified patients during the studied time period, 94
patients suffered from diabetes mellitus and were finally examined. Twentynine non-diabetic patients served as controls. The mean age was 71.8  10.3
and 70.0  12.1 years in patients and controls, respectively. Microangiopathy
was found in 68% of patients and in 17% of controls (p 5 0.001). The wall-tolumen relation was 0.31 (0.230.46) in patients with diabetes mellitus compared
with 0.18 (0.130.24) in controls (p 5 0.001). The records did not include any
information about gastrointestinal symptoms. There was no association between
microangiopathy and clinical picture available.
CONCLUSION: Microangiopathy in the large intestine is more common in
patients with diabetes mellitus than in controls. This may contribute to dysmotility secondary to diabetes mellitus.
REFERENCES
1. Gupta R, Sharma A, Gupta R, et al. Morphometry of non-inflammatory
arteriolar changes in lupus nephritis: a study of 40 cases. Saudi J Kidney Dis
Transpl 2012; 23: 1196-1201.
2. Kayler LK, Mohanka R, Basu A, et al. Correlation of histologic findings on
preimplant biopsy with kidney graft survival. Transplant Int 2008; 21: 892-898.
Disclosure of Interest: None declared
P0972 CHARACTERISATION OF NAUSEA IN WELL-CONTROLLED
AND LONG-TERM, OPEN-LABEL STUDIES OF LUBIPROSTONE
FOR CHRONIC IDIOPATHIC CONSTIPATION, OPIOID-INDUCED
CONSTIPATION, AND IRRITABLE BOWEL SYNDROME WITH
CONSTIPATION
B. Cryer1, L.R. Webster 2, T. Losch-Beridon 3,*
1
Department of Internal Medicine, Digestive and Liver Diseases, University of
Texas, Southwestern Medical School, Dallas, TX, 2PRA International, Salt Lake
City, UT, 3Sucampo Pharma Americas, LLC, Bethesda, MD, United States
Contact E-mail Address: Byron. Cryer@UTSouthwestern.edu
INTRODUCTION: Lubiprostone (LBP) has been studied for the treatment of
chronic idiopathic constipation (CIC) in adults, opioid-induced constipation
(OIC) in adults with chronic non-cancer pain who are taking full-agonist opioids
other than diphenylheptanes, and irritable bowel syndrome with constipation
(IBS-C). LBP has a favourable overall safety profile, with nausea being the
most common adverse event (AE). Here, we provide a detailed characterization
of nausea in pivotal studies of LBP across all 3 indications.
AIMS & METHODS: The CIC analysis includes data pooled from 3 short-term
(34 weeks duration), randomised, placebo (PBO)-controlled and 3 long-term
(one 24-week and two 48-week), open-label studies of LBP. Overall, 316 CIC
patients received PBO and 1113 received LBP 24 mcg twice daily (BID). The OIC
analysis includes data pooled from three 12-week, randomised, PBO-controlled
studies and one 36-week, open-label extension study. OIC patients received PBO
(n 652) or LBP 24 mcg (n 889) BID. The IBS-C analysis includes data pooled
from three 12-week, randomised, PBO-controlled studies and one 36-week, openlabel study. In total, 435 IBS-C patients received PBO and 1011 received LBP 8
mcg BID.
RESULTS: The crude incidence of nausea in patients receiving LBP was 31.1%,
13.9%, and 11.4% in the CIC, OIC, and IBS-C populations, respectively, when
exposed to LBP for up to 12 months; corresponding rates in patients treated with
PBO over 4- and 12-week periods ranged from 5.1%6.7%. For the same timeperiods, the incidence of severe nausea in patients receiving LBP was 3.5%,
1.0%, and 0.9% in the CIC, OIC, and IBS-C populations, respectively, with

corresponding rates in patients treated with PBO ranging from 0%1.1%.


Nausea led to discontinuation in 8.7%, 2.1% and 1.3% of the CIC, OIC, and
IBS-C populations receiving LBP, respectively, with corresponding discontinuation rates in patients treated with PBO ranging from 0%0.7%. Of those CIC,
OIC, and IBS-C patients who received LBP and reported nausea at any time
during the treatment period, 83.6%, 87.9%, and 88.7%, respectively, reported
only 1 event of nausea. Of these patients, 62.1%, 75.2%, and 63.7% did not
require a change to their assigned dosing regimen for CIC, OIC, or IBS-C,
respectively, with nearly three-quarters of these patients completing the full treatment period with LBP (72.7%, 70.7%, and 73.8%, respectively). Of those CIC,
OIC, and IBS-C patients who reported only 1 nausea event, 12.0%, 8.3%, and
17.7%, respectively, either reduced their intake to once daily (QD) dosing or
temporarily withheld medication, which allowed for 54.5%, 66.7%, and 100%
of these patients, respectively, to complete LBP dosing in the clinical trial. Across
the 3 indications, the majority of reported nausea events occurred during the first
5 days after beginning LBP treatment (66.9%).
CONCLUSION: Most patients report only a single event, with a majority of
events being mild-to-moderate severity and occurring early in the treatment
period. In addition to an emphasis on dosing with meals, dose reduction and/
or temporary withholding of doses are strategies that may be employed for
management of nausea in patients taking lubiprostone.
Disclosure of Interest: B. Cryer: None declared, L. R. Webster: None declared, T.
Losch-Beridon Shareholder of: Sucampo, Other: Sucampo employee
P0973 PUBORECTALIS MUSCLE AND EXTERNAL ANAL SPHINCTER
DO NOT, BY DEFINITION, BEHAVE AS ONE FUNCTIONAL UNIT IN
PATIENTS WITH FUNCTIONAL DEFECATION DISORDER
H.K. De Boer1,2,*, E. Heineman1,2, P.M. Broens2
University of Groningen, 2Department of Surgery, University Medical Center
Groningen, Groningen, Netherlands
Contact E-mail Address: p.m.a.broens@umcg.nl
1

INTRODUCTION: Functional defecation disorder (FDD) is common and


underlies about half of the cases of chronic constipation. Rome III-classification
distinguishes dyssynergic defecation and inadequate defecatory propulsion,
which can be further subdivided according to a classification proposed by Rao
et al.1,2
Both classifications are based on the unsubstantiated assumption that puborectalis muscle and external anal sphincter behave as one functional unit during
attempted defecation. What if it turns out that puborectalis muscle and external
anal sphincter do not, by definition, function as one unit and are therefore not,
by definition, equally affected in patients suffering from FDD? That could have
an impact on both classification, diagnostics and treatment of FDD.
AIMS & METHODS: Anorectal manometry and defecometry test were performed in 124 adult patients suffering from FDD. Pressure changes were
recorded at three levels: rectum, puborectalis muscle and external anal sphincter.
RESULTS: Defecometry test revealed that puborectalis muscle and external anal
sphincter do not consistently contribute equally to FDD. Three main groups can
be identified: congruent FDD (puborectalis muscle and external anal sphincter
are more or less equally affected; n 105), anal sphincter-dominated FDD
(external anal sphincter is significantly more affected than puborectalis muscle;
n 10) and puborectalis-dominated FDD (puborectalis muscle is significantly
more affected than external anal sphincter; n 9).
Defecatory propulsive force (increase in rectal pressure that is required for defecation) is stronger correlated to pressure increase at the level of the puborectalis
muscle ( 0.794) than to pressure increase at the level of the external anal
sphincter ( 0.488).
Male patients generate a higher defecatory propulsive force than female patients
(p 5 0.001). They also build more pressure on the level of the puborectalis
muscle (p 0.003) and suffer relatively more often from puborectalis-dominated
FDD.
CONCLUSION: Puborectalis muscle and external anal sphincter do not, by
definition, behave as one functional unit in patients suffering from FDD and
may thus differ in degree of dyssynergia. This understanding might have some
important consequences for classification, diagnostics and treatment of FDD. It
questions, for example, the reliability of the single probe electromyographic
devices currently used in treatment of FDD.
REFERENCES
1. Bharucha AE, Wald A, Enck P, et al. Functional anorectal disorders.
Gastroenterology 2006; 130: 1510-1518.
2. Rao SS. Dyssynergic defecation and biofeedback therapy. Gastroenterol Clin
North Am 2008; 37: 569-586.
Disclosure of Interest: None declared
P0974 CONFIRMATORY FACTOR ANALYSIS OF THE PATIENT
ASSESSMENT OF CONSTIPATION-SYMPTOMS (PAC-SYM) IN
PATIENTS WITH CHRONIC CONSTIPATION
L. Neri1,*, P.M. Conway2, G. Basilisco3 on behalf of Laxative Inadequate Relief
Survey (LIRS)
1
Clinical Science and Community Health, University of Milan, Milano, Italy,
2
Psychology, University of Copenhagen, Copenhagen, Denmark, 3Gastroenterology
and Endoscopy Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore
Policlinico, Milano, Italy
Contact E-mail Address: luca.neri@unimi.it
INTRODUCTION: PAC-SYM is widely adopted to evaluate constipation severity. However it has been validated in a small sample, few items have been
included based on expert opinion and not on empirical grounds and its factor
structure has never been replicated. We sought to assess its psychometric

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United European Gastroenterology Journal 2(1S)

properties, its responsiveness to clinical changes and characterizing its relationship with key outcomes such as quality of life and treatment satisfaction in a
large sample of patients with chronic constipation.
AIMS & METHODS: We enrolled 2203 outpatients with chronic constipation in
two waves. We used the wave I sample to test psychometric properties and
construct validity of the PAC-SYM and wave 2 sample to cross-validate the
factor structure with confirmatory factor analysis (CFA), and to assess criterion
validity, responsiveness to clinical changes and the minimal clinically important
difference.
RESULTS: We observed a large floor effect for rectal tearing (62%). Deletion of
such item lead to a 11-item version (M: PAC-SYM). Exploratory Factor Analysis
revealed a bifactor model with 2 subscales (stool and abdominal symptoms) and
a general severity factor. CFA consucted on the second wave dataset supported
this solution. The M:PAC-SYM demonstrated excellent reliability ( 0.89),
moderate correlation with SF-12 and treatment satisfaction (r 0.28-0.45), discrimination across Rome III criteria for functional constipation and abdominal
pain (table 1), and responsiveness to clinical change ( -0.49; !2 0.25). M:PACSYM minimal clinically important difference was 0.24.
Clinical Characteristics*

Rome III
Lumpy/Hard Stools
Incomplete Evacuation
Obstruction
Manual Maneuvers
53 defecations/wk
Strain
Abdominal Pain

M-PAC-SYM
 ( )

M-ABD

M-STO

0.32
0.44
0.57
0.26
0.03
0.29
0.26

0.16
0.29
0.29
0.04
0.13
0.22
0.44

0.39
0.52
0.68
0.39
0.13
0.33
0.16

(0.40)
(0.63)
(0.74)
(0.33)
(0.04)
(0.37)
(0.32)

(0.17)
(0.36)
(0.33)
(0.04)
(0.15)
(0.25)
(0.48)

(0.42)
(0.65)
(0.78)
(0.43)
(0.14)
(0.36)
(0.17)

CONCLUSION: We developed a modified version of the PAC-SYM which


might better represent symptom severity of most patients seeking care in gastroenterology referral centers.
REFERENCES
1. Frank L, Kleinman L, Farup C, et al. Psychometric validation of a constipation symptom assessment questionnaire. J Scand J Gastroenterol 1999; 348: 7077.
2. Tack J, Quigley E, Camilleri M, et al. Efficacy and safety of oral prucalopride
in women with chronic constipation in whom laxatives have failed: an integrated
analysis. United Eur Gastroenterol J 2013; 1: 4859.
Disclosure of Interest: L. Neri: None declared, P. Conway: None declared, G.
Basilisco Lecture fee(s) from: Shire Italia spa
P0975 DIFFERENT
INNERVATIONS
FOR
CONSCIOUS
AUTONOMIC ANAL SPHINCTER CONTRACTIONS IN ADULT
PATIENTS

AND

M.M. van Meegdenburg1,2,*, E. Heineman1,2, P.M. Broens1,2


1
Surgery, University Medical Center Gorningen, 2University of Groningen,
Groningen, Netherlands
Contact E-mail Address: m.van.meegdenburg02@umcg.nl
INTRODUCTION: Fecal continence is partially maintained by external anal
sphincter contraction and the anal-external sphincter continence reflex1,2.
Whereas the first system is supplied by the pudendal nerve3, it is unknown if
the reflex part of the external anal sphincter is also mediated by the pudendal
nerve.
AIMS & METHODS: The present study aims to determine if in patients with
pudendal neuropathy both continence systems, concerning the external anal
sphincter, are malfunctioning. Retrospectively, we reviewed the medical records
of all patients older than seventeen who had undergone an anorectal function test
between January 2010 and March 2013 and in which nerve supply to and functional anatomy of the external anal sphincter was not damaged by surgery,
trauma, and/or polyneuropathy (N 70). The study was conducted at
University Medical Center Groningen, the Netherlands.
RESULTS: The patients were divided into two groups, one group without signs
of pudendal neuropathy (anal electrosensibility  4 mA at one and two centimeter into the anal canal, PudNP-), and the other group with signs of pudendal
neuropathy (anal electrosensibility 4 4 mA at one and two centimeter into the
anal canal, PudNP). Of the seventy patients, 76% had pudendal neuropathy.
PudNP were significantly older than PudNP- (P .013). Maximum anal
sphincter contractility, i.e. conscious contraction, was significantly lower in
PudNP than in PudNP- (median: 165 versus 235 mm Hg, P .007). By contrast, pressure in the anal canal at maximum tolerable or retainable sensation, i.e.
autonomic contraction, did not significantly differ between the two groups
(median: 135 versus 153 mm Hg). Furthermore, no relation was found between
maximum anal sphincter contractility and pressure in the anal canal at maximum
tolerable or retainable sensation. Multiple linear regression analyses demonstrated that age and electrosensibility, measured at two centimeters into the
anal canal, significantly predicted conscious contraction, but not autonomic
contraction.
CONCLUSION: Autonomic reflex contraction of the external anal sphincter is
most probably mediated by nerve fibers different from those responsible for
conscious contraction (the pudendal nerve). A potential source might be a
direct branch from the fourth sacral nerve. This needs to be elucidated in a
prospective study set up.

REFERENCES
1. Rao SS. Pathophysiology of adult fecal incontinence. Gastroenterology 2004;
126: S14-S22.
2. Broens PM, Penninckx FM and Ochoa JB. Fecal continence revisited: the anal
external sphincter continence reflex. Dis Colon Rectum 2013; 56: 1273-1281.
3. Shafik A. Neuronal innervation of urethral and anal sphincters: surgical anatomy and clinical implications. Curr Opin Obstet Gynecol 2000; 12: 387-398.
Disclosure of Interest: None declared
P0976 LUBIPROSTONE IS WELL TOLERATED FOR TREATMENT OF
OPIOID-INDUCED CONSTIPATION IN CHRONIC NON-CANCER
PAIN PATIENTS: RESULTS OF THREE PHASE 3, RANDOMISED,
DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS
P. Lichtlen1,*, T. Losch-Beridon 2, M. Wang 2
Sucampo AG, Zug, Switzerland, 2Sucampo Pharma Americas, LLC, Bethesda,
MD, United States
Contact E-mail Address: plichtlen@sucampo.com
1

INTRODUCTION: Chronic opioid use is often associated with the common


adverse effect of serious constipation; however, there are limited treatment
options for patients with opioid-induced constipation (OIC) in patients with
non-cancer pain. The efficacy and safety of lubiprostone (LBP), a selective
ClC-2 activator, for treating OIC in subjects taking opioids for chronic, noncancer pain was evaluated in three multicentre, 12-week, randomised, doubleblind, placebo-controlled, Phase 3 trials. An integrated analysis of data from
those 3 trials was conducted to determine the overall safety profile of LBP in
this population.
AIMS & METHODS: Adults on chronic opioid therapy with documented OIC
(i.e., defined as having, on average 5 3 spontaneous bowel movements/week),
were randomised to receive double-blind LBP 24 mcg or placebo twice daily
(BID). Adverse events (AEs) were recorded electronically by the subject or investigator; graded as mild, moderate, or severe; and assessed for seriousness and
relationship to study drug.
RESULTS: The combined safety population from the 3 trials (N 1315; LBP,
n 663; placebo, n 652; mean age, 50.4 years) comprised mostly female
(62.7%) and white (82.6%) subjects. The most common (5% in the LBP
arm) treatment-emergent AEs (TEAEs) were gastrointestinal (GI) disorders,
with nausea, diarrhea, and abdominal pain reported 2.1, 2.5, and 3.3 times
more with LBP than with placebo. Incidences of other TEAEs were comparable
with LBP and placebo. In both the LBP and placebo arms, most subjects experienced mild (38.3% vs 36.5%) or moderate (31.5% vs 26.7%) TEAEs, with few
severe TEAEs (8.9% vs 8.0%); the rest had no TEAEs. The incidence of severe
TEAEs was similar with LBP or placebo, except for diarrhea (1.8% vs 0.3%),
vomiting (0.3% vs 0.8%), and abdominal distension (0% vs 0.6%). Significantly
more subjects in the LBP arm had 1 treatment-related AE (TRAE; 30.8% vs
20.2%; P50.0001) or 1 GI TRAE (24.7% vs 12.9%). The most common (5%
in the LBP arm) TRAEs were GI disorders, with nausea and diarrhea reported
2.5 and 4.3 times more in the LBP arm. The other TRAEs (1% of LBP arm)
were, in order of decreasing frequency, abdominal pain, abdominal distension,
flatulence, vomiting, headache and oedema peripheral experienced 3.5, 2.2, 1.3,
1.9, 1.4 and 3.7 times more in the LBP-treated patients vs placebo, respectively.
Percentages of subjects experiencing 1 serious AE (SAE) were similar in the
LBP and placebo arms (3.9% vs 3.2%; p 0.554). The only SAEs reported in 41
subject were migraine and back pain (LBP arm) and upper abdominal pain,
fecaloma, and back pain (placebo arm). No SAEs were attributed to LBP; 3
SAEs (pneumonia, hypersensitivity, and fecaloma) were attributed to placebo.
One death was reported in the LBP arm (multiple drug toxicity), but was assessed
as unrelated to study drug by the investigator. Significantly more subjects treated
with LBP (7.2%) compared with placebo (3.1%) withdrew from the studies
because of AEs (p 0.001), most commonly GI AEs (LBP, 4.4% vs placebo,
0.9%; P50.001).
CONCLUSION: An integrated safety analysis from 3 randomised, double-blind,
placebo-controlled trials demonstrates that LBP, when used in chronic noncancer pain subjects with OIC, is well tolerated.
Disclosure of Interest: P. Lichtlen Consultancy for: Sucampo, T. Losch-Beridon
Shareholder of: Sucampo, Other: Sucampo employee, M. Wang Other: Sucampo
employee
P0977 LANREOTIDE AUTOGEL 120 MG FOR CHRONIC REFRACTORY
DIARRHEA: A MULTICENTER PROSPECTIVE TRIAL
R. Bisschops1,*, V. De Ruyter2, G. Demolin3, D. Baert4, T. Moreels5, P. Pattyn6,
H. Verhelst7, L. Lepoutre8, J. Arts9, P. Caenepeel10, P. Ooghe11, P. Maisonobe2,
J. Tack1
1
GASTROENTEROLOGY, UZ LEUVEN, Leuven, 2Ipsen NV, Merelbeke,
3
GASTROENTEROLOGY, CHC Saint-Joseph, Lie`ge,
4
GASTROENTEROLOGY, AZ Maria Middelares, Ghent,
5
GASTROENTEROLOGY, University Antwerp, Antwerp, 6Thoracic Surgery,
Unversity of Ghent, Ghent, 7Surgery, ZOL, Genk, 8GASTROENTEROLOGY,
OLV-Ziekenhuis, Aalst, 9GASTROENTEROLOGY, AZ St Lucas, Brugge,
10
GASTROENTEROLOGY, ZOL, Genk, 11GASTROENTEROLOGY, CHU
Charleroi, Charleroi, Belgium
Contact E-mail Address: raf.bisschops@uzleuven.be
INTRODUCTION: Lanreotide has an inhibitory effect on gastrointestinal secretions and motility. We evaluated the efficacy and safety of the prolonged-release
somatostatin analogue lanreotide Autogel 120 mg for the treatment of persistent
diarrhea in a multicenter, prospective, open label study.
AIMS & METHODS: The study was performed in 10 centers between July 2009
and August 2012. The study protocol was approved by the Ethics Committee of

A401

United European Gastroenterology Journal 2(1S)


UZ Leuven, Belgium (V). Male or female adult patients with refractory diarrhea
(mean of 4 3 stools/24 h) for at least 1 month after workup to rule out inflammatory, infectious causes, and rectum disorders, and insufficient /non-response
to standard anti-diarrheal were treated for 8 weeks with lanreotide autogel 120
mg deep s.c. every 4 weeks. Patients stool frequency and consistency (Bristol
Stool Form Scale) were recorded in a daily diary. Quality of life (QOL) was
assessed using the SF-36 and IBS-QOL questionnaires. Responders were patients
with a 50% decrease or a normalization of the mean number of stools. Adverse
events (AEs) were recorded during the entire study.
RESULTS: In total, 36 patients (24 women, 12 men) with chronic refractory
diarrhea were studied. The mean age was 55.2  16.4 years. Four weeks after
the first injection (Day 28), 44.4% of patients were responders, which increased
to 54.3% at Day 56. Response rates were higher in male patients (58.3%) compared to females (37.5%). Overall, the mean number of stools decreased significantly from 5.5  2.3 at baseline to 3.6  2.2 at Day 56 (-30.7%) (p 0.0006). In
the responder subgroup at Day 56 this number changed significantly from 5.3 
2.4 to 2.2  0.8 (p 5 0.0001). The median percentage of days per week with less
than 3 stools/day increased from 7.1% at baseline to 57.1% at Day 56. In the
responder subgroup at Day 56, the mean stool consistency score dropped significantly from 6.4  0.7 to 5.2  1.2(p 0.0005). At Day 56, the mean IBS-QOL
score increased with 16.3 points. Similarly, the SF36-QOL scores improved at
Day 56, especially in the domains of social functioning (14.0), physical role
(11.8) and mental health (10.1). The improvement in IBS-QOL was very
significant in the responder group with an increase from 48.4 to 76.7
(p 0.0001), indicating that the improvement in stool consistency and frequency
resulted in an improvement of QOL. In total, 93 treatment emergent AEs were
reported, of which the majority (79) were mild to moderate and 9 were serious.
The most frequently reported AEs were gastrointestinal disorders (abdominal
pain, 25% of patients; nausea, 11.1% and steatorrhea, 8.3%), injection site
reactions (16.7%) and asthenia/fatigue (11.1%).
CONCLUSION: This study showed improvement of diarrheal symptoms and
QOL during therapy with lanreotide autogel 120 mg treatment, which suggest it
is effective for the management of persistent refractory diarrhea. Confirmatory
studies are needed.
Disclosure of Interest: R. Bisschops Financial support for research from: Ipsen
NV, V. De Ruyter Other: employee Ipsen NV, G. Demolin: None declared, D.
Baert: None declared, T. Moreels: None declared, P. Pattyn: None declared, H.
Verhelst: None declared, L. Lepoutre: None declared, J. Arts: None declared, P.
Caenepeel: None declared, P. Ooghe: None declared, P. Maisonobe Other:
employee Ipsen NV, J. Tack: None declared
P0978 SMALL-BOWEL ABNORMALITIES IN PATIENTS
IRRITABLE BOWEL SYNDROME - A CAPSULE ENDOSCOPY
STUDY

WITH

S. Oka1,*, S. Tanaka1, M. Nakano2, A. Igawa2, T. Aoyama2, M. Ito2,


K. Chayama2
1
Endoscopy, 2Gastroenterology and Metabolism, Hiroshima University Hospital,
Hiroshima, Japan
Contact E-mail Address: oka4683@hiroshima-u.ac.jp
INTRODUCTION: Irritable bowel syndrome (IBS) is the most common functional digestive disorder globally, affecting 10-20% of the adult population in
several western countries. IBS is diagnosed when the symptoms fulfill the Rome
III criteria, however, the small bowel was not examined.
AIMS & METHODS: We conducted a case-control study to determine whether
capsule endoscopy (CE) detects small-bowel abnormalities in IBS patients. Study
subjects were 57 patients who met the Rome III criteria for IBS and were scheduled to undergo CE (PillCam SB or SB2; Given Imaging Ltd., Yoqneam, Israel)
for investigation of their symptoms at Hiroshima University Hospital between
April 2006 and December 2013 (IBS group) and 57 patients with occult obscure
gastrointestinal bleeding (OGIB) were selected as control (OGIB [control]
group). Patients in the IBS group were further classified according to the type
of IBS: constipationprevalent IBS (subgroup A, n 40); diarrhea-prevalent IBS
(subgroup B, n 26); or mixed IBS (subgroup C, n 9). CE was evaluated in all
groups according to the total enteroscopy achievement rate, mean small-bowel
transit time, small-bowel lesion detection rate, and the types of small-bowel
lesions detected. All statistical analyses were carried out with JMP statistical
software version 5.0.1J (SAS Institute Inc., Cary, NC, USA). P50.05 was considered significant.
RESULTS: Total enteroscopy was achieved by CE in 82% (47/57) of patients in
the IBS group and 80% (45/57) of patients in the OGIB group; the difference
between the two groups was not significant. For patients in whom total enteroscopy was achieved by CE, mean small-bowel transit time was 270 minutes in the
IBS group and 268 minutes in the OGIB group, with no significant betweengroup difference. In the IBS group, total enteroscopy was achieved per subgroup
as follows: subgroup A, 76% (22/29); subgroup B, 89% (17/19); and subgroup C,
89% (8/9). The mean small-bowel transit times were 280 minutes, 254 minutes,
and 277 minutes, respectively, with no significant difference among them. The
small-bowel lesion detection rates were 29% (20/57) and 28% (16/57) in the IBS
group and OGIB group, respectively. Small-bowel lesions detected by CE in the
IBS group were non-specific enteritis (n 16), non-specific ulcer (n 1), eosinophilic enteritis (n 1), ischemic enteritis (n 1), and lesioning due to a parasitic
worm (n 1); otherwise, no abnormality was found (n 37). Small-bowel lesions
detected by CE in the OGIB group were non-specific enteritis (n 6), non-specific ulcer (n 6), submucosal tumor (n 3), and diverticulum (n 1); otherwise
no abnormality was found (n 41). The prevalence of non-specific enteritis was
significantly high in the IBS group versus the OGIB group (p50.05). Smallbowel lesion detection rates in the IBS subgroups were as follows: subgroup A,
17% (5/29); subgroup B, 68% (13/19); and subgroup C, 22% (2/9). The detection

rate in subgroup B (versus subgroup A and subgroup C) was significantly high


(p50.05).
CONCLUSION: CE detected no significant abnormalities that explained the
symptoms in the majority of our patients with IBS; thus, the use of CE in IBS
patients is not supported by the current data.
Disclosure of Interest: None declared
P0979 A PHASE 1 STUDY TO INVESTIGATE THE ABSORPTION,
METABOLISM AND EXCRETION OF 14C PRUCALOPRIDE AFTER
A SINGLE ORAL DOSE
S. Flach1,*, S. Troy2, T. Pankratz3, J. Ding1, G. Scarfe4, J. Getsy2
Covance, Madison, 2Shire, Wayne, 3Xceleron Inc, Germantown, United States,
4
Shire, Basingstoke, United Kingdom
1

INTRODUCTION: Prucalopride is a 5-hydroxytryptamine receptor agonist that


stimulates intestinal motility and is approved in Europe for the treatment of
women with chronic constipation in whom laxatives fail to provide adequate
relief. The absorption, metabolism and excretion (AME) of prucalopride has
been reported previously; however, poor recovery of total radioactivity led to
uncertainty regarding the mass balance properties of the drug.
AIMS & METHODS: The aim of this phase 1 study (NCT01807000) was to use
microtracer dosing (200 nCi radioactivity) with accelerator mass spectrometry
(AMS) to investigate the AME profile of 14C-radiolabelled prucalopride after a
single oral dose and to obtain more robust data. Healthy men aged 1850 years
were enrolled in the study. A single oral dose of 2 mg 14C-prucalopride (200 nCi
radioactivity) was administered on day 1. Blood samples were collected at 0, 0.5,
1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours on day 1, and once daily thereafter until day
11. Urine and stool samples were collected and electrocardiogram and vital signs
were recorded on every day of the study. Pharmacokinetic parameters were
calculated from concentrations of prucalopride measured by liquid chromatographytandem mass spectrometry (LCMS/MS). Total radioactivity and metabolites from LC fractions were measured using AMS. Metabolites were identified
using authentic standards, when available, and by LC coupled with high resolution MS. Results presented are mean  standard deviation unless otherwise
specified.
RESULTS: Six men were enrolled in the study (mean age: 35.5  10.45 years).
Following oral administration, 14C-prucalopride was absorbed rapidly (median
time to maximum plasma concentration [tmax]: 2.75 h [range: 1.134.00 h]) and
was eliminated with a half-life (t) of 20.6  5.35 h. For prucalopride, the
maximum plasma concentration (Cmax: 3.79  1.10 ng/mL) and area under the
concentrationtime curve (AUC01: 96.5  9.64 ngh/mL) accounted for 92%
and 95% of the total radioactivity in plasma, respectively. The blood:plasma
radioactivity concentration ratios ranged from 1.74 to 2.06 up to 48 hours
post-dose. Most of the administered dose of prucalopride (84.2  8.9%) was
recovered in urine, and an additional 13.3  1.7% of the dose was recovered
in faeces (total recovery: 97.5  8.6%). Approximately 65% of the dose recovered in urine and 5% in faeces was intact prucalopride. Quantitatively important
metabolites identified in the urine and faeces were products of O-demethylation,
N-dealkylation and oxidation.
CONCLUSION: The AMS with microtracer approach was used successfully in
this study, with good total recovery of radioactivity in urine and faeces (97.5 
8.6% of the administered radioactive dose). Following oral administration of a 2
mg dose of prucalopride, at least 84% of the drug was absorbed. The observed
blood:plasma ratio of radioactivity indicates that there was moderate uptake of
prucalopride (and metabolites) into blood cells. Systemic exposure to prucalopride metabolites was low, and both prucalopride and its metabolites were eliminated in urine and, to a lesser extent, faeces. This shows that renal clearance is the
primary route of elimination of prucalopride.
Disclosure of Interest: S. Flach Financial support for research from: Shire, S.
Troy Shareholder of: Shire, Other: Shire, T. Pankratz Financial support for
research from: Shire, J. Ding Financial support for research from: Shire, G.
Scarfe Shareholder of: Shire, Other: Shire, J. Getsy Shareholder of: Shire,
Other: Shire
P0980 EFFICACY AND SAFETY OF PRUCALOPRIDE IN MEN WITH
CHRONIC CONSTIPATION: A PHASE 3, RANDOMIZED, DOUBLEBLIND, PLACEBO-CONTROLLED TRIAL
Y. Yiannakou1,*, M. Bouchoucha2, I. Schiefke3, H. Piessevaux4, R. Filip5,
L. Gabalec6, D. Stephenson7, R. Kerstens8, A. Levine9
1
County Durham and Darlington NHS Foundation Trust, Durham, United
Kingdom, 2Universite Paris V-Rene-Descartes, Paris, France, 3Klinik fur
Gastroenterologie und Hepatologie, Klinikum St. Georg, Leipzig, Germany,
4
Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels,
Belgium, 5Institute of Rural Health, Lublin, Poland, 6Orlickoustecka nemocnice,a.s, Ust nad Orlic, Czech Republic, 7Shire, Basingstoke, United Kingdom,
8
Shire-Movetis, Turnhout, Belgium, 9Shire, Wayne, United States
INTRODUCTION: Prucalopride (PRU) is a high-affinity serotonin receptor (5HT4) agonist approved in Europe for the symptomatic treatment of chronic
constipation (CC) in women in whom laxatives fail to provide adequate relief.
AIMS & METHODS: The aim of this phase 3, multicenter, parallel-group,
double-blind trial was to evaluate the efficacy and safety of PRU in men
(NCT01147926). Men aged 18 years with CC who had 2 spontaneous complete bowel movements (SCBMs) per week were randomized to receive placebo
(PLA) or PRU 2mg (starting dose of 1mg for patients 65 years) once daily for
12 weeks. The primary endpoint was the proportion of patients achieving a mean
of 3 SCBMs per week over 12 weeks. Secondary endpoints included the Patient
Assessment of Constipation-Symptoms (PAC-SYM) and -Quality of Life (PACQOL) questionnaires. Safety was assessed throughout the study.

A402
RESULTS: In total, 374 patients from 10 European countries were randomized
(187 per treatment group). Baseline demographics were similar between treatment groups with an overall mean age of 58.5 (SD: 16.91) years and mean
duration of CC of 9.2 (SD: 11.63) years. The primary endpoint was achieved
by significantly more patients in the PRU group (37.9%) than in the PLA group
(17.7%, p50.0001). More patients on PRU than PLA achieved an improvement
of 1 SCBM/week (53.7% vs 45.3%; p 0.0743) and an improvement of 1
SBM/week (65.5% vs 43.1%; p50.0001). At the final on-treatment assessment,
there was no significant difference between groups in the proportion of patients
with a clinically relevant improvement of 1 point in total PAC-SYM score
(PRU: 34.9%; PLA: 30.4%; p 0.3152), abdominal (39.1% vs 35.1%;
p 0.4874) or rectal subscale score (34.9% vs 29.2%; p 0.2759). However,
there was a significant difference in stool symptoms score (53.3% vs 36.3%;
p 0.0005). The proportion of patients with an improvement of 1 in PACQOL score was higher with PRU (40.2%) than PLA (32.7%; p 0.0755), particularly in the satisfaction (52.7% vs 38.8%; p 0.0035) and physical discomfort
subscales (50.3% vs 39.2%; p 0.0249). The overall safety profile was consistent
with previous studies. The most common adverse events (AEs) were abdominal
pain (PRU vs PLA: 4.3% vs 5.9%), diarrhoea (6.5% vs 1.6%), nausea (6.0% vs
2.2%), headache (9.2% vs 3.8%) and dizziness (2.2% vs 1.6%). The incidence of
serious AEs and ischaemic cardiovascular adverse events was low and comparable between treatment groups.
CONCLUSION: In this first study of efficacy of PRU in an exclusively male
patient population, PRU significantly increased the proportion of men achieving
an average of 3 SCBMs per week compared with PLA. No new safety concerns
were identified. These results demonstrate a positive benefitrisk profile for the
use of PRU in men with CC.
Disclosure of Interest: Y. Yiannakou Financial support for research from: Shire,
Lecture fee(s) from: Shire, M. Bouchoucha: None declared, I. Schiefke: None
declared, H. Piessevaux: None declared, R. Filip: None declared, L. Gabalec:
None declared, D. Stephenson Shareholder of: Shire, Other: Shire, R. Kerstens
Other: Shire-Movetis, A. Levine Shareholder of: Shire, Other: Shire
P0981 EVALUATION OF A NEW DIAGNOSTIC METHOD FOR ANAL
SPHINCTER RUPTURE BY THREE-DIMENSIONAL HIGHRESOLUTION ANORECTAL MANOMETRY
A. Benezech1,*, M. Behr2, M. Bouvier1, J.-C. Grimaud1, S. Berdah1,2, V. Vitton1
1
Hopital Nord, 2IFSTTAR, Marseille, France
Contact E-mail Address: benezech.alban@gmail.com

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: We prospectively investigated the efficacy of rectal BT
injection in 21 patients with FI. In 11 patients, FI was related to anal sphincter
incompetence, in 4 patients to overactive rectum and in 6 patients to overactive
colonic pouch after proctectomy. All patients failed medical therapy, and 7
patients were unresponsive to sacral nerve root stimulation. BT injection consisted in a session of 10 injections of 50 UI of Dysport (3-4 injections every 5
cm) in the submucosa of the rectum or of the colonic pouch as previously
reported (1). Clinical efficacy and quality of life were assessed at baseline, at 3
and 6 months after BT injection with the Cleveland Clinic and the FIQL scores,
respectively. Anorectal manometry was performed before and 3 months after BT
injection.
RESULTS: Compared to pre-operative values of the 21 patients, Cleveland
Clinic (12.7  1.2) and the FIQL (1.9  0.2) scores improved at 3 months (9.7
 1.2 and 2.4  0.2, respectively; p50.05 for both). After a single session of
injection (n 6), the Cleveland Clinic and the FIQL scores at 6 months returned
to pre-operative values. By contrast, in patients with a second session performed
3 months after the first one (n 8), the Cleveland Clinic and the FIQL scores
remained decreased at 6 months compared to pre-operative values (p50.01 for
both). At 3 months, neither anal tone and squeezing pressures, nor rectal volume
and compliance were affected by BT injections. Univariate analysis failed to
evidence factors associated with a poor clinical response. In particular, similar
improvement was noted in patients with anal sphincter incompetence or with an
overactive reservoir. No serious adverse events were reported.
CONCLUSION: Our study is the first to demonstrate that injection of BT in the
rectum or in the colonic pouch is effective at 3 months to treat FI. A second
injection seems to be necessary to achieve improvement at 6 months. Efficacy of
BT is not related to FI origin (anal sphincter incompetence vs with an overactive
reservoir) and is not explained by modification of rectal volume and/or
compliance.
REFERENCES
(1) Bridoux V, Gourcerol G, Kianifard B, et al. Botulinum A toxin as a treatment
for overactive rectum with associated faecal incontinence. Colorectal Dis 2012;
14: 342-348.
Disclosure of Interest: None declared
P0983 TRICYCLIC
ANTIDEPRESSANTS
FOR
SYMPTOMATIC
TREATMENT OF INTRACTABLE TENESMUS IN THE SETTING OF
RECTAL PROLAPSE
D.M. Livovsky1,*, T. Adar1, J. Lysy1
Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
Contact E-mail Address: danlivo@szmc.org.il
1

INTRODUCTION: Anorectal manometry is the gold standard to explore anorectal disorders. Endoanal ultrasound (EUS) is commonly associated for the diagnosis of anal sphincter rupture. 3-Dimensional High-Resolution Anorectal
Manometry (3DHRAM) seems able to provide new topographic information,
including an assessment of the integrity of the sphincters.
AIMS & METHODS: The aim of the study was to develop a method for computerized analysis of 3DHRAM results to optimize the diagnosis of anal sphincter defect, compared with the EUS as gold standard.
All patients referred to our center to explore anal incontinence or dyschesia by
3DHRAM and EUS were eligible. 3DHRAM measured anal resting and voluntary contraction pressure which reflected internal anal sphincter and external
anal sphincter respectively. A software was created to analyze 3DHRAM
records. Significant pressure parameters were calculated to separate patients
with anal sphincter rupture and patients without rupture. The combination of
these parameters resulted in a 3DHRAM diagnostic score for anal sphincter
rupture, compared with the EUS.
RESULTS: A total of 206 patients (91% females) with a mean age of 54.6  14.9
years were included. The EUS diagnosed an anal sphincter defect in 130 (63%)
patients, 76 (37%) patients were without rupture. 40 pressure parameters were
defined from 3DHRAM records by the software. 5 most significant pressure
parameters were selected for the construction of diagnostic scores. Overall, the
diagnostic score for the internal anal sphincter defect had a sensitivity of 65%
and a specificity of 65%, with a positive predictive value of 75% and a negative
predictive value of 53%. For the external anal sphincter defect, the diagnostic
score had a sensitivity of 43% and a specificity of 87%, with a positive predictive
value of 82% and a negative predictive value of 53%.
CONCLUSION: A computerized diagnostic method of 3DHRAM results was
developed for a systematic and comprehensive analysis. However, 3DHRAM has
not shown sufficient diagnostic capacity for sphincter defect, compared to EUS.
A better distinction between anal sphincter defect and neurological damage,
which can also affect the pressure recorded at the 3DHRAM, could improve
our diagnostic scores.
Disclosure of Interest: None declared
P0982 PROSPECTIVE EVALUATION OF RECTAL BOTULINUM TOXIN
INJECTION IN FECAL INCONTINENCE
C. Benard1,2,*, G. Gourcerol2, O. Touchais2, A.-M. Leroi2, V. Bridoux3,
C. Melchior1,2, P. Ducrotte1
1
Gastroenterology department, 2Physiology department, 3Surgery department,
CHU rouen, Rouen, France
Contact E-mail Address: coralie.benard@yahoo.fr
INTRODUCTION: Botulinum Toxin (BT) has been widely used to treat urinary
incontinence in the context of overactive bladder. It has been previously suggested in 6 patients that injection of BT in the reservoir may relieve faecal
incontinence (FI) in patients with either overactive rectum or colonic pouch
after protectomy (1). However, the efficacy of rectal BT injection in patients
with FI related to anal sphincter incompetence has never been investigated.

INTRODUCTION: The spurious feeling of the need to evacuate the bowels, with
little or no stool passed (tenesmus) can cause severe distress and a negative
impact on quality of life. Management is focused on the primary cause of tenesmus and not on tenesmus itself. Rectal prolapse is occasionally encountered as
the main etiology of tenesmus, in those patients surgical consultation is warranted. Tenesmus in this setting is particularly problematic since it leads the
patient to a vicious cycle of straining with deterioration of prolapse and subsequent worsening of tenesmus. Tricyclic antidepressants (TCAs) have been shown
to reduce ano-rectal hypersensitivity in patients with irritable bowel syndrome
(IBS), by centrally mediated mechanisms and are commonly used to treat functional chronic pelvic pain syndromes. We have used the same approach to treat
patients referred to our tertiary center suffering from intractable tenesmus that
are poor surgical candidates or refuse surgical correction.
AIMS & METHODS: From 2010 we created a registry of patients with rectal
prolapse that were poor surgical candidates or refused surgical correction and
received treatment with TCA for rectal tenesmus. Only patients with rectal mucosal prolapse or full-thickness rectal prolapse with high internal intussusception or
externally visible only with straining were included. Patients with full-thickness
rectal prolapse externally visible at all times or with an impending surgical indication were excluded.
RESULTS: Twenty one patients were treated by this approach, 81% were
female, the mean age was 74.8114.39 years, and symptoms were present for a
mean of 97 months. The feeling of an anal protrusion on straining, anal pain,
fecal incontinence and constipation were present in 75, 42.9, 36.8 and 26.3% of
patients respectively. Full thickness rectal prolapse was present in 57% of
patients, while 43% had internal rectal mucosal intussusceptions. Nortryptiline
25mg, amitriptyline 10mg and desipramine 25mg were used in 43, 38 and 19% of
patients respectively. After a mean follow up of 7.185.5 months 76% of patients
reported significant improvement in symptoms, 14% were lost to follow up and
10% (n 3) failed to respond. The response rates were 88% (7/8) for nortryptiline, 100% (4/4) for desipramine and 55% (5/9) for amitriptyline. Noteworthily
in 5 patents, symptoms were completely resolved obviating the need for surgery,
most probably due to cessation of the vicious cycle of tenesmus, straining and
worsening of prolapse. Additionally the treatment was very useful in patients
suffering from dementia, who could not be convinced to stop straining.
CONCLUSION: To our knowledge this is the first report to address the symptomatic treatment of tenesmus in patients with rectal prolapse. TCAs may be an
acceptable option for poor surgical candidates or patients refusing surgical treatment. Nortryptiline or desiparamine had a trend to better response rates compared to amitryptiline in an uncontrolled setting.
REFERENCES
Beahrs OH, Theuerkauf FJ Jr and Hill JR. Procidentia: surgical treatment. Dis
Colon Rectum 1972; 15: 337-346.
Morgan V, Pickens D, Gautam S, et al. Amitriptyline reduces rectal pain related
activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut 2005; 54: 601-607.
Stein SL. Chronic pelvic pain. Gastroenterol Clin North Am 2013; 42: 785-800.
Disclosure of Interest: None declared

A403

United European Gastroenterology Journal 2(1S)


P0984 NORMAL VALUES FOR 3D ANO-RECTAL HIGH RESOLUTION
MANOMETRY: A PRELIMINARY REPORT
S. Roman1,2,*, A. Ropert3, F. Prieur4, H. Damon1, M. Bouvier5, C. Brochard3,
S. Marjoux1, V. Vitton6, N. Lesavre7, L. Siproudhis8, F. Mion1
1
Digestive Physiology, Hospices Civils de Lyon, 2Digestive Physiology, Lyon I
university, Lyon, 3Digestive Physiology, CHU Rennes, Rennes, 4LabTAU,
INSERM1032, Lyon, 5Physiology, 6Gastroenterology, 7CIC, CHU Marseille,
Marseille, 8Gastroenterology, CHU Rennes, Rennes, France
Contact E-mail Address: sabine.roman@chu-lyon.fr
INTRODUCTION: 3D ano-rectal high resolution manometry (3D ARHRM)
has been recently developed. Closely spaced pressure sensors allow a precise
definition of pressure profile within the anal canal. However normal values are
scarce with this device.
AIMS & METHODS: This study aimed to determine normal values for 3D
ARHRM and to compare them to those obtained in patients with fecal incontinence. Fifty seven women (29 controls and 28 patients with fecal incontinence
(FI)) were included in 3 centers. Vaizey score was used to define fecal incontinence: controls had a score of 0 or 1 and patients a score greater than 6. Anal
ultrasound was performed to search for anal sphincter defect in patients with FI.
3D ARHRM was performed using a rigid probe (Given Imaging, Duluth, GA).
The protocol consisted of a 2-minute resting period, 2 squeezing periods and 2
bearing down maneuvers. The high-pressure zone (HPZ) corresponding to the
anal canal was delineated at the 20-mmHg isobaric contour. The height and
mean pressure of the HPZ were measured over a 20-s period at the end of the
resting period and after the beginning of each squeezing period. Resting pressure
volume and squeezing contractile volume (expressed in mmHg.cm.s) were calculated as the product of HPZ height x HPZ mean pressure x 20 seconds. Data are
expressed in median (range) and compared between groups using non-parametric
tests.
RESULTS: Controls were younger than FI patients (mean age 45 years (18-70)
vs 58 (31-74), p50.01). Fourteen women with FI presented an anal sphincter
defect on ultrasound examination. All manometric variables were significantly
different between controls and FI women (Table).

Resting HPZ height (cm)


Resting HPZ pressure (mmHg)
Resting pressure volume
(mmHg.cm.s)
Squeezing HPZ height (cm)
Squeezing HPZ pressure
(mmHg)
Squeezing contractile volume
(mmHg.cm.s)

Controls

FI

3 (2-5)
51 (29-74)
3217 (1444-6512)

3 (0-5)
40 (11-70)
2552 (307-7006)

0.02
50.01
50.01

4 (3-5)
79 (49-135)

4 (1-5)
53 (14-124)

50.01
50.01

7175 (4051-10536)

4195(583-11307)

50.01

No difference was seen during the bearing down maneuvers between controls and
FI women. The 2D map of the 3D sensor plot showed a constant lambda aspect
at rest and during squeezing in controls: this aspect may be representative of the
posterior pressure applied by the puborectal in the upper part of the anal canal,
and the anterior pressure applied by the lower part of the anal sphincter. This
typical aspect was much less evident in FI women, especially when a sphincter
defect was present.
CONCLUSION: This preliminary study established normal values for 3D
ARHRM, and clearly showed differences between controls and patients with
FI. 3D data may be interpreted as a typical image pattern rather than as quantified variables.
Disclosure of Interest: S. Roman Financial support for research from: Given
Imaging, Lecture fee(s) from: Given Imaging, Consultancy for: Given Imaging,
A. Ropert: None declared, F. Prieur: None declared, H. Damon: None declared,
M. Bouvier: None declared, C. Brochard: None declared, S. Marjoux: None
declared, V. Vitton: None declared, N. Lesavre: None declared, L. Siproudhis:
None declared, F. Mion: None declared
P0985 LONG TERM OUTCOMES OF BOTULINUM TOXIN IN THE
TREATMENT OF CHRONIC ANAL FISSURE 5 YEAR FOLLOW-UP
S.P. M. Barbeiro1,*, C. Martins1, C. Goncalves1, M. Canhoto1, B. Arroja1,
F. Silva1, I. Cotrim1, H. Vasconcelos1
1
Gastrenterologia, Centro Hospitalar de Leiria, Leiria, Portugal
Contact E-mail Address: sandrabarbeiro@gmail.com
INTRODUCTION: Chronic anal fissure is a frequent and disabling disease,
affecting especially young adults. Botulinum toxin (BT) and internal lateral
sphincterotomy are therapeutic options for refractory cases. BT is minimally
invasive and safer, compared to surgery, which carries a more difficult postoperative state and fecal incontinence risk. The long term effectiveness of BT
is not known.
AIMS & METHODS: Evaluate the long term outcomes of BT treatment in
chronic anal fissure.
Observational and retrospective study, including the patients treated with BT
from 2005 to 2009, each followed over a period of 5 years. Patients were treated
with injection of 25U of BT in the intersphincteric groove. The response was
registered as complete (CR), partial (PR), refractory (RR) and relapse (RP).
RESULTS: One hundred and twenty-six patients were treated, of which 69.8%
(n 88) were followed over a period of 5 years [48 females (52.3%), mean age 48

years]. The majority presented with a fissure in the anal posterior midline (n 68,
77.3%). After 3 months, 46.6% (n 41) had CR, 23.9% (n 21) had PR and
29.5% (n 26) had RR. Relapse was observed in 1.2% (n 1) at 6 months,
11.4% (n 10) at 1 year, 2.3% (n 2); no relapse at 5 years. Treatment with
BT had a long term efficiency of 64.8%. There was no difference between the
groups with CR and RR for gender, age, duration of symptoms, fissure localization and constipation. The treatment was well tolerated by all patients and there
were no complications. Patients with no response were assigned to second injection with BT or surgery. The authors highlight the occurrence of two cases of
fecal incontinence in the surgery group.
CONCLUSION: BT was an effective and safe alternative to chronic anal fissure
long term treatment.
REFERENCES
1. Berkel AE, Rosman C, Koop R, et al. Isosorbide dinitrate ointment versus
botulinum toxin A (Dysport) as primary treatment for chronic anal fissure: a
randomized multicentre study. Colorectal Dis 2014 Mar 15.
2. Godevenos D, Pikouli E, et al. The treatment of chronic anal fissure with
botulinum toxin. Acta Chir Belg 2004; 104: 577-580.
3. Brisinda G, Maria G, et al. A comparison of injections of botulinum toxin and
topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J
Med 1999; 341: 65-69.
4. Chen HL, Woo XB, Wang HS, et al. Botulinum toxin injection versus lateral
internal sphincterotomy for chronic anal fissure: a meta-analysis of randomized
control trials. Tech Coloproctol 2014 Feb 6.
Disclosure of Interest: None declared
P0986 PATIENT PERSPECTIVES FOR ENDPOINTS IN CLINICAL
TRIALS FOR FECAL INCONTINENCE
W.E. Whitehead1,2,*, O.S. Palsson1,2, S. Heymen1,2, S.M. Kim1, S. Twist1
Medicine (Division of Gastroenterology and Hepatology), 2Center for Functional
Gastrointestinal and Motility Disorders, UNIVERSITY OF NORTH
CAROLINA, CHAPEL HILL, Chapel Hill, United States
Contact E-mail Address: William_Whitehead@med.unc.edu
1

INTRODUCTION: Pivotal trials of new treatments for fecal incontinence (FI)


often define responders by a 50% reduction in frequency of FI or a report of
adequate relief, but there has been no patient input into these responder
definitions.
AIMS & METHODS: Our aim was to survey patient preferences for endpoints
in FI treatment trials. In Phase I (focus groups), 30 patients with FI (29 women)
were recruited by advertisement to participate in internet chat rooms of 1-5
persons. They were asked open-ended questions on how to define FI treatment
success as well as questions about 50% improvement and adequate relief. Based
on this input, 3 questions were developed for a national internet survey of individuals with FI (Phase II). This sample, stratified by age, sex, and race/ethnicity,
was provided by Cint USA, Inc., a market research company. Descriptive statistics followed by regression analyses were used to identify personal characteristics that influence preferences for endpoints. Subjects also completed the Fecal
Incontinence Severity Index (FISI).
RESULTS: In Phase I focus groups, most participants did not believe a 50%
reduction in frequency was an adequate definition of success, but neither did they
think complete cure was required. When asked how much improvement was
needed, the consensus was about 75%. Some did not know what adequate
relief meant. In the Phase II national survey, 48/234 (20.5%) of responders
were excluded because they gave inconsistent responses to two questions that
were repeated as a quality control, leaving 186 for analysis: 52% were women,
mean age was 48.9 years (range 20-91), and race/ethnicity was 9% Hispanic and
8% African American. Post-bacalaurate education was over-represented
(39.2%). Average FISI score was 29.9 on a 0-61 scale. The national survey
confirmed focus group findings: only 57.5% thought a 50% reduction is
enough to consider a treatment successful (only 26.2% of people over age 65)
and 78% considered adequate relief a good measure of treatment success.
Logistic regression analysis identified several significant predictors of finding a
50% reduction in the frequency of FI an acceptable endpoint in clinical treatment
trials: greater severity of FI, younger age, male gender, and higher household
income. These would be potential confounders when a 50% reduction is used as
the definition of clinical success. For adequate relief, bivariate analyses confirmed that better educated and wealthier subjects are more likely to accept
adequate relief as an endpoint. However, in a multivariate logistic regression,
only younger age was an independent predictor of endorsing adequate relief.
When asked how much improvement is needed to consider a treatment as successful, the average was a 77% decrease in FI episodes (95% confidence interval
74.5%, 79.5%).
CONCLUSION: Endpoints in clinical trials should be redefined as at least a
75% reduction in the frequency of FI because (a) the 50% decrease criterion is
satisfactory to only 57.5% of people with FI (26% of people over age 65), (b)
multiple demographic variables predict endorsement of the 50% reduction definition of a responder and are therefore potential confounders, and (c) adequate
relief appears to be difficult to understand for patients with lower levels of
education. [Supported by a grant from Salix Pharmaceuticals]
Disclosure of Interest: W. Whitehead Financial support for research from: Salix
Pharmaceuticals, Consultancy for: Takeda Pharmaceuticals, Ironwood
Pharmaceuticals, Entera Health, O. Palsson: None declared, S. Heymen: None
declared, S. Kim: None declared, S. Twist: None declared

A404

TUESDAY, OCTOBER 21, 2014


NERVE GUT AND MOTILITY
XL_____________________

United European Gastroenterology Journal 2(1S)

II

POSTER

EXHIBITION

9:0017:00
HALL

P0987 MANOMETRICS CHARACTERISTICS OF OESOPHAGEAL


MOTOR ACTIVITY IN TYPE 2 DIABETICS WITH COMPLAINTS
OF CONSTIPATION: COMPARISON WITH DIABETICS WITHOUT
CONSTIPATION
J.X. Jorge1,2,*, L.S. Fernandes3, C.C. Almeida2, F.J. Delgado4, M.A. Simoes2,
E.A. Panao5
1
Faculty of Medicine, Agostinho Neto University, Luanda, Angola, 2Faculty of
Medicine, University of Coimbra, Coimbra, 3Medicine Urgency, Hospital
Fernando Fonseca, Lisboa, 4Medicine, Hospital de Alcobaca, Alcobaca,
5
Gastroenterology, Hospital dos Covoes, Coimbra, Portugal
Contact E-mail Address: cambombo@hotmail.com
INTRODUCTION: Some studies support that there is a significant overlap
between the different functional disorders of the digestive tract1, 2.
AIMS & METHODS: The aim of this study was to compare oesophageal motor
characteristics between type 2 diabetics with and without constipation.
Oesophageal manometry was performed in 16 type 2 diabetic individuals with
complaints of constipation and 20 without constipation. Glycaemia control was
similar. Waves were evaluated in the 3 thirds of the oesophagus (P1 upper,
P2 middle, and P3 distal). Results are in mean  standard error.
RESULTS: In constipated vs. non-constipated diabetics, oesophageal wave distribution was as follows: peristaltic waves, 85.543.85% vs. 91.452.32%,
p 0.16; simultaneous waves, 3.50%1.19% vs. 0.930.28%, p 0.015. The
percent of no transmitted waves and of retrograde waves between groups were
similar. Wave amplitude did not reveal significant differences between groups.
Wave duration (sec.) in constipated vs. non-constipated was as follow: P1-P2,
4.76 0.67 vs. 4.150.53, p50.47; P2-P3, 7.240.93 vs. 4.900.47, p50.017 and
P1-P3, 6.711.20 vs. 3.370.42 p 0.013. Wave velocity (cm/s) registered in
constipated vs. non-constipated was: P1-P2, 2.930.64 vs. 4.030.58, p50.21;
P2-P3, 3.420.67 vs. 5.070.51, p50.05 and P1-P3, 2.690.58 vs. 4.270.37, p5
0.01.
CONCLUSION: (1) Simultaneous oesophageal waves were significantly more
frequent in constipated diabetics. (2) Wave duration was significantly higher
within the middle and distal oesophagus of constipated diabetics. (3) Wave velocity was significantly higher within the esophagus of non-constipated individuals.
(4) There are some differences in esophageal motility in type 2 diabetic patients
with or without constipation
REFERENCES
1-Jiang X, et al. Zhonghua Nei Ke Za Zhi 2013; 52: 806-810.
2-Baran M, et al. Turk J Gastroenterol 2012; 23: 634-638.
Disclosure of Interest: None declared
P0988 ANO-RECTAL SENSORIAL AND MOTOR CHARACTERISTICS
IN TYPE 2 DIABETICS WITH OR WITHOUT COMPLAINTS OF
FAECAL INCONTINENCE: A COMPARATIVE STUDY
J.X. Jorge1,2,*, L.S. Fernandes3, C.C. Almeida2, F.J. Delgado4, E.A. Panao5,
M.A. Simoes2
1
Faculty of Medicine, Agostinho Neto University, Luanda, Angola, 2Faculty of
Medicine, University of Coimbra, Coimbra, 3Medicine Urgency, Hospital
Fernando Fonseca, Lisboa, 4Medicine, Hospital de Alcobaca, Alcobaca,
5
Gastroenterology, Hospital dos Covoes, Coimbra, Portugal
Contact E-mail Address: cambombo@hotmail.com
INTRODUCTION: Faecal incontinence is a complaint that some type 2 diabetic
patients refer1. For some authors, alterations in recto-anal sensory-motor thresholds may be present2.
AIMS & METHODS: The aim of this study was to compare rectal sensorial and
motor characteristics of type 2 diabetics with and without faecal incontinence.
Recto-anal manometry was performed in 35 type 2 diabetics, without signs of
autonomic neuropathy, 5 with complaints of faecal incontinence and 30 without
this complaint, matched by age and gender. Results are in mean  standard
error.
RESULTS: In diabetics with faecal incontinence vs. without faecal incontinence
the values were the follow: rectal resting pressure, 11.51.8 vs 12.12.3mmHg;
p 0.27 internal anal sphincter resting pressure, 40.020. vs 43.623.3mmHg,
p 0.24; 39.87.02 vs. 47.73.30, p 0.36; minimum rectal sensibility,
56.76.7% vs. 80.07.6ml, p 0.28; first urge, 80.86.1 vs. 132.313.5ml,
p 0.69; Intense urge,108,36.0 vs. 152.814.7, p 0.80; maximum tolerable
rectal capacity, 169.215.6 vs. 225.5 20.8ml, p 0.95. The relaxing percent
during the recto-anal reflex and the sphincters pressures during the squeeze
and squeeze endurance were statistically similar. The anal sphincter fatigue
during the squeeze endurance was 0.150.70 vs. 0.040.32 mmHg/sec, p40.05.
CONCLUSION: 1-In type 2 diabetics with faecal incontinence the rectal resting
pressure, the resting internal and external sphincter pressures, the volume for
minimum rectal sensibility and for maximum tolerable rectal capacity were similar to diabetics without the symptoms. 2-The anal sphincter fatigue was similar
between groups. 3-There is no significant differences in recto-anal sensory-motor
characteristics in type 2 diabetics with or without faecal incontinence studied.
REFERENCES
1 Ditah I, et al. Clin Gastroenterol Hepatol 2014; 12: 636-643.
2 Worse J, et al. Dis Colon Rectum 2010; 53: 1308-1314.
Disclosure of Interest: None declared

P0989 RECTO-ANAL SENSORIAL AND MOTOR CHARACTERISTICS


IN TYPE 2 DIABETICS WITH OR WITHOUT COMPLAINTS OF
CONSTIPATION: A COMPARATIVE STUDY
J.X. Jorge1,2,*, L.S. Fernandes3, C.C. Almeida2, F.J. Delgado4, M.A. Simoes2,
E.A. Panao5
1
Faculty of Medicine, Agostinho Neto University, Luanda, Angola, 2Faculty of
Medicine, University of Coimbra, Coimbra, 3Medicine Urgency, Hospital
Fernando Fonseca, Lisboa, 4Medicine, Hospital de Alcobaca, Alcobaca,
5
Gastroenterology, Hospital dos Covoes, Coimbra, Portugal
Contact E-mail Address: cambombo@hotmail.com
INTRODUCTION: Constipation is a very frequent complaint in type 2 diabetic
patients1 and some authors believe that alterations in recto-anal thresholds may
be present in individuals with these symptoms2.
AIMS & METHODS: The aim of this study was to compare rectal sensorial and
motor characteristics of type 2 diabetics with and without constipation.
Recto-anal manometry was performed in 35 type 2 diabetics, without signs of
autonomic neuropathy, 15 with complaints of constipation and 20 without this
symptom, matched by age and gender. Results are in mean  standard error.
RESULTS: In diabetics with complaints of constipation vs. without constipation, the values registered were the follow: rectal resting pressure, 11.51.8 vs.
12.12.3mmHg; p 0.8; internal anal sphincter resting pressure, 40.04.7 vs.
43.66.1mmHg, p 0.6; minimum rectal sensibility, 65.56.8 vs. 78.69.2ml,
p 0.2; first urge, 107.5.814.1 vs. 119.313.1ml, p 0.5; Intense urge,
132.014.2 vs. 145.315.5ml, p 0.5; maximum tolerable rectal capacity,
197.022.6 vs. 208.6 19.0ml, p 50.7. The relaxing percent during the rectoanal reflex was 40.96.0% vs. 30.54.5%, p40.05. The sphincter pressure
during the squeeze was significantly lower in diabetics with symptoms
67.211.2 than without it, 109.716.4, p50.03; but during the squeeze endurance, 88.011.7 vs. 114.917.4, was statistically similar. The anal sphincter fatigue during the squeeze endurance, 0.290.41 vs. -0.260.40 mmHg/sec, was
similar. When comparing the recto-anal characteristics according to the severity
of constipation, there were no statistic differences between diabetics with slight to
moderate or severe to very severe symptoms.
CONCLUSION: 1-In type 2 diabetics with complaints of constipation the resting
rectal pressure, the volume for minimum rectal sensibility, first urge, intense urge
and maximum tolerable rectal capacity, and the relaxing degree during the rectoanal inhibitory reflex were statistically similar to diabetics without the symptoms.
2-The pressure augment during the squeeze was higher in diabetics without constipation. 3-In general recto-anal sensorial and motor thresholds were similar in
type 2 diabetics with or without constipation.
REFERENCES
1 Ueno N, et al. Diabetes Res Clin Pract 2010; 87: 27-32.
2 Scott SM et al. Best Pract Res Clin Gastroenterol 2011; 25: 103-118.
Disclosure of Interest: None declared
P0990 MANOMETRICS CHARACTERISTICS OF OESOPHAGEAL
MOTOR ACTIVITY IN PEOPLE WITH COMPLAINTS OF
CONSTIPATION: COMPARISON WITH INDIVIDUALS WITHOUT
CONSTIPATION
J.X. Jorge1,2,*, L.S. Fernandes3, C.C. Almeida2, F.J. Delgado4, E.A. Panao5,
M.A. Simoes2
1
Faculty of Medicine, Agostinho Neto University, Luanda, Angola, 2Faculty of
Medicine, University of Coimbra, Coimbra, 3Medicine Urgency, Hospital
Fernando Fonseca, Lisboa, 4Medicine, Hospital de Alcobaca, Alcobaca,
5
Gastroenterology, Hospital dos Covoes, Coimbra, Portugal
Contact E-mail Address: cambombo@hotmail.com
INTRODUCTION: Epidemiological and clinical studies in the pediatric1 and
adult2,3 population support that there is a significant overlap between the different functional disorders of the digestive tract.
AIMS & METHODS: The aim of this study was to compare oesophageal motor
characteristics between individuals with complaints of constipation and individuals without this symptom.
Oesophageal manometry was performed in 28 individuals with complaints of
constipation and 42 without constipation. Waves were evaluated in the 3 thirds
of the oesophagus (P1 upper, P2 middle, and P3 distal). Results are in
mean  standard error.
RESULTS: In constipated vs. controls, oesophageal wave distribution was as
follows: peristaltic waves, 85.543.85% vs. 91.452.32%, p 0.16; simultaneous
waves, 3.50%1.19% vs. 0.930.28%, p 0.015. The percent of no transmitted
waves and of retrograde waves were similar between groups. Wave amplitude did
not reveal significant differences between groups. Wave duration (sec.) in constipated vs. non-constipated was as follow: P1-P2, 4.76 0.67 vs. 4.150.53, p 5
0.47; P2-P3, 7.240.93 vs. 4.900.47, p50.017 and P1-P3, 6.711.20 vs.
3.370.42 p 0.013. Velocity duration (cm/s) registered in constipated vs. nonconstipated was: P1-P2, 2.930.64 vs. 4.030.58, p50.21; P2-P3, 3.420.67 vs.
5.070.51, p50.05 and P1-P3, 2.690.58 vs. 4.270.37, p50.01.
CONCLUSION: (1) Simultaneous oesophageal waves were significantly more
frequent in constipated. (2) Wave duration was significantly higher within the
middle and distal oesophagus of constipated individuals. (3) Wave velocity was
significantly higher within esophagus of non-constipated individuals. (4)
Constipated individuals have some differences in esophageal motility when compared with non-constipated individuals.
REFERENCES
1 Baikie G et al. J Pediatr Gastroenterol Nutr 2014; 58: 244-251.
2 Jiang X et al. Zhonghua Nei Ke Za Zhi 2013; 52: 806-810.
3 Baran M et al. Turk J Gastroenterol 2012; 23: 634-638.
Disclosure of Interest: None declared

A405

United European Gastroenterology Journal 2(1S)


P0991 INTERACTIONS OF HERBAL CONSTITUENTS INFLUENCES
THE EFFECTS OF STW 5 ON INFLAMMATORY PROCESSES AND
DISTURBED MOTILITY
K. Nieber1,*, S. Hoser1, V. Winkelmann1, A. Baumgartel1, N. Mishenzon1,
S. Okpanyi2, H. Abdel-Aziz2, D. Weiser2, O. Kelber2
1
Institute of Pharmacy, UNIVERSITY OF LEIPZIG, Leipzig, 2Scientific
Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
Contact E-mail Address: nieber@rz.uni-leipzig.de
INTRODUCTION: The multi-herbal drug STW 5 (Iberogast) was effective for
treatment of symptoms in patients with functional dyspepsia or irritable bowel
syndrome (IBS). Its mode of action is still not fully elucidated. Modulation of
gastric motility and an anti-inflammatory action were hypothesized. These findings provide the basis for investigating STW 5 and its components in inflamed
small and large intestinal preparations to identify novel anti-inflammatory
pathways.
AIMS & METHODS: The aim of this study was to investigate the effect of
individual constituents as well as selected combinations on different parameters
related to inflammatory processes in the gastrointestinal tract.
For analysis of lactate dehydrogenase (LDH) activity using a commercially available LDH cytotoxicity assay (Roche). TNFa concentration was detected by
ELISA in the supernatants. The inflammation was elicited by intraluminal preincubation with TNBS (10 mM). The herbal extracts were applied together with
TNBS. For analysing synergism or antagonism the isobologram method was
used.
RESULTS: STW 5, STW 5-II (a combination containing only 6 of the 9 extracts)
and lemon balm reduced LPS (10 ng/ml)-induced lactate dehydrogenase (LDH)
release from CaCo-2 cells by 74-75 %. Iberis amara, peppermint, chamomile,
angelica and milk thistle inhibited this parameter by 25-37 %. Liquorice, caraway
and celandine had no effect. The combinations of Iberis amara and peppermint as
well as peppermint and milk thistle revealed synergistic or additive effects,
whereas the combination of chamomile and angelica evoked additive or antagonistic effects depending on their compositions (i.e. relative ratios of individual
extracts).
STW 5, STW 5-II, Iberis amara, peppermint, liquorice, caraway, milk thistle and
lemon balm inhibited LPS (100 ng/ml)-induced TNFa release from THP-1 cells
to 51-67 %. Chamomile and angelica revealed a more potent effect. The combinations of Iberis amara and peppermint as well as chamomile and liquorice had
additive or antagonistic effects depending on their compositions.
STW 5 and STW 5-II reduced the acetylcholine (ACh)-induced contractions in
rat ileum preparations to 81-83 %. The individual components inhibited the
contractions to 83-91 % except for lemon balm which had no effect. The combinations of Iberis amara and peppermint as well as liquorice and caraway had
additive or antagonistic effects depending on their compositions.
CONCLUSION: Our results indicate that synergistic, additive and antagonistic
interactions exist between the constituents within STW 5 and STW 5-II. The
overall effects depend on their combination and therefore confirm that combined
extracts produce an effect different from or greater than the sum of their individual effects. Our results allow greater insight into the interactions between individual herbal constituents of STW 5 and confirm the concept of multi-target
actions.
Disclosure of Interest: K. Nieber Financial support for research from: Steigerwald
Arzneimittelwerk, S. Hoser: None declared, V. Winkelmann: None declared, A.
Baumgartel: None declared, N. Mishenzon: None declared, S. Okpanyi
Shareholder of: Steigerwald Arzneimittelwerk, H. Abdel-Aziz Shareholder of:
Steigerwald Arzneimittelwerk, D. Weiser Shareholder of: Steigerwald
Arzneimittelwerk, O. Kelber Shareholder of: Steigerwald Arzneimittelwerk
P0992 NON-GSHR1A MEDIATED EFFECTS OF ULIMORELIN IN
ISOLATED RODENT ARTERIES
J. Broad1,*, B.P. Callaghan2, G. Sanger1, J. Furness2, J. Brock2
National Centre for Bowel Research and Surgical Innovation, London, United
Kingdom, 2Anatomy and Neuroscience, University of Melbourne, Melbourne,
Australia
Contact E-mail Address: j.broad@qmul.ac.uk
1

INTRODUCTION: Ghrelin receptor agonists cause changes in blood pressure in


humans (1) and rodents. The ghrelin receptor agonist ulimorelin (TZP101),
recently in clinical trials for the treatment of gastroparesis, has been shown to
cause alterations in blood pressure and mesenteric artery tone in rats (2). Here we
investigate the role of the canonical ghrelin receptor, GHSR1a, in mediating this
effect.
AIMS & METHODS: Saphenous, mesenteric and basilar arteries from SpragueDawley rats (male, 8 weeks), and saphenous arteries from mice lacking the
GHSR1a receptor or littermates (male, 6-8 weeks) were studied. Arteries were
suspended between steel wires in myography chambers containing an oxygenated
modified Krebs solution (36.5 C) and given an effective transmural pressure of
100mmHg- mesenteric and basilar arteries were then reduced in diameter by
10%. Phenylephrine (PE) 3-10mM, or 60mM [K] in basilar arteries, was used
to confirm tissue viability. Ulimorelin was applied non-cumulatively following
increases in artery tension induced by application of PE 3-10mM or 60mM [K].
To investigate direct changes in artery tension, ulimorelin was applied cumulatively. Responses were measured as the % change from the plateau response of
the stimulus applied prior to application of agonists. Changes between groups
were investigated using 2-way ANOVA and Bonferroni post-tests.
RESULTS: PE 3-10mM contracted saphenous (n 19 rat, n 4 mouse) and
mesenteric (n 6) arteries, but had no effect on basilar arteries (n 4).
Ulimorelin (0.03-30mM) caused concentration-dependent inhibition of PEinduced contractions of rat saphenous (IC50 697nM; Imax 665% PE

response; n 3-6) and mesenteric arteries (IC50 5mM, Imax 11316%;


n 3-4), but had no effect on contractions induced by 60mM [K] in basilar
arteries. In rat saphenous and basilar arteries ulimorelin 10-100mM caused an
increase in artery tension (EC50 9.9mM Emax 507%; and EC50 8 mM
Emax 9916% respectively) but had no effect in mesenteric arteries. These
effects were not attenuated by the ghrelin receptor antagonist YIL 781 3mM
(e.g. ulimorelin 10M inhibited the PE response by 625% in the absence and
488% in the presence of YIL 781 respectively; P40.05; n 4) or mimicked by
ghrelin 0.001-1mM (n 3-4), desacyl ghrelin 0.001-1mM (n 3-4), capromorelin
0.01-10mM (n 3-4) or AZP-531 0.001-1mM (n 3-4). In mesenteric arteries preincubation of ulimorelin 1-10mM caused a parallel rightward shift in the cumulative response to PE (0.01-1000mM; pA2 5.7; n 3-4). No differences were
observed between wild type mice and mice lacking the GHSR1a receptor in
the ability of ulimorelin 1-10mM to inhibit PE responses (at 10mM by 6117
and 5116 respectively; P40.05; n 3, 3) or increase in artery tension (10100mM; EC50 21mM Emax 153%; EC50 16mM Emax 236%; n 3,
3; P40.05).
CONCLUSION: Ulimorelin inhibited PE induced contractions and, at higher
concentrations, increased artery tension. These effects were regionally dependent,
and it is likely they were not mediated by GHSR1a as they were not mimicked by
other ghrelin receptor agonists, and not attenuated in mice lacking GHSR1a or
by the antagonist YIL 781. A possible competitive antagonist action at the adrenoceptor is suggested for the inhibition of PE-induced contractions.
REFERENCES
1. Nagaya et al. Am J Physiol Regul Intergr Comp Physiol 2001; 280: R1483R1487.
2. Callaghan et al. Br J Pharmacol 2014; 171: 1275-1286.
Disclosure of Interest: None declared
P0993 A DECREASE OF ENTERIC PLEXUS AND GANGLION CELLS IN
SIGMOID VOLVULUS
K. Fujiya1,*, J.-M. Chong2, M. Ando1, H. Akita2, H. Amagasa1, K. Arai1
1
Surgery, 2Pathology, Toshima hospital, Tokyo, Japan
Contact E-mail Address: fujiya7@nms.ac.jp
INTRODUCTION: Although sigmoid volvulus (SV) causes acute obstruction,
the pathogenesis and pathological mechanism of SV are unknown.
AIMS & METHODS: The aim of our study is to evaluate the clinicopathological
characteristics of volvulus and factors contributing to volvulus of the sigmoid
colon. Fourteen patients with SV (10 men and 4 women; median age, 78.5 years)
were compared with 14 age- and sex-matched control patients with respect to
differences in clinical characteristics, focusing on dysmotility (enteric visceral
myopathy, neuropathy, and mesenchymopathy).
RESULTS: Of the 14 patients with SV, 7 had recurrent volvulus, 11 had an
associated condition, and 5 required emergency surgery. The prevalence of atrophy and fibrosis of the inner muscle in patients with SV was higher than that of
the control patients (P 0.041). Median extents (per cm of muscularis propria) of
the myenteric plexus (12.5 versus 17.5, P 5 0.001) and submucous plexus (15.0
versus 25.5, P 5 0.001) in patients with SV were lower than those of the control
patients. Median numbers of myenteric (9.7 versus 30.4, P 5 0.001) and submucous ganglion cells (10.0 versus 23.2, P 5 0.001) were also lower than those of
the controls. The prevalence of inflammatory neuropathy in patients with SV was
higher than that of the control patients (P 0.046). There were no differences in
mesenchymopathy (P 0.481).
CONCLUSION: A decrease in the extent of enteric plexus and ganglion cells
may play an important role in the diagnosis and recognition of a clear mechanism
leading to torsion in SV.
REFERENCES
1) Knowles CH, De Giorgio R, Kapur RP, et al. Gastrointestinal neuromuscular
pathology: guidelines for histological techniques and reporting on behalf of the
Gastro 2009 International Working Group. Acta Neuropathol 2009; 118: 271301.
2) Knowles CH and Farrugia G. Gastrointestinal neuromuscular pathology in
chronic constipation. Best Pract Res Clin Gastroenterol 2011; 25: 43-57.
3) Amiot A, Cazals-Hatem D, Joly F, et al. The role of immunohistochemistry in
idiopathic chronic intestinal pseudoobstruction (CIPO): a case-control study. Am
J Surg Pathol 2009; 33: 749-758.
Disclosure of Interest: None declared
P0994 POSTERIOR TIBIAL NERVE STIMULATION IMPROVES BOTH
URGE AND MIXED URGE PLUS PASSIVE FAECAL INCONTINENCE
K. I. Kemal1,*, L. Kumar1, A. Alam1, J. Liwang1, A. Raeburn1, E. Athanasakos1,
A. Emmanuel1
1
GI Physiology Unit, University College London, London, United Kingdom
Contact E-mail Address: k.kemal@nhs.net
INTRODUCTION: Percutaneous Tibial nerve stimulation (PTNS) is a minimally invasive, well tolerated emerging treatment for patients who have not
responded to conservative treatment for faecal incontinence (FI). There is limited
information about the difference in its efficacy in patients with different FI
symptoms. The aim of this retrospective study was to assess the efficacy of
PTNS in patients with FI, comparing between patients with different faecal
incontinence symptoms.
AIMS & METHODS: Consecutive patients were studied: all had improved following the initial 12 weeks of weekly PTNS treatment and were receiving maintenance. Based on initial presenting FI symptoms the patients were placed into
three categories: 1) Urge incontinence 2) Passive 3) Passive Urge incontinence.
The outcome parameters were Wexner FI incontinence score, stool consistency
and FI episodes per week (based on diary). Outcomes were compared between

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United European Gastroenterology Journal 2(1S)

the pre- and post-treatment, and between pre-treatment and latest maintenance
(mean 12.4 (SD 7.2 months) scores.
RESULTS: Data is presented on 44 patients (6 male, mean age of 59[25 to 77])
with a mixture of aetiologies. (As there was only 3 patients in the passive incontinence group, no statistical analysis was undertaken.) There was a statistically
significant improvement in both other groups when comparing pre-vs post-treatment Wexner Scores (mean and SD in table). In addition, in the pre vs maintenance analysis there was a significant improvement seen in symptoms. There
was a statistically significant improvement observed in faecal continence episodes
in the pre vs maintenance analysis, but no statistically significant change in stool
consistency between any groups in pre vs post and pre vs maintenance analysis.
Table- Wexner Score Comparison table

Preprocedure

Pre vs
Post
Postprocedure P value

Urge Incontinence (n 21) 14.4 2.7 7.2  2.1


Passive incontinence (n 3) 12.0  4.0 6.3  5.3
Urge passive inconti16.1  2.2 9.3  3.5
nence (n 24)

Pre vs
Maintenance Maintenance

5 0.0001 8.5  3.4


10.7  8.3
5 0.0001 9.6  4.4

5 0.0001
5 0.0001

CONCLUSION: We have shown that PTNS improves symptoms in patients


with urge incontinence and in also in those with a combination of urge and
passive symptoms. The symptom improvement was maintained in all our
patients. Larger numbers of patients with passive incontinence need to be
studied.
Disclosure of Interest: None declared
P0995 THE EFFICACY OF PERCUTANEOUS TIBIAL
STIMULATION IN DIFFERENT ANAL SPHINCTER DEFECTS

NERVE

K. I. Kemal1,1,*, L. Kumar1, A. Alam1, J. Liwang1, A. Raeburn1,


E. Athanasakos1, A. Emmanuel1
1
GI Physiology Unit, University College London, London, United Kingdom
INTRODUCTION: Percutaneous Tibial nerve stimulation (PTNS) is an emerging step-up treatment for patients who have not responded to conservative
treatment for faecal incontinence (FI). There is limited information about its
efficacy in patients with different sphincteric defects. The aim of this retrospective
study was to assess the efficacy of PTNS in patients with FI, comparing between
patients with different sphincter pathologies.
AIMS & METHODS: Consecutive patients were studied: all had improved following the initial 12 weeks of weekly PTNS treatment and were receiving maintenance. Based on baseline endoanal ultrasound patients were placed into four
categories: 1) Both sphincters intact 2) External anal sphincter (EAS) defect 3)
Internal anal sphincter (IAS) defect 4) Both sphincters damaged. The outcome
parameters were Wexner FI incontinence score, stool consistency and FI episodes
per week (based on bowel diary). Outcomes were compared between the pre- and
post-treatment, and between post-treatment and latest maintenance (mean 12.3
(SD 7.2 months) scores.
RESULTS: Data is presented on 46 patients (40 female, mean age of 57[25 to 78])
with a mixture of aetiologies. There was statistically significant improvement in
all groups comparing pre- vs post-treatment Wexner Scores (mean and SD in
table). In the post vs maintenance analysis there was significant symptom exacerbation only for the intact sphincter groups, whilst persistent improvement was
seen in the other three groups. In all groups incontinence episodes were reduced
after PTNS, and remained at low levels during maintenance (p50.05 vs prePTNS for both). No such difference in stool consistency was seen however
(p40.05 vs pre-PTNS for both).
Table- Wexner score mean  SD in the different sphincter states

Intact sphincters (n 23)


EAS defecit (n 8)
IAS defecit (n 7)
Both sphincters damaged
(n 8)

Preprocedure

Pre vs
Post
Postprocedure p value

Post vs
Maintenance
Maintenance p value

14.4  2.5
15.7  1.9
15  3.7
16.6  1.7

7.4  2.3
7.9  1.2
7.4  3.3
11  4.5

9.7  4.2
7.6  1.7
8.1  2.5
11.5  18.3

5 0.0001
5 0.0001
0.0003
0.0063

0.0214
0.3559
0.1824
0.7627

CONCLUSION: We have shown that PTNS improves symptoms in patients


who have both anal sphincter defects and intact sphincters. The symptom
improvement with PTNS was maintained in the sphincter damaged patients
but not those with intact sphincters. The effect of PTNS on patients with sphincter disruption suggests a mechanism of action directed at the anorectal unit
beyond just the anal sphincter.
Disclosure of Interest: None declared

P0996 THE ROLES OF LENGTH, DURATION OF ESOPHAGEAL


HYPERTENSIVE CONTRACTIONS IN DIFFERENT DIAGNOSIS
STRATEGIES OF NUTCRACKER ESOPHAGUS
K. Wang1, L.-P. Duan1, Z.-W. Xia1, Y.-X. Leng1,*, Z.-J. Xu1
1
Department of Gastroenterology, Peking University Third Hospital, Beijing,
China
Contact E-mail Address: duanlp@bjmu.edu.cn
INTRODUCTION: Some patients with chest pain or dysphasia present esophageal hypertensive contractions (HCs) during esophageal manometry test, but the
contraction pattern did not meet any criteria of Chicago classification 2012.
AIMS & METHODS: To evaluate the esophageal segmental or short-time HCs
(s-HCs) with Chicago classification criteria and conventional criterion respectively in NCCP or dysphasia patients and preliminarily analyze the roles of
HCs location, pressure and duration in diagnosis strategy.
Methods: Patients with NCCP or dysphasia were enrolled. All underwent gastroscopy to exclude organic diseases. Esophageal peristalsis conditions of 10 wet
swallows were recorded by HRM with 36 channels of pressure sensors. We
defined the area in 180mmHg isobaric contour as hypertensive contraction
area (HCA). According to Gothenburg criterion (GC), patients with peristaltic
contractions of amplitude 4180mmHg at any level of the esophagus was considered as conventional nutcracker esophagus (c-NE). Patients with mean distal
contraction index (DCI) 45000 mmHgscm, normal integrity relaxation pressure
and distal latency were diagnosed as Chicago NE, with DCI48000 mmHgscm as
Chicago Jackhammer. Patients who met GC but not Chicago criteria were considered as s-HCs.
RESULTS: AThirty one patients present HCs and 3 of them were excluded for
their EGJ obstructions. The remainder 28 patients (51.812.3y, M/F 10:18)
were diagnosed as c-NE (100%, 28/28). Among them, five (17.9%, 5/28) patients
were diagnosed as Jackhammer and 2 NE (7.1%, 2/28). The other 21 patients
(75%, 21/28) were diagnosed as normal group by Chicago criteria, which
considered as s-HCs in our study. Bseventy swallows in Chicago abnormal
group and 210 swallows in s-HCs group were compared. The lengths (3.8(3.34.9) vs. 6(5.5-9) cm, p 0.023), durations (3(2.6-3.2) vs. 4.8(4.4-5.1)s, p50.001)),
peak amplitudes (212.8(203.8-233.6) vs. 304.9(221.4-347.7) mmHg, p 0.001) of
HCA in s-HCs patients were significantly lower than that of Chicago abnormal
group. The mean pressure (132(118-144.1) vs. 188.1(179.6-206.2) mmHg,
p50.001) and duration (3.5(3-3.8) vs. 4.9(4.4-5.2) s, p50.001) of 3-8cm esophageal segment above LES in s- HCs group were significant lower than that of
Chicago abnormal group. There were no differences in IRP 4s, upper margin of
HCs, pressure of 8cm and 13cm above LES between the two groups (p40.05).
Further analysis showed negative correlation (r -0.435, p 0.021) between the
upper margin of HC area and DCI value, while the length (r 0.634, p50.001),
peak amplitude(r 0.721, p50.001) and contraction duration (r 0.819,
p50.001)of HC area were positively correlated with DCI.
CONCLUSION: A large proportion of c-NE diagnosed by conventional
Gothenburg criterion was considered as normal in Chicago criteria because
the hypertensive contractions were segmental or short-time. For patients with
typical NCCP or dysphasia, the roles of s-HCs and the relationship between sHCs and esophageal symptoms need to be clarified.
Disclosure of Interest: None declared
P0997 PATIENTS WITH DYSPEPSIA SYMPTOMS ARE MORE
RESPONSIVE THAN HEALTHY SUBJECTS AFTER SPRAYING
MENTHOL INTO THE UPPER GASTROINTESTINAL TRACT
K. Hiroaki1,*, H. Ken2, J. Hata3, Y. Naohito1, K. Honda1, K. Tomoari2,
S. Akiko2, K. Tomoko1, I. Kazuhiko1, T. Machi1
1
Department of General Medicine, 2Department of Gastroenterology, 3Division of
Endoscopy and Ultrasonography, Kawasaki Medical School, Kurashiki, Japan
INTRODUCTION: In Japan, the use of antispasmodics such as anticholinergic
agents as pretreatment for upper gastrointestinal tract endoscopy has become
standard. However, endoscopy without antispasmodics has frequently been performed in recent years; when antral contraction interferes with intragastric observation, 0.8% L-menthol (MINCLEA 20 mL) is sprayed into the gastrointestinal
tract to stop such contractions. However, the mechanism of antral contraction
suppression after spraying menthol into the stomach has not been fully elucidated, and differences in gastric and duodenal responsiveness have also not yet
been sufficiently studied.
AIMS & METHODS: By focusing on post-spray responsiveness, we separately
applied menthol to the antrum and the duodenal bulb using a spray tube and
studied associations between changes in antral contractile activity and dyspepsia
symptoms. [Subjects] The 18 subjects who underwent endoscopy without antispasmodics consisted of nine patients with dyspepsia symptoms (patient group)
and nine healthy subjects without abdominal symptoms (healthy group).
[Method] The subjects fasted for a minimum of 12 hours starting the day
before the examination and underwent endoscopy without receiving pre-administration of drugs into the stomach or injection of antispasmodics. Prior to
detailed intragastric observation, an endoscope was fixed to the site where
antral contraction could be evaluated; after spraying 2 mL of menthol solution
into the antral region using a spray tube, changes in contraction were observed
for two minutes. A tube was then inserted into the duodenal bulb and 2 mL of
menthol solution were sprayed in a similar manner, and changes in contraction
were observed for two minutes thereafter. In patients in whom antral contractions did not stop, the antral region was again sprayed with another 16 mL of
menthol solution. After menthol spraying, we continued normal endoscopy in the
subjects and recorded dilatation of the proximal stomach, opening/closing of the
pyloric ring, the frequency and intensity of antral contractions, the presence or

United European Gastroenterology Journal 2(1S)

A407

absence of hernia, and the presence or absence of bile retention in the stomach
and the duodenum.
RESULTS: After menthol spraying we found that the examination time was
extended by approximately six minutes on average as compared to normal endoscopy. However, there was no major interference with intragastric observation.
In the patient group, antral contraction stopped after spraying menthol into the
duodenum in eight of nine patients, while it stopped in only three of nine subjects
in the healthy group. No clear difference was identified in responses after
menthol spraying between the stomach and duodenum.
CONCLUSION: Although no differences in responses after spraying were identified between the stomach and duodenum, it was revealed that there are differences in responsiveness after menthol spraying which depend on the presence or
absence of dyspepsia symptoms. Accordingly, after further improvement and
accumulation of patients, this could become a useful examination method for
elucidating the pathology of dyspepsia symptoms.
Disclosure of Interest: None declared

98%) and sensitivity 96%(CI 90-99%), a positive predictive value of 97% (CI 9399%) and negative predictive value 94% (CI 88-98%).
CONCLUSION: The F-PAR is a highly sensitive instrument to identify treatment failure in chronic constipation in
setting.
a tertiary care setting. A single positively reported item out of five in this easy to
use tool can identify patients who need a change of treatment. Further validation
will come from utilization of the tool in a primary care setting.
Disclosure of Interest: None declared

P0998 IMPLICATION OF THE ENTERIC GLIAL CELLS IN THE


IMMUNOREGULATORY PROCESSES

N. Pedersen1, K. Vinding1, Z. Vegh1, C. Casen2,*, S. Dzankovic2, M. Karlsson2,


D. Ankersen1, L. Jensen1, K. Carlsen1, A. Petersen3, J. Burisch1, P. Munkholm1
1
Gastroenterology, Herlev University Hospital, Herlev, Denmark, 2Genetics,
Genetic Analysis AS, Oslo, Norway, 3Gastroenterology, Hvidovre University
Hospital, Hvidovre, Denmark
Contact E-mail Address: natalia.pedersen@zeniavej.dk

L. Kermarrec1,*, T. Durand1, M. Neunlist1, I. Neveu1, P. Naveilhan1


inserm U913, inserm U913, Nantes, France
Contact E-mail Address: laetitia.kermarrec@etu.univ-nantes.fr
1

INTRODUCTION: The enteric nervous system (ENS), also referred as the


second brain, is well-known for its role in the control of intestinal functions
such as motility, secretion and absorption. A growing bulk of evidence suggests
that cells of the ENS such as the enteric glial cells (EGC) may play an important
role in case of inflammatory bowel diseases (IBD). Indeed, astrocytes, their
counterparts in the central nervous system, have immunomodulatory properties
that might be shared by the EGC.
AIMS & METHODS: To study the immunoregulatory properties of the EGC,
glial cells were isolated from the myenteric plexus of the rat digestive tract
(rEGC), and their effects were tested in vitro, on activated rat T lymphocytes.
Spleen-derived T cells stimulated by anti-CD3 and anti-CD28 antibodies were
labeled with CFSE and incubated for three days with increasing ratios of rEGC.
The rate of T cell proliferation was analyzed by flow cytometry. Similar
approaches were used with human EGC isolated from the myenteric plexus of
colonic biopsy. The immunoregulatory properties of human EGC were tested on
human peripheral blood mononuclear cells (PBMC) activated with phytohemagglutinin (PHA).
RESULTS: The results show that rEGC inhibit the proliferation of activated T
cells. Pretreatment of rEGC with pro-inflammatory stimuli (LPS, interleukine-1/
TNFalpha) does not modify these immunomodulatory effects. Preliminary
experiments with EGC derived from a human colonic biopsy suggest similar
properties as the cells inhibit the proliferation of PHA-activated CD3 cells in
a dose-dependent manner. Investigations are currently performed to determine
whether EGC derived from other control patients have the same properties. We
also are also analyzing if EGC derived from IBD patients have similar
potentialities.
CONCLUSION: The present data show that EGC are able to modulate the
proliferation of T cells in vitro. They suggest that neuroimmune interactions
between EGC and T cells could occurr in vivo.
Disclosure of Interest: None declared
P0999 USE OF CONSENSUS DEFINITION OF FAILURE OF A
TREATMENT TO PROVIDE ADEQUATE RELIEF (F-PAR) FOR
CHRONIC FUNCTIONAL CONSTIPATION IN CLINICAL PRACTICE
L. Kumar1,*, S. Butt1, A. Aalam1, D. Chatoor1, A. Emmanuel1
1
GI Physiology Department, UCLH, London, United Kingdom
INTRODUCTION: Chronic constipation is a common condition characterized
by multiple inter-related symptoms. Treatments range from initial self-management by lifestyle modification and laxatives, through to prokinetic drugs, bowel
irrigation and complex surgical options. However rates of objective and subjective treatment success are low and the subjective nature of symptoms means that
success itself is hard to define. A recent consensus process (funded by Shire)
Delphi- has yielded a tool to identify failure of a treatment to provide adequate
relief (F-PAR).
AIMS & METHODS: Aims: To establish utility of F-PAR scoring system in
identifying treatment failures amongst patients with constipation. Find out specificity of the F-PAR scoring system. Methods: The 5-item self-report F-PAR
tool was offered to 236 consecutive patients attending a tertiary care center with
Rome III defined functional constipation. Only one patient could not complete it
and a total of 281 forms were analysed (196 patients with one form, 32 patients
presented twice and 7 presented three times). The form with the tool was filled in
by the patient in the waiting room prior to being seen by the clinician, who then
consulted ignorant of the responses on the tool, and a clinical decision (gold
standard) about treatment success made. After the consultation an independent
researcher reviewed the relationship between results of the tool and clinical
assessment.
RESULTS: All 235 patients (212 female, mean age 41) had completed a timedefined prescribed treatment at the time of assessment. The treatments (number,
%, of successes as defined by clinic assessment in parentheses) were: 121 (42,
35%) laxatives or enemas, 76 (35, 46%) prokinetics or secretagogues, 64 (36,
56%) biofeedback, 11 (2, 18%) trans-anal irrigation, 9 (1, 11%) sacral nerve
stimulation. In total 165 (59%) were deemed not to have responded to treatment.
There were 5 false positives and 7 false negatives generated by the F-PAR. Of
163 F-PAR identified patients, 136 (83%) had 1 item positive, 21 (13%) had 2
items positive, 7 (4%) had 3 items positive. This gives specificity 96% (CI 91-

TUESDAY, OCTOBER 21, 2014


9:0017:00
IMMUNOLOGY AND MICROBIOLOGY POSTER EXHIBITION HALL
XL_____________________
P1000 GUT MICROBIOTA ALTERATIONS IN IBS PATIENTS BEFORE
AND AFTER 6 WEEKS OF LOW FODMAP DIET VERSUS
LACTOBACILLUS RHAMNOSUS GG

INTRODUCTION: Low fermentable Oligo-Di- and Mono- saccharides and


Polyols (FODMAP) diet (LFD) may be effective in patients with irritable
bowel syndrome (IBS), and these patients may have altered microbiota (MB).
The aim of the study was to investigate the impact of LFD and lactobacillus
rhamnosus GG (LGG) on fecal MB.
AIMS & METHODS: Fecal samples were collected from IBS patients (Rome III
criteria) and randomized to LFD, LGG or normal Western/Danish diet (ND).
IBS severity score (IBS-SSS) was registered by patients at week 0 and 6 on an ehealth application, www.ibs.constant-care.dk. Bacteria in fecal samples were
analyzed by Genetic Analysis ASs GA-mapTM Dysbiosis Test, a test utilizing
16SrRNA DNA to recognize the gut bacteria found to best correlate with dysbiosis in IBD/IBS patients. Dysbiosis Index (DI) is calculated by an algorithm
based on bacterial abundance and profile in a fecal sample. DI is measured on a
scale from 1-10, where values above 2 is considered dysbiotic. Dysbiosis class is
defined as either non-dysbiotic or dysbiotic. Change in DI and dysbiosis class
between week 0 and 6 were investigated.
RESULTS: In total 58 patients (median age 39, range 20-74 years, 81% females)
were included in the study: 17 LFD, 20 LGG and 21 ND. A significant improvement in IBS-SSS total score in LFD and LGG patients was observed at week 6
compared to week 0, 308 [150-460] vs. 189 [25-478], p50.001 and 296 [157-431]
vs. 212 [11-471], p50.01. No significant improvement was observed in ND
patients, 303 [82-450] vs. 289 [62-428], p 0.28. There was no significant
improvement in DI at week 6 compared to week 0 in LFD (6 vs 6, p 0.53),
LGG (5 vs 8, p 0.88) or ND (7 vs 6, p 0.4). However, a substantial part of the
patients (35-43%) changed dysbiosis class (dysbiotic, non-dysbiotic) following
the 6 week intervention and alterations in DI were observed in all three
groups, both as decreased and increased DI. At week 0, 88% LFD, 65% LGG
and 76% ND patients were dysbiotic (DI42), while 76% LFD, 75% LGG and
81% ND patients were dysbiotic at week 6.
There was no correlation between change in IBS-SSS and DI in either LFD or
LGG group.
CONCLUSION: Both LFD and LGG groups reported significant reduction in
IBS-SSS from week 0 to 6. High proportions (65-88%) were dysbiotic at week 0,
and alteration in MB was observed in 35-43% of the patients who changed
dysbiosis class following dietary intervention. LFD did not significantly alter
the gut MB in this study population, however, the test provides information
on alterations in bacterial abundance and profiles that may prove valuable for
individual patients.
Disclosure of Interest: None declared
P1001 PROTON PUMP INHIBITORS ALTER GASTRIC MICROBIOTA
COMPOSITION IN SUBJECTS WITH UPPER GASTROINTESTINAL
SYMPTOMS: PRELIMINARY METAGENOMICS ANALYSIS
F. Paroni Sterbini1, G. Cammarota2, F. Bugli1, S. Bibbo`2, G. Ianiro2,*,
M. Iacono3, E.D. Capoluongo4, F. Scaldaferri2, A. Gasbarrini2, M. Sanguinetti1,
L. Masucci1
1
Institute of Microbiology, 2Dept of Internal Medicine, Division of
Gastroenterology, CATHOLIC UNIVERSITY SCHOOL OF MEDICINE,
ROME, 3Roche Diagnostics, MILAN, 4Laboratory of Clinical Molecular Biology,
CATHOLIC UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: H. pylori is known to play a paramount role in the development of both gastric and extragastric diseases.
However, human stomach harbours also a broad variety of microorganisms,
often not cultivable with conventional microbiology methods. Metagenomic
techniques are improving our understanding of gut microbiota composition,
using the 16S rRNA gene as a molecular fingerprint to analyze microbial diversity. Chronic therapy with proton-pump inhibitors is known to increase the risk
of gut microbiota-related diseases such as C. difficile infection and spontaneous
bacterial peritonitis. Influence of proton-pump inhibitors (PPIs) in modifying
gastric microbial ecosystem has not yet been described.
AIMS & METHODS: Our aim is to assess, through metagenomic tools, the
composition of gastric microbiota in subjects with upper gastrointestinal symptoms either taking or not PPIs. We analyzed gastric biopsy samples from 10

A408
consecutive patients undergoing upper endoscopy. We enrolled 5 patients taking
PPIs (group A) and 5 ones free from gastrointestinal drugs (group B). We collected two biopsy samples for each patient. Roche 454 GS Junior was used for
metagenomic analysis. Obtained data were assessed by Qiime suite.
RESULTS: Main indications to upper endoscopy were epigastric pain and/or
heartburn and/or dyspepsia. Bacteria amplicons were detected in all samples. H.
pylori was found in 3 patients from group A and 2 patients from group B,
respectively. Overall, prevalent bacteria classes were Epsilonproteobacteria
(26.5%), Bacilli (21%), Bacteroidia (19.3%), and Gammaproteobacteria
(7.8%). Generally, a higher number of microorganisms was found in group A.
Differences in gut microbiota composition were observed between two groups of
patients. Respectively, higher abundance of Actinobacteria (9.74% VS 0.98%),
Bacilli (27.78% VS 14.22%), Betaproteobacteria (7.68% VS 1.32%) and
Gammaproteobacteria (13.86% VS 1.86%) and a lower presence of
Epsilonproteobacteria (1.06% VS 51.8%) were found in group A when compared
with group B.
CONCLUSION: Until a short time ago the uncultivability of microorganisms
did not allow the assessment of gastric microbiota composition. The diffusion of
metagenomics tools, not depending on microbial culture, has incredibly enlarged
our knowledge on gut microbiota. In this preliminary report, we demonstrated
that PPIs modify gastric microbiota composition in subjects with upper gastrointestinal symptoms. Such phenomenon may explain the role of PPIs in the
development of many gut-microbiota related diseases. Further investigations
are needed to improve our understanding of this cutting-edge topic.
Disclosure of Interest: F. Paroni Sterbini: nothing to declare, G. Cammarota:
nothing to declare, F. Bugli: nothing to declare, S. Bibbo`: nothing to declare,
G. Ianiro: nothing to declare, M. Iacono: nothing to declare, E. D. Capoluongo:
nothing to declare, F. Scaldaferri: nothing to declare, A. Gasbarrini: nothing to
declare, M. Sanguinetti: nothing to declare, L. Masucci: nothing to declare
P1002 COMPARATIVE
ANALYSIS
OF
GASTROINTESTINAL
BACTERIAL MICROBIOTA BETWEEN NORMAL AND CDX2
TRANSGENIC MICE
H. Sakamoto1,*, T. Asahara2, O. Chonan2, N. Yuki2, H. Mutoh1, S. Hayashi3,
H. Yamamoto1, K. Sugano1
1
Division of Gastroenterology, Department of Medicine, Jichi Medical University,
Shimotsuke, 2Yakult Central Institute for Microbiological Research, Kunitachi,
3
Department of Microbiology, Kitasato University School of Medicine,
Sagamihara, Japan
Contact E-mail Address: 94036hs@jichi.ac.jp
INTRODUCTION: Cdx2 is expressed in human intestinal metaplastic mucosa
and induces intestinal metaplastic mucosa in Cdx2-transgenic mouse stomach. In
humans, atrophic gastritis and intestinal metaplasia due to Helicobacter pylori
(H. pylori) infection commonly lead to gastric achlorhydria. These conditions
predispose the stomach to bacterial overgrowth. To date, the few studies have
been reported that explored the microbiota of the stomach in negative or positive
status for H. pylori using molecular methods. However, the studies on characterization of the gastric microbiota in severe atrophic gastritis or intestinal metaplasia have not been published.
AIMS & METHODS: The aim of the present study was to determine the differences in the gut microbiota between normal and Cdx2-transgenic mice using a
quantitative RT-PCR method with 16S rRNA-genetargeted species-specific
primers.
Twelve normal and twelve Cdx2 transgenic mice (7 weeks age, 6 male and 6
female respectively) were sacrificed, and the gastric, jejunal, ileac, cecal and
colonic mucosa, and feces were collected. To analyze bacterial microbiota quantitatively, we used a real time RT-PCR method with 16S rRNA-gene-targeted
species-specific primers. Seven primer sets for obligate anaerobes (Clostoridium
coccoides group, Clostridium leptum subgroup, Bacteroides fragilis group,
Bifidobacterium, Atopobium cluster, Prevotella, Clostridium perfringens), 5 sets
for facultative anaerobes (Lactbacillus, Enterobacteriaceae, Enterococcus,
Streptococcus, Staphylococcus) and 1 set for a obligate aerobe (Pseudomonas)
were used.
RESULTS: The total bacterial numbers in the gastric (log10(7.7  0.4)/g), jejunal
(log10(6.7  0.7)/g), ileac (log10(6.3  0.4)/g), cecal (log10(7.6  0.3)/g) and colonic (log10(7.7  0.4)/g) mucosa of Cdx2-transgenic mice were significantly higher
than those (log10(5.3  1.0) / g, log10(3.4  1.2)/g, log10(4.9  0.8)/g, log10(6.6 
0.4)/g and log10(5.4  1.3)/g, respectively) of normal mice. Bacteroides fragilis
group and Prevotella were not detected in the stomach of normal mice while they
were detected in that of Cdx2-transgenic mice. Moreover, C. coccoides group, C.
leptum subgroup, Bacteroides fragilis group and Prevotella were not detected in
the jejunum and ileum of normal mice while they were detected in that of Cdx2transgenic mice. In contrast, the fecal microbiota in normal mice was similar to
that in Cdx2-transgenic mice.
CONCLUSION: Gastric achlorhydria due to intestinal metaplasia makes an
obvious effect on gastrointestinal microbiota.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1003 TOLL-LIKE RECEPTOR 7-DEPENDENT MODULATION OF
COLONIC PERMEABILITY DEPENDS UPON THE INTEGRITY OF
THE EPITHELIAL BARRIER
J. Estevez1, V. Martinez1,*
Dept. of Cell Biology, Physiology and Immunology, Universitat Autonoma de
Barcelona, Bellaterra, Spain
Contact E-mail Address: javier.estevez@uab.es
1

INTRODUCTION: Toll-like receptors (TLRs) are a key component in hostbacterial interactions within the gut. TLRs have been implicated in the regulation
of epithelial permeability through the modulation of tight junctions.
AIMS & METHODS: To assess in vivo changes in colonic permeability associated to the local stimulation of TLR7 and the implication of tight junctionsrelated proteins. Adult SD rats were treated intracolonically with the selective
TLR7 agonist imiquimod (300 mg/rat) or its vehicle (0.2 ml). In some cases, 4 h
after imiquimod administration, the colonic epithelium was challenged with
100% dimetilsulfoxide (DMSO). Colonic epithelial permeability to macromolecules was determined assessing the accumulation of 4 kDa fluorescein isothiocyanatedextran (FD4; 10 mg/animal, 0.2 ml, intracolonically) in the colonic wall
and the passage to blood and urine. Expression of tight-junction-related proteins
[occludin, Zona Occludens-1 (ZO-1), claudin-2 and -3, tricellulin and junctional
adhesion molecule 1], inflammatory markers (IFN1 and IL-6) and the barrier
modifier factors [Glucagon-Like Peptide 2 (GLP-2) and Myosin Light-Chain
Kinase (MLCK)] was assessed by RTqPCR.
RESULTS: Acute stimulation of TLR7 with imiquimod did not alter the colonic
passage of FD4. Challenge of the colonic mucosa with DMSO slightly increased
colonic permeability (Table). TLR7 stimulation after the challenge with DMSO
resulted in an enhancement of FD4 accumulation in colonic tissues and an
increased passage to blood and urine (Table). Neither macroscopical nor microscopical nor molecular signs of inflammation were observed, regardless the treatment considered. Intracolonic imiquimod did not modify the expression of the
main tight-junction-related proteins or the barrier modifier factors (proglucagon
and MLCK).

FD4
Serum (mg/ml)
Urine (mg/ml)
Colon (% of
FD4 in tissue)

VehicleVehicle

IMQVehicle

VehicleDMSO

IMQDMSO

0.49  0.07
0.79  0.27
7.93  2.31

0.45  0.07
1.06  0.20
4.16  1.78

0.74  0.11
3.14  0.68
5.73  3.14

1.12  0.10**
6.66  1.21**
14.25  4.12

CONCLUSION: Local stimulation of TLR7 results in an enhanced colonic


permeability only in states of epithelial disruption. The mechanisms mediating
these effects seem to be independent of a modulation of the expression of the
main tight junction-related proteins or the expression of GLP-2 and MLCK.
These observations suggest that microbial factors do not trigger, per se, epithelial
alterations, but they can contribute, as enhancing factors, in states of epithelial
disruption. Similar mechanisms might operate in functional and inflammatory
gastrointestinal disorders. In these conditions, after an initial disturbance of the
epithelial barrier, the microbiota would act as an enhancing and/or perpetuating
factor.
Disclosure of Interest: None declared
P1004 THE PERSISTENCE OF COLON CANCER-ASSOCIATED
ESCHERICHIA COLI WITHIN HUMAN MACROPHAGES INDUCES
COX-2 EXPRESSION
J. Raisch1, A. Darfeuille-Michaud1, M.-A. Bringer1,*
1
M2iSH, UMR1071 Inserm-Universite dAuvergne; INRA USC2018, ClermontFerrand, France
Contact E-mail Address: m-agnes.bringer@udamail.fr
INTRODUCTION: Independent studies have shown that colonic adenomas,
carcinomas and the mucosa of patients with colorectal cancer are abnormally
colonized by Escherichia coli belonging to the B2 phylogroup, with a high prevalence of E. coli producing a genotoxin termed colibactin. Macrophages are one
of the predominant cellular components of tumor-infiltrating immune cells where
they support key processes in tumor progression through the expression of protumoral factors such as the cyclooxygenase-2 (COX-2).
AIMS & METHODS: In the present study, we aimed to analyze the interaction
of B2 phylogroup E. coli isolated from tumors of patients with human macrophages and the subsequent COX-2 expression.
The ability of B2 E. coli isolated from colon cancer to resist macrophages killing
was assessed in human THP-1 macrophages using gentamicin assay and microscopy analysis. COX-2 expression and PGE2 secretion were quantified by
Western blot and ELISA, respectively. Involvement of MAPK signaling pathways were analyzed by Western blot using specific inhibitors.
RESULTS: Colon cancer associated-E. coli were able to survive within human
THP-1 macrophages at 24h post-infection indicating that these bacteria are able
to resist macrophages killing. Transmission electron microscopy revealed that
bacteria are enclosed in two kinds of compartments, some vacuoles containing
single bacteria and other ones containing numerous bacteria. In addition, colon
cancer-associated E. coli induced COX-2 expression and PGE2 secretion to levels
significantly higher than those induced by the commensal E. coli strain ED1a
belonging also to B2 phylogroup. Induced-COX-2 expression by colon cancerassociated E. coli was not related to the production of colibactin, since we
observed similar COX-2 levels in macrophages infected with wild-type strain

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United European Gastroenterology Journal 2(1S)


11G5 or a clbQ mutant unable to produce colibactin. Interestingly, when macrophages were treated with ofloxacin, a fluoroquinolone antibiotic with intracellular tropism, a decrease in the number of intracellular E. coli was observed
together with a decrease in COX-2 expression. In addition, in infected macrophages with colon cancer-associated E. coli, the p38 MAPK signalling pathway
was involved in the control of the number of intracellular bacteria and in COX-2
expression.
CONCLUSION: Colon cancer-associated E. coli strains belonging to B2 phylogroup are able to resist macrophages killing and the presence of live intracellular bacteria induces COX-2 expression. We identify the p38 MAPK signalling
pathway as a target to control the number of intracellular bacteria within macrophages and to limit the expression of the pro-tumoral factor COX-2.
Disclosure of Interest: None declared

returned to baseline community structure but in one subject, where the change
persisted. In the third group (Group C), there was variability in community
structure over time that could not be ascribed to PEG intervention. The table
shows species richness according to Chao1 in the three groups.

Chao 1
Group A
Group B
Group C

P1005 GUT
MICROBIOTA
DYNAMICS
DURING
RADIATION
PROCTITIS AND ITS POTENTIAL ROLE IN CONTROLLING
DISEASE SEVERITY
S. Gerassy Vainberg1,*, A. Blatt2, Y. Danin poleg1, A. Dahan2, Y. Kashi1,
Y. Chowers2
1
Biotechnology and food engineering, Technion, 2Gastroenterology, Rambam
Health Care Campus, Ruth and Bruce Rappaport School of Medicine, TechnionIsrael Institute of Technology, Haifa, Israel
Contact E-mail Address: y_chowers@rambam.health.gov.il
INTRODUCTION: A balanced gut microbiota, is essential for host well-being.
Radiation proctitis (RP) may develop following radiation treatment of pelvic
malignancies. Microbial changes may occur following radiation and impact
radiation-induced tissue damage.
AIMS & METHODS: Aim: To investigate gut microbiota dynamics during different stages of RP in a mouse RP model.
Methods: The microbiome was analysed using fingerprinting and high-throughput approaches, based on fecal samples and colonic biopsies for up to 36 weeks.
Biologic effects of microbiota at different stages were investigated using coculture
of bacteria with HT-29 cells.
RESULTS: A shift in the gut microbiome during RP was observed (p-value
Bonferroni-corrected 5 0.0001 based on unweighted UniFrac mesure) and
each clinical stage was represented by a unique microbial signature. These signatures were correlated with disease progression and immunologic parameters, as
analyzed by colonic mRNA expression of several cytokines including TNF,
IL1, IL6 and TGF (p-value50.05), histopathology (p-value50.001) and
macroscopic symptoms of body weight, diarrhea and rectal bleeding in irradiated
mice Vs controls. Using cocultures, RP-induced fecal microbiome obtained from
active disease stages was found to induce secretion of TNF (3.6-fold increase, pvalue50.05) from the intestinal epithelial cells as compared to control flora,
while na ve flora caused a decrease in IL1 secretion (2.3-fold, p-value50.05).
Supernatants and UV inactivated bacteria had no effect on cytokine secretion
from the cells.
CONCLUSION: Rectal irradiation alters the local microbiota which have proinflammatory effects and loss of anti-inflammatory activity. Live bacteria are
needed in order to mediate these effects. Better understanding of the mucosalmicrobiome interaction may aid in future attemps to control disease severity and
may potentially allow for manipulation of the microbiota in a clinically beneficial
manner.
Disclosure of Interest: S. Gerassy Vainberg: None declared, A. Blatt: None
declared, Y. Danin poleg: None declared, A. Dahan: None declared, Y. Kashi:
None declared, Y. Chowers Lecture fee(s) from: Abbvie, Takeda, Janssen,
Consultancy for: Abbvie, Takeda, Janssen, Pharmacosmos
P1006 PEG-GUT LAVAGE MAY INDUCE CHANGES IN THE FAECAL
MICROBIOME OF HEALTHY VOLUNTEERS
V. Robles1,*, S. Panda1, A. Santiago1, E. Navarro1, C. Herrera1, N. Borruel1,
F. Casellas1, C. Manichanh1, F. Guarner1
1
GASTROENTEROLOGY, VALL DHEBRON UNIVERSITY HOSPITAL,
BARCELONA, Spain
INTRODUCTION: Dysbiosis may play a role in some gastrointestinal conditions such as IBD, IBS and C diff diarrhoea. Metagenomic studies indicate that
such conditions are associated with reduced bacterial diversity of the gut microbial ecosystem. Using high-throughput 16S rRNA sequencing technique, we
explored whether intestinal cleansing with a polyethylene glycol solution (PEG)
induces changes in the faecal microbiome of healthy individuals, and whether the
eventual changes are reversible over time.
AIMS & METHODS: We analysed the faecal microbiome of 12 healthy volunteers through 7 time points before and after bowel cleansing with PEG. Faecal
samples obtained at day -30 (T1) and day -1 (T2) before PEG evaluated stability.
A solid sample was obtained during PEG lavage (T3), and further samples on
days 1 (T4), 15 (T5), 30 (T6), and 60 (T7) were used to investigate changes
induced by PEG and eventual resilience. DNA extracts were analysed by pyrosequencing of the 16S rRNA gene (V4). Raw sequence data collected were analysed with Qiime. We use Chao1 as species richness estimator and Unifrac as
Phylogenetic Similarity Index.
RESULTS: Regarding the overall structure of bacterial communities, main
enterotype drivers (Bacteroides genus for enterotype 1 and Prevotella genus for
enterotype 2) did not change with PEG or during the follow-up. Interestingly,
principal component analysis based on the weighted Unifrac distance metric
indicated three different outcomes from the intervention. First, six individuals
(Group A) showed no change of microbiome structure after PEG. Second, three
individuals (group B) showed a clear change in community structure after PEG,
since T4 samples did not cluster with T1 and T2. During the follow-up, T7

Timepoint 2
Mean and CI95%

Timepoint 4
Mean and CI95%

Timepoint 7
Mean and CI95%

744,92
(685,24-804,60)
694,12
(481,86-906,32)
878,55
(846,68-910,43)

713,57
(609,94-824,21)
520,80
(385,61-656)
663,86
(537,86-789,86)

713,99
(685,62-762,35)
610,46
(232,11-988,80)
638,91
(138,89-1138,93)

At species level, counts of Faecalibacterium prausnitzii (Fprau) markedly


increased in T4 samples from group A and C individuals (p 0.07), but decreased
in all samples from group B. The increase may be explained by the flushing effect
of PEG, since Fprau is usually abundant at ileo-caecum. On the other hand,
Akkermansia muciniphila was detected at baseline in 6 out of 12 individuals, but
only in 3 out of 12 T4 samples and in 4 T7 samples. Mean (SEM) relative
abundance decreased (T2 3.82.3; T4 0.130.09; T7 and 0.900.72).
CONCLUSION: PEG exposure did not modify the overall microbial community
structure. In most subjects, detectable changes fell within the expected over time
fluctuations. However, changes may persist in a subset of individuals.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS II POSTER
EXHIBITION HALL XL_____________________
P1008 THE CLINICAL CHARACTERISTICS AND MANIFESTATION OF
CMV ESOPHAGITIS
C.J. Kuo1,*, H.-W. Wang1, M.-Y. Su1, C.T. Chiu1
Department of Gastroenterology and Hepatology, Chang Gung Memorial
Hospital, Taoyuan, Taiwan, Province of China
Contact E-mail Address: m7011@adm.cgmh.org.tw
1

INTRODUCTION: Esophagitis is the second most common gastrointestinal


(GI) manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, longterm renal dialysis and human immunodeficiency virus (HIV) infection
AIMS & METHODS: This study aimed to investigate the clinical characteristics
of CMV esophagitis in patients undergoing diagnostic endoscopy.
A total of 23 patients with histologically proven cytomegalovirus infection from
1539 cases with esophageal ulcers (2003-2013) were identified and analyzed retrospectively. Patients personal data (age, smoke, alcohol drinking), underlying
systemic disease (diabetes mellitus, end stage renal disease, COPD), malignancy,
indication of EGD, endoscopic characteristics in viral esophageal ulcer and diagnostic methods (pathological or serological finding) were collected for further
analysis.
RESULTS: Among this data base, 23 patients were diagnosed to have cytomegalovirus esophageal ulcers. The age range was 23-84 yr and the male/female
ratio 2.3/1. Odynophagia and epigastralgia were common symptoms. Most (15 of
23) of the CMV related ulcers were located at middle to lower third or distal
esophagus. 21.7% (5/23) patients were infected with the human immunodeficiency virus. 47.8% (11/23) patients have underlying malignancy, including
lung cancer (4), esophageal cancer (4), gastric cancer (1), ampulla vater cancer
(1) and lymphoma (1). Eight of 11 patients (73%) had ever received concurrent
chemoradiotherapy.
CONCLUSION:
In our study, patients with malignancy who had ever received concurrent chemoradiotherapy are at increased risk for CMV esophagitis, which had not been
reported before in the literature review.
Disclosure of Interest: None declared
P1009 UPPER GASTROINTESTINAL ENDOSCOPIC FINDINGS IN HIVINFECTED ASIAN PATIENTS ACCORDING TO AGE AND CD4
LYMPHOCYTE COUNT
J. Choi1,*, S.W. Nam1, J.W. C. W. Chung1
1
Department of Internal Medicine, National Medical Center, Seoul, Korea,
Republic Of
Contact E-mail Address: cjk@nmc.or.kr
INTRODUCTION: Upper gastrointestinal (GI) tract diseases are common
among patients infected with human immunodeficiency virus (HIV). Upper GI
endoscopic evaluation of the GI tract disease remains a cornerstone of diagnosis,
especially in a highly prevalent area of gastric cancer and Helicobacter infection.
AIMS & METHODS: The study aimed to evaluated the upper GI endoscopic
findings by CD4 lymphocyte count and age. We retrospectively studied 191 HIVinfected patients who underwent upper GI endoscopy for any indications from
January 1, 2010 to December 31, 2013. The patients were classified in two
groups, according to CD4 cells counting (200 cells/mm3 or 5200 cells/mm3).
The subjects were divided into five groups (those aged 2029, 3039, 4049, 50
59, and 6069 years old). Parameters studied included age, gender, indications for
endoscopic procedure, CD4 cell counts, antiretroviral therapies, upper GI endoscopic finding and histology.

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United European Gastroenterology Journal 2(1S)

RESULTS: The median age of 191 patients was 43 years (interquartile range
[IQR], 35-52 years), and 182 patients were predominantly male (95.3 %). The
median CD4 cell count was 398 cells /mm3 (IQR, 205- 588 cells/mm3). GI
symptoms including abdominal pain, discomfort, soreness, and dyspepsia were
noted in 133 patients (69.6%). The endoscopic diagnosis of upper GI disease is
shown in Table. Opportunitic infections were seen exclusively in patient with
CD4 5 200 cells/ mm3 except candidial esophagitis. There was no difference
in the prevalence of gastric or duodenal ulcer according to CD4 cell count
groups. However, Helicobacter pylori related ulcers were seen in only group
with CD4 200 cells/mm3.

Candidal esophagitis
Cytomegalovirus disease
HIV-related idiopathic ulcer
Malignant lymphoma
Reflux esophagitis, n(%)
Atrophic gastirits, n(%)
Helicobacter related
peptic ulcer, active stage
Gastric adenoma/
adenocarcinoma, n(%)

P1011 DABIGATRAN- A RISK FACTOR OF SEVERE BLEEDING IN


DISTAL ESOPHAGUS IN ELDERLY WOMEN

All
(n 191)

CD 4 200
cells/mm
(n 146)

CD4 5200 cells


(n 45)

11(5.8)
4(2.1)
8(4.2)
1(0.005)
48(29.1)
28(14.7)
3(1.5)

6(4.1)
0(0)
3(2.1)
0(0)
39(26.7)
23(15.8)
3(2.1)

5(11.1)
4(8.9)
5(11.1)
1(0.02)
19
5(11.1)
0(0)

.134
.003
.019
.31
.696
-

2(1.0)

1 (adenoma)

1 (early gastric
cancer)

CONCLUSION: Low CD4 count is considered to be a predictive factor for


opportunity GI infection in HIV-infected Asian patients except candidial
esophagitis.
Disclosure of Interest: None declared
P1010 MULTICENTRIC
EXTERNAL
VALIDATION
OF
PREENDOSCOPIC CLINICAL PREDICTION RULES IN PATIENTS
WITH NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING
M. Burgos Andeliz1, J.M. Tenias2,*, A. Lucendo3, O. Redondo2
1
GAI Mancha Centro, 2Research Suppot Unit, Hospital General Mancha Centro,
Alcazar de San Juan, 3Digestive Department, Hospital General de Tomelloso,
Tomelloso, Spain
Contact E-mail Address: jmtenias@sescam.jccm.es
INTRODUCTION: The risk scoring systems are increasingly used to evaluate
patients with Upper Gastrointestinal Bleeding (UGIB). Some of these use clinical
and laboratory data, which are collected at the emergency room. Most of them
also use the results of procedures such as endoscopy to stratify the results. We are
still looking for the optimal scoring system, which is simple, easy to use and
remember by the clinicians at the time of the patients reception.
AIMS & METHODS: Aims. To validate externally the discriminant ability of the
pre-endoscopic clinical prediction rules (CPR) (based on clinical and laboratory
data) in patients with Non-Variceal UGIB (NVUGIB) in four tertiary hospitals.
Methods. We carried out an observational retrospective study using the hospital
discharges registry Minimum Basic Data Set (MBDS) for cases of NVUGIB in
Castilla la Mancha, and Valencian Community, Spain which is based on ICD-9
diagnostic codes. We estimated the predictability of ten CPR: pre-endoscopic
Rockall score, Blatchford score, modified Blatchford score, AIMS65 score,
Zaragoza score, Tammaro score, Rangson score, Cambridge score,
Adamopoulos score and UNAL score1-10. We estimated the area under the
ROC curve (AUC) for each CPR versus every outcome indicator (adverse clinical
course, hospital mortality, interventional therapy, unstable bleeding, prolonged
hospital stay).
RESULTS: 483 patients from four different hospitals were studied in two different time periods: 2003 to 2006 (Valencian Community centers), those from the
oldest cohort and 2009 to 2013 (Castile La Mancha centers), those of the recent
cohort. The CPR with better discrimination ability of each analyzed indicator are
shown in table 1. In general, the discrimination ability is below 0.70 in almost all
analyzed indicators and rules.
Table. Discriminant ability of the Clinical Prediction Rules
Discriminant ability

CPR (Scores)

Area under ROC curve

Adverse clinical course


Unstable bleeding
Interventional therapy
Hospital Mortality
Prolonged hospital stay

Adamopoulos1
Rockall7
Adamopoulos1
AIMS658
Rockall7

0.58
0.62
0.57
0.86
0.67

(0.50
(0.50
(0.49
(0.65
(0.61

3. Cameron E, et al. Eur J Gastroenterol Hepatol 2002; 14: 497501.


4. Chaikitamnuaychok R et al. Gatroenterology Res 2012; 5: 219226.
5. Cheng DW et al. Aliment Pharmacol Ther 2012; 36: 782789.
6. Gomez Zuleta MA et al. Acta Medica Colomb 2006; 31: 244258.
7. Rockall TA et al. Gut 1996; 38: 316321.
8. Saltzman JR et al. Gastrointest Endosc 2011; 74: 12151224.
9. Tammaro L et al. World J Gastroenterol 2008; 14: 50465050.
10. Zaragoza Marcet A, et al. Rev Esp Enferm Dig 2002; 94: 139148.
Disclosure of Interest: None declared

0.67)
0.73)
0.66)
1.00)
0.72)

CONCLUSION: The CPRs discriminant ability for estimating the evolution of a


NVUGIB is relatively moderate when they are externally validated in other
different centers to which were derived. Rockal, Adamopoulos and AIMS 65
are the rules that best meet the evolution of these diseases and might be the most
suitable for assessing their prognosis.
REFERENCES
1. Adamopoulos AB et al. Eur J Gastroenterol Hepatol 2003; 15: 381387.
2. Blatchford O et al. Lancet 2000; 356: 13181321.

M. Stefanova1,*, M. Pelikanova2, M. Burian1, D. Erhart2, R. Spacek2


dept of Internal Medcine, 2Hospital Na Frantisku, Prague, Czech Republic
Contact E-mail Address: magdalena.stefanova@seznam.cz

INTRODUCTION: A new generation of oral anticoagulants Dabigatran has


been shown to be effective. New studies showed, that the risk of gastrointestinal
(GI) bleeding of Dabigatran is increased compared with Warfarin, but the incidence of life-threatening or fatal GI bleeding is lower. The source and localization of the bleeding in patients took Dabigatran are not detailed studied.
AIMS & METHODS: To compare a localization and severity of upper GI
bleeding of patients with Dabigatran vs Warfarin.
All anticoagulated patients on Dabigatran or Warfarin with non variceal upper
GI bleeding were enrolled in our study from November 2012 to November 2013.
The demographic details, laboratory studies, concomitant medication were collected. Urgent endoscopy was performed in 24 hours from admission. A localization of GI bleeding and severity according Rockall score were describe.
All enrolled patients were divided in to two groups. Group A patients on
Dabigatran 2x110 mg. Group B patients on Warfarin 1 x 5 mg.
RESULTS: A total of 78 patients with non variceal GI bleeding were examinated
in our department. Twenty of them (26%) were anticoagulated (14 women and 6
men, medium age 78 range (47-92)).
A total of 12 patients (60%) 9 women medium age 82 and 3 men medium age 75
were on Dabigatran- group A.
8 patients (40%) (5 women, medium age 80, 3 men medium age 78 was on
Warfarin- group B.
The source of bleeding had been found in distal esophagus or GE junction in 9
patients (9/12 (75%) 7 women and 2 man) in the group A compared to one
patient (man) 1/8 (13%) in the group B, p 50.05).
Rockall score in the group A was medium 8 (range 4-8) in patients with source of
bleeding in distal esophagus or GE junction compared with Rockall score 5
(range 3-8) in patients with the source of bleeding in other upper GI locality.
Rockall score in the group B was 5 in patients with source of bleeding in distal
esophagus compared with Rockall score 5 (range 4-7) in patients with the source
of bleeding in other upper GI locality. A total of 2 patients (2/12, 17%) in the
group A had a fatal bleeding from source in distal esophagus compared with no
patients in the group B.
CONCLUSION: Our study results revealed that Dabigatran is significant frequent cause of severe upper GI bleeding in distal esophagus or GE junction in
elderly women compared with warfarin. Dabigatran should be indicated very
carefully in this group of the patients.
Disclosure of Interest: None declared
P1012 STANDARD PRE-ENDOSCOPIC AND REDESIGNED POSTENDOSCOPIC GLASGOW BLATCHFORD SCORE PERFORMED
BETTER IN TERMS OF PREDICTING REBLEEDING IN PATIENTS
WITH BLEEDING PEPTIC ULCER AS COMPARED TO ROCKALL
SCORE - RESULTS OF A PROSPECTIVE DATABASE STUDY
I. Budimir1, N. Ljubicic1, M. Nikolic1, T. Pavic1, A. Bis canin1, B. Troskot1,
M. Gomercic Palcic1,*, G. Miros evic2, I. Kruljac2, L. Kirigin1
1
Division of Gastroenterology, Department of Internal Medicine, 2Division of
Endocrinology, Department of Internal Medicine, Sestre milosrdnice University
Hospital Center, Medical and Dental Faculty, Zagreb, Croatia
Contact E-mail Address: marijagomercic@yahoo.com
INTRODUCTION: We present new diagnostic scores that successfully predicted
the treatment outcome and the need for early repeated endoscopy in patients with
bleeding peptic ulcer.
AIMS & METHODS: The aim of the study was to determine optimal pre-endoscopic and post-endoscopic scores in order to most optimally predict mortality,
rebleeding rate, as well as the necessity for surgical intervention, and blood
transfusions in patients with bleeding peptic ulcer.
Patients and methods: We prospectively studied 633 patients with bleeding stomach or duodenal ulcer admitted to Department of Internal medicine at the
University Hospital Center Sestre milosrdnice between January 2009 and
December 2012. For every patient we calculated pre-endoscopic (Rockall (RS)
and Glasgow Blatchford score (GBS)) as well as post-endoscopic diagnostic
scores, according to urgent upper endoscopy findings. In post-endoscopic
GBS, the GBS and Forrest classification with redesigned and upgraded formula
were integrated.
RESULTS: In the group of patients with bleeding stomach and duodenal ulcer
when comparing AUROC for pre-endoscopic GBS and RS we found that latter
is superior in predicting mortality (AUROC 0.82 vs 0.67, p 0.002) while GBS was
better in predicting the rebleeding rate (AUROC 0.75 vs 0.61, p 50.001). Postendoscopic RS was also better in predicting mortality (AUROC 0.82 vs 0.66,
p50.001) and post-endoscopic GBS in rebleeding rate (AUROC 0.79 vs 0.70, p
0.002). Pre and post-endoscopic GBSs better predict the need for blood transfusion and surgical intervention when compared to RS in the same group of

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United European Gastroenterology Journal 2(1S)


patients. Post-endoscopic GBS was better in predicting rebleeding rate (AUROC
0.79 vs 0.75, p50.036) and the need for blood transfusions (AUROC 0.83 vs
0.76, p 50.001) compared to pre-endoscopic GBS.
CONCLUSION: In patients with bleeding stomach and duodenal ulcer, preendoscopic and newly designed post-endoscopic GBSs are better in predicting
the rebleeding rate, surgical intervention and the need for blood transfusion while
pre and post-endoscopic RSs are superior in predicting mortality.
REFERENCES
1. Rockall TA, Logan RF, Devlin HB, et al. Risk assessment after acute upper
gastrointestinal haemorrhage.Gut 1996; 38: 316-321.
2. Blatchford O, Davidson LA, Murray WR, et al. Acute upper gastrointestinal
haemorrhage in west of Scotland: case ascertainment study. BMJ 1997; 315: 510514.
3. Forrest JA, Finlayson ND and Shearman DJ. Endoscopy in gastrointestinal
bleeding. Lancet 1974; 2: 394-397.
4. Laursen SB, Hansen JM and Schaffalitzky de Muckadell OB. The Glasgow
Blatchford score is the most accurate assessment of patients with upper gastrointestinal hemorrhage. Clin Gastroenterol Hepatol 2012; 10: 1130-1135.
5. Ljubicic N, Puljiz Z, Budimir I, et al. The influence of etiologic factors on
clinical outcome in patients with peptic ulcer bleeding. Dig Dis Sci 2012; 57:
3195-3204.
Disclosure of Interest: None declared
P1013 THE PERFORMANCE OF THE GLASGOW BLATCHFORD
SCORE (GBS) DEPENDS ON PREDICTING A BLOOD
TRANSFUSION
M. Horibe1,2,*, S. Toda2, O. Okawa2, W. Shinomiya2, Y. Nakatani2
1
Keio University Hospital, 2Tokyo MetropolitanTama medical center, Tokyo,
Japan
Contact E-mail Address: aries24sirius@yahoo.co.jp
INTRODUCTION: Among the several scoring systems currently available for
calculating the risk of upper-gastrointestinal bleeding (UGIB), the best option at
present is the Glasgow Blatchford Score (GBS), which is used widely for assessing the need for admission. 1 The outcome is intervention (blood transfusion,
endoscopic treatment, and surgery) or death. However, blood transfusion as an
outcome measurement is superfluous in any scoring system since vital signs and
hemoglobin level are sufficient to determine the need for a blood transfusion,2
which in any case does not necessarily indicate either the need for intervention or
a high-risk outcome. 3
AIMS & METHODS: For the reasons stated above, the GBS should be validated based on outcomes that do not include blood transfusion. At Tama
Medical Center, Tokyo, Japan, all patients suspected of suffering from UGIB,
who were seen between January, 2008 and December, 2012, were enrolled in a
validation study of the GBS without blood transfusion in the outcome. The first
outcome comprised endoscopic treatment, surgery or death. The second outcome
added blood transfusion to this list. We compared the area under the curve
(AUC) of both outcomes with the GBS using Delongs test. We then assessed
the predictive value of the second outcome with hemoglobin alone against that of
the GBS by comparing their respective AUCs.
RESULTS:

GBS
GBS
Hemoglobin alone

Outcome

AUC

95%CI

Intervention without blood


transfusion or death
Intervention or death
Intervention or death

0.645

0.606-0.684

0.757
0.738

0.718-0.796
0.701-0.776

Of the 763 patients, 435(57.0%) received a blood transfusion and 19 patients died
(2.5%). With regard to the GBS, the AUC of the first outcome was 0.645
[95%CI(0.606-0.684)] and that of the second outcome, including blood transfusion, was 0.757 [95%CI(0.718-0.796).]It was clear that the performance of the
GBS depended largely on predicting the need for blood transfusion. (p50001 by
DeLongs method). On the other hand, the AUC of the hemoglobin level alone
for the second outcome including blood transfusion was 0.738 [95%CI(0.701.40.776)], which was identical to that of the GBS.
CONCLUSION: The hemoglobin level alone was as useful as the GBS when the
outcome measurements for the latter included blood transfusion. The results of
this study suggest that the performance of risk assessments scores for UGIB
should be validated after removing blood transfusion from the outcome
measurements.
REFERENCES
1. Stanley AJ, Ashley D, Dalton HR, et al. Outpatient management of patients
with low-risk upper-gastrointestinal haemorrhage: multicentre validation and
prospective evaluation. Lancet 2009; 373: 42-47.
2. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper
gastrointestinal bleeding. N Engl J Med 2013; 368: 11-21.
3. Hyett BH, Abougergi MS, Charpentier JP, et al. The AIMS65 score compared
with the Glasgow-Blatchford score in predicting outcomes in upper GI bleeding.
Gastrointest Endosc 2013; 77: 551-557.
Disclosure of Interest: None declared

P1014 ACUTE ESOPHAGEAL MUCOSAL LESIONS MIGHT NOT BE A


RARE DISEASE
N. Tsuruoka1,*, E. Takeshita1, T. Noda2, R. Iwakiri1
SAGA UNIVERSITY, saga, 2Karatsu Red Cross Hospital, karatsu, Japan

INTRODUCTION: Acute esophageal mucosal lesion (AEML) that includes


acute necrotizing esophagitis (ANE) and acute erosive esophagitisis relatively
rareamong upper gastrointestinal bleedings. Recently, AEML is widely recognized with the development of endoscopic techniques.
AIMS & METHODS: This study aimed to clarify clinical features of AEML. We
retrospectively analyse clinical and endoscopic findings of experienced
AEMLcases of between January 2008 and March 2014.
RESULTS: We experienced 19cases (16patients)of AEML with 12male patients
(75%) and 4 female patients (25%) with an average age of 56 years. Among
them, only one patient had repeated 4 times of AEML (once ANE and 3 times
of acute erosive esophagitis). During the period, we performed 14746 upper
gastrointestinal endoscopies include 807 emergent upper gastrointestinal endoscopies. The rate of AEML accounted for emergency upper gastrointestinal
endoscopies was 2.35% and 0.13% for all upper gastrointestinal endoscopies.
AEML predominantly affected the lower third of the esophagus, and sliding
hernia was the most common (94.7%) coexisting endoscopic finding. AEML
was often accompanied by gastro-duodenal mucosal lesion. Two-thirds of
ANE cases were accompanied by gastro-duodenal mucosal lesion, however
only 7.69% of acute erosive esophagitis cases were accompanied by gastro-duodenal mucosal lesion. All patients had some comorbidity. Thirty three percent of
patients with ANE, and fifteen percent of patients with acute erosive esophagitis
received non-steroidal anti-inflammatory drugs (NSAIDs). Thirty percent of
patients with acute erosive esophagitis had taken PPI or H2RA,however no
ANE patient took gastric secretion inhibitor. Gastric secretion inhibitor is possible to attenuate esophageal damage because the pathology of the 2 diseases is
essentially same. Five cases (26.3%) were complicated by esophageal stenosis and
eventually 3 cases died. All dead cases were associated with underlying diseases.
CONCLUSION: AEML was considered to be rare disease. However, more cases
might be noticed with frequent application of upper gastro-intestinal endoscopy.
Disclosure of Interest: None declared
P1015 THE EFFICACY OF A SECOND-LOOK ENDOSCOPY WITH OR
WITHOUT CLIPPING AFTER ENDOSCOPIC RESECTION FOR
GASTRIC AND DUODENAL TUMORS: INTERIM RESULTS OF
ONGOING PROSPECTIVE RANDOMIZED TRIAL
R. Plakhov1, O. Buntseva1,*, E. Fedorov1, Z. Galkova1, E. Ivanova1,
V. Lebedeva1
1
Moscow University Hospital 31, Moscow, Russian Federation
Contact E-mail Address: roma_vp@mail.ru
INTRODUCTION: The benefit of postoperative EGD in order to control/prevent bleeding after endoscopic resection (ER) of gastric and duodenal tumors is
still debatable.
AIMS & METHODS: The aim of this ongoing study is to evaluate whether
second-look endoscopy (SLE) and haemostatic endoclipping is essential to prevent delayed gastrointestinal bleeding (GIB) after ER. A total of 35 patients (m9, f-26, mean age Ms 68.3  8.2 years) who underwent ER for gastric (31) and
duodenal (4) tumors: endoscopic mucosal resection (EMR) 20(57.2%), endoscopic submucosal dissection (ESD) 9(25.7%), removal of submucosal tumor
(RST) 6(17.1%) from November 2012 to April 2014 were included in this study.
All patients were randomly divided into 2 comparable groups. After ER the
patients of both groups received antisecretory therapy with proton pump inhibitors (PPI): the first 3 days - pantoprazole 80 mg intravenously, the next 4 weeks pantoprazole 80 mg per day orally. Each SLE was performed next day after the
ER; endoscopic hemoclipping (EHC) was used to prevent GIB. In the group 1
(IPPEHC) (19 pts.) endoscopic hemostasis (EH) was performed in all cases of
visible vessels on the bottom and margins of the mucosal defect. In the group 2
(IPP alone) (16 pts.) EH was performed only in exceptional situations - at active
bleeding or extremely high risk of bleeding (major vessels exposed on the mucosal
defect). ER was performed under general anesthesia in 26 cases and local - in 9
cases. Coagulating forceps FD-410LR and argon plasma coagulation probe with
electrocoagulator VIO 300 were used for hemostasis. Moreover, at the final stage
clip fixing device HX-110LR with clips HX-610-135 was applied for the prevention of GIB.
RESULTS: EH at the final step of ER was performed in 52.6% (10/19) patients of
Group 1 and 56.3% (9/16) patients of Group 2. The mean size of mucosal defects
after ER was 21.214.9 mm and 25.318.1 mm respectively. All patients underwent
SLE at the second day after the ER. In Group 1 EH was performed in 7 patients with
stigmata, including 2 patients with vessels size more than 1.5 mm. In Group 2 only
one patient had exposed major vessels on the bottom of the postoperative defect
after removal of a large villous duodenal tumor that required prophylactic placement of hemoclips. Only one 60-year-old female patient (5,3% from Group 1) had
mild GIB on the second day after ESD for ulcerated tubulovillous adenoma of the
stomach. It is remarkable that this complication occured a few hours after preventive endoclipping of all thrombosed vessels during SLE. The patient had a malignant
course of hypertonic disease. In our opinion, an uncontrolled sharp increase in
blood pressure was the main cause of postoperative bleeding. After succesfully
perfomed EH the patient recovered on the background of intensified therapy for
hypertention and doubled antisecretory therapy.
CONCLUSION: According to our preliminary data SLE with prophylactic clipping after ER for gastric and duodenal tumors has no significant impact on the
frequency of postoperative GIB. SLE is feasible in selected patients with large
postoperative mucosal defects after the wide excision of the tumor.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)

P1016 COMPARATIVE ASSESSMENT OF TOLERABILITY, DURATION


AND COSTS BETWEEN THE 36-SOLID-STATE AND THE 24-WATERPERFUSED HIGH RESOLUTION MANOMETRY FOR ESOPHAGEAL
MOTILITY TESTING DATA FROM A PROSPECTIVE,
RANDOMIZED, DOUBLE BLIND, CROSSOVER STUDY
E. Savarino1,*, R. Salvador1, G. Capovilla1, L. Nicoletti1, G. Zaninotto2,
M. Costantini1
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, Italy, 2Imperial College, London, United Kingdom
INTRODUCTION: High Resolution Manometry (HRM) is a new technique for
intraluminal esophageal pressure measurement, performed with a multitude of
closely spaced (52cm) pressure sensors. Currently, two systems are most widely
used in clinical practice: the 36-channel solid-state (SS) HRM and the 24-channel
water perfused (WP) HRM. Comparative data regarding their ambulatory use
are lacking.
AIMS & METHODS: We aimed to assess and compare the tolerability, procedure duration and costs between the 36-SS and the 24-WP system. These data
have been collected conducting a prospective, randomized, double blind, crossover study aimed to measure and compare normal values of conventional and
high-resolution manometry metrics as well as to assess the inter-rater and interdevice agreement for the diagnosis of esophageal motility disorders between the
36-SS (Given Imaging, Los Angeles, CA) and the 24-WP system (EB Neuro,
Firenze, Italy). Twenty healthy volunteers [HVs; 11M/9F; median age 29 (IQR
26-33)] and 20 patients [11M/9F; 48 (43-55)] with esophageal symptoms (i.e.
reflux symptoms, chest-pain or dysphagia) were enrolled. They underwent both
procedures blinded and in random order. Tolerability was assessed by using a
self-made questionnaire investigating the occurrence of symptoms, presence and
location of discomfort and which procedure was better tolerated. System set-up
time, procedure duration and analysis time were measured separately. Finally,
costs related to their ambulatory use were provided by the Resources
Management Office.
RESULTS: Details about tolerability are shown in the Table. Overall, HVs did
not found any difference between the two systems, whereas the patients tolerated
better the 36-SS HRM procedure [9 (45%) vs. 12 (60%), p ns]. Significantly
longer set-up (454sec vs. 222sec, p50.01) and plot analysis (601sec vs. 345sec,
p50.01) time was required by the 24-WP system compared to the 36-SS system.
No difference was observed between the 24-WP and 36-SS system in terms of
tracing acquisition time (483sec vs. 552sec, p 0.6). The single-procedure cost
was 58.48 E for the 24-WP HRM and 79.18 E for the 36-SS HRM.
HVs
24-WP
HRM

HVs 36-SS Patients


Patients
HRM
24-WP HRM 36-SS HRM

Symptoms Occurrence, n (%)


None
4 (20%) 3 (15%)
Pain
4 (20%) 3 (15%)
Heartburn
4 (20%) 5 (25%)
Nausea and Vomiting
1 (5%) 1 (5%)
Globus
10 (50%) 9 (45%)
Location of Discomfort, n (%)
Nose/ Throat
16 (80%) 11 (55%)
Chest/Stomach
1 (5%) 0 (0%)

1
6
1
4
9

(5%)
(30%)
(5%)
(20%)
(45%)

14 (70%)
2 (10%)
0 (0%)
3 (15%)
4 (20%)

16 (80%)
1 (5%)

7 (35%)
0 (0%)

CONCLUSION: The 36-SS system was better tolerated by patients and required
shorter set-up and analysis time. This may be explained by a heightened sensitivity of the patients to intraesophageal stimuli (i.e. water outflow). The procedure cost was substantially higher for the 36-SS system due to the higher price of
the 36-SS catheter.
Disclosure of Interest: None declared
P1018 GRADE OF EOSINOPHILIA VS. SYMPTOMS IN PATIENTS
WITH EOSINOPHILIC ESOPHAGITIS
H. Larsson1,*, E. Norder Grusell1, B. Tegtmeyer2, H. Bergquist3, M. Bove1
1
ENT/H&N Surgey, Ear Nose and Throat dep., 2Pathology, Pathology,
Trollhattan, 3ENT/H&N Surgey, Ear Nose and Throat dep., Gothenburg, Sweden
Contact E-mail Address: helen.m.larsson@vgregion.se
INTRODUCTION: The diagnosis of eosinophilic esophagitis (EoE) is established by symptoms of esophageal dysfunction not caused by GERD and with
at least 15 eosinophils/high power field in biopsies from the esophageal
mucosa.(1)
AIMS & METHODS: The aim of this study was to assess the correlation
between the number of eosinophils and symptoms in untreated EoE-patients
both by histopathological staining with haematoxylin-eosin (HE) and by immunohistochemical (IHC) technique against Eosinophil Major Basic Protein. The
biopsy slides were encoded, scanned and examined. At the peak value area the
eosinophils were separately marked and counted (d 0.52mm circle at x400).
Symptoms and health-related quality of life (HRQL) were recorded using the
Watson Dysphagia Scale (WDS), the European Organization for Research and
Treatment of Cancer Quality of LifeOesophageal Module 18 (EORTC QLQOES18) and the Short Form36 (SF-36) questionnaires. Data on the presence of
allergies and bolus impaction were reviewed from medical records.

RESULTS: EoE patients (n 66) were consecutively included from Jan 2007
until May 2012. The mean age was 45 years (19-88) and 74% were males.
Allergy occurred in 73% of the patients and 39% were diagnosed in connection
with an incident of esophageal bolus impaction. More eosinophils were counted
after IHC- than after HE- staining (p50.001). Age correlated weakly and negatively with the number of eosinophils in the IHC slides (R -0.24 peak, R -0.32
upper part). Bolus impaction was associated with higher numbers of eosinophils
in the mucosa from the upper part of the esophagus (IHC p 0.05 and HE
p50.05). The response rate for WDS and SF-36 were 92% and for the
EORTC QLQ-OES18 100%, however, the number of eosinophils did not correlate with any of the scores from these questionnaires.
CONCLUSION: The significantly higher eosinophil counts obtained after IHC
as compared to HE-staining is uncontroversial.(2) So is the non-existing correlation between subjective symptoms and the numbers of eosinophils.(3) Still, higher
eosinophil counts were found in biopsies obtained during the course of acute
bolus impaction, which might be considered the ultimate grade of dysphagia. The
weak negative correlation found between age and numbers of eosinophils should
be carefully interpreted but might reflect the ageing immune system.(4) The
significantly higher eosinophil numbers in the upper esophagus in patients with
concomitant bolus impaction may motivate increased attention to this level
regarding histopathology and motility in EoE.
REFERENCES
1. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. J Allergy Clin Immunol
2011; 128: 3-20.
2. Mueller S, Aigner T, Neureiter D, et al. Eosinophil infiltration and degranulation in oesophageal mucosa from adult patients with eosinophilic oesophagitis: a
retrospective and comparative study on pathological biopsy. J Clin Pathol 2006;
59: 1175-1180.
3. Pentiuk S, Putnam PE, Collins MH, et al. Dissociation between symptoms and
histological severity in pediatric eosinophilic esophagitis. J Pediatr Gastroenterol
Nutr 2009; 48: 152-160.
4. Busse PJ and Mathur SK. Age-related changes in immune function: effect on
airway inflammation. J Allergy Clin Immunol 2010; 126: 690-699.
Disclosure of Interest: None declared
P1019 IN VIVO HISTOPATHOLOGICAL ASSESSMENT
MUSCULARIS PROPRIA IN ACHALASIA BY USING
ENDOCYTOSCOPY

OF

THE

H. Sato1,2,*, H. Inoue1, H. ikeda1, C. Sato1, C. Phalanusitthepha1, E.G.


R. Santi1, S.-E. Kudo1
1
Digestive Disease Center, Showa University, Northern Yokohama Hospital,
Yokohama, 2Department of gastroenterology, Niigata University, Niigata, Japan
INTRODUCTION: Histopathology of muscularis propria (MP) is still unknown
in patients with achalasia. Endocytoscopy (EC) was developed as ultra-high
magnification endoscopy, and through the submucosal tunnel created during
per-oral endoscopic myotomy (POEM), not only access but also subsequent
consecutive assessment of the MP can be performed endoscopically.
AIMS & METHODS: In 7 achalasia patients (mean [SD] age; 3518.1 years,
male:female; 4:3) who underwent POEM (myotomy length: 122.2 cm), subsequent EC examination was performed from mid esophagus to gastric side. EC
images were taken and compared with histopathologic results (two biopsy from
mid esophagus and lower esophageal sphincter) which was considered gold
standard.
RESULTS: In all the cases, favorable EC images were taken, and spindle-shaped
smooth muscle cells were clearly demonstrated. In our series, none of those
showed particularly notable features such as atrophy or hypertrophy of
smooth muscle cells. And the EC assessment was consistent with the results of
biopsy. There were no complications encountered in all the procedures.
CONCLUSION: In clinical setting, real time assessment of the MP is feasible by
using EC. It is expected that this technique will play an important role in unraveling the pathology of achalasia and other gastrointestinal functional diseases.
REFERENCES
1. Sumiyama K, Kiesslich R, Ohya TR, et al. In vivo imaging of enteric neuronal
networks in humans using confocal laser endomicroscopy. Gastroenterology
2012; 143: 1152-1153.
2. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy
(POEM) for esophageal achalasia. Endoscopy 2010; 42: 265-271.
Disclosure of Interest: None declared
P1020 AN INVESTIGATION OF GASTROESOPHAGEAL REFLUX
DISEASE AFTER PERORAL ENDOSCOPIC MYOTOMY (POEM):
CLINICAL RESULTS OF 40 CASES
H. Shiwaku1,*, K. Yamashita1, T. Sasaki1, R. Beppu1, H. Shimaoka1,
T. Ohmiya1, R. Nakashima1, S. Takeno1, S. Hoshino1, S. Nimura2, H. Inoue3,
Y. Yamashita1
1
Department of Gastroenterological Surgery, 2Department of pathology, Fukuoka
University Faculty of Medicine, Fukuoka, 3Digestive Disease Center, Showa
University Koto Toyosu Hospital, Tokyo, Japan
Contact E-mail Address: hiro.shiwaku@gmail.com
INTRODUCTION: POEM is a surgical procedure for esophageal myotomy
similar to Heller myotomy, the frequency and the degree of postoperative
reflux esophagitis are major outcomes that should be examined in the clinical
setting. The purpose of this study was to examine the incidence and degree of
reflux esophagitis after performing POEM, and to determine whether POEM
causes reflux esophagitis.

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United European Gastroenterology Journal 2(1S)


AIMS & METHODS: AIMS: POEM has shown promise in overcoming limitations of current treatments for achalasia. This prospective study examined the
effectiveness and risk of complications, especially reflux esophagitis, associated
with POEM performed on achalasia patients. METHODS: Patients with achalasia
were recruited from a single center where all POEM procedures were performed.
The pre- and postoperative (3 months after POEM) assessments included Eckardt
scores, manometry, endoscopy, and pH monitoring (Demeester score).
RESULTS: Forty patients (22 males; mean age, 46.216.1 years) underwent
POEM between September 2011 and June 2013. A significant reduction was
observed postoperatively in the lower esophageal sphincter pressure (from
39.016.5 mmHg to 18.611.0 mmHg [P50.05]) and Eckardt scores (from
6.32.6 to 0.60.8 [P50.05]). Four patients developed symptomatic gastroesophageal reflux disease (GERD; 3 patients, grade A; 1 patient, grade B). Twentyseven patients were diagnosed with erosive esophagitis (19 patients, grade A; 6
patients, grade B; 2 patients, grade C). Both erosive esophagitis and GERD were
well controlled with protein pump inhibitors intake without requiring surgery.
Univariate logistics regression analysis identified postoperative duration of reflux
(odds ratio [OR], 1.15; 95% confidence intervals [CI], 1.01-1.30) and Demeester
score (OR, 1.04; 95% CI, 1.00-1.08) as predictors of development of reflux
esophagitis (grade B). None of the POEM factors were found to be related
to reflux esophagitis.
CONCLUSION: POEM is safe and effective in providing symptomatic relief for
achalasia patients. Additionally, it is not associated with the development of
erosive esophagitis. Periodic postoperative interviews and endoscopic examinations are helpful in evaluating reflux esophagitis.
Disclosure of Interest: None declared
P1021 LIQUID VERSUS VISCOUS SWALLOWS IN HIGH RESOLUTION
IMPEDANCE MANOMETRY FOR THE EVALUATION OF PATIENTS
WITH DYSPHAGIA
I. Castel De Lucas1,*, C. Ciriza de los R os1,2, F. Canga Rodr guez Valcarcel1,2,
G. Castellano Tortajada1,2
1
gastroenterology, 2Hospital Universitario 12 de Octubre, Madrid, Spain
Contact E-mail Address: isabelcastel@yahoo.es
INTRODUCTION: Oesophageal high resolution impedance manometry
(HRiM) is an emerging tool used to assess oesophageal motility and function
though it measures the efficiency of oesophageal motility and bolus transit.
AIMS & METHODS: The aim of this study is to assess the changes in HRM
parameters and diagnosis as well as the bolus transit depending on the bolus type
in patients with dysphagia. 46 patients with dysphagia referred for oesophageal
function evaluation. All patients had upper endoscopy to exclude organic disease.
Oesophageal HRiM was also performed on all (Manoscan, Given) administering
ten liquid and ten viscous swallows in the supine position: The data were analyzed according to 2012 Chicago Classification criteria. Swallows were classified
as having complete bolus transit or incomplete bolus transit according to criteria
previously reported. Statistical analysis: Chi-Square or Fischer and T-test.
RESULTS: 18 male patients (39.1%), mean age 55.8 [39.9-71.5], mean BMI 25.9
[21.6-30.5]. HRiM parameters and diagnosis are expressed in the table. All
patients had dysphagia, also associated with chest pain in 6 patients (13%)
and heartburn in 4 (8.7%). 47.8 patients had pervious oesophageal treatment.
There were significant differences in DCI between liquid and viscous swallows
(2287.9 vs. 2718.1; p 0.001), and between complete bolus transit depending on
the bolus type (21.7% liquid swallows vs. 13% viscous swallows; p 0.002).
HRiM parameters
Liquid
IRP-4s (mmHg)
18.6 [16.2-21.1]
DCI (mmHg.cm.s)
2287.9 [1548.2-3027.6]
VFC (cm/s)
7.0 [4.7-9.3]
IBP (mmHg)
16.9 [14.9-19.7]
Complete bolus transit 10 (21.7%)
HRiM diagnosis (p 0.620)
Normal
13 (28.3%)
Oesophageal
33 (71.7%)
Motility Disorder

Viscous
19.9 [16.9-22.8]
2718.1 [1897.5-3538.7]
9.1[2.8-15.5]
20.3 [15.3-25.1]
6 (13%)

p
0.135
0.001
0.401
0.062
0.002

14 (30.4%)
32 (69,6%)

CONCLUSION: There were some changes in HRiM parameters depending on


the type of bolus consistency, but their involvement in final HRiM diagnosis was
not relevant, although complete bolus transit was more frequent with liquid
swallows. Therefore, viscous swallows are not discriminative enough compared
to liquid swallows for the diagnosis of patients with dysphagia.
Disclosure of Interest: None declared
P1022 PERORAL ENDOSCOPIC MYOTOMY: SAFE AND EFFECTIVE. A
PROSPECTIVE EVALUATION OF 40 CONSECUTIVE CASES
J. Martinek1,*, J. Spicak1, H. Svecova1, Z. Vackova1, E. Kieslichova2,
R. Dolezel3, R. Janousek4, A. Pazdro5, T. Roesch6
1
Hepatogastroenterology, 2Anesthesiology and Intensive Care, Institute for Clinical
and Experimental Medicine Prague, 3Surgery, Military University Hospital,
4
Radiology, Institute for Clinical and Experimental Medicine Prague, 5Surgery,
University Hospital Motol, Prague, Czech Republic, 6Interdisciplinary Endoscopy,
University Hospital Hamburg-Eppendorf, Hamburg, Germany
Contact E-mail Address: jan.martinek@volny.cz

INTRODUCTION: Peroral endoscopic myotomy (POEM) is an endoscopic


alternative to laparoscopic myotomy. This promising procedure is still considered experimental. Herein, we report single-center mid-term results of POEM in
the Czech Republic.
AIMS & METHODS: Since 2012, a total of 41 POEM procedures have been
performed in 40 patients (15 women, 25 men, mean age 45). All patients had a
diagnosis of achalasia (n 40) or Jackhammer esophagus (n 1) based on endoscopic, manometric and radiologic examinations. A 3, 6, and 12 months followup was completed in 33, 24 and 12 patients. The primary outcome was treatment
success defined as Eckhard score 5 3. At three months, high resolution manometry and 24-hour pH metry monitoring were performed.
RESULTS: A. PROCEDURE: POEM was successfully completed in all
patients. The median length of procedure was 80 minutes (range 43-145). The
median myotomy length was 13 cm (8-15). In 17 patients (42%), capnoperitoneum had to be decompressed and 19 patients (47%) experienced a subcutaneous
emphysema which resolved spontaneously. Fever was present on the first postoperative day in 6 patients (15%). We did not experience any serious intraoperative or postoperative complications and all patients were dismissed the 2nd or 3rd
postoperative day. We observed the following minor complications: inadvertent
mucosotomy 3x (treated with clips), respiratory instability during POEM 2x
(decompression of capnoperitoneum was necessary), bleeding at the entry site
1x, difficult entry site closure 2x (necessary to use high resolution clips) and large
subcutaneous emphysema 1x.
B. TREATMENT RESULTS: 3, 6 and 12 months after POEM, treatment success (Eckhard score 5 3) was achieved in 31, 24 and 12 patients (94%, 100%,
100%), median score pre- vs. post-treatment was 7 vs. 0 at 3 and 6 months, and
vs. 1 at 12 months; p50.001. The median percentage of overall symptomatic
improvement was 90%. Quality of live significantly improved (median score 107
before POEM vs. 130, 136 and 137 3, 6 and 12 months after POEM, p50.001).
Manometric parameters (IRP and LES pressure) normalized in a majority of
patients.
Heartburn was present in 7 (21%), 4 (17%) and 2 (17%) patients 3, 6 and 12
months after POEM. Eight patients (20%) have been treated with proton pump
inhibitors or antacids on demand. Three months after POEM, a mild reflux
esophagitis (LA A) was diagnosed in 10 patients (30%) and a pathological
gastro-esophageal reflux (DeMeester score 414) was detected in 16 (48%)
patients.
CONCLUSION: POEM is a safe and effective treatment modality in patients
with achalasia with excellent mid-term results which seems durable. There is
significant (though almost asymptomatic) reflux postoperatively in 48% of
patients in 3-months pH metry studies.
Supported by a grant form IGA NT-13634-4
Disclosure of Interest: None declared
P1023 PREVALENCE OF GERD IN
EROSION: CASE-CONTROL STUDY

PATIENTS

WITH

DENTAL

I. Martinucci1,*, N.de Bortoli1, C. Mannucci2, E. Savarino3, I. Tei2, L. Bertani1,


M. Furnari4, M. Bellini1, V. Savarino4, M.R. Giuca2, S. Marchi1
1
Gastroenterology Unit, 2Odontology Unit, University of Pisa, Pisa,
3
Gastroenterology Unit, University of Padua, Padua, 4Gastroenterology Unit,
University of Genoa, Genoa, Italy
Contact E-mail Address: martinucci.irene@gmail.com
INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the most
common gastrointestinal disorders in Western countries, affecting up to 20% of
the general population, with relevant impact on quality of life and health care
costs. Apart from the presence of more classic esophageal manifestations, GERD
is increasingly associated with extra-esophageal syndromes such as dental erosions (DE). DE is defined as the loss of tooth structure in connection with
environmental acidification in the oral cavity, without bacterial activity.
AIMS & METHODS: We aimed to evaluate the prevalence of GERD symptoms
in patients with DE. We enrolled 119 patients, who presented at the Dentistry
Unit to perform dental hygiene. During the visit, a distinct investigator completed a structured interview to the patients, including a careful medical history
and current medications. All patients underwent an accurate evaluation for DE
through a validated test: the Basic Erosive Wear Examination (BEWE).
Moreover, the presence of behavioral risk factors for DE was evaluated (i.e.,
consumption of acidic foods and drinks). All patients completed a validated
questionnaire (VAS and Likert scale) in order to assess the frequency and intensity of typical reflux symptoms (i.e., heartburn, regurgitation, non-cardiac chest
pain -NCCP-) in patients with (cases) and without (controls) DE.
RESULTS: Male/female ratio was 0.54 (44/77). Mean age was 48.214.5 yrs.
Twenty-three out of 199 patients (17.6%) showed DE clinical signs (BEWE41).
Eleven out of 119 patients (9.2%) had risk factors for DE, of whom only three
had DE. Reflux symptoms were more frequent in patients with DE (18/23;
78.3%) than in patients without DE (41/96; 42.7%) (p 0.001). In detail, regurgitation was reported in 14/23 (60.9%) (p50.001), and NCCP in 13/23 (56.5%)
(p50.001). Heartburn showed a similar prevalence between patients with DE
and controls but was more frequent (Likert scale; p 0.001) and more intense
(VAS; p 0.001) in DE subgroup. Neither patients with DE or patients with
positive reflux-symptom questionnaire had ever undertaken PPI therapy. No
patients undertaking PPI therapy had DE.
CONCLUSION: Patients with DE showed more frequent and troublesome
reflux symptoms than controls without DE. During dental hygiene, patients
with DE should be allowed to complete a GERD questionnaire to better identify
those with reflux symptoms.
REFERENCES
Picos A, Chisnoiu A and Dumitrasc DL. Dental erosion in patients with gastroesophageal reflux disease. Adv Clin Exp Med Off Org Wroclaw Med Univ 2013;
22: 303-307.

A414
Disclosure of Interest: I. Martinucci: None, N. de Bortoli: None, C. Mannucci:
None, E. Savarino: None, I. Tei: None, L. Bertani: None, M. Furnari: None, M.
Bellini: None, V. Savarino: None, M. Giuca: None, S. Marchi: None
P1024 THE RELATIONSHIP
BETWEEN
GASTROESOPHAGEAL
REFLUX DISEASE AND ATRIAL FIBRILLATION
J.J. Hwang1,*, D.H. Lee1, K.C. Yoon1, H.J. Lee1, Y. Jeong1, A.-R. Lee1,
Y.H. Kwon1, H. Yoon1, C.M. Shin1, Y.S. Park1, N. Kim1, S.Y. Seol2
1
Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
2
Internal Medicine, Inje University Paik Hospital, Busan, Korea, Republic Of
Contact E-mail Address: frontierassa@hanmail.net
INTRODUCTION: Gastroesophageal reflux disease (GERD) and atrial fibrillation (AF) are common diseases, but the relationship between these two diseases
remains controversial. Previous studies suggest a potential association between
GERD and AF. We aimed to investigate the association between GERD and
AF.
AIMS & METHODS: This was a retrospective study created from chart review
for patients who newly diagnosed by GERD or AF between January 1, 2011 and
March 31, 2014. Patients were classified by two groups. The patients who diagnosed by newly GERD with presence of AF were classified by Group-1 (n 129),
the patients who diagnosed by newly AF with presence of GERD were classified
by Group-2 (n 134). We analyzed the association and risk factors between two
groups.
RESULTS: The average age of two group were 69.3  10.6 years / 73.5  9.5
years (p 0.001). The duration of diagnosis between GERD and AF were 40.1 
37.4 months / 44.5  33.4 months (p 0.32). In univariate and multivariate
analysis, age, alcohol, underlying coronary artery disease, sustained arrhythmia,
chronic obstructive pulmonary disease (COPD), hyperthyroidism, use of ACE
inhibitor, B-blocker and warfarin were related to incidence of GERD in Group-1
(p 5 0.05). COPD and proton pump inhibitor (PPI) were related to incidence of
newly AF in Group-2 (p 5 0.01). The presence of AF increased the relative risk
(RR) of GERD (RR: 1.37, 95% confidence interval [CI]: 1.33-1.47), and the
presence of GERD increased the risk of AF (RR: 1.12, 95% CI: 1.08-1.19).
CONCLUSION: GERD and AF were significantly associated with an increased
risk of diagnosis of each other. The presence of AF increased the relative risk
(RR) of GERD (RR: 1.37, 95% CI: 1.33-1.47), and the presence of GERD
increased the risk of AF (RR: 1.12, 95% CI: 1.08-1.19). A large cohort study
to assess the potential relationship between GERD and AF is needed.
Disclosure of Interest: None declared
P1025 QUALITY OF LIFE, PATIENT SATISFACTION, AND DISEASE
BURDEN IN PATIENTS WITH GASTROESOPHAGEAL REFLUX
DISEASE WITH OR WITHOUT LARYNGOPHARYNGEAL REFLUX
SYMPTOMS
K.D. Choi1,*, H.-K. Jung2, Y.H. Yoon3, B.-H. Min4, K.H. Song5, K.C. Huh5
1
Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine,
2
Internal Medicine, Ewha Womans University School of Medicine, 3Internal
Medicine, Yonsei University College of Medicine, 4Medicine, Sungkyunkwan
University School of Medicine, Seoul, 5Internal Medicine, Konyang University
College of Medicine, Daejeon, Korea, Republic Of
Contact E-mail Address: keedon@amc.seoul.kr
INTRODUCTION: Patients with gastroesophageal reflux disease (GERD) have
lower health-related quality of life (HRQL) than general population. Increasing
frequency and severity of reflux symptom has negative impact on well-being.
HRQL in patients with laryngopharyngeal reflux (LPR) is also significantly
impaired. However, study comparing HRQL in GERD patients with and without LPR symptoms is rare.
AIMS & METHODS: The aim of the study was to compare HRQL, patient
satisfaction, and disease burden in GERD patients with and without LPR symptoms. A national, random-sample, and face-to-face survey of 300 Koreans was
conducted. The sampling frame was based on the previous national wide, population-based telephone survey, in terms of distribution of age, gender, occupation, and region of residence by quota sampling. Gastroesophageal reflux
symptoms were assessed by the Rome III questionnaire, LPR symptoms by
reflux symptom index (RSI), and the quality of life by EuroQol-5 dimension
questionnaire (EQ-5D). Structured questionnaire on health service utilization,
sickness-related absence, and patient satisfaction were also used.
RESULTS: Face to face interview was conducted from Jan to Mar 2013 in 300
subjects (141 male, 159 female, Mean age 43.512.6, GERD without LPR,
n 150, GERD with LPR, n 150). Median RSI in patients with GERD and
LPR was 19.5 (14-36). Mean EQ-5D index was lower in GERD patients with
LPR than GERD patients without LPR (0.88 vs. 0.91, p 0.002). GERD
patients with LPR reported more problems in pain/discomfort (58.7% vs.
47.8%, p 0.049), and anxiety/depression dimensions (39.3% vs. 22.0%,
p 0.001). Severity of LPR was related with HRQL when adjusted for age,
gender, marital status, BMI, severity of GERD, household income and comorbidity. GERD patients with LPR have lower overall satisfaction (40.0% vs.
69.1%, p 0.040). Satisfaction scores were lower in GERD patients with LPR:
satisfaction with physicians concern (3.5 vs 3.9, p 0.002), physicians professional knowledge (3.5 vs 3.9, p 0.005), physicians explanation (3.5 vs 3.9,
p 0.003), medical cost (3.3 vs 3.7, p 0.003), and treatment outcomes (3.1 vs
3.5, p 0.005). There were no significant differences in the patterns of health
service utilization between two groups. GERD patients with LPR reported
longer sickness related absent hour per week (0.371.43 vs. 0.020.20,
p 0.016), and poorer work productivity score (3.082.28 vs. 2.081.72,
p 0.001).

United European Gastroenterology Journal 2(1S)


CONCLUSION: GERD patients with LPR have lower HRQL than GERD
patients without LPR, and the severity of LPR was related with decreased
HRQL. GERD patients with LPR have lower satisfaction with physician, medical cost, and treatment outcomes. The economic burden seems to be higher in
GERD patients with LPR in terms of increased loss of work and decreased
productivity.
Disclosure of Interest: None declared
P1026 NO INCREASE IN GASTRIC ACID SECRETION IN THE
JAPANESE OVER PAST TWO DECADES
N. Ishimura1, Y. Owada2, M. Aimi1,*, T. Oshima3, T. Kamada4, K. Inoue5,
H. Mikami1, T. Takeuchi6, H. Miwa3, K. Higuchi6, Y. Kinoshita1
1
Department of Gastroenterology and Hepatology, Shimane University School of
Medicine, Izumo, 2Osaka Pharmacology Clinical Research Hospital, Osaka,
3
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of
Medicine, Nishinomiya, 4Division of Gastroenterology, Department of Internal
Medicine, 5Department of General Medicine, Kawasaki Medical School, Kurashiki,
6
Second Department of Internal Medicine, Osaka Medical College, Takatsuki,
Japan
Contact E-mail Address: ishimura@med.shimane-u.ac.jp
INTRODUCTION: The prevalence of gastro-oesophageal reflux disease
(GORD) has been increasing worldwide over recent decades. Although the prevalence was considered to be lower in Asia, GORD has become more prevalent in
Asia including Japan [1, 2]. A previous study demonstrated that gastric acid
secretion in Japanese individuals increased in the era from the 1970s to 1990s
[3]. That increased secretion is thought to be one of the important factors for the
increase in rate of GORD. However, it remains to be elucidated whether that
increasing trend has continued from the 1990s to the present.
AIMS & METHODS: The aim of this study was to evaluate whether gastric acid
secretion has altered over the past 2 decades with and without the influence of H.
pylori infection in non-elderly and elderly Japanese.
Seventy eight healthy Japanese subjects were enrolled, and divided into those
aged between 20 and 25 (young group), around 50 (non-elderly group), and
around 75 (elderly group) years old. Gastric acid secretion, concentrations of
serum gastrin and pepsinogen I and II, and H. pylori infection were determined in
each case, and the data were compared among the groups. Furthermore, those
findings were compared with data obtained in the 1990s.
RESULTS: Basal acid output (BAO) and maximal acid output (MAO) gradually
decreased with age even in H. pylori-negative subjects. In addition, those with H.
pylori infection tended to show decreased gastric acid secretion as compared with
those without infection, particularly in the elderly group. Consistently, serum
gastrin concentration was significantly higher in the elderly as compared to
non-elderly subjects. As for sex difference, MAO decreased gradually with age
in males, while it remained unchanged with age in females. Interestingly, gastric
acid secretion has not changed over the past 2 decades in Japanese individuals
irrespective of the presence of H. pylori infection.
CONCLUSION: In contrast to the increased prevalence of GORD, gastric acid
secretion has not increased over the past 2 decades in the Japanese as a whole. On
the other hand, secretion has decreased with age in males but not in females,
which may partly explain the female preponderance of GORD in the Japanese
elderly.
REFERENCES
1. Ronkainen J and Agreus L. Epidemiology of reflux symptoms and GORD.
Best Pract Res Clin Gastroenterol 2013; 27: 325-337.
2. Kinoshita Y, Adachi K, Hongo M, et al. Systematic review of the epidemiology of gastroesophageal reflux disease in Japan. J Gastroenterol 2011; 46: 10921103.
3. Kinoshita Y, Kawanami C, Kishi K, et al. Helicobacter pylori independent
chronological change in gastric acid secretion in the Japanese. Gut 1997; 41: 452458.
Disclosure of Interest: N. Ishimura: None declared, Y. Owada: None declared,
M. Aimi: None declared, T. Oshima: None declared, T. Kamada: None declared,
K. Inoue: None declared, H. Mikami: None declared, T. Takeuchi: None
declared, H. Miwa: None declared, K. Higuchi Consultancy for: AstraZeneca
K. K., DAIICHI SANKYO HEALTHCARE CO., LTD., Esai. Co.,Ltd., Other:
DAIICHI SANKYO HEALTHCARE CO., LTD., Astellas Pharma Inc.,
Mitsubishi Tanabe Pharma Corporation, Y. Kinoshita: None declared
P1027 PREDICTIVE FACTORS OF SILENT REFLUX IN SUBJECTS
WITH EROSIVE ESOPHAGITIS
W.-Y. Lei1,*, C.-L. Chen1, H.-C. Yu1, T.-T. Liu1, C.-H. Yi1
1
Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical
Foundation, Hualien, Taiwan, Province of China
Contact E-mail Address: Aquarious@seed.net.tw
INTRODUCTION: Gastroesophageal reflux disease (GERD) is a chronic disease which can cause troublesome symptoms. Asymptomatic erosive esophagitis
(AEE) is a subgroup of patients with a lack in any symptom. The purpose of the
study was to investigate the prevalence of AEE in a large population undergoing
health checkups and to identify the predictive factors for the disease.
AIMS & METHODS: From March 2012 to August 2013, 2752 consecutive
subjects who underwent upper gastrointestinal endoscopy during health checkup
were enrolled. The severity of erosive esophagitis was evaluated according to the
Los Angeles classification. A GERD subject was defined as any individual who
has a diagnosis of endoscopic LA grade=A or Barretts esophagus or having
troublesome symptoms as identified by Reflux Disease Questionnaire (RDQ)
score. All participants were recorded with demographic characteristics, biochemical data, and evaluated with questionnaires including Pittsburgh Sleep Quality

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United European Gastroenterology Journal 2(1S)


Index (PSQI) score, Taiwanese Depression Questionnaire (TDQ) score, and
State-Trait Anxiety Inventory (STAI) score. The independent predictive factors
for asymptomatic erosive esophagitis were analyzed by the logistic regression
method.
RESULTS: A total of 676 GERD subjects with erosive esophagitis (EE) were
recruited for final analysis, and about 59.2% of subjects with EE had no reflux
symptoms. In the univariate analysis, subjects with AEE have more female
gender, older age, lower level of education, less alcohol and tea consumption,
less depression, less anxiety, lower serum level of triglyceride, and lower prevalence of metabolic syndrome, compared with subjects with symptomatic EE.
Multivariate analysis revealed that female sex (OR 1.645, p 0.0146) was a
positive predictive factor for AEE, and higher level of education (OR: 0.564,
p 0.044), higher TDQ score (OR: 0.922, p 50.001), and with the metabolic
syndrome (OR: 0.625, p 0.0379) were significant negative predictive factors
for AEE.
CONCLUSION: Asymptomatic erosive esophagitis is common in subjects
undergoing health checkup. Female sex, lower education level, less depression,
and lower prevalence of metabolic syndrome are independent predictive factors
for developing asymptomatic erosive esophagitis, compared with symptomatic
erosive esophagitis.
REFERENCES
1. Cho JH, Kim HM, Ko GJ, et al. Old age and male sex are associated with
increased risk of asymptomatic erosive esophagitis: analysis of data from local
health examinations by the Korean National Health Insurance Corporation. J
Gastroenterol Hepatol 2011; 26: 1034-1038.
2. Wang PC, Hsu CS, Tseng TS, et al. Male sex, hiatus hernia, and Helicobacter
pylori infection associated with asymptomatic erosive esophagitis. J
Gastroenterol Hepatol 2012; 27: 586-591.
3. Lee D, Lee KJ, Kim KM, et al. Prevalence of asymptomatic erosive esophagitis and factors associated with symptom presentation of erosive esophagitis.
Scand J Gastroenterol 2013; 48: 906-912.
Disclosure of Interest: None declared
P1028 IS PH IMPEDANCE MORE USEFUL THAN TRADITIONAL PH
MONITORING FOR PATIENTS MANAGEMENT IN CLINICAL
PRACTICE? RESULTS OF A PROSPECTIVE STUDY
D. Pugliese1,*, A. Mauro1, D. Consonni2, I. Bravi1, A. Tenca1, A. Elvevi1,
D. Conte1, R. Penagini1
1
Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca Granda Ospedale
Maggiore Policlinico and Department of Pathophysiology and Transplantation
Universita` degli Studi di Milano, 2Epidemiology Unit - Department of Preventive
Medicine, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan,
Italy
Contact E-mail Address: delia.pugliese@unimi.it
INTRODUCTION: Oesophageal pH tests are deemed to be useful in management of selected gastro-oesophageal reflux (GOR) disease patients. Development
of pH impedance (pH-MII) tests has increased the diagnostic yield by documenting the role of weakly acidic refluxes. However to which extent results of pH-MII
tests improve patients management is largely unknown.
AIMS & METHODS: Aim of our study was to prospectively evaluate usefulness
of pH MII monitoring in the patients clinical management compared with traditional pH monitoring. One hundred and eighty four consecutive patients (72
men, median age 52, range 19-82 yrs) were enrolled for traditional pH or pHMII monitoring. A telephone interview was done 3 and 12 months after the test.
A standardized questionnaire was used in the visit before the test and in the
telephone interviews, dealing with improvement ( 50% reduction of symptom
frequency) of the dominant symptom, patients satisfaction with regards to the
dominant symptom (1-10 visual analogue scale, satisfied if VAS  7) and treatment for GOR disease. Nineteen patients were lost at follow up at the 12 month
interview. Indications of pH and pH-MII test were evaluated for appropriateness1. Mann-Whitney or Krusal-Wallis tests for comparison of quantitative variables and chi-square test for categorical variables were used.
RESULTS: Demographic and endoscopic variables, frequency of previous PPI
use were similar in the two arms. Thirty-nine (42.4%) of the pH tests and 34
(37.0%) of the pH-MII tests were positive for GOR disease (pathological GOR
and/or positive symptom association probability [SAP]); in the pH-MII arm 10
patients had an increased number of weakly acid refluxes and/or a positive SAP
for weakly acid reflux whereas their acid reflux variables were normal/negative.
See table for main outcome results. Outcomes were similar for tests with appropriate and those with inappropriate indication (p NS) in both arms. After the
test, as assessed at the 3 months interview, treatment for GOR disease (PPIs
except in one pH-MII arm patient who underwent fundoplication) was undertaken in 87.2% of positive, 59.1% of indeterminate (i.e. normal GOR and no
symptomatic episodes during the test), and 35.5% of negative tests in the pH
arm, and in 97.1% of positive, 47.6% of indeterminate and 54.1% of negative
tests in the pH-MII arm (p50.001 among groups in both arms).

pH tests
pH-MII tests
p-value

positive outcome*

satisfaction#

3 months

12 months

3 months

12 months

53/92 (57.6%)
58/92 (63.0%)
0.621

52/79 (65.8%)
60/86 (69.8%)
0.234

47/92 (51.1%)
45/92 (48.9%)
0.768

43/79 (54.4%)
49/86 (57.0%)
0.225

CONCLUSION: Patients outcome and satisfaction were similar in the two arms
and independent of the appropriateness of test indication. Although PPI

prescription was more frequent after a positive pH or pH MII monitoring, physicians often did not take into account a negative result. Our data cast doubts on
the added value of pH MII monitoring for patients management in clinical
practice.
REFERENCES
1. Hirano I, Richter JE and the Practice Parameters Committee of the American
College of Gastroenterology. ACG practice guidelines: esophageal reFux testing.
Am J Gastroenterol 2007; 102: 668685.
Disclosure of Interest: None declared
P1029 ROLE OF GASTRO-OESOPHAGEAL REFLUX IN SYMPTOMS
GENERATION AND PROTON PUMP INHIBITORS USE AMONG
PATIENTS WITH AUTOIMMUNE ATROPHIC CHRONIC
GASTRITIS: A STUDY WITH OESOPHAGEAL PH-IMPEDANCE
MONITORING
A. Tenca1, D. Pugliese1,*, S. Massironi1, M. Franchina1, M. Spampatti1,
D. Conte1, R. Penagini1
1
Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca Granda Ospedale
Maggiore Policlinico and Department of Pathophysiology and Transplantation
Universita` degli Studi di Milano, Milan, Italy
Contact E-mail Address: delia.pugliese@unimi.it
INTRODUCTION: Patients affected by autoimmune atrophic chronic gastritis
(AACG) often refer digestive symptoms and are prescribed proton pump inhibitors (PPIs). No data are available on the role of gastro-oesophageal reflux
(GOR) in clinical presentation and on the appropriateness of anti-secretory
drugs prescription.
AIMS & METHODS: Aims of this prospective observational study were to
investigate GOR, psychopathological profile and frequency of use/response to
anti-secretory medications (PPIs and H2 receptor antagonists [H2RA]) in patients
with AACG.
All patients affected by AACG with or without digestive symptoms and in regular follow-up at our hospital who were seen between January 2013 and
December 2013 (n 51) were asked to participate to this study. The study protocol included: (i) 24h intra-oesophageal and intra-gastric pH impedance monitoring (MII-pH) off-PPIs; median intragastric pH, number of acid and weakly
acidic (WA) reflux as well as of Symptom Index (SI) and Symptom Association
Probability (SAP) were calculated, (ii) a validated questionnaire evaluating psychopathological profile (SCL-90R) and (iii) a standardized clinical questionnaire
including items on anti-secretory medications use/response.
RESULTS: Baseline characteristics. Thirty-one of the 51 patients agreed to be
investigated, 4 men, median age 60, range 29-78 yrs. Twenty-two of them (71%)
were symptomatic: n 12 symptoms suggestive of GOR (i.e. heartburn, epigastric burning, regurgitation, non cardiac chest pain) and n 10 dyspeptic symptoms. MII-pH. Median intragastric pH was 6.3 (IQR 5.8-6.8). None of the
patients had acid reflux. Six patients had an increased number of WA reflux
episodes (3 with GOR symptoms, 2 with dyspeptic symptoms and 1 asymptomatic according to our clinical questionnaire) and 4 additional patients had SI
and/or SAP positive for WA reflux and GOR symptoms (n 2) or epigastric pain
(n 2). SCL-90R questionnaire. Altered somatisation (defined as t-score  63)
was present in 11/22 (50%) symptomatic patients and 3/9 (33%) asymptomatic
patients (p 0.40 by Chi-Square Test). Focusing on symptomatic patients,
altered somatisation was similarly present in those with increased WA reflux
or positive SI/SAP and in those without, n 4/9 (44%) and n 7/13 (54%),
respectively. Anti-secretory drugs were prescribed in 13/22 (59%) symptomatic
patients (PPIs in 12 and H2RA in 1). A clinical benefit was reported by 8/13
patients, increased WAR being present in 2 of them and altered somatisation in
5.
CONCLUSION: In symptomatic patients with AACG: 1) acid reflux never
occurred whereas increased WA reflux was not infrequent, 2) PPIs were often
used, however their clinical benefit seemed to be more associated with altered
somatizations than with objective variables suggesting GOR as cause of patients
symptoms and 3) MII-pH may be useful to diagnose GOR disease in a minority
with severe symptoms who could benefit from anti-reflux surgery.
Disclosure of Interest: None declared
P1030 ESOPHAGOGASTRIC JUNCTION MORPHOLOGY MAY BE
USEFUL TO PREDICT A POSITIVE IMPEDANCE-PH
MONITORING IN PATIENTS WITH GERD
E. Savarino1,*, C.de Cassan1, F. Galeazzi1, R. Salvador1, E. Marabotto2,
M. Furnari2, P. Zentilin2, N.de Bortoli3, S. Marchi3, R. Bardini1,
G.C. Sturniolo1, V. Savarino2
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, 2Department of Internal Medicine, University of Genoa, Genoa,
3
Department of Internal Medicine, University of Pisa, Pisa, Italy
INTRODUCTION: High-resolution manometry (HRM) provides a better representation of the esophagogastric junction (EGJ) making it possible to isolate the
crural diaphragm (CD) contraction from expiratory lower esophageal sphincter
(LES) pressure. According to the Chicago Classification (CC), three different
EGJ morphologic subtypes can be detected based on the separation between
the LES and the CD. Recently, these EGJ subtypes have been positively correlated with the objective evidence (i.e. endoscopy or pH-metry) of gastroesophageal reflux disease (GERD). To date, data on the correlation between
EGJ subtypes and esophageal acid exposure as well as impedance-detected
reflux episodes are lacking.
AIMS & METHODS: We aimed to correlate the different EGJ subtypes with
impedance-pH findings in GERD patients. Consecutive patients with heartburn
and/or regurgitation and a recent endoscopic assessment were enrolled. All

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patients underwent a 36-Solid State HRM with a 5-min baseline recording to


assess the EGJ and 10 single water swallows (5 mL) at 30-s intervals to evaluate
the esophageal peristalsis and EGJ function. The tracings were analyzed based on
the CC for motility disorders and each EGJ was classified as: Type I, no separation between the LES and the CD; Type II, minimal separation (41 and 52 cm)
between the LES and the CD; Type III, 42 cm separation between the LES and
the CD. The patients also underwent impedance-pH testing off-therapy. We
measured esophageal acid expsosure time (AET), total number of impedancedetected reflux episodes and symptom-reflux association using symptom association probability (SAP if 95%) and symptom index (SI if 50%).
RESULTS: We enrolled 53 [28M/25F; mean age 53 (21-76)] consecutive GERD
patients. At upper endoscopy, 12 patients had erosive esophagitis, 2 had Barrett
esophagus and 39 had no mucosal breaks. Based on CC, we identified 21 (40%)
patients with Type I EGJ, 19 (36%) with Type II EGJ and 13 (24%) with Type
III EGJ. Patients with Type III EGJ had an higher median number of reflux
episodes [61 (12-305) vs. 38 (4-109) vs. 30 (6-98), respectively; p50.01)], a greater
mean AET [20.6 (4.4-43.4) vs. 14.1 (0.2-48.3) vs. 11.9 (0.1-54.3), respectively;
p50.01)] and had more frequently a positive symptom-reflux association [9
(69%) vs. 9 (47%) vs. 11 (52%), respectively; p50.05)] compared to patients
with Type II and Type I EGJ. Moreover, patients with Type II EGJ tended to
have a higher median number of reflux episodes and mean AET compared to
patients with Type I EGJ, but statistically significance was not reached (p 0.06).
CONCLUSION: With increasing separation between the LES and CD, from
Type I to Type III EGJ, patients had a gradual and significant increase of
reflux episodes and esophageal acid exposure. Thus, EGJ morphology may be
useful to predict an abnormal impedance-pH testing in patients with GERD.
Disclosure of Interest: None declared
P1031 CLINICAL
AND
ENDOSCOPIC
FEATURES
GASTROESOPHAGEAL REFLUX DISEASE IN PATIENTS WITH
CHRONIC OBSTRUCTIVE PULMONARY DISEASE

OF

E. Kostiakova1,*
1
endoscopy, Clinical Hospital 1, Smolensk, Russian Federation
Contact E-mail Address: katyalimova@yandex.ru
INTRODUCTION: According to the literature data, up to 37 % of patients with
chronic obstructive pulmonary disease (COPD) suffer from gastroesophageal
reflux disease (GERD) [Hom C., et al., 2013], which is higher than in general
population (10-20%) [Gadel A. A. et al., 2012]. However, despite the obvious
relationship between these pathological conditions, investigators are still looking
for risk factors associated with GERD development and progression in COPD
patients.
AIMS & METHODS: Aim was to establish clinical, endoscopic and chromoendoscopic features of GERD in COPD patients in association with inhalation
corticosteroid treatment. The study involved 75 patients with COPD, 50 of
them received inhalation corticosteroid treatment and 25 received no inhalation
corticosteroid treatment. The comparison group covered 65 patients without
COPD. Esophagogastroduodenoscopy was performed with the endoscope
Pentax 290. In esophagoscopy a dye congo red changing its color in acid
medium from red into blue-black was injected through a spray-catheter at a
maximal air insufflation in the lower third portion of the esophagus. This property of congo red can be used to diagnose acid gastroesophageal reflux. The
affected area was calculated with the formula 2 rhK (r is a radius of esophagus
abdominal part equal to 1 cm, h is a length of the affected area from Z-line in cm,
K is a coefficient of staining fullness measured as 1, 3/4, 1/2, 1/4).
Statistical analysis was made with the software package Statistica 7.0 (StatSoft,
USA) using nonparametric criteria. Statistical significance was considered at p
value less than 0.05.
RESULTS: COPD patients complained of heartburn, acid regurgitation and
dysphagia rarely in relation to the comparison group (14.7% and 35.4%,
2 8.13; p 0.004). However, erosive esophagitis (66.7% and 9.2%,
2 36.6; p50.001), and well known risk factors for the development of
GERD, such as cardioesophageal relaxation (65,6% and 7,8%; 2 43,43,
p50.001) and hiatal hernia (p 0.011) were more frequently observed in patients
with COPD. It is worth mentioning that Grade 2 of erosive esophagitis was
detected only in patients receiving inhalation corticosteroid treatment (24%
and 0%, p 0.005). Presence of esophagitis (r 0,85; p50.001) had a direct
correlation with the congo red color changing in the main group. The affected
area of esophagus in the main group was 6,38 cm2 [3,14-8,38], in comparison
group the size of the area was 2,36 cm2 [1,57-3,14] (p50.001)] and in COPD
patients receiving inhalation corticosteroid treatment it was 6,38 cm2 [2,36-9,42]
(4.71 cm2 [4,71-6,28] in COPD patients receiving no inhalation corticosteroid
treatment, p 0.041). Esophagitis grade in COPD patients had a direct correlation with the extension of the affected area (r 0,75, p50.001).
CONCLUSION: In spite of the unmarked clinical picture GERD in a form of
erosive esophagitis, induced by the acid gastroesophageal reflux, is more frequently seen in COPD patients. Grade 2 of erosive esophagitis is typical for
patients receiving inhalation corticosteroid treatment. Extension of the affected
esophageal area is a valid criterion for the quantitative assesment of the pathological acid gastroesophageal reflux in patients with COPD.
Disclosure of Interest: None declared

P1032 OESOPHAGEAL INTRALUMINAL BASELINE IMPEDANCE


LEVELS IN PATIENTS WITH NON-EROSIVE REFLUX DISEASE
AND IN PATIENTS WITH SYSTEMIC SCLEROSIS
P. Zentilin1,*, E. Marabotto1, G. Murdaca2, E. Savarino3, V. Savarino4
1
Department of Internal Medicine, Gastroenterolgy Unit, 2Department of Internal
Medicine, Internal Medicine Unit, Genova, 3Departement of Surgery, Oncology
and Gastroenterology, Gastroenterology Unit, Padova, 4Department of Internal
Medicine, Gastroenterology Unit, Genova, Italy
Contact E-mail Address: pzentilin@unige.it
INTRODUCTION: Oesophageal intraluminal baseline impedance (BI) levels are
determined by the conductivity of the oesophageal wall. Patients with non-erosive reflux disease (NERD) showed decreased distal oesophageal BI levels compared to healthy controls and this finding has been correlated to the presence of
abnormal distal oesophageal acid exposure time (AET) in them. On the other
hand, no differences have been found in the proximal esophagus probably due to
the lower amount of acid reflux arriving at the most proximal sites. Systemic
sclerosis (SSc) is a clinically heterogeneous and systemic disease characterized by
deposition of collagen and other extracellular matrix proteins in the connective
tissue of the skin and visceral organs, such as the gastrointestinal tract. This event
could potentially affect the conductivity of the oesophageal wall and consequently BI levels, but data in this regard are lacking.
AIMS & METHODS: We aimed to prospectively investigate and compare BI
levels between NERD and SSc patients. Consecutive patients with typical reflux
symptoms (i.e. heartburn and/or regurgitation) and those with a defined diagnosis SSc underwent upper endoscopy in order to assess the presence of oesophageal mucosal lesions. Then, within 3 days from endoscopy, all endoscopynegative patients underwent oesophageal manometry and impedance-pH testing
off-therapy. During blinded and manual analysis of impedance-pH tracings, we
evaluated esophageal AET, reflux episodes (acid/weakly acidic), symptom-reflux
association using both symptom association probability (SAP if 95%) and
symptom index (SI if 50%) and BI values at 3, 5 and 17cm above the LES,
during the overnight rest, for at least 30 minutes after excluding swallows and
reflux induced changes. NERD were diagnosed in case of abnormal AET and/or
positive symptoms-reflux association.
RESULTS: Thirty patients with NERD and 30 with SSc were enrolled. Among
SSc patients, 10/30 (33%) had an abnormal AET and 20/30 (67%) showed a
normal. Among NERD patients, 14 (57%) had a pathological AET and 16/30
(53%) showed a normal acid exposure. In patients with SSc, median (25th-75th)
BI impedance was 961.3 (734.3-1610.8)  at 3cm, 1114.9 (845.4 to 1512.7)  at 5
cm, and 2222.4 (1511.6 to 2734.3)  at the most proximal impedance recording
site. All these BI values were lower than those observed in NERD patients, not
only in the distal esophagus [at 3cm 1409.2 (1264.1 to 2118.6) , p 0.0065; at 5
cm 1650.1 (1228.4 to 2266.4) , p 0.0054], but also in the proximal esophagus
[at 17cm 2678.7 (2183.0 to 3309.1) , p 0.0736].
CONCLUSION: Despite the lower median AET and percentage of patients with
abnormal AET, all BI values in SSc patients were lower than in NERD patients,
suggesting that BI levels are related not only to oesophageal AET, but also to
oesophageal tissue damage SSc-related. This finding is further corroborated by
the differences observed at the proximal oesophagus. Thus, BI levels may be used
as indirect markers of alteration of the oesophageal wall and, therefore, of oesophageal involvement in patients with SSc.
Disclosure of Interest: None declared
P1033 EVALUATION OF SLEEP DISRUPTIONS BY MEANS OF
IMPEDANCE-PH MONITORING IN PATIENTS WITH NERD
I. Martinucci1,*, N.de Bortoli1, E. Savarino2, R. Tutuian3, L. Bertani1,
R. Franchi1, R. Salvatore1, M. Furnari4, M. Bellini1, V. Savarino4, S. Marchi1
1
Gastroenterology Unit, University of Pisa, Pisa, 2Gastroenterology Unit,
University of Padua, Padua, Italy, 3Gastroenterology Unit, Hospital of Bern, Bern,
Switzerland, 4Gastroenterology Unit, University of Genoa, Genoa, Italy
Contact E-mail Address: martinucci.irene@gmail.com
INTRODUCTION: Gastroesophageal reflux disease (GERD) adversely impacts
on sleep, representing a major cause of disrupted sleep mainly due to reflux
symptoms. This may lead to an impaired quality of life. Impedance and pH
monitoring (MII-pH) is the gold standard technique for GERD diagnosis.
During the sleep period, impedance values remain stable unless the occurrence
of arousals.
AIMS & METHODS: We aimed to evaluate sleep disruptions in patients with
heartburn and negative endoscopy by means of MII-pH. A group (33) of endoscopy negative patients with heartburn underwent MII-pH and were classified
accordingly: 18 with non-erosive reflux disease (NERD) (i.e., pathological acid
exposure time, AET); 15 with functional heartburn (FH) (i.e., normal AET and
reflux number, negative symptom association). MII-pH tracings were reviewed
manually using a 5-min window. During recumbent time, we identified sleep
disruptions when at least 2 swallows were observed in a 5-min window. This
data was evaluated in each group. We also calculated the overnight swallowing
breaking sleep (OSBS) index (i.e., number of windows with swallows/total
number of 5-min windows during the sleep period). All patients performed a
validated questionnaire to assess the quality of sleep.
RESULTS: Male/female ratio was 7/11 in NERD and 3/12 in FH patients. Mean
age was 51.312.4 in NERD and 49.39.7 in FH. The quality of a restful sleep
was 64.38.3% in NERD and 67.37.8% in FH (p 0.299). Mean AET was
higher in NERD (5.40.4) than in FH (0.40.4) (p50.05). NERD group
recorded higher total reflux number and acid reflux number (p50.05). The
total recumbent time was 541.464.7 min in NERD and 547.359.3 min in
FH (p 0.39). During the sleep period, NERD patients recorded higher reflux
number (9.88.7) than FH patients (0.60.9) (p50.05). Moreover, the total

A417

United European Gastroenterology Journal 2(1S)


number of 5-min windows presenting at least 2 swallows was higher in NERD
patients (49.7 6.4) compared to those with FH (27 5.3; p50.01). The OSBS
index was 46.24.0 in NERD and 25.35.5 in FH (p 0.023).
CONCLUSION: The manual analysis of the MII-pH tracings during the recumbent period might be useful to estimate sleep disruptions in patients with NERD,
thus helping to identify those patients in whom GERD is perceived more severe
and quality of life is much more impaired.
REFERENCES
1. Dent J, Holloway RH and Eastwood PR. Systematic review: relationships
between sleep and gastro-oesophageal reflux. Aliment Pharmacol Ther 2013;
38: 657-673.
2. Pohl D, Arevalo F, Singh E, et al. Swallowing activity assessed by ambulatory
impedance-pH monitoring predicts awake and asleep periods at night. Dig Dis
Sci 2013; 58: 1049-1053.
Disclosure of Interest: I. Martinucci: None, N. de Bortoli: None, E. Savarino:
None, R. Tutuian: None, L. Bertani: None, R. Franchi: None, R. Salvatore:
None, M. Furnari: None, M. Bellini: None, V. Savarino: None, S. Marchi: None
P1034 BASAL
CELL
HYPERPLASIA
AND
DILATION
OF
INTERCELLULAR SPACES ARE THE MAIN HISTOLOGIC
FEATURES ASSOCIATED TO THE ENDOSCOPIC/IMPEDANCE-PH
DIAGNOSIS OF GERD AND ITS RELATED MUCOSAL INTEGRITY
IMPAIRMENT
M. Furnari1,*, N.de Bortoli2, P. Zentilin1, S. Marchi2, L. Mastracci3,
E. Marabotto1, I. Martinucci4, V. Savarino1, E. Savarino5
1
Di. M. I., Gastroenterology Unit, UNIVERSITY OF GENOA, GENOA, ITALY,
genoa, 2Dep. of Internal Medicine, Gastroenterology Unit, University of Pisa, Pisa,
3
DICMI, Pathologic Division, UNIVERSITY OF GENOA, GENOA, ITALY,
genoa, 4Dep Internal Medicine, Gastroenterology Unit, University of Pisa, Pisa,
5
Division of Gastroenterology, Department of Surgery, Oncology and
Gastroenterology, University of Padua, Padua, Italy
Contact E-mail Address: manuelefurnari@gmail.com
INTRODUCTION: During pathological assessment of esophageal biopsies several histological features characterizing the diagnosis of microscopic esophagitis
[basal cell hyperplasia (BCH), papillary enlongation (PE), dilated intercellular
spaces (DIS) and epithelial neutrofilic/eosinophilic infiltration (Neu/Eos)] can be
assessed. Limited data are available about the single contribution of these histological abnormalities on the diagnosis of GERD and its related mucosal integrity
in well-defined patients with reflux disease.
AIMS & METHODS: To determine whether these histological features contribute differently to the diagnosis GERD and to the impairment of mucosal integrity as expressed by baseline impedance (BI) levels. One hundred and four
consecutive patients with typical reflux symptoms underwent upper endoscopy
and multiple biopsies were taken at Z-line and 2 cm above it, in order to assess
the presence and severity of BCH, PE, DIS and Neu/Eos [0 (absent), 1 (mild),
and 2 (marked)]. Within 3 days from endoscopy, patients underwent impedancepH testing off-therapy. During manual analysis of the impedance-pH tracings,
we measured the esophageal acid expsosure time (AET) over the 24 hours and the
total (acid non-acid) number of impedance-detected reflux episodes. We evaluated BI values at 3 and 5cm above the LES, during the overnight rest, for at
least 30 minutes after excluding swallows and reflux induced changes. Twenty
healthy volunteers (HVs; 11F/9M; mean age 44) who underwent the same procedures were also enrolled as controls.
RESULTS: We included 85 patients with an endoscopic/impedance-pH diagnosis of GERD (45F/40M; mean age 46) who had esophageal mucosal breaks at
upper endoscopy or an abnormal esophageal acid exposure or a normal esophageal acid exposure but a positive reflux-symptom association at impedance-pH
testing. Among these patients, BI values at both 3 and 5 cm above the LES
positively correlated with the esophageal AET (r2 0.2033, P50.001 and
r2 0.1859, P50.001, respectively) and the number of impedance-detected
reflux episodes (r2 0.1373, P50.001 and r2 0.1526, P50.001, respectively).
Moreover, as shown in the Table, BCH and DIS were the lesions more significantly correlated with the endoscopic/impedance-pH diagnosis of GERD. No
significant correlation was observed between BI values and impedance-pH parameters or histological lesions in HVs (p ns).

BI at 3 cm
BI at 5 cm

BCH

DIS

PE

Neu

r2 0.2150;
P50.001
r2 0.2182;
P50.001

r2 0.1357;
p 0.001
r2 0.1405;
P50.001

r2 0.0526;
p 0.035
r2 0.0484;
p 0.043

r2 0.0516;
p 0.036
r2 0.0523;
p 0.035

CONCLUSION: BCH and DIS contribute more than PE and Eos/Neu to the
endoscopic/impedance-pH diagnosis of GERD. Moreover, the same lesions seem
to play a greater role than PE and Eos/Neu in determining mucosal integrity
impairment as expressed by BI values in GERD patients. Overall, BCH and DIS
can be considered the histological markers requiring more careful evaluation
during pathologic assessment in order to help the diagnosis of GERD.
Disclosure of Interest: None declared

P1035 PPI RESPONSIVE VS. PPI NON-RESPONSIVE FUNCTIONAL


HEARTBURN: THE DIFFERENCE LIES IN THE IMPEDANCE
BASELINE
N.de Bortoli1,*, I. Martinucci1, E. V. Savarino2, R. Tutuian3, M. Frazzoni4,
L. Bertani1, S. Russo1, R. Franchi1, M. Furnari5, M. Bellini1, V. Savarino5,
S. Marchi1
1
Gastroenterology Unit, University of Pisa, Pisa, 2Division of Gastroenterology,
University of Padua, Padua, Italy, 3Gastroenterology Unit, University of Bern,
Bern, Switzerland, 4Gastroenterology Unit, Hospital of Modena, Modena,
5
Division of Gastroenterology, University of Genoa, Genoa, Italy
Contact E-mail Address: nick.debortoli@gmail.com
INTRODUCTION: Recent data indicate that low esophageal basal impedance
may reflect impaired mucosal integrity and increased acid sensitivity.
AIMS & METHODS: We compared baseline impedance levels in patients with
heartburn and pathophysiological characteristics related to functional heartburn
(FH) divided into two groups on the basis of symptom relief after proton pump
inhibitors (PPIs). Moreover, we aimed to compare these results with a group of
patients affected by hypersensitive esophagus (HE) and with healthy volunteers
(HVs).
Patients with heartburn and normal endoscopy underwent MII-pH testing off
PPI therapy and those with negative symptom association an 8-week PPI (esomeprazole or pantoprazole 40 mg daily) therapy. Patients with 450% symptom
improvement were classified as PPI response FH (FHPPI) and those with
550% improvements as PPI non-response FH (FH-PPI). In addition we
included patients with hypersensitive esophagus (HE) defined as normal endoscopy, normal acid exposure and positive symptom association and a group of
healthy volunteers (HV). For each patient and HVs, we evaluated acid exposure
time (AET), number of MII-detected reflux episodes, baseline impedance levels
at channel 3, during the overnight rest, at three different times and PSPW index.
RESULTS: Data are summarized in the Table. Patients with FHPPI showed a
higher mean AET (1.4%0.8 vs 0.5%0.6, p50.05), mean reflux number
(30.48.7 vs 246.9, p50.05), proximal reflux number (11.15.2 vs 8.23.6,
p50.05) and acid reflux number (17.96.1 vs 10.76.9, p50.05) compared to
FH-PPI. Patients with HE showed mean AET (1.8%0.8) and total reflux
number (34.48.2) similar to those recorded in FHPPI (p ns). Baseline impedance levels were lower in FHPPIand in patients with HE then in FH-PPI and
in HVs (p50.001). No differences were found for PSPW index between
FHPPIand HE; in those groups PSPW index was lower than in FH-PPI and
HV.

HE (N 30)

FHPPI
(N 30)

FH-PPI
(N 30)

HV
(N 20)

P
(FHPPI
vs HE)

AET tot (sd) 1.80.8#


1.40.8*
0.50.6
0.70.6
n.s
N refluxes (sd)34.48.2#
30.48.7*
246.9x
17.910.8 n.s
Baseline (sd) 2125.3450.8#2169.7580.4*3782.2821.53427.842.7n.s.
PSPW (sd)
55.94.6#
56.28.8*
71.16.1
76.113
n.s.
PPI Response 100%
100%
0%
N. A.

Table legend: (*) p50.05 group FHPPI versus FH-PPI; (x) p50.05 group FHPPI versus HV; (#) p50.05 HE vs. FH-PPI vs HV
CONCLUSION: Patients with PPI responsive functional heartburn (FHPPI)
present similar MII-pH features as patients with HE. Esophageal baseline impedance measurements might allow to identify reflux patients who are not confirmed by MII-pH monitoring likely due the day-to-day variability or the
limitations of the current reflux-symptom association indexes.
REFERENCES
Martinucci I, et al. Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn. Neurogastroenterol Motil
2014; 26: 546-555.
Disclosure of Interest: N. de Bortoli: none, I. Martinucci: none, E. Savarino:
none, R. Tutuian: None declared, M. Frazzoni: none, L. Bertani: none, S.
Russo: none, R. Franchi: none, M. Furnari: none, M. Bellini: none, V.
Savarino: None declared, S. Marchi: none
P1036 DISTAL AND PROXIMAL ESOPHAGEAL IMPEDANCE BASAL
VALUES IN PATIENTS WITH NON-EROSIVE REFLUX DISEASE
AND FUNCTIONAL HEARTBURN
N.de Bortoli1,*, I. Martinucci1, E. Savarino2, R. Tutuian3, S. Russo1, L. Bertani1,
R. Franchi1, M. Furnari4, M. Bellini1, V. Savarino4, S. Marchi1
1
Gastroenterology Unit, University of Pisa, Pisa, 2Gastroenterology Unit,
University of Padua, Padua, 3Gastroenterology Unit, University of Bern, Bern,
4
Gastroenterology Unit, University of Genoa, Genoa, Italy
Contact E-mail Address: nick.debortoli@gmail.com
INTRODUCTION: Several studies have shown that proximal extent of reflux
episodes plays an important role in gastro-esophageal reflux symptom perception. The relative hypersensitivity of the proximal esophagus is most evident in
patients with non-erosive reflux disease (NERD). Recent studies demonstrated
that low distal basal impedance values may reflect impaired mucosal integrity
and increased acid sensitivity.
AIMS & METHODS: The aim was to compare distal and proximal basal impedance values in patients with NERD and functional heartburn (FH).

A418
According to impedance and pH (MII-pH) monitoring off-therapy, we selected
patients with NERD (i.e. pathological acid exposure time, AET) and FH (i.e.
normal AET and reflux number; negative symptom association). FH patients did
not show any symptom relief after acid suppression therapy. For each patient, we
evaluated basal impedance values at the distal (3 cm) and proximal (17 cm)
channel, during the overnight rest, at three different times: 1, 2, 3 am.
RESULTS: Male/female ratio was 23/23 in NERD and 13/33 in FH patients.
Mean age was 52.313.2 in NERD and 49.211.3 in FH. Mean AET was higher
in NERD (6.1%3.8%) than in FH (0.6%0.7%) (p50.05). NERD group
recorded higher total reflux number (67.818.2) than FH group (23.79.4)
(p50.05).
Basal impedance values were significantly (p50.05) lower in NERD than in FH,
both at the distal (1294.3529.9 Ohm vs 3502.1809.2 Ohm) and proximal
(3480.7 1322.6 Ohm vs 4344.9976.2 Ohm) channels. Distal basal values
were significantly lower than proximal basal values, both in NERD and FH
group (p50.05). Moreover, in NERD group, 24/46 patients (52.2%) had an
abnormal number of proximal refluxes. These NERD patients with pathological
proximal refluxes did not show lower basal impedance values than NERD
patients with normal number of proximal refluxes even if distal (1226.7453 vs
1243.1497.1; p 0.5239) or proximal channels (2670.81163.4 vs
2849.21434.2; p 0.5046) were compared.
CONCLUSION: Patients with NERD showed lower basal impedance values
both at the distal and proximal esophagus. Consistently with the concept that
low basal impedance may reflect impaired mucosal integrity, our results might be
helpful to better investigate the pathophysiological role of proximal refluxes.
Disclosure of Interest: None declared
P1037 ARE WE ANY CLOSER TO A BLOOD-BASED TEST TO
MONITOR DISEASE PROGRESSION IN THE BARRETTS
OESOPHAGUS MODEL?
H.N. Haboubi1,*, B. Rees2, C. Thornton3, G. Johnson2, G. Jenkins1
1
Cancer Biomarker Group, 2DNA Damage Group, 3Department of Immunology,
Swansea University, Swansea, United Kingdom
Contact E-mail Address: h.n.y.haboubi@swansea.ac.uk
INTRODUCTION: The increasing incidence of Barretts Oesophagus (BO) and
Oesophageal Adenocarcinoma (OA) has culminated in intensified efforts to
better stratify patients at risk of progression. Endoscopic surveillance allows
for such monitoring to take place but there still remains a potential for physical
and psychological harm to patients undergoing regular surveillance, not to mention increased cost and resource allocation. Given the DNA damage induced by
acid and bile reflux to the distal oesophagus as well as to blood cells circulating
through this inflamed tissue, the application of novel blood-based toxicological
approaches to the monitoring of patients with BO could offer a less invasive
approach to current surveillance strategies.
The phosphatidylinositol glycan biosynthesis class A (Pig-A) gene is critical for
glycophosphatidyl inositol (GPI) anchor synthesis. GPI-anchors tether specific
epitopes to the cell surface membrane and are important in cellular responses to
inflammation. Losses of gene function, as a result of a single mutational event
within the Pig-A gene form a GPI-anchor negative phenotype, detectable using
flow-cytometric methodology. Use of an adapted ex-vivo Pig-A gene mutation
assay on whole blood, may have the potential to predict patients at a higher risk
of progression through the dysplastic process as it is possible that circulating
blood cells may acquire mutations whilst passing through the oesophageal
mucosa.
AIMS & METHODS: Blood based cell lines were exposed to physiological
carcinogens such as bile and the Pig-A mutant frequency measured.
Subsequent ex-vivo analysis of blood was undertaken in patients attending endoscopy with symptoms suggestive of GORD. Pig-A analysis of erythrocytes and
leucocytes was performed and results correlated with histopathological analysis
of oesophageal biopsies as well as a detailed lifestyle questionnaire. Finally, a
challenge assay was undertaken whereby physiological doses of bile acids were
used to treat enriched lymphocytes of patients with GORD, BO and OA and the
change in mutational frequency measured.
RESULTS: In-vitro investigations confirmed the carcinogenicity of bile acids to
blood based cell lines, with increased mutant frequencies detected through the
Pig-A gene mutation assay (p50.05).
Subsequent ex-vivo erythrocyte analysis demonstrated higher mutant frequencies
in OA patients compared to both normal GORD patients and those with
Barretts (p50.01) but there was no significant difference between BO and
normal controls. Patient age, gender and length of Barretts segment did not
appear to have any influence on mutant-frequency, but smoking status suggests
some effect.
CONCLUSION: The application of this simple, non-invasive blood-based mutation assay to patients with GORD suggests OA patients have higher mutational
events than patients with Barretts or normal oesophageal mucosa. Whilst it is
not clear if Pig-A mutations in these patients are due to exposure to DNA
damage inducing chemicals or an increased predisposition to mutation at a
bone-marrow level, data from the challenge assay may allow for these questions
to be answered. Furthermore, analysis of patients with dysplastic Barretts will
permit for this test to be better validated as a future biomarker for risk of
progression.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1038 IMMUNE
MICROENVIRONMENT
IN
ESOPHAGEAL
CARCINOGENESIS: CD80 REGULATES EPITHELIAL-CD8
LYMPHOCYTES CROSS TALK AND IT PEAKS IN INTESTINAL
METAPLASIA
M. Scarpa1, M. Scarpa1,*, A. Kotsafti1, M. Cagol1, R. Alfieri1, T. Morbin2,
S. Realdon2, L. Galzignato1, G. Battaglia2, I. Castagliuolo3, C. Castoro1
1
Oncological Surgery Unit, 2Veneto Institute of Oncology (IOV-IRCCS), 3Dept of
Molecular Medicine, University of Padova, Padova, Italy
INTRODUCTION: Recent studies showed that in patients with Barretts esophagus (BE) the pooled estimate for annual esophageal adenocarcinoma (EAC)
incidence varies between 0.12% and 0.14%. It is unclear whether dysplasia can
regress over time but the difficulty in confirming low grade dysplasia presence
seems to suggest it. The expression of costimulatory molecules CD80 and CD86
in the esophageal cancer tissue is significantly lower than in the mucosa of
healthy patients. In inflammatory colonic carcinogenesis CD80 expression
seem to trigger immune surveillance mechanisms in dysplasia. The aim of the
study is to investigate the interplay between epithelium and CD8 T cells that
characterizes the immune environment of inflammatory esophageal
carcinogenesis.
AIMS & METHODS: Fresh esophageal biopsies were obtained from healthy
subjects (n 7) and from patients with BE (n 17) eleven with previous history
of dysplasia on BE and six with current dysplasia on BE, Biopsies were analysed
by flow cytometry to quantify the expression of CD80 and HLA ABC on esophageal epithelial cells, whereas on CD8 infiltrating lymphocytes the activation
marker CD38 and CD28 (CD80 receptor) were determined. Primary human
cardia epithelial cells (CEC) were co-cultured with mesenteric nodal lymphocytes
in the presence or not of anti-CD80 antibody and assessed by flow cytometry to
quantify the frequency of activated cytotoxic lymphocytes. Non parametrical
statistics was used.
RESULTS: CD80 esophageal epithelial cells rate resulted higher in BE during
inflammatory esophageal carcinogenesis compared to healthy subjects and to
patients with BE and adenocarcinoma (p 0.08 and p 0.03, respectively).
The mean intensity of CD28 was higher in patients with BE and previous history
of dysplasia compared to those with BE and adenocarcinoma (p 0.04). In vitro,
co-culture of mesenteric lymphocytes with CEC significantly increased
CD8CD38 rate that returned to baseline if antiCD80 antibody was added
(p 0.06).
CONCLUSION: In inflammation-driven esophageal carcinogenesis, there is evidence of an early active immune surveillance process mediated by CD80 overexpression on metaplastic esophageal epithelial cells. In vitro, CEC activated
CD8 T-cells through a CD80-dependent pathway confirming the role of this
molecule in triggering immune surveillance mechanism in esophageal inflammatory carcinogenesis.
REFERENCES
de Jonge PJ, et al. Gut 2014; 63: 191-202.
Scarpa M, et al. Eur J Cancer 2011; 47: 611-619.
Disclosure of Interest: None declared
P1039 HOXA13 OVEREXPRESSION IN BARRETTS ESOPHAGUS IS A
POTENTIAL MEDIATOR OF ITS POSTERIOR PHENOTYPE
V. Janmaat1,*, A. Verhaar1, M. Bruno1, M. Peppelenbosch1, M. Spaander1
1
Gastroenterology and Hepatology, ErasmusMC, Rotterdam, Netherlands
Contact E-mail Address: v.janmaat@erasmusmc.nl
INTRODUCTION: Barretts Esophagus (BE) is a metaplastic and precancerous
condition. It is induced by bile and acid reflux and defined by the presence of
intestinal-type tissue in the esophagus. The morphology of this tissue resembles a
posterior phenotype, as observed in the colon. Identifying the cause of this positional misspecification can lead to a better understanding of BE pathophysiology. The mammalian Hoxa cluster encodes master regulators of embryonic
anterior to posterior specification, making it a potential effector of positional
misspecification. The 3 to 5 sequence of genes in the Hoxa cluster, corresponds
to the sequence in which they act along the anterior to posterior axes of the body.
Acquired deregulation of HOXA genes during adulthood can be linked to carcinogenesis and HOXA13 overexpression to poor survival in gastric cancer.
However, HOXA cluster expression has never been thoroughly investigated in
the gastrointestinal (GI) tract, nor in BE. Therefore, the aim of this study was to
analyze the expression of HOXA genes along the gut, characterize HOXA expression in BE and investigate whether exposure of an esophageal cell line to acid
induces HOXA gene overexpression.
AIMS & METHODS: Firstly, we collected biopsy specimens from nine places
along the GI tract in patients who underwent double balloon enteroscopy for
unexplained symptoms. Secondly, we collected biopsy specimens of BE and
squamous epithelium from other patients. RT-qPCR was used to quantify the
expression of HOXA1, 2, 3, 4, 5, 6, 7, 9, 10, 11 and 13. Thirdly, an immunohistochemical staining for HOXA13 was done on BE and squamous epithelium.
Additionally, the esophageal cell line HET1A was exposed to an acidic environment, after which HOXA13 levels were measured.
RESULTS: In this study HOXA cluster gene expression differed significantly
along the GI tract. Expression of HOXA genes in the proximal part of the GI
tract, from the esophagus to the proximal ileum, revealed a downward trend.
Anterior genes had a higher expression compared to posterior genes. The expression of posterior genes HOXA11 and 13 was low or absent. From the terminal
ileum to the rectum, expression of HOXA genes revealed an upward trend.
Notably, expression of HOXA11 and 13 was only found in the colon.
HOXA13 showed the highest expression of all HOXA genes in the GI tract.
Furthermore, in BE, HOXA genes revealed an upward trend of expression
with a very high expression of HOXA13. Whereas the expression of HOXA13

United European Gastroenterology Journal 2(1S)


in squamous epithelium was undetectable. These observations were confirmed on
protein level for HOXA13. Furthermore, exposure of an esophageal cell line to
acid led to overexpression of HOXA13.
CONCLUSION: Our data reveal position-dependent HOXA coding along the
GI tract. This suggests a prominent role of this gene cluster in mediating locational genetic identity. The expression of HOXA cluster genes in BE resembles
colonic HOXA cluster expression. This was confirmed on protein level for
HOXA13. Additionally, exposure of an esophageal cell line to acid can induce
HOXA13 overexpression. The high overexpression of HOXA13 found in BE, is a
potential mediator of posterior phenotype in this disease and may play a role in
neoplastic progression.
Disclosure of Interest: None declared
P1040 HIGH DOSE ESOMEPRAZOLE INDUCES ROS-DEPENDENT
APOPTOSIS IN OESOPHAGEAL ADENOCARCINOMA CELLS
E. Chueca1,*, J. Godino1, A.de Martino1, M.A. Garc a-Gonzalez1,2, A. Lanas2,3,
E. Piazuelo1,2
1
INSTITUTO ARAGONES DE CIENCIAS DE LA SALUD, Zaragoza,
2
CIBERehd, Madrid, 3Servicio de Gastroenterologa, Hospital Clnico
Universitario Lozano Blesa, Zaragoza, Spain
Contact E-mail Address: echueca.iacs@aragon.es
INTRODUCTION: Proton pump inhibitors (PPIs) are the most potent and
widely used drugs for the treatment of Barretts oesophagus (BE) and have
been suggested to decrease neoplastic progression. Recently, PPIs have been
reported to disrupt tumour pH homeostasis and, in turn, cell viability, by the
inhibition of vacuolar ATPase (H-VATPase), a proton pump overexpressed in
the membrane of some tumour cells. This aspect has not been investigated in
Barretts carcinogenesis yet.
AIMS & METHODS: Aim: To investigate the expression of H-VATPase in the
human oesophageal adenocarcinoma (EAC) sequence, to evaluate in vitro the
effects of PPIs on proliferation, apoptosis and invasion of EAC cells and to
further elucidate the mechanisms involved in these effects. Methods: HVATPase expression was assessed by immunohistochemistry in 22 human
biopsy samples of normal oesophagus, BE and EAC. The expression and location of H-VATPase was also assessed in cell lines by confocal laser scanning
microscopy (Leica TCS SP2) and flow cytometry (ImageStreamX). Two different
Barretts-derived EAC cell lines were used: OE33 (ECACC) and SK-GT-4
(DSMZ); and one metastatic cell line, OACM5.1C (ECACC), obtained from a
lymph node metastasis derived from a Barretts adenocarcinoma. In addition, the
effects of PPIs were tested in a non-dysplastic BE cell line, CP-A (ATCC).
Esomeprazole (0, 1, 10, 50, 100, 200 mM) was added to the culture medium.
Cell proliferation was assessed by ELISA (BrdU, colorimetric assay). Cell invasion was evaluated in a fluorometric assay. Apoptosis was determined by flow
cytometry (FACSAria, BD) by staining the cells with Annexin V-FITC and
propidium iodide (PI). Intracellular reactive oxygen species (ROS) levels were
evaluated at different time points (1-6 hours) in a fluorometric assay using the
ROS-sensitive probe DCFDA. Experiments were performed at least in triplicate.
Statistical analysis was performed by student-t test.
RESULTS: H-VATPase expression was found to be increased in high grade
dysplasia and adenocarcinoma samples compared to normal esophagus or nondysplastic Barretts samples. In addition, H-VATPase was shown both in the
cytosol and plasma membrane in EAC cell lines. Treatment with esomeprazole
(10-200mM) induced the apoptosis of cancer cells and reduced in a dose-dependent manner cell proliferation (50-200 mM). Conversely, addition of the PPI
didnt affect apoptosis of Barrett cells whereas significantly decreased the proliferation rate at the highest dose (100-200 mM). Moreover, the highest dose of
esomeprazole significantly diminished cell invasiveness in all three tumour cell
lines. ROS seem to be involved in the antineoplastic effect of esomeprazole since
the addition of esomeprazole was followed by a significant increase in ROS levels
and the proapototic effect of the PPI was abrogated when tumoral cells were
preincubated with the ROS scavenger N-acetylcysteine.
CONCLUSION: Esomeprazole exerts in vitro antineoplastic effects on esophageal adenocarcinoma cells, suggesting that the use of high doses of PPIs might be
effective in the treatment of EAC. These effects seem to be dependent from ROS
overproduction. Additional preclinical studies are required to further confirm
these results
Disclosure of Interest: None declared
P1041 OESOPHAGEAL
CRYOABLATION
USING
THE
NEW
CRYOBALLOON FOCAL ABLATION SYSTEM: DEEP TISSUE
ABLATION WITH LITTLE OR NO LATE FIBROSIS IN ANIMAL AND
HUMAN MODELS
D. Scholvinck1,2,*, B. Weusten1,2, G. Triadafilopoulos3, T. Valli4, S. Friedland3
Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein,
2
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,
Netherlands, 3Gastroenterology and Hepatology, Stanford University School of
Medicine, Stanford, California, 4VDx Veterinary Diagnostics, Davis, California,
United States
1

INTRODUCTION: Eradication of Barretts oesophagus (BO) can be achieved


by either mucosal heating (RFA, APC) or freezing. If the energy penetrates too
deeply into the oesophageal wall, heating causes denaturation and destruction of
extracellular architecture, resulting in fibrosis and stenosis. In contrast, cryotherapy affecting deeper oesophageal wall layers is believed to cause cell death while
preserving the wall architecture, potentially enabling deeper ablation without
causing fibrosis, stenosis, or perforation.
AIMS & METHODS: We evaluated the depth of tissue injury after cryotherapy
using the newly developed Cryoballoon Focal Ablation System (CbFAS) -

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consisting of a balloon-based, through-the-scope catheter with a battery-powered
handle containing a small disposable canister for delivering cryogenic fluid into
the inflated balloon - in various therapeutic as well as supra-therapeutic doses.
Ablations of several durations (ranging from 4 to 24 seconds) were performed in
pigs (surviving 12 hours, or 2.5, 4 or 28 days) and in normal squamous mucosa of
oesophageal cancer patients (directly prior to their scheduled oesophagectomy).
All oesophagi were sent for blinded histopathological analysis. For all oesophageal wall layers (mucosa, submucosa, inner and outer muscularis propria, and
serosa) histopathological parameters, such as inflammation, necrosis and fibrosis
were scored by a injury grading system (scoring for presence/absence of layers,
oedema, inflammation, necrosis and fibrosis) with a maximum score of 3 or 4
points per layer (max. total of 17 points). Primary outcomes were the short- and
long-term effects of cryoablation on the oesophageal wall.
RESULTS: Animals: Forty ablations were performed in 8 pigs, all surviving the
pre-determined period without any symptoms or complications. Nine ablations
(2x 6 sec, 7x 8 sec) in one pig surviving 12 hours resulted in inflammation, cell
necrosis and oedema throughout the entire oesophageal wall (median injury
grading system score 11 [IQR 10-11.5]). Depth and severity of these ablation
effects was even more severe after 2.5 and 4 days: median scores of 13 (IQR
13-13) in 8 ablations (4x 6 sec, 4x 8 sec) in one pig surviving 2.5 days and 14 (IQR
13-14) in 12 ablations (2x 4 sec, 8x 6 sec, 2x 8 sec) in 3 pigs surviving 4 days.
Eleven ablations (3 ablations of 6 and 8 seconds, and 1 ablation of 10, 12, 16, 20,
and 24 seconds each) were performed in three pigs surviving 28. Neither necrosis
nor fibrosis remained present in these specimens (median score 1 [IQR 1-2]), not
even after high ablation doses.
Human: Four cryoablations (6 seconds) on squamous epithelium directly prior to
oesophagectomy in three humans showed moderate inflammation mainly limited
to the submucosal layer with a median score of 5 (IQR 5-7.3).
CONCLUSION: In both humans and animals, CbFAS cryoablation penetrates
deeply through the oesophageal wall resulting in severe early ablation injury.
After four weeks, little injury and no fibrosis remain, even after high doses,
suggesting that CbFAS cryoablation combines deep ablation with a favorable
long-term safety and efficacy profile.
Disclosure of Interest: D. Scholvinck: None declared, B. Weusten Lecture fee(s)
from: BEST Academia (Covedien), G. Triadafilopoulos: None declared, T. Valli:
None declared, S. Friedland: None declared
P1042 THORACOLAPAROSCOPIC DISSECTION OF ESOPHAGEAL
LYMPH NODES: A FEASIBILITY AND PRE-CLINICAL SAFETY
STUDY
H.T. Kunzli1,2,*, M. I.van Berge Henegouwen3, S.S. Gisbertz3, K.A. Seldenrijk4,
S.M. Lagarde3, E.J. Hazebroek5, K.C. Kuijpers4, S.L. Meijer6, J.J. Bergman2,
M.J. Wiezer5, B.L. Weusten1,2
1
Gastroenterology, St. Antonius Hospital, Nieuwegein, 2Gastroenterology and
Hepatology, 3Surgery, Academic Medical Center, Amsterdam, 4Pathology,
5
Surgery, St. Antonius Hospital, Nieuwegein, 6Pathology, Academic Medical
Center, Amsterdam, Netherlands
Contact E-mail Address: h.kunzli@antoniusziekenhuis.nl
INTRODUCTION: Low-risk early esophageal adenocarcinoma (EAC) can
safely be managed endoscopically. In case of high-risk early EAC (i.e. submucosal invasion 4500 nanometers, poor differentiation and/or presence of lymphovascular invasion), esophagectomy with lymph node dissection is currently
advocated given the relatively high rates of lymph node (LN) metastases.
However, esophagectomy is associated with substantial morbidity and mortality
and a reduced quality of life. Endoscopic radical local resection, followed by
thoracolaparoscopic dissection of esophageal LNs without concomitant esophagectomy could be an alternative.
AIMS & METHODS: In this study, we aimed to evaluate the feasibility and
safety of thoracolaparoscopic dissection of LNs involved in the drainage of the
esophagus in human cadavers (1), living swine (2), and two pilot-cases (3).
(1) In human cadavers, thoracolaparoscopic dissection of LNs involved in drainage of the esophagus was performed. Thereafter, esophagectomy was performed
and the esophagectomy specimens (ES) were analysed for any retained LNs.
Outcome parameters included the number of dissected LNs, the number of
retained LNs in the ES and technical success, which was defined as a ratio 
0.9 between the number of dissected LNs during lymphadenectomy and the total
(resected plus retained) number of LNs. (2) In swine, a thoracolaparoscopic LN
dissection was performed. 28 days after the procedure, the swine were sacrificed
and esophagectomy was performed. Outcome parameters included the presence
of ischemia or stenosis in the ES (safety parameters), and other complications. (3)
In the first human pilot-cases, thoracolaparoscopic LN dissection was performed, directly followed by esophagectomy with gastric tube reconstruction
(same session). Outcome parameters included the number of dissected LNs
during lymphadenectomy, the number of tumor-positive LNs, and the number
of retained LNs in the ES.
RESULTS: (1) In 5 human cadavers, a median of 26 LNs (IQR 22-46) was
dissected. In 2 ES, 1 retained LN was found. Technical success rate was 100%.
(2) None of the 7 porcine ES showed signs of ischemia or stenosis. One swine died
because of ventricular fibrillation during surgery; during follow-up no complications were observed in the remaining 7 swine. (3) In 2 patients with early EAC
(T1bN0M0), 23 and 43 LNs were dissected, all without evidence of metastasis. In
the ES, 2 and 1 retained paraesophageal LNs were found, proximal and distal,
respectively.
CONCLUSION: In conclusion, thoracolaparoscopic dissection of LNs involved
in the drainage of the esophagus is feasible. The porcine survival study suggests
that esophageal vascularity is not severely compromised by this procedure.
Disclosure of Interest: None declared

A420
P1043 ENDOSCOPIC TREATMENT OF EARLY ESOPHAGEAL
CARCINOMA: A PROSPECTIVE EVALUATION OF 47
CONSECUTIVE CASES WITH PROMISING RESULTS IN PATIENTS
WITH T1B CANCERS
J. Martinek1,*, J. Krajciova1, J. Maluskova2, M. Kollar2, M. Stefanova3,
J. Spicak1
1
Hepatogastroenterology, 2Pathology, Institute for Clinical and Experimental
Medicine Prague, 3Internal Medicine, Nemocnice Na Frantisku, Prague, Czech
Republic
Contact E-mail Address: jan.martinek@volny.cz
INTRODUCTION: Endoscopic therapy has become an accepted treatment
option for T1a esophageal carcinoma while for T1b cancers, surgery is still
considered as a treatment of choice. Endoscopic resection (or dissection)
allows precise histopathologic staging which is used to guide therapeutic
decisions.
AIMS & METHODS: The aim of this prospective, single center study was to
assess the long-term efficacy of endoscopic treatment for early esophageal carcinoma. The main outcome measurement was complete remission defined as an
absence of any neoplasia (CR-neoplasia).
RESULTS: The study involved 47 consecutive patients (mean age 65, range 3585; 41 males and 6 females) undergoing endoscopic treatment (42x endoscopic
resection; 5x endoscopic submucosal dissection) for esophageal carcinoma. Forty
patients (85%) were diagnosed with early adenocarcinoma (EAC) within
Barretts esophagus, the remaining 7 patients (15%) had early squamous neoplasia (ESC). In 22 patients (47%), ER/ESD was combined with radiofrequency
ablation (RFA). The median follow-up was 24 months (range 3-70).
Thirty-one patients (66%) were diagnosed as T1a cancers with mucosal invasion.
Among them, four patients were referred for surgery (three patients with multifocal cancer not allowing complete local remission, one patient in which RFA of
remaining dysplastic mucosa was not technically feasible). In the remaining 27
patients the endoscopic treatment was considered as curative.
Sixteen patients (34%) were diagnosed as T1b cancers with submucosal invasion
(13 patients with sm1 and three patients with sm2-3). Among them, 5 patients
were referred for surgery (3 of them achieved a complete local remission after
endotherapy, one patient is just waiting for surgery). The remaining 11 patients
did not undergo surgical treatment (comorbidity, patients preference, age etc.)
and endoscopic treatment was considered as a definitive treatment.
In all 38 patients who underwent only endotherapy, a 100% local remission rate
of neoplasia was achieved and no patients presented with lymph node metastases
during the follow up.
CONCLUSION: Endoscopic therapy is effective in the treatment of T1a early
esophageal cancer. It appears to be a good alternative to esophagectomy in
patients with T1b cancers.
Disclosure of Interest: None declared
P1044 CONTINUOUSLY CESSATION OR REDUCTION OF DRINKING
HABIT IMPROVES THE LUGOL VOIDING LESIONS IN PATIENTS
OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER
ENDOSCOPIC RESECTION
K. Hori1,*, H. Okada1, K. Konishi2, T. Tsuda3, C. Katada 4, T. Yokoyama5,
K. Kaneko6, I. Oda7, Y. Shimizu8, H. Doyama9, T. Koike10, K. Takizawa11,
M. Hirao12, T. Yoshii13, T. Yamanouchi14, T. Omori15, N. Kobayashi16,
T. Shimoda7, A. Ochiai6, H. Ishikawa17, A. Yokoyama18, M. Mutou19
1
Department of Endoscopy, Okayama University Hospital, Okayama, 2Showa
University, Shinagawa, 3St. Marianna University. School of Medicine, Kawasaki,
4
Kitasato University, Sagamihara, 5National Institute of Public Health, Wako,
6
National Cancer Center Hospital East, Kashiwa, 7National Cancer Center
Hospital, Tokyo, 8Hokkaido University, Sapporo, 9Ishikawa Prefectural Central
Hospital, Kanazawa, 10Tohoku University Graduate School of Medicine, Sendai,
11
Shizuoka Cancer Center, Shizuoka, 12Osaka National Hospital, Osaka,
13
Kanagawa Cancer Center, Yokohama, 14Kumamoto Regional Medical Center,
Kumamoto, 15Keio University, Tokyo, 16Tochigi Cancer Center, Utsunomiya,
17
Kyoto Prefectural University of Medicine, Kyoto, 18Kurihama Alcoholsho
Center, Yokosuka, 19Kyoto University, Kyoto, Japan
Contact E-mail Address: doctattori@yahoo.co.jp
INTRODUCTION: Esophageal squamous-cell carcinomas (ESCC) have a high
incidence of multiple ESCCs. Lugol-voiding lesions (LVLs) recognized by using
iodine chromoendoscopy were reported to be precursors for multiple primary
cancers in the esophagus associated with the field cancerrization phenomenon.
LVLs are highly associated with alcohol abuse.
AIMS & METHODS: The aims of this study were to assess the improvement of
LVLs according to cessation or reduction of drinking habit after the initial
endoscopic treatment of ESCCs. On 331 patients with newly diagnosed ESCC,
endoscopic mucosal resection or endoscopic mucosal dissection were performed
between September 2005 and May 2010. At initial diagnosis of ESCC, patients
were examined by iodine chromoendoscopy and assessed the extent of LVLs
according to the number of LVLs per endoscopic view. At study entry, drinking
and smoking histories and dietary habits were recorded. All patients were
instructed to abstain from smoking and drinking alcohol. After endoscopic treatment, all patients were prospectively followed up by iodine chromoendoscopy
every six months with record of LVLs, drinking and smoking habit. Associations
between improvement of LVLs and change of drinking habit are analyzed.
RESULTS: Of the 331 patients, 55 patients with no LVLs and 44 patients with
no drinking habit at the initial treatment were excluded. Of the remaining 232
patients, 158 patients continuously ceased or reduced the drinking habit (Group
A) and 74 patients continued drinking (Group B). Eighteen of 158 patients
(11.4%) of Group A had shown improvement of LVLs, whereas two of 74

United European Gastroenterology Journal 2(1S)


(2.7%) patients of Group B had shown improvement of LVLs (p 0.04).
Patients of Group A are significantly had higher cumulative improvement of
LVLs than patients of Group B (log rank p 0.023). Univariate and multivariate
analysis including smoking habit and dietary habit show that only continuously
cessation or reduction of drinking habit was a significant factor to improve the
extent of LVLs (univariate analysis: HR 4.6, CI 1.3-29.1, p 0.013, multivariate analysis: HR 8.6, CI 1.7-156.3, p 0.004).
CONCLUSION: By the continuous cessation or reduction of drinking habit,
LVLs were significantly improved. To prevent the metachronous multiple occurrences of ESCCs, continuous instruction to abstain from the drinking habit is
needed.
Disclosure of Interest: None declared
P1045 LAPAROSCOPIC ESOPHAGECTOMY FOR CANCER: IMPACT
ON POSTOPERATIVE INFLAMMATORY AND NUTRITIONAL
STATUS
M. Scarpa1, L. Saadeh1,*, F. Cavallin1, E. Pinto1, M. Cagol1, R. Alfieri1,
G. Noaro1, A.D. Roit1, P. Elisa1, C. Castoro1
1
Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova,
Italy
Contact E-mail Address: marcoscarpa73@yahoo.it
INTRODUCTION: Recent studies confirmed the feasibility and the safety of
minimally invasive esophagectomy for cancer. The purpose of this case-control
study was to evaluate the impact of laparoscopic gastric tubulization during
esophagectomy for cancer on postoperative inflammatory and nutritional status.
AIMS & METHODS: We retrospectively evaluated all consecutive patients
undergoing laparoscopic gastric tubulization (LGT) during esophagectomy for
cancer referred to our surgical unit between 2008 and 2013. A group of patients
undergoing esophagectomy with open gastric tubulization (OGT) - matched for
neoadjuvant therapy, pathological stage, gender and age were enrolled as
controls.
Demographic data, tumor features and post-operative course were compared. In
particular, systemic inflammatory and nutritional status were monitored during
the postoperative hospital stay. Quality of life was evaluated at one month after
surgery using EORTC QLQ-C30 functional scales, EORTC OES-18 Eating scale
and EORTC BR23 Body Image scale.
RESULTS: We enrolled 34 patients per group, with similar demographic and
tumor characteristics and ASA score. Patients in LGT group had longer procedure (p 0.04). Postoperative course was similar in term of complication rate
and severity and of functional result. ICU length of stay was shorter patients in
LGT group (p 0.002). In the first postop day LGT patients had lower C-reactive protein (CRP) levels (p 0.001) and white cell blood count (p 0.05), and
higher albumin serum level (p 0.001). In this group, albumin remained higher
also at third (p 0.06) and seventh (p 0.008) postop day, and CRP resulted
lower at third post day (p 0.04). No difference was observed in term of quality
of life.
CONCLUSION: LGT during esophagectomy for cancer significantly improved
the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter ICU length of stay. Quality of life and esophageal function were
comparable between LGT and OGT patients.
Disclosure of Interest: None declared
P1046 RISK FACTORS OF INTRAOPERATIVE PERFORATION DURING
ENDOSCOPIC SUBMUCOSAL DISSECTION OF SUPERFICIAL
ESOPHAGEAL SQUAMOUS CELL CARCINOMA
M. Noguchi1,*, T. Yano1, T. Kato1, T. Kadota1, H. Morimoto1, S. Osera1,
T. Odagaki1, Y. Oono1, H. Ikematsu1, K. Kaneko1
1
Department of Gastroenterology, Endoscopy division, National Cancer Center
Hospital East, Kashiwa, Japan
INTRODUCTION: Perforation is the major complication during endoscopic
submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC),
and the frequency is reported to be approximately 5%. However, there are few
reports about the risk factors for intraoperative perforations and the subsequent
clinical course.
AIMS & METHODS: A total of 147 patients with 157 ESCC lesions were
treated by ESD in our hospital from April 2008 to October 2012. We divided
the group into intraoperative perforation cases and nonperforation cases, and
compared the characteristics and endoscopic findings of the 2 groups. We also
retrospectively reviewed the clinical courses after the perforations. A dual knife
or an insulation-tipped diathermic knife were used for the ESD procedures. In
addition, 0.4% sodium hyaluronate diluted with normal saline solution including
epinephrine (1:1) was used as the submucosal injection solution. Intraoperative
perforation was defined as the detection of a perforation site during ESD, and
the presence of mediastinal emphysema seen on computed tomography (CT) or
radiograph.
RESULTS: Intraoperative perforation was recorded as having occurred in 9
lesions from 9 patients (5.7%). No significant differences were observed between
the perforation group (n 9) and the nonperforation group (n 148) for age,
lesion location, depth of invasion, or history of treatment for esophageal cancer.
However, in the perforation group the lesion maximum dimension was larger
(42.9 mm vs. 30.7 mm, p 0.015) and the rate of 3/4th or larger circumference of
mucosal deficiency after ESD was higher (78% vs 31%, p 0.007). Furthermore,
the procedure time was longer (183.8 minutes vs 102.5 minutes, p 5 0.001), and
the en bloc resection rate was lower (33.3% vs 93.9%, p 5 0.001) in ESD for
patients who developed perforation during the procedure. The left wall was the
predominant site of perforation (67%), and 6 of 9 perforations were successfully
closed by clips during the procedures. Two of 9 patients required drainage for

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United European Gastroenterology Journal 2(1S)


pleural effusions; however, all 9 patients recovered with conservative treatment
without surgical intervention. The median fasting duration and hospital stay
after the procedure were 6 days (522 days) and 12 days (741 days), respectively.
Three of 9 patients underwent additional treatments including chemoradiotherapy or esophagectomy due to submucosal infiltrations. At the median follow up
of 42 months after ESD, no case of local recurrence or metastasis was observed.
CONCLUSION: This study suggests that a larger maximum dimension and
mucosal defects after ESD are risk factors for intraoperative perforation
during ESD for ESCC.
Disclosure of Interest: None declared
P1047 DIVERGING
INCIDENCE
OF
OESOPHAGEAL
ADENOCARCINOMA AND NON-CARDIA GASTRIC CANCER
SUGGESTS A COMMON ENVIRONMENTAL FACTOR
PREDISPOSING TO ONE AND PROTECTING FROM OTHER
M.H. Derakhshan1,*, D.H. Brewster2, J.J. Going3, M. Arnold4, D. Forman4,
K.E. McColl1
1
Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow,
2
Scottish Cancer Registry, NHS Scotland, Edinburgh, 3Institute of Cancer
Sciences, University of Glasgow, Glasgow, United Kingdom, 4Section of Cancer
Information, International Agency for Research on Cancer, Lyon, France
Contact E-mail Address: mohammad.derakhshan@glasgow.ac.uk
INTRODUCTION: During the last three decades, the global incidence of oesophageal adenocarcinoma has increased more rapidly than most other cancers in
certain populations. A concurrent reduction in the incidence of gastric cancer has
been reported from some populations. We aimed to examine the geographical
pattern of oesophageal adenocarcinoma versus non-cardia gastric cancer across
the world where reliable cancer registry data were available.
AIMS & METHODS: Data were abstracted from Cancer Incidence in Five
Continents Volume 10. Oesophageal and gastric cancers were selected based
on ICD-10 codes C15 and C16, respectively. Oesophageal adenocarcinomas were
classified according to histological groups based on ICD-O morphology codes.
Out of 424 datasets from 290 cancer registries, 288 were selected as they reported
410 cases for oesophageal adenocarcinoma. We examined the association
between the incidence of oesophageal adenocarcinoma and non-cardia gastric
cancer. Spearmans test of correlation was used to explore the relationship
between Age-Standardised Incidence Rates (ASR) of the two cancers and
expressed as correlation coefficients (CC). Furthermore, all cardia cancer cases
within a registry were assumed to be either oesophageal or non-cardia based
upon the different gender ratios for oesophageal versus non-cardia gastric
cancer on individual registries.
RESULTS: A total of 288 datasets covering 62 countries were included in the
analyses. There was a statistically significant inverse correlation between oesophageal adenocarcinoma and gastric non-cardia cancer in males (CC -0.685, p
value50.001) and females (CC -0.566, p value50.001). After dividing cardia
cancer into two subtypes with potentially oesophageal or gastric origin and
adding them to original oesophageal adenocarcinoma or gastric non-cardia
groups, the correlation remained strong (CC -0.688, p value50.001) in males
and (CC -0.656, p value50.001) in females. Oesophageal adenocarcinoma only
showed a rise when the incidence of non-cardia gastric cancer fell below 9/
100.000 person-years for males and 4.5/100.000 person-years for females.
CONCLUSION: This cross-sectional study is consistent with a common underlying factor predisposing to non-cardia gastric cancer and protecting from oesophageal adenocarcinoma, such as H.pylori atrophic gastritis. If this is the case,
then the incidence of non-cardia gastric cancer would need to fall to substantially
lower levels than currently seen in the Far East populations before any rise in
oesophageal adenocarcinoma would be apparent.
Disclosure of Interest: None declared
P1048 RECURRENT ESOPHAGEAL CANCER AFTER RADICAL
ESOPHAGECTOMY: PROGNOSTIC FACTORS AND TREATMENT
STRATEGIES
S. Matono1,*, T. Tanaka1, N. Mori1, H. Hino1, K. Kadoya1, H. Fujita2,
Y. Akagi1
1
Surgery, Kurume University School of Medicine, Kurume, 2Surgery, Fukuoka
Wajiro Hospital, Fukuoka, Japan
INTRODUCTION: The prognosis of patients with recurrent disease after esophagectomy for esophageal cancer is generally poor.
AIMS & METHODS: The purpose of this study was to examine the prognostic
factors in esophageal cancer patients with recurrence after esophagectomy and to
determine the appropriate treatment strategy for such patients. Patients: Seventyeight patients (33 %) developed recurrent disease among 237 patients with thoracic esophageal cancer who underwent R0 esophagectomy between 2001 and
2010.
RESULTS: Thirty-three (43%) patients had locoregional recurrence, 26 (33%)
patients had recurrence in distant sites, and 19 (24%) had both recurrences.
Recurrence occurred within one year in 45 patients (57%), within 2 years in 67
patients (85%), and within 3 years in all these 78 patients (100%). The overall 5year survival rates after recurrence was 9%. Although there was no significant
difference in survival between patients with only locoregional recurrence and
those with only distant site recurrence (p 0.3032), patients with recurrence in
both locoregional and distant sites had poorer prognosis compared with only
locoregional recurrence (p 0.0003) or only distant site recurrence (p 0.0050).
Of 78 patients, 23 (30%) patients received chemoradiotherapy, 18 (23%) patients
received chemotherapy, 8 (10%) patients received radiotherapy, 15 (19%)
patients received surgery, and the remaining 14 (18%) patients received best
supportive care alone. Surgery was performed in selected patients only when

the lymph node did not invade the neighboring structures, and the distant
lesion was detected as a single metastasis in a single organ. The 5-year survival
rates after recurrence in patients who received anti-cancer treatment was 11%,
and the patients with best supportive care survived less than one year
(p 0.0166). Furthermore, the 5-year survival rates for patients with surgery
was 14% compared with 7% for patients without surgery (p 0.0166). On univariate analysis, tumor location, depth of tumor invasion (pT), recurrent type,
time to recurrence and treatment were found to be factors affecting the survival
(p50.05). In multivariate analysis, the depth of tumor invasion (pT3T4 vs.
pT1T2: hazard ratio 1.919; 95 % confidence interval 1.0053.850; p 0.0481),
recurrent type (both vs. alone: hazard ratio 2.062; 95 % confidence interval
1.1263.641; p 0.0199) and treatment (best supportive care vs. anti-cancer
treatment: hazard ratio 9.031; 95 % confidence interval 4.13019.210; P
50.00001) were independent prognostic factors.
CONCLUSION: The prognosis of patients with both locoregional and distant
sites recurrence was poorer than those with each recurrence. The prognosis of
patients who received anti-cancer treatment was better than that of the patients
who received best supportive care alone. Surgery might be an option for selected
patients.
Disclosure of Interest: S. Matono: The authors declare no conflict of interest, T.
Tanaka: The authors declare no conflict of interest, N. Mori: The authors declare
no conflict of interest, H. Hino: The authors declare no conflict of interest, K.
Kadoya: The authors declare no conflict of interest, H. Fujita: The authors
declare no conflict of interest, Y. Akagi: The authors declare no conflict of
interest
P1049 ESOPHAGEAL CANCER DEVELOPMENT DURING
COURSE OF H. PYLORI-INFECTED CHRONIC GASTRITIS

THE

T. Yoshida1,*, J. Kato1, I. Inoue1, M. Watanabe1, S. Enomoto1, S. Miyamoto1,


H. Deguchi1, M. Iguchi1, T. Maekita1, H. Tamai1, M. Ichinose1
1
The 2nd Department of Internal Medicine, Wakayama Medical University,
Wakayama City, Japan
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is the most
prevalent esophageal cancer worldwide. Although the etiology of ESCC remains
unclear, recent studies have revealed that, because they presumably generate an
anacidic intraluminar environment that favors bacterial overgrowth in the upper
gastrointestinal tract (GI), which leads to an accumulation of carcinogens such as
nitrosamines, H. pylori (HP) infection and atrophic gastritis are both important
risk factors for ESCC. However, studies investigating this association, particularly follow-up studies, are limited, and thus the role of chronic HP infection in
ESCC development remains controversial.
AIMS & METHODS: Therefore, we investigated ESCC development during the
progression of HP-associated chronic gastritis in a study of 4655 male subjects.
Healthy, middle-aged, male subjects (n 4655; mean age, 49.5  4.6 years) were
screened annually for ESCC and gastric cancer (GC) for up to 16 years. Chronic
atrophic gastritis (CAG) was diagnosed based on the following prostaglandin
(PG)-test positive criteria: PG I 70 ng/ml and PG I/II ratio 3.0. Highly active
gastritis was determined by serum levels of PG II 30 ng/ml or HP antibody titer
500 U/ml. The stages of HP-associated chronic gastritis were evaluated by
serum levels of pepsinogen and HP antibody, and were categorized into 4
groups representing the progression of HP-associated chronic gastritis as follows:
Group A (CAG-negative, HP-negative); Group B (CAG-negative, HP-positive);
Group C (CAG-positive, HP-positive); and Group D (CAG-positive, HPnegative).
RESULTS: During the study period, 87 GCs developed (annual incidence rate:
0.16%). Cancer development increased in a stepwise manner from Groups A to
D, reaching a peak annual incidence rate of 1.1%. In Group B subjects with mild
atrophic gastritis (annual incidence rate: 0.14%), highly active gastritis assessed
by serum tests showed an annual incidence rate of around 0.25%, which was
comparable to that in Group C subjects (0.30%). Eight ESCCs developed during
the same period (annual incidence rate: 0.015%). Both smoking and alcohol
consumption elevated the risk of ESCC, but only smoking showed a marginal
significance (p 0.08). The annual cancer incidence rate in Group A was 0.008%,
and neither HP infection nor CAG significantly increased the risk of cancer.
Highly active gastritis in a mildly atrophic stomach tended to increase the risk
of cancer (p 0.04).
CONCLUSION: Unlike GC, the incidence of which increases with establishment
of HP-associated gastritis and the progression of CAG, ESCC development
appeared not to be affected by the stages of gastritis. However, the possibility
that the activity of gastritis is somehow involved in esophageal carcinogenesis
should be further investigated.
Disclosure of Interest: None declared
P1050 LONG TERM OUTCOMES OF ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS
CELL CARCINOMA
T. Kato1,*, T. Yano1, T. Kadota1, M. Imajoh1, M. Noguchi1, H. Morimoto1,
S. Osera1, T. Odagaki1, Y. Oono1, H. Ikematsu1, K. Kaneko1
1
Gastroenterology, Endoscopy Division, National cancer center east hospital,
Kashiwa, Japan
Contact E-mail Address: tomkato@ncc.east.go.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widespread treatment for superficial esophageal squamous cell carcinoma (ESCC),
since en bloc resection can be performed even in large ESCC lesions of which
could not be performed in conventional endoscopic resection. However, there are
few reports regarding the long-term outcomes of ESD for ESCC.

A422
AIMS & METHODS: The aim of this retrospective study was to clarify the longterm results of ESCC patients treated by ESD. Between January 2006 and
October 2012, a total of 185 patients with 191 lesions underwent ESD in our
institution. We analyzed the patients who met the following criteria: 1) histologically confirmed initial ESCC or metachronous ESCC after prior endoscopic
resection; 2) depth of lesions suspected as limited to within SM1; 3) absence of
lymph node or distant metastasis; 4) a follow up period of 1 year or longer from
the ESD procedure; and Cumulative overall, and disease-specific survival rate
were calculated by the Kaplan-Meier method along with the log-rank test.
RESULTS: A total of 171 patients with 177 lesions were evaluated in this study.
The median age was 67 years ranging from 39 to 85 years, and men were predominant (86%). In addition, 77 of 171 patients (45%) had a history or concomitance of cancer in other organs. Of 177 lesions, 169 (95%) were initial
ESCC, and the remaining 8 lesions were metachronous ESCC. In the location,
upper, middle, and lower esophagus was in 12, 100, and 65 lesions, respectively,
with the median tumor size of 28 mm (range: 770). The median operation time
during ESD was 100 minutes, and the en bloc resection rate was 89%. While
esophageal perforation complicated in 8 patients during the procedure, all recovered with conservative therapy. Esophageal strictures required endoscopic balloon dilation after ESD was found in 55 patients (31%). Additional therapy was
recommended in 34 (20%) patients because of the histological diagnosis, such as
positive vertical margins, invasion into the submucosal layer, or lymphatic infiltration. Of the 34 patients, 20 received additional chemoradiotherapy, 5 underwent surgery, and the remaining 9 were followed up without additional treatment
because of poor physical condition. At the median follow up period of 36 months
(range: 1292 months) after ESD, The presence of local recurrence, metastatic
recurrence, and metachronus ESCC were 1.1%(2/172), 2.8%(5/177) and 14.7%
(26/177) respectively. The overall survival at 3 and 5 years was 95.5% and 93.5%,
respectively. During the follow up period, 11 patients died from the following
causes: 2 from esophageal cancer, 7 from other cancers, and 2 from benign
diseases. Therefore, disease-specific survival at 3 years and 5 years was 99.2%
and 97.1%, respectively.
CONCLUSION: The long-term outcomes of ESD for ESCC was excellent.
However, during the follow up periods, physicians should pay attention to not
only the possibile local and metastatic recurrence or metachronous ESCC, but
also the occurrence of other organ cancers
Disclosure of Interest: None declared
P1051 SALVAGE PHOTODYNAMIC THERAPY FOR PATIENTS WITH
LOCAL FAILURE AFTER CHEMORADIOTHERAPY FOR
ESOPHAGEAL SQUAMOUS CELL CARCINOMA
T. Yano1,*, K. Hatogai2, T. Kojima2, Y. Yoda1, H. Morimoto1, K. Kaneko1
1
Department of Gastroenterology, Endoscopy division, 2Department of
Gastroenterology, Oncology division, NATIONAL CANCER CENTER
HOSPITAL EAST, Kashiwa, Japan
Contact E-mail Address: toyano@east.ncc.go.jp
INTRODUCTION: Local failure is a major problem after chemoradiotherapy
(CRT) in patients with esophageal squamous cell carcinoma (ESCC), and salvage
surgery for local failures associate with high complication and mortality rate. We
have introduced photodynamic therapy (PDT) for local failures to develop a less
invasive salvage treatment.
AIMS & METHODS: The aim of this study to clarify the long-term outcome
and prognostic factors of salvage PDT. Between 1998 and 2008, 716 patients with
ESCC were treated with definitive CRT in our institution. The indication criteria
of PDT were as follows: 1) absence of lymph node and distant metastasis, 2) local
failures limited within T2, 3) patients who could not tolerate or who refused
surgery, 4) provision of written informed consent. PDT involved 2 mg/kg of
porfimer sodium followed 48-72 hours later by excimer dye laser with a fluence
of 75 J/cm2. We assessed overall survival (OS), progression free survival (PFS),
and also prognostic factors. This study was approved by an institutional review
board in our institution.
RESULTS: A total of 113 patients with local failure underwent salvage PDT.
The characteristics before CRT were as follows; male/ female: 107/ 6, median
age: 66 y-o (range: 50-84), T1/ 2/ 3/ 4: 18/ 18/ 60/ 17, N0/ N1: 54/ 59; and those of
before PDT were as follows; T1/T2: 72/41; residue after CRT/recurrence after
achieving CR with CRT: 64/49. Total 66 patients could achieved CR with PDT
(CR rate: 58.4% (95% CI 49.3 67.5). Five patients developed esophageal
perforation, and two of them died with bleeding due to esophago-aortic fistula
after PDT, therefore treatment-related death rate was 1.7%. At the median
follow up period of 61 months, the PFS rate and OS rate at 5 years from salvage
PDT was 22.1% (95% CI 14.330.0) and 35.9% (95% CI: 26.745.1), respectively. N0 before CRT and period longer than six months between CRT and
PDT were significantly associated with better survival.
CONCLUSION: PDT demonstrated a favorable outcome in an analysis of a
large number of patients with local failure after definitive CRT for ESCC.
Disclosure of Interest: None declared
P1052 MULTIMODALITY THERAPY FOR ESOPHAGEAL CANCER
WITH DISTANT ORGAN METASTASIS: TREATMENT OUTCOMES
AND PROGNOSTIC FACTORS
T. Tanaka1,*, S. Matono1, N. Mori1, H. Hino1, K. Nishimura1, K. Shirouzu1,
H. Fujita2
1
Surgery, Kurume University, Kurume, 2Surgery, Fukuoka Wajiro Hospital,
Fukuoka, Japan
Contact E-mail Address: totanaka@med.kurume-u.ac.jp
INTRODUCTION: Multimodality therapy has been established as an effective
treatment for locally advanced esophageal cancer. However, esophageal cancer

United European Gastroenterology Journal 2(1S)


patients with distant organ metastasis have usually been treated to palliate symptoms without multimodality therapy, and the prognosis of these patients is extremely poor.
AIMS & METHODS: The aim of the study is to evaluate the role of multimodality therapy in esophageal cancer patients with organ metastasis. A prospectively maintained database identified 112 esophageal sqamous cell cancer
patients with distant organ metastasis who were treated at our institution
between 1989 and 2011.
RESULTS: The metastatic organ was the liver (n 59), the lung (n 47), bone
(n 16), and other (n 10). Twenty patients had metastasis in two and more
organs. Multimodality therapy was performed in 78 patients: 62 patients received
chemoradiotherapy (CRT), and 17 underwent surgery with chemotherapy (CT)
and/or radiation therapy (RT). Twenty patients received single-modality therapy;
CT, RT, or surgery alone. The remaining 13 patients received best supportive
care (BSC) alone. The median survival (MS) for the whole group was 5.6 months.
The MS was 9 months for patients treated with multimodality therapy, 2.8
months for patients with single-modality therapy, and 2 months for patients
with BSC alone (P 0.0001, P 5 0.0001). There was no difference in survival
between single-modality therapy and BSC (P 0.1505). By univariate analysis,
an improved survival was associated with less advanced N stage (N0-1), the
number of metastatic organ site (one organ), and type of therapy (multimodality
therapy). Age, gender, performance status, location of tumor, T stage, and organ
of metastasis did not affect survival. Multivariate analysis identified multimodality therapy to be the only independent factor for improved survival (hazards
ratio, 0.317; 95% confidence interval, 0.207-0.495; P 5 0.0001).
CONCLUSION: These results suggested that multimodality therapy could
improve survival of the esophageal cancer patients with distant organ metastasis.
A randomized study is necessary to confirm any definitive role for multimodality
therapy in esophageal cancer patients with organ metastasis.
Disclosure of Interest: None declared
P1053 LONG-TERM PROGNOSIS OF SUPERFICIAL ESOPHAGEAL
CANCERS AT LEAST 50MM IN DIAMETER TREATED BY
ENDOSCOPIC SUBMUCOSAL DISSECTION
T. Oyama1,*, A. Takahasi1, M. Takeuchi2, R. Ishihara3, M. Tanaka4, I. Odfa5,
S. Abe5
1
Endoscopy, Saku Central Hospital Advanced Care Center, Saku,
2
Gastroenterology, NIigata University hospital, Niigata, 3Gastroenterology, Osak
medical center of cancer and cardiovascular disease, Osaka, 4Gastroenterology,
Shizuoka cancer center, Shizuoka, 5Gastroenterology, National Cancer Center,
Tokyo, Japan
Contact E-mail Address: oyama@coral.ocn.ne.jp
INTRODUCTION: The advantage of ESD is high R0 resection rate and low
local recurrence rate. However, usefulness of ESD for big ESCC and long term
prognosis after ESD for big ECCS is unknown.
AIMS & METHODS: The aim of this study is to clarify the usefulness of ESD
for ECCS at least 50mm in diameter, and long term prognosis after ESD.
Superficial ECCS at least 50mm in diameter treated by ESD were enrolled to
this retrospective study. A total of 138 superficial ECCS at least 50mm in diameter were treated by ESD in 5 territorial hospitals from 2000 to 2013. Patients
characteristics were as follows; Male/Female is 118/20, respectively. Median age
was 69 (42 88), An additional treatment (AT) such as esophagectomy, chemotherapy (CT), radiation (RT) and chemo radio therapy (CRT) was recommended for the patients who had T1b ESCC.
RESULTS: Result 1. En bloc resection rate was 99 % (137/138), and R0 resection rate was 88% (122/138). Horizontal and vertical margin was positive in 14
(10%) and 2 (1.4%), respectively. There werent severe complication that needs
surgical operation. Invasion depth T1a EP, LPM, MM, and T1bSM1 (200m or
less) and SM2 was 30/51/34/6/17, respectively. Result 2. Local recurrence rate
was 1% (1/138). The patient had T1bSM2 ESSC, and refused an additional
treatment. A local recurrence was diagnosed 51 months after ESD, and esophagectomy was performed. Result 3. Prognosis of T1a: No recurrence was found in
T1aEP and LPM. Eight of 34 MM patients had lymph duct invasion. Four
patients were treated by CRT, and two patients were alive without metastasis.
Remaing two patients had lymph node metastasis (LNM) and treated by CRT
again. One patient who was treated by RT was alive. The remaining 3 patients
were followed up without AT, and LNM was found in one patient, and CRT was
performed. One patient is alive without recurrence, and the other patient died of
other disease. Twenty six patients who didnt have ductal invasion were followed
up without AT. Two patients had LNM. One patient was treated by esophagectomy and alive. The other patient was treated by CRT and died of ESCC. Result
4. Prognosis of T1bSM1: One patient of 6 T1bSM1 had LNM, and treated by
CRT. The patient is alive without recurrence for 60 months. The remaining 5
patients were followed up without AT, and one patient died of lymph node
metastasis, and remaining 5 patients were alive without recurrence. Result 5.
Prognosis of T1bSM2: Six of 18 patients had lymph duct or venous invasion.
Five of these 6 patients were treated by CRT, and alive without recurrence. The
remaining one patient was followed up without AT, and died of other disease 49
months after ESD. Three of 11 patients who didnt have ductal invasion were
treated by CRT, and alive without recurrence. Eight patients were followed up
without additional therapy. One patient had local recurrence 51 months after
ESD, and was treated by esophagectomy. Remaining seven patients were alive
without recurrence.
CONCLUSION: ESD is a safe and useful treatment for ECCS at least 50mm.
The prognosis of T1aEP and LPM is excellent. And, prognosis of T1aMM,
T1bSM1 or SM2 with an adequate AT was also excellent.
Disclosure of Interest: None declared

A423

United European Gastroenterology Journal 2(1S)


P1054 DISTRIBUTION OF LYMPH NODE METASTASES
ESOPHAGEAL CARCINOMA: A SYSTEMATIC REVIEW

IN

S.S. Gisbertz1, W. Borstlap1,*, S. Lagarde1, M. I.van Berge Henegouwen1


1
Surgery, AMC, Amsterdam, Netherlands
Contact E-mail Address: s.s.gisbertz@amc.nl
INTRODUCTION: Lymph node status is an important prognostic parameter in
esophageal carcinoma and an independent predictor of survival. Distribution of
metastatic lymph nodes may vary with tumor location, tumor histology, tumor
invasion depth and neoadjuvant therapy. Surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy differs worldwide. Aim of the present study was to evaluate the
distribution of lymph node metastases in esophageal carcinoma specimens following transthoracic esophagectomy.
AIMS & METHODS: The Cochrane database of systematic reviews, the
Cochrane central register of controlled trials, Embase and Medline databases
were searched by two independent researchers using a combination of keywords
relating to esophageal cancer, surgery, lymphadenectomy and lymph nodes.
Studies were included if published from 1990 until July 1st 2013. Excluded
were studies with 1-field lymphadenectomy, studies with neo-adjuvant therapy,
studies describing only the sentinel node, animal studies and case reports. The
primary end point was the distribution of lymph node metastases.
RESULTS: Out of 2406 articles, 8 studies, reporting on 5038 patients, fulfilled
the eligibility criteria and were included. Seven studies described the distribution
of nodal metastases in squamous cell carcinoma (4869 patients) and 2 studies in
adenocarcinoma (169 patients; 1 study described both squamous cell and adenocarcinoma). All studies were retrospective analyses except for 1 prospective
cohort trial on squamous cell carcinoma (1893 patients). The studies on squamous cell carcinoma discriminated between tumor location in the upper, middle
and lower esophagus. All selected studies used a different classification system for
lymph node stations and were therefore not comparable in a meta-analysis. For
adenocarcinoma both studies found mediastinal and abdominal lymph node
metastases, but in only 1 of 2 studies cervical metastatic lymph nodes were
reported (10/32 patients; 27%). For squamous cell carcinoma all studies
described cervical, mediastinal and abdominal lymph node metastases, independent of the location of the tumor, except for 1 trial with 9 patients, in which there
were no abdominal lymph node metastases in upper esophageal squamous cell
carcinoma and 1 trial with 41 patients in which there were no cervical lymph node
metastases in lower esophageal squamous cell carcinoma.
CONCLUSION: Esophageal cancer frequently metastasizes to the neck, mediastinum and abdomen. However, few studies describe the distribution of lymph
node metastases for esophageal adenocarcinoma. Additionally, there is no homogeneity concerning classification of lymph node stations, which makes interpretation of studies difficult and data hard to compare. This makes the choice for
surgical strategy demanding, especially when considering the significant morbidity involved in esophageal surgery. A multicenter prospective study is needed to
determine distribution of lymph node metastases in order to establish optimal
surgical treatment for esophageal cancer patients.
Disclosure of Interest: None declared
P1055 LOCOREGIONAL STEROID INJECTION TO PREVENT
STRICTURE FORMATION AFTER ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR SUPERFICIAL ESOPHAGEAL CANCER USING A
PROPENSITY SCORE MATCHING ANALYSIS
Y. Nagami1,*, M. Shiba1, K. Tominaga1, M. Ominami1, S. Fukunaga1,
S. Sugimori1, H. Yamagami1, T. Tanigawa1, T. Watanabe1, Y. Fujiwara1,
T. Arakawa1
1
Gastroenterology, Osaka City University Graduate School of Medicine, Osaka,
Japan
Contact E-mail Address: yasuaki-75@med.osaka-cu.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) to treat superficial
esophageal cancer has become accepted owing to its high quality control for the
disease. However, incidence of strictures caused by ESD for widespread lesions is
high and sometimes leads to a low quality of life. Locoregional steroid injection
was reported to be useful for prevention of such strictures formation (1).
However, no prospective randomized comparative study about steroid has
been observed.
AIMS & METHODS: We evaluated the prophylactic efficacy of locoregional
steroid injection for stricture formation after ESD for superficial esophageal
cancer using a propensity score matching analysis.
This is a retrospective study in single referral center. Between April 2006 and July
2013, a total of 357 patients with superficial esophageal cancer underwent ESD in
our hospital. Four patients treated with metallic stent and 4 patients with lacking
data were excluded. Consequently, 349 patients were enrolled in this study. We
have used two fashions of locoregional steroid injection: one is an injection of 80
mg triamcinolone once just after ESD; second is an injection of 6.6 mg dexamethasone just after ESD and twice a week (1-6 times). Endoscopic evaluation of
the stricture was performed after 4 and 8 weeks after the treatment. A propensity
score matching analysis was performed to reduce the effects of selection bias of
steroid injection and potential confounding factors. We compared the incidence
of stricture formation by univariate analysis between patients with and without
locoregional steroid injection before and after matching. In addition, multivariate analysis was used.
RESULTS: Of 349 patients, 42 patients underwent locoregional steroid injection
(dexamethasone/triamcinolone, 23/19) after ESD and esophageal stricture formation occurred in 36 patients. Twenty-eight patients with or without steroid
injection were matched after a propensity score matching. In univariate analysis,
the incidence of stricture formation with steroid injection decreased to 10.7% (3/

28) from 35.7% (10/28) as without steroid (p 0.035). Multivariate analyses


indicated that lcoregional steroid injection decreased the incidence of stricture
formation (OR, 0.15; 95% CI, 0.030.73; p 0.02). No serious adverse events
such as delayed bleeding and perforation were encountered.
CONCLUSION: Locoregional steroid injection was efficient for preventing stricture formation after ESD for superficial esophageal cancer.
REFERENCES
(1) Hanaoka N, Ishihara R, Takeuchi Y, et al. Intralesional steroid injection to
prevent stricture after endoscopic submucosal dissection for esophageal cancer: a
controlled prospective study. Endoscopy 2012; 44: 10071011.
Disclosure of Interest: Y. Nagami: None declared, M. Shiba: None declared, K.
Tominaga: None declared, M. Ominami: None declared, S. Fukunaga: None
declared, S. Sugimori: None declared, H. Yamagami: None declared, T.
Tanigawa: None declared, T. Watanabe Financial support for research from:
Eisai Co., Ltd., Y. Fujiwara: None declared, T. Arakawa Consultancy for:
Eisai Co., Ltd., Other: Otsuka Pharmaceutical Co. Ltd
P1056 ROLE OF ENDOGENOUS AND EXOGENOUS HYDROGEN
SULFIDE (H2S) IN GASTRIC PROTECTION AGAINST
EXPERIMENTAL GASTRIC LESIONS
M. Magierowski1,*, K. Jasnos1, M. Wierdak1, A. Ptak-Belowska1, R. Pajdo1,
G. Krzysiek-Maczka1, S. Kwiecien1, T. Brzozowski1
1
Department of Physiology, Jagiellonian University Medical College, Cracow,
Poland
INTRODUCTION: Hydrogen sulfide (H2S) plays an important role in a number
of physiological actions including vasodilatation, inhibition of oxidant stress, the
anti-inflammatory activity and the inhibition of apoptosis. Three enzymes
cystathionine -lyase (CSE), cystathionine -synthetase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST) are essentioal in the biosynthesis of H2S by
gastric epithelium. However, whether this gaseous molecule could be effective in
protection against acid-dependent stress-induced lesions and whether the expression of CSE and CBS and the gastric mucosal biosynthesis of H2S could affect
the mucosal damage induced by stress in the presence or absence of exogenous
H2S, have been little elucidated.
AIMS & METHODS: We studied the effect of NaHS, a H2S-donor and Lcysteine, a H2S precursor against 3.5 h of water immersion restraint stress
(WRS)-induced gastric lesions in rats with intact and capsaicin-denervated sensory nerves (large dose 125 mg/kg s.c for 3 days). Animals were pretreated i.g. 30
min before the oneset of WRS with A) NaHS (5 mg/kg); B) L-cysteine (10 mg/kg)
with or without the combination with inhibitors of CSE activity, D,L-propargylglycine (PAG 15 - 80 mg/kg) and beta-cyano-L-alanine (BCA, 50 mg/kg). The
number of gastric lesions was measured by planimetry, the gastric blood flow
(GBF) by H2-gas clearance technique and the gastric H2S production resulting
from CSE/CBS and 3-MST activity pathways and the gastric H2S content were
determined by modified methylene blue method and ELISA, respectively. In
addition, the mucosal mRNAs expression of CSE, CBS, 3-MST, HIF1 and
antioxidizing enzymes SOD and GPx were evaluated by RT-PCR.
RESULTS: Exposure to WRS caused mucosal hemorrhagic lesions accompanied
by the fall in GBF, gastric H2S content and an increase in H2S production via
CSE/CBS and 3-MST pathways and mRNA expression of CSE and CBS. NaHS
(1-20 mg/kg) and L-cysteine (5-40 mg/kg) dose-dependently reduced WRSinduced gastric damage and significantly raised GBF and mucosal content of
H2S and these effects were completely lost in animals with capsaicin denervation.
BCA and PAG which dose-dependently augmented the number of WRS lesions
and decreased H2S production and its tissue content, reversed the NaHS and Lcysteine-induced decrease in the WRS lesions and the accompanying increase in
the GBF. Upregulation of mRNAs expression for HIF-1 mRNA, CSE and CBS
in the gastric mucosa exposed to WRS was diminished by NaHS (5 mg/kg i.g.)
and L-cysteine (10 mg/kg i.g.) and these effects were further enhanced in capsaicin-denervated rats treated with NaHS and L-cysteine. The increased expression
of SOD and GPx mRNA was observed in NaHS- and L-cysteine-pretreated rats
but not in those with capsaicin-denervation.
CONCLUSION: We conclude that: 1) an increase in H2S production and the
expression of CSE and CBS, two key enzymes in H2S biosynthesis, could compensate for the stress-induced impairment of gastric mucosal defense; 2) an
increase in endogenous production of H2S in gastric mucosa contributes to the
NaHS-induced protection against stress lesions, and 3) H2S-induced gastroprotection and hyperemia against WRS-induced ulcerogenesis is mediated by
vasoactive sensory neuropeptides such as CGRP and the activity of antioxidizing
enzymes SOD and GPx.
Disclosure of Interest: None declared
P1057 CARBON MONOXIDE (CO) RELEASED FROM CORM-2
RELEASING CO ATTENUATES ASPIRIN-INDUCED GASTRIC
LESIONS. INVOLVEMENT OF GASTRIC SECRETION, HEME
OXYGENASE (HO-1) AND NITRIC OXIDE
K. Jasnos1,*, R. Pajdo1, S. Kwiecien1, M. Magierowski1, T. Brzozowski1
1
Department of Physiology, Jagiellonian University Medical College, Cracow,
Poland
INTRODUCTION: Previuos studies revealed that enzyme heme oxygenase
(HO)-1 exerts an important protective action in acute and chronic inflammation
of the gastrointestinal mucosa. Carbon monoxide (CO) synthesized due to activity of HO-1 has been shown to exert important physiological functions in the
regulation of blood flow and motility but the contribution of this gaseous molecule to the mechanism of protection against nonsteroidal anti-inflammatory
drugs (NSAID)-induced gastric mucosal damage has been little studied.

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United European Gastroenterology Journal 2(1S)

AIMS & METHODS: We determined the effect of tricarbonyl dichloro


ruthenium(II) dimer (CORM-2), a CO releasing molecule, on gastric acid secretion in rats equipped with chronic gastric fistulas (GF) (series A) and gastric
lesions induced by acidified aspirin (ASA) (series B). Rats were treated with
CORM-2 (0.1-50 mg/kg i.g.) and received 30 min later ASA (125 mg/kg i.g.)
without or with: 1) NO-synthase inhibitor L-NNA (20 mg/kg i.p.) without or
with L-arginine (200 mg/kg i.g.), a substrate for NO-synthase activity, 2) ODQ
(10 mg/kg i.g.), a guanylyl cyclase inhibitor, and 3) zinc protoporphyrin IX
(ZnPPIX), an inhibitor of HO-1 activity. In addition, the effect of hemin, a
HO-1 inducer which provides endogenous CO, and biliverdin, the product of
heme catalysis, on ASA damage and the alterations in the GBF were also studied.
The area of gastric lesions was measured by planimetry, the gastric blood flow
(GBF) determined by H2-gas clearance technique, plasma proinflammatory cytokines (IL-1 and TNF-) were determined by ELISA and the mRNA and proteins for HO-1-, HO-2- and COX-1- and proinflammatry markers COX-2-, IL1-, and TNF- were assessed by RT-PCR.
RESULTS: CORM-2 inhibited basal and histamine stimulated gastric acid secretion in rats with GF (series A) and dose-dependently attenuated ASA damage
while increasing GBF; the dose inhibiting ASA damage by 50% (ED50) being 5
mg/kg (series B). These protective and hyperemic effects of CORM-2 were significantly attenuated by L-NNA and restored when L-arginine but not D-arginine was co-administered with CORM-2. ODQ also significantly attenuated the
gastroprotective and hyperemic effects of CORM-2. Pretreatment with hemin (5
mg/kg i.g.) significantly reduced ASA-induced gastric damage and significantly
increased the GBF similarly as in case of CORM-2 while biliverdin was less
effective. ZnPPIX which exacerbated ASA damage significantly atternuated
the protection and the rise in GBF induced by CORM-2 (5 mg/kg i.g.). The
increased mucosal expression of mRNA for HO-1, COX-2 mRNA, IL-1 and
TNF- and plasma levels of these cytokines were detected in rats exposed to ASA
and these effects were significantly ameliorated by pretreatment with CORM-2.
CONCLUSION: We conclude that 1) CO released from CORM-2 exhibits gastroprotective activity against ASA-induced gastric lesions via mechanism involving an increase in the gastric microcirculation mediated by activation of HO-1/
CO, NO-NOS and PG-COX systems and the inhibition of the expression and
activity of proinflammatory markers COX-2, IL-1 and TNF-, and 2) antisecretory activity of CORM-2 releasing CO can contribute to CO-induced protection against acid-dependent mucosal damage evoked by ASA.
Disclosure of Interest: None declared
P1058 THE PECULIARITIES OF COLONIC MICROBIOTA
HELICOBACTER PYLORI-NEGATIVE PATIENTS WITH NSAIDSGASTROPATHY

IN

A. Antonenko1,*, T. V. Beregova2, A.S. Svintsitsky1


1
Department of Internal Medicine 3, Bogomolets National Medical University,
2
Pharmacology and Experimental Pathology, Taras Shevchenko National
University, Kiev, Ukraine
Contact E-mail Address: tonyaant@yandex.ru
INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are
pommonly prescribed for a variety of inflammatory conditions. Among the
most common side effects are NSAID-enteropathy/-gastropathy. It is known
that in animal models NSAID-enteropathy is accompanied by shifts in numbers
and types of intestinal bacteria. Thats why probiotics (P) are thought as potential drugs for treatment and prevention of NSAID-enteropathy. The peculiarities
of colonic microbiota and its correlation with the severity of gastric lesions in
patients who used NSAIDs for more than 3 months havent been studied before.
AIMS & METHODS: to study the peculiarities of colonic microbiota in H.
pylori-negative patients who used NSAIDs more than 3 months with and without
NSAIDs-gastropathy; to determine a correlation between the intensity of dysbiosis and age, severity of gastric mucous lesions (GML); and to optimize the
treatment of NSAIDs-associated GML with the help of P. We observed 45
patients who were H. pylori-negative and used NSAIDs more than 3 months.
The mean age was 64.16.1. For all of them gastroscopy, laboratory examination were performed. The fecal microflora has been analyzed by bacteriological
culture methods. Patients with GML were divided into 2 equal groups. The first
group (control) was treated with pantoprazole (20 mg 2 times daily) for 28 days.
The second group (main) received combined therapy: pantoprazole (20 mg 2
times daily) for 4 weeks and P Symbiter acidophilic concentrated in dose 10
ml per day for 20 days. Over 1 month after the beginning of treatment we
repeated all examinations which were done before. Normal distribution of studied parameter for each sampling was checked using Shapiro-Wilkas criteria.
Average value (L) error and standard deviation (SD) were calculated to discover
significant changes of investigated indices. Sampling comparison was performed
using the paired Students t-test.
RESULTS: Among 45 patients, who were examined, in 30 patients GML were
observed, in 15 patients visible changes of GM were absent. Changes in colonic
microbiota were observed in all patients who used NSAIDs for more than 3
monts. In 33.3% of them the level of Lactobacillus was less than 106. It was
detected correlative conjunction between the severity of injuries and intensity of
dysbiosis (r 0.67, p50.001). The correlation between the intensity of dysbiosis
and age of the patients is also observed (r 0.43, p50.003). Over 1 month in the
control group erosive lesions of GM were observed in 26.7%, in the main group
erosive lesions after the treatment were absent (p50.05). In the main group the
elevation of the level of haemoglobin, red blood cells were significantly more
expressed. In the control group the intensity of dysbiosis was enhanced, in the
main group dysbiosis was not registered.
CONCLUSION: The changes in the colonic microbial community structure
correlate with the intensity of the GML and age of patients with NSAIDs-gastropathy. The inclusion of P in the general scheme of treatment of NSAIDsgastropathy eliminates the detected dysbiosis and improves the indicators of

complete blood count and what is important - it leads to the total healing of
gastric mucous over 4 weeks from the beginning of treatment that allows us to
recommend the inclusion of P in the general scheme of the treatment of NSAIDsgastropathy.
Disclosure of Interest: None declared
P1059 THE ROLE OF SINGLE NUCLEOTIDE POLYMORPHISMS
LINKED TO VITAMIN B12 MALABSORPTION IN ATROPHIC
GASTRITIS AND PERNICIOUS ANEMIA
F. Purchiaroni1,*, E. Lahner1, G. Gentile2, M. Simmaco2, G. Esposito1, G. Galli1,
B. Mora3, B. Annibale1
1
Digestive and Liver Disease, 2Biochemical Sciences, 3Experimental Medicine,
Universita` Sapienza, Rome, Italy
Contact E-mail Address: flaminia.purchiaroni@hotmail.it
INTRODUCTION: Atrophic body gastritis (AG) is characterized by oxyntic
glands and parietal cells destruction with loss of hydrochloric acid and intrinsic
factor production. Vitamin B12 (vitB12) malabsorption may occur and lead to
pernicious anemia (PA), the global burden of which is still unknown. AG and PA
pathogenesis are linked to autoimmune mechanisms and to Helicobacter pylori
(Hp) infection1. The role of single nucleotide polymorphisms (SNPs) in vitB12
malabsorption and PA is unknown.
AIMS & METHODS: To determine the frequency of SNPs potentially related to
vitB12 absorption pathway in AG patients, with or without PA, compared to
healthy controls.
83 AG caucasian patients were enrolled: 43 with PA (51% F, median age 59
years) and 40 without (85% F, median age 51 years). Controls included 173
caucasian subjects (73% F, median age 51 years). Genomic DNA from peripheral blood leukocytes was extracted. Fourteen SNPs potentially related to vitB12
absorption were analyzed by genotyping: TCN1 rs526934, TCN2 rs9606756,
CUBN rs1801222, rs11254363, FUT2 rs492602, rs601338, rs602662, FUT6
rs3760776, GIF rs35211634, rs121434322, MUT rs9473555, rs1141321,
MTHFR rs1801133, CLYBL rs41281112 2,3. Results are expressed as allele
and genotype frequencies.
RESULTS: TCN2 (rs9606756) C/C genotype was significantly more frequent in
all cases compared to controls: 3.6% vs 0%, 2 0.02. MUT (rs9473555) G allele
was significantly less frequent in all cases compared to controls: 27% vs 72%, 2
50.0001. The genotype and allele frequencies of remaining SNPs were similar in
the two groups.
TCN2 (rs9606756) C/C and FUT6 (rs3760776) T/T genotypes were more prevalent in PA cases compared to controls: respectively, 4.6% vs 0%, 2 0.02; 9.3%
vs 1.7%, 2 0.01. No difference was found in terms of allele frequency. GIF gene
(rs121434322) T allele was not expressed in the examined population.
CONCLUSION: Compared to controls, AG patients, with and without PA,
have a higher prevalence of TCN2 C/C genotype, which may be associated
with altered plasma transcobalamin and thus with altered cellular vitB12
uptake. Among PA cases, FUT6 T/T genotype is more prevalent; this may
alter FUT6 activity and individual susceptibility to Hp infection, a trigger of
gastric autoimmunity. MUT G allele is more prevalent in controls and it has
been linked to higher vitB12 levels, as it is expected in an healthy gastric body
mucosa. This study shows that genetic polymorphisms related to vitB12 absorption pathway are associated to AG and PA; this suggests that specific SNPs in
AG may lead to vitB12 malabsorption.
REFERENCES
1) Lahner E and Annibale B. Pernicious anemia: new insights from a gastroenterological point of view. World J Gastroenterol 2009; 15: 5121-5128.
2) Lin X, Lu D, Gao Y, et al. Genome-wide association study identifies novel loci
associated with serum level of vitamin B12 in chinese men. Hum Mol Genet 2012;
21: 2610-2617.
3) Nielsen MJ, Rasmussen MR, Andersen CB, et al. Vitamin B12 transport from
food to the bodys cellsa sophisticated, multistep pathway. Nat Rev
Gastroenterol Hepatol 2012; 9: 345-354.
Disclosure of Interest: None declared
P1060 THE IL-1B GENETIC POLYMORPHISM IS ASSOCIATED WITH
LOW-DOSE ASPIRIN-INDUCED PEPTIC ULCER IN KOREANS
H.M. Kim1,*, K.J. Lee1, J.S. Choi2, K.H. Choi3, S. Lee3, S.W. Yi3, S.W. Chun2,
J.H. Cho4, K.J. Han5
1
Department of Internal Medicine, Yonsei University Wonju College of Medicine,
Wonju, 2Department of Internal Medicine, Myongji Hospital, Goyang,
3
Department of Internal Medicine, International St. Marys Hospital, 4Department
of Internal Medicine, Gachon University Gil Medical Center, Incheon, 5Department
of Internal Medicine, Kwandong University College of Medicine, Gangneung,
Korea, Republic Of
Contact E-mail Address: loverkorea2009@gmail.com
INTRODUCTION: Single nucleotide polymorphisms (SNPs) are associated with
aspirin-induced peptic ulcer, but they are discrepant among races. There are few
data on Koreans.
AIMS & METHODS: This study investigated the relationship of SNPs of COX1, IL1B, TNF and IL-1RN genes on aspirin-induced peptic ulcer in Korean
adults.
The subjects taking a low-dose aspirin of 100 mg for at least 4 weeks were
enrolled in the study, and they underwent an upper GI endoscopy at Myongji
Hospital. The subjects were divided into two groups: the control group that had
no peptic ulcer in upper GI endoscopy, and the peptic ulcer group that had
gastric or duodenal ulcer in upper GI endoscopy. The DNA was extracted
from the subjects whole blood, polymerase chain reaction was performed to
detect SNP, and mutation analysis was performed.

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United European Gastroenterology Journal 2(1S)


RESULTS: A total of 48 patients consisting of 23 patients with peptic ulcer and
25 healthy controls were enrolled. In IL-1 -581C/T (rs1143627), the prevalence
of CC, CT and TT alleles were 21.74%, 65.22%, and 13.04% in the peptic ulcer
group, whereas 16%, 40%, and 44% in the control group, respectively. In IL1B1061C/T (rs16944), the CC, CT and TT alleles were 13.04%, 65.22%, and
21.74% in peptic ulcer group, whereas 44%, 40%, and 16% in the control
group, respectively. After adjustment for age and gender, the CT and CC allele
of IL-1 -581C/T had an odds ratio of 4.625 (95% confidence interval: 1.05420.303) for peptic ulcer. In IL-1 -1061C/T, the CT and TT allele had an odds
ratio of 4.625 (95% confidence interval: 1.054-20.303) for peptic ulcer.
CONCLUSION: The C allele of IL-1 -581C/T and T allele of IL-1 -1061C/T
had an increased risk of low-dose aspirin-induced peptic ulcer in Korean adults.
It would be reasonable to screen patients for these SNPs before low-dose aspirin
is prescribed, and to prevent peptic ulcer induced by low-dose aspirin.
Disclosure of Interest: H. M. Kim Financial support for research from: a grant
from the Basic Science Research Program through the National Research
Foundation of Korea, K. J. Lee: None declared, J. S. Choi: None declared, K.
H. Choi: None declared, S. Lee: None declared, S. W. Yi: None declared, S. W.
Chun: None declared, J. H. Cho: None declared, K. J. Han: None declared
P1061 LOCAL
IMPLANTATION
OF
ADIPOSE-DERIVED
MESENCHYMAL STEM CELLS (ADMSCS) ENHANCED HEALING
OF GASTRIC ULCER VIA ACTIVATION OF ERK1/2-MAPK
PATHWAY
L. Liu1, P. Lam1, E. Ng2, P.W. Chiu2,*
THE CHINESE UNIVERSITY OF HONG KONG, Hong Kong, Hong Kong,
2
Department of Surgery, THE CHINESE UNIVERSITY OF HONG KONG,
Hong Kong, Hong Kong
Contact E-mail Address: philipchiu@surgery.cuhk.edu.hk
1

INTRODUCTION: Numerous studies confirmed the efficacy of ADMSCs in


enhancing healing in injury to various organs including heart, liver, colon,
brain and kidney. The aim of our study was to investigate the effect of
ADMSCs in enhancing the healing of gastric ulcer and to explore the potential
mechanisms for this effect.
AIMS & METHODS: Gastric ulcer model was successfully created in rats using
70% acetic acid. These ulcers were divided into three groups and received one of
the following treatments: 1. Single dose of 1107 ADMSCs directly transplanted
to around ulcer by injection; 2. intragastric administration of pantoprazole; 3.
Phosphate buffered saline alone (PBS). The healing of ulcer was assessed by the
area measured at different time points after sacrifice of rat. Molecular mechanisms and potential signal pathway activated by ADMSCs were assessed using
PCR-array. In addition, the therapeutic potentials of ADMSCs were also
assessed when NSAIDs was simultaneously used.
RESULTS: The results showed that ADMSCs accelerated healing of peptic ulcer
as evidence by the significant reduction in ulcer area at day 10 and 15 for
ADMSC group compared to other two groups (ADMSCs vs. PBS group:
P50.01 for day 10 and P50.05 for day 15). Histological assessment indicated
that ADMSCs significantly increased re-epithelialization, angiogenesis and collagen deposition, meanwhile suppressing inflammatory reaction. ADMSCs
group had more cell proliferation and angiogenesis compared with PBS group.
Transplanted ADMSCs homed into the gastric ulcer and differentiated into
endothelial and smooth muscle cells. The results of PCR-array indicated that
genes for anti-inflammation, chemokines, growth factors and remodeling
enzymes were significantly up-regulated in ADMSCs group. In addition,
ADMSCs activated Erk1/2-MAPK signal pathway, which has been suggested
as the most important pathway for the healing of peptic ulcer. Simultaneous use
of indomethacin (a commonly used NSAIDs) greatly attenuated the therapeutic
effect of ADMSCs as shown by reduced cell proliferation and angiogenesis,
increased apoptosis and delayed ulcer healing at day 10.
CONCLUSION: Local injection of ADMSCs enhanced healing of gastric ulcer
through activation of Erk1/2-MAPK signal pathway.
Disclosure of Interest: None declared
P1062 FEASIBILITY OF ENDOSCOPIC SUBMUCOSAL DISSECTION
(ESD) FOR EARLY GASTRIC CANCER IN ELDERLY PATIENTS
H. Noda1,*, N. Ogasawara1, K. Nagao1, A. Shimozato1, Y. Kondo1, Y. Ito1,
K. Yanamoto1, M. Sasaki1, K. Kasugai1
1
Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan
Contact E-mail Address: bisaipan@aichi-med-u.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) for early gastric
cancer can achieve a higher rate of en bloc resection which allows more accurate
pathological diagnosis, even for large lesions. If the correct indications are used,
ESD can be a radical treatment with results comparable to open surgery.
Therefore, ESD is thought to greatly improve the patients quality of life
(QOL). In Japan, life expectancy is approximately 80 years, and Japan has the
longest life expectancy in the world for both men and women. In its increasingly
aged society, a growing number of endoscopic treatments are performed on the
elderly with age-associated comorbidities such as cardiovascular diseases. The
proportion of people who regularly attend hospital for at least one chronic disease is nearly 70% among people who are 7584 years of age, which is the highest
rate compared to other age groups. Therefore, even esophagogastroduodenoscopy (EGD) itself can have risks for elderly patients, and further caution is
particularly needed for those with comorbidities of heart or lung diseases.
Elderly patients often have surgically operative risks due to complicated diseases,
and the feasibility of ESD for such patients will improve the QOL. In the present
study, we aimed to evaluate the efficacy and safety of ESD for early gastric
cancers in elderly patients aged 75 years or older. The technical feasibility, the

en bloc resection rate, and the complications of ESD in the treatment of early
gastric cancers were compared with those of younger patients.
AIMS & METHODS: The subjects were selected from 213 consecutive patients
with early gastric cancers for which ESD was performed between January 2006
and December 2013. They were divided into two group; 74 patients who were 75
years of age or older (elderly group) and 139 patients under 75 years old (nonelderly group). The following were used for analysis between the groups: pre- and
postoperative performance status (PS) of subjects, prevalence rates of pre-existing comorbidities, characteristics of lesions, treatment outcomes, durations of
hospitalization, operating times and incidence rates of complications.
RESULTS: In the elderly, there was one patient (1.4%) with PS of 3 before ESD.
None of the non-elderly had a PS of 3 before or after the procedure. The PS
increased in only one elderly patient (1.4%) after the ESD procedure. However,
none of the non-elderly had the PS increase after the ESD procedure. There was
no significant difference related with PS increase between the two groups. The
ratio of patients with a pre-existing comorbidity was higher in the elderly than in
the non-elderly. There were no differences between the two groups in the characteristics of the lesions, operating times, duration of hospitalization, or the
incidence rates of complications such as perforation and post-ESD bleeding.
The percentage of the patients taking anticoagulant drugs was significantly
higher in the elderly. Of the patients on anticoagulant therapy, the duration of
hospitalization tended to be longer in the elderly but no significant difference was
found.
CONCLUSION: The present study shows feasibility of ESD for early gastric
cancers in elderly patients. We conclude that ESD is useful in elderly patients
because there is a similar risk as for the non-elderly regardless of PS or preexisting comorbidity.
Disclosure of Interest: None declared
P1063 SUCCESSFUL TREATMENT OF MENETRIERS DISEASE USING
THE EGF-RECEPTOR-ANTIBODY CETUXIMAB
H.H. Nietsch1,*
Department of Gastroenterology, St. Elisabeth Medical Center, Halle (Saale),
Germany
Contact E-mail Address: h.nietsch@krankenhaus-halle-saale.de
1

INTRODUCTION: Menetriers disease (hypertrophic gastropathy) named after


French physician Pierre E. Menetrier; (18591935) is a rare, acquired, premalignant disease of the stomach characterized by enlarged gastric folds, excessive
mucous production with resultant protein loss. The histology is characterized
by massive foveolar hyperplasia. The glands are elongated with a corkscrewlike appearance and cystic dilation is common. There is no standard therapy
as of yet. A few case series describe a dramatic response to the inhibition of
the EGF-Receptor pathway (NEJM 2000; 343: 1697-1701).
AIMS & METHODS: We report the case of a 48-year old Caucasian male with a
three year history of dyspepsia associated with lower extremity edema caused by
hypoalbuminemia. Helicobacter serology was negative. The epigastric pain was
only minimally responsive to PPI-treatment. An EGD was performed and
showed large, tortuous gastric folds in the fundus and body of the stomach,
with sparing of the antrum. Radial EUS at 10 mHz showed significant thickening
of the gastric wall up to 9 mm caused by effacement of the first three wall layers.
Five large biopsies using a hot snare were obtained. The histology did reveal the
characteristic findings of Menetriers disease with extensive foveolar hyperplasia.
RESULTS: Given the persistent epigastric complaints and significant enteral
protein loss leading to edema, we did recommend the off-label use of cetuximab,
a monoclonal antibody against the EGF-receptor, according to the Vanderbilt
University/Nashville/TN- study protocol. After informed consent and approval
by the internal review board, four weekly infusions of cetuximab were administered (400mg/m2 loading dose, followed by 250mg/m2). Prophylactic Pliazon
(Merck Serono) cream was applied in order to prevent drug-induced skin rash,
which is a common side effect of anti-EGFR therapy. The patient only developed
a mild erythematous rash without pruritus after the second infusion. The epigastric discomfort was relieved completely and the serum albumin level normalized
after 6 weeks leading to resolution of the peripheral edema. EGD 8 weeks after
completion of the anti-EGFR therapy showed normal gastric folds with only
mild chronic gastritis on histology. The patient is currently without and GI
symptoms 6 months after completion of therapy and will undergo annual
EGDs for surveillance.
CONCLUSION: Anti-EGFR antibody therapy using cetuximab seems to be an
effective treatment of symptomatic Menetriers disease and should be considered
before more aggressive treatment options like gastrectomy are entertained.
REFERENCES
Burdick S, et al. NEJM 2000; 343: 1697-1701.
Disclosure of Interest: None declared
P1064 CAN THE FICE ENDOSCOPY IDENTIFY INDIVIDUALS WITH
ADVANCE STAGES OF GASTRIC ATROPHY AND/OR
INTESTINAL METAPLASIA?
I. Kikuste1,2,*, I. Tolmanis2, D. Stirna2, M. Barene2, L. Filipsone2, E. Blodniece2,
M. Leja1,2
1
University of Latvia, 2Digestive Diseases Centre Gastro, Riga, Latvia
Contact E-mail Address: ikikuste@gmail.com
INTRODUCTION: Patients with chronic atrophic gastritis (AG) or intestinal
metaplasia (IM) should be considered to be at higher risk for gastric adenocarcinoma [1]. This study aimed to evaluate if the flexible spectral imaging color
enhancement (FICE) endoscopic assessment of gastric mucosa could replace
random biopsies to identify individuals with advance stages of gastric atrophy
and/or intestinal metaplasia.

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AIMS & METHODS: We included 191 consecutive patients (male 28%, average
62, range 50-87) from January 2013 to April 2014 aged over 50 undergoing FICE
(gastroscope EG-590WR) endoscopy at Digestive diseases centre GASTRO.
Targeted biopsies were obtained at the locations of visually suspected lesions.
If no changes were determined by FICE, random biopsies were performed in
antrum, incisura and corpus according to Sydney-Houston protocol. Histology
assessment was performed according to the updated Sydney System. Both OLGA
and OLGIM were used and individuals classified accordingly.
RESULTS: Table 1. FICE diagnostic accuracy for AG and IM.

Atrophy (OLGA III/IV)


IM (OLGIM III/IV)
Atrophy (OLGA I/II)
IM (OLGIM I/II)

Sensitivity

Specificity

LR

LR-

82.35
78.57
46.88
61.45

78.57
86.17
78.57
86.17

3.84
5.68
2.19
4.44

0.22
0.25
0.68
0.45

The overall prevalence of endoscopically and histologically diagnosed AG and


IM cases were 48% and 93% (68% OLGA I), 39% and 50% (45% OLGIM I),
respectively.
CONCLUSION: FICE endoscopy yielded favourable results in the endoscopic
diagnosis of advance stages of gastric atrophy and/or intestinal metaplasia
(OLGA/OLGIM III/IV) and this is very practical and easy way to use in a
daily clinical practice for unselected patients.
REFERENCES
1. Dinis-Ribeiro M, et al. Management of precancerous conditions and lesions in
the stomach (MAPS). Endoscopy 2012; 44: 7494.
Disclosure of Interest: None declared
P1065 RISK STRATIFICATION AND MANAGEMENT OF
CURATIVE RESECTION AFTER ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR EARLY GASTRIC CANCER

NON-

J.P. Han1,*, S.J. Hong1, H.J. Jung1, Y.S. Myung1, T.H. Lee1, B.M. Ko1,
J.Y. Cho1, J.S. Lee1
1
Digestive Disease Center, Department of Internal Medicine, Soon Chun Hyang
University School of Medicine, Bucheon, Korea, Republic Of
Contact E-mail Address: rock5014@schmc.ac.kr
INTRODUCTION: Non-curative resection after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) can contribute to local recurrence or
lymphatic and distant metastasis of the tumor. We stratified the risk of local
recurrence in non-curative resection after ESD for EGC.
AIMS & METHODS: There were 892 EGC cases treated with ESD from 2001
2012; histology determined that 152 (17.0%) cases resulted in non-curative resection after ESD. These cases included positive cancer cells in the margin, lymphovascular invasion, or were beyond the expanded criteria of ESD from ESD
specimens. The clinical outcomes and risk factors associated with local recurrence were analyzed retrospectively in non-curative resections after ESD.
RESULTS: Among 152 non-curative resections, 46 (30.3%) were interpreted as
incomplete resection based on the margin and criteria fulfillment, 31 (20.4%) as
complete resection based on margin and beyond the criteria, 41 (27.0%) as
incomplete resection based on margin and beyond the criteria, and 34 (22.4%)
as lymphovascular invasion regardless of complete resection. The patients with
factors related to incomplete margin resection beyond the criteria (odds ratio
[OR], 3.991; P 0.015) or lymphovascular invasion (OR, 4.487; P 0.014)
showed a higher rate of local recurrence in non-curative resection. In those
high-risk groups, endoscopic surveillance without additional treatment allowed
significantly more local recurrence than those received additional treatment
(P 0.029).
CONCLUSION: Risk stratification for non-curative resection is important for
EGC prognosis after ESD. Moreover, additional treatment for non-curative
resection influences long-term outcomes, in a high-risk group that have incomplete resection of margin beyond the ESD criteria or lymphovascular invasion.
Disclosure of Interest: None declared
P1067 STUDY FOR CASES OF RECURRENCE AFTER ENDOSCOPIC
RESECTION IN EARLY GASTRIC CANCER
S.K. Bae1, J.H. Kim1,*
Internal medicine, Myongji hospital, Goyang-si, Korea, Republic Of

INTRODUCTION: Endoscopic resection (ER) is widely accepted treatment for


early gastric cancer (EGC), but little is known about recurrence after ER.
AIMS & METHODS: The aim of this study is to investigate cases of recurrence
after ER for EGC.
We performed a retrospective review of medical records of 126 patients with
EGC underwent ER.
RESULTS: The median follow up period was 26.7 months. During a follow up, a
total of 10 patients (7.94%) developed recurrence in enrolled patients. According
to univariate logistic regression analysis, piecemeal resection (odds ratio [OR]
7.067, 95% confidence interval [CI] 1.706-29.285, P 0.007) and tumor-positive
resection margin (OR 33.292, 95% CI 7.064-159.904, P50.0001) were significant
risk factors for cancer recurrence after ER. However, there was no significant
factor for recurrence in multivariate logistic regression analysis.
CONCLUSION: This study showed that piecemeal resection and tumor-positive
resection margin were probable risk factors for recurrence after ER for EGC.
Therefore, a study in a large number of patients and a longer period might show

that piecemeal resection and tumor-positive resection margin are risk factors for
recurrence.
REFERENCES
1. Oka S, Tanaka S, Kaneko I, et al. Endoscopic submucosal dissection for
residual/local recurrence of early gastric cancer after endoscopic mucosal resection. Endoscopy 2006; 38: 996-1000.
2. Yoo JH, Shin SJ, Lee KM, et al. How can we predict the presence of missed
synchronous lesions after endoscopic submucosal dissection for early gastric
cancers or gastric adenomas? J Clin Gastroenterol 2013; 47: e17-22.
3. Tanabe S, Ishido K, Higuchi K, et al. Long-term outcomes of endoscopic
submucosal dissection for early gastric cancer: a retrospective comparison with
conventional endoscopic resection in a single center. Gastric Cancer 2014; 17:
130-136.
4. Park JC, Lee SK, Seo JH, et al. Predictive factors for local recurrence after
endoscopic resection for early gastric cancer: long-term clinical outcome in a
single-center experience. Surg Endosc 2010; 24: 2842-2849.
5. Yoon H, Kim SG, Choi J, et al. Risk factors of residual or recurrent tumor in
patients with a tumor-positive resection margin after endoscopic resection of
early gastric cancer. Surg Endosc 2013; 27: 1561-1568.
Disclosure of Interest: None declared
P1068 VESSEL PLUS SURFACE CLASSIFICATION SYSTEM OF
MAGNIFYING-NARROW BAND IMAGING FOR PREDICTING
PRESENCE CANCEROUS LESION AND OTHER PROGNOSTIC
HISTOLOGIC FACTORS IN GASTRIC EPITHELIAL NEOPLASMS: A
RETROSPECTIVE SINGLE CENTER STUDY
J.H. Kim1,*
Gastroenterology, Busan Paik Hospital, Inje University College of Medicine,
Busan, Korea, Busan, Korea, Republic Of
1

INTRODUCTION: Although studies have addressed the predictive role of magnifying-narrow band imaging (MNBI) for gastric epithelial neoplasms, little is
known of the relationship between MNBI indicators and histologic prognostic
factors other than the presence of cancer.
AIMS & METHODS: We conducted this study to validate MNBI indicators for
differential diagnosis of gastric neoplasms and as predictors for other prognostic
histologic factors, using vessel plus surface classification system. The medical
records of 171 consecutive gastric epithelial neoplasms which received MNBI
before undergoing curative surgery or endoscopic treatment were retrospectively
reviewed.
RESULTS: Irregular and absent microvascular pattern (MVP) (p 0.008),
absent microsurface pattern (MSP) (p 0.028), presence of demarcation line
(DL) (p 0.03) and presence of irregular type white opaque substance (WOS)
(p 0.015), along with flat or depressed macroscopic morphology (p 5 0.001),
were significantly and independently correlated with presence of cancerous
lesion. There was no significant difference in the AUC value prediction of
cancer between MSP and MVP, while the AUC value of DL and WOS was
lower than that of the MVP and MSP. Significant correlations were also evident
between irregular or absent MVP, irregular WOS and submucosal cancer invasion. Absent MSP was independently correlated with presence of undifferentiated
cancer and microscopic ulcer. Presence of irregular WOS was also significantly
related with presence of LVI.
CONCLUSION: MNBI findings are valuable for predicting the presence of
cancerous lesions, cancer differentiation, depth of cancer invasion, presence of
microscopic ulcer and LVI.
Disclosure of Interest: None declared
P1069 RETROGRADE ENDOSCOPIC SUBMUCOSAL DISSECTION OF
GASTRIC NEOPLASM INVOLVING THE PYLORIC CHANNEL
J.W. Choe1, J.S. Koh1,*, M.K. Joo1, B.J. Lee1, J.-J. Park1, J.S. Kim1, Y.-T. Bak1
1
Korea University College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: neucjw@naver.com
INTRODUCTION: Recently, successful resection of the pyloric tumors by endoscopic submucosal dissection (ESD) using retroflexion in the duodenum has been
reported. However, the detailed dissection method of the procedure was not well
defined yet. We also had done the retroflexion ESD of dissecting retrogradely
from the duodenum to the pyloric channel of duodenal part, after then antegradely from the antrum to the pyloric channel. But, we introduced a new retroflexion method of retrogradely dissecting mucosa from duodenum to transpyloric antrum as extensively as possible since February 2012. We studied the
feasibility and effectiveness of the new retrograde prepyloric antral dissection
using retroflexion ESD.
AIMS & METHODS: 61 patients with gastric neoplasm involving the pyloric
channel underwent ESD from January 2007 to March 2013. In 27 patients, the
conventional anterograde ESD were performed without using the endoscope
retroflexed in the duodenum. The other 34 patients were procedured by the
retroflexion method. Among that 34, the latest 16 patients underwent the new
retrograde trans-pyloric antral dissection method. We retrospectively analyzed
the procedure times, en bloc rates, complete resection rates and complications
associated with each different techniques.
RESULTS: In retroflexion ESD group (N 34), the rate of en bloc resection was
97%, and the rate of complete resection was 96%. The conventional group
(N 27) shows relatively 89% and 88%. There were statically significant differences between the 2 procedure methods (p 0.01, p 0.02). But, procedure times
had no statically significant (45min vs 33 min, p 0.10). In newly attempted
retrograde trans-pyloric antral dissection method group, en bloc resection rate
was 100%, and the rate of complete resection was 94%. The average time of
procedure was 42min. Compared with the previously procedured retroflexion

United European Gastroenterology Journal 2(1S)


ESD, the new technique had an advantages of saving procedure time (42min vs
48min, p 0.035). but there was no statically significant differences at En-block
resection and complete resection (100% vs 94%, p 0.054 / 94% vs 83%,
p 0.059). Major procedure-related complications consisting of perforation
and major bleeding were not encountered in all cases.
CONCLUSION: This new retrograde trans-pyloric antral dissection method for
resecting tumors involving the pyloric channel tumor is feasible and effective
therapeutic ESD method. So it could be the standard treatment method in
such cases, based on the favorable outcomes.
Disclosure of Interest: None declared
P1070 PERIOPERATIVE CHEMOTHERAPY IN ELDERLY PATIENTS
WITH GASTRIC CARCINOMA: YES OR NO?
J. Moleiro1,*, D. Trabulo2, A. Ferreira3, R. Dion sio4, C. Cardoso5, A. Pimenta6,
S. Mao de Ferro1, M. Serrano1, S. Ferreira1, A. Lu s5, J. Freire5, R. Casaca7,
A. Bettencourt7, A. Dias Pereira1
1
Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.
P. E., Lisboa, 2Gastroenterology, Hospital de Sao Bernardo, Setubal,
3
Gastroenterology, Centro Hospitalar do Algarve, Portimao, 4Medical Oncology,
Centro Hospitalar do Algarve, Faro, 5Medical Oncology, 6Radiation Oncology,
7
Digestive Surgery, Instituto Portugues de Oncologia de Lisboa Francisco Gentil,
E. P. E., Lisboa, Portugal
Contact E-mail Address: joana_moleiro@hotmail.com
INTRODUCTION: Perioperative chemotherapy (POC) is recommended for
patients with advanced resectable gastric (GC) or esophagogastric junction
(EGJ) carcinoma. However, its application in elderly patients could be limited
due to comorbidities.
AIMS & METHODS: We intend to assess compliance, toxicity and survival in
patients proposed to POC who are 470 years old. Among 418 patients with GC
or EGJ carcinoma (February 2009 June 2013), 148 were eligible for POC, of
whom 54 were 470 years old (group 1) and 94 570 years old (group 2). We
evaluated clinical characteristics, Charlson comorbidity index (CCI), compliance
and toxicity, resectability and survival. In our institution, patients who are 480
years old are excluded from POC. Statistics: chi2, t-Student, Kaplan Meier,
Logrank (Stata 10).
RESULTS: Group 1: 54 patients (34 males, mean age 74 years, intestinal type
adenocarcinoma 75.9%, diffuse carcinoma 24.1%. Mean CCI 7 (44 patients had
43 comorbidities). Out of 54 patients, 50 started pre-operative chemotherapy
but 9 did not complete it (6 treatment complications; 1 disease progression; 1
refusal; 1 death). 45/50 (90%) patients were submitted to surgery (R0 35; R1
2; R2 1; unresectable disease 1). Among 23 patients proposed to postoperative chemotherapy, 21 completed 3 cycles. Comparing both groups, 21/54
patients (39%) in group 1 completed POC vs 51/94 (54%) in group 2 (p 0.1). In
group 1, patients experienced more complications during pre-operative chemotherapy (major complications: 15/54 vs 11/94; p 0.006), fewer patients
were submitted to surgery (45/54 vs 94/94; p 0.002) and started post-operative
chemotherapy (22/54 vs 24/94; p 0.036). However, recurrence and survival were
not influenced by age (p 0.8).
CONCLUSION: In patients with 470 years old, POC is associated with more
risks. However, overall and disease free survival in this group is similar to the one
observed in younger patients. Therefore, elderly patients should not be excluded
from POC considering only their age.
Disclosure of Interest: None declared
P1071 SHOULD WE PERFORM PERIOPERATIVE CHEMOTHERAPY
TO ALL PATIENTS WITH LOCALLY ADVANCED GASTRIC
CANCER?
J. Moleiro1,*, C. Calle2, S. Mao de Ferro1, D. Trabulo3, A. Ferreira4,
C. Cardoso5, R. Dion sio6, A. Pimenta7, M. Serrano1, S. Ferreira1, A. Lu s5,
J. Freire5, R. Fonseca2, P. Chaves2, A. Dias Pereira1
1
Gastroenterology, 2Pathology, Instituto Portugues de Oncologia de Lisboa
Francisco Gentil, E. P. E., Lisboa, 3Gastroenterology, Hospital de Sao Bernardo,
Setubal, 4Gastroenterology, Centro Hospitalar do Algarve, Portimao, 5Medical
Oncology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E. P. E.,
Lisboa, 6Medical Oncology, Centro Hospitalar do Algarve, Faro, 7Radiation
Oncology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E. P. E.,
Lisboa, Portugal
Contact E-mail Address: joana_moleiro@hotmail.com
INTRODUCTION: Perioperative chemotherapy (POC) is currently the goldstandard treatment of locally advanced gastric cancer, increasing in 10% the
overall survival. Histopatological tumor regression (HTR) is an important objective parameter of response, being associated with a better outcome. However, in
patients with limited response, surgery delay may compromise a curative
treatment.
AIMS & METHODS: To evaluate in patients proposed to POC: 1) disease
progression during POC; 2) HTR and its correlation with clinicopathological
variables. 148 patients were proposed for POC and 2 for POC plus intraperitoneal chemotherapy. All surgical specimens were reviewed by two pathologists.
HTR was defined by Becker s classification (Ia no residual tumor; Ib residual
tumor: 510%; II residual tumor: 10-50%); III residual tumor: 450%) and
correlated with clinicopathological variables and survival. Statistics: chi2,
Kaplan-Meier, Logrank (Stata 10).
RESULTS: Among 150 patients, 143 were treated with POC (5 excluded due to
disease progression). 135 of whom were submitted to surgery (no surgery: 1
treatment complications; 4 death due to chemotherapy; 2 refusal; 1 disease
progression). Type of resection: R0 102; R1 5; R2 11; unresectable disease
17. Therefore, disease progression was observed in 34 patients and complications

A427
/ death in 5. HTR was evaluated in all patients submitted to resection: Ia 11
(9.3%), Ib 9 (7.6%), II 30 (25.4%), III 68 (57.6%). Besides early tumor
staging (T 1/2) (p 0.008) no other variables (age, sex, differentiation degree,
histologic subtype, tumor location) predicted HRT. All patients with palliative
resections had partial (II) or minimal (III) HRT. Patients with Ia/Ib HTR
showed less relapse rate (1/20 vs 26/87, p 0.037) and better overall survival
(88 vs 54%, p 0.041).
CONCLUSION: We didnt find predictive variables of HRT and 39 patients
(26%) could have been harmed due to delayed surgery. We admit that the benefit
from POC is observed in a small group of patients. It is necessary to identify new
markers of HTR which could help in the selection of patients who can really
benefit from POC.
Disclosure of Interest: None declared
P1072 CLINICOPATHOLOGIC FEATURES OF TYPE 3 GASTRIC
NEUROENDOCRINE TUMOR
K.J. Lee1,*, H.M. Kim1, S.K. Lee2, W.J. Lee3, S.J. Park4 on behalf of Korean
Gastroenteropancreatic Neuroendocrine Tumor Study Group
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Yonsei University Wonju College of Medicine, Wonju, 2Department of Internal
Medicine, Yonsei University College of Medicine, Seoul, 3Center for Liver Cancer,
National Cancer Center, Goyang, 4Department of Internal Medicine, Kosin
University College of Medicine, Busan, Korea, Republic Of
Contact E-mail Address: smild123@yonsei.ac.kr
INTRODUCTION: Type 3 gastric neuroendocrine tumor (NET) is different
from type 1 and type 2 gastric NET in view of management approach. The
standard treatment of type 3 gastric NET is suggested as radical gastrectomy.
Clinically endoscopic treatment has been tried. The aim of this study was to
investigate clinicopathologic features of type 3 gastric NET according to the
treatment modalities.
AIMS & METHODS: The Korean Society of Gastrointestinal Cancer has been
conducting the Korean Gastroenteropancreatic Neuroendocrine Tumor Registry
from 2012. This is a retrospective registry database of gastroenteropancreatic
neuroendocrine tumor collected from 16 hospitals between 2002 and 2012.
From the Registry, gastric NET patients with normal serum gastrin level
(5100 pg/mL) were selected for analysis.
RESULTS: A total of 20 patients from 327 patients with gastric NET were
classified as type 3 Gastric NET. The mean age was 55.5  11.52 years. The
mean tumor size was 1.08  1.10 cm. According to the WHO 2010 classification,
14 (70%) patients had grade 1, and 5 (25%) patients had grade 2. Endoscopic
treatment was performed in 13 (65%) patients, and surgery was performed in 6
(30%) patients. Endoscopic treatment group was younger than surgery group. T1
stage was more prevalent in endoscopic treatment group than in surgery group.
After treatment, the median follow-up time was 10 months, during when there
was no death related to NET, but there was one disease-progression in surgery
group.
CONCLUSION: Clinically, Type 3 gastric NET has been frequently managed by
endoscopy. However, proper evidence for endoscopic management should be
further evaluated.
Disclosure of Interest: None declared
P1073 ASSESSMENT
OF
THE
SAFETY
OF
ENDOSCOPIC
SUBMUCOSAL DISSECTION IN VERY ELDERLY PATIENTS
M. Nishimura1,*, H. Kanbbayashi2, Y. Ushio2, K. Nakajima2, M. Sasaki2,
S. Uegaki2
1
Department of Gastrointestinal Endoscopy, 2Department of Gastroenterology,
Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
Contact E-mail Address: nimakoto@gmail.com
INTRODUCTION: Since endoscopic submucosal dissection (ESD) has been
developed for en bloc resection of large superficial tumors, it is widely accepted
as a reliable therapeutic procedure. This recent innovation allows safe treatment
in elderly patients; however, there are only few reports of ESD in very elderly
patients, aged 85 years old or above. This study aimed to assess the safety and
feasibility of ESD in very elderly patients.
AIMS & METHODS: Between 2013 and 2014, patients with superficial gastrointestinal lesions at our institution were treated with ESD. A standard gastroscope (GIF-Q 260Z, Olympus) and a Dual knife (KD-650Q, Olympus) were used
for ESD. All patients were treated under conscious sedation with midazolam (110mg). Patients were divided to an elderly group (60-84 years of age) and a very
elderly group (85-92 years of age). For both groups, lesion sizes, procedure times,
total amounts of midazolam, and ESD-related complications (hypotension,
hypertension, hypoxia, arrhythmia, and bleeding) were analyzed.
RESULTS: From the database, we collected data on a total of 67 patients who
underwent ESD for esophageal (5 cases), gastric (44 cases), and colorectal lesions
(18 cases). In the elderly group, 49 patients were treated (35 males/ 14 females,
60- 84 years of age, mean age 78) and in the very elderly group, 19 patients were
treated (4 males / 14 females, 85-92 years of age, mean age 87.9). All patients were
successfully treated with ESD in both groups. The mean resected specimen size
was 29.8 mm in the elderly group and 28.37 mm in the very elderly group
(p 0.8). ESD time was 79.5 minutes in the elderly group and 64.5 minutes in
the very elderly group (p 0.4). Midazolam doses of 6.7mg and 3.9 mg were
administered (p50.01), and the complication rate was 12.0% and 57.9%
(p50.01), in the same groups, respectively. Complications were 1 event of hypotension, 1 of hypertension, 4 of hypoxia, and 3 of bleeding in the elderly group,
and 4 of hypotension, 1 of hypertension, 6 of hypoxia, and 0 of bleeding in the
very elderly group. Based on the final pathological results, there were 2 cases on
whom additional gastrectomy was performed, and 1 case of radiation in the

A428

United European Gastroenterology Journal 2(1S)

elderly group; and no additional therapy was performed in the very elderly
group.
CONCLUSION: Our data suggests that ESD is safe and feasible in very elderly
patients; however, such patients tended to be more sensitive to sedation. Our data
also suggests that general anesthesia might not necessary for elderly and very
elderly patients undergoing ESD, as long as there is intraoperative management.
Further investigations to evaluate various other factors including past medical
history, performance status, and anticoagulant medicine are necessary.
Disclosure of Interest: None declared

infected patients are showing mainly a Th17 response (for ulcer 75%, for nonulcer 60 %) instead of Th1 response (for ulcer 25%, for nonulcer 40 %).
CONCLUSION: Overall our data suggests that patients infected with H.pylori
strains positive for cagA, vacAs1m2, and HpaA are at higher risk for developing
Th17- driven intestinal metaplasia.
Disclosure of Interest: None declared

P1074 PREVALENCE OF GASTRIC PRECANCEROUS


AMONG CHRONIC DYSPEPTIC PATIENTS AND RELATED
COMMON RISK FACTORS

R. Meharich1,*, M. Tahiri1, S. Oussama1, A. Bellabah1, F. Haddad1, W. Hliwa1,


W. Badre1
1
Gastroenterology, Ibn Rochd University Hospital, Casablanca, Morocco

LESIONS

M. Sohrabi1,*, F. Zamani1, H. Ajdarkosh1, M. Moradiani1, N. Rakhshani1


1
Gastrointestinal and Liver Disease Research Centre, Iran University, Tehran,
Iran, Islamic Republic Of
Contact E-mail Address: sohrab_r@yahoo.com
INTRODUCTION: Gastric cancer is one of the leading causes of cancer-related
deaths worldwide. Progression of gastric cancer follows a several steps from
gastritis to atrophy, intestinal metaplasia, dysplasia, and finally cancer.
AIMS & METHODS: To determine the prevalance of precancerous gastric
cancer lesions and related common risk factors in our area.
A total of 688 Iranian chronic dyspeptic patients over the age of 40 years were
enrolled. The exclusion criteria were pregnancy, history of gastric cancer and
gastric surgery. A questionnaire including demographic and clinical data, smoking habits, alcohol use, NSAIDs and regular aspirin use was completed for all
subjects. Upper endoscopy was done for all of participants and biopsies were
taken according to biopsy protocol. The specimens were studied by two expert
GI pathologists blindly.
RESULTS: The prevalence of intestinal methaplasia, gastric atrophy, and dysplasia were 19.8%, 12.8%, and 3.2%, respectively. The mean age of participants
was 57.879.10. Positive H.pylori infection was 64.5%. Age and H.pylori infection had a significant association with pathological findings with OR 3.10, P5
0.01, 95%CI: 1.91-4.72 and OR 1.03, P5 0.01, 95%CI: 1.03-1.07 respectively.
Male gender also had an association with gastric atrophy (OR 1.57, 95%
CI 1.00-2.46).
CONCLUSION: According to high prevalence of precancerous lesions in
patients with chronic dyspepsia over 40 years old, upper endoscopy and gastric
mapping sampling for detection of these lesions is recommended in intermediate
to high risk areas.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
H. PYLORI II POSTER EXHIBITION HALL XL_____________________

P1076 THE
RELATIONSHIP
BETWEEN
THE
DENSITY
OF
HELICOBACTER PYLORI COLONIZATION AND THE DEGREE OF
GASTRITIS SEVERITY

INTRODUCTION: Helicobacter pylori (H. pylori) is a major factor in determining the risk for development of gastric adenocarcinoma through the intermediate
steps of atrophic gastritis and intestinal metaplasia. Because H. pylori infection is
highly prevalent in asymptomatic populations and only a few people develop
cancer, additional factors may influence the risk for development of cancer
and preneoplastic lesions, once infection is established.
AIMS & METHODS: The aim of this study is to examine the relationship
between the density of H. pylori colonization in gastric mucosa and the degree
of severity of certain histologic parameters of gastritis, such as inflammation
activity, atrophy and intestinal mataplasia.
Upper gastrointestinal endoscopy was performed in 410 H. pylori positive
patients. Status and semiquantitative assessment of H. pylori was determined
by histology. Gastric biopsies were examined under hematoxylin and eosin and
Giemsa stains. Density of H. pylori colonization, activity of gastritis, gastric
atrophy and intestinal metaplasia at different parts of stomach were graded
according to Updated Sydney system.
RESULTS: There were 410 H. pylori positive patients (214 males and 196
females), whose age ranged from 18 to 90 years (mean age 46 years).
The density of H. pylori was mild in 30.2%, moderate in 51.5%, and marked in
18.3% of cases.
The results of the study showed that along with the increase of density of H.
pylori colonization there was a tendency of increasing the gastritis severity:

Active gastritis
Gastric atrophy
Intestinal metaplasia

Mild density
of H. pylori

Moderate
density of
H. pylori

Marked
density
of H. pylori

58.1%
26.6%
7.3%

70.1%
33.2%
10%

88%
42.7%
14.7%

p 5 0.01
p 5 0.01
p 5 0.1

P1075 CAGA, VACAS1M2 , AND HPAA H. PYLORI STRAINS


PROMOTES TH-17 DRIVEN INTESTINAL METAPLASIA IN H.
PYLORI-INFECTED PATIENTS

CONCLUSION: It can be concluded that a marked density of H. pylori colonization significantly increases the gastritis severity.
Disclosure of Interest: None declared

A. Tiftikci1, S.O. Okullu2,3, M. Saruc1, E.N. Vardareli1, B. Cicek1, S. Goksel4,


A. Bozbas5, T. Kocagoz3, N.A. Tozun1,*, A.S. Yazgan2
1
Gastroenterology Department, Acibadem University Medical Faculty,
2
Department of Molecular Biology & Genetics, Istanbul Techncal University,
3
Department of Medical Microbiology, Acibadem University Medical Faculty,
4
Department of Pathology, 5Gastroenterology Department, Acibadem Hospitals
_
Group, Istanbul,
Turkey

P1077 PREVENTION OF LARGE INTESTINE DYSBIOSIS IN THE


PATIENTS WITH DUODENAL ULCER ASSOCIATED WITH
HELICOBACTER PYLORI

INTRODUCTION: Helicobacter pylori (H.pylori) is a gram-negative bacterium


that colonizes the stomach of more than half of the worlds population during
their life span. H.pylori infection can cause peptic ulcer, chronic gastritis,
mucosa-associated lymphoid tissue (MALT) lymphomas in 20 % of infected
individuals. H.pylori-induced diseases can be associated with virulence factors
of bacteria, host genetic factors and immune response. Virulence factors with
potential value for specific pathologies are the cytotoxin associated gene A (cag
A), vacuolating cytotoxin A (vacA), outer inflammatory protein A (oipA), the
blood group antigen binding adhesin gene A (babA), and the putative neuraminyllactose-binding hemaggluttinin homolog (hpaA). H.pylori infection induces T
helper 1 (Th1) & T helper 17 (Th17) driven immune response in patients.
AIMS & METHODS: The aim of this study was to investigate the correlation of
H.pylori- induced gastric pathologies with various H.pylor virulence factors and
T cell response. Eighty consecutive H.pylorii positive endoscopy patients were
included in the study. Mucosal biopsy samples were obtained from corpus and
antrum parts of the stomach during endoscopy. All samples were tested for
various H.pylori virulence factors using multiplex polymerase chain reaction
(Multiplex-PCR) including cagA, vacA (s1,s2;m1,m2), hpaA, oipA, babA.
Also, IFN-g (Th1) and IL-17 (Th17) mRNA expression levels of patients were
measured using Quantitative RT-PCR.
RESULTS: Our study group consisted of 43 women and 37 men, mean age was
35 years (range 16-65 y). Twenty-three out of 80 H.pylori positive patients also
had peptic ulcer. The majority of H.pylori strains are positive for hpaA (82% of
ulcer, 75% of nonulcer patients) and vacA s1, m2 (52% of ulcer, 73% of nonulcer
patients) but negative for oipA and babA. Also, the vast majority of the H.pylori
strains isolated from nonulcer patients were cagA positive (61%). However, 56%
of peptic ulcer patients carry cag A negative H.pylori strains. Eleven out of the 80
patients had intestinal metaplasia also (4 of 11 were peptic ulcer patients). All
H.pylori strains isolated from ulcer and non-ulcer patients with intestinal metaplasia are positive for vacA s1/m2 genotype. All patients with the peptic ulcer and
71% of the nonulcer with intestinal metaplasia patients positive for hpa A. Also
the H.pylori hpaA positive strains are negative for babA. Additionally, H.pylori

S.M. Atabaeva1,1,*, F. Khamrabaeva1


1
The Faculty of Gastroenterology and Physiotherapy, Tashkent Institute of
Postgraduate Education of Doctors, Tashkent, Uzbekistan
Contact E-mail Address: doctorcaodat@mail.ru
INTRODUCTION: To study efficacy of eradication therapy and inclusion of
Enterojermin as prevention of intestine dysbiosis in the patients with gastroduodenal ulcer disease in association with the Helicobacter pylori.
AIMS & METHODS: In the investigation there were participated 64 patients
with ulcer disease of duodenum associated with H.pylori. The patients were
randomly divided into 2 groups by 32 patients in each group. Group 1 received
three-component therapy in the complex with Enterojermin 1 bottle 3 times a day
for 14 days. Diagnosis was verified by endoscopy findings. In order to study the
state of microbiocenosis of the large intestine the microbiological examination of
the feces was performed in the patients before and after treatment.
Group 2 received only three-component therapy with inclusion of IPP pantoprasol (Kontrolok) and 2 antibiotics during 14 days.
RESULTS: The standard three-component scheme of eradication on the basis of
kontrolok and two antibiotics seem to be effective in relation to the scarring of
the ulcer defect (96.6%), however, exactly in this group of patients to the end of
treatment, by data of bacteriological feces cultivation there was noted dysbiosis
of stage 3, while by the results of the same data in patients from group 2 who
additionally received enterojermin the ulcer scarring was achieved in 97.2% of
patients without changes of the state of microbiocenosis of the large intestine.
CONCLUSION: The results of investigations performed showed, that inclusion
of the Enterojermin into the complex of eradication therapy of the duodenal
ulcer associated with H.pylori resulted in attenuation of the undesirable actions
of the used antibiotics which effected on the obligatory flora of the large
intestine.
Disclosure of Interest: None declared

A429

United European Gastroenterology Journal 2(1S)


P1078 A RAPID AND ACCURATE METHOD TO EVALUATE
HELICOBACTER PYLORI INFECTION, CLARITHROMYCIN
RESISTANCE AND CYP2C19 GENOTYPES SIMULTANEOUSLY
FROM GASTRIC JUICE
F.-C. Kuo1,2,*, C.-C. Yang3, C.-J. Liu4, G.-H. Jheng5, H.-Y. Shih6, C.-H. Kuo4,
L.-L. Chang3, D.-C. Wu4,6
1
Department of Obstetrics and Gynecology, E-Da Hospital, 2School of Medicine,
College of Medicine, I-Shou University, 3Department of Microbiology, Kaohsiung
Medical University, 4Division of Gastroenterology, Kaohsiung Medical University
Hospital, 5Department of Internal Medicine, Kaohsiung Municipal United
Hospital, 6Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang
Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Province of China
Contact E-mail Address: dechwu@yahoo.com
INTRODUCTION: Because Helicobacter pylori (H.pylori) can cause carcinogenesis of the stomach, we need sufficient information for deciding on an appropriate strategy of eradication. Many factors affect the efficacy of eradication
including antimicrobial resistance (especially clarithromycin resistance) and
CYP2C19 polymorphism. This study was to survey the efficiency of gastric
juice for detecting the clarithromycin resistance and CYP2C19 polymorphism.
AIMS & METHODS: The specimens of gastric juice were collected from all
patients while receive gastroendoscopy. DNA was extracted from gastric juice
and then urease A and cag A were amplified by polymerase chain reaction (PCR)
for detecting the existence of H.pylori. By PCR-RFLP, the 23S rRNA of H.pylori
and CYP2C19 genotypes of host were examined, respectively. During endoscopy
examination, biopsy-based specimens were also collected for rapid urease test,
culture and histology. The blood samples were also collected for analysis of
CYP2C19 genotypes. We compared the results of gastric juice tests with the
results of traditional clinical tests.
RESULTS: Our results showed that the sensitivity(SEN), specificity(SPE), positive predictive value(PPV), negative predictive value(NPV) and accuracy(ACC)
of gastric juice test to detect H.pylori infection were 92.1%(105/114), 92.9%(143/
154), 90.5%(105/116), 94.1%(143/152) and 92.5%(248/268) respectively. The
SEN, SPE, PPV and NPV to detect clarithromycin resistance were 97.3% (36/
37), 91.5% (43/47), 90.0%(36/40) and 97.7%(43/44) respectively. By using PCRRFLP, the consistency of human CYP2C19 gene polymorphism from blood
samples and gastric juice was as high as 94.9%(149/157).
CONCLUSION: The manipulated gastric juice is actually an effective diagnostic
sample for evaluation of H.pylori existence, clarithromycin resistance, and host
CYP2C19 polymorphism.
Disclosure of Interest: None declared
P1079 HIGH RESOLUTION MELT CURVE ASSAY FOR
DETECTION OF POINT MUTATIONS ASSOCIATED WITH
CLARITHROMYCIN RESISTANCE IN HELICOBACTER PYLORI

THE

T.T. Perets1, E. Shporn1, D. Hamouda1, F. Valle2, R.M. Dickman3,*, Y. Niv3


1
Gastroenterology Laboratory, Rabin Medical Center - Beilinson Hospital, Petah
Tikva, Israel, 2Faculty of Engineering, Catholic University of Portugal, Rio de
Mouro, Portugal, 3Department of Gastroenterology, Rabin Medical Center Beilinson Hospital, Petah Tikva, Israel
Contact E-mail Address: kaiser1974@gmail.com
INTRODUCTION: Clarithromycin is used in the first line treatment of
Helicobacter pylori (HP) infection and therefore, the prevalence of HP resistance
to clarithromycin is increasing continuously. Clarithromycin resistance, the
major cause of HP treatment failure, is attributed to three point mutations
(PM): A2142C, A2142G and A2143G within the peptidyl-transferase region of
the 23S rRNA gene.
AIMS & METHODS: To develop a fast and accurate method for the detection
of the three mutations mentioned previously, from HP isolates. A total of 85 HP
isolates, previously obtained from patients with general gastric discomfort, were
analyzed using a high resolution melt (HRM) curve analysis. The isolates were
compared to 4 reference plasmids that incorporate the three mutations and the
wild type (WT) sequences.
RESULTS: There was a perfect correlation between the HRM results and the 85
positive isolates all were positive using the HRM analysis. Of the 85 isolates, 18
had a WT sequence (21.2%), and 67 (78.8%) contained a 23S rRNA PM. Of the
67 isolates that include 23S rRNA PM, 18 had an A2142G PM sequence
(26.8%), 22 had an A2142C PM sequence (32.8%) and 27 had an A2143G
PM sequence (40.4%).
CONCLUSION: Our developed HRM assay has a perfect correspondence in its
accuracy to other detection methods, including HP isolation. It serves as an
option for detecting Clarithromycin resistance prior to administration of HP
eradication therapy.
Disclosure of Interest: None declared
P1080 STABILITY OF 13CO2 BREATH TESTS SAMPLES OVER TIME IN
THE DIAGNOSIS OF HELICOBACTER PYLORI
T.T. Perets1, E. Shporn1, D. Hamouda1, R.M. Dickman2,*, Y. Niv2
1
Gastroenterology Laboratory, 2Department of Gastroenterology, Rabin Medical
Center - Beilinson Hospital, Petah Tikva, Israel
Contact E-mail Address: kaiser1974@gmail.com
INTRODUCTION: The accuracy and repeatability of breath test in the diagnosis of Helicobacter pylori (HP) infection is debatable. Although it has been shown
that storage for long periods does not affect the analysis results, no data are
available, on the effect of repetitive testing.

AIMS & METHODS: To evaluate the repeatability of the analysis of the breath
samples. A total of 202 breath samples were collected in duplicates, before and
after administration of 75 mg urea-13C dissolved in 50 ml of orange juice and the
results were expressed as delta 13CO2 (d13CO2). The cut-off value was 3.5 parts
per thousand. Each sample was analyzed in a mass spectrometer 7 days after
collection and in intervals of 7 days for the duration of additional 3 weeks. The
precision calculation was based on the comparison of the d13CO2 obtained in the
three consecutive weeks following the first run to the d13CO2 obtained in the first
run. The samples were stored at room temperature.
RESULTS: In the second run, 200 out of the 202 (99%) samples were tested
positive for HP and the precision of the d13CO2 was 98.6%. In the third run, 197
out of the 202 (97.52%) samples tested positive and the precision was 99.2%. In
the fourth and final run 196 out of the 202 (97%) samples tested positive and the
precision was 96.7%.
CONCLUSION: We conclude that short term storage of 1 month, does not
affect sample stability and the results of HP diagnosis for up to three consecutive
repeats.
Disclosure of Interest: None declared
P1081 HIGH PREVALENCE OF MULTI-DRUG RESISTANCE IN H.
PYLORI ISOLATES IN 1001 TREATED NAIVE PATIENTS
V. Castelli1,*, J.M. Bland2, G. Fiorini1, N. Vakil3, I.M. Saracino1, C. Zaccaro1,
C. Ricci4, A. Zullo5, L. Gatta6, D. Vaira1
1
Department of Medical and Surgical Sciences, University of Bologna, Bologna,
Italy, 2Department of Health Sciences, University of York, York, United Kingdom,
3
School of Medicine & Public Health, University of Wisconsin, Madison, United
States, 4Gastroenterology Unit, University of Brescia, Brescia, 5Department of
Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital,
Rome, 6Gastroenterology and Digestive Endoscopy Unit, Versilia Hospital, Lido di
Camaiore, Italy
Contact E-mail Address: berardino.vaira@unibo.it
INTRODUCTION: Antibiotic resistant strains of H pylori have been increasing
worldwide, and it has been speculated that this may account for progressive
decrease in eradication rates reported in the literature.
AIMS & METHODS: To assess the prevalence of resistant strains to metronidazole, clarithromycin, and levofloxacin in a cohort of treatment na ve patients
undergoing EGDS for dyspeptic symptoms in Italy. 1065 H.pylori infected
patients who had never been treated for H pylori (median age: 51 years; IQR:
39 and 62 years) underwent upper endoscopy and a biopsy sample was also
obtained to perform culture and an in vitro antimicrobial susceptibility testing.
According to EUCAST 2012 guidelines, susceptibility testing was performed by
epsilometer test (Etest) and the following MIC breakpoints were used: resistance
to clarithromycin (40.5 microgram/ml); resistance to metronidazole (48 microgram/ml), and resistance to levofloxacin (41 microgram/ml).
RESULTS: Data on resistance were available for 1001 out of 1065 (93.9%)
patients. Resistance to metronidazole was found in 38.3%; to clarithromycin
in 32.7%; and to levofloxacin in 23.7% of the strains. Double resistance to
clarithromycin metronidazole was found in 10.4%; to clarithromycin levofloxacin in 2.8%; and to metronidazole levofloxacin in 5.6% whilst 10.4% of
the strains were resistant to metronidazole clarithromycin levofloxacin.
Female sex was found to be an independent factor of both metronidazole resistance (OR: 2.5, 95% CI 1.9-3.3; p 0.0001) and double resistance to metronidazole and clarithromycin (OR: 2.5, 95% CI 1.5 4.0; p 0.0001). Similarly, an
association with single metronidazole and clarithromycin resistance was found
among non-Italian patients (OR: 2.0, 95% CI 1.4 3.0; p 0.0001 and OR: 1.8,
95% CI 1.2- 2.6, p 0.003 respectively). Smoking, alcohol consumption, and
BMI were not significant risk factors.
Resistance

ClaR (overall)
MetroR (overall)
LevoR (overall)
ClaR MetroR
ClaR LevoR
MetroR LevoR
ClaR MetroR LevoR

32.7
38.3
23.7
10.4
2.8
5.6
10.4

CONCLUSION: 1. Single and multiple-drug resistant strains are widely prevalent in patients who have never been treated for H pylori. 2. First line therapies
for H pylori need to account for these changes because failure rates for clarithromycin based therapy will increase further 3. Levofloxacin based triple therapies are unlikely to represent an alternative front-line therapy as the resistance
rates are already quite high.
Disclosure of Interest: V. Castelli: None declared, J. M. Bland: None declared, G.
Fiorini: None declared, N. Vakil Consultancy for: Astra Zeneca, Takeda,
Shareholder of: Meridian Diagnostic, Orexo, I. M. Saracino: None declared,
C. Zaccaro: None declared, C. Ricci: None declared, A. Zullo: None declared,
L. Gatta: None declared, D. Vaira: None declared

A430

United European Gastroenterology Journal 2(1S)

P1082 THE MEANING OF THE BORDERLINE RANGE OF THE 13C-UBT


VALUE AFTER HELICOBACTER PYLORI ERADICATION
Y.H. Kwon1,*, N. Kim1, J.Y. Lee1, Y.J. Choi1, K.C. Yoon1, J.J. Hwang1,
H.J. Lee1, A.R. Lee1, Y. Jung1, H. Yoon1, C.M. Shin1, Y.S. Park1, D.H. Lee1
1
Internal medicine, Seoul National University Bundang Hospital, Sungnam, Korea,
Republic Of
INTRODUCTION: The 13C-urea breath test (13C-UBT) (UBiTkit; Otsuka
Pharmaceutical, Tokyo, Japan) is a reliable non-invasive method for diagnosing
Helicobacter pylori (H. pylori) infection. However, in some range of 13C-UBT
value, the accuracy is doubtful after eradication of H. pylori infection.
AIMS & METHODS: In this study, we evaluated the diagnostic accuracy of the
13
C-UBT value ranging from 2.0% to 3.0% and affecting factors were evaluated.
Among 820 patients who showed the result of the 13C-UBT value from 2.0% to
3.0%, one hundred seventy one patients were compared with the results of endoscopic biopsy-based methods (modified Giemsa study, CLOtest, and culture)
from antrum as well as body for two years or more endoscopic surveillance. In
addition, the possible affecting factors such as age, gender, underlying disease,
history of gastrectomy, number of eradications, and histological atrophy and
intestinal metaplasia were analyzed.
RESULTS: Of 91 and 80 patients who showed 13C-UBT positive and negative
results after H. pylori eradication, 38 patients (41.8%) and 2 patients (2.5%) were
proved false positive and false negative results by biopsy-based methods evaluation, respectively. The sensitivity, specificity, false positive rate, and false negative
rate of 13C-UBT were 96.4%, 67.2%, 33.8%, and 3.6%. The positive predictive
value and negative predictive value were 58.2% and 97.5%. The positive likelihood ratio and negative likelihood ratio is 2.85 and 0.05. In multivariate analysis (Table 1), moderate to severe intestinal metaplasia (OR 1.953,
95%CI 1.208-3.159, p 0.006) and two or more trial of treatment for H.
pylori (OR 2.482, 95%CI 1.109-5.555, p 0.027) were significantly related
false positive result of 13C-UBT value after H. pylori eradication.
Table 1. The risk factors of false positive results for 13C-Urea breath test
Final UBT result
Positive
Gender (Male:Female)

30(56.6%)/
23(43.4%)
Age ( 60 years old)
23 (43.4%)
Diabetes mellitus
6 (11.38%)
Hypertension
11 (20.8%)
History of gastrectomy
12 (22.6%)
The number of eradication 40(75.5%)/
for Helicobacter pylori 13(24.5%)
(Once / Two or more)
The degree of gastric
49(92.4%)/
mucosal atrophy (None 4(7.5%)
to mild/moderate to
severe)
44 (83.0%)/
The degree of gastric
9(17.0%)
intestinal metaplasia
(None to mild/moderate
to severe)

Univariate Multivariate
False positive p-value
p-value
24(63.2%)/
14(36.8%)
18 (47.4%)
3 (7.9%)
7 (18.4%)
8 (21.1%)
19(50.0%)/
19(50%)

NS
NS
NS
NS
NS
0.034

31(81.6%)/
7(18.4%)

NS

21(55.3%)/
17(44.7%)

0.015

0.027

0.006

CONCLUSION: In the range of 13C-UBT value from 2.5% to 3.0%, false positive was found to be increased in this study. In this case endoscopic surveillance
with biopsy based evaluation would be helpful to avoid unnecessary additional
treatment for H. pylori infection.
Disclosure of Interest: None declared
P1083 THE EFFECTS OF N-ACETYLCYSTEINE ON FIRST-LINE 10-DAY
SEQUENTIAL THERAPY FOR HELICOBACTER PYLORI
INFECTION: A RANDOMIZED CONTROLLED TRIAL
H. Yoon1,*, D.H. Lee1,2, A.-R. Lee1, J.J. Hwang1, C.M. Shin1, Y.S. Park1,
N. Kim1,2, H.C. Jung2, I.S. Song1
1
Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
2
Internal Medicine and Liver Research Institute, Seoul National University College
of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: bodnsoul@hanmail.net
INTRODUCTION: There have been a few reports suggesting that N-acetylcysteine (NAC) which is mucolytic and antioxidant could destroy biofilm formed by
Helicobacter pylori (H. pylori). The aim of this study was to identify whether the
addition of NAC on first-line sequential therapy for H. pylori infection could
improve the eradication rate.
AIMS & METHODS: Ninety nine patients with H. pylori infection were randomly assigned to receive either sequential therapy with (study group, n 49) or
without (control group, n 50) NAC. Sequential therapy consisted of rabeprazole 20mg and amoxicillin 1g for the first 5 days, followed by rabeprazole 20mg,
clarithromycin 500mg and metronidazole 500mg for the remaining 5 days; all
drugs are given twice daily. For study group, NAC 400mg b.i.d. was added for
the first 5 days of sequential therapy. Four weeks after completing therapy, H.
pylori eradication was evaluated by the 13C-urea breath test, histology, or the

rapid urease test. The eradication rate, drug compliance, and adverse event rates
were compared between the two groups.
RESULTS: The eradication rates by intention-to-treat analysis were 58.0% (29/
50) and 67.3% (33/49) in the control group and the study group, respectively
(P 0.336). The eradication rates by per-protocol analysis after excluding16.2%
of patients who were lost to follow-up were 70.0% (28/40) and 80.5% (33/41) in
the control group and the study group, respectively (P 0.274). Compliance was
very good in the both groups (control/study group: 95.2%/100%). The adverse
event rates were 26.2% (11/42) and 26.8% (11/41) in the control group and the
study group, respectively (P 0.947).
CONCLUSION: The addition of NAC to first-line sequential therapy for H.
pylori infection resulted in an approximately 10% increase in eradication rate.
However, this feature did not reach statistical significance, indicating that larger
trials are needed.
REFERENCES
Huynh HQ, et al. N-acetylcysteine, a novel treatment for Helicobacter pylori
infection. Dig Dis Sci 2004; 49: 1853-1861.
Gurbuz AK, et al. Effect of N-acetyl cysteine on Helicobacter pylori. South Med
J 2005; 98: 1095-1097.
Tran CD, et al. Novel combination therapy for the eradication of Helicobacter
pylori infection in a mouse model. Scand J Gastroenterol 2010; 45: 1424-1430.
Cammarota G, et al. Biofilm demolition and antibiotic treatment to eradicate
resistant Helicobacter pylori: a clinical trial. Clin Gastroenterol Hepatol 2010; 8:
817-820 e813.
Makipour K, et al. The potential role of N-acetylcysteine for the treatment of
Helicobacter pylori. J Clin Gastroenterol 2011; 45: 841-843.
Cammarota G, et al. Review article: biofilm formation by Helicobacter pylori as
a target for eradication of resistant infection. Aliment Pharmacol Ther 2012; 36:
222-230.
Disclosure of Interest: None declared
P1084 THE EFFECT OF MOXIFLOXACIN CONTAINING TRIPLE
THERAPY AS SECOND-LINE TREATMENT FOR HELICOBACTER
PYLORI ERADICATION INFECTION
J.J. Hwang1,*, D.H. Lee1, K.C. Yoon1, H.J. Lee1, Y. Jeong1, A.-R. Lee1,
Y.H. Kwon1, H. Yoon1, C.M. Shin1, Y.S. Park1, N. Kim1, S.Y. Seol2
1
Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
2
Internal Medicine, Inje University Paik Hospital, Busan, Korea, Republic Of
Contact E-mail Address: frontierassa@hanmail.net
INTRODUCTION: The aim of this study was to evaluate the efficacy of a
moxifloxacin-containing triple therapy as second-line treatment for
Helicobacter pylori infection. We investigated the value of triple therapy with
rabeprazole, moxifloxacin, and amoxicillin in second-line treatment and the
impact of treatment of treatment duration on eradication success.
AIMS & METHODS: Between 2011 and 2013, one hundred and thirty-three
patients who had failed first-line proton pump inhibitor-based triple therapy
were randomized to oral rabeprazole (20 mg b.i.d.), axoxicillin (1000 mg
b.i.d.), and moxifloxacin (400 mg q.d.) for either 7 (RAM-7 group, n 52) or
14 days (RAM-14 group, n 81). The eradication was compared by confirming
of eradication rate. H. pylori status was evaluated by histologic finding,
Campylobacter-like organism test and 13C urea breath test. Antibiotic susceptibility test for H. pylori was not done in all cases.
RESULTS: The eradication rates by intention-to-treat analysis were 69.2% (36/
52) and 81.4% (66/81) in the RAM-7 group and the RAM-14 group, respectively
(p 0.031). The eradication rates by per-protocol analysis after excluding 8.4%
of patients who were lost to follow-up were 73.5% (36/49) and 90.4% (66/73) in
the RAM-7 group and the RAM-14 group, respectively (p 0.013). Compliance
was very good in the both groups (RAM-7/RAM-14 group: 100%/100%). The
adverse event rates were 26.5% (13/49) and 20.5% (15/73) in the RAM-7 group
and the RAM-14 group, respectively (p 0.441). There was no significant difference in the 1st-line treatment, previous ulcer history, smoking, alcohol, and endoscopic finding between RAM-7 and RAM-14 group.
CONCLUSION: Second-line H.pylori eradication therapy with rabeprazole,
amoxicillin, and moxifloxacin is very effective and well tolerated. Fourteen
days of treatment significantly showed lower adverse event rates (20.5% vs
26.5%) and higher eradication rates (90.4% vs 73.5%, p 0.013) than seven
days of treatment. Compliance was very good in both groups (100%).
Disclosure of Interest: None declared
P1085 OPTIMIZED TRIPLE AND CONCOMITANT THERAPY FOR H.
PYLORI INFECTION: THE OPTRICON STUDY
J. Molina- Infante1,*, A.J. Lucendo2, T. Angueira2, M. Rodriguez-Tellez3,
A. Balboa4, A. Perez-Aisa5, E. Martin-Noguerol6, J. Barrio7, A. Huerta8,
B.J. Gomez-Rodriguez9, F. Mearin4, J.M. Botargues-Bote10, J. GomezCamarero11, I. Modolell12, I. Arino13, M.T. Herranz Bachiller14, A. Lima15,
M.A. Tejero Bustos8, J. Rodriguez-Sanchez16, J. Perez-Lasala8, N. ManasGallardo8, J. Millastre17, M. Gracia17, F.J. Rancel-Medina6, A. Lanas13,
J.P. Gisbert18
1
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, 2Gastroenterology,
Hospital General, Tomelloso, 3Gastroenterology, Hospital Virgen Macarena,
Sevilla, 4Gastroenterology, Clinica Teknon, Barcelona, 5Gastroenterology, Agencia
Sanitaria Costa del Sol, Marbella, 6Gastroenterology, Hospital Virgen del Puerto,
Plasencia, 7Gastroenterology, Hospital Rio Hortega, Valladolid,
8
Gastroenterology, HM Sanchinarro, Madrid, 9Gastroenterology, Hospital
Sagrado Corazol, Sevilla, 10Gastroenterology, Hospital Bellvitge, Barcelona,
11
Gastroenterology, Hospital Gregorio Maranon, Madrid, 12Gastroenterology,
Consorci Sanitari, Terrassa, 13Gastroenterology, HCU Lozano Blesa, Zaragoza,

United European Gastroenterology Journal 2(1S)


14

Gastroenterology, Hospital Nta Sra Sonsoles, Avila, 15Gastroenterology,


Hospiten Estepona, Estepona, 16Gastroenterology, Hospital General Universitario,
Ciudad Real, 17Gastroenterology, Hospital Miguel Servet, Zaragoza,
18
Gastroenterology, Hospital Universitario de la Princesa, Madrid, Spain
INTRODUCTION: Triple therapy for H. pylori infection is discouraged when
clarithromycin resistance rate is 4 15-20%. Despite increasing antimicrobial
resistance, triple therapy keeps on being the most prescribed eradication therapy,
almost always on an empirical basis (this is, with unknown resistance rates). In
this context, it remains unknown whether a non-bismuth quadruple concomitant
therapy may be a preferable choice as empiric first-line eradication therapy.
AIMS & METHODS: To compare the effectiveness and safety of two optimized
triple and concomitant quadruple therapies for H. pylori empiric treatment.
Prospective multicenter study in 16 Spanish hospitals in which triple therapy
was the first-line eradication regimen in clinical practice. In a first 3-month
phase, patients received an optimized triple therapy, defined by esomeprazole
(40 mg/12h), amoxicillin (1 g/12h) and clarithromycin (500 mg/12h) for 14
days. Over the second 3-month phase, patients received an optimized concomitant treatment, which consisted of an optimized triple therapy plus metronidazole
(500 mg/12h) for 14 days.
RESULTS: 658 consecutive patients have been included so far (360 triple, 298
concomitant). Mean age 50 years, 58% females, 21% smokers, and 26% peptic
ulcer. Intention-to-treat eradication rates were 82.6% (95%CI 79-87%) and
91.2% (88-96%) for triple and concomitant therapy (p 0.008). Respective
per-protocol rates were 83% (79-88%) and 93.7% (89-96%) (p 0.003).
Compliance was 92% for both therapies. Adverse events (AEs) were reported
in 54% of patients (triple 42% vs. concomitant 61%, p50.001). The most
common AEs were metallic taste (46%), diarrhea (18%) and nausea (11%),
with significant differences (p50.05) between therapies. Concomitant therapy
achieved good eradication rates (4 90%) in a higher proportion of centers
(64% vs. 35%) and triple therapy led to unacceptable cure rates (580%) in a
higher proportion of centers (41% vs. 14%).
CONCLUSION: On an empiric basis, an optimized non-bismuth quadruple
therapy achieved significantly higher cure rates (490%) when compared to an
optimized triple therapy. Addition of metronidazole to an optimized triple therapy increased eradication rates by 10%, resulting in a higher rate of adverse
events but withouth impairing compliance. An optimized triple therapy achieved
unacceptable cure rates in 41% of participating centers, so concomitant therapy
should be the choice for empiric eradication in clinical practice.
Disclosure of Interest: None declared
P1086 SECOND-LINE RESCUE THERAPY WITH LEVOFLOXACIN
AFTER FAILURE OF TREATMENT TO ERADICATE
HELICOBACTER PYLORI INFECTION: TIME TRENDS IN A
SPANISH MULTICENTER STUDY OF 1,400 PATIENTS
J.P. Gisbert1,2,*, A. Perez-Aisa3, F. Bermejo4, M. Castro-Fernandez2,5,
P. Almela6, J. Barrio7, A. Cosme8, I. Modolell9, F. Bory10, M. FernandezBermejo11, L. Rodrigo12, J. Ortuno13, P. Sanchez-Pobre14, S. Khorrami15,
A. Franco14, A. Tomas16, I. Guerra4, E. Lamas5, J. Ponce2,13, X. Calvet2,17
1
Gastroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid,
3
Gastroenterology Unit, Agencia Sanitaria Costa del Sol, Malaga,
4
Gastroenterology Unit, Hospital de Fuenlabrada, Madrid, 5Gastroenterology
Unit, Hospital de Valme, Sevilla, 6Gastroenterology Unit, Hospital General de
Castellon, Castellon, 7Gastroenterology Unit, Hospital Rio Hortega, Valladolid,
8
Gastroenterology Unit, Hospital de Donostia, San Sebastian, 9Gastroenterology
Unit, Consorci Sanitari de Terrassa, 10Gastroenterology Unit, Hospital del Mar,
Barcelona, 11Gastroenterology Unit, Hospital San Pedro de Alcantara, Caceres,
12
Gastroenterology Unit, Hospital Central de Asturias, Oviedo, 13Gastroenterology
Unit, Hospital La Fe, Valencia, 14Gastroenterology Unit, Hospital Clnico San
Carlos, Madrid, 15Gastroenterology Unit, Hospital Son Espases, Mallorca,
16
Gastroenterology Unit, Hospital Sant Camil, 17Gastroenterology Unit, Hospital
de Sabadell, Barcelona, Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing
levofloxacin is a potential alternative; however, resistance to quinolones is
rapidly increasing.
AIMS & METHODS: AIM: To evaluate the efficacy and tolerability of a
second-line triple regimen containing levofloxacin in patients whose
Helicobacter pylori eradication treatment failed and to assess whether the efficacy
of the regimen decreases with time.
METHODS: Design: Prospective multicenter study. Patients: Patients in whom
treatment with a regimen comprising a proton pump inhibitor (PPI), clarithromycin, and amoxicillin had failed. Intervention: Levofloxacin (500 mg b.i.d.),
amoxicillin (1 g b.i.d.), and PPI (standard dose b.i.d.) for 10 days. Outcome:
Eradication was confirmed using the 13C-urea-breath test 4-8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and
recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire.
RESULTS: The study sample comprised 1,400 consecutive patients (mean age 49
years, 49% males, 28% peptic ulcer and 72% with functional or non-investigated
dyspepsia), of whom 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 74.6% (95% CI, 72-77%) and 73.4% (7176%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70%
in 2008, 76% in 2009, 73% in 2010, 71% in 2011, 75% in 2012, and 76% in 2013.
In the multivariate analysis, none of the studied variables (including diagnosis
and year of treatment) were associated with success of eradication. Adverse
effects were reported in 19% of patients, most commonly nausea, metallic
taste, myalgia, abdominal pain, diarrhea and aphthous stomatitis. In 9 cases,

A431
the adverse effects were classified as intense (nausea, metallic taste and myalgia), but none of them was severe.
CONCLUSION: Ten-day levofloxacin-containing therapy is an encouraging
second-line strategy, providing a safe and simple alternative to quadruple therapy
in patients whose previous standard triple therapy has failed. The efficacy of this
regimen remains stable with time.
Disclosure of Interest: None declared
P1088 THE ULTIMATE ERADICATION RATE OF H. PYLORI AFTER
1ST, 2ND OR 3RD LINE THERAPY IN KOREA
K. Yoon1,*, N. Kim1, Y.H. Kwon1, J.Y. Lee1, Y.J. Choi1, J.J. Hwang1, H.J. Lee 1,
A.R. Lee1, Y. Jung1, H.J. Jo1, H. Yoon1, C.M. Shin1, Y.S. Park1, D.H. Lee1
1
Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea, Republic Of
Contact E-mail Address: paradise_city@hanmail.net
INTRODUCTION: The resistance rates of H. pylori to clarithromycin, metronidazole and quinolone are known to be over 20% at the tertiary hospital in S.
Korea.
AIMS & METHODS: The aim of this study was to evaluate the ultimate eradication rate of H. pylori after 1st, 2nd or 3rd line therapy and to compare the
efficacy of each treatment regimen at the tertiary institute in Korea. 2,444
patients infected with H. pylori were prospectively treated with proton pump
inhibitor (PPI)-based triple therapy for 7 days. In case of treatment failure or
recurrence, moxifloxacin-based triple therapy (MNA) or bismuth-based quadruple therapy (QUAD) was randomly given. When the 2nd-line treatment failed or
H. pylori recurred, the unused MNA or QUAD was used as a third-line
treatment.
RESULTS: The intention-to-treat (ITT) and per-protocol (PP) rates of final
eradication up to 3rd line treatment were 69.1% and 92.1%, respectively. In
detail, six-hundred eleven patients (25% of total population) were lost to
follow up or refused further treatment at certain time during specific treatment
plan. For the patients with 1st-line treatment failure (n 415), the eradication
rates (ITT/PP) with 2nd-line treatment were 49.9%/74.4%. There was no significant difference in the efficacy between MNA and QUAD as 2nd line treatment
(p 0.862/0.480, as ITT/PP, respectively). The final eradication rates (ITT/PP)
of recurred patients after the 1st line treatment (n 63, mean interval from 1st
line to recurrence: 26.919 mos) were 84.1%/94.1%.
CONCLUSION: The final PP eradication rate was relatively high, 92.1% at the
tertiary hospital in Korea in spite of high antibiotic resistance rates. However,
high rate of refusal of further treatment and follow-up loss made ITT eradication
rate low. There should be strategy to raise the treatment adherence.
Disclosure of Interest: None declared
P1089 PREVALENCE OF ACTIVE H. PYLORI INFECTION AND
CLARITHROMYCIN-CONTAINING TRIPLE THERAPY EFFICACY
IN PATIENTS WITH DYSPEPSIA - EXPERIENCE OF A TERTIARY
CENTRE IN NORTH OF ITALY
M. Furnari1,*, A. Moscatelli1, M. Brunacci1, E. Savarino2, F. Mazza1, L. Del
Nero1, L. Gemignani1, M. Giacchino1, L. Mastracci3, V. Savarino1
1
Di. M. I., Gastroenterology Unit, UNIVERSITY OF GENOA, genoa, 2Division
of Gastroenterology, Department of Surgery, Oncology and
Gastroenterology,Department of Surgery, Oncology and Gastroenterology,
University of Pisa, Pisa, 3DICMI, Pathologic Division, University of Genoa,
genoa, Italy
Contact E-mail Address: manuelefurnari@gmail.com
INTRODUCTION: H. pylori (Hp) infection affects almost 50% of the world
population, and it is recognized as first grade risk factor for gastric cancer.
Moreover, it is commonly considered a potential cause of dyspepsia and peptic
ulcer. In European populations, without alarm signs, the test-and-treat strategy is
usually preferred rather than other invasive investigations. Clarithromycin-containing triple therapy is considered the first line treatment. However, several
warnings about the reduction of its efficacy has been published in the last years.
AIMS & METHODS: To assess the prevalence of active Hp infection in patients
with dyspepsia and the eradication rate of the clarithromycin-based triple
therapy.
We retrospectively evaluated the presence of active Hp infection in consecutive
patients undergoing urea breath test (UBT) because of dyspepsia (i.e. epigastric
pain, bloating, nausea, early satiety, post-prandial fullness, belching) without
alarm signs and family history of gastric cancer. Patients were asked to stop
proton pump inhibitors or antibiotics at least 15 days prior to testing. All the
tests were performed directly at our Department, by specialized nurses, after an
overnight fast, with the same kit (Sofar, Milano, Italy). Two basal breath samples
and two breath samples 30 min after the ingestion of labelled urea diluted in
acidic solution, were collected from every patients.
RESULTS: From July 2010 to July 2012, 3000 patients referred to our ambulatory (1881F/1119M; mean age 54, 6-92) because of dyspeptic symptoms.
Prevalence of active H pylori infection was 32.1% (963). The prevalence per
age-related decades was: 26%(520yy), 33%(21-30), 34%(31-40; 41-50; 51-60),
33% (61-70), 32%(71-80; 480yy) [p n.s.]. Prevalence was higher in women
33.7% (n 634) than in men 29.4% (n 329), but this tendency failed to reach
statistical significance [p 0.07]. No differences in terms of age were found
between male and female Hp-positive patients (n.s). One hundred and fortyfive patients (10.9%) were originally from South-America (111F/703M; mean
age 41, 10-76) and younger than Italian patients [p50.001]. Higher UBT
values were positively related with female sex (r2:0.01; p50.01). Only 789
(82%) positive patients returned after the first treatment attempt and 31%

A432
(n 244) had a second positive test, but no differences in terms of age, sex and
ethnic group were found.
CONCLUSION: In our population, the prevalence of active H. pylori infection
in patients with dyspepsia was similar to that reported by previous analysis in the
general Italian population. Nevertheless, we found a dramatic low eradication
rate achieved by using clarithromycin-containing triple therapy, thus confirming
the worrisome reports of recent studies.
Disclosure of Interest: None declared
P1090 DIFFERENT
ANTIBIOTIC
SUSCEPTIBILITY
BETWEEN
ANTRUM AND CORPUS OF THE STOMACH, A POSSIBLE
REASON FOR TREATMENT FAILURE OF HELICOBACTER PYLORI
INFECTION
M. Selgrad1,*, I. Tammer2, C. Langner1, J. Bornschein1, J. Meissle1,
M. Varbanova1, A. Kandulski1, T. Wex1, D. Schluter1, P. Malfertheiner1
1
Department of Gastroenterolgy, Hepatology, 2Institute of Medical Microbiology,
OTTO-VON-GUERICKE UNIVERSITY, Magdeburg, Germany
Contact E-mail Address: michael.selgrad@med.ovgu.de
INTRODUCTION: H. pylori eradication rates with standard triple therapy show
a constant decrease, mainly due to increasing antibiotic resistance. Antibiotic
susceptibility guided therapy is recommended in patients receiving rescue therapy. So far, there are no reports whether only one biopsy from one anatomic site
of the stomach is sufficient to detect antibiotic resistant H. pylori strains.
AIMS & METHODS: Aim: We assessed whether antibiotic resistance varies
between the antrum and corpus of the stomach of patients that are either H.
pylori therapy-naive or pre-treated.
Methods: H. pylori strains were isolated from antrum and corpus biopsies from
66 patients that underwent gastroscopy for different clinical indications.
Susceptibility to commonly used antibiotics for H. pylori treatment was determined by Etest.
RESULTS: Primary, secondary and tertiary resistance to clarithromycin was
6.9%, 53.8% and 83.3%, retrospectively. Metronidazole and levofloxacin resistance also increased according to the number of previous treatments (17.2%,
69.2%, 83.3%; 13.8%, 23.1%, 33.3%). Tertiary resistance to rifabutin was
detected in 12.5% of patients. Discordant antibiotic susceptibility between
antrum and corpus isolates for different antibiotics was seen in 15.2% of the
patients. DNA fingerprinting analysis revealed no substantial differences among
DNA patterns between antrum and corpus isolates in the majority of patients
suggesting an infection with a single H. pylori strain.
CONCLUSION: Different antibiotic susceptibility between antrum and corpus
biopsies is a common phenomenon and a possible explanation for treatment
failure. Resistant H. pylori strains may be missed if just one biopsy from one
anatomic site of the stomach is taken for H. pylori susceptibility testing.
Disclosure of Interest: None declared
P1091 THE RESULTS OF USING SEQUENTIAL THERAPY IN H.
PYLORI ERADICATION

United European Gastroenterology Journal 2(1S)

TUESDAY, OCTOBER 21, 2014


9:0017:00
SMALL INTESTINAL II POSTER EXHIBITION HALL XL_____________________
P1092 MARKERS
OF
INTESTINAL
INFLAMMATION
ARE
COMMONLY ELEVATED IN LUNG-TRANSPLANTED PATIENTS
WITH CYSTIC FIBROSIS
E. Halilbasic1,*, K. Staufer2, S. Harm1, P. Jaksch3, W. Klepetko3, H. Vogelsang3,
M. Trauner1, L. Kazemi-Shirazi1
1
Department of Internal Medicine III, 2Department of Surgery, 3Department of
Thoracic Surgery, Medical University of Vienna, Vienna, Austria
Contact E-mail Address: emina.halilbasic@meduniwien.ac.at
INTRODUCTION: With increased survival in cystic fibrosis (CF), gastrointestinal complications are becoming more prevalent. Small intestinal bacterial overgrowth (SIBO) has been discussed as a determinant of intestinal inflammation in
CF patients before lung transplantation (LuTx). Data on intestinal inflammation
in CF patients in the post-transplant setting are scarce.
AIMS & METHODS: Aim of this ongoing prospective study is to evaluate
intestinal inflammation and its underlying mechanisms in CF patients after
LuTx. So far, 23 adult CF patients after LuTx (all with pancreatic insufficiency,
median age 34y, range 24-58y; 42% male) attending our outpatient clinic were
evaluated for presence of intestinal symptoms. Intestinal inflammation was
assessed by stool calprotectin (Buhlmann Co, Switzerland) and serum antisaccharomices cerevisiae antibodies (ASCA IgG, IgA, INOVA Co, San Diego,USA)
measurement. Intestinal infection was excluded by stool cultures, celiac disease
by negative EMA/TTG antibodies. Glucose-H2 breath test was performed to
diagnose SIBO. 5 non-CF patients with solid organ transplantation were
recruited as controls.
RESULTS: 10 of 23 (43%) patients presented with intestinal symptoms.
Calprotectin was increased (cut off 100 mg/g stool) in 65% of patients (mean
18682 mg/g). 83% of patients were positive for either serum IgG (65%, mean
4923 U/ml) or IgA (61%, mean 3517 U/ml) ASCA. In 53% of patients SIBO
was diagnosed. Patients with SIBO had markedly increased fecal calprotectin
levels (median 17794 mg/g) compared with patients without SIBO (median
9863 mg/g) (p50,05). Patients with intestinal symptoms had significant increase
in IgG and IgA ASCA, but no difference in calprotectin was found in comparison to asymptomatic CF patients. No differences in serum IgG, IgA ASCA or
stool calprotectin levels were observed between transplanted patients with or
without CF.
CONCLUSION: Gastrointestinal symptoms and elevated markers of intestinal
inflammation are common in CF patients after LuTx. SIBO may be a causative
factor for increased calprotectin in these patients. Our data suggest that not only
CF, but also other factors, such as immunosuppression, may contribute to the
intestinal inflammation in transplant setting.
Disclosure of Interest: None declared
P1093 FEMALES ARE BETTER PROTECTED FROM GUT INJURY
DURING ISCHEMIA-REPERFUSION THAN MALES: SEX MATTERS

L. Prokhorova1, N. Shchanova2,*, E. Petrova2, A. Kopytov2, J. Beikin3,


N. Sbitneva3
1
Ural State Medical University, Co Ltd MC New Hospital, 2Co Ltd MC New
Hospital, 3MAO Clinicodiagnostic centre, Yekaterinburg, Russian Federation
Contact E-mail Address: nshchanova@mail.ru

I. Hundscheid1,2,*, J. Grootjans3, D. Schellekens1,2, J. Derikx1,2, R.Van Dam1,2,


W. Buurman1,2, K. Lenaerts1,2, C. Dejong1,2
1
Department of Surgery, 2School for Nutrition, Toxicology and Metabolism
(NUTRIM), Maastricht University Medical Center , Maastricht, 3Department
of Internal Medicine, Slotervaart Ziekenhuis, Amsterdam, Netherlands
Contact E-mail Address: i.hundscheid@maastrichtuniversity.nl

INTRODUCTION: To evaluate efficiency of using sequential H. pylori eradication therapy in patients with gastric and duodenal ulcer disease of Yekaterinburg.
AIMS & METHODS: 95 patients (55 male, 40 female, average age 43 (16-74)
years) with exacerbated gastric and duodenal peptic ulcer with severe and complicated clinical course: giant and multiple ulcers (42 patients), gastroenterorrhagia in near-term (2-3 weeks) anamnesis (48 patients), perforations (5 patients) are
examined. Biopsy material of gastric and duodenal mucous tunic from standard
and periulcerous areas is researched with electronic and light microscopy methods on machine Morgagni 268. H. pylori diagnostic methods are histological,
immunological methods, such as identification the quantity of anti - H. pylori
IgG in blood serum, evaluation of H. pylori antigen in stool, detection DNA and
pathogenic factors of H.pylori (CagA, VacA s1/s2) by PCR with fluorescent
detection in real time. Intensity of gastritis is estimated by visual-analogy scale
and system OLGA. Sequential therapy (pantoprazole, amoxycillin, clarithromycin, metronidazole) used in 75 patients (1 group), standard triple therapy (pantoprazole, amoxycillin, clarithromycin) in 20 patients (2 group). All patients did
not previously receive an eradication therapy. Control carried out in 2, 4, 8
weeks.
RESULTS: Ulcer cicatrization is attained in 70 (93%) of 1 group patients and 15
(75%) of 2nd group patients in 2 weeks. 100% ulcer cicatrization is attained in
both groups in 4 weeks. Intensity of gastritis and efficiency of H. pylori eradication are estimated after 8 weeks. Before treatment the I grade of inflammation is
discovered in 7 (9%) of 1 group patients, 1 (5%) of 2nd group patients, the II
grade of inflammation in 10 (13%) of 1 group, 3 (15%) of 2 group, III 52
(69%) of 1 group, 13 (65%) of 2 group, IV 6 (8%) of 1 group, 3 (15%) of 2
group. After treatment the I grade of inflammation is discovered in 45 (60%) of 1
group, 10 (50%) of 2 group, II 29 (39%) of 1 group, 7 (35%) of 2 group, III 1
(1%) of 1 group, 3 (15%) of 2 group, IV grade of inflammation arent discovered
at all (p50,05). Efficiency of H. pylori eradication in using sequential therapy is
96%, standard triple therapy 87%.
CONCLUSION: Using sequential regimen of eradication of H.pylori infection in
Russian patients with severe peptic ulcer disease demonstrated higher efficacy
compared with standard triple therapy.
Disclosure of Interest: None declared

INTRODUCTION: Gender differences in the pathophysiological response to


ischemia-reperfusion (IR) have particularly been recognized in cardiovascular
and cerebral systems. However, it is unknown if sexual dimorphism exists in
human intestinal IR, a frequent occurring and highly lethal disease.
Recognition of such differences and elucidation of the underlying pathophysiological mechanisms could lead to more evidence-based medicine for females, and
the development of novel therapeutic strategies to reduce IR-associated morbidity and mortality. Therefore, we aimed to investigate sex differences in human
intestinal mucosal responses to IR.
AIMS & METHODS: Intestinal IR was studied using a human experimental
model. In 16 patients (M8:F8) undergoing pancreaticoduodenectomy, an isolated
part of jejunum was subjected to 45 minutes of ischemia (45I) followed by 30
(30R) or 120 minutes of reperfusion (120R). Intestinal tissue was collected at all
time points to assess morphology (hematoxylin/eosin (HE)), neutrophil influx
(myeloperoxidase (MPO)) and Paneth cell apoptosis (Lysozyme/M30 double
staining). Endoplasmic reticulum (ER) stress was analyzed using an X-box binding protein-1 (XBP1) splicing assay and XBP1-spliced/XBP1-unspliced (XBP1s/
XBP1u) ratios were calculated. QPCR techniques were used to determine inflammatory cytokine expression. Arteriovenous (V-A) concentration differences of
intestinal fatty acid binding protein (I-FABP) were measured using an enzymelinked immunosorbent assay (ELISA) to assess the level of enterocyte damage.
Results were analyzed using Mann-Whitney U tests. Data are presented as
meanSEM. A P-value 50.05 is considered statistically significant.
RESULTS: HE staining revealed more extensive small intestinal epithelial
damage in male subjects compared to females. In line, I-FABP V-A concentrations differences were higher in males compared to females, both at 45I
(233.973.3 ng/ml vs 55.518.3 ng/ml, P5.05) and at 45I30R (79.219.4 ng/
ml vs 24.46.6 ng/ml, P5.05). Furthermore, male small intestine showed higher
XBP1s/XBP1u ratios at 45I30R than female small intestine (4.30.8 vs 2.20.4,
P5.05), indicating enhanced ER stress in males. As expected, this was associated
with a higher number of apoptotic Paneth cells per crypt in male subjects compared to females at 45I (5.81.2 vs 1.70.4, P5.05) and 45I30R (18.32.9 vs
7.61.9, P5.05). Furthermore, males had a more pronounced influx of neutrophils per villus at 45I30R (6.91.2 vs 3.60.6, P5.05) and a higher relative

United European Gastroenterology Journal 2(1S)


mRNA expression of inflammatory cytokines TNF-a and IL-10 after 45I120R,
compared to females (2.6 fold and 6.4 fold respectively, P5.05).
CONCLUSION: The human female small intestine is better protected from IRinduced epithelial damage than the male small intestine, and correspondingly
displayed notably less inflammatory responses. Unravelling the molecular
mechanisms underlying this effect could lead to new therapeutic strategies for
intestinal IR.
Disclosure of Interest: None declared
P1094 ENVIRONMENTAL ENTEROPATHY: IMAGING THE CELLULAR
BASIS OF DISRUPTED BARRIER FUNCTION
P. Kelly1,*, J. Louis-Auguste1, T. Banda2, R. Soko2, E. Besa2, R. Banda2
1
BLIZARD INSTITUTE, London, United Kingdom, 2TROPGAN, Lusaka,
Zambia
Contact E-mail Address: m.p.kelly@qmul.ac.uk
INTRODUCTION: Environmental enteropathy (EE), originally termed tropical
enteropathy, is very common in overcrowded living conditions in developing
countries. It predisposes to growth failure in the young, and probably to poor
performance of oral vaccines. By permitting microbial translocation it probably
contributes to insidious systemic immune activation. In order to understand the
impairment of barrier function in EE, we performed confocal laser endomicroscopy (CLE) in 57 healthy volunteers from a poor community in Lusaka,
Zambia.
AIMS & METHODS: These asymptomatic volunteers were drawn from a community in which we have been conducting studies for 15 years. On day 1 a 3 hour
lactulose: mannitol permeability and zinc absorption test was performed. On day
2 CLE of the duodenal mucosa was performed with diazepam/pethidine sedation
and 5-10ml 2% intravenous fluorescein, and images collected for 10 minutes
exactly (mean number of images analysed 135, SD57). Biopsies were subsequently taken to analyse villous morphology and markers of bacterial translocation and inflammation.
RESULTS: In the first 57 volunteers (40 female, 17 male) studied, a wide range
of villous architectural patterns was observed from leaf-like to convolutions.
Similarly, a wide range of barrier abnormalities was observed, with some volunteers showing severe fluorescein leakage within one minute of fluorescein injection. Epithelial breaks, particularly multicellular breaks (microerosions), were
strongly correlated with the rate of fluorescein efflux (Spearmans rho 0.92;
P50.0001). The number of plumes was almost as strongly correlated
(rho 0.69; p 0.0004). Fluorescein leakage and epithelial barrier defects were
not correlated with villous architectural change (rho 0.01: p 0.96), suggesting
that villous remodelling and barrier defects are differentially determined.
Fluorescein plumes were correlated with serum CD163, a marker of Kupffer
cell activation, but only in HIV seropositive individuals (rho 0.76; P,0.05).
CONCLUSION: CLE permits imaging of small intestinal epithelial barrier
defects and suggests that cellular breaches are major routes of intestinal permeability but independent of villous architecture.
Disclosure of Interest: None declared
P1095 CELECOXIB MONOTHERAPY DEVELOPED FEWER SMALL
INTESTINAL MUCOSAL BREAKS COMPARED TO LOXOPROFEN
AND LANSOPRAZOLE CONCOMITANT TREATMENT: A DOUBLEBLIND, RANDOMIZED, CONTROLLED TRIAL
S. Fujimori1,*, R. Hanada2, M. Hayashida3, T. Sakurai4, M. Keigo1,
I. Ikushima2, C. Sakamoto1
1
Depertment of Gastroenterology, Graduate School of Medicine, Nippon Medical
School, 2Medical Co. LTA, Sumida Hospital, 33)The Third Department of Internal
Medicine, Kyorin University School of Medicine, 4Department of Gastroenterology
and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan
INTRODUCTION: Two American studies report that COX-2 selective inhibitor
celecoxib develops fewer small intestinal injuries than non-selective NSAIDs
(1,2). Loxoprofen, which is a pro-drug for gastroprotection of non-selective
NSAIDs, is the most frequently used in Japan for pain relief.
AIMS & METHODS: The purpose of the study was to compare celecoxib with
loxoprofen for small intestinal protection, and to confirm celecoxib suppression
of small intestinal mucosal injury compared with non-selective NSAIDs in
Japanese people. 150 healthy volunteers between 40 to 70 years of age were
enrolled. After medical check-up including physical, bloody, urinary examination, and fecal occult blood test, subjects were randomly assigned to either the
CEL-group to receive celecoxib (200 mg daily) or the LOX-group to receive
loxoprofen (180 mg daily) in addition to lansoprazole (15 mg daily). All drugs
were pulverized to fill capsules and were prepared in the same manner as placebo
capsules. After randomization, all subjects were first examined by baseline capsule endoscopy (baseline CE). After 14 days, subjects underwent post-treatment
CE. Baseline and post-treatment CE were evaluated for small intestinal mucosal
breaks, and the findings compared between the two groups. All capsule endoscopy data including baseline and post-treatment CE were evaluated blindly by 3
reviewers. Final evaluation of small intestinal mucosal breaks was made based
upon the agreement of reviewers agreement before opening the key. This study
was approved by the Ethics Committee at Nippon Medical School and Kyushu
clinical pharmacology research clinic institutional review board, and all subjects
provided written informed consent for enrollment (UMIN: 000007936). The
study was funded by Pfizer Japan Inc.
RESULTS: Among 74 subjects (496 years of age, F/M: 36/38)in the CELgroup, five were excluded from analysis due to four incomplete CE examinations
and one withdrawal from the study due to influenza. Among 76 subjects (497
years of age, F/M: 39/37)in the LOX-group, four were excluded from analysis
due to three incomplete CE examinations and one withdrawal due to non-

A433
compliance for study protocol. Thus, 69 subjects in the CEL-group and 72 subjects in the LOX-group were compared. Small intestinal mucosal breaks were
detected 0.21.1 at baseline and 0.31.0 at post-treatment in the CEL-group,
and 0.41.8 at baseline and 6.821.5 at post-treatment in the LOX-group. Small
intestinal mucosal breaks were much fewer in the CEL-group than in LOX-group
(P50.0001). The percentage of subjects with at least one mucosal break at posttreatment was also lower in the CEL-group (10%) than in the LOX-group (49%)
(P50.0001).
CONCLUSION: Celecoxib monotherapy developed fewer small intestinal mucosal breaks than loxoprofen and lansoprazole concomitant treatment in the
Japanese population.
REFERENCES
1) Goldstein JL, et al. Clin Gastroenterol Hepatol 2005; 3: 133-141.
2) Goldstein JL, et al. Aliment Pharmacol Ther 2007; 15: 1211-1222.
Disclosure of Interest: S. Fujimori Financial support for research from: Pfizer
Japan Inc., Lecture fee(s) from: Given Imaging Ltd., R. Hanada: None declared,
M. Hayashida: None declared, T. Sakurai: None declared, M. Keigo: None
declared, I. Ikushima: None declared, C. Sakamoto Financial support for
research from: Pfizer Japan Inc., Lecture fee(s) from: Pfizer Japan Inc.,Takeda
Pharmaceuticals Co., Ltd., Consultancy for: Pfizer Japan Inc.,Takeda
Pharmaceuticals Co., Ltd.
P1096 DIETARY WHEAT ALPHA-AMYLASE/TRYPSIN INHIBITORS
(ATIS) EXACERBATE ALLERGIC AIRWAY INFLAMMATION
V.F. Zevallos1,*, V. Raker2, J. Maxeiner3, M. Kahn1, K. Steinbrink 2,
D. Schuppan1
1
Institute of Translational Immunology, 2Dermatology, 3Asthma Core Facility,
Research Centre Immunology (FZI), University Medical Center of the Johannes
Gutenberg-University Mainz, Mainz, Germany
Contact E-mail Address: zevallos@uni-mainz.de
INTRODUCTION: Wheat alpha-amylase/trypsin inhibitors (ATIs) are potent
activators of innate immunity by engaging the toll like receptor 4 (TLR4)-MD2CD14 complex in monocytes, macrophages and dendritic cells (Junker Y et al, J
Exp Med 2012). ATIs, non-gluten proteins, that occur as contaminants even in
pure gluten preparations are implicated in the pathogenesis of celiac disease
(CD) and other autoimmune / inflammatory diseases.
AIMS & METHODS: We would like to investigate the effects of dietary ATIs on
allergic airway inflammation. Therefore, female C57BL/6 mice on a gluten-free
diet (GFD) were sensitised and challenge with ovalbulmine (OVA). Animals were
divided in 5 groups: 1 continued with the GFD and mock-sensitised with PBS, 2:
continued with the GFD and sensitised with OVA, 3: changed to a diet containing 25% gluten (containing amounts of ATIs equivalent to the human wheat
based diet), 4: changed to a diet containing purified ATIs, and 5: changed to a
diet containing 25% gluten de-enriched of ATIs. Furthermore, we evaluated the
effect of ATIs, OVA or both during sensitisation and challenge.
We measured invasive lung function, bronchoalveolar lavage (BAL), IgG1 levels
and proliferation of splenocytes and cytokine secretion after OVA stimulation. In
addition, histological sections of lung were stained with Hematoxylin and Eosin
(HE) and Periodic acidSchiff (PAS) and scored according to the degree of cell
infiltration and goblet cell hyperplasia.
RESULTS: Mice on a GFD sensitized with PBS did not develop airway hyperreactivity (AHR) after local provocation with OVA. Interestingly, mice on a GFD
or on a diet containing 25% gluten de-enriched of ATIs and sensitized with OVA
developed a reduced AHR compared to mice fed the pure ATIs rich diet or 25%
gluten diet. Similar results were observed for IgG1 production, eosinophilic infiltration in BAL (HE) and mucus production (PAS) in the lung. We also observed
that animals sensitised with OVA/ATIs and challenged with OVA, showed higher
AHR compared to animals sensitised with OVA or ATIs alone.
CONCLUSION: We demonstrate that 1) dietary ATIs enhance allergic airway
inflammation in OVA-challenged mice 2) sensitization with ATIs/OVA enhances
further AHR in OVA-challenged mice 3) a gluten-free (ATI-free) diet appears to
have a protective effect on allergic airway inflammation 4) Gluten depleted of
ATIs has a reduced stimulatory effect compared with gluten containing ATIs or
ATIs alone. Therefore, ATIs appear to be major and clinically relevant nutritional triggers of innate immunity in allergic airway inflammation and other
autoimmune diseases.
REFERENCES
Junker Y, Zeissig S, Kim S, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. JEM 2012; 209: 23952408.
Disclosure of Interest: None declared
P1097 MILD HISTOLOGICAL ABNORMALITIES IN NON-COELIAC
GLUTEN SENSITIVITY DO NOT REPRESENT EARLY COELIAC
DISEASE
I. Aziz1,*, T. Key2, J.G. Goodwin2, D.S. Sanders1
1
Department of Gastroenterology, 2Department of Histocompatability &
Immunogenetics, Royal Hallamshire Hospital, Sheffield Teaching Hospitals,
Sheffield, United Kingdom
INTRODUCTION: Coeliac disease (CD) is defined by positive serology plus
Marsh (M) grade 1-3 on duodenal biopsies; CD-M1 to CD-M3. In contrast,
non-coeliac gluten sensitivity (NCGS) is defined by negative serology and duodenal biopsies that are normal, or show mild histological abnormalities, whilst on
a gluten containing diet; NCGS-M0 to NCGS-M1.
AIMS & METHODS: As coeliac serology can be negative in those with mild
histological abnormalities we aimed to determine whether NCGS-M1 actually
represents early CD.

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United European Gastroenterology Journal 2(1S)

Baseline clinical characteristic, biochemical parameters and human leukocyte


antigen (HLA) DQ2-DQ8 typing was compared between 100 NCGS-M0, 50
NCGS-M1 and 30 CD-M1 patients. Finally, serological and histological
response to a repeat gluten challenge was assessed between HLA-DQ positive
NCGS-M1 and CD-M1.
RESULTS: There was no statistical difference in age, sex, autoimmunity, family
history of CD or baseline body mass index between the three groups. However,
anaemia was significantly more prevalent in CD-M1 (20%) compared to NCGSM1 (6.4%, p 0.05, OR 4.7, C. I 1.0-21.6) and NCGS-M0 (3%, p 0.009, OR 7.58,
C. I 1.67-34.4).
Furthermore, HLA-DQ positivity was seen in 100% (n 30) of CD-M1 patients, in
contrast to 70% NCGS-M1 (n 35, p 0.001) and 55% NCGS-M0 (p 50.001).
26/30 CD-M1 patients and 30/35 HLA-DQ positive NCGS-M1 individuals
agreed to undergo repeat gluten challenge. In CD-M1 there was a significant
rise in coeliac serology (mean TTG value 124 U/ml before: 164 U/ml after, p
0.04) and histological deterioration on duodenal biopsies (35% M1, 15% M2,
50% M3, p 5 0.0001). In contrast, all individuals with HLA-DQ positive
NCGS-M1 maintained negative coeliac serology (mean TTG value 7 U/ml
before; 8 U/ml after, p 0.12) and the majority improved their duodenal biopsies
from M1 to M0 (23/30, 77%, p 5 0.0001), with 7 cases persisting as NCGS-M1
CONCLUSION: NCGS-M1 individuals do not represent CD as demonstrated
by i) negative HLA-DQ typing in 30% of cases or a ii) a lack of immune deterioration following repeat gluten challenge in those with HLA-DQ positivity. In
cases with persisting NCGS-M1 duodenal immunohistochemical analysis may
shed further light on the eventual diagnosis.
Disclosure of Interest: None declared
P1098 PREDICTORS FOR COELIAC
LYMPHOCYTIC DUODENOSIS

DISEASE

IN

CASES

OF

I. Aziz1,*, T. Key2, J.G. Goodwin2, D.S. Sanders1


1
Department of Gastroenterology, 2Department of Histocompatability &
Immunogenetics, Royal Hallamshire Hospital, Sheffield Teaching Hospitals,
Sheffield, United Kingdom
INTRODUCTION: Lymphocytic duodenosis (LD) is an early marker for coeliac
disease (CD). However, the majority of cases are due to non-CD related
conditions.
AIMS & METHODS: We aimed to identify the predictors of CD when presented
with LD.
215 LD patients had undergone prospective and systematic evaluation for CD
and other recognized associations.
The gold-standard diagnosis of CD was based upon the presence of HLA-DQ2
and/or DQ8, persistence or progression of LD following a gluten challenge,
followed by a symptomatic improvement on a gluten-free diet.
Binary logistic regression models, adjusting for age and gender, were subsequently performed to compare presenting variables between CD and non-CD
cases, and to determine their sensitivity, specificity, positive and negative predictive values (PPV and NPV).
RESULTS: CD was diagnosed in 48 cases (22%) and non-CD in 167 cases
(78%). There was no statistical difference in demographics, clinical symptoms
(i.e. diarrhea, weight loss, abdominal pain), anemia or hematinics between the
CD and non-CD group.
Patients with CD, in comparison to non-CD, were significantly more likely to
have a positive family history of CD (21% vs. 3.6%, OR 6.73; PPV 62.5%, NPV
81%, specificity 96.4%), positive HLA-DQ status (100% vs. 49.1%; PPV 36.4%,
NPV 100%, specificity 50.9%), and presence of endomysial antibody [EMA]
(48% vs. 0%; PPV 100%, NPV 87%, specificity 100%); all p 0.001
A normal tissue transglutaminase antibody (TTG) level was seen in 29.2% CD
and 83.2% non-CD cases (OR 0.084, p 5 0.001; PPV 9.2%). There was no
difference in the prevalence of TTG levels 1-2 x upper limit of normal (ULN)
between the groups (29.2% CD vs. 14.4% non-CD; PPV 33-38%). However,
TTG levels between 3-20 x ULN were significantly more prevalent in the CD
group (33.3% vs. 2.4%; PPV 66.6%489%), whilst a TTG 4 20 x ULN was
exclusive to CD (8.3%, p 5 0.001, PPV 100%).
CONCLUSION: In the setting of LD, only the presence of a positive EMA or
TTG 4 20 x ULN at the outset can be used to make an immediate diagnosis of
CD. Gastrointestinal symptoms, family history, anemia, or other celiac serology
results do not reliably distinguish CD from non-CD without further
investigations.
Disclosure of Interest: None declared
P1099 CHANGE IN AWARENESS OF GLUTEN-RELATED DISORDERS
AMONGST CHEFS AND THE GENERAL PUBLIC IN THE UNITED
KINGDOM: A 10 YEAR FOLLOW-ON STUDY
I. Aziz1,*, M.A. Karajeh1, J. Zilkha1, E. Tubman1, C. Fowles1, D.S. Sanders1
1
Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching
Hospitals, Sheffield, United Kingdom
INTRODUCTION: For individuals with gluten-related disorders (GRD) eating
out has traditionally been difficult, and socially impacting, due to concern over
the lack of public awareness regarding GRD and a gluten-free diet (GFD).
However, the recent rise in media coverage highlighting these conditions may
have altered knowledge amongst the general public and chefs.
AIMS & METHODS: We assessed whether knowledge of GRD has altered
amongst the general public and chefs.
A face-to-face questionnaire about coeliac disease (CD) and gluten sensitivity
(GS) was performed on the general public and chefs based in Sheffield, United
Kingdom. The assessment was first conducted in 2003 and repeated in 2013.

RESULTS: 513 public members in year 2003 (mean-age 49.2, 62% female) were
compared to 575 public members in year 2013 (mean-age 37.8, 57% female).
There was a significant rise in the awareness of GRD from the years 2003 to
2013; CD (44.2% to 74.4%, AOR 3.9 [C. I 3-5.19]) and GS (58.3% to 89%, AOR
7.1 [C. I 5-9.98]), p-value 5 0.001.
322 chefs in year 2003 (mean age 37.6, 15% female) were compared to 265 chefs
in year 2013 (mean age 27.1, 38% female). There was a significant rise in the
awareness of GRD from the years 2003 to 2013; CD (17.1% to 78.1%, AOR 12.5
[C. I 7.9-19.6]) and GS (9.3% to 87.5%, AOR 65.7, C. I [35.4-122]), p 5 0.001.
Whereas in 2003 the public were significantly more aware of GRD than chefs, by
2013 this had reached similar prevalence in both groups. In addition, the correct
recognition of the gluten-free symbol was 44% for the public and 40% for chefs
(p 0.28). 41% of restaurants and 27% of takeaways sold gluten-free products (p
0.07).
CONCLUSION: There has been a dramatic rise in both the public and chefs
awareness of GRD. This may ease the social phobia that individuals with GRD
have traditionally been accustomed to.
Disclosure of Interest: None declared
P1100 UNSUSPECTED
PREVALENCE
OF
CONDITIONS
PREDISPOSING TO CELIAC DISEASE IN THE AMERINDIAN
TOBA COMMUNITY OF ARGENTINA: A STUDY ON GLUTEN
CONSUMPTION, GENETIC PREDISPOSITION AND
AUTOIMMUNITY MARKERS
M.P. Temprano1, H. Vazquez1, E. Sugai 1, G. I. Longarini1,1,*, E. Smecuol1,
S. Scachi1, S. Niveloni1, A.F. Costa1, R. Mazure1, D. Cisterna1, R.de Miguel1,
A. Gonzalez1, M.A. Bartellini1, E. Maurino1, J.C. Bai1
1
Medicine, Hospital Udaondo, Buenos Aires, Argentina
Contact E-mail Address: hvazquez@intramed.net
INTRODUCTION: The Toba indigenous ethnic community comprises more
than 60,000 individuals living in very poor conditions in northeastern
Argentina. The lower than average life expectancy in this population has been
attributed, in part, to primary malnutrition, and very low socio-economic, sanitary and educational conditions. In recent years, they have experienced a change
in dietary habits with wheat and wheat-products replacing ancestral alimentary
practices mainly due to the governmental support. No studies have explored
conditions predisposing to celiac disease (CD) in Amerindians.
AIMS & METHODS: Aims: 1- To estimate the consumption of gluten; 2- To
explore the genetic background (HLA DQ2/ DQ8 haplotype); and 3- To determine the prevalence of CD autoimmunity in a population of members of the
Toba community requesting medical attention by a multidisciplinary sanitary
mission.
Methods: After written consent, individuals attending the mission underwent a
detailed questionnaire by an expert nutritionist recalling the last 48-hs dietary
intake. Gluten consumption was estimated by conventional formula. Clinical,
biochemical and anthropometric parameters were collected. CD specific gene
typing for the detection of HLA class II alleles was performed on DNA extracted
from peripheral blood (DQ-CD Typing Plus. BioDiagene S. R. L.; Palermo;
Italy). Serum samples were tested for IgA antibodies to tissue transglutamise
(IgA tTG) and the deamidated gliadin peptides (DGP)/tTG Screen test. Those
with positive results were tested for IgA endomysial (EmA) antibodies (INOVA
Diagnostics Inc. San Diego, Ca).
RESULTS: One hundred and forty-three subjects (63% females) were enrolled.
The median age of the study population was 30 yr (range: 3 to 72), and the mean
body mass index was 27.1 kg/m2 (SD: 6.7). The estimated mean gluten consumption was 47 g/day (range: 4 to 185), which resulted higher than that recommended
by National Nutritional Guideline (18 g/day). Sixty out of 116 subjects (51.7%)
had alleles associated with CD. Fifty-six cases (95%) had alleles codifying for
HLA DQ8 and three for DQ2. Three and four subjects had serum concentrations
above the cut-off of risk established by our group (43 times the upper limit of
normal) for tTG and DGP/tTG Screen antibodies, respectively. Three of these
patients had concurrent positivity for both assays and EmA was positive in two
of these patients who also presented the haplotype HLA DQ2 and DQ8.
CONCLUSION: Our study explores for the first time an Amerindian population
previously unsuspected of having conditions predisposing to CD. The dietary
analysis estimated a very high consumption of gluten due to the alimentary
governmental support. The genetic background was dominated by alleles codifying for DQ8 antigen. We detected evidence of CD autoimmunity and, at least,
two subject fulfilled serologic criteria of CD.
Disclosure of Interest: M. Temprano: None declared, H. Vazquez: None declared,
E. Sugai: None declared, G. Longarini: None declared, E. Smecuol Financial
support for research from: Astra Zeneca, Lecture fee(s) from: Astra Zeneca;
Takeda, Consultancy for: Astra Zeneca, S. Scachi: None declared, S. Niveloni:
None declared, A. Costa: None declared, R. Mazure: None declared, D.
Cisterna: None declared, R. de Miguel: None declared, A. Gonzalez: None
declared, M. Bartellini: None declared, E. Maurino: None declared, J. Bai:
None declared

A435

United European Gastroenterology Journal 2(1S)


P1101 ADHERENCE
TO
DUODENAL
BIOPSY
GUIDELINES
INCREASES THE DETECTION OF COELIAC DISEASE: A
MULTICENTRE UK STUDY
P.D. Mooney1, M. Kurien1,*, M. Finegan2, F. Khan3, R. Keld2, G. Naylor3,
D.S. Sanders1
1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield,
2
Gastroenterology, Royal albert Edward Infirmary, Wigan, 3Gastroenterology,
Chesterfield Royal Infirmary, Chesterfield, United Kingdom
INTRODUCTION: Coeliac disease (CD) is a common autoimmune condition
affecting 1% of the adult population. However large numbers of patients remain
undiagnosed which may have significant health consequences and so methods to
increase detection should be sought. Guidelines suggest that at least 4 duodenal
biopsies should be taken to rule out CD. A previous US study showed that
biopsy guidelines were only followed in 35% of cases. The aim of the present
study was to see whether guidelines were being followed in the UK and if adherence to the guidelines improved detection of CD.
AIMS & METHODS: Endoscopy and histology reports were retrospectively
reviewed for all patients who had a duodenal biopsy in a 3 month period between
November 2012 and January 2013 from 4 UK hospitals. Indications for biopsy,
role of the endoscopist (physician, surgeon, nurse endoscopist), number of duodenal biopsies received by histopathology and the final diagnosis were recorded.
The presence of villous atrophy was required for CD diagnosis. Patients were
excluded if they had known CD.
The difference between a double and single bite biopsy technique was also
assessed.
RESULTS: 1423 patients underwent duodenal biopsy for possible CD across the
4 sites in the study period. 97 (6.8%) of these were diagnosed with CD.
Guidelines to take at least 4 biopsies were met in 40% of patients and the
median number of duodenal biopsies taken for all patients was 3. CD was
more likely to be diagnosed if guidelines were followed (10.1% vs 4.6%,
P50.0001). The median number of biopsies was greater in patients diagnosed
with CD (4 vs 3) P50.0001. Gastroenterologists and nurse endoscopists were
more likely than surgeons to follow guidelines (41.8% vs 51.2% vs 18.2%,
P50.0001) and took a higher median number of biopsies (3 vs 4 vs 2,
P50.0001). As a result gastroenterologists and nurse endoscopists made a diagnosis of CD in more cases than surgeons (7.1% vs 6.7% vs 3.0%, P 0.1). All
presenting characteristics (other than positive serology in which guidelines were
followed in 65%) were associated with poor adherence to guidelines. 12.4% of
newly diagnosed CD patients had at least 1 non-diagnostic gastroscopy in the 5
years prior to diagnosis. Changing biopsy technique to single bites resulted in
improvement of median D2 biopsies from 3 to 4. (P 0.02).
CONCLUSION: We have shown that 12.4% of patients with CD had a previous
gastroscopy 5 years prior to their diagnosis. Taking 4 duodenal biopsies results in
increased detection of CD. We are the first investigators to demonstrate that
there is variation in biopsy rates based on the speciality of the endoscopist and
biopsy technique (single or double bite). Furthermore this variability has a direct
relationship with the detection rate of CD. Education of all groups of clinicians
in duodenal biopsy techniques may result in more patients receiving a prompt
diagnosis of CD.
Disclosure of Interest: None declared
P1102 POINT OF CARE TESTING FOR ADULT COELIAC DISEASE: A
POTENTIAL ROLE IN ENDOSCOPY
P.D. Mooney1, M. Kurien1,*, S. Wong1, D.S. Sanders1
1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, United
Kingdom
Contact E-mail Address: peter.mooney@sth.nhs.uk
INTRODUCTION: Endoscopic markers of coeliac disease (CD) lack sensitivity;
therefore many centers take routine duodenal biopsies or have a low threshold
for biopsy, ensuring high detection rates. Newly available, point of care tests
(POCT) provide rapid findings unlike conventional serological markers, potentially reducing the need for duodenal biopsies. This study evaluates a new POCT
(Simtomax) which detects IgA and IgG deamidated gliadin peptide (DGP) with
comparisons made to conventional serological markers and duodenal biopsies.
AIMS & METHODS: Patients referred from primary and secondary care for a
gastroscopy to a specialist CD list were prospectively recruited between March
2013 to November 2013. Patients were excluded if they were on a gluten free diet
at the time of the test or if they had previously been diagnosed with seronegative
villous atrophy or coeliac disease. All patients had a duodenal biopsy as the gold
standard for detecting coeliac disease. Concurrently serological testing for IgA
tissue transglutaminase (TTG), endomysial antibody (EMA), total IgA immunoglobulin level and the DGP based rapid test was performed. Sensitivity, specificity, positive predictive and negative predictive values were calculated.
RESULTS: 354 patients met the inclusion criteria (45.8% male mean age 53.3
18.5). Of these, 52 (14.7% 11.2 18.9) had newly diagnosed CD and 302 were
controls with a normal duodenal biopsy. The sensitivity, specificity, positive
predictive value (PPV) and negative predictive value (NPV) for the POCT were
94%, 83%, 49% and 99% respectively. This compares with results for TTG of
92%, 88%, 57%, 99% and EMA of 88%, 97%, 85%, and 98% respectively.
CONCLUSION: This is the first study to prospectively demonstrate the value of
a novel POCT for adult CD in endoscopy compared to the gold standard of
histology. The sensitivity and specificity of the POCT is comparable to conventional serology. Simtomax could be used to appropriately identify patients
requiring a duodenal biopsy within the endoscopic setting. This strategy may
be cost effective by reducing the number of routine duodenal biopsies taken.

Disclosure of Interest: P. Mooney: None declared, M. Kurien: None declared, S.


Wong: None declared, D. Sanders Financial support for research from: Tillotts
Pharma
P1103 COMPARISON OF THREE COMMERCIALLY
POINT OF CARE TESTS FOR COELIAC DISEASE

AVAILABLE

P.D. Mooney1, M. Kurien1,*, S. Wong1, D.S. Sanders1


1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, United
Kingdom
INTRODUCTION: Coeliac disease (CD) remains an underdiagnosed condition.
A rapid finger prick based point of care test may increase uptake of serological
testing in appropriate patient groups. There are 4 commercially available point of
care tests (POCT) on the market in the UK: Biocard an IgA tissue tranglutaminase (tTG) test (BHR pharmaceuticals); Coeliac Quick Test (Biohit healthcare)
which detects IgA, IgG and IgM tTG; Xeliac Test Pro (Personal Diagnostics)
which detects IgA and IgG tTG; and Simtomax (Tillotts Pharma) which detects
IgA and IgG de-amidated gliadin peptides (DGP). However there is a limited
evidence base for these tests (Biocard 10 studies; Simtomax 2 studies; Coeliac
Quick Test and Xeliac Test Pro have no published data) and frequently patients
only have a duodenal biopsy if the POCT is positive leading to ascertainment
bias. In our recent cohort the sensitivity of Biocard was disappointing at 70.1%
when results were compared to histology in all patients 1. For this reason we
decided to compare 3 commercially available tests in an endoscopic setting.
AIMS & METHODS: Patients referred with a positive endomysial antibody
(EMA) for duodenal biopsy to confirm CD were invited to take part. All patients
had whole blood taken for repeat serum EMA, tTG and immunoglobulins. All
patients were tested simultaneously with the 3 POCTs as per the manufacturers
instructions. All patients had quadrantic duodenal biopsies from the second part
of the duodenum as well as a duodenal bulb biopsy. Demonstration of villous
atrophy on duodenal biopsy was required to diagnose CD.
RESULTS: 47 patients (27 female, mean age 39.1) have been recruited. In 9
patients the EMA had normalised on repeat testing. None of these patients
had villous atrophy on duodenal biopsy. 7 of these patients were referred with
a weak EMA and had a negative tTG. Of the other 2, 1 patient referred with a
positive EMA, had a tTG of 155 and subsequent gluten challenge revealed a
positive EMA and villous atrophy.
Of the remaining 38 patients 30 new cases of coeliac disease were confirmed with
the presence of villous atrophy, of the remaining 8 EMA positive patients 6 had
Marsh 1 or 2 changes present with the remaining 2 patients having normal
histology. Full sensitivity, specificity PPV and NPV for all of the tests compared
to villous atrophy on duodenal biopsy are shown in the table below.
Test

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

Serum tTG
Biocard
Coeliac Quick Test
Simtomax

97
63
80
93

41
76
59
35

74
83
77
72

88
54
63
75

(81-99)
(44-79)
(61-92)
(76 -99)

(19-67)
(50-92)
(33-81)
(15-61)

(58-86)
(60-94)
(58-90)
(55-84)

(47-99)
(33-74)
(36-84)
(36-96)

CONCLUSION: In this pilot data set Simtomax appears to be the most sensitive
of the POCTs when compared to histology with similar results to serum tTG as
screening test. Further work is required in larger cohorts and lower prevalence
populations to confirm the utility of these tests in adult coeliac disease.
REFERENCES
1. Mooney PD, Kurien M, Evans KE et al. Point of care testing has a low
sensitivity in endoscopy. Gastrointest Endosc. April 2014 in press.
Disclosure of Interest: P. Mooney: None declared, M. Kurien: None declared, S.
Wong: None declared, D. Sanders Financial support for research from: BHR
Pharmaceuticals, Tillotts Pharma
P1104 ASSESSING ADHERENCE TO GLUTEN FREE DIET IN COELIAC
DISEASE: CAN WE AVOID DUODENAL BIOPSY?
P.D. Mooney1, M. Kurien1,*, S. Wong1, D.S. Sanders1
1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, United
Kingdom
Contact E-mail Address: peter.mooney@sth.nhs.uk
INTRODUCTION: Up to 30% of patients with coeliac disease will have persistent symptoms despite the introduction of a gluten free diet. Assessment of
adherence in coeliac disease can involve any combination of patient self-reporting
adherence, dietetic assessment, serology and biopsy with histology. Histology is
considered to be the gold standard but this requires a repeat endoscopic examination with its associated risks and problems with tolerance. As a result surrogate markers of persistent gluten exposure and histological changes such as
serology are frequently used but the relationship between serology and persistent
histological changes is not linear. A structured interview with a dietician has been
shown to be the most accurate method of assessing gluten exposure however this
is time consuming and requires extra clinic visits. The aim of this study was to
assess the usefulness of two novel options. Firstly a previously internally validated scoring system for assessing dietary adherence1 (which has never been
externally validated) and secondly a rapid de-amidated gliadin peptide based
point of care test (POCT, Simtomax) for the prediction of persistent VA.
AIMS & METHODS: All patients with known coeliac disease and persistent
symptoms coming to a specialist coeliac endoscopy list for the re-assessment of
histology were invited to take part. All patients were tested for Endomysial

A436

United European Gastroenterology Journal 2(1S)

Antibody (EMA), tissue transglutaminase (tTG), immunoglobulins and the


POCT. They were also asked to complete a questionnaire to calculate a 5
point score (0 4) with a high score representative of improved adherence to a
gluten free diet. All patients underwent gastroscopy with at least 4 biopsies from
the second part of the duodenum and 1 to 2 biopsies from the bulb.
RESULTS: 60 patients (78% female, mean age 51.4 range 16-79) were recruited
between April 2013 and April 2014. 22 (36.7%) of these patients had persistent
VA on duodenal biopsy. The POCT was the most sensitive marker with 73% of
patients with VA having a positive test. EMA was the most specific surrogate
marker at 84% although it was highly insensitive with only 36% of patients with
VA having a positive EMA. No patients with completely normalised histology
had a positive EMA. The adherence score could not be reliably used to predict
villous atrophy with a sensitivity of only 32%.
Measure

Sensitivity

Specificity

PPV

NPV

Adherence Score
tTG
EMA
POCT

32%
55%
36%
73%

82%
76%
84%
66%

50%
57%
57%
55%

67%
74%
70%
81%

CONCLUSION: An accurate surrogate marker for villous atrophy could reduce


the number of endoscopies required. In this cohort the POCT had the best
sensitivity, detecting 16/22 (73%) cases of villous atrophy, however this is pilot
data and further work is required. It maybe that additive methods for assessing
adherence could achieve 100% sensitivity
REFERENCES
1. Biagi F, Bianchi P, Marchese A, et al. A score that verifies adherence to a
gluten-free diet: a cross-sectional, multicentre validation in real clinical life. Br J
Nut 2012; 108: 1884-1888.
Disclosure of Interest: P. Mooney: None declared, M. Kurien: None declared, S.
Wong: None declared, D. Sanders Financial support for research from: Tillotts
Pharma

TUESDAY, OCTOBER 21, 2014


9:0017:00
NUTRITION II POSTER EXHIBITION HALL XL_____________________
P1105 METABOLIC ADAPTATION OF COLONIC MICROBIOTA TO
DIET
F. Azpiroz1,2, E. Barba3, M. Mego1, A. Bendezu1, M. Mego3, A. Accarino3,*,
X. Merino4, S. Mendez1, J.R. Malagelada5, A. Accarino1, E. Monclus6,
M. Izquierdo6, I. Navazo6
1
Digestive System Research Unit, University Hospital Vall dHebron, 2Medicina,
Universitat Auto`noma de Barcelona, 3Digestive System Research Unit, University
Hospital Vall dHebron, 4Radiology, University Hospital Vall dHebron, 5Digestive
System Research Unit, University Hospital Vall d?Hebron, 6MOVING Research
Group, Universidad Politecnica de Cataluna., Barcelona, Spain
Contact E-mail Address: azpiroz.fernando@gmail.com
INTRODUCTION: We recently showed that a diet rich in non-absorbable, fermentable residues in the short term increases intestinal gas production and
induces digestive symptoms such as flatulence, bloating and abdominal distention. On the contrary, it has been shown that some prebiotics, which are also
fermented by colonic bacteria, improve this type of symptoms. Hence, it is not
clear whether fermentable residues from the diet have a beneficial or deletereous
effect on digestive symptoms.
AIMS & METHODS: To demonstrate changes in metabolic activity of gut
microbiota and colonic biomass induced by prebiotics. Healthy subjects
(n 20) were administered a prebiotic (Bimuno prebiotic powder, Clasado,
London, UK; 2.8 mg/d) for three weeks; they also received a standardized diet
during three days immediately before, at the beginning and at the end of the
treatment. During these periods the following outcomes were measured: a)
number of gas evacuations during daytime, by means of an event marker; b)
volume of gas evacuated per anus during four hours after a test meal, by means
of a rectal tube connected to a barostat that maintains a minimal resistance to
flow across the collection line; and c) the volume of content in the undisturbed
colon in the 24-h period after a bowel movement (n 5), by means of magnetic
resonance imaging of the abdomen using an original, previously validated analysis program.
RESULTS: Before treatment healthy subjects evacuated gas per anus 12.6  0.9
times during daytime and evacuated 151  15 mL of gas during four hours after
the test meal. At the beginning of treatment, prebiotic administration significantly increased the number of anal gas evacuations (18.6  1.8 times daily; p
5 0.001) and the volume of gas evacuated after the test meal (235  24.6mL; p 5
0.001). Interestingly, by three weeks treatment, both the daily number of gas
evacuations (11.2  1.3), as well as the volume of gas evacuated after the test
meal (161  24) decreased and returned to pre-treatment levels. Prebiotic intake
significantly increased the volume of content in the undisturbed colon (740  73
vs 628  62 pre-treatment; p 50.05), and this increase in colonic biomass was
maintained during the treatment period (792  64 by three weeks; p 50.05 vs
pre-treatment).
CONCLUSION: Availability of substrates induces an adaptation of colonic
microbiota ativity towards more efficient metabolic pathways.
Disclosure of Interest: F. Azpiroz Financial support for research from: Danone,
Given, Beneo, Shire, Consultancy for: Danone, E. Barba: None declared, M.
Mego: None declared, A. Bendezu: None declared, M. Mego: None declared,
A. Accarino: None declared, X. Merino: None declared, S. Mendez: None

declared, J. Malagelada: None declared, A. Accarino: None declared, E.


Monclus: None declared, M. Izquierdo: None declared, I. Navazo: None
declared
P1106 FODMAP-RESTRICTED DIET AND EFFECTS ON FUNCTIONAL
DYSPEPSIA
I. Thun1,*, J.G. Hatlebakk2, G.E. Kahrs3
1
Clinical Institute 1, University of Bergen, 2Department of Medicine, 3Department
of Clinical Nutrition and Section of Gastroenterology, Haukeland University
Hospital, Bergen, Norway
Contact E-mail Address: ingvild_t90@hotmail.com
INTRODUCTION: FODMAPs (fermentable oligo-, di-, monosaccharides and
polyols) is a group of carbohydrates poorly absorbed in the small intestine
some will therefore serve as substrate for colonic fermentation. Studies show
effect of FODMAP-restricted diet on symptoms of irritable bowel syndrome
(IBS) none have been conducted on patients with functional dyspepsia (FD).
We aimed to see whether a 6-week diet low in FODMAPs would have an effect
on symptoms (epigastric pain, postprandial fullness and nausea), quality of life
(QoL) and gas produced during lactulose breath-test.
AIMS & METHODS: 11 FD patients according to the ROME III-criteria were
included in the study (8F/3M, 32.412.2), instructed and followed up closely by a
dietician during a 6-week diet. FD-symptoms (VAS 0-100) and QoL (SF-36) were
collected at baseline, 3 and 6 weeks. FODMAP-intake (grams) was calculated at
baseline and 6w using 4-day food records. Lactulose breath testing (n 10) was
performed at baseline and 6w to observe changes in gas production. Results were
compared using t-tests, one-way ANOVA and correlation.
RESULTS: There was a significant reduction in FODMAP-intake (mean from
53.2g to 3.3g, p50.001). High compliance to the diet was reported (mean 90.4%)
and it was somewhat challenging (mean 50.6%). Epigastric pain (median 54.1 to
0%, p 0.0002), postprandial fullness (median 52 to 0%, p50.001) and nausea
(mean 47.6 to 19.9%, p50.05) significantly reduced from baseline to 6w. SF-36
total score (mental health p 0.37 and physical health p 0.07). Hydrogen gas
production (median 5558 to 2228ppmmin, p 0.0059) significantly declined.
CONCLUSION: In this study, FODMAP-restricted diet significantly reduced
FD-symptoms and hydrogen gas production in 6 weeks.
Disclosure of Interest: None declared
P1107 MALNUTRITION IN HOSPITALIZED IBD- A CALL FOR
RECOGNITION AND TREATEMENT
I. Chermesh1,*, T. Mashiach2, Y. Chowers1
1
gastroenterology, 2Quality assurance unit, RAMBAM HEALTH CARE
CAMPUS, Haifa, Israel
INTRODUCTION: Malnutrition is frequent in IBD patients. Protein-calorie
malnutrition leads to fatigue, inability to carry on every-day life activities and
make the patient prone to prolonged and complicated hospitalizations. Diagnosis
of malnutrition relies upon integration of history taking, physical examination
and laboratory results. Low Urea, Creatinine, CPK and lymphopenia are cornerstone laboratory findings of muscle wasting.
AIMS & METHODS: In this study, we set to check the frequency of recognition
and treatment of malnutrition in hospitalized patients with IBD. Retrieval of
data from electronic files of all hospitalized IBD patients 2012-2013. Screening
criteria for risk of malnutrition included any two of the following: Weight
loss45%; lymphopenia51000/mm3; BUN5; Creatinine0.4; Uric acid2;
CPK20
RESULTS: 134 patients, of whom 113 had complete data, 51% males, 73% with
Crohns disease; age 32.2 years/-13.6. 55% lost 45% weight; 58% diagnosed at
risk for malnutrition, 53% of Crohns and 73% of UC patients (p50.05). Length
of stay (LOS) was 5.1 days and 8.1 days for well-nourished and malnourished
patients (p50.05). On multivariate analysis, only nutritional state and hypoalbuminemia were independent factors for prolonged LOS. Only 15% of patients
received the diagnosis of malnutrition, 38% were given nutritional therapy and
32% had recommendations to take nutritional therapy after discharge from the
hospital.
CONCLUSION: Malnutrition is common in hospitalized patients with IBD and
is associated with prolonged hospitalizationX1.5 times than patients who are well
nourished. Assessment of patients at risk, recognition and treatment of malnutrition are suboptimal. Measures to optimize identification of patients at risk for
malnutrition and provision of adequate treatment are needed.
Disclosure of Interest: None declared
P1108 HOW OFTEN DO WE RECOGNIZE MUSCLE WASTING AND
MALNUTRITION IN HOSPITALIZED IBD PATIENTS
I. Chermesh1,*, T. Mashiach2
1
gastroenterology, 2Quality assurance unit, RAMBAM HEALTH CARE
CAMPUS, Haifa, Israel
Contact E-mail Address: i_chermesh@rambam.health.gov.il
INTRODUCTION: Malnutrition and an inflammatory state can combine to
contribute to muscle wasting in IBD patients. Since muscle wasting is directly
related to frailty and quality of life it is of utmost importance to diagnose. Low
Blood Urea Nitrogen (BUN), Uric Acid, Creatinine, and CPK are cornerstone
laboratory findings of muscle wasting (MW). Weight loss characterizes proteincalorie malnutrition.
AIMS & METHODS: In this study, we set to check the frequency of recognition
of muscle wasting and malnutrition in hospitalized IBD patients. Retrieval of
data from electronic files of all hospitalized IBD patients 2011-4.2014. Screening

United European Gastroenterology Journal 2(1S)


criteria for risk of MW and malnutrition included: Weight loss45%; BUN5;
Creatinine0.4; Uric acid2; CPK20. Suspected MW was defined as a combination of two or more of the following low BUN, Creatinine, Uric acid or CPK.
Malnutrition risk if one of the above and weight loss was present.
RESULTS: 169 patients, with active IBD, 54%% males, 73% with Crohns
disease; age 35 years/-14. 38% lost 45% weight; 11% had laboratory findings
compatible with MW, 16% of patients with MW lost weight. Length of stay
(LOS) was longer for patients with MW irrespective of WL or age (15.2/-23
vs. 5.3/-4 (p50.0001). None of the patients were diagnosed with MW, only
15% of patients received the diagnosis of malnutrition
CONCLUSION: MW is prevalent in more than 10% of hospitalized IBD
patients and is associated with prolonged hospitalization X3 times than patients.
MW is a known factor associated clinical deterioration. The data herein presented, manifests lacking diagnosis and calls for measures to raise recognition of
this important clinical manifestation.
Disclosure of Interest: None declared
P1109 INTRAGASTRIC PRESSURE DURING DIFFERENT NUTRIENT
DRINK INFUSIONS
J.R. Biesiekierski1,*, J. Tack1
1
KU Leuven, Leuven, Belgium
Contact E-mail Address: Jess. Biesiekierski@med.kuleuven.be
INTRODUCTION: Recent intragastric pressure (IGP) measurements, used to
assess gastric accommodation1, have shown that intragastric nutrient infusion
induces an initial drop in IGP, followed by a gradual recovery, with significant
correlation to satiation and the volume required to induce maximal satiation.
The type of nutrient(s) that drive(s) these IGP responses have not been identified.
AIMS & METHODS: The objectives were to assess the role of specific nutrients
in inducing IGP response and their contribution to satiation. A manometry and
infusion catheter were positioned in the proximal stomach of 15 healthy volunteers. After a stabilization period, one of three nutrient drinks (high lipid [10%
lipid emulsion], high protein [whey protein isolate], or high carbohydrate [glucose]) were intragastrically infused at 60 mL/min, three days to one week apart in
a single-blinded randomised order. There were no differences in caloric or osmotic load between the drinks. The experiment ended when subjects scored maximum satiation. IGP was presented as change from baseline (mean  SEM).
Satiation scores were measured before, during and after the infusion at 10minute intervals using a 100 mm visual analogue scale. Results were compared
using a repeated measures ANOVA.
RESULTS: 15 eligible volunteers (21-52 y, 7 men) were randomised. Volunteers
scored maximal satiation after a higher volume of the carbohydrate drink infusion (1231  126 mL) compared to the other nutrients (protein 1049  99 mL,
lipid 1006  49 mL; p 0.0027). In all subjects and with each nutrient infusion,
the IGP decreased initially to gradually recover thereafter. Maximum IGP
decrease (termed nadir) was 7.6  0.9 mmHg after 8.1  1.3 min, 9.4  1.0
mmHg after 10.1  1.2 min, and 7.7  0.6 mmHg after 8.7  1.2 min for
carbohydrate, protein and lipid respectively (nadir p 0.1461; time to nadir
p 0.4422). Overall, the area above the IGP curve was greater for the lipid
(114.7  14.7 mmHg/min) compared to the carbohydrate and protein (94.6 
19.3 and 81.0  9.5 mmHg/min, respectively) (p 0.1020). Post hoc analysis
showed significant correlations between IGP and satiation score increase, with
slightly greater satiation induced with the lipid (84  3.5 mm; carbohydrate 78 
5.2 mm, protein 76  6.3 mm; p 0.1764).
CONCLUSION: This study indicates all three macronutrients induce an IGP
response in the healthy state. The findings offer opportunities to objectively
identify whether these specific nutrients drive the impaired gastric accommodation seen in functional gastroduodenal patients (e.g., functional dyspepsia).
REFERENCES
1. Janssen P, et al. Intragastric pressure during food intake: a physiological and
minimally invasive method to assess gastric accommodation. Neurogastroenterol
Motil 2011; 23: 316-322.
Disclosure of Interest: None declared
P1110 DIETARY ASSESSMENT AND EVALUATION OF MYCOTOXIN
EXPOSURE IN CELIAC PATIENTS
L. Roncoroni1,*, C. Tomba1, L. Elli1, M.T. Bardella1, D. Conte1, T. Mazzeo2,
C. DallAsta2, C. Agostoni3, V. Lombardo1, G. Galaverna2, F. Brighenti2,
N. Pellegrini2
1
IRCCS Ca` granda Ospedale Policlinico, University of Milan, Center Prevention
and Diagnosis of Celiac Disease, Gastroenterology and Digestive Endoscopy,
Milan, 2Department of Alimentary Sciences, University of Parma, Parma, 3IRCCS
Ca` granda Ospedale Policlinico, Clinic Pediatric 2, Milan, Italy
Contact E-mail Address: leda.roncoroni@tiscali.it
INTRODUCTION: Gluten free diet (GFD) is currently the only available therapy for patients with celiac disease (CD), the most common autoimmune enteropathy in Western Countries, occurring in genetically susceptible individuals and
triggered by gluten ingestion. As gluten rich products are an important source of
nutrients, it is not clear if GFD could have a negative effect on the nutritional
status of CD patients and if GFD could expose to mycotoxins contained in
gluten free flours.
AIMS & METHODS: Aim of the study was to estimate the nutrient intake and
the dietary exposure to mycotoxins in treated CD vs. controls.
Sixty participants, thirty histologically proven CD and thirty sex-age matched,
healthy control were enrolled. Total food and beverage consumption was
assessed by means of a food record filled in every day for a total of 7 days.
The nutrient intake was calculated using a Microsoft Access application linked
to the food database of the European Institute of Oncology and integrated with

A437
the nutrient composition of sixty commercial GF (Gluten-Free) foods. Test for
mycotoxins (fumonisin B1 and deoxynivalenol) biomarkers was carried out on 24
hour urine collection.
RESULTS: Compared to controls, CD patients on GFD consumed a lower
percentage of energy as carbohydrates and a higher percentage of energy as
fats (48 % vs 51% and 37 % vs 33%, respectively). Moreover, GFD has a
higher intake of vitamin C, vitamin E and sodium than normal diet (142 mg vs
118; 18 mg vs 13 mg; 3340 mg vs 2959 mg respectively). Concerning mycotoxins
exposure, preliminary results on urinary fumonisin B1 and deoxynivalenol excretion failed to evidence any differences between GFD and control diet.
CONCLUSION: Present data show a higher consumption of fruit and vegetables
rich in micronutrients and an increased intake of fat and sodium (due to GF
packaged product) in GFD.
Exposure to mycotoxins does not differ between CD patients and controls.
Disclosure of Interest: None declared
P1111 HYPERNATRAEMIA AND C REACTIVE PROTEIN ARE
INDEPENDENTLY RELATED TO 1-,3-MONTH AND LONG TERM
MORTALITY IN PATIENTS WHO UNDERWENT PERCUTANEOUS
ENDOSCOPIC GASTROSTOMY (PEG) FOR DYSPHAGIA - A
SINGLE-CENTRE EXPERIENCE
A. Caponi1, G. Gibiino1,*, A. Lisotti1, F. Azzaroli1, F. Bazzoli1, G. Mazzella1,
R. Muratori1
1
Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Contact E-mail Address: giulia.gibiino@gmail.com
INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is performed
to provide enteral nutrition to patients with swallowing disorders. Previous studies demonstrated that advanced age, low BMI, low serum albumin and high
levels of C reactive protein (CRP) are related to worst clinical outcomes. The aim
of our study was to evaluate predictive factors of morbidity and mortality in
patients who underwent PEG placement.
AIMS & METHODS: Data from all consecutive patients undergoing PEG placement for oropharyngeal dysphagia between March 1999 and December 2013,
were collected; in particular indication for PEG placement, comorbidities, concomitant medications and lab-tests were recorded.
All patients received antibiotic prophylaxis; anti-thrombotic drugs were discontinued when possible. Coagulation defects and serum potassium alterations were
corrected. All procedures were performed under deep sedation administered by
anaesthesiologists. Enteral feeding was started at least 24 hours after the
procedure.
Patients were followed up and periprocedural (within 48h) major complications,
1- and 3-month mortality rates were recorded. Cox-proportional hazard regression and Kaplan-Meyer analyses were used to identify prognostic indicators of
mortality; ROC curves were used to identify the best cut-off points.
RESULTS: 438 patients (178 Male; 77.4  12.1 years) were included; causes of
dysphagia were stroke (149), dementia (137), neurodegenerative disease (81),
coma (40) and cancer (31); mean follow-up was 14.6 months. No periprocedural
complications or death were observed; 1- and 3-month mortality rates were 4.0%
and 8.1%, respectively. Gender (male), underlying neoplasia, presence of diabetes, low serum albumin, thrombocytopenia, hypernatraemia, increased CRP
and leucocytosis were significantly related to mortality on univariate analysis.
Cox-regression identified serum sodium  150 mmol/L (OR 25.4; 95%CI 7.486.8; P50.0001) as factor independently related to 1- month mortality and CRP
44,34 mg/dL (OR 5.3; 95%CI 1.8-15.9; p 0.003) to 3-month mortality. On
Kaplan-Meyer analysis patients with CRP44,34 mg/dL (HR 3.5; 95%CI 1.58.3) and Na  150 mmol/L (HR 4.3; 95%CI 1.1-17.6) presented a significantly
increased risk of long term mortality.
The presence of an underlying neoplasia (as indication for PEG placement or
comorbidity) is an independent risk factor for 1-, 3-month and long-term mortality (OR 3.69, 3.30 and 2.32, respectively). Finally, we observed that dementia
was not associated with an increased risk of mortality (HR 1.21; 95%CI 0.751.96; p 0.42).
CONCLUSION: Significant hypernatraemia ( 150 mmol/L) and high levels of
serum CRP (4 4,34 mg/dL) are independent predictors of short- and long-term
mortality. Improvement in patients selection criteria and pre-procedural management could lead to better outcomes after PEG placement. Our results suggest
that serum hypernatraemia, reflecting an underlying modifiable dehydration
status, has to be properly assessed and even corrected.
Disclosure of Interest: None declared
P1112 EFFICACY AND COMPLICATION OF ENTERAL FEEDING
AFTER LIVER TRANSPLANTATION
J.H. Chun1,*, J.Y. Ahn1, H.Y. Jung1, K.D. Choi1, J.H. Lee1, K.S. Choi1,
K.W. Jung1, D.H. Kim1, H.J. Song1, G.H. Lee1, J.H. Kim1
1
Department of Gastroenterology, Asan medical center, Seoul, Korea, Republic Of
Contact E-mail Address: joohyunchun@nate.com
INTRODUCTION: Adequate nutrition support for patients undergoing major
surgery has been shown to impact significantly on postoperative recovery. Data
on the enteral feeding after liver transplantation (LT) are scarce.
AIMS & METHODS: We tried to know about the efficacy and complication of
feeding tube which was inserted by fluoroscopic assistance, endoscopic assistance
or transperitoneal jejunostomy in patients who were underwent LT. Between
January 2008 and August 2013, 2058 cases of LT were performed at Asan
Medical Center, Seoul, Korea and enteral feeding tube was inserted in
155(7.5%) patients after LT. Among 155 patients fluoroscopic placement was
performed in 81 patients (52%), endoscopic placement in 49 patients (32%), and

A438
transperitoneal jejunostomy in 25 patients (16%). We retrospectively analyzed
the efficacy and complication of enteral feeding tube.
RESULTS: Median age was 55 years (interquartile range [IQR] 49-60years).
Indication of enteral feeding were high risk of gastric aspiration (n 90), gastric
stasis (n 27), pneumonia (n 23), gastrointestinal bleeding (n 12), and bowel
rest (n 3). Duration of enteral feeding was 14.5 days (IQR 8.0-30.7 days) in
fluoroscopic placement, 20.0 days (IQR 8.0-40.0 days) in endoscopic placement,
37.5 days (IQR 18.2-86.2 days) in transperitoneal jejunostomy. Time to establishment of oral feeding was 13.0 days (IQR 6.2-25.7 days) in fluoroscopic placement, 24.0 days (IQR 10.5-43.5 days) in endoscopic placement, 37.0 days (IQR
17.0-64.2 days) in transperitoneal jejunostomy. After tube insertion, dislocation
of tube and blockage of tube were found on 34 patients (22%) and 16 patients
(25%). Most common enteral feeding related complications were diarrhea
(n 68, 44%).
CONCLUSION: Enteral feeding tube insertion to the patients who cannot maintain nasogastric tube or start oral intake for a long time is important for the
nutritional support after LT. Each methods of tube insertion by fluoroscopy,
endoscopy, or surgery show its own advantage and disadvantage. Proper selection of feeding methods according to the patients condition can improve the
prognosis of patients by better nutritional support after major surgery such as
LT.
REFERENCES
1. Han-Geurts IJ, Hop WC, Verhoef C, et al. Randomized clinical trial comparing feeding jejunostomy with nasoduodenal tube placement in patients undergoing oesophagectomy. Br J Surg 2007; 94: 31-35.
2. Abu-Hilal M, Hemandas AK, McPhail M, et al. A comparative analysis of
safety and efficacy of different methods of tube placement for enteral feeding
following major pancreatic resection. A non-randomized study. JOP: J Pancreas
2010; 11: 8-13.
3. Gerritsen A, Besselink MG, Cieslak KP, et al. Efficacy and complications of
nasojejunal, jejunostomy and parenteral feeding after pancreaticoduodenectomy.
J Gastrointest Surg Off J Soc Surg Aliment Tract 2012; 16: 1144-1151.
Disclosure of Interest: None declared
P1113 GLUCOSE HOMEOSTASIS IN CRITICALLY ILL PATIENTS IS
NOT AFFECTED BY DIFFERENT ENTERAL NUTRITION
FORMULAS
M. Wewalka1,*, A. Drolz1, M. Schmid1, C. Zauner1
Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

INTRODUCTION: Hyperglycemia is common in critically ill patients and associated with increased mortality. It has been suggested that different nutrition
formulas may beneficially influence glucose levels in surgical ICU patients. We
investigated glucose homeostasis in response to different enteral nutrition formulas in medical critically ill patients.
AIMS & METHODS: A total of 60 patients were randomized to receive continuous fat-based (group A, n 30) or glucose-based enteral nutrition (group B,
n 30) for seven days. Indirect calorimetry was performed to determine energy
demand at baseline and repeated on days 3 and 7 to evaluate substrate oxidation.
Glucose levels, insulin demand, insulin/glucose ratio, calorie and substrate intake
per 24 hours, as well as nutrition related side effects were assessed for 7 days.
RESULTS: Patients presented with similar age (6012 vs. 5816 years,
p 0.657), Body Mass Index (26.25.2 vs. 27.54.4 kg/m2, p 0.294) and
SAPS II score (5814 vs. 6313, p 0.147). At baseline patients did not differ
with regard to energy demand (1542382 vs. 1485384 kcal, p 0.566) or fasting
glucose levels (14965 vs. 13968 mg/dl, p 0.571). Over the course of 7 days
patients had similar glucose AUC (710172 vs. 763122, p 0.193), similar
average glucose concentrations per 24 hours (repeated measures ANOVA
p 0.655), similar overall insulin demand (187165 vs. 186125 IE,
p 0.991), and a similar insulin/glucose ratio (repeated measures ANOVA
p 0.962). Furthermore they received similar amounts of enteral nutrition per
24 hours and showed no difference in nutrition related side effects such as gastric
reflux, vomiting, diarrhea, and hyperlipidemia.
CONCLUSION: Patients showed similar glucose homeostasis and insulin
demand regardless of whether continuous enteral nutrition was fat-based or
glucose-based. Special nutrition formulas do not seem to influence glucose homeostasis in the acute phase of illness in medical critically ill patients.
Disclosure of Interest: None declared
P1114 HEALTHCARE PROFESSIONALS KNOWLEDGE ON THE
INSERTION & BASIC CARE OF NASOGASTRIC FEEDING TUBES
M. Carter1, P. Eadala1,*, C. Planello1
Gastroenterology, Morriston Hospital, Swansea, United Kingdom
Contact E-mail Address: matthewphillip.carter@wales.nhs.uk
1

INTRODUCTION: In the UK, thousands of nasogastric (NG) feeding tubes are


inserted each day to administer enteral feeds and medication. The main risk
associated with NG tubes is misplacement into the respiratory tract. Between
2005-2010, the National Patient Safety Agency (NPSA) reported 100 serious
incidents relating to the misplacement of NG tubes, with 21 resulting deaths.
Guidelines set by the NPSA aim to ensure that thorough checks are carried out to
minimise patient risk.
AIMS & METHODS: The aim was to evaluate the knowledge of healthcare
professionals on the basic principles behind inserting and caring for NG tubes.
NPSA guidelines were analysed and a multiple choice questionnaire was created.
Questions covered contraindications to NG tubes, basic safety checks to confirm
correct placement (pH of aspirates and interpretation of chest x-rays) and basic
care of NG tubes once sited. 120 questionnaires were distributed on one day to all
available doctors and nurses in the ED, medical, surgical & intensive care wards

United European Gastroenterology Journal 2(1S)


in a South Wales hospital. Questionnaires were completed without time constraints and collected the same day. They were then marked against a prescored questionnaire.
RESULTS: 120 questionnaires were distributed. 73% were returned. 45% were
completed by doctors & 55% by nurses. 38% were able to identify all contraindications to NG tube insertion. Participants were asked to estimate the length
an NG tube should be inserted. A NEX (Nose-Ear-Xiphysternum) measurement
should be taken prior to insertion. 32% of participants were able to identify the 3
correct anatomical landmarks. Questions regarding safety checks following insertion of an NG tube were answered well. 79% were able to identify the first line
test (pH paper) that should be used to confirm correct placement. 82% were
aware that chest x-ray is a second line test. Only 42% were aware of the correct
pH which confirms correct NG placement. No participants were able to identify
all situations requiring immediate re-confirmation of NG tube site. Worryingly,
16% did not identify that NG tube position should be reconfirmed before administering enteral medication/feeds. 14% were unaware that NG tube position
should be reconfirmed after vomiting. 10% did not identify new signs of respiratory distress as a situation requiring reconfirmation of site. Participants trained
to interpret chest x-rays were asked to identify chest x-ray features seen with a
correctly sited NG tube. 29% correctly identified all features. The remaining
participants did not identify one or more features that are essential to look for
when checking NG placement on a chest x-ray. 56% did not identify bisecting the
carina as a feature, and 15% did not select clearly identifiable NG tube as a
required feature.
CONCLUSION: Amongst clinical staff there is poor knowledge on NG tubes.
Many participants were unable to identify absolute contraindications and were
unaware of the NEX measurement. Less than half the cohort were aware of the
aspirate pH that confirms correct positioning. There was poor knowledge of
situations requiring immediate re-confirmation of NG site and chest x-ray features confirming placement. These results highlight the need for improvement in
training staff receive on NG tubes, to ensure that patent safety is not
compromised.
REFERENCES
Patient Safety Alert NPSA/2011/PSA002: Reducing the harm caused by misplaced nasogastric feeding tubes in adults, children and infants.
Disclosure of Interest: None declared
P1115 FACTORS
INFLUENCING
GASTROSTOMY INSERTION

MORTALITY

FOLLOWING

M. Kurien1,*, R. Andrews1, M.E. McAlindon1, D.S. Sanders1


1
Department of Gastroenterology, ROYAL HALLAMSHIRE HOSPITAL,
Sheffield, United Kingdom
INTRODUCTION: High mortality rates have previously been reported following gastrostomy insertion, particularly among certain patient groups (e.g. dementia). With the increasing use of prophylactic gastrostomy for head and neck
cancer (HNC), our group aimed to examine survival in this cohort compared
to other referral indications and assess risk factors.
AIMS & METHODS: Gastrostomy insertions were examined from two hospitals
in Sheffield between 2004 - 2013. Data was prospectively collected from all
referred patients including demographic data, biochemical parameters, referral
indications and gastrostomy type. Statistical analysis was performed with Chisquared or Fishers exact tests.
RESULTS: 1733 patients were included (1004 male, mean age 65). 30 day and
1 year mortality was 9.66% and 44.98% respectively. Indications for gastrostomy
included; HNC (n 591), neurological disease (n 429), dysphagic stroke
(n 393), dementia (n 9) and other (n 311). The lowest mortality was seen
in patients with HNC (30 day mortality 5.2%, 1 year mortality 32.6%). In
comparison, 30 day mortality in all other groups was significantly higher (8.47%
in neurological diseases, 15.86% in dysphagic stroke, 33.3% in dementia and
11.25% in other indication, p50.01). Mortality was also significantly higher
at one year (p50.01). There was no significant difference in mortality when
comparing radiologically inserted and percutaneous endoscopic gastrostomies.
Higher mortality rates were seen in patients aged 60 years or above at 30 days
(OR 2.439 (1.666 3.731) p50.0001) and also at 1 year (OR 3.140 (0.268 0.600)
p50.0001). Albumin less than 30g/L was also associated with significantly higher
30 day (OR 4.486 (3.067 6.561) p50.0001) and 1 year mortality outcomes (OR
2.319 (1.830 to 2.939) p50.0001). In accordance with recent published data, our
findings would support an elevated CRP (45mg/L) being a factor associated
with 30 day mortality (OR 8.930 (1.199 to 66.51) p 0.006).
CONCLUSION: Referral indication for gastrostomy significantly impacts 30
day and 1 year mortality outcomes, with lowest rates demonstrated in patients
with HNC. Identification of factors associated with mortality as seen in this
study could help improve patient selection and be of relevance in the decision
making process for gastrostomy.
Disclosure of Interest: None declared
P1116 20 YEARS EXPERIENCE OF PERCUTANEOUS ENDOSCOPIC
GASTROSTOMY IN A PORTUGUESE TERTIARY CENTER
P. Sousa1,*, H. Cortez-Pinto1, S. Carvalhana1, M. V. Machado1, L. Carrilho
Ribeiro1, J. Velosa1
1
Gastrenterologia, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria,
Lisboa, Portugal
Contact E-mail Address: patlizbms@gmail.com
INTRODUCTION: Gastrostomy may be indicated in several situations usually
when oral intake is not adequate. It can be done surgically or with endoscopy:
percutaneous endoscopic gastrostomy (PEG). PEG placement allows adequate
nutrition, in dysphagic patients of different etiologies.

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United European Gastroenterology Journal 2(1S)


AIMS & METHODS: The aim of this study was to characterize the patients in
whom a PEG was placed and the complications associated with the procedure.
Retrospective study of all patients in whom a PEG was placed between
November 1993 until April 2014 in a referral center, based on data prospectively
collected, including follow-up visits. All PEGs were performed using the pullthrough technique by one experienced endoscopist.
RESULTS: 865 patients were included; 515 were male with a mean age of 63.28
years. The mean follow-up time was 19.21 months (0-158).
The most common indication for the procedure was motor dysphagia. Most
patients were referred from neurology: 309 (35%), otorhinolaryngology: 227
(26%), and internal medicine: 94 (11%).
507 patients had neurologic disease and 292 had cancer. Of the neurologic diseases the most common were amyotrophic lateral sclerosis (216; 43%); stroke
(87; 17%); dementia (58; 11%); Parkinson (32; 6%); traumatic brain injury (21;
4%) and cerebral palsy (17; 3%). The most common malignancies were pharyngeal-laryngeal (207; 71%); esophagic (40; 14%) and central nervous system
(30; 10%. In 5 patients the procedure was not done because there was no gastric
transillumination (4 had previous abdominal surgeries).
The most frequent complication in our series: Minor: inadvertent PEG tube
removal (about 100, difficult to be exact), mucosal extrusion (150), significant
peristomal leakage (20); Major: pneumoperitoneum with abdominal pain, leucocytosis and elevated C reactive protein (5), wound infection (4), buried bumper
syndrome (4), small bowel perforation during PEG/PEJ placement (1), interposed bowel (3) and cardio-respiratory arrest (3), one during the procedure
and the other 2 in the 48 h after the procedure. Only one patient needed surgical
intervention.
There were three other procedure related deaths. One patient refused surgery
after small bowel perforation during the procedure; other had peritonitis after
inadvertent PEG tube removal and the other patient in the sequence of an abscess
after buried bumper syndrome.
CONCLUSION: In our series PEG was quite a safe procedure that was more
commonly used in patients with neurologic disease and cancer.
Disclosure of Interest: None declared

TUESDAY, OCTOBER 21, 2014


9:0017:00
PAEDIATRIC: UPPER GI POSTER EXHIBITION HALL XL_____________________
P1117 ARE DILATATIONS
CHILDREN EFFECTIVE?

OF

ESOPHAGEAL

STRICTURES

IN

F. Benhassine1,*, A. Yagoubi1, L. Benhassine1, M. Baghriche1


1
Hopital Bologhine, Algiers, Algeria
Contact E-mail Address: f_benhassine@yahoo.fr
INTRODUCTION: Esophageal strictures in children are most of the time
acquired and benign. Although they have multiple etiologies, they all respond
to the same treatment: instrumental dilatations.
Our objective is to specify the etiology of esophageal strictures and to assess their
response to dilatation treatment depending on the etiology.
AIMS & METHODS: The study covers all the cases of esophageal strictures
treated in our pediatric digestive explorations unit, that benefited from dilatations between January 1996 and December 2011. Out of 1,022 cases of diagnosed
esophageal strictures, 422 benefited from dilatations. The dilatations were performed using Savary-Gillard bougies in an outpatient setting, under heavy sedation, or general anesthesia for complex strictures. Three to four bougies are
passed per session. The response to treatment is judged good when obtaining a
quasi-normal oral feeding without food hangings.
RESULTS: 422 children, aged between 2 months and 15 years, benefited from
repeated dilatations, performed at short intervals in the beginning, then at longer
intervals depending on the results. The strictures were caustic (330 cases of which
16 presented an anastomotic stricture after oesophagoplasty), peptic (48 cases),
and anastomotic (operated eosophagal atresia (25 cases), congenital (9 cases),
thermal (2 cases), caustic plant ingestion (1 case), and unknown nature (9 cases)).
The response to the treatment, all causes combined, is good in 345 cases out of
422 (82%). The results are better for the peptic strictures (98%) compared to
anastomotic (90%), caustic (79%) and congenital (78%) strictures.
The 422 patients required 2,711 dilatation sessions. The average number of sessions is higher in caustic strictures than in other etiologies: 8 sessions versus 4
respectively.
Complications consisted in 5 cases of perforation (4 caustic strictures and 1
congenital), 1 case of digestive bleeding and 1 case of septicemia that responded
well to medical treatment.
CONCLUSION: Caustic esophageal strictures are the most frequent cause in our
practice. Globally, the response to dilatations is relatively good but their future,
on the long term, remains a subject of preoccupation and an endoscopic surveillance of these children in adulthood is necessary in order to detect a possible
dysplasia.
Disclosure of Interest: None declared

P1118 THE CHARACTERISTIC OF GASTROESOPHAGEAL REFLUX IN


CHILDREN WITH CYSTIC FIBROSIS
M. Dziekiewicz1,*, A. Banaszkiewicz1, A. Urzykowska2, A. Lisowska3,
M. Rachel4, J. Walkowiak3, D. Sands2, A. Radzikowski1
1
Department of Pediatric Gastroenterology and Nutrition, Medical University of
Warsaw, 2Department of Pediatrics, Institute of Mother and Child, Warsaw,
3
Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan
University of Medical Sciences, Poznan, 4Allergology Outpatient Department,
Provincial Hospital No 2, Rzeszow, Poland
INTRODUCTION: Previously published studies have indicated that gastroesophageal reflux disease (GERD) is very common in patients with cystic fibrosis
(CF), also in paediatric population. However, it hasnt been well characterized
so far.
AIMS & METHODS: The aim of the study was to assess the frequency of
GERD and characterize gastroesophageal reflux episodes (GER) in children
with cystic fibrosis.
This was a multicenter, prospective study of children with cystic fibrosis older than
12 months of age. All children underwent 24 hour multichannel intraluminal pHimpedance (MII-pH) monitoring. The characteristic of GER was made with
BioVIEW analysis software and manual revision made by single investigator.
RESULTS: 44 consecutive patients (22 boys, median age 10.65 3.6, range 6.317.8) were enrolled into the study. GERD was diagnosed in 26/44 (59.1%)
patients. A total of 1585 reflux episodes were detected by MII-pH. 1199
(75.6%) of them were acid, 382 (24.1%) weakly acid and 4 (0.3%) weakly
alkaline. 691 (43.6%) GER episodes reached the proximal oesophagus. In only
14/44 (31.7%) patients typical GERD symptoms were present.
CONCLUSION: It was the largest study characterising GERD in children with
CF with a use of MII-pH performed so far. The frequency of GERD in children
with CF is very high, similar to previously raised. Majority of GER episodes were
acid, so proton pump inhibitors may be an effective therapeutic option in this
population. Number of proximal GER was relatively high, which may increase
the risk of aspiration. In children with cystic fibrosis GERD should be diagnosed
regardless of presence of its typical symptoms.
Disclosure of Interest: None declared
P1119 TRAVERSING DIFFICULT ESOPHAGEAL STRICTURES IN
CHILDREN
P.P. Elia1,2,*, A. Freire1, D. Pestana3, V. Sousa3, A. Lima3, L. Fernandes3,
P. Melo3, P. Boechat3
1
Digestive Endoscopy, Gastroendo, 2Pediatric Surgery, 3Instituto Fernandes
Figueira - FIOCRUZ, Rio de Janeiro, Brazil
Contact E-mail Address: paulaelia@iff.fiocruz.br
INTRODUCTION: Esophageal stricture (ES) may arise in children from a
number of etiologies, mainly as a primary anomaly, after esophageal surgery
and as a result of chemical injury. Esophageal balloon or bougie dilation is a
nonsurgical method for treatment of most esophageal strictures in children. Some
strictures may be complex and require a divergent treatment approach.
AIMS & METHODS: The aim of this study was to determine the efficacy and
safety of esophageal dilatations for symptomatic esophageal strictures in
children.
A retrospective longitudinal study was carried out on children with ES who were
submitted to esophageal dilatation in two pediatric hospitals in Rio de Janeiro
over a median follow-up period of 6 years. The data collected were age, sex, type
of ES, type of dilatation treatment, number of dilatations, intralesional injection
of corticosteroid, use of rigid scope and dilatation with different accessories for
endoscopes. All the procedures were under general anesthesia. The objective of
each dilatation session was to break the stricture or to increase the esophageal
diameter.
RESULTS: 63 patients were included in this study. Patients age ranges one
month-old to 10 years-old and 54% were male. The most common stricture
cause was postoperative (after esophageal atresia repair) in 46 patients (73%),
followed by caustic stricture in 17% patients. A total of 453 bougie dilatations
were carried out with the mean number of dilatations per patient being 7.
Eighteen patients (29%) had complex strictures and require a special treatment.
In 9 (14.3%) patients only the ERCP guide-wire pass the ES, 4 patients (6.3%)
were treated with intralesional triamcinolone, 3 (4.8%) were first dilated with
ERCP balloon, 2 (3.2%) require rigid esophagoscopy to the first dilatation, 2
were submitted to gastrostomy and retrograde positioning of the guide-wire, 2
were first dilated with biopsy forceps, 1 patient (1.6%) had been treated by
electrocautery therapy and 1 with total esophageal occlusion were treated by
anterograde-retrograde Rendez-vous approach. Dilatation was successful in 39
patients (62%), 13 patients (21%) are still being submitted to dilatation, 6 (9.5%)
were referred to surgical treatment and 5 (8%) abandoned the treatment.
There were one (0.2%) anesthetic complication and 3 (0.6%) endoscopic perforations (2 treated clinically and 1 surgically).
CONCLUSION: Savary-Gilliard bougie dilatation is a safe and effective procedure in the management of the most ES in children. In ours series the most
children (90%) had been treated endoscopically with low number of complications. Complex ES may require different treatment. The creativity of the endoscopist using different accessories for endoscopes allow many patients with
complex stenosis to be treated in non surgical method.
REFERENCES
1. Pyrtle J and Obando J. Endoscopic management of the difficult benign esophageal stricture. Tech Gastrointest Endosc 2007; 9:74-83.
2. Gupta SK. Esophagogastroduodendoscopy in pediatric patients including
biopsy techniques and dilatation. Tech Gastrointest Endosc 2002; 4: 174-180.
Disclosure of Interest: None declared

A440

United European Gastroenterology Journal 2(1S)

P1120 PRIMITIVE
PEPTIC
ULCER
DISEASE:
A
5-YEAR
RETROSPECTIVE STUDY IN A CHILDRENS HOSPITAL FROM
NORTH-EASTERN ROMANIA
S. Diaconescu1,*, C. Olaru1, G. Paduraru1, G. Ciubotariu1, M. Burlea1,
N. Gimiga1
1
Pediatrics, "Gr. T. Popa" University of Medicine and Pharmacy, Jassy, Romania
INTRODUCTION: Primitive peptic ulcer disease is still frequent in children
from middle income countries with a high incidence of H. Pylori infection and
a large amount of population with impaired socioeconomic status.
AIMS & METHODS: To investigate the prevalence, clinical features and risk
factors of primitive peptic ulcer disease (PUD) in a pediatric population from
North-Eastern Romania. We examined retrospectively all endoscopy records
from 2009-2013. Demographical, clinical, laboratory, endoscopical and therapeutic data were analysed.
RESULTS: We report an incidence of 6.09/100.000 individuals for primary PUD
and a frequency of 4.61%. 49.36% of children were 14-16 years old (range: 7-18
years), male to female ratio was 1.46:1 and 77.41% of patients were living in
urban areas. Clinical features included chronic abdominal pain (50.89%), followed by vomiting (34.18%) and upper digestive bleeding (11.39%). We found 65
douodenal ulcers (DU) and 19 gastric ulcers (GU). Family history was positive in
55.33 % of DU; in this group we found type O blood in 55.56% of the patients.
71.42% were HP-related PUD; from these, 77.42 % were DU. Non HP-PUD
was found in 28.58 % children We identify an improper diet (63.16%), smoking
(57.39%), alcohol consumption (15, 78 %), psychological stress represented by
school difficulties (27.27%), family conflicts (22.73%) and conflicts with entourage (13.64%) as additional risk factors for the disease. We noticed a significant
correlation between a high number of family members (r 0.63, p 0.002), low
socioeconomic status (r 0.87, p 0.0003) and H.pylori infection. We used standard triple therapy in 73.33% of the patients, bismuth-based quadruple therapy
in 16.66 % children and sequential therapy in 10% of the cases. The global
eradication rate was 66.66 % on all series of patients; we didnt have technical
conditions to search antibiotic resistance of the bacteria but previous studies
indicate a resistance to clarithromycin around 33 % in Romania.
CONCLUSION: In North-Eastern Romania, primitive PUD affects mainly
teenagers from urban areas, originating from large families with a low socioeconomic status and a high incidence of H.pylori infection. DU were more frequent, associated with blood type O and family history; we also identified
associated risk factors for the disease as diet, smoking, alcohol consumption
and stress. Since we obtain a moderate eradication rate using the first line recommended therapies we considered this as an indirect proof of high clarithromycin
resistance in romanian children due to the wide-spread practice of empirical
antymicrobial therapy in our country.
REFERENCES
1. Guariso G and Gasparetto M. Update on peptic ulcers in the pediatric age.
Ulcers 2012; 2012: Article ID 896509, 9 pages. DOI:10.1155/2012/896509
2. Ciobanu L, Prundus R, Andreica V, et al. Epidemiological trends of
Helicobacter pylori infection in Romania. Bridging meeting of EAGE and postgraduate course Targu Mures, Romania, 30 October1 November 2008.
3. Koletzko S, Jones NL, Goodman KJ, et al. Evidence-based guidelines from
ESPGHAN and NASPGHAN for Helicobacter pylori infection in children. J
Pediat Gastroenterol Nutr 2011; 53: 230243.
Disclosure of Interest: None declared

n
w
a
ithdr

P1121 PRIMARY ANTIBIOTICS SUSCEPTIBILITY AND EFFICACY OF


SUSCEPTIBILITY-GUIDED TRIPLE THERAPY FOR
HELICOBACTER PYLORI AMONG JAPANESE CHILDREN WITH
HIGH CLARITHROMYCIN RESISTANCE RATE IN THE LAST
DECADE - A MULTI-CENTER OBSERVATION STUDY
Y. Nakayama1,*, N. Hidaka1, S. Kato1, M. Kusakari1, A. Horiuchi2,
H. Yamada3, Y. Etani3, S. Ida3
1
Pediatrics, Shinshu University School of Medicine, Matsumoto,
2
Gastroenterology, Showa Inan General Hospital, Komagane, 3Pediatric
Gastroenterology, Nutrition and Endocrinology, Osaka Medical Center and
Research Institute for Maternal and Child Health, Osaka, Japan
Contact E-mail Address: ynaka@shinshu-u.ac.jp
INTRODUCTION: Recently, the prevalence of Helicobacter pylori infection in
Japanese children has been reduced to 3-5%. The drug susceptibility is different
depending on the country or region, so that it is necessary to consider the regional characteristics to eradicate H. pylori. We are inspired to re-evaluate the
eradication therapy among Japanese chidlren by high eradication rate of sequential therapy in European children.
AIMS & METHODS: The present study aimed to evaluate the drug resistance
rate and the eradication rate of H. pylori in the last 10 years in Japanese children.
From April 2003 to March 2012, in Japanese three facilities, total 74 (mean age
12.3  3.2, male 47.3%) children and adolescents under 18 years old, who had no
history of eradication therapy in the past, were included in this study. H. pylori
was cultured using biopsy specimens from gastric antrum and corpus then the
drug susceptibility was evaluated. Patients were treated with susceptibility-based
triple therapy and were examined the rate of eradication. Successfulness of eradication was evaluated by the 13C-urea breath test and/or stool antigen test at
least 8 weeks later after the end of treatment.
RESULTS: H.pylori susceptibility test showed that 47.2% were resistance
(MIC 41) to clarithromycin (CAM), 30.1% (MIC 416) to metronidazole
(MNZ). Susceptibility of amoxicillin (AMPC) (MIC 40.06) was 21.3 %, but
MIC 41 was only 2 strains. The MIC 50 of CAM during the first five-years of
study period was 0.12 and resistance rate was 44.4%. On the other hand, in the
last five-years period, MIC of CAM was 2.0 and resistance rate was 52.2%, so it

was speculated to be in the increasing trend in CAM-resistant strain. The overall


eradication rate was 89.4%(59/66) by intention-to-treat analysis (ITT) and
96.7% by per-protocol analysis (PP). The PPI, AMPC and CAM regimen was
the first choice for CAM susceptible strain. The ITT and PP eradication rates
were 91.7% (33/36) and 100% (33/33), respectively. The PPI, AMPC and MNZ
regimen was the first choice for CAM resistant strain and the ITT and PP
eradication rates were 91.3% (21/23) and 100% (21/21), respectively.
CONCLUSION: An antimicrobial susceptibility-guided triple eradication therapy for H. pylori is effective in Japanese children with very high, approximately
50%, CAM resistance rate and it was comparable to or greater than the previously described sequential therapy in western countries.
Disclosure of Interest: None declared
P1122 ARE ESPGHAN 2011 GUIDELINES FOR CELIAC DISEASE ALSO
SUITABLE FOR ASYMPTOMATIC PATIENTS?
C.M. Trovato1,*, F. Valitutti1, I. Celletti1, S. Leoni1, S. Gatti1, D. Iorfida1,
M. Montuori1, C. Anania1, A.R. Vestri2, M. Barbato1, S. Cucchiara1
1
Department Of Pediatrics, 2Department of Public Health and Infectious Disease,
"SAPIENZA", UNIVERSITY OF ROME, Rome, Italy
Contact E-mail Address: chiaramaria.trovato@uniroma1.it
INTRODUCTION: In 2011, the European Society for Pediatric
Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has released its
updated guidelines on celiac disease (CD) diagnosis.1 According to these new
guidelines, symptomatic children with anti-transglutaminase (anti-tTG2) antibody levels  10 times upper limit normal (ULN) could avoid duodenal biopsies
if the HLA test and serum anti-endomysial antibodies (EMA) are positive.1 So
far, both symptomatic patients with anti-tTG2 titer 510 times ULN and those
asymptomatic should undergo upper endoscopy with multiple duodenal biopsies
to confirm a suspected CD.
AIMS & METHODS: The aim of this study was to assess the accuracy of
serological tests in asymptomatic patients to diagnose CD. We retrospectively
assessed 286 children and adolescents (mean age: 8.3 years; age range: 10 months17 years) who had received a CD diagnosis based on elevated titer of anti-tTG2,
EMA positivity, histology and HLA typing. All patients (95 boys, 191 girls) were
positive for anti-tTG2 and EMA. Patients were distinguished between symptomatic and asymptomatic while histological lesions were graded according to the
Marsh-Oberhuber (MO) criteria. Statistical evaluation was made with the Fisher
exact test.
RESULTS: Among the 286 EMA positive biopsied children, 196 (68.53%) had
anti-tTG2 titers  10 times ULN. Among them, a group of 156 (86.02 %)
children also had symptoms suggestive of CD (namely high-titer symptomatic
children); of these, 142 (91.02%) showed severe lesion degree (3a, 3b, 3c MO). On
the contrary, 40 out of 196 (13.98%) children were asymptomatic (namely hightiter asymptomatic children); 37 (92.5%) of them showed severe lesion degree
(3a,3b, 3c MO). No difference was found between high-titer symptomatic
children and high-titer asymptomatic children with regards to histological
damage (Fisher exact test p 1.000).
CONCLUSION: Our results indicate that the absence of symptoms in children
with anti-tTG2 titers 410 times ULN and positive EMA antibodies does not
undermine a biopsy-sparing CD diagnosis. The biopsy-sparing protocol
seems to be applicable to both symptomatic and asymptomatic patients with
anti-tTG2 titer 410 times ULN, positive EMA and HLA-DQ2/DQ8.
REFERENCES
Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric
Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of
coeliac disease. J Pediatr Gastroenterol Nutr 54: 136-160.
Disclosure of Interest: None declared
P1123 SOCIOECONOMIC VARIATION IN THE INCIDENCE
CHILDHOOD COELIAC DISEASE IN THE UNITED KINGDOM

OF

F. Zingone1.2,*, J. West1, C. Crooks1, K.M. Fleming1, T.R. Card1, C. Ciacci2,


L.J. Tata1
1
Division of Epidemiology and Public Health, University of Nottingham,
Nottingham, United Kingdom, 2Department of Medicine and Surgery, University of
Salerno, Salerno, Italy
Contact E-mail Address: z.fabiana@hotmail.it
INTRODUCTION: Socioeconomic status has been proposed as a potential risk
factor for coeliac disease (CD), but the few studies that have investigated this
possible association report conflicting results. We aimed to estimate the current
diagnostic patterns among children in the United Kingdom (UK) and how they
vary by socioeconomic status.
AIMS & METHODS: All children aged 0-18 years who were actively registered
with a large population-based general practice database between 1993 and 2012
were identified. The incidence of CD was evaluated in each quintile of the
Townsend Index of Deprivation, a measure of socioeconomic status, and stratified by age, sex, country of residence and calendar year.
RESULTS: Among 2.063,421 children we identified 1.247 coeliac disease diagnoses, corresponding to an overall CD incidence of 11.8 per 100.000 personyears, which was similar across the UK countries and higher in girls than in
boys. We found a gradient of CD diagnosis across socioeconomic groups, with
the rate of disease being 80% higher in children from the least socioeconomically
deprived areas than in those belonging to the most deprived areas (Incident Rate
Ratio (IRR) 1.80, 95% CI 1.45-2.22). This pattern held for both boys and girls
and across all ages. Across all four countries of the UK, we found similar associations between CD incidence and socioeconomic status. Whilst CD incidence
up to age 2 remained stable over the study period, diagnoses at older ages have
doubled over the past 20 years.

A441

United European Gastroenterology Journal 2(1S)


Table 1. Incidence rates and Incidence rates ratios of Coeliac Disease across
socioeconomic status
Table to abstract P1123
Socioeconomic
deprivation (Quintile
of Townsend Index)

Rate per 100.000


person-years (95%
confidence interval)

Unadjusted
Incidence Rate Ratios
(95% confidence interval)

1 (least deprived)
2
3
4
5 (most deprived)

14.1 (12.7-15.7)
14.5 (12.9-16.2)
10.8 (9.5-12.3)
10.4 (9.0-11.9)
7.8 (6.5-9.4)

1.80 (1.45-2.22)
1.85 (1.48-2.30)
1.37 (1.09-1.73)
1.32 (1.05-1.67)
reference

CONCLUSION: Despite a doubling in childhood coeliac disease diagnoses over


20 years, children from the most socioeconomically deprived areas are half as
likely to be diagnosed as those from less deprived areas. Awareness campaigns
and implementation of national guidance may help to implement strategies for
case-finding in all children and reduce this inequality. Moreover, future studies
should explore the possible association between exposures to different specific
risk factors and the risk of CD across socioeconomic groups.
Disclosure of Interest: None declared
P1124 NARROW BAND IMAGING (NBI) COMBINED WITH WATER
IMMERSION TECHNIQUE (WIT): ANY DIAGNOSTIC YIELD FOR
CELIAC DISEASE? A PEDIATRIC PROSPECTIVE STUDY
F. Valitutti1,*, D. Iorfida1, S. Oliva1, I. Celletti1, S. Leoni1, S. Gatti1,
C.M. Trovato1, M. Barbato1, M. Montuori1, C. Anania1, A. Tiberti2, G. Di
Nardo1, S. Cucchiara1
1
Department of Pediatrics, 2Depertment of Internal Medicine and Medical
Specialties, Sapienza University of Rome, Rome, Italy
INTRODUCTION: Upper GI endoscopies are still required to diagnose the
majority of children with celiac disease (CD), notwithstanding the recently
updated ESPGHAN criteria.1 The multiple-biopsy approach both in the duodenum and in the bulb has been suggested by several guidelines as the best
strategy to confirm the diagnosis of CD; however, this approach increases the
invasiveness of the endoscopic procedure itself and is fairly time-consuming
AIMS & METHODS: Our aim was to evaluate the diagnostic yield of a single
biopsy guided by narrow-band imaging (NBI) combined with water immersion
technique (WIT), in a prospective study of children with CD. We enrolled 43
children (12 males; mean age: 7.2 years; age range: 1.25-15.25 years) with suspected CD undergoing upper GI endoscopy to compare single NBI plus WITguided biopsy versus the standard, duodenal and bulbar, multiple-biopsy
approach (2 random biopsies in the bulb, 4 random biopsies in the 2nd-3rd
duodenal portion). NBI-plus-WIT endoscopic severity was classified on a
Likert scale as normal, altered with mild modifications (nodular mucosa, scalloping) or clearly altered (reduction and flattening of plicae); inter-observer variability between two different physicians was also assessed with regards to
endoscopic judgments. Histology was graded according to the MarshOberhuber classification.
RESULTS: Diagnosis of CD was confirmed in 40 out of 43 children. NBI plus
WIT approach correctly diagnosed 35 out of 40 celiac children, with a diagnostic sensitivity of 87.5 % (C. I.: 77.3-97.7); none among the studied patients
showed an exclusive, NBI plus WIT-detected histological damage. Clearly
altered pattern at NBI plus WIT endoscopic visualization was significantly
associated to villous atrophy both at NBI plus WIT-guided biopsy and at
multiple biopsy sampling (Spearman Rho 0.637 and 0.496). High anti-transglutaminase antibody titer (10 times upper limit normal) was also associated to
clearly altered pattern at NBI plus WIT endoscopic visualization.
Concordance of NBI plus WIT endoscopic assessments was fairly high
between two different operators (K: 0.884). After the passage through the pylorus
of the endoscope, mean NBI plus WIT procedure time was 53.6 sec (DS: 12.7
sec), whereas mean time for multiple biopsy sampling was 218.2 sec (DS: 38.3 sec)
(p0.0001).
CONCLUSION: Albeit time- and resource- saving, single NBI plus WITguided biopsy is not as effective as the well established multiple-biopsy
approach in confirming the diagnosis of CD. However, in presence of an altered
NBI-plus-WIT pattern coupled to high anti-transglutaminase antibodies, a
single NBI plus WIT-driven biopsy might suffice to diagnose CD.
When no altered mucosal pattern is visible even at NBI plus WIT, multiple
bulbar and duodenal biopsies must be obtained to confirm diagnosis.
Disclosure of Interest: None declared

P1125 ANTI-TRANSGLUTAMINASE TITER, MARSH-OBERHUBER


GRADING AND BONE MINERAL DENSITY IN CHILDREN WITH
CELIAC DISEASE AT DIAGNOSIS
C.M. Trovato1, I. Celletti1, S. Gatti1, S. Leoni1, F. Valitutti1,*, D. Iorfida1,
M. Montuori1, C. Anania1, M. Barbato1, S. Cucchiara1
1
Department of Pediatrics, "SAPIENZA", UNIVERSITY OF ROME, Rome,
Italy
Contact E-mail Address: chiaramaria.trovato@uniroma1.it
INTRODUCTION: Metabolic bone disease remains a significant and common
complication of celiac disease (CD). Several studies have demonstrated low bone
mineral density (BMD) at the time of celiac disease diagnosis in both children
and adults.1 Low bone density in children and adolescents is defined as an areal
BMD (aBMD) less than 2 SD below the age-adjusted mean value (Z-score 5 2
SD).2 The pathogenesis of bone loss in celiac disease has not been completely
elucidated: two major causal factors are malabsorption and inflammation.
Calcium and Vitamin D might be poorly absorbed substances in celiacs.1
Several studies demonstrated an increased RANKL/OPG ratio in vitro and an
increased osteoclastogenesis in untreated celiac patients due to chronic release of
pro-inflammatory cytokines.3.4
AIMS & METHODS: Aim of our study was to correlate Z-score value and antitissue transglutaminase type 2 (anti-tTG2) antibody titer and Z-score value and
Marsh-Oberhuber grade (MO) in children with celiac disease at diagnosis. We
enrolled 99 celiac patients (M 35; F 64; age-range: 4-15 years). All patients had
positive test results for anti-tTG2 antibodies, histological lesions graded according to MO classification; all of them underwent lumbar DXA performed by
Lunar Prodigy Advance (GE Healthcare, USA). Bone mineral density was estimated by Z-score. The linear correlation between the anti-tTg2 titer and Z-score
value and between MO grade and Z-score was evaluated by the Pearson productmoment correlation coefficient (Pearsons r).
RESULTS: Anti-tTG2 antibody titers 10 times the upper limit of normal were
found in 65 of 99 patients. 84 patients showed severe lesion degree (3c 3b 3a)
in Marsh-Oberhuber classification, 3 patients showed MO2, 4 MO1, 4 no lesions
and 4 didnt undergo conventional upper GI endoscopy (diagnosed according to
the biopsy-sparing ESPGHAN 2012 criteria). Low BMD (Z-score  2DS)
was found in 13 (13.13%) patients; 20 (20.20%) patients showed 25 Z-score
5 1; 43 (43.43%) patients showed -1 Z-score 50 and Z score 0 was detected
in 23 (23.23%) patients. No correlations were found between Z-score value and
anti-tTG2 title (Pearsons r -0.06) and between Z-score value and MO degree
(Pearsons r 0.07). Low bone mineral density does not correlate to the antitTG2 title and to Marsh-Oberhuber degree in a cohort of Italian children at CD
diagnosis.
CONCLUSION: Our results indicate that there is no clear clinical predictor to
identify children with low BMD and who should undergo DXA at the diagnosis.
A follow up evaluation after few months of GFD might be more reasonable.
REFERENCES
1) Bianchi ML. Inflammatory bowel diseases, celiac disease, and bone. Arch
Biochem Biophys 2010; 503: 54-65.
2)Gordon CM, Baim S, Bianchi ML, et al. Special report on the 2007 pediatric
position development conference of the international society for clinical densitometry. South Med J 2008; 101: 740-743.
3) Buckley KA and Fraser WD. Receptor activator for nuclear factor kappaB
ligand and osteoprotegerin: regulators of bone physiology and immune
responses/potential therapeutic agents and biochemical markers. Ann Clin
Biochem 2002; 39: 551-556.
4) Taranta A, Fortunati D, Longo M, et al. Imbalance of osteoclastogenesisregulating factors in patients with celiac disease. J Bone Miner Res 2004; 19:
1112-1121.
Disclosure of Interest: None declared
P1127 EFFICACY OF DEAMIDATED GLIADIN PEPTIDE-BASED
POINT-OF-CARE TEST (SIMTOMAX) FOR THE EARLY
DIAGNOSIS OF COELIAC DISEASE IN PAEDIATRIC PATIENTS
I. Polanco1, T.K. Weber1,*, E.M. Ojinaga1, M. Molina1, J. Sarria1
1
Department of Pediatric Gastroenterology and Nutrition, Chidrens University
Hospital La Paz, Madrid, Spain
Contact E-mail Address: thabataweber@yahoo.com.br
INTRODUCTION: Coeliac disease (CD) is currently under diagnosed. It is
estimated that 90% of patients remain undiagnosed. Early diagnosis is essential
to avoid complications.
AIMS & METHODS: The objective of the study is to assess the effectiveness of a
rapid, minimally-invasive point-of-care test (POCT) that detects both IgA and
IgG anti-DGP antibodies and total IgA (Simtomax) in the early detection of
coeliac disease in paediatric patients.
A prospective study was conducted in which children (18a) under suspicion of
CD (risk groups and/or symptomatic patients) were selected, including brothers
of coeliac children under gastroscopy for other gastrointestinal conditions. Those
with severe disease, gluten-free diet, gastrointestinal bleeding, coagulopathy and/
or infections during the last month were excluded. All children were evaluated
with Simtomax. A further genetic HLA-DQ study was performed in patients
under suspicion of CD. Results were compared against the detection of tissue
transglutaminase antibodies ELISA IgA or IgG-tTG (EliATM Celikey, cut-off
10U/ml) and/or EMA as well as results of duodenal biopsy (DB), used for CD
diagnosis according to the current ESPGHAN criteria.
RESULTS: 100 children were studied; including 6 brothers of CD diagnosed
patients. 18 children were under 2 years-old, and 14 were found CD positive (1
missed with Ttg). Prevalence of CD found in the present study was 47% (confidence interval of 95% (CI95%): 37.9 58.2%). The results of the rapid test

A442
were highly concordant with the diagnosis established to CD: a sensitivity of
95.8% (CI95%: 85.7 99.4%), specificity of 98.1% (CI95%: 89.7 99.7%),
positive predictive value of 97.9% (88.7 99.6%) and negative predictive value
of 96.2% (87.0 99.4%). Positive and negative likelihood ratios were, respectively, 49.8 (CI95%: 72 347.5) and 0.04 (CI95%: 0.01 0.17). We found two
false-negative patients and a false-positive (the latter with a coeliac brother).
CONCLUSION: Taking into account its high diagnostic accuracy in the pediatric population, this rapid test could be considered an effective tool for the early
diagnosis of CD, especially in primary care High LR and low LR- imply
Simtomax is a suitable tool for ruling in and ruling out CD and results suggest
that this POCT could potentially replace standard serology for CD diagnosis in
children. Further studies should also cover potential cost savings with Simtomax.
REFERENCES
Bienvenu F, Besson Duvanel C, Seignovert C, et al. Evaluation of a point-of-care
test based on deamidated gliadin peptides for celiac disease screening in a large
pediatric population. Eur J Gastroenterol Hepatol 2012; 24: 1418-1423.
Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric
Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of
coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54: 136-160.
Polanco I. Celiac disease. J Pediatr Gastroenterol Nutr 2008; 47(Suppl. 1): S3-S6.
Disclosure of Interest: None declared
P1128 UNVEILED. THE HIDDEN SHAPE OF NUMBERS. DATA MINING
TECHNIQUES APPLIED TO HYDROGEN LACTOSE BREATH TEST
A. Rodriguez Herrera1,*, Y. Hernandez-Mendoza 2, J. Valverde Fernandez1,
C. Rubio-Escudero3, I. Nepomuceno-Chamorro4, B. Pontes-Balanza4
1
GASTROENTEROLOGY AND NUTRITION UNIT, INSTITUTO
HISPALENSE DE PEDIATRIA, SEVILLE, Spain, 2Networks and Computers,
Universidad Ciego del Avila, Ciego del Avila, Cuba, 3 Computer Science and
Languages, 4Computer Science and Languages, Universidad de Sevilla, SEVILLE,
Spain
INTRODUCTION: Informatics applied to clinical data collection provide huge
sets of data. Interpretation of these sets with classical descriptive techniques can
miss relevant conclusions. Clustering is a method to discover hidden groups or
patterns in big sets of data. No initial groups are provided but the clustering is
allowed to form groups to maximize the similarity of the patients in each group.
AIMS & METHODS: Application of data mining techniques to identification of
hidden patterns in data from hydrogen breath test with lactose. The goal was to
identify non evident groups of patients than can potentially share common characteristics not easily evident. Secondarily, we conducted a classic descriptive
study of our data set.
Mathematical review with use of clustering techniques of hydrogen breath test.
Time range of 4 years, from June 2009 to June 2013. Cluster analysis as such is
not an automatic task, but an iterative process of knowledge discovery or interactive multi-objective optimization that involves trial and failure. Measures were,
taken at 0 minutes (baseline), 30, 60, 90, 120, 150, 180. Test with an increased
level of 20 ppm over baseline were considered "positive".
RESULTS: Data sets from 2751 lactose hydrogen breath test were included. A
set of 6 different typologies of data curves were identified:1. Straight line, nonascending, linked to baseline minor than 20 ppm.2. Straight line, non-ascending,
linked to baseline bigger than 20 ppm.3. Curved line, ascendant before 90 minutes.4. Curved line, ascending after 90 minutes.5. Curved line, with doubly ascendant, before and after 90 minutes.6. Curved line, ascendant only at 180 minutes
839 children (32.63 %) were "positive", when increase in 20 ppm was considered
independently from the net value of baseline. Otherwise when"positive" is
defined strictly as patient with baseline bigger 20 ppm result is similar, showing
32.61 % of children with positive test. 166 patients (6.5 %) had showed high
vallues only at 180 minutes.
CONCLUSION:
Although data mining is being incorporated into clinical practice, there is currently no literature on the same test in hydrogen. Using clustering techniques, we
have identified a total of 6 curves type in our patients undergoing the test. As
6.5% shows elevation at 180 minutes,test should be always extended up this
duration in any case. Early interruption of test is an usual practice in some
institutions. A future research option will be to link these 6 groups to different
sets of symptoms or metabolic activity of gut flora. Data mining provide an
identification of groups not decided in advance, providing less selection bias in
clinical research.
Disclosure of Interest: None declared
P1129 EVALUATION OF METHANOGENIC FLORA THROUGH
BREATH TEST IN CHILDREN WITH SUSPECTED LACTOSE
INTOLERANCE
D. Ummarino1.2,*, B. Hauser1, A. Staiano2, Y. Vandenplas1
1
Department of Pediatrics, Universitair Ziekenhuis of Brussels, Brussels, Belgium,
2
Department of Pediatrics, University of Naples "Federico II", Naples, Italy
Contact E-mail Address: dario.ummarino@hotmail.it
INTRODUCTION: Several studies evaluate the efficacy of the Hydrogen (H2)
breath test as a non-invasive study with high sensitivity and specificity to diagnose lactose intolerance. Moreover, it has been reported that an increase in
breath CH4 excretion occurs in children with lactose intolerance. Several
papers used different methods to evaluate CH4 on expired air.
AIMS & METHODS: The aim of the study is to evaluate the importance of CH4
measurements in the diagnosis of lactose intolerance using different cut-off.
We evaluated 133 children with symptoms suggestive of lactose intolerance. All
patients underwent a Lactose H2 and CH4 Breath Test (LHMBT). Lactose was
administered orally (dose of 2 mg/kg, max 50 mg) diluted in max 250 ml of water.

United European Gastroenterology Journal 2(1S)


The expired air was collected in specific syringes with a capacity of 20 ml. One
breath sample was taken before the intake of lactose and breath samples were
taken after the ingestion of lactose every 15 min for 3 hours. The expired H2 and
CH4 was measured with a specific analyzer (Microlyzer DP; Quintron
Instruments, Milwaukee, Wis.). The result was considered positive when a H2
peak exceeded 20 part per milion (ppm) over the baseline value. Whilst, CH4 was
considered positive using three different cut-off, 20 ppm above the baseline
(Method 1), 12 ppm above the baseline (Method 2) or 5 ppm above the baseline
(Method 3). A clinician, blinded for the results of the breath test, registered the
symptoms of the patients during the test. Statistical evaluation was considered
statistically significant for a p50.05).
RESULTS: Fifty-four patients (40.6%) out of 133 resulted positive with methods
1 and 2. Whilst, 63 patients (47.4%) out of 133 can be defined positive with
method 3. The percentage of patients positive for hydrogen only (H2CH4-)
was 57.4% using method 1 and 33.3% using method 2. No patients showed
H2-CH4 values using these methods. Contrary, using method 3, 47/63
(74.6%) patients were positive for both the gases (H2CH4) and 9/63
(14.3%) children resulted H2-CH4. The peak level of H2 in H2CH4 patients
was significantly higher than in H2CH4- patients using method 1 and 2
(P50.0001; p50.007, respectively); but not using method 3 (P 0.09). Twentyseven (50%) out of 54 symptoms was registered in positive patients using method
1 and 2 (p 0.0006); using method 3 we registered 28/63 symptoms in positive
children (44.4%) (p 0.008). Sixteen/28 symptoms appeared at the same time of
the maximum level of H2 (p5 0.001), and in 13/28 symptoms appeared at the
same time of the maximum level of CH4 (p5 0.001). Patients positive only for
methane did not respond to the free-lactose diet, showing different disease that
explain the symptoms.
CONCLUSION: Our results show that CH4 had no added value to a simple H2
breathtest. Moreover, low cut-off of methane may reduce the specificity of the
test.
Disclosure of Interest: D. Ummarino: no conflict of interest, B. Hauser: no conflict of interest, A. Staiano: no conflict of interest, Y. Vandenplas: no conflict of
interest
P1130 CAN BLOOD CITRULLINE LEVEL IN INFANTS, WITH GLUTEN
INDEPENDENT ENTEROPATHY, SCREENING TEST FOR SMALL
INTESTINE MUCOSA ATROPHY?
K. Marakhouski1,*, I. Pauk2, S. Kletski3, A. Portianko4, D. Bulyga5,
T. Gnedzko2, O. Popova5, Z. Kuvaeva5
1
Endoscopy, 2RSPC "MOTHER AND CHILD", 3Morphology, Minsk municipal
pathomorphological buro., 4Morphology, Belorussian state medical university,
5
Institute of Physical Organic Chemistry mf National Academy of Sciences of
Belarus, Minsk, Belarus
Contact E-mail Address: kmarakh@tut.by
INTRODUCTION: Blood citrulline level is subject of several investigations but
majority concern celiac disease. Can citrulline be a universal indicator of intestinal atrophy?
AIMS & METHODS: Inclusion criteria were: children with histological confirmed intestinal (duodenal) atrophy. Biopsy specimen was taken endoscopically
before age 6 months. Endoscopy was provide on the EXERA III with an endoscope GIF - N180 Olympus. Group A (N 4) have to be gluten independent
enteropathy or congenital atrophy (presumably), with diarrhea and progressive
malnutrition resistant to intensive treatment. Two cases of tufting enteropathy
were detected prospectively. Age at time of biopsy sampling: median - 2.9 (1090th percentile 0.4-5, 6) months. Control group (B, N 11) were included children without symptom of diarrhea, with normal weight, height and head circumferential. Endoscopy wasnt done. Blood samples were taken 5.9 days (CI
95% 4, 5 - 7, 4). Such age was chosen based on data that citrulline is a indicator
of mass enterocytes and this group will have lowest citrulline level per life.
Serum level of citrulline, threonine and taurine was detected by standard validation method -high performance liquid chromatography (HPLC) by AGILENT
1100 chromatograph on the column Zorbax Eclipse C18 with the fluorimetric
detector.
RESULTS: Significant difference in citrulline level between two groups atrophy/
not atrophy was detected. Group A (n 4) median citrulline level 12.2 mmol/l
(CI 95% 6.1 - 12.9), group B 24.1 mmol/l (CI95% 22.0-40.6), p 0.002
(Mann-Whitney U or Wilcoxon rank-sum for difference in median).
CONCLUSION: We can assume that the level of blood citrulline in infants can
be used as a screening test to assess the risk of the small intestine mucosa atrophy. Endoscopy with biopsy sampling must be followed after low blood citrulline
was detected. Further studies are required to clarify.
Disclosure of Interest: K. Marakhouski Other: "Olympus" CIS expert, I. Pauk:
None declared, S. Kletski: None declared, A. Portianko: None declared, D.
Bulyga: None declared, T. Gnedzko: None declared, O. Popova: None declared,
Z. Kuvaeva: None declared

United European Gastroenterology Journal 2(1S)


P1131 RISK FACTORS FOR NECROTISING ENTEROCOLITIS IN
PRETERM INFANTS WITH GESTATIONAL AGE  32 WEEKS
L. Olariu1,*, G. Olariu2, M. Tunescu3, S. Olariu3, O. Belei4
1
First Pediatric Clinic, UNIVERSITY OF MEDICINE AND PHARMACY
VICTOR BABES, Timisoara, Romania, 2Neonatology Department, 2. Municipal
Emergency Hospital, 3Neonatology Department, Municipal Emergency Hospital,
4
First Pediatric Clinic, UNIVERSITY OF MEDICINE AND PHARMACY
VICTOR BABES, TIMISOARA, Romania
Contact E-mail Address: tunealaura@yahoo.com
INTRODUCTION: Necrotizing enterocolitis (NEC) is an acute inflammatory
necrosis of small bowel, being the most common neonatal gastrointestinal emergency, that mainly affects preterm low birth weight. NEC incidence is inversely
proportional to gestational age (GA), only 10% of term infants develop this
disease. Because the etiology and pathogenesis of NEC are still incompletely
understood, therapeutic options, morbidity and mortality were not significantly
improved in the last decade of time. NEC is a major cause of mortality (up to
25%) and morbidity including recurrent sepsis, dependence on parenteral nutrition, need for surgery and survival with short bowel syndrome. Taking into
account the catastrophic development of this disease, it is necessary to focus
research on prevention strategies and identify predictive risk factors for its
occurrence.
AIMS & METHODS: To identify the risk factors for NEC in preterm infants
with GA32 weeks in a third level maternity in Romania, using data registered in
the National Registry of Respiratory Distress. Methods: We retrospectively studied 442 preterm infants  32 weeks of gestation, born in a third level maternity
in Romania between 2010-2013. GA was between 23-32 weeks (with a medium of
29.60  2.26, birth weight was between 480g-2350 g (1309.86  369.44), gender:
female 230 (52.0%); male 212(48.0%). Incidence of NEC was 2.7% (12 preterm
infants with GA  32 weeks, stage II and III of disease). The risk factors were
selected in four categories: maternal factors, fetal factors, therapeutic factors and
factors related to newborns diseases. Statistical analysis of data was performed
using Independent Samples T-test and Pearson Chi-Square correlation. p was
calculated for confidence interval of 95% (statistical significance p 50.05). To
establish NEC predictors we used binominal logistic regression, the Wald model
of regressive elimination. There were anlysed the characteristics that differentiates preterm babies who developed NEC of those who did not developed this
condition.
RESULTS: The final model of regression indicates the fact that the higher risk in
developing NEC have had those who presented: mother with ruptures membranes over 18 hours and nosocomial infections. Other most frequend factors
implicated in the development of NEC, are, in order of frecvency: maternal-fetal
infections, sepsis, maternal hipertension, corioamniotitis, persistent ductus arteriosus, ventilation in CPAP system, lack of antenatal corticotherapy, oxigenoteraphy. There was a statistically significant correlation between NEC and birth
weight (p 0.003), chorioamnionitis (p 0.02), bronchopulmonary disease
(p 0.02), ruptures membranes over 18 hours (p 0.03).
CONCLUSION: In this study the incidence of NEC was 2.7%, similar to that
reported in the literature.
The variability depends on the diagnostic possibilities of each center. The most
predictive factors for NEC in our study are: nosocomial infections, ruptures
membranes over 18 hours and materno-fetal infections. The knowledge of risk
factors for NEC can allow healthcare providers to assess and adjust care practices for preterm infants who presents a higher risk for NEC, based on empirical
data.
Disclosure of Interest: None declared
P1132 EFFICACY OF PROBIOTICS IN PATIENTS WITH LACTOSE
INTOLERANCE A PRELIMINARY STUDY
T.T. Perets1, E. Shporn1, I. Blechman1, S. Levy2, S. Aizic1, Y. Niv1,
R. Dickman1,*
1
Gastroenterology, Rabin Medical Center, Petach Tikva, 2The Academic College
of Tel Aviv-Jaffa, Biostatistics, Tel Aviv, Israel
Contact E-mail Address: dickmanr1@gmail.com
INTRODUCTION: Lactobacillus bulgaricus and Streptococcus thermophilus
produce lactase enzyme. Probiotics may alleviate lactose intolerance by modifying the intestinal flora into one which contains lactase-producing bacteria.
AIMS & METHODS: To assess the efficacy of probiotics in improving lactose
intolerance.
Patients were treated with a unique probiotic formulation (Bio-25, Ambrosia SupHerb, Israel) for 6 months. All patients completed a demographic questionnaire as well as a visual analog scale (VAS) for the assessment of the intensity and
frequency of bloating, flatulence, abdominal pain and change in bowel habits, at
entry, every 8 weeks and at the end of treatment period. Measurement of hydrogen levels (parts per million - ppm) at each of these time points was also performed. Study end points were: Improvement in symptom intensity or frequency,
and the decrease below cut off point of 20ppm of the breath test. The Wilcoxon
signed-rank test was used to compare symptom intensity and severity before and
after treatment.
RESULTS: The study group comprised eight symptomatic female patients with a
positive lactose intolerance breath test. Mean age and mean body mass index
(BMI) (kg/m2) were: 36.418.6 years and 25.2, respectively. Treatment with
probiotics was associated with a significant improvement in the reported intensity
of bloating (z 2.55, p 0.11) and flatulence (z 2.21, p 0.027); frequency of
bloating (z 2.06, p 0.039) and flatulence (z 2.04, p 0.041); abdominal pain
(z 2.06, p 0.039), and constipation (z 2.07, p 0.039). Lactose breath test
was successfully normalized in two (25%) patients.

A443
CONCLUSION: Treatment with probiotics may lead to symptomatic improvement in patients with lactose intolerance. A larger study is warranted to confirm
our findings.
Disclosure of Interest: None declared
P1133 IMPAIRED SECRETION OF SATIATION HORMONES
ASSOCIATED WITH INSULIN RESISTANCE IN OBESE
ADOLESCENTS

IS

A.C. Meyer-Gerspach1,*, S. Beglinger2, S. Graf2, U. Zumsteg2, J. Drewe1, J.P. Gutzwiller1, C. Beglinger1


1
University Hospital Basel, 2University Childrens Hospital, Basel, Switzerland
INTRODUCTION: The role of gastrointestinal (GI) hormones in the pathophysiology of obesity is unclear, although they are involved in the regulation of
satiation and glucose metabolism. The objectives of this study were i) to examine
glucagon-like peptide 1 (GLP-1), amylin, ghrelin and glucagon responses to a test
meal in obese adolescents and ii) to test which GI peptides are associated with
insulin resistance.
AIMS & METHODS: A total of 16 obese (8 male and 8 female; mean age: 12.8 
0.6 yr; mean BMI 31.2  1.0 kg/m2) and 14 control (5 male and 9 female; mean
age: 14.2  0.4 yr; mean BMI 20.7  0.6 kg/m2) adolescents were included.
Subjects were instructed to eat a test meal (490 kcal). Plasma samples were
collected before and after meal ingestion for hormone and glucose analysis.
RESULTS: Obese adolescents were insulin resistant as expressed by the HOMA
index and had significantly increased fasting glucagon and amylin levels compared to the control group (P 0.003 and 0.044, respectively). In response to the
test meal, the increase in GLP-1 levels was reduced in obese adolescents (P 5
0.001). In contrast, amylin secretion was significantly increased in the obese
population compared to the control group (P 5 0.005).
Bivariate analysis for HOMA index and post-prandial GLP-1 levels showed a
negative correlation (R2 0.343, P 5 0.001). Amylin post-prandial levels and
amylin basal concentration demonstrated both a significant positive correlation
(R2 AUC 0.42, R2 basal 0.46, both P 5 0.001). Fasting glucagon showed a
positive correlation to HOMA (R2 0.46, P 5 0.001).
CONCLUSION: We conclude that hyperglucagonemia, hyperamylinemia and
reduced post-prandial GLP-1 secretion are important pathophysiological steps
in the development of metabolic syndrome in adolescents.
Disclosure of Interest: None declared
P1134 USE OF THE PROBIOTIC LACTOBACILLUS REUTERI DSM
17938 IN THE PREVENTION OF ANTIBIOTIC-ASSOCIATED
INFECTIONS IN HOSPITALIZED BULGARIAN CHILDREN: A
RANDOMIZED, CONTROLLED TRIAL
M. Georgieva1, R. Pancheva2, N. Rasheva3,*, N. Usheva4, L. Ivanova5,
K. Koleva3
1
Pediatric gastroenterology, 2Hygiene, Medical University of Varna, 3Pediatric
gastroenterology, UMBAL St. Marina, 4Social medicine, Medical University of
Varna, 5Microbiology, UMBAL St. Marina, Varna, Bulgaria
INTRODUCTION: Antibiotic-associated diarrhoea (AAD) occurs in up to 25%
of all individuals receiving antibiotics. In hospitalized patients, AAD is related to
significant increases in mortality, length of stay, and cost of medical care.
Twenty-nine percent of hospitalized patients may develop diarrhoea after antibiotic use; therefore, identifying strategies to minimize antibiotic-associated diarrhoea could be of significant medical and economic advantage.
AIMS & METHODS: Objective:
To evaluate the effectiveness of Lactobacillus reuteri DSM 17938 for the prevention of antibiotic-associated diarrhoea and Clostridium difficile-related infections
in hospitalized children in a Bulgarian hospital.
Study design:
Children (n 100, aged 3 to 12 years) admitted to the hospital for acute infections were enrolled in a randomized, double- blind, placebo-controlled trial. They
were assigned to receive either a probiotic supplement containing 1 x 108 CFU
Lactobacillus reuteri DSM 17938 in the form of one chewable tablet once per day
(n 49) (BioGaia AB, Stockholm, Sweden) or placebo (n 48). The probiotic or
placebo was taken 2 hours after lunch each day, during the entire period of
antibiotic treatment at the hospital and for additional 7 days.
RESULTS: Data from 97 children were included in the final analysis. The incidence of diarrhoea (defined as at least 3 loose or watery stools per day in a 48hour period that occurred during or up to 21 days after cessation of antibiotic
treatment) was unexpected low in both groups-L. reuteri (n 1) versus placebo
(n 1): 2.04 vs 2.1 per 100 (p40.05, risk ratio 1.02, 95% CI 0.7-1.4). L reuteri
DSM 17938 did not significantly affect the incidence or severity of AAD diarrhoea and Clostridium difficile infection. We found unusually high colonisation
rate of non-symptomatic C. difficile measured by toxin-specific ELISA. There
was no difference between the probiotic and placebo groups for any of the other
secondary outcomes (i.e., incidence of mild diarrhoea, frequency of stool samples
positive for C. difficile toxin A and B at the beginning and at the end of study
period, frequencies of other gastrointestinal symptoms in the same study period)
(p50.05). No adverse events were reported.
CONCLUSION: Due to the low incidence of antibiotic-associated diarrhoea in
both groups, no conclusion can be made on the efficacy of L. reuteri DSM 17938
on AAD in hospitalized Bulgarian children. The probiotic did not affect the nonsymptomatic high rate of C. difficile colonisation (33.3% in the placebo and
38.8% in the L. reuteri group at baseline) in this population. There was also
no difference between groups regarding different gastrointestinal side-effects.
Disclosure of Interest: None declared

A444

United European Gastroenterology Journal 2(1S)

TUESDAY, OCTOBER 21, 2014


9:0017:00
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE
II POSTER EXHIBITION HALL XL_____________________

These findings suggest that TSA and SSA have different genetic alterations from
TA or HP.
Disclosure of Interest: None declared

P1135 EFFECT OF DNA TREATMENT AND PHYSICAL ACTIVITY ON


TUMOUR GROWTH ON C57BL/6 C38 COLORECTAL
ADENOCARCINOMA MICE MODELL

P1138 DNA ORIGINATED FROM TUMOROUS COLONIC EPITHELIUM


SEEMS TO BE A MORE POTENT IMMUNOMODULATOR ON
PBMCS THAN THOSE OF NORMAL DNA
00
00
I. Fu ri1,*, G. Mu zes1, F. Sipos1, A. V. Patai1, B. Wichmann2, G. Valcz1,
A. Kalmar2, B.K. Bartak1, Z. Tulassay1, B. Molnar1
1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular
Medicine Research Unit, Hungarian Academy of Science, Budapest, Hungary
Contact E-mail Address: istvan.furi@yahoo.com

A. Scholler1.2,*, S. Spisak3, T. Szekely4, B. Bartak1, A. Kalmar1.3, B. Wichmann1,


G. Valcz3, Z. Tulassay3, B. Molnar1
1
2nd Department of Internal Medicine, 22nd Department of Surgery,
SEMMELWEIS UNIVERSITY, 3Magyar Tudomanyos Akademia, Molekularis
Biologiai Munkacsoport, 41st Department of Pathology and Experimental Cancer
Research, SEMMELWEIS UNIVERSITY, Budapest, Hungary
Contact E-mail Address: andreascholler@yahoo.co.uk
INTRODUCTION: Numerous studies have investigated the positive effect of
physical activity in cancerous diseases regarding disease-free survival, presence
of recidive tumours and lower risk of metastasis. In physiological and pathological conditions as well, circulating free DNA (cfDNA) level increases. During
physical activity higher cfDNA was detected however the risk of malignancies
decreased. Effect of cfDNA may depend on its origin.
AIMS & METHODS: Our aim was to study the influence of elevated cfDNA
level on tumour progression using animal model. DNA was isolated by our
standard method using Zymo DNA columns (DNA Clean & ConcentratorTM500, Zymo Research). We had five groups with fifteen C57BL/6 mice in each.
C38 non-necrotic colorectal adenocarcinoma tissue was implanted subcutaneously in every group at the same time. Group I got high concentration subcutaneous healthy C57BL/6 spleen-derived DNA (sdDNA), pretreatment started
three weeks before tumour implantation and was continued until the end of the
study. Group II got the same DNA treatment started at the date of tumour
implantation. Treatment of group III started at the same time than in group
II, but we used C38 tumour derived DNA (tdDNA). Group IV was used as a
control group injected with PBS. Group V was subjected to five hours long
physical activity five times per week in a rodent wheel started three weeks earlier
than tumour implantation. On the 22nd day mice were slaughtered, peripheral
blood, fresh frozen and paraffin embedded tumour tissue and colon samples was
collected. Hematoxylin-eosin, cytokeratin, Ki-67, CD3 markers were used to
investigate the cell proliferation, necrosis and T-cell invasion. RNA was isolated
from tumour tissue (MagNA Pure 96 Cellular RNA LV Kit, Roche) and realtime PCR validation was performed of tumour growth and cell proliferationrelated genes.
RESULTS: The size of the tumour in group V was 51%, in group I was 71% and
in group II was 48% compared to control group IV. Investigation of implanted
tumour tissue showed that proliferation increased in tdDNA treated group III
and tumour tissue was less differentiated. CD3 expression was lower in group III
than in control group IV, and group V showed strong positivity. The mucosa in
colon samples of group III was destruated and showed IBD-like morphology.
The number of lymphoid tissue plaques decreased as well. A group of genes
showed expression alteration between group I and group V.
CONCLUSION: Plasma cfDNA level may regulate gene expression. The physical activity and DNA treatment has similar preventive effect. The ratio of tumour
cell derived and healthy cells derived cfDNA in plasma may regulate immunitiy
and tumour progression.
Disclosure of Interest: None declared
P1137 BRAF MUTATION AND IGFBG7 HYPERMETHYLATION IN
COLORECTAL SERRATED POLYPS, TUBULAR ADENOMA AND
HYPERPLASTIC POLYP
H.M. Kim1, H.S. Kim1,*, K.J. Lee1, H.J. Park1, J.W. Kim1, M.Y. Cho2, H.S. Kim1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
2
Department of Pathology, Yonsei University Wonju College of Medicine, Wonju,
Korea, Republic Of
Contact E-mail Address: wiseplant@hotmail.com
INTRODUCTION: In colorectal cancer carcinogenesis, serrated neoplasia pathway is characterized with BRAF mutation and aberrant DNA methylation. The
aim of this study was to compare serrated polyps to conventional tubular adenoma in BRAF mutation and DNA methylation.
AIMS & METHODS: For DNA extraction, 146 paraffin embedded tissue samples including 47 tubular adenomas (TAs), 53 traditional serrated adenomas
(TSAs), 17 sessile serrated adenoma/polyp (SSAs) and 29 hyperplastic polyps
in proximal colon (HPs) were collected in Yonsei University Wonju College of
Medicine. BRAF V600E mutation was identified through polymerase chain reaction and pyrosequencing assay, and methylation of LINE1, IGFBP7, hMLH1,
and CD133 was evaluated through disulfite conversion, polymerase chain reaction, and pyrosequencing assay.
RESULTS: BRAF V600E mutation was found in 2.1% of TA, 47.2% of TSA,
41.2% of SSA, and 20.7% of HP. TSA and SSA had higher BRAF mutation
than TA (P50.0001). TSA had higher BRAF mutation than HP (p 0.018).
IGFBP7 hypermethylation was found in 17% of TA, 37.7% of TSA, 88.2% of
SSA, and 37.5% of HP. TSA and SSA had higher hypermethylation of IGFBP7
than TA (p 0.021 and P50.0001, respectively). SSA had higher hypermethylation of IGFBP7 than HP (p 0.002). hMLH1 hypermethylation was found in
2.1% of TA, 5.7% of TSA, 0% of SSA, and 0% of HP. CD133 hypermethylation
was found in 21.3% of TA, 9.4% of TSA, 35.3% of SSA, and 17.4 % of HP.
CONCLUSION: TSA and SSA had different expression of BRAF mutation and
IGFBP7 hypermethylation from TA. HP in proximal colon had different expression of BRAF mutation from TSA, and IGFBP7 hypermethylation from SSA.

INTRODUCTION: In case of tumorous and inflammatory conditions, the


amount of self-DNA is elevated in the serum The methylation pattern of genomic
DNA fragments may related to its organ and disease origin. Self-DNA sequences
are recognized by TLR9 on human immune and other types of cells.
AIMS & METHODS:: We compared the immunostimulatory effect of DNA
originated from normal and tumorous colonic tissue using isolated peripheral
mononuclear cells (PBMCs) from healthy volunteers.
DNA was isolated from fresh-frozen colonic epithelium samples. PBMC was
isolated from healthy volunteers by Ficoll-Paque (Sigma). After isolation the
viability of PBMCs was determined by Trypane blue dying. PBMCs were incubated for 6 hours with 15-15 mg of self-DNA either of normal and tumorous
origin. The expression level of the pro-inflammatory cytokine-related genes was
measured by qPCR. Changes of PBMC-associated mRNA expression level of 84
genes were determined by qPCR-based Qiagen T and B cell activation arrays.
After 24h incubation with DNA Affymetrix U133 2.0 whole-genome expression
analysis was performed.
RESULTS: Incubation with normal DNA resulted in higher IL-2 mRNA expression of PBMCs (dCt of non-treated controls: 11.74  0.1650; dCt of tumorous
DNA-treated samples: 10.18,  0.1900; dCt of normal DNA-treated samples:
9.45  0.2900). After incubation either with normal or tumorous DNA IL-6
mRNA expression increased (dCt of non-treated controls: 4.67  0.2800 dCt
of tumorous DNA-treated samples: 3.45,  0.1150 dCt of normal DNA-treated
samples: 3.55 0.1450).
Based on the results of whole-genome array (Affymetrix U133 2.0) analyses upon
treatment with normal DNA overexpression of several matrix metalloproteinases
(MT1E, MT1X, MT1G, MT1H, MT1M) and that of phosphatidic acid phosphatase (PPAP2B) were observed. Moreover, the fold changes of several other
genes, like EEA1, IL1A, KCNJ2, NLRP3, THBD, OSM were also increased
(p0.05). However, following tumorous-DNA treatment no expression changes
of these genes were detected.
CONCLUSION: Overexpression of IL-2 on PBMCs induced by normal-DNA
treatment may affect T cell maturation and differentiation along with T cell
reactivity. IL-6 overexpression in cases of normal and tumorous DNA-treatments may indicate the activation of pro-inflammatory mechanisms leading
finally to the overexpression of MMPs.
Disclosure of Interest: None declared
P1139 EFFECTS OF MODIFIED SELF-DNA SEQUENCES ON CELL
KINETIC PARAMETERS AND DIFFERENTIATION OF HT29 CELLS
I. Fu ri1,*, M. Constantinovits1, F. Sipos1, B. Molnar1, Z. Tulassay1, G. Mu zes1
1
2nd Department of Internal Medicine, SEMMELWEIS UNIVERSITY,
Budapest, Hungary
Contact E-mail Address: dr.siposf@gmail.com
00

00

INTRODUCTION: We have reported that Toll-like receptor 9 (TLR9)-signaling


pathway activiation by modified self-DNA depends on the structural characteristics of DNA sequences. However, no concrete data exists on how the characteristics of TLR9 activating self-DNA fragments influence the viability,
proliferation, death, and differentiation of cancer cells, which all may have
important immunobiologic consequences in inflammatory and tumorous colonic
disorders.
AIMS & METHODS: To understand the biologic role of modified self-DNA
bound to TLR9, we assayed its effect on cell viability, proliferation, death and
differentiation in HT29 cells. HT29 cells were incubated separately with type-1
(normally methylated / non-fragmented), type-2 (normally methylated / fragmented), type-3 (hypermethylated / non-fragmented), or type-4 (hypermethylated /
fragmented) self-DNAs for 24, 48 and 72 hours. Cell viability was examined by
MTT-assay, cell proliferation by TUNEL method, cell proliferation by Ki-67
assay, while cell differentiation by pancytokeratin (CK) immunohistochemistry.
RESULTS: Treatments with type-1, -3 and -4 DNA sequences resulted in
remarkable decrease of cell viability and proliferation, and increase of apoptosis
after 72h. The effects of type-3 DNA incubation were the most significant. Type2 DNA treatment resulted in a slight decrease of cell viability after 48h, but at
72h all parameter of cell kinetics were similar to that of control cells. Regarding
cell differentiation, CK expression was only increased after type-3 DNA
treatment.
CONCLUSION: Activation of TLR9-signaling pathways by modified self-DNA
sequences may display significant effects on cell kinetic parameters like viability,
proliferation or death, moreover may influence cell differentiation, which may
have clinical importance in the future.
REFERENCES
00
1. Fu ri I, Sipos F, Germann TM, et al. Epithelial toll-like receptor 9 signaling in
colorectal inflammation and cancer: clinico-pathogenic aspects. World J
Gastroenterol 2013; 19: 4119-4126.
00
2. Fu ri I, Sipos F, Spisak S, et al. Association of self-DNA mediated TLR9related gene, DNA methyltransferase, and cytokeratin protein expression

United European Gastroenterology Journal 2(1S)


alterations in HT29-cells to DNA fragment length and methylation status. Sci
World J 2013; 2013: 293296.
Disclosure of Interest: None declared
P1140 DNA ORIGINATED FROM NORMAL AND TUMOROUS
COLONIC TISSUE ACTS DIFFERENTLY VIA TLR9 SIGNALING ON
HT29 CARCINOMA CELLS
00
00
I. Fu ri1,*, B. Wichmann2, G. Mu zes1, F. Sipos1, C. Miklos1, S. Spisak3,
B.K. Bartak1, A. Kalmar2, B. Molnar2, Z. Tulassay2
1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular
Medicine Research Unit, Hungarian Academy of Science, 3Molecular Medicine
Research Unit, Semmelweis University, Budapest, Hungary
Contact E-mail Address: istvan.furi@yahoo.com

INTRODUCTION: Within tumorous and chronic inflammatory conditions selfDNA is released to the extracellular compartment. The Toll-like receptor 9
(TLR9)-mediated immunobiologic effects of self-DNA however are not fully
clarified
AIMS & METHODS: Using HT29 carcimoma cells we compared the effects of
self-DNA originated from normal and tumorous colonic tissue on the expressions of TLR9- and pro-inflammatory cytokine-related genes. DNA was isolated
from fresh-frozen normal and tumorous colonic epithel tissues. HT29 cells were
then incubated with DNA samples for 6 hours. After total RNA isolation
Affymetrix U133 2.0 microarray analysis and qRT-PCR were performed regarding the genes of the TLR9 signaling pathway. CK20, E-cadherin and DNMT3A
immunocytochemistries were also performed for cell differentiation analysis.
RESULTS: After treatment either with normal or tumorous DNA IL-1beta
overexpression was observed (dCt in controls vs. tumorous DNA-treated vs.
normal DNA-treated samples: 25.87  0.1627 vs. 23.54  0.2613 vs. 24.28 
0.2253, p50.05).
Based on the results of whole-genome expression analyses overexpressions of 3
types of metalloproteinase genes (MT1X, MT1F, MT1H), 3 of metastasis associated genes (TACSTD2, MACC, MALAT1), 1 differentation-associated gene
(CEACAM), and 2 metabolism-associated genes (INSIG1, LIPG) were detected.
Following incubation with tumorous DNA expressions of CK20, E-cadherin and
DNMT3A proteins were increased.
CONCLUSION: Incubation with tumorous DNA binding to TLR9 may promote cancer cell invasion via increased activity of MMPs and other pro-metastatic proteins. Moreover, our results suggest a possible link between TLR9signaling and DNMT3A regulation.
Disclosure of Interest: None declared
P1142 DIAGNOSIS AND CLASSIFICATION OF REFRACTORY CELIAC
DISEASE IN CELIAC PATIENTS DESPITE STRICT ADHERENCE TO
A GLUTEN FREE DIET
T.T. Perets1, D. Luria2, E. Shporn1, D. Hamouda1, Y. Niv3,*, R. Shamir4
Gastroenterology Laboratory, Rabin Medical Center - Beilinson Hospital,
2
Pediatric Hemato-Oncology Laboratory, Schneider Childrens Medical Center,
3
Department of Gastroenterology, Rabin Medical Center - Beilinson Hospital,
4
Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Childrens
Medical Center, Petah Tikva, Israel
Contact E-mail Address: kaiser1974@gamil.com
1

INTRODUCTION: Patients with celiac disease (CD) are defined as suffering


from refractory celiac disease (RCD) when clinical and histological symptoms
persist or recur, despite strict adherence to a gluten free diet (GFD).
Intraepithelial T lymphocytes (IETLs) may show normal phenotype and are
attributed to RCD type 1 (RCD-1). The IETLs that present an aberrant and
even clonal phenotype are attributed to RCD type 2 (RCD-2). These IELs are
associated a high risk for development of enteropathy associated T lymphocytes
lymphoma (EATL). EATL is the main cause of death in these patients and has a
5 year survival of only 8%. Without detailed phenotyping of IELs, diagnosis of
RCD could be missed.
AIMS & METHODS: To establish a diagnostic scheme, in Israel, for RCD
diagnosis in CD patients with persistence of CD related symptoms and reported
adherence to a GFD based on previously described diagnostic systems. RCD
type was determined by performing flow cytometry analysis (FCA) and T-Cell
receptor rearrangements PCR (TCR) on small duodenal biopsies, obtained from
11 distinct CD-GFD patients. In addition, Peripheral blood was also obtained
and assessed from these patients and served as an internal control.
RESULTS: FCA exhibited RCD-1 phenotype in the duodenal biopsies of 10
patients all IETLs were normal although abundant. Furthermore no IETLs
clonality was demonstrated in these patients by TCR. RCD-2 phenotype was
diagnosed in the biopsy of 1 patient who demonstrated a high presence of aberrant IETLs and distinct clonality observed by TCR. Peripheral blood samples, in
both RCD-1 and RCD-2 patients, showed no presence of IETLs, nor clonality of
T lymphocytes implying duodenal locality of the IETLs.
CONCLUSION: Characterization of IETLs as normal and aberrant by FCA, in
CD patients with persistent symptoms despite adhering to a GFD is important
for the diagnosis of RCD. Using FCA as an RCD diagnostic tool is as good as
exploring IETLs clonality by TCR. Moreover, FCA is preferable and may be
solely used for differentiating RCD patients at risk for EATL development. In
these patients TCR serves as a complementary instrument for a complete
diagnosis.
Disclosure of Interest: None declared

A445
P1143 ACTIVATION OF TOLL-LIKE-RECEPTORS (TLR) ON ISOLATED
KUPFFER CELLS (KC) AND SINUSOIDAL ENDOTHELIAL CELLS
(SEC) OF THE LIVER: OPPOSING EFFECTS ON THE PRODUCTION
OF THE VASOCONSTRICTOR THROMBOXANE B2
J. Schewe1,*, L. Selzner1, I. Liss1, A.L. Gerbes1, C.J. Steib1
1
Department of Medicine II, LMU Klinikum Grohadern, Munich, Germany
Contact E-mail Address: Julia. Schewe@med.uni-muenchen.de
INTRODUCTION: The role of TLR-dependent formed Thromboxane (TX) for
portal hypertension in cirrhosis, we have already shown in previous work
(including Steib CJ et al., Hepatology 2010). To develop risk stratification ratifications and targeted new therapeutic strategies for patients in the future, the
aim of this study was to determine, which liver cells play a relevant role for TXproduction and which TLR are involved in this process.
AIMS & METHODS: KC and SEC were isolated from mouse livers (male C57/
Bl6) and stimulated over 24h with various TLR-agonists (Pam3CSK4 [TLR 1/2]
0.1g/ml; HKLM [TLR 2] 10e8 cells/ml; Poly (I:C) [TLR 3] 10ng/ml; LPS-EK
[TLR 4] 10ng/ml; ST-FLA [TLR 5] 10ng/ml; FSL-1 [TLR 6/2] 1ng/ml; ssRNA40
[TLR 7] 0.25mg/ml; ODN1826 [TLR 9] 5mM; n 6). Thromboxane B2 (TXB2)
efflux before and after stimulation into the cell media was measured by ELISA
(meanSD, *p50.05).
RESULTS: In KC TXB2-efflux increases differently (before stimulation vs. after
stimulation in pg/ml; TLR 1/2:21290 vs. 24243; TLR 2:25124 vs.
1271255*; TLR 3:30296 vs. 400139; TLR 4:23175 vs. 717363*; TLR
5:25446 vs. 640250*; TLR 6/2:27132 vs. 22911446*; TLR 7:21391 vs.
296206; TLR 9:22934 vs. 704232*), however in SEC after stimulation
increasingly there is a decrease in TXB2-secretion (TLR 1/2:544187 vs.
4227*; TLR 2:47789 vs. 8245*; TLR 3:408204 vs. 10762*; TLR
4:49770 vs. 8853*; TLR 5:238150 vs. 284306; TLR 6/2:301191 vs.
10053*; TLR 7:420131 vs. 11135*; TLR 9:324207 vs. 8455*).
CONCLUSION: The activation of TLR 2, 4, 5, 2/6, and 9 on isolated KC of
healthy livers lead to a significant production of vasoconstrictive effective TXB2,
whereas the activation of SEC through TLR 1/2, 3, 4, 6, 7 and 9 led to a decrease
of TXB2 production. These findings are important to identify relevant early stage
microbial products for the formation of TXB2 in the future and to develop new
targeted therapeutic strategies.
Disclosure of Interest: None declared
P1144 UNIQUE PROFILE OF LIVER PERFUSATE MONONUCLEAR
CELLS TRANSFERABLE TO LIVER TRANSPLANTATION
RECIPIENTS -ANALYSIS OF THE LIVING DONOR LIVER
PERFUSATE BY MULTICOLOR FLOWCYTOMETRY
K. Koike1,*, A. Takaki1, N. Watanabe2, R. Tsuzaki,1, M. Utsumi3, T. Yagi3,
Y. Miyake1, K. Yamamoto1
1
Gastroenterology and hepatology, OKAYAMA UNIVERSITY, Okayama,
2
FACS Core Laboratory, The Institute of Medical Science, The University of
Tokyo, Tokyo, 3Gastroenterological Surgery Transplant and Surgical Oncology,
OKAYAMA UNIVERSITY, Okayama, Japan
INTRODUCTION: Liver transplantation induces relative immune tolerance
than the other organ transplantation. The mechanisms responsible for this phenomenon have been acknowledged as the liver resident tolerant immune cells that
could be transferred to donor. In living donor liver transplantation, the effluent
solution passing through the graft livers during perfusion before transplantation
has been shown to be useful to characterize the leukocytes. Recent advances in
multicolor flowcytometry enabled us to investigate the character of the leukocytes in detail. We analyzed the perfusate cells with multicolor flowcytometry,
revealed the characteristics of the cells, and detected them after an early period
post transplantation.
AIMS & METHODS: Liver perfusates were collected from 11 human liver
grafts. During the backtable procedure, the grafts were perfused through the
portal vein with 1-2L of Univeristy of Wisconsin solution under hydrostatic
pressure, and the perfusate was collected from the vena cava. Mononuclear
cells (P) were isolated within 12 hrs by density gradient centrifugation.
Peripheral blood mononuclear cells (B) were drawn on the same day from peripheral vein. After isolation, cells were stained with cell surface antibodies collecting the population of B cell, CD4 T cell, CD8 T cell, NK cell,
plasmacytoid dendritic cell (DC), myeloid DC, Programmed death (PD)-1 positive cells, CD45RA CCR7 na ve T cells, CD45RA CCR7- effector T cells,
CD45RA- CCR7-effector memory T cells, and CD45RA- CCR7 central
memory T cells, and CD4 CD25 CD127- regulatory T (Treg). To reveal the
perfusate involvement in recipient after transplantation, we studied peripheral
blood donor cell microchimerism in human leucocyte antigen (HLA) mismatched
17 patients.
RESULTS: Results: CD8 T cells (P: 27.8%, B: 16.6%), CD14 cells (P: 2.13%,
B: 0.156%), NK (CD56) cells (P: 82.9%, B: 66.8%), plasmacytoid DC
(CD123) (P:10.3%, B: 2.16%) and myeloid DC (CD11c) (P: 6.38%, B:
0.926%) were increased and CD4CD25CD127low/- regulatory T cells
(Treg) (P: 3.37%, B: 6.75%) was decreased in perfusate compared with peripheral
blood. Furthermore, na ve subsets of T cells were lower, and effector memory
subsets of T cells and PD-1 T cells were higher in perfusate lymphocyte than
peripheral blood. The microchimerism was found in CD14 cells (0.8%), CD8
T cells (1.7%), CD4 T cells (1.5%), B cells (0.95%) and NK (CD56) cells
(4.5%) as the perfusate pattern likely.
CONCLUSION: The perfusate contains CD4T cells, CD8 T cells, with
higher exhaustion marker PD-1 and plasmacytoid DC, myeloid DC with lower
activation marker CD86, probably not to react with many antigens flow into the
liver via portal vein. This might explain one reason why liver transplantation
exhibit more tolerant than other organ transplantation.

A446
Disclosure of Interest: None declared
P1145 INTERLEUKIN-10 EXPRESSION IS REGULATED BY TOLL LIKE
RECEPTORS 2 AND 4 IN INTESTINAL EPITHELIUM
E. Latorre1,*, E. Layunta1, M. Castro1, L. Grasa1, J. Pardo2, J.E. Mesonero1, A.
I. Alcalde1
1
Pharmacology and Physiology, 2Biochemistry and Cellular and Molecular
Biology, Zaragoza University, Zaragoza, Spain
Contact E-mail Address: eva.latorre@unizar.es
INTRODUCTION: Intestinal epithelium constitutes a physical and functional
barrier which is essential for intestinal immunological activity. In fact, Toll-like
receptors expressed in intestinal epithelium are responsible for microbiota recognition, and they also contribute to both intestinal homeostasis and inflammation.
The balance between pro and anti-inflammatory cytokines seems to be crucial for
homeostasis, and also for the development of inflammation. In this context,
interleukin-10 (IL-10), a prototypical anti-inflammatory cytokine mainly produced by immune cells, has been shown to inhibit immune activation (1), and
to be essential in tolerance to self (2) and mucosal antigens (3). In addition,
deficient IL-10 expression seems to contribute to gut inflammation (4).
Intestinal epithelium has been well documented as a rich source of proinflammatory cytokines, however little is known about the relation between intestinal
epithelium and IL-10. Several studies have described IL-10 production mediated
by TLR2 and TLR4 activation in immunological cells, however the role of TLRs
expressed in intestinal epithelium in the modulation of molecular expression and
release of IL-10 remains unknown.
AIMS & METHODS: The purpose of this work has been to assess the involvement of intestinal epithelium and TLR2 and TLR4 activation in the expression
and release of IL-10. To carry out the study, we have used the human enterocytelike cell line Caco-2 and intestine from WT, TLR2-/- and TLR4-/- mice. IL-10
release levels were measured by ELISA, and IL-10 mRNA and protein expression were analyzed by RT-qPCR and Western Blot respectively.
RESULTS: Caco-2 cells have shown to express and release IL-10. In addition
activation of TLR2 or TLR4 in these cells showed to increase IL-10 mRNA and
release. Surprisingly, IL-10 mRNA levels in TLR2-/- and TLR4-/- ileum and
colon resulted increased, and IL-10 release levels were also augmented in
TLR4-/- ileum whereas in TLR2-/- colon resulted decreased. TLR4 expression
was increased in TLR2-/- ileum and reciprocally, TLR2 expression was augmented in TLR4-/- ileum, thus suggesting a cross talk between TLR2 and TLR4
which may maintain IL-10 release in the epithelium.
CONCLUSION: The present work shows that intestinal epithelial cells were able
to synthesize and release IL-10, and that the activation of TLR2 or TLR4 stimulated IL-10 expression in these cells. In addition, IL-10 expression and release
in mice intestine might be guaranteed by cross- regulation between TLR2 and
TLR4. In summary, the results of the present work suggest that intestinal epithelial cells might contribute to the immune response by modulating IL-10 expression, and demonstrate cross-talk regulation of IL-10 expression between TLR2
and TLR4 in the intestine.
REFERENCES
1. Moore, et al. Annu Rev Immunol 2001; 19: 683-765.
2. Seddon and Madon. Immunol Today 2000; 21: 95-99.
3. Powrie, et al. J Exp Med 1996; 183: 2669-2674. F 1996
4. Iyer and Cheng. Crit Rev Immunol 2012; 32: 23-63.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
POSTER PLUS VIDEO III POSTER EXHIBITION HALL XL_____________________
P1146 CLINICAL IMPACT OF THE SEQUENTIAL USE OF EUS
ELASTOGRAPHY FOLLOWED BY CONTRAST-ENHANCED EUS
IN PATIENTS WITH FOCAL PANCREATIC MASSES AND
NEGATIVE EUS-GUIDED FNA
S. Iordache1, M.-I. Costache1, C.-T. Streba2, D.-I. Gheonea1,*, A. Saftoiu1
1
Research Center in Gastroenterology and Hepatology, 2UNIVERSITY OF
MEDICINE AND PHARMACY CRAIOVA, Craiova, Romania
Contact E-mail Address: sevastita@gmail.com
INTRODUCTION: It is well known that EUS-guided FNA has a high sensitivity
(over 85%) and specificity (100%) for diagnosis of pancreatic cancer. EUS elastography and contrast-enhanced EUS (CE-EUS) are useful methods for the
assessment of patients with pancreatic masses, with high sensitivity and specificity reported in recent meta-analyses. In most of the cases, pancreatic adenocarcinoma is a hard (low strain), hypoenhanced (hypovascular) tumor.
AIMS & METHODS: The aim of the study is to establish an EUS based diagnostic algorithm in patients with pancreatic masses and negative cytopathology
after EUS-FNA, based on previously published results and cut-offs of elastography and contrast-enhancement (CE-EUS).
We included in the study a subgroup of 50 consecutive patients with focal pancreatic masses who underwent an EUS examination with negative EUS-FNA for
malignancy: 19 patients with pancreatic cancer and 31 patients with pseudotumoral chronic pancreatitis. Real-time elastography and contrast-enhancement
during EUS were performed sequentially in all patients. The sensitivity, specificity and accuracy of these methods were calculated separately. Moreover, we
established a clinical decision making algorithm based on real-time elastography
(for characterization of tissue hardness), followed by contrast-enhanced EUS (for
characterization of vascularity).
RESULTS: For the diagnosis of possible malignancy, the sensitivity, specificity
and accuracy of EUS elastography were: 97.7%, 77.4% and 84% respectively,
while CE-EUS has similar results: 89.5%, 80.7% and 84%, respectively.

United European Gastroenterology Journal 2(1S)


Subsequently, we selected the subgroup of 25 patients with soft/mixed appearance in elastography for sequential assessment using contrast-enhanced EUS.
Thus, the sensitivity of CE-EUS in this set of patients was excellent (100%)
while the specificity was 75%, with 76% accuracy. Overall, for the sequential
evaluation with elastography, followed by contrast-enhanced EUS, there were no
false negative results for possible malignancy, while the negative predictive value
of this method was 100%.
CONCLUSION: The proposed algorithm of sequential use of real-time elastography, followed by contrast-enhanced EUS could be a good clinical tool to help
select the patients with possible pancreatic adenocarcinoma in the setting of
patients with negative EUS-FNA results.
Disclosure of Interest: None declared
P1147 PILOT STUDY TO ASSESS THE POTENTIAL GASTRICDUODENAL TRACT EXAMINATION USING A MAGNETICALLY
CONTROLLED CAPSULE ENDOSCOPY
A. Pezzoli1,*, D. Moneghini2, A. Mussetto3, N. Fusetti4, R. Cestari5, O. Triossi6,
S. Gullini7
1
Dep of Gastroenterology and Endoscopy Unit, SantAnna Hospitla, Ferrara,
2
Dept of Surgical Endoscopy, Spedali Civili, Brescia, 3Dept of Gastroenterology,
Ospedale S. Maria delle Croci, Ravenna, 4Depst of Gastroenterology, Sant Anna
Hospital, Ferrara, 5Dept of Surgical Endoscipy, Spedali civili, Brescia, 6Dept of
Gastroenterology, Ospedale SM delle croci, Ravenna, 7Dept of Gastroenterology,
SantAnna Hospital, Ferrara, Italy
Contact E-mail Address: a.pezzoli@ospfe.it
INTRODUCTION: CE progresses inside the gastrointestinal tract only using
intestinal motility and several approaches to actively guide the capsule have
been proposed. Currently, the most promising solution seems to be the magnetic
steering. Up to now the only system of CE magnetic steering available on the
market is the Mirocam Navi CE. Aim: To evaluate the feasibility of exploring the
gastric cavity and duodenal bulb using the guided CE Mirocam Navi system.
AIMS & METHODS: A small group of patients (18 pts, 9 females, mean age
65.5 yrs, range 52-81 yrs) undergoing CE was included in the study. The indications for CE included 13 pts with occult gastrointestinal bleeding (OGIB), 2 pts
with suspected Crohns disease, 2 pts with polyposis syndrome and 1 suspected
ileal neoplasia. Patients with cardiac pacemakers or other implanted metallic
devices were excluded. After the patient swallowed the capsule in a sitting position, the external controller was placed in the abdomen over the cardia in order
to block the capsule and visualize the Z line. Then the aim of the study was to
navigate the capsule through the stomach visualizing the gastric fundus, gastric
body, and antrum. Each author moved the external controller and steered the
capsule under direct vision through a real time view system. No specific movements were suggested and the attempts to visualize the gastric cavity lasted no
more than 20 minutes. The authors reported if the gastric cavity visualization was
satisfactory or not. Finally the authors tried to crawl the capsule through the
pylorus using the external controller to visualize the duodenal bulb. Patients were
asked to judge the tolerability of the procedure using a visual analogical scale
(VAS) and any adverse event was registered.
RESULTS: A positive finding was observed in 11/18 of CE (diagnostic yield
61%). A complete visualization of the Z line, antrum, body, fundus and duodenal
bulb was registered in 1/18 cases (5.5%), 18/18 cases (100%), in 12/18 (66.6%), 5/
18 (27%) and in 6/18 (33%) of the cases, respectively. The crawl of the capsule
into the bulb under external magnetic control was obtained successfully in 8/18 of
the cases (44%). The mean score of the VAS scale was 9.3 cm (well tolerated). No
adverse event was reported.
CONCLUSION: The Mirocam navi system is a promising method for controlled
locomotion of CE; it is well tolerated and safe but the ability to control the
movement in the upper gastro-intestinal tract is still unsatisfactory.
Disclosure of Interest: None declared
P1148 SUPCAM
EUROPEAN
PROJECT:
PRELIMINARY
PROTOTYPING AND TEST OF A NEW GENERATION ACTIVE
ENDOSCOPIC COLON CAPSULE
A. Tozzi1,*, G. Ciuti2, G. Lucarini2, M. Mura2, C. Quaglia2, A. Menciassi2,
G. Battaglia3
1
Dipartimento Medico UO Gastroenterologia Epatologia ed Endoscopia Digestiva,
Ospedale San Giuseppe, ASL 11, Empoli, 2The BioRobotics Institute, Polo
SantAnna Valdera, Scuola Superiore SantAnna, Pontedera, 3Endoscopia ad alta
tecnologia, Istituto Oncologico Veneto IOVIRCCS, Padova, Italy
Contact E-mail Address: aletozzi@yahoo.it
INTRODUCTION: Optical colonoscopy is currently the diagnostic gold standard for colic diseases, however it is also invasive, risky and embarrassing and
minimally invasive diagnostic procedures are required. Market available video
endoscopic capsules (VCE) explore the GI tract proceeding by means of visceral
peristalsis and gravity. Higher diagnostic accuracy, more extensive clinical application and shorter times of investigation would be achieved by controlling the
VCE locomotion. Some authors demonstrated that magnetic fields allow controlling the VCE movement. However the cylindrical shape, while may be suitable for the small intestine, esophagus and stomach, in the colon, due to its
anatomical features, has intrinsic disadvantages as regard to VCE propulsion,
surface friction and cleaning. Other limits of the previous solutions depend on the
movement control precision, or in the use of a very cumbersome and expensive
external instrumentation. The SUPCAM concept is based on the development of
an innovative Active VCE (AVCE) whose design allows to safely and accurately
guide it along the colonic lumen from the outside, using an innovative electromagnetic approach and an external compact assisted handle adapted to be transported and suitable for common outpatient setting. The SUPCAM EU Project is

A447

United European Gastroenterology Journal 2(1S)


aimed at developing a new generation of AVCE able to investigate the colon,
ensuring a high level of navigation and diagnostic accuracy.
AIMS & METHODS: The aim of this study is to present a new mechanical
configuration of a colon capsule and to demonstrate its precise locomotion in
the colon from the anus to the cecum and vice versa through external magnetic
fields generated by an external low-cost and assisted magnetic handle. An external electromagnetic handle and a capsule prototype were developed within the
SUPCAM Project. Experimentally the prototype locomotion capabilities were
assessed with motion control tests inside an insufflated human-sized plastic phantom colon.
RESULTS: A prototype of a double sphere colon capsule and external low-cost
and assisted magnetic handle for magnetic fields generation and capsule propulsion have been fabricated. The prototype has been inserted transanally into the
phantom colon. The endoscopist, moving manually the external handle, drove
and accurately oriented the SUPCAM capsule within the phantom colon from
the anus to the cecum and vice versa.
CONCLUSION: Our study demonstrated the development and test of a capsule
prototype with a completely new double sphere mechanical configuration and an
innovative electromagnetic approach. SUPCAM mechanical prototype allowed a
precise, effective and safe propulsion and orientation in a phantom model
through a low-cost, compact and easily manageable external assisted magnetic
handle. In our opinion, SUPCAM endoscopy represents a highly innovative and
disruptive solution for colon diseases diagnosis and screening. The further development of this innovative magnetically controlled AVCE, reducing clinical risk,
improving tolerance, acceptability, territory availability and adherence to colorectal cancer screening programs, will provide significant benefits for patients and
the whole healthcare system. Other studies are planned to test performance of
more advanced SUPCAM prototypes in ex-vivo and in-vivo settings.
Disclosure of Interest: A. Tozzi Other: Supcam Patent co-owner, G. Ciuti: None
declared, G. Lucarini: None declared, M. Mura: None declared, C. Quaglia:
None declared, A. Menciassi: None declared, G. Battaglia: None declared
P1149 ACCURACY OF COLON CAPSULE FOR THE DETECTION OF
COLONIC TUMORS
C. Carretero1,*, C. Prieto1, M. Munoz-Navas1
1
Gastroenterology, University of Navarra Clinic, Pamplona, Spain
Contact E-mail Address: ccarretero@unav.es
INTRODUCTION: Colon capsule has shown to be a safe and accurate procedure for the study of colonic pathology. Previous studies have been focused on
the diagnostic yield of colonic polyps and, to date, there is scarce data regarding
its ability to detect colon cancer. We describe our experience in this field.
AIMS & METHODS: From December 2007 to February 2014 we have performed 211 colon capsules. We describe our experience regarding colon cancer
detection.
RESULTS: In our study population, there were 14 colon cancers (12 male, mean
age 63 years old). All but one were detected by the capsule. The one not detected
by the capsule was due to battery life, as it expired before reaching tumor location. The main reason for referral was colorectal cancer screening in 61.5% of
cases, followed by rectal bleeding in 23.1%. Regarding tumor location, 3 tumors
were located in the rectum, 3 in sigmoid, 4 in descending, 2 in transverse, 1 in
ascending and 1 in cecum. 3/14 patients had a stenosing tumor, in those patients
the capsule was retained although it did not cause any obstructive symptoms. In
two of these three cases capsule excretion took place after chemotherapy treatment and in the other case we retrieved the capsule with a Roth Net.
Colon cleansing level was adequate in 92.3% of cases.
CONCLUSION: According to our experience, colon capsule is accurate also for
colon cancer detection. Despite the theoretical risk of obstructive symptoms
associated to stenosing tumors, we havent found any obstructive complication.
Disclosure of Interest: C. Carretero Lecture fee (s) from: Given Imaging, C.
Prieto: None declared, M. Munoz-Navas: None declared
P1150 CAN MAGNETIC ASSISTED CAPSULE ENDOSCOPY (MACE)
REPLACE GASTROSCOPY?
I. Rahman1,*, M. Pioche2, C.S. Shim3, I.-K. Sung3, J.-C. Saurin2, P. Patel1
1
University Hospital Southampton, Southampton, United Kingdom, 2Hopital
Edouard Herriot, Lyon, France, 3Konkuk University Medical Center, Seoul,
Korea, Republic Of
Contact E-mail Address: imdi81@hotmail.com
INTRODUCTION: Attempts in employing a simple technique of capsule endoscopy for visualisation of the upper GI tract has, thus far, been experimental,
cumbersome and potentially expensive. We describe the first human series for
comprehensive visualisation of the upper GI tract using the simple Intromedic
MiroCam-Navi system. Our aim was to demonstrate the manoeuvrability of this
magnetic capsule and evaluate its ability to completely visualise and maintain
views in the upper GI tract.
AIMS & METHODS: 26 volunteers observed a 12hr overnight fast. 30mins
before the examination volunteers drank a preparation mixture of 20mg of maxalon syrup with simethicone and pronase. After capsule ingestion, volunteers
were allowed sips of water during the procedure. The MiroCam-Navi magnet
was placed at strategic points on the body surface and rotated to hold and
manoeuvre the capsule. Control was assessed by moving and holding the capsule
for 1 minute to visualise each of the following stations: lower oesophagus, cardia,
fundus, body, incisura, antrum and pylorus and also traversing across the stomach and through the pylorus. Total procedure time was taken from the moment
of ingestion of the capsule to either reaching the duodenum, or after attempting a
maximum of 10mins to traverse the pylorus. All the procedures were performed
on the same day in Seoul Konkuk University Hospital by 6 endoscopists (experts

in capsule endoscopy). All volunteers subsequently underwent a standard upper


GI endoscopy within 3 days.
RESULTS: Volunteers median age was 38yrs (range 26-45), median BMI 24
(range 19-38), median volume of water consumed 800 mls (range 200mls1500mls) and median procedure time 24 minutes (range 12-39 minutes). Table
1 shows the success of clear visualisation of landmarks

GOJ
Cardia
Fundus
Body
Incisura
Antrum
Pylorus

Landmark Visualised

Landmark Not Visualised

92% (n 24)
88% (n 23)
96% (n 25)
100% (n 25)
96% (n 25)
96% (n 25)
100% (n 26)

8% (n 2)
12% (n 3)
4% (n 1)
0% (n 0)
4% (n 1)
4% (n 1)
0% (n 0)

The capsule could be held overall in 88% of designated stations for 1 minute. The
capsule could be moved from the fundus to the antrum in all cases and traverse
the pylorus in 50% (n 13). Age 40 was associated with successful pyloric
traversing (p 0.04).
There was positive concordance for 8 out of 9 minor pathological findings with
standard upper GI endoscopy. A small 4 mm submucosal lesion was missed by
capsule endoscopy in the cardia of one volunteer where views were obscured.
CONCLUSION: This is the first convincing demonstration of the potential value
of MACE in the upper GI tract. There is a high degree of visualisation and
control, with some improvement required for optimising fundal views and traversing the pylorus.
Disclosure of Interest: None declared
P1151 NON-EXPOSED ENDOSCOPIC WALL-INVERSION SURGERY
(NEWS) AS A NOVEL FULL-THICKNESS RESECTION TECHNIQUE
FOR GASTRIC TUMOR
K. Niimi1.2,*, S. Aikou3, Y. Sakaguchi2, S. Kodashima2, N. Yamamichi2,
H. Yamashita3, M. Fujishiro2.4, Y. Seto3, K. Koike2
1
Department of Center for Epidemiology and Preventive Medicine, 2Department of
Gastroenterology, 3Department of Gastrointestinal Surgery, 4Department of
Endoscopy and Endoscopic Surgery, THE UNIVERSITY OF TOKYO, Tokyo,
Japan
INTRODUCTION: Non-exposed endoscopic wall-inversion surgery (NEWS) is
a new advanced method of endoscopic full-thickness resection without transluminal communication, causing intra-abdominal contamination or possible tumor
dissemination, applying endoscopic submucosal dissection (ESD) technique.
AIMS & METHODS: The aim of this study is to investigate the efficacy, safety
and advantages of NEWS for gastric submucosal tumors (SMT). Between July
2011 and March 2014, 12 patients (5 females, 7 males; mean age 65.8 years, range
49-79 years) underwent NEWS for intragastric-type gastric SMT within 4cm in
size at the University of Tokyo Hospital. After marking around a tumor on both
the mucosal and serosal surfaces and submucosal injection of sodium hyaluronate, circumferential seromyotomy and sero-muscular suturing were made laparoscopically, followed by circumferential muco-submucosal incision
endoscopically. The resected specimen was perorally retrieved. Clinical data
and pathological features were analyzed.
RESULTS: The mean resected specimen and tumor size were 23.9 mm (range,
10-45 mm) and 35 mm (range, 25-50 mm), respectively. All lesions were successfully resected in an en-bloc fashion. The mean operation time was 229.5 minutes
(range, 140-397 minutes), and the mean estimated blood loss was 41.7 g (range, 0250 g). Patients started oral intake on mean postoperative day 2.1 (range, 2-3),
and the mean length of postoperative hospital stay was 7.9 days (range, 6-13
days). Micro perforation occurred in the three cases due to technical inadequacy,
which were treated successfully without open surgery. There were no severe
complications, such as hemorrhage, anastomosis insufficiency, delayed gastric
emptying or surgical site infection. Histopathological examination of the
tumors showed GIST (n 11) and schwannoma (n 1).
CONCLUSION: NEWS enabled en bloc full-thickness resection effectively and
safely with minimum possible margin without contamination and tumor dissemination into the peritoneal cavity. This treatment may be promising not only
for gastric SMT but also for node-negative early gastric cancer difficult to resect
by ESD.
Disclosure of Interest: None declared
P1152 MUCOSAL-INCISION ASSISTED BIOPSY FOR SUSPICIOUS
GASTROINTESTINAL STROMAL TUMORS
J. Chung1,*, Y. Seok1
1
Internal medicine, gastroenterology department, Sahmyook Medical Center,
Seoul, Korea, Republic Of
INTRODUCTION: Tissue sampling is necessary for definitive diagnosis of
GIST. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has
been developed for tissue sampling of suspected GIST and is generally accepted
to be a very useful for the diagnosis of this lesion, but the success rate for
histology does not seem to be satisfactory (62%).
Recently Eikichi et al has published of retrospective review of mucosal incision
assisted biopsy (MIAB) of suspected GISTs. So we performed prospective study
of MIAB associated with suspicious GISTs.

A448
AIMS & METHODS: To evaluate the diagnostic yield of the procedure, mucosal-incision assisted biopsy (MIAB), for the histological diagnosis of gastric gastrointestinal stromal tumor (GIST),and to know the complications of MIAB, we
performed prospective study of the 14 patients with suspected gastric GIST who
underwent MIAB in our hospitals.
RESULTS: Tissue samples obtained by MIAB were sufficient to make a histological diagnosis (diagnostic MIAB) in 12 out of the 14 patients (86%), where the
lesions had intraluminal growth patterns. Histologic diagnosis were GIST (9, 64
%), Leiomyoma (2, 14 %) and inflammatory change (1.7 %). Locations were
fundus (3, 21 %), cardia (3.21 %), body (5, 36%) and antrum (3, 21 %). Mean
size 15.3  0.8.
1patient had significant bleeding after MIAB but well controlled by endoscopic
hemostasis.
CONCLUSION: Although it is generally accepted that EUS-FNA is the gold
standard for obtaining biopsies for histological and cytological analysis of suspected gastric GIST, MIAB may be chosen as an alternative diagnostic modality
only when the lesion has an intraluminal growth pattern. Further studies will be
required to further assess MIAB, including randomized controlled trials to compare MIAB with EUS-FNA.
REFERENCES
World J Gastrointest Endosc 2013; 5: 191196.
Disclosure of Interest: None declared
P1153 DETECTION OF SESSILE SERRATED ADENOMAS IN IBD
SURVEILLANCE COLONOSCOPY BY ELECTRONIC VIRTUAL
CHROMOENDOSCOPY AND DYE CHROMOENDOSCOPY
M. Iacucci1,*, X. Gui2, M. Fort Gasia1, G. Eustace3, R. Panaccione3, S. Ghosh3
1
IBD Clinic. Division of Gastroenterology, 2Department of Pathology, 3University
of Calgary, Calgary, Canada
Contact E-mail Address: miacucci@ucalgary.ca
INTRODUCTION: In IBD sessile serrated adenomas/polyps (SSAs) are difficult
to detect by standard white light colonoscopy. We aimed to determine the frequency of finding SSAs during surveillance colonoscopy in IBD and to define the
characteristics and endoscopic findings of SSAs developed in a background of
IBD.
AIMS & METHODS: Biopsies from a cohort of 87 patients (male 43, female 44,
median age 53, range 23-82 years), with long-standing (8 years or more median
duration of the disease 13 years) colonic IBD (UC 42, CD 42, IC 3) undergoing surveillance colonoscopy were reviewed. The lesions of dysplasia (ALM or
DALM), SSAs, adenoma-like polyps (ALPs), hyperplastic polyps (HPs), and
inflammatory polyps (IPs) were identified. Detection procedures were as follows:- Twenty five were assessed by high definition colonoscopy, Thirty four
by high definition iscan virtual chromoendoscopy and 28 patient by high definition dye chromoendoscopy with methylene blue 0.1%.(Pentax EC-3490Fi;
Pentax, Tokyo, Japan).
RESULTS: 14 SSAs were detected (16%). Two in the HD group (8%), seven in
the HD-iScan virtual chromoendoscopy group (21%) and 5 in the HD dye
chromoendoscoy with methylene blue (18%). These were predominantly in
younger patients. The endoscopic characteristics of SSAs were: flat lesion predominantly localized in the right colon (11 in the cecum and ascending colon and
3 in the sigmoid colon), more than 45 mm in size, cloudy cover, Kudo pit
pattern modified type IIO and irregular spiral vascular pattern. In comparison,
10 ALPs (11 %) were detected 2 in HD group (8%), 3 in iScan-HD group (9%)
and 5 in HD dye chromoendoscopy group (18%). Only 1 patient had a DALM
lesion.
CONCLUSION: 16% of patients had sessile serrated adenomas detected at
surveillance colonoscopy in longstanding IBD patients. This detection rate of
SSAs was more than ALPs. SSAs can be detected more frequently by HDiScan virtual chromoendoscopy and by dye chromoendoscopy than by HD endoscopy alone. Sessile serrated adenoma is a common finding at surveillance colonoscopy for IBD and may be missed if electronic virtual chromoendoscopy or
dye chromoendoscopy are not used.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
LIVER & BILIARY III POSTER EXHIBITION HALL XL_____________________
P1154 DOES LEPTIN PROFILE MODULATE OXIDATIVE STRESS AND
DISEASE SEVERITY IN NON-ALCOHOLIC FATTY LIVER DISEASE
B. Canbakan1,*, H. Senturk2, M. Tuncer1, I. Hatemi1, E. Koroglu1, K. Atay1,
A. Sonsuz1, N. Kepil3
1
Gastroenterology, Istanbul University Cerrahpasa Medical Faculty,
2
Gastroenterology, Bezmialem University, 3Pathology, Istanbul University
Cerrahpasa Medical Faculty, Istanbul, Turkey
Contact E-mail Address: billurcanbakan@yahoo.com
INTRODUCTION: Upregulated oxidative stress is recognized as important
mechanism contributing to inflammation and fibrogenesis of the liver in nonalcoholic fatty liver disease (NAFLD). Leptin promotes oxidative stress and the
fibrogenesis in the liver. Therefore, we aimed to evaluate the association between
leptin levels, oxidative stress parameters and histopathological findings in
NAFLD subjects.
AIMS & METHODS: Fifty-eight non-drinker patients with biopsy-proven diagnosis of NAFLD were studied (M/F: 31/ 27 mean age 47.4 6.3 years).
Histopathological examination was done using the system described by Brunt
et al. For the determination of oxidative stress parameters malondialdehyde
(MDA), and superoxide dismutase (SOD) activities were measured in serum
and as well as in tissue specimens. Glutathione (GH) was measured in tissue

United European Gastroenterology Journal 2(1S)


homogenates. Nitric oxide (NO) and TNF-alpha receptor (TNF-sRp55) levels
were measured in serum. Serum leptin levels were measured by radioimmunoassay. Statistical analysis was done using chi-squared test, Students t-test, MannWhitney test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve. Comparison between the patients with nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) were
performed using Students t test. Multivariate regression analysis and ROC
curve were used to identify the independent predictors for NASH. All statistical
analyses were performed using SPSS statistical software program (Ver.10.0).
RESULTS: In bivariate analysis serum leptin levels didnt show any significant
correlation with steatosis grade, necroinflammatory grade and stage. Serum
leptin levels were neither significantly correlated with serum NO, SOD and
MDA levels nor with tissue SOD, MDA and GH levels. The increases in
TNF-sRp 55 levels correlated inversely with serum leptin levels (r - 0.03,
p 0.04). Patients with NASH had significantly higher serum NO and tissue
MDA and GH levels (p 0.03, 0.04, 0.042, respectively). Using serum leptin
levels the ROC curve for distinguishing between NASH and NAFL didnt
show any respective sensitivity and specificity (AUROC 0.48). In linear regression analysis serum NO ( 0.21, p 0.018), tissue MDA ( 0.06, p 0.01),
and stage ( 2.6, p 0.01) were independently associated with increased leptin
levels. In multivariate regression analysis increase of tissue MDA (OR:1.8; %95
CI:1.04-4.25, p 0.04) and serum NO levels (OR:1.9; %95 CI:1.02-4.6, p 0.04)
were risk factors for NASH and increase of leptin activity had preventive effect
against NASH (OR:0.052; %95 CI:0.004-0.72, p 0.04).
CONCLUSION: Serum leptin levels did not show any significant correlations
between oxidative stress parameters and overall histological severity. Patients
with NASH had enhanced oxidative stress. In patients with NASH oxidative
stress parameters and stage were independently associated with increased leptin
levels with a preventive effect against NASH.
These data indicate that leptin may have preventive effect against oxidative stress
and progression of hepatic injury in NAFLD.
Disclosure of Interest: None declared
P1155 ROLE OF LEPTIN AND INSULIN RESISTANCE IN THE DISEASE
SEVERITY AND HEPATOCYTE APOPTOSIS IN NON-ALCOHOLIC
FATTY LIVER DISEASE
B. Canbakan1,*, H. Senturk2, M. Tuncer1, I. Hatemi1, E. Koroglu1, K. Atay1,
A. Sonsuz1, N. Kepil3
1
Gastroenterology, Istanbul University Cerrahpasa Medical Faculty,
2
Gastroenterology, Bezmialem University, 3Pathology, Istanbul University
Cerrahpasa Medical Faculty, Istanbul, Turkey
INTRODUCTION: Apoptosis and insulin resistance (IR) are major contributors
in the pathogenesis and the disease severity of non-alcoholic fatty liver disease
(NAFLD). Leptin plays a key role in insulin sensitivity. We aimed to evaluate
whether serum leptin levels correlate with IR, apoptosis parameters and histopathological disease severity in NAFLD subjects with and without IR.
AIMS & METHODS: Sixty non-drinker patients with biopsy-proven diagnosis
of NAFLD were studied (M/F:32/ 28; mean age 47.510.2 years). Thirty-six
NAFLD patients with IR were compared with 24 subjects without IR. Insulin
resistance index (HOMA IR) was calculated using the homeostasis model assessment method. Histopathological examination was done using the system
described by Brunt et al. Serum leptin levels were measured by radioimmunoassay. For apoptotic activity immunohistochemistry was performed for caspase-3
and 8, transcription nuclear factor kB (NF-kB), and antiapoptotic Bcl-2 protein.
Tumor necrosis factor receptor (TNF-sRp55) level was measured in serum.
Statistical analysis was done using chi-squared test, Students t-test, MannWhitney test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve. P-values 5 0.05 were considered statistically
significant. All statistical analyses were performed using SPSS statistical software program (Ver.10.0).
RESULTS: HOMA-IR index correlated positively with the necroinflammatory
grade, the stage, caspase-3 and 8 levels (p 0.02, 0.002, 0.04, 0.021, respectively).
The ROC curves revealed statistically significant discriminative power of
HOMA-IR index for necroinflammatory grade,stage and non-alcoholic steatohepatitis (NASH) (AUROC 0.7, 0.66, 0.65, respectively). Patients with IR had
significantly higher steatosis grade, necroinflammatory grade, stage, caspase-3,
caspase-8, TNF-sRp55, and serum leptin levels than those without IR.
In bivariate analysis serum leptin levels didnt show any significant correlation
with fasting insulin, serum glucose, HOMA-IR index, steatosis grade, necroinflammatory grade and stage. Using serum leptin levels the ROC curve for distinguishing between NASH and simple steatosis didnt show any respective
sensitivity and specificity (AUROC 0.4). In linear regression analysis caspase3 ( 0.11, p 0.002), caspase-8 ( 0.04, p 0.02), and stage ( 3.2,
p 0.002) were independently associated with increased leptin levels In multivariate regression analysis caspase-3 (OR:2.2; %95 CI:1.06-5.26, p 0.042) and
caspase-8 levels (OR:2.3; %95 CI:1.06-5.72, p 0.048) were risk factors for
NASH and increase of leptin activity had preventive effect against NASH
(OR:0.06; %95 CI:0.002-0.86, p 0.043).
CONCLUSION: Insulin resistance in NAFLD is associated with enhanced hepatocyte apoptosis and histopathological disease severity. In patients with IR fibrosis severity and apoptosis parameters were independently associated with high
leptin levels and increase of leptin activity showed preventive effect against
NASH.
Our findings show that NAFLD patients with IR may have increased risk for
disease progression and leptin has preventive effect against apoptosis and liver
fibrosis.
Disclosure of Interest: None declared

A449

United European Gastroenterology Journal 2(1S)


P1156 LONG-TERM OBSERVATION OF WILSON DISEASE PATIENTS
EXPERIENCE OF A SINGLE CENTER
D. Gancheva1,*, I. Kotzev1, M. Kaneva2, A. Kaprelyan3, M. Grudkova3
1
Gastroenterology, Hepatology and Nutrition, University Hospital "St. Marina" Varna, 2Department of Statistics, University of Economics of Varna, 3Department
of Neurology, University Hospital "St. Marina" - Varna, Varna, Bulgaria
Contact E-mail Address: gancheva_vn@abv.bg
INTRODUCTION: Wilson disease (WD) is an inherited copper metabolism
disorder. If the patient remains undiagnosed and untreated, disease outcome
may be fatal. Lifelong therapy provides normal WD patients survival.
AIMS & METHODS: Aim: To evaluate the clinical course and long-term outcome of WD patients.
Material and methods: Sixty-five WD patients (22 females and 43 males) at a
mean age of 37 years (range, 18-65 years) were analysed from January, 2003 to
December, 2013. Survival analysis by Kaplan-Meier method and Logit model
were used.
RESULTS: Twenty-eight patients (43.08%) were with liver disease alone, thirtytwo (49.23%) - with hepatic and neurological presentation, three - with neurological features without any signs of a liver injury. There were two asymptomatic
patients, too. The following hepatic forms were proved: steatosis (in 6.6%),
hepatitis (in 41.7%), and cirrhosis (in 51.7% of the patients). There was a
mean delay of diagnosis of 39 months. At the end of the study, 74.2% of cirrhotic
patients were in Child A stage. Two patients developed acute liver failure after
treatment discontinuation. We observed a hepatocellular carcinoma in one cirrhotic patient. Six patients with liver cirrhosis of Child C stage had fatal outcome
during the observation. Three of them were with concurrent diseases HBV and
autoimmune cirrhosis. Kayser-Fleischer ring was detected in 35.4% of the
patients being more common in those presenting with neurological symptoms.
The cumulative survival rate of people with WD after first onset of symptoms
was up to 76.38% at the end of 15th year, and that after diagnosis - 77.29%. It
was estimated the impact of the lag in the diagnosis of WD on overall survival.
At each year delay in the diagnosis the probability of death was increased by
approximately 10%. There was a beneficial effect of D-penicillamine (D-p) treatment in almost all the patients. There were no complications during the pregnancies, with stable disease and normal birth.
CONCLUSION: Our observation showed a delayed diagnosis of WD. In most
patients, the course of the disease was stable or even improved during the treatment. Mortality rate increased in the patients with cirrhosis. There was a favourable response after long-term treatment with D-p as first-line therapy in WD.
Disclosure of Interest: None declared
P1157 NON-INVASIVE PARAMETERS OF NASH AND LIVER FIBROSIS
IN DAILY PRACTICE
K. Dvorak1,*, J. Stritesky2, L. Vitek3, R. Sroubkova4, J. Petrtyl4, M. Lenicek3,
V. Smid4, R. Bruha4
1
4TH DEPARTMENT OF MEDICINE, GENERAL UNIVERSITY
HOSPITAL AND 1ST MEDICAL FACULTY CHARLES UNIVERSITY IN
PRAGUE, Prague 2, 2INSTITUTE OF PATHOLOGY, 3INSTITUTE OF
MEDICAL BIOCHEMISTRY AND LABORATORY DIAGNOSTICS, 1ST
MEDICAL FACULTY, CHARLES UNIVERSITY IN PRAGUE, 44TH
DEPARTMENT OF MEDICINE, GENERAL UNIVERSITY HOSPITAL
AND 1ST MEDICAL FACULTY CHARLES UNIVERSITY IN PRAGUE,
PRAGUE, Czech Republic
Contact E-mail Address: k2dvorak@gmail.com
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Risk of progression to cirrhosis is related to
inflammatory reaction (NASH) and fibrosis. Despite all its limitations liver
biopsy is still the gold standard in distinguishing NASH and staging of fibrosis,
but non-invasive approaches are emerging.
AIMS & METHODS: The aim was to evaluate the usefulness of non-invasive
laboratory parameters for detection of NASH and fibrosis in patients with
NAFLD in routine clinical practice. Liver biopsy was performed in 56 patients
with NAFLD (mean age 48.9  15 years) and Kleiner score was used for histological staging and grading. Non-invasive parameters of fibrosis (hyaluronic
acid, OELF, AST/ALT, BARD, APRI, NAFLD fibrosis score) and inflammation (M30 and M65 cytokeratin 18 fragments) were measured and calculated.
The same parameters were applied to a group of other 56 patients not indicated
to biopsy. 14 healthy individuals formed a control group.
RESULTS: NASH was bioptically diagnosed in 38 patients, simple steatosis in
18 patients. F0-F2 fibrosis was present in 39 patients; F3-F4 in 17 patients.
Serum concentration of hyaluronic acid was significantly higher in patients
with advanced fibrosis (p=0.01), cut-off value 25 mg/l discriminated patients
with F3-4 with 90% sensitivity and 84% specificity from those with F0-F2
(AUROC 0.94). AUROC for OELF score was 0.97; other parameters did not
reach statistical significance. Serum concentrations of M30 a M65 in patients
with NASH differed from subjects without NASH (p=0.01). Examination of
M65 discriminated patients with NASH with 80% sensitivity and 82% specificity
(AUROC 0.89). Interestingly, when these non-invasive criteria were applied to a
group of patients without biopsy, NASH would be diagnosed only in 15%, but
the advanced fibrosis in 35% of them.
CONCLUSION: Non-invasive serum parameters in patients with NAFLD can
differ with high accuracy those with steatohepatitis and advanced fibrosis.
Among the patients not indicated for liver biopsy in the routine praxis a substantial part may have advanced fibrosis.
Supported by IGA MZ CR NT 12290/4, NT 11247/4 and SVV 260032-2014.
Disclosure of Interest: None declared

P1158 ISOFLAVONES SUPPLEMENTATION ATTENUATES


PROGRESSION OF NON-ALCOHOLIC FATTY LIVER DISEASE
VIA THE DECREASE IN OXIDATIVE STRESS-MODIFIED
PROTEINS

THE

K. Katada1,*, Y. Naito1, T. Oya-Ito1, M. Morita1, K. Mizushima1,


Y. Higashimura1, S. Wada2, Y. Kobayashi2, T. Okayama1, N. Yoshida1,
K. Kamada1, K. Uchiyama1, Y. Sumida1, T. Ishikawa1, O. Handa1, T. Takagi1,
H. Konishi1, T. Yoshikawa1, Y. Itoh1
1
KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, 2Kyoto Prefectural
University, Kyoto, Japan
Contact E-mail Address: katada@koto.kpu-m.ac.jp
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), a phenotype of
metabolic syndrome in liver, is generally believed as a high-risk group in arteriosclerotic disease and type 2 diabetes. The progression of NAFLD is associated
with oxidative stress; however, the proper treatment of NAFLD remains to be
established. Recent studies have suggested that isoflavones have beneficial effects
on metabolic syndrome-related disorders. Here we assessed the effects and
mechanisms of isoflavones in Western diet (WD)-induced mice and NAFLD
patients.
AIMS & METHODS: C57BL/6J mice were fed for 8 weeks on AIN93G (control)
or WD (high in fat, cholesterol and sucrose) with or without 0.05% isoflavones
(daidzein derivatives 50%, genistein derivatives 10%, and glycitein derivatives
40%). For human trial, nutrition survey was performed for 20 NAFLD patients
and 20 healthy subjects. 25 mg of isoflavone aglycons were orally taken to 10
NAFLD patients for 28 days to evaluate blood tests and parameters related to
oxidative stress.
RESULTS: The increases in ALT, blood glucose, liver fat accumulation and
triglyceride in liver of WD-fed mice were improved by isoflavones treatment.
The expression of hepatic genes related to steatosis, such as acetyl-coA carboxylase and peroxisome proliferator-activated receptor gamma, were also normalized by isoflavones. Further, isoflavones supplementation showed a tendency to
improvement in the increases in oxidative stress (4-hydroxy-2-nonenal (HNE)modified proteins) and glycation (methylglyoxal (MG)-modified proteins) in
WD-fed mice. Nutrition survey showed that presumed oral intakes of daidzein
and genistein in NAFLD patients were significantly lower compared to those in
healthy subjects. Diet intervention trial indicated that isoflavones supplementation significantly reduced body weight and ALT as well as 7-ketocholesterol (7KC) and hexanoyl-lysin (HEL)-modificed proteins in plasma.
CONCLUSION: Isoflavones supplementation attenuated liver function, and
decreased oxidative stress or glycation in WD-fed mice and NAFLD patients.
Further examinations are required due to low number of cases; however, isoflavones supplementation may be a treatment option for NAFLD.
Disclosure of Interest: None declared
P1159 NONINVASIVE DIAGNOSTIC OF NONALCOHOLIC FATTY
LIVER DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
K. Aksentiychuk1,*, E. Sklyarov1, A. Bochar1
1
Therapy #1 and Medical Diagnostics, Lviv National Medical University by
Danylo Galytskyi, Lviv, Ukraine
INTRODUCTION: It is known that in 72% of patients with type 2 diabetes
mellitus diagnosed NAFLD. Patients with NAFLD are usually asymptomatic,
high values of liver enzyme tests being the most common finding. The definitive
diagnosis of NAFLD is based of liver biopsies. Although liver biopsy is the
current gold standart for diagnosis of NAFLD, it is not a practical screening
tool given the cost, time-consuming nature and potential mortality of this procedure. However, more attention is attracted to early diagnosis NAFLD by using
a special set of design formulas biochemical parameters, data Fibroscan or
respiratory tests with 13C-methacethine (C13-MBT)
AIMS & METHODS: A comparative analysis of methods for diagnostics of
clinical forms NAFLD using specially developed formulas 13C-methacethine
breathe test (MBT), biochemical parameters.
The study involved 131 patients with type 2 diabetes mellitus (DM) (male 48,
female 83, aged 43 to 82 years, mean age 60.94  0.82 years). Control group, 106
patients without diabetes, men 47, women 59, aged 35 to 69 years (mean age
60.26  1.27). Biochemical tests were performed: total bilirubin (TB), AST, ALT,
AST / ALT, GGTP, lipidogram, carried ultrasonographic examination, the calculation formulas of Angulo, Forns, Fib-4, Apri. Defining the antitoxic function
of the liver by 13C- MBT.
RESULTS: Total cholesterol (TC) (p 0.00127), HDL (p 0.0001), triglycerides
(p 0.0001), AST / ALT (p 0.09594) were reliable indicators between the main
and control groups. Among the patients of the main group were detected 91
patients with NAFLD, control -32. There were higher TB, AST, ALT and
AST / ALT levels among patients with NAFLD, none of the indicators does
not exceed the upper limit of normal. Formula Forns correlated with the clinical
form NAFLD. Marked strong negative relationship between the Forns and ALT
levels (r -0.944) and TB (r -0.967) with fibrosis, and TC (r -0.805) and LDL
(r -0.846) with steatosis. 13C-MBT was conducted on 32 patients. In patients
with steatosis and steatohepatitis, index MDT replied a moderate decrease liver
(10-20%), marked reduction with fibrosis (510%). A strong negative correlation
was noticed between LDL (r -0.878) and TG (r -0.933) and MBT in fibrosis.
CONCLUSION: In the resulting formula Forns over 4.25, 13C-MBT least 10%,
lower levels of ALT but TB, and TC more than 2.6 mmol / L, triglycerides more
than 2.6 mmol / l - high probability of fibrotisis. The result of the Forns least
4.25, 13C-MBT between 10-20% TC more 5.2 mmol / l and LDL more than 2.6
mmol / L indicates liver steatosis.
Disclosure of Interest: None declared

A450
P1160 SOMATOSTATIN ANALOGUES IMPROVE HEALTH RELATED
QUALITY OF LIFE IN POLYCYSTIC LIVER DISEASE
M. Neijenhuis1,*, T.J. Gevers1, W. Kievit2, F. Nevens3, M.C. Hogan4,
V.E. Torres4, J.P. Drenth1
1
Department of Gastroenterology and Hepatology, 2Department of Health
Evidence, Radboud University Medical center, Nijmegen, Netherlands,
3
Department of Gastroenterology and Hepatology, University Hospital Leuven,
Leuven, Belgium, 4Division of Nephrology and Hypertension, Department of
Internal Medicine, Mayo clinic, Rochester, Minnesota, United States
Contact E-mail Address: myrte.neijenhuis@radboudumc.nl
INTRODUCTION: Polycystic liver disease (PLD) is characterized by progressive hepatomegaly resulting from liver cysts and is associated with an impaired
physical dimension of Health Related Quality of Life (HRQL). Somatostatin
analogues reduce hepatomegaly in PLD.
AIMS & METHODS: We pooled data of two randomized placebo controlled
trials (NCT00565097/NCT00426153) that evaluated HRQL with the short-form
Health survey (SF-36) in 96 PLD patients treated 6-12 months with somatostatin
analogues or placebo. SF-36 contains a summarizing physical component score
(PCS) and was administered at baseline and end of treatment. We used multiple
linear regression analysis with correction for trial (random effect) and baseline
PCS (fixed effect) to delineate the effect of somatostatin analogues. As a secondary analysis, we determined the effect of severe hepatomegaly (475th percentile),
delta liver volume, underlying disease, gender, age and occurrence of adverse
events on PCS change independent of treatment. Results are given as estimated
mean score  standard error. The PCS is standardized to the healthy population
with a score of 50 points.
RESULTS: We included 87 patients (89% female, mean age 48 yrs) with a baseline PCS of 44.32 points and median liver volume of 4504 mL. PCS improved
with somatostatin analogues, but remained unchanged with placebo (3.41  1.29
vs. -0.71  1.54, p50.05). Severe hepatomegaly and adverse events significantly
contributed to PCS decrease, while delta liver volume, gender, age and underlying diagnosis did not impact PCS.
CONCLUSION: Somatostatin analogues improve the physical dimension of
HRQL in polycystic liver disease patients after 6-12 months of treatment.
Besides treatment, severe hepatomegaly is independently associated with a
decline in HRQL during follow up.
Disclosure of Interest: None declared
P1161 FEATURES OF UPPER GASTROINTESTINAL ABNORMALITIES
IN NON-ALCOHOLIC STEATOHEPATITIS (NASH) PATIENTS
S. Yamamoto1,*, M. Komori1, M. Nishiyama1, M. Fukuoka1, S. Kudo1,
K. Maesaka1, K. Shirai1, S.-Y. Kimura1, T. Okahara1, Y. Okuda1,
M. Konoshita1, M. Hirao1, A. Hosui1, H. Yoshihara1
1
Gastroenterology, Osaka Rosai Hospital, Sakai, Japan
Contact E-mail Address: shun0515suke@gmail.com
INTRODUCTION: Non-alcoholic steatohepatitis (NASH), hepatic manifestation of metabolic syndrome has been considered the most common liver disease
today. NASH patients are reported to have higher incidence of colon polyps,
however, features of their upper gastrointestinal findings have not been reported.
AIMS & METHODS: The aim of this study is to clarify the upper gastrointestinal abnormalities of NASH patients by comparing with those of health check
subjects.
This is a retrospective study. We diagnosed 94 patients as NASH in our hospital
from March 1998 to July 2012. 1) Among them, 36 who underwent esophagogastroduodenoscopy (EGD) were enrolled in this study. 2) From 118 subjects
who underwent health-check at our hospital from January 2012 to September
2012, 73 were selected as healthy control (group) excluding those with obesity
(body mass index; BMI425), hepatic dysfunction, fatty liver, and diabetes, and
3) 14 obese subjects without hepatic dysfunction were selected as obesity group.
Following findings in EGD were compared among 3 groups; esophageal hernia,
reflux esophagitis, Barretts esophagus, atrophic gastritis, superficial gastritis,
erosive gastritis, gastric ulcer including scar, and gastric polyp.
RESULTS: Age, sex, and BMI of NASH/health/obesity groups were 65  12/ 64
 14/ 65  12 (mean  SD); 22, 14/ 35, 38/ 10, 4 (male, female); 26.6  3.8/ 21.6
 1.8/ 26.2  1.0, respectively. Age was comparable among three groups. BMI of
NASH and obesity group was significantly higher than that of healthy group
(p50.0001), while that of NASH and obesity was not different. Among NASH
group, 6 (17%) were cirrhosis. Esophageal hernia and reflux esophagitis were
significantly more observed in NASH group than in healthy group (77.8/50.7%
and 50/26%, p 0.01/0.01), while prevalence of these findings were not different
between healthy and obesity group. Prevalence of Barretts esophagus, atrophic
gastritis, superficial gastritis, gastric ulcer, and gastric polyp showed no significant difference among three groups. Prevalence of erosive gastritis in NASH
patients was significantly higher than that in healthy group (44%, 16/36; 12%,
9/73; p 0.0002), while no significant difference of this finding was observed
between NASH and obesity group. Only in NASH group, portal hypertensive
gastropathy and esophageal varices were found in 2 cirrhotic patients.
CONCLUSION: NASH patients have higher risk of esophageal hernia and
reflux esophagitis than healthy subjects.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1162 HYPERHOMOCYSTEINEMIA AS A PREDICTOR OF THE
DEVELOPMENT AND PROGRESSION OF NONALCOHOLIC
FATTY LIVER DISEASE
S. V. Glushchenko1,*, T.D. Zvyagintseva1
Gasrtoenterology, Kharkov Medical Academy of Postgraduate Education,
Kharkov, Ukraine
Contact E-mail Address: stadias@mail.ru
1

INTRODUCTION: Studied the influence of the pathogenetic mechanisms of


hyperhomocysteinemia on the formation and progression of nonalcoholic fatty
liver disease (NAFLD) by inducing oxidative stress. It is shown knots in the
degree of hyperhomocysteinemia depending on the stage of the disease.
AIMS & METHODS: Examine the degree of hyperhomocysteinemia (HHcy) in
patients with non-alcoholic steatosis and steatohepatitis (NASH). Determine the
correlation between homocysteine serum level and indicators of oxidative stress
(nitric oxide (NO) and TBA-active metabolites in blood plasma). We observed 65
patients with NAFLD. The first group included 33 patients with hepatic steatosis. In the second group there were 32 patients with NASH.
RESULTS: HHcy degree increases with disease severity: normal levels of homocysteine (Hcy) were reported in 6 patients (18.2%) in the first group (12.44  1.6
mol/L), while in the second group, only 2 patients (6, 2%) patients (12.96 
0.74 mol/L). Mild degree HHcy was detected in 13 (39.4%) and 8 (25%)
patients in the first (21.65  3.93 mol/L) and the second group (20.03  3.24
mol/L) respectively. HHcy moderate detected in 14 (42.4%) patients in the first
group (42.19  16.96 mol/L) and 18 (56.3%) in the second (62.88  22.24
mol/L). Heavy HHcy occurred in 4 (12.5%) patients in the second group
(113.22  14.96 mol/L), while the first group of patients had no evidence of
violations. Significant correlation between the level of Hcy and NO: the first
group - r 0.79; p 50.05; second group - r 0.89; p 50.05.
CONCLUSION: Our results show that the degree of HHcy increases with the
severity of NAFLD. There are positive correlations between the Hcy and indicators of oxidative stress in patients with NAFLD.
REFERENCES
1. Kimura Y, Goto Y and Kimura YH. Hydrogen sulfide increases glutathione
production and suppresses oxidative stress in mitochondria. Antioxid Redox
Signal 2010; 12: 1-13.
2. McCully KS. Homocystcine, vitamins, and vascular disease prevention. Am J
Clio Nutr 2007; 86: 1563-1568.
3. Hwang SY, Sarna LK, Siow YL, et al. High-fat diet stimulates hepatic
cystathionine -synthase and cystathionine -lyase expression. Can J Physiol
Pharmacol 2013; 91: 913-919.
Disclosure of Interest: None declared

n
w
a
r
d
h
t
i
W

P1163 LIVER SPECIFIC SERUM MICRO RNA122 AS A PROGNOSTIC


MARKER IN PATIENTS WITH LIVER CIRRHOSIS
M.A. Amin1, D.A. F. Sabri2, H. Sedrak1, A. Al-Saadi1,*
1
internal medicine, 2medical biochemistry, Cairo University, Cairo, Egypt
Contact E-mail Address: monasleman@hotmail.com
INTRODUCTION: Recent research has shown that miRs are emerging as
important regulators of cellular differentiation and undifferentiation. The miR122 accounts for approximately 70% of all miRs in the liver, whereas other
organs express much lower amounts of this miRs. And due to almost exclusive
expression of miR-122 in the liver the presence of it in the serum is highly
indicative of liver processes.
AIMS & METHODS: was to study the role of miR-122 as a prognostic new
marker in patients with liver cirrhosis. MiR-122 that was detected by quantitative
real-time reverse transcription (RT)-PCR technique. Eighty patients with liver
cirrhosis were included in our study, we divided them into 4 equal groups according to the complications of liver cirrhosis (1-compensated cirrhotics, 2- ascites, 3spontanious bacterial peritonitis SBP, and 4- hepatorenal syndrome HRS group)
to evaluate if the serum level of miR-122 might be a suitable parameter for
disease severity and prognosis in such patients.
RESULTS: miR-122 was statistically significantly higher in group 1 "compensated" compared to both groups 2 "ascites" and 3 "SBP" (p 0.001), while the
difference was highly significant when compared to its level in group 4 HRS
(P50.001). Serum miR-122 levels were positively correlated with serum albumin,
PC, and serum Na levels while it was negatively correlated with creatinine, urea,
and INR. Also there was strong negative correlation between serum miR-122
level and MELD score (p 0.001), and very strong negative correlation between
serum miR-122 level and Child score (p 50.001).
CONCLUSION: Lower serum miR-122 levels are associated with ascites, spontaneous bacterial peritonitis and hepatorenal syndrome. Therefore, serum miR122 could be a new potential parameter for liver function and a prognostic
parameter in patients with liver cirrhosis.
Disclosure of Interest: None declared

A451

United European Gastroenterology Journal 2(1S)


P1164 THE NEUTROPHIL CAUGHT BETWEEN CIRRHOSIS, GUT
PERMEABILITY AND VIRAL HEPATITIS C
A. Horvath1,*, B. Leber2, W. Spidelboeck1, P. Stiegler2, R. Stauber1, S. Lemesch1,
P. Douschan1, F. Durchschein1, P. Fickert1, E. Krones1, G. Zollner1,
V. Stadlbauer1
1
Department of Gastroenterology and Hepatology, 2Department of
Transplantation Research, Medical University Graz, Graz, Austria
Contact E-mail Address: angela.horvath@medunigraz.at
INTRODUCTION: Cirrhosis has been linked to high risk for infection and
dysfunctional neutrophil granulocytes have been proposed to be one of the reasons for this ineffective immune response. However, contradictory reports have
emerged regarding the nature and direction of their dysfunction, leaving the
pathophysiological mechanism and underlying causes yet to be discovered.
AIMS & METHODS: Therefore we aimed to explore neutrophil granulocytes in
cirrhosis as well as the role of aetiology, opsonisation, gut permeability and
underlying diseases in neutrophil functionality.
Neutrophil function (oxidative burst, phagocytic and opsonisational capacity),
gut permeability and hepatitis C virus infection (HCV) parameters of 98 liver
cirrhosis patients of different aetiologies (56 alcoholic, 20 HCV, 22 other) and 72
controls (33 healthy, 39 HCV infected without cirrhosis) were analysed.
Neutrophil function was assessed by flow cytometry, gut permeability by high
performance liquid chromatography (differential sugar absorption) or ELISA
(diamine oxidase, soluble cluster of differentiation 14) and HCV parameters by
routine methods.
RESULTS: Compared to healthy control values, phagocytic capacity
(Phagoindex, PI) is decreased in patients with HCV induced cirrhosis (0.7fold), not significantly influenced in alcoholic cirrhosis (1.1-fold), and increased
in cirrhosis of non-viral/non-alcoholic aetiologies (1.5-fold). In addition, the
amount of neutrophils without measurable phagocytosis shows a significant
increase in HCV induced cirrhosis but is not as prominent in alcoholic and
other cirrhosis (5.0-, 1.9- and 1.2-fold, respectively). The progression from
Childs A to B cirrhosis decreases PI approximately 30% regardless of the aetiology. Furthermore, alcoholic cirrhosis is accompanied by high amounts of primed
neutrophils in the bloodstream, and HCV induced cirrhosis results in impaired
production of reactive oxygen species after bacterial stimulation. However, opsonisation is sufficient in all cirrhosis groups and shows no differences compared to
controls. Gut permeability is elevated in all aetiologies, most pronounced in
alcoholic cirrhosis which shows a significant increase in every marker. High
permeability is associated with neutrophil dysfunction but explains only partially
the observed alterations. In HCV induced cirrhosis a part of the phagocytic
dysfunction originates from HCV infection itself. Before the onset of cirrhosis
and with normal gut permeability, HCV infected controls already display a 2.5fold increase in neutrophils without phagocytosis and a slight non-significant
decrease in PI, compared to healthy controls.
CONCLUSION: Aetiology, gut permeability and HCV infection impact strongly
and diversely on neutrophil function in cirrhosis. Still, causal links between
already published and well established explanations need to be explored.
Disclosure of Interest: None declared
P1165 INCREASING PREVALENCE OF MULTIDRUG-RESISTANT
INFECTIONS IN PATIENTS WITH CIRRHOSIS
K. Klimova1, C. Padilla Suarez1,*, A. Matilla Pena1, G. Clemente Ricote1,
R. Banares Canizares1
1
Gastroenterology and Hepatology, Hospital General Universitario Gregorio
Maranon, Madrid, Spain
INTRODUCTION: Bacterial infections are an important complication of liver
cirrhosis. Moreover, they represent a common motive of its descompensation,
hospitalization and health-care related costs. Recently, infections caused by
gram-positive and multidrug-resistant bacteria have become more frequent,
with a significant impact on patients morbidity and mortality.
AIMS & METHODS: Aim: To asses the rate of infections caused by multidrugresistant bacteria in hospitalized patients with liver cirrhosis. The most frequent
infections (pneumonia, urinary tract infection, SBP, bacteriemia) were included.
Methods: We evaluated 277 cirrhotic patients admitted to our center between
Junuary 2012 and July 2013 due to a bacterial infection.
RESULTS: 340 infections were evaluated in 277 patients. Their mean age was
64.6 years (range 31 - 91). The etiology of the cirrhosis was: due to alcohol abuse
(50%), hepatitis C infection (43.3%), hepatitis B infection (14%). 56 (20.2%)
patients had hepatocellular carcinoma, 61 (22%) chronic renal insufficiency, 96
(34.7%) were diabetic and 127 (45.8%) were on beta blockers. The mean MELD
on admission was of 14.6, and Child-Pugh score of 7.8 points.
The most frequent infections were UTI in 155 patients (56%), followed by SBP in
84 patients (30%), pneumonia (70%) and bacteriemia in 54 (19.5%). The infections were community-adquired in 104 patients (37%), health-care related in 120
(43%) and nosocomial in 83 (30%). We obtained microbiological isolation in 187
of the 277 patients, 73 of those had 2 or more different bacterial isolations, i.e. in
total 290 isolations, 39.8% by gram positive bacteria and 60.2% gram negative
bacteria, being E. coli the most frequent one. 42 (15%) of the bacteria were multidrug resistant, 32 BLEEs and 10 MRSA, and in 10 Enterobacteriaceae, Amp C
betalactamase was identified. Risk factors for a multiresistant infection were:
hospital admission and use of antibiotics during previous 90 days.
Global mortality rate during the episode was of 15.2 % (15 patients), with
accumulated mortality of 30% during the following 6 months. In the univariate
analysis, the factors associated to mortality were: acute renal insufficiency,
microbiological isolation in control bacterial cultures, sepsis or septic shock,
and diagnosis of pneumonia. The independent risk factors were: acute renal

insufficiency (p: 0.022, OR 1.73 IC95: 1.15 2.58), and isolations in control
cultures (p: 0.002, OR 1.98 IC95: 1.3 3.25).
As for the antibiotics, the third-generation cephalosporines remained the treatment of choice in 45.5% of patients, followed by carbapenems (23.8%). 54.5% of
patients requiered the use of more than one antibiotic, mainly carbapenems or
vancomycine.
CONCLUSION: In our group of cirrhotic patients with bacterial infections a
relatively high rate of multidrug resistant infections were observed, especially as
far as BGN are concerned. Treatment with broad-spectrum antibiotics is recommendable in high-risk group of patients.
REFERENCES
Fernandez J and Arroyo V. Bacterial infections in cirrhosis: A growing problem
with significant implications. Clin Liver Dis 2013; 2: 102-105.
Disclosure of Interest: None declared
P1166 COMPARISON OF THE LIMON SYSTEM TO ICG-CLEARANCE
MEASUREMENT BY HPLC
P. Deibert1,*, K. Unteregger1, D. Konig1, R. Greinwald2, P. Thomann3,
W. Kreisel4
1
Exercise medicine and Sports, University hospital, 2Dr. Falk Pharma, 3KinetiCon
GmbH, 4Hepatology, Gastroenterology, Endocrinology and Infectious Diseases,
University hospital, Freiburg, Germany
Contact E-mail Address: peter.deibert@uniklinik-freiburg.de
INTRODUCTION: Indocyanine green (ICG) elimination is a test to evaluate
hepatic function in patients with liver disease and to quantify liver perfusion.
Conventional ICG clearance is dertermined by measuring the rate of elimination
of the synthetic dye using several venous samples after its intravenous administration. With the new infrared-based transcutaneous pulse spectrophotometry
(LIMONTM) a plasma disappearance rate (PDR) and a calculated remaining
concentration after 15 minutes (R15) are provided. Several studies have suggested that the LIMONTM system is able to measure ICG-concentration accurately, however a direct comparison to conventional ICG clearance
measurements in patients with liver cirrhosis has not been performed yet.
AIMS & METHODS: In a randomized controlled double-blind study to test the
effect of Udenafil, a new phosphodiesterase-5-inhibitor, in patients with liver
cirrhosis a conventional ICG clearance measurement as well as a determination
by the LIMONTM system was performed. Included patients had a proven compensated liver cirrhosis. After enrolment, two visits to evaluate hemodynamics
and ICG kinetics before and after ingestion of a placebo or Udenafil were
scheduled within 7 days. 0.3 mg/kg ICG were administered via an antecubital
vein. Blood samples were drawn from the opposite cubital vein before and
exactly 3, 6, 9, 12, 15, 18, 21, 30 and 40 minutes after ICG injection.
All samples were centrifuged immediately and stored at -80 C until analysis.
Calculation of PDR and R15 were done by P. Thomann (Kineticon, Freiburg,
Germany). In parallel, with transcutaneous spectrophotometry PDR and R15
were are measured with the LiMONTM-device (PULSION Medical Systems AG,
Munich, Germany). For this analysis, the results of the ICG determination via
blood samples and LIMON before the drug ingestion on both study days are
compared.
RESULTS: 20 patients with liver cirrhosis were included (4 female, age
54.910.8 years, Child-Score 6.71.3). One female patient stopped the study
after Visit 1 because of side effects (dizziness, malaise) a few hours after application of ICG and 100mg Udenafll. 20 analyses were performed at Visit 1 and 19
analyses at Visit 2. In 2 patients a stable transcutaneous signal was not obtained
at Visit 1 so the LIMONTM-system failed. The plasma disappearance rate at Visit
1 was 9.825.68% for blood analyses and 10.345.54% for the LIMON device,
respectively. The results for the R15 were 35.2622.66% for blood analyses and
27.4718.71% for the LIMON device. At Visit 2 the PDR results were
8.795.64% versus 10.376.58%, respectively. The results for R15 were
37.6422.49% versus 29.2021.34%, respectively. The correlation between the
two methods was high (r for PDR Visit 1: 0.938, r for R15 Visit 1: 0.968; r for
PDR Visit 2: 0.892, r for R15 Visit 2: 0.921).
CONCLUSION: This is the first analysis to compare conventional analysis of
ICG clearance with a transcutaneous spectrophotometry in patients with compensated liver cirrhosis. ICG plasma disappearance rate and R15 estimated with
the LIMONTM device correspond well to conventional ICG clearance. With the
LIMONTM device the ICG kinetics can be obtained in an easy way within 5
minutes with only minor effort.
Disclosure of Interest: None declared
P1167 OSTEOPOROSIS IN PRIMARY BILIARY CIRRHOSIS: TWO
BIPHOPHONATES COMPARED
G. Iafrancesco1, R. Filippetti2,*
Ospedale S. Sebastiano M, Frascati (Roma), 2Ospedale San camillo-Forlanini,
Roma, Italy
Contact E-mail Address: prof_filippetti@yahoo.it
1

INTRODUCTION: Osteoporosis characterized by loss of bone strength leading


to fragility fractures is a common event in women who have Primay Biliary
Cirrhosis (PBC). Although its pathogenesis is not well known it results mainly
from low bone formation. At present the treatment of osteoporosis in patients
with PBC mostly relies on oral biphosphonates,particularly in weekly 70 mg
alendronate,but there are a concern because of poor compliance. The efficacy,adherence and safety of monthly 150 mg ibandronate were compared in a 2-year
study in 20 postmenopausal women with osteoporosis and PBC.
AIMS & METHODS: Bone mineral density (BMD) of the lumbar spine and
proximal femur by dual-energy x-ray-absorptiometry (DXA),liver function and
bone markers were measured at entry and every 6 months at entry and every 6

A452
months over 2 years. Adherence to therapy was assessed by the Moriski score. At
enrollment
the
two
groups
were
similar
with
respect
to
age,BMD,cholestasis,previous fractures and bone markers. Eighteen patients,nine in the alendronate group and nine in the ibandronate completed the study.
RESULTS: At 2 years both treatments resulted in a significant increase in BMD
at the lumbar spine,the mean percentage change was 4.5% in alendronate and
5.7% in ibandronate group (p not significant) BMD increased at the total hip
by 2% and 1.2% respectively. Change in bone markers were similar in both
groups and one patient with alendronate developed a new vertebral fracture.
Adherence to the therapy was higher with ibandronate. Neither treatment
impaired liver function or cholestasis. One patient in the alendronate group
discontinued treatment because of gastrointestinal adverse effects such as dyspepsia,nausea and vomiting.
CONCLUSION: Both regimens,weakly alendronate and monthly ibandronate,improve bone mass and are comparable in safety for osteoporosis therapy in
patients with PBC,although adherence is higher with the monthly regimen.
Further larger studies are needed to assess fracture prevention.
Disclosure of Interest: None declared
P1168 HFE GENE C282Y AND H63D MUTATIONS ARE ASSOCIAED
WITH LIVER CIRRHOSIS IN LITHUANIAN POPULATION
S. Juzenas1,*, I. Valantiene1.2, J. Kupcinskas1.2, L. Kucinskas1, J. Sumskiene2,
V. Petrenkiene2, J. Venteriene1, J. Kondrackiene2, J. Skieceviciene1,
L. Kupcinskas1.2
1
Institute for Digestive Research, 2Department of Gastroenterology, Lithuanian
University of Health Sciences, Kaunas, Lithuania
INTRODUCTION: Liver cirrhosis is an ultimate complication of different
chronic liver disorders. Cirrhosis is commonly caused by alcohol use, viral hepatitis B and C and many other causes. The search for epidemiological, biological
or genetic factors that could help to select patients at higher risk of developing
cirrhosis is necessary. The literature data on impact of HFE-gene C282Y and
H63D heterozygous mutations for liver cirrhosis risk in different populations and
depending on cirrhosis etiology is controversial.
AIMS & METHODS: The aim of this study was to determine the association
between the presence of HFE gene C282Y and H63D mutations and liver cirrhosis in Lithuanian population. A cohort of consecutive cirrhosis patients consisted of 209 individuals with different disease etiologies. The diagnosis of
cirrhosis was confirmed by clinical features, liver biopsy and radiological imaging
tests. Control group consisted of 1004 healthy blood donors. HFE gene mutations in cirrhotic patients and control group were detected using PCR-RFLP
method. Statistical analysis were performed using statistical software for genetic
association studies PLINK v2.050.
RESULTS: The presence of C282Y mutation was associated with higher risk of
the liver cirrhosis when compared with controls (OR-2.07, p 0.005). The carriage
of C282Y/wt genotype increased the risk of liver cirrhosis compared with individuals having wt/wt genotype (OR-2.00, p 0.012). A similar pattern was observed
in a dominant model for C282Y mutation (wt/wt vs. C282Y/wt C282Y/C282Y)
which showed increased risk of developing liver cirrhosis (OR-2.07, p 0.007).
This link was even more evident in males as carriers of C282Y allele had increased
risk of liver cirrhosis with an OR of 2.58 (p 0.002). The presence of H63D
mutation was not associated with cirrhosis risk in overall study population; however, after stratification into genders H63D allele was associated with higher risk of
liver cirrhosis in males (OR 1.5, p 0.018), but not in females (OR 0.84,
p 0.43).
CONCLUSION: HFE gene C282Y mutation is associated with liver cirrhosis
irrespective of disease aetiology, while H63D mutation was linked with liver
cirrhosis only in males. These genetic alterations might contribute to faster progression of chronic liver diseases of different aetiology to end stage in Lithuanian
population.
Disclosure of Interest: None declared
P1169 AUTOLOGOUS BONE MARROW - DERIVED LIVER STEM
CELLS REDUCE LIVER FIBROSIS AND IMPROVE LIVER
FUNCTION IN CARBON TETRACHLORIDE - TREATED HEPATIC
CIRRHOTIC RAT
X. Guo1,*, J. Chen1
General Hospital of Shenyang Military Area, Shenyang, China
Contact E-mail Address: guoxiaozhong1962@163.com
1

INTRODUCTION: To determine the safety, feasibility and therapeutic effect of


in vitro-expanded autologous bone marrow-derived liver stem cells (BMDLSC)
transplantation in hepatic cirrhotic rats treated with carbon - tetrachloride.
AIMS & METHODS: Liver cirrhosis rat models were prepared and then divided
randomly into three groups, 25 in each group. In rats, we analyzed the effect of
different cells infusion in three experimental groups (group A, bone marrow cell
infusion CCl (4); group B, bone marrow - derived liver stem cell infusion
CCl (4); group C, bone marrow stem cell infusion CCl (4)).
RESULTS: We observed significantly increased average serum albumin levels
and higher expression of Differentiated liver cells, green fluorescent protein
(GFP), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen in the livers of group A. We observed MMP9/GFP double-positive cells in
the cirrhotic livers. A significant decrease in the liver fibrosis areas was observed
in group A. There were significant differences in ALT, ALB, TBIL and AFP in
three groups, P50.05.
CONCLUSION: Infusion of bone-marrow-derived cultured liver stem cells
improved liver function and liver fibrosis in rat with CCl4-induced cirrhosis.

United European Gastroenterology Journal 2(1S)


REFERENCES
Liao X, AnCheng JY, Zhou QJ, et al. Therapeutic effect of autologous bone
marrow-derived liver stem cells transplantation in hepatitis B virus-induced liver
cirrhosis. Hepatogastroenterology 2013; 60: 406-409.
Disclosure of Interest: None declared
P1170 THE RISK OF MALIGNANT TRANSFORMATION OF THE
COLORECTAL POLYPS- PROSPECTIVE STUDY
A. Goldis1,*, L. Daniela1, I. Ratiu1
1
gastroenterology, V Babes Medical University, Timisoara, Romania
Contact E-mail Address: goldisadi@yahoo.com
INTRODUCTION: Because colonic polyps are highly prevalent in the general
population (especially with increasing age), they confer an important predisposition to colon cancer
AIMS & METHODS: We performed a prospective study including 659 patients,
with amean age of 60.1  11.5 years, in which a number of 928 polyps were
resected. We have evaluated the correlation between the dimension of the polyps
and the risk of malignant transformation on the ground of the grade of epithelial
dysplasia revealed by the histopathological examination.
RESULTS: From the total number of the studied polyps, 324 were without
dysplasia, 514 with mild/moderate dysplasia and 89 with high grade dysplasia/
malignant polyps. The mean dimension of the polyps without dysplasia was
significantly lower in comparison to the dimension of the polyps with high
grade dysplasia/malignant polyps: 8.69  0.5978 mm vs. 15.64  1.626 mm,
p50.0001 ES. There were no statistically significant diferencies between the
mean dimension of the polyps without dysplasia vs. the dimension of the
polyps with mild/moderate dysplasia: 8.69  0.5978 mm vs. 8.85  0.3489 mm
(p40.05). The mean dimension of the polyps with mild/moderate dysplasia was
significantly lower in comparison to the dimension of the polyps with high grade
dysplasia/malignant polyps: 8.85  0.3489 mm vs. 15.64  1.626 mm, p50.0001
ES. According to the dimension, the studied polyps were subdivided into two
groups: polyps515 mm, and polyps415mm, respectively. In the first group
there were 803 polyps included, from which 286 (35.6%) without dysplasia,
460 (57.2%) with mild/moderate dysplasia and 57 (7%) with high grade dysplasia/malignant polyps. The second group was formed by 121 polyps, from which
38 (31.4%) without dysplasia, 54 (44.6%) with mild/moderate dysplasia and 29
(23.9%) with high grade dysplasia/malignant polyps. Comparing these two
groups, we noticed that high grade dysplasia was found in a significantly
higher number of polyps415mm in comparison with those 515 mm,
p50.0001 ES, OR 3.829 95% CI (2.185 to 6.709), RR 1.470 95% CI (1.186
to1.822).
CONCLUSION: Our results demonstrate the existence of a statistically significant correlation between the dimension of the polyps and the risk of malignant
transformation, namely, the bigger the polyps are, the higher the risk of malignant transformation is. Polyps over 15 mm diameter hold a risk of malignant
transformation 1.5 times higher than the smaller polyps.
Disclosure of Interest: None declared
P1171 MANAGEMENT OF SPONTANEOUS BACTERIAL PERITONITIS
IN A LARGE DISTRICT GENERAL HOSPITAL. ARE WE
FOLLOWING EUROPEAN GUIDELINES?
C. Kanagasundaram1,* on behalf of Dr A Chander, Dr J Bhattacharya, Dr
M Hall, Dr D Morris
1
Gastroenterology, Lister & QE2 Hospital, East and North Herts Trust, London,
United Kingdom
Contact E-mail Address: cynthia.kanagasundaram@nhs.net
INTRODUCTION: Spontaneous Bacterial Peritonitis (SBP) is the most frequent
and life-threatening infection in patients with liver cirrhosis. It requires prompt
recognition and treatment. Mortality is high for patients admitted with decompensation which is a growing problem due to the increasing prevalence of cirrhosis. Hence early detection of complications such as SBP is critical to improve
outcome. EASL (European Association for the Study of the Liver) released
Clinical Practise guidelines on management of SBP in 2010. We have compared
our data on managing SBP and determine if this is compliant with guidelines and
if there is uniformity within our DGH.
AIMS & METHODS: Our aim was to assess whether we are managing SBP in
our DHG in accordance with EASL guidelines from 2010. We collected data
retrospectively from October 2011 to November 2012. Then we collected data for
1 year following intervention from November 2012- November 2013. We
requested our pathology lab to supply patient details of any ascitic fluid samples
with a white cell count 4 500/mm3. We Investigated and recorded the following
data:
1. Did patients receive an ascitic tap on admission
2. Was a Neutrophil count 4250/mm3 recorded
3. Was a WCC 4 500/mm3 recorded
4. Positive culture results documented
5. Was Antibiotics started before culture results
6. Was Intravenous albumin given
7. Evidence of Hepatorenal syndrome (HRS) documented
8. Was a Repeat ascitic tap performed
9. Prophylactic antibiotics

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RESULTS:

Outcomes measured
Ascitic tap on admission
Neutrophil count 4250/mm3
recorded
Positive culture results
documented
Antibiotics started before culture
results
Intravenous albumin given
Hepatorenal Syndrome
Repeat Ascitic Tap performed
Prophylactic Antibiotics
Mortality

Oct 11 Oct 12
(n 15)

Nov 2012
Nov 2013
(n 12)

Percentage
improvement

47%
0%

50%
0%

3%
0%

40%

17%

-23%

93%

100%

7%

27%
53%
17%
33%
60%

83%
33%
67%
33%
17%

56%
20%
50%
0%
43%

CONCLUSION: It was alarming to see the variation in management amongst


doctors, especially gastroenterologists and hepatologists. Following education
there has been improvement in outcomes which hopefully has a positive
impact on morbidity and mortality. It is unclear why ascitic neutrophil count
is not done in this trust and many other trusts.
This audit highlights the need to ensure that there is a standardised approach to
the diagnosis and management of SBP. By adhering to guidelines it may help
mortality and morbidity.
REFERENCES
EASL clinical practise guidelines on the management of ascites, spontaneous
bacterial peritonitis and hepatorenal syndrome in cirrhosis. J Hepatol 2010; 53:
397417.
Disclosure of Interest: C. Kanagasundaram: nil
P1172 SYMPTOMATIC
TREATMENT
OF
ENCEPHALOPATHY WITH CHOLINE ALPHOSCERATE

HEPATIC

E.G. Manzhalii1,*, O.M. Baka2


1
Internal medicine, Bogomolets of National Medical University, 2Gastroenterology,
Hospital for Scientists of the National Academy of Science, Kiev, Ukraine
Contact E-mail Address: elinam@ukr.net
INTRODUCTION: The treatment of hepatic encephalopathy (HE) involves
multiple drugs that may lead to recovery of consciousness and thinking but
therapeutic options are often limited.
AIMS & METHODS: The aim of our work now was to assess the efficacy of
choline alphoscerate for the treatment of HE in patients with liver cirrhosis. In
this prospective study, we included 34 patients with liver cirrhosis and HE, stage
I-II. The control group comprised 17 patients receiving standard treatment.
Patients from the intervention group received choline alphoscerate (L-alpha-glyceryl phosphorylcholine, Gliatilin; 800 mg per day) for one month in addition to
the basic treatment. HE was assessed by clinical symptoms, number connection
test, and electroencephalography (EEG).
RESULTS: In the intervention group vs. controls the normalization of sleep and
movement disturbance improved in 88% and 72% of the patients, respectively.
In the control group only 53% of the patients improved in sleep patterns and
40% in motor coordination. Of note on the 10th day of treatment, patients in the
intervention group started to perform in the number connection tests 27.2  1.2s
faster, whereas in the control group the improvement was significantly (P 5 0.05)
less (12.7  1.4s). Patients on choline alphoscerate showed a marked clinical
improvement correlating with EEG changes. Before treatment, a reduction of
-rhythm was detected in 82% of the patients; after treatment this proportion
was only 41% (P 5 0.05), indicating normalization of brain function in the
majority of patients. In the control group 73% of patients showed abnormal
EEG findings before and after treatment. The presence of -waves was observed
in 45% of patients before and 24% after treatment with choline alphoscerate (P
5 0.05); in the control group the corresponding frequencies were 54% and 47%
(P 4 0.05).
CONCLUSION: Choline alphoscerate eliminates pathological neurological
symptoms in 78% patients with cirrhosis, whereas improvement is only detected
in 38% of patients with HE on conventional therapy. The natural choline supplement has a favorable safety profile and should be studied further in randomised controlled trials.
Disclosure of Interest: None declared
P1173 DIFFERENT SCORING SYSTEMS IN PREDICTING SURVIVAL IN
CHINESE PATIENTS WITH LIVER CIRRHOSIS UNDERGOING
TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT
F. Zhang1,*, Y. Zhuge1, X. Zou1
1
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing
University Medical School, Nanjing, China
Contact E-mail Address: fzdndx@126.com
INTRODUCTION: Transjugular intrahepatic portosystemic shunt (TIPS) is an
established minimal-invasive procedure to treat complications of portal hypertension, and several scoring systems have been used to help choose suitable
patients. But the accuracy remains controversial.

AIMS & METHODS: To compare the performance of the Child-Turcotte-Pugh


(CTP) classification system, Model for end-stage liver disease (MELD) score,
Emory score, Bonn TIPS early mortality (BOTEM) score, and serum bilirubin
and platelet count (SB/PLT model) in predicting survival in Chinese patients with
liver cirrhosis undergoing Transjugular intrahepatic portosystemic shunt (TIPS).
The clinical data of patients undergoing TIPS in our department were retrospectively analyzed to compare the 5 scoring systems based on survival after TIPS.
RESULTS: A cohort of 159 patients was involved. The survival curves showed
statistical significance between classification B and C of CTP (2 9.451,
p 0.002), between MELD510 and MELD10 (2 10.099, p 0.001) and
between low risk and moderate risk groups of Emory score (2 4.656,
p 0.031), indicating a better discriminatory ability. By ROC curves and logistic
regression model, MELD score and CTP system had a better power to predict 3month, 12-month, and 24-month survival. MELD score and CTP classification
system had smaller values of -2Ln(L), Akaike Information criterion (AIC), and
Schwarz-Bayesian criterion (SBC), respectively.
CONCLUSION: MELD score and CTP classification system provide better
prognostic stratification for a cohort of Chinese patients with advanced cirrhosis
undergoing TIPS. However, MELD score is not significantly superior to CTP
system.
Disclosure of Interest: None declared
P1174 IN MELD FIT A PREDICTIVE FACTOR FOR IN HOSPITAL
MORTALITY IN CHIRROTICS PATIENTS WITH OESOPHAGEAL
VARICEAL BLEEDING?
J. Silva1,*, R. Cerqueira1, M. Correia1, C. Manso1
1
Centro Hospitalar entre Douro e Vouga, Santa Maria da Feira, Portugal
Contact E-mail Address: joanasilva67@hotmail.com
INTRODUCTION: The model for end stage liver disease (MELD) score is very
accurate for predicting mortality in patients with end stage liver disease. Since
2002, MELD is used for patient allocation on liver transplant waiting lists.
Oesophageal variceal bleeding (OVB) is a high mortality rate complication in
patients with cirrhosis. The aim of this study was to compare the prognostic value
of MELD and MELD fit for in-hospital mortality (IHR) in cirrhotic patients
with OVB.
AIMS & METHODS: The study cohort consisted of 135 patients [mean age 54.9
(12.2), 73.3% male] consecutively admitted to our hospital with OVB. All the
patients were submitted to upper endoscopy within 12h, and sclerotherapy or
band ligation was performed in case of active bleeding. Octeotride or terlipressin
therapy was started at admission and continued for 5 days. In order to calculate
MELD and MELD fit scores, data of the laboratory results from blood samples
taken within 6h from admission were used. The level of significance was set at
p50.05.
RESULTS: The IHM was 17.0% (23 patients). On univariate analysis the predictive factors for IHM were rebleeding (OR 17.3 (5.6-53.35), p50.001), antibiotic prophylaxis (OR 5.05 (1.7-14.7), p 0.001), MELD score 3 15 (OR 5.7
(1.8-17.8), p 0.001) and MELD fit score 3 14 (6.9 (1.9-24.6), p 0.001). On
multivariate analysis all remain independently associated to IMH. Applying a
receiver operating characteristic (ROC) analysis after multivariate logistic
models, the area under the curve (AUC) derived from the MELD and MELD
fit scores were, respectively, 0.87 (95%CI: 0.79-0.95) and 0.88(0.8-0.95) for IHM.
CONCLUSION: In cirrhotic patients with OVB MELD score (best cut-off of 15)
and MELD fit score (best cut-off of 14) identifies a group of patients with a
higher risk of IHM.
Disclosure of Interest: None declared
P1175 EFFICACY OF ENDOSCOPIC BAND LIGATION AS PRIMARY
PROPHYLAXIS OF BLEEDING FROM ESOPHAGEAL VARICES
J. Santos-Antunes1,*, H. Cardoso2, E. Rodrigues-Pinto2, R. Morais2,
A. Albuquerque2, F. Vilas-Boas2, S. Rodrigues2, A. Ribeiro2, M. Marques1,
R. Goncalves2, S. Lopes2, G. Macedo1
1
Gastroenterology, 2Centro Hospitalar S. Joao, Porto, Porto, Portugal
INTRODUCTION: Endoscopic band ligation is a very effective procedure for
the treatment of esophageal varices. Its use is recommended for primary prophylaxis as an alternative to beta-blockers, for the treatment of acute hemorrhage or
for secondary prophylaxis.
AIMS & METHODS: The aim of this study was to evaluate our experience
regarding elastic band ligation for primary prophylaxis of variceal bleeding.
Analysis of patients undergoing variceal eradication program as primary prophylaxis of variceal hemorrhage, from January 2010 until February 2014.
RESULTS: From a total of 213 patients, 93 were treated for primary prophylaxis; 79% of those were male, with a mean age of 6012 years, with a median
follow- up of 11.4 months. The main cause of portal hypertension was alcoholic
cirrhosis (54%), followed by HCV (20%) and HBV (6%) infection. Most patients
had a Child-Pugh score of A (48%), with the remaining scoring B (28%) or C
(24%). In 55% of the patients it was possible to eradicate varices, with a median
number of 2 sessions and 12 rubber bands. The presence of hepatocellular carcinoma was related to the inability to eradicate varices (p 0.001), and concomitant use of propranolol did not influence the efficacy of eradication (p 0.937).
The mortality rate in one year was 15%. Five patients had variceal bleeding
(5%), which was significantly related to mortality at one year (p 0.022). No
patients had bled from the scar. Patients with Child C had greater difficulty in
eradicating varices than those with Child A (38% vs 60%, p 0.101), and higher
mortality during follow-up (24% vs 4%, p 0.036).
CONCLUSION: Endoscopic band ligation was effective in preventing variceal
bleeding, with an overall success rate of 95%.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)

P1176 THE SAFETY AND EFFECTIVENESS OF SEDATION WITH


MIDAZOLAM IN CIRRHOTIC PATIENTS UNDERGOING
ENDOSCOPIC VARICEAL LIGATION
J.K. Lee1,*
1
Internal medicine, Dongguk University Ilsan Hospital, Goyang, Korea, Republic
Of
INTRODUCTION: Endoscopic variceal ligation (EVL) is the established treatment for acute esophageal variceal bleeding. Unlike other therapeutic endoscopic
procedure, sedation is generally not used in a cirrhotic patient for fear of hepatic
encephalopathy (HE). However, a successful procedure might not be guaranteed
due to poor cooperation and/or delirious behavior. In this study, we evaluated
safety and effectiveness of midazolam in a cirrhotic patient undergoing EVL.
AIMS & METHODS: The medical records of 320 cirrhotic patients who underwent EVL between October 2005 and December 2012 were reviewed retrospectively. The main outcomes were treatment success and adverse drug reaction
(ADR) that might be related with sedation. Also, risk factors for development
of HE were pursued.
RESULTS: Midazolam was used in 151 patients and not in 161 and baseline
characteristics were similar. The rates of treatment success were not differ in both
groups (95.8% vs. 96.2%, p 0.999). Although the incidence of ADR didnt
differ (46.2% vs. 55.0%, p 0.115), development of HE (6.6% and 0%,
p 0.001) and desaturation (23.2% vs. 7.7%, p 0.001) were more common in
the midazolam group. A patient from the midazolam group died due to uncontrolled bleeding. There were a total of 10 cases of HE. With logistic regression,
ECOG score 2 turned out to be associated with ADR (OR 2.69, 95% CI 1.684.29, p). However, age, body mass index, Child-Pugh classification and variceal
grade were not related.
CONCLUSION: Because midazolam was associated with ADR including HE in
a cirrhotic patient undergoing EVL, it should be used with extreme caution
including appropriate intra- and post-procedural monitoring, especially when
the ECOG score of a patient is not less than 2.
Disclosure of Interest: None declared

n
w
a
r
d
h
t
i

P1177 RESPONSE TO TERLIPRESSIN AND ALBUMIN IS ASSOCIATED


WITH IMPROVED OUTCOME IN PATIENTS WITH CIRRHOSIS
AND HEPATORENAL SYNDROME (HRS)
M. Nguyen-Tat1,*, E. Gotz1, J. Ahrens1, V. Sivanathan1, J. Schattenberg1,
J. Rey2, M.A. Worns1, P.R. Galle1, J.U. Marquardt1
1
Department of Medicine I, University Medical Center Mainz, Mainz,
2
Department of Medicine, St Marys Hospital, Frankfurt, Germany
Contact E-mail Address: marc.nguyen-tat@unimedizin-mainz.de
INTRODUCTION: Hepatorenal syndrome (HRS) is a severe but potentially
reversible complication in patients with cirrhosis, left untreated it is associated
with a very poor prognosis. Several randomized controlled trials (RCT) have
proven that treatment with terlipressin and albumin improves renal function,
however the effect on overall survival has not been well established.
AIMS & METHODS: Aim of the study was to gain further insight into the effect
of terlipressin treatment in patients with HRS on renal function, overall survival
and renal-replacement-free-survival.
All patients presenting with HRS and treated with terlipressin in our tertiary referral liver and transplantation center between April 2013 and March 2014 were
included, and clinically relevant parameters such as response to therapy, overall
survival and renal-replacement-free-survival were prospectively investigated.
RESULTS: Overall 57 patients were followed-up over a median of 65 days.
Cirrhosis was in an advanced stage in the majority of patients (Child-Pugh C:
46; 81%). Median cumulative terlipressin dosage and treatment duration were 20
mg and 5 days. Complete or partial response to terlipressin with recovery from
HRS was observed in 20 and 3 out of 57 patients (51%; 5%). Median overall
survival was significantly better in patients with response to terlipressin than in
patients with non-response (167 vs. 27 days; p50.0001), as well as median survival free of renal-replacement-therapy (82 vs. 4 days; p50.0001). In univariate
analysis, non-response was associated with a high baseline serum-bilirubinconcentration.
CONCLUSION: Terlipressin in combination with albumine is effective in a
majority of patients with HRS. Response to therapy is associated with improved
survival.
Disclosure of Interest: None declared
P1178 NON INVASIVE ASSESSMENT OF LIVER FIBROSIS WITH
SIMPLE BLOOD PARAMETERS, MYRIADS OF MARKERS. . ..
WHAT TO MIX AND WHERE TO MATCH!
R.B. Thandassery1,*, A.K. John1, S.A. Mohiuddin1, S.R. Al Kaabi1
1
Gastroenterology, Hamad General Hospital, Doha, Qatar
Contact E-mail Address: doc.ragesh@gmail.com
INTRODUCTION: There are many simple scores (that require only routine
blood parameters) for non-invasive assessment of liver fibrosis. But there are
only limited data comparing these scoring systems.
AIMS & METHODS: Our aim was to compare simple scores for non-invasive
assessment of liver fibrosis with liver biopsy in patients with chronic hepatitis C
virus (HCV) infection and validate the recently proposed fibrosis cirrhosis index
(FCI)1.
In 193 chronic HCV patients who underwent liver biopsy, we compared the liver
biopsy (Scheuer classification) fibrosis scores with AAR (AST/ALT ratio), APRI
(AST/Platelet ratio), FIB-4, Fibrosis Index (FI) and FCI.

These
scores
are
calculated
as;
AAR [AST(IU/l)/ALT(IU/l)],
APRI [{AST(IU/l)/ AST(ULN)(IU/l)}100]/ platelet count (109/l), FIB4 [Age (Years)  AST (IU/l)]/ [Platelet count ( 109/l)  ALT (IU/l)1/2],
FI [8.0 - 0.01  Platelet count (109/l) - Albumin (g/dl)], FCI [Alkaline phosphatase (IU/ml)  Bilirubin (mg/dl)] / (Albumin  Platelet count)
RESULTS: The mean age of patients was 41.49.6 years (160 males), genotype-4
(144, 74.6%) was the commonest followed by genotype-1 (66, 34.2%).
Liver biopsy showed stage-0 fibrosis in 19 (9.8%), stage-1 in 77 (39.9%), stage-2
in 69 (35.8%), stage-3 in 25 (13%) and stage-4 in 3 (1.6%) patients. Compared
with liver biopsy, AAR, APRI, FIB-4, FI and FCI showed correlation coefficient
indices of 0.144, 0.409, 0.414, 0.558, and 0.54 respectively. The AUROCs for
these indices for advanced fibrosis (F0-2 v/s F3.4) were; AAR (for cutoff 41)
0.52, APRI (cutoff 41.5) 0.83, FIB-4 (cutoff 43.25) 0.79, FI (cutoff 43.3) 0.92,
and FCI (cutoff 4 1.25) 0.92.
The sensitivity and positive predictive value for FI (80% and 84% respectively)
and FCI (82% and 83% respectively) was significantly higher than other indices.
CONCLUSION: The fibrosis index (FI) and fibrosis-cirrhosis index (FCI) accurately predicted advanced fibrosis stage in chronic HCV infected patients; they
seem more accurate than other frequently used serum indices.
REFERENCES
1. Ahmad W, Ijaz B, Javed FT, et al. A comparison of four fibrosis indexes in
chronic HCV: development of new fibrosis-cirrhosis index (FCI). BMC
Gastroenterol 2011; 11: 44.
Disclosure of Interest: None declared
P1179 RISK FACTORS AND OUTCOME IN ICU PATIENTS WITH END
STAGE LIVER DISEASE
S. Mohamed1,*, S. Soud1
1
Tropical medicine & Gastroenterology, Assiut University, Assiut, Egypt
INTRODUCTION: Acute or chronic liver failure is associated with numerous
complications which may occur in combination and patients may require intensive care unit (ICU) treatment. Therefore, it seems necessary to identify prognostic clinical parameters and risk factors at the time of ICU admission.
AIMS & METHODS: To estimate the frequency of mortality and cirrhosis
morbidity among patients with end stage liver disease (ESLD) admitted to the
ICU and to evaluate the relation between demographic, clinical and laboratory
data (potential risk factors) of those patients and mortality.
120 patients with ESLD were enrolled [102 males (85%) and 18 females (15%)].
History taking,clinical examination,full investigations and classification of
patients according to Child-Turcotte-Pugh (CTP) and MELD score were done.
RESULTS: Regarding clinical presentation, hepatic encephalopathy (HE) was
found in 87.5%, jaundice in 60%, hematemesis in 41.7%, hepatorenal syndrome
(HRS) in 35.8% and spontaneous bacterial peritonitis (SBP) in 20.8%. Mortality
rate was 57.5%; the main causes of death were HRS (40.8%), HE (21.7), aspiration pneumonia (10%), septic shock (2.5%) and irreversible shock in only 1.7%.
There was a significant relation between mortality and old age, CTP and MELD
scores and a longer stay at the ICU. Increased white blood cell count, increased
hemoglobin and decreased prothrombin concentration and raised creatinine were
independent risk factors of mortality in ESLD patients in the ICU. Mortality
rates were higher (86.2%) with 5-6 risk factors and (21.7%) with 1-2 risk
factor(s).
CONCLUSION: The mortality rate in of ESLD patients admitted to the ICU
was 57.5% and the most common cause of death was HRS. CTP, MELD score,
HE, HRS and jaundice were significant predictors of mortality in ESLD patients.
Mortality increased with increased number of risk factors. Creatinine level, white
blood cell count, hemoglobin and prothrombin concentration were independent
risk factors affecting the outcome of ESLD patients in the ICU.
Disclosure of Interest: None declared
P1180 SAFETY AND EFFICACY OF TOLVAPTAN FOR TREATMENT OF
REFRACTORY ASCITES IN CIRRHOTIC PATIENTS
S. Kawazoe1,*, S. Nakashita2, W. Yoshioka1, K. Tanaka1, T. Akiyama1,
T. Kumagai1, T. Otsuka2, Y. Kawaguchi1
1
Hepatobiliary and Pancreatology, SAGA-KEN MEDICAL CENTRE
KOSEIKAN, 2Internal medicine, Saga medical school, Saga university, Saga,
Japan
Contact E-mail Address: kawazoe-s@excite.co.jp
INTRODUCTION: Since September 2013 in Japan, the vasopressin V2 receptor
antagonist tolvaptan (7.5 mg/day) has been approved for the treatment of cirrhotic patients with hepatic ascites and edema that do not respond to diuretics.
Thirty-one patients with refractory ascites were given tolvaptan at two
institutions.
AIMS & METHODS: We prospectively evaluated its safety and efficacy, and
determined the predictive factors of a good response. From 14 September 2014 to
31 March 2015, among 31 (19 males, 12 females; 71 (range, 4989) years) patients
with refractory ascites treated with diuretics (furosemide 2080 mg/day, spironolactone 0100 mg/day), 29 patients were given tolvaptan at 7.5 mg/day and 2
patients were administered 3.75 mg/day. 15 patients were Child-Pugh class B and
16 were C in their hepatic function reserve. Underlying disease was constituted as
follows, HCV was 24, HBV was 1, Alchohol was 4, NASH was 4. Correlations
between pre-treatment data and decrease in body weight were determined using
logistic regression analyses and scatter diagrams.
RESULTS: Pre-treatment parameters were: estimated glomerular filtration rate,
53.2 mL/min/1.73 m2; serum osmolarity, 292.6 mOsm/L; albumin, 2.5 g/dL;
serum sodium, 129.9 mEq/L; blood-urea-nitrogen, 34.9 mg/dL; hemoglobin,
10.1 g/dL. Twenty-two patients had a loss in body weight of 2 kg and were
termed responders. With regard to pre-treatment parameters, there were no

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United European Gastroenterology Journal 2(1S)


significant differences between responders and non-responders. There were no
differences in the response rate for each ChildPugh class. Responders had a
higher rate of increase in urine volume in the first 24-h collection after tolvaptan
administration than non-responders (183% vs 143%, p 0.047). In six patients,
the rate of change in urine osmolarity 24 h after tolvaptan administration was
closely correlated with rate of change in body weight (R2 0.77). Rupture of
esophageal varices occurred in four patients in the observation period (three in
G3 and one in G2). Hypernatremia (4150 mEq/L) was not experienced.
CONCLUSION: These data suggest that for cirrhotic patients with refractory
ascites, tolvaptan is effective and safe. In the pre-treatment state, finding predictive parameters for responders is very difficult. However, 24 h after tolvaptan
administration, the increasing urine rate and rate of change of urine osmolarity
are useful guides to identify responders.
Disclosure of Interest: None declared
P1181 TREATMENTS
HYPERTENSION

OF

ECTOPIC

VARICES

WITH

PORTAL

T. Sato1,*
1
Gastroenterology, SAPPORO KOSEI GENERAL HOSPITAL, Sapporo, Japan
INTRODUCTION: Ectopic varices that are not esophagogastric are located
predominantly in the duodenum, jejunum, ileum, colon, rectum, or enterostomy
stoma. Bleeding from ectopic varices, which is rare in patients with portal hypertension, is generally massive and life threatening.
AIMS & METHODS: From January 1994 to September 2013, we performed
endoscopic treatments or interventional radiologic treatments for 1530 portal
hypertensive patients with esophagogastric varices. In this study, we evaluated
the clinicopathological features and treatments of ectopic varices.
RESULTS: Seventy-seven patients were hospitalized in our ward for treatments
of ectopic varices. The underlying pathologies of portal hypertension included
liver cirrhosis in 46 patients, cirrhosis associated with hepatocellular carcinoma
in 12, primary biliary cirrhosis in 6, idiopathic portal hypertension in 7, extrahepatic portal vein obstruction in 5, and the other disease in 1. The location of
the ectopic varices were rectal varices in 58, duodenal varices in 9, intestinal
varices in 4, urinary bladder varices in 2, stomal varices in 1, colonic varices in
3. Seventy-three of 77 patients (94.8%) with ectopic varices had previously
received emergency or prophylactic endoscopic injection sclerotherapy (EIS)
for esophageal varices. In 47 of the 58 rectal variceal patients, EIS was performed
with no complications. In 9 of the 58 patients, endoscopic band ligation (EBL)
was performed, and 8 of whom experienced no operative complications after
EBL. Percutaneous transhepatic obliteration (PTO) was successfully performed
for the remaining 2 large rectal variceal patients. We successfully performed the
treatments for 9 duodenal variceal patients (the bulbs in 1, the second portion in
6, and the third portion in 2); balloon occluded retrograde transvenous obliteration (B-RTO) in 4, EIS using Histoacryl in 3, EIS plus B-RTO in 1, PTO in 1.
Four small intestinal variceal patients (3 jejunal varices, 1 ileal varices) had
undergone B-RTO in 2, PTO in 1, endoscopic treatments in 1. B-RTO was
successfully performed for ileal varices and jejunal varices. One jejunal variceal
patient died 3 days after PTO because of poor general condition, and endoscopies
revealed the recurrence of varices in the other jejunal variceal patient after endoscopic treatments. PTO was successfully performed for 2 urinary bladder variceal
patients. Endoscopic treatments or interventional radiologic treatments were
successfully performed for remaining ectopic varices.
CONCLUSION: Hemorrhage from ectopic varices should be kept in mind in
patients with portal hypertension presenting with lower gastrointestinal bleeding.
Disclosure of Interest: None declared
P1182 CANDIDATES FOR CONSERVATIVE TREATMENT AMONG
PATIENTS WITH PORTAL VENOUS GAS
C. Sakaguchi1,*, R. Takenaka1, Y. Baba1, N. Okazaki1, D. Kawai1,
K. Takemoto1, H. Tsugeno1, S. Fujiki1
1
Tsuyama Chuo Hospital, Tsuyama, Japan
Contact E-mail Address: chrskgc@yahoo.co.jp
INTRODUCTION: Although hepatic portal venous gas (HPVG) is a sign of
poor prognosis, there have been recent reports of cases treated conservatively.
However, it remains difficult to determine whether emergency surgery is
required. The aim of this study was to clarify the indications for conservative
treatment in patients with HPVG.
AIMS & METHODS: Of 107.787 cases in which computed tomography (CT)
was performed between April 2009 and September 2013 at our hospital, HPVG
was detected in 117 patients. Seventy three patients were excluded because they
presented with cardiovascular arrest. Therefore, a total of 44 patients were
included in this study. The patients were divided into two groups, group A
(n 26), patients treated conservatively, and group B (n 18), patients who
required surgery or died within 30 hospital days. The factors associated with
conservative treatment were analyzed using Fischers exact test, Mann-Whitney
U test and logistic regression analysis. The variables included age, gender, comorbidities (hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular disease, liver cirrhosis, renal failure and malignancy), subjective symptoms
(abdominal pain, constipation, vomiting and diarrhea), physical findings (systolic
blood pressure, pulse rate, body temperature, abdominal tenderness and peritoneal irritation sign), laboratory findings, including blood gas analysis, and CT
findings (pneumatosis intestinalis, ascites and location of HPVG). A receiver
operating characteristic curve was used to determine the cut-off value.
RESULTS: The study subjects were 23 men and 21 women with a median age of
78.5 (range, 20 - 102). The major etiologies of HPVG in group A were ileus and
enterocolitis. On the other hand, the etiologies in group B were mesenteric ischemia and emphysematous cholecystitis. Idiopathic HPVG was seen in 7 patients in

group A and 1 in group B. In the univariate analysis, there were significant differences between the two groups related to body temperature and level of C-reactive
protein (CRP), lactate dehydrogenase, aspartate aminotransferase, creatine
kinase, lactate and base excess (BE). In the multivariate analysis, CRP and BE
were identified as independent risk factors associated with poor prognosis. The
cut-off values were 12 mg/dl for CRP and -4.0 mmol/l for BE. When CRP 12 mg/
dl and BE -4.0 mmol/l were used to identify candidates for conservative treatment, the sensitivity and specificity were 91% and 89%, respectively.
CONCLUSION: CRP and BE might be useful markers to determine the conservative treatment of patients with HPVG.
Disclosure of Interest: None declared
P1183 PORTAL VEIN THROMBOSIS IN THE SETTING OF LIVER
TRANSPLANTATION
M. Hernandez Conde1, E. Llop1,*, J.L. Calleja1, J.de la Revilla1, F. Pons1,
N. Fernandez Puga1, M. Trapero1, J.L. Mart nez1, V. Cuervas-Mons1,
V. Sanchez Turrion1
1
Puerta de Hierro University Hospital, Madrid, Spain
INTRODUCTION: The prevalence of portal vein thrombosis (PVT) in patients
that have been undergone liver transplantation (LT) is 9.7%4.5%. The factors
associated with its presence and involvements in post-transplant prognosis are
unknown. The aim of our study was to determine the prevalence, assess the
factors that are associated with its presence as well as to clarify their association
with the prognosis in patients with liver cirrhosis (LC) and LT.
AIMS & METHODS: From January 2005 to May 2013, laboratory, radiological
and surgical data were retrospectively collected from patients with LC who had
undergone LT in our center for the first time.
RESULTS: 165 patients who had (46.7%) or had not been diagnosed of hepatocellular carcinoma (HCC) were included, all of them without tumoral thrombosis. The mean age was 55 (SD9), male 73.3% and HVC 44.8%. Child-Pugh
was (A/B/C:31.5/40.6/21.2%) and MELD 15 (SD6). Previous decompensations
were: ascites 61.2%, hepatic encephalopathy 33.9%, variceal bleeding 26.1%,
spontaneous bacterial peritonitis (SBP) 15.2%. The mean post-transaplant
follow-up was 36 months (0-100).
TVP was diagnosed while LT in 16 (9.7%) patients. The TVP was previously
diagnose with image tests in 4 patients (25%) (1(0.1% by Doppler ultrasound
(DU) and 4(43.8%) by computed tomography(CT)). All patients had a DU in a
mean time of 4 months prior the LT(0-10) and 7(43.8%) had a CT in a median
time of 1 month before the LT(0-45).
TVP was significantly related to the presence of SBP (37.5 vs 13.1%;p 0.01),
high levels of creatinine (1.4(SD1.8) vs 1(SD0.6;p 0.04), and low levels of albumin (3.1(SD0.9) vs 3.5(SD0.6);p 0.03). MELD was higher in patients with TVP
(16 (SD6) vs 14(SD5);p40.05). Surgery time was similar in both groups (6:05h vs
6:10h, p 0.8), transfusion of blood products was higher in patients with
TVP(plasma bags 15.5 vs 12.5, platelets pool 3 vs 4 and Red cells 7.5 vs 7.9),
although the results were not statistically significant.
TVP was correlated with the mortality in the first 30 days (18.8 vs 8.4%;p40.05).
CONCLUSION: TVP is a common complication in patients with cirrhosis
undergoing LT. Its presence is correlated with suffering from SBP, high levels
of creatinine and low levels of albumin. The pre-transplant diagnosis rate is very
low (25%) and its presence may have implications for short-term mortality.
Disclosure of Interest: None declared
P1184 COMPARISON
OF
PLATELETS
FUNCTION
USING
MULTIPLATE TEST IN CIRRHOTIC PATIENTS WITH AND
WITHOUT PORTAL VEIN THROMBOSIS
M.Z_ orniak1,*, P. Wosiewicz1, M. Hartleb1
1
Department of Gastroenterology and Hepatology, Medical University of Silesia,
Katowice, Poland
Contact E-mail Address: rzurio@interia.pl
INTRODUCTION: Portal vein thrombosis (PVT) occurs significantly more
often in cirrhotic patients, compared with total population. PVT diminishes
survival in patients with cirrhosis, by increasing incidence of other complications
such as bleeding from esophageal varices, loss of ascites responsiveness to diuretics or hepatic encephalopathy. Moreover, PVT complicates qualification for
liver transplantation, in some cases preventing this procedure. Factors which
influence development of PVT in cirrhosis as well as adaptive changes in coagulation system to this vascular complication are unclear.
AIMS & METHODS: Our study compares platelets function between cirrhotic
patients with and without PVT.
Material and methods: 33 patients with liver cirrhosis were qualified for this study
and PVT was diagnosed in 10 patients (spiral CT). Etiology of cirrhosis was:
alcoholic (n 18), HCV-infection (n 6), HBV-infection (n 4), autoimmune
hepatitis (n 3) and unknown (n 2). The blood samples from all patients was
collected for assessment of aggregation function using MultiPlate system.
RESULTS: Cirrhotic patients with PVT had lower platelets aggregation activity
related to stimulation with thrombin receptor activating-peptide (TRAPtest;
33.515.2 vs 59.822.9 U; P50.05), arachidonic acid (ASPItest; 25.113.4 vs
44.323 U; P50.05) and ADP (ADPtest; 2112.5 vs 38.218.6 U; P50.05).
CONCLUSION: Our study showed decreased aggregation activity of platelets in
cirrhotic patients with PVT that is probably an adaptive mechanism counteracting the expansion of thrombosis.
Disclosure of Interest: None declared

A456

United European Gastroenterology Journal 2(1S)

P1185 LOW-DENSITY LIPOPROTEIN CHOLESTEROL EXERTS A


POTENT INFLUENCE ON RESPONSE TO TELAPREVIR-BASED
TRIPLE THERAPY FOR CHRONIC HCV GENOTYPE 1 INFECTION
1,*

Hematological alterations

A. Kawano , E. Ogawa , N. Furusyo , H. Nomura , M. Nakamuta ,


E. Kajiwara5, K. Dohmen6, K. Takahashi7, T. Satoh8, K. Azuma9, Y. Tanabe10,
K. Kotoh11, S. Shimoda12, J. Hayashi2 on behalf of The Kyushu University Liver
Disease Study (KULDS) Group
1
Department of Internal Medicine, Kitakyushu Municipal Medical Center,
Kitakyushu, 2Department of General Internal Medicine, Kyushu University
Hospital, Fukuoka, 3The Center for Liver Disease, Shin-Kokura Hospital,
Kitakyushu, 4Department of Gastroenterology, Kyushu Medical Center, National
Hospital Organization, Fukuoka, 5Department of Hepatology, Steel Memorial
Yawata Hospital, Kitakyushu, 6Department of Internal Medicine, Chihaya
Hospital, 7Department of Medicine, Hamanomachi Hospital, Fukuoka, 8Center for
Liver Disease, National Hospital Organization Kokura Medical Center,
Kitakyushu, 9Department of Medicine, Kyushu Central Hospital, 10Department of
Medicine, Fukuoka City Hospital, 11 Department of Medicine and Bioregulatory
Science, Graduate School of Medical Sciences, 12Department of Medicine and
Biosystemic Science, Graduate School of Medical Sciences, Kyushu University,
Fukuoka, Japan
Contact E-mail Address: k-akira1971july@jcom.home.ne.jp
INTRODUCTION: The aim of this study was to investigate the relation between
baseline characteristics including the serum lipid levels and the treatment outcome from telaprevir (TVR) in combination with pegylated-interferon (PEGIFN) 2b and ribavirin (RBV).
AIMS & METHODS: This prospective study consisted of 218 treatment-experienced patients infected with HCV genotype 1. All received 12 weeks of TVR in
combination with 24 weeks of PEG-IFN2b and RBV.
RESULTS: The SVR rate was 83.0% (181 of 218) by intention-to-treat analysis.
In multivariable logistic regression analysis of pretreatment predictors of SVR,
low-density lipoprotein cholesterol (LDL-C) level (odds ratio [OR], 1.02,
p 0.0036), IL28B TT genotype (rs8099917) (OR, 3.21, p 0.0139), and prior
relapse (OR, 4.77, p 0.0006) were extracted as independent predictors of SVR.
Receiver operating characteristic analyses to determine the optimal threshold
values of the baseline LDL-C level for predicting SVR showed that the area
under the curve was relatively high (AUROC 0.78, P50.0001, cutoff value 95
mg/dL). IL28B TT genotype (OR, 6.89, P50.0001), prior relapse (OR, 2.33,
p 0.0289), and platelet count (x109/L) (OR, 1.01, p 0.0048) were extracted
as independently associated with LDL-C  95 mg/dL. For patients with prior
partial/null responses, the SVR rates of the groups with LDL-C  95 mg/dL were
significantly higher than those of the 5 95 mg/dL groups with any IL28B genotypes and pretreatment platelet count ( 150 or 5 150x109/L).
CONCLUSION: The baseline LDL-C level had a strong impact on outcome
from TVR-based triple therapy, especially for patients with prior partial/null
responses, irrespective of IL28B genotypes and platelet count.
Disclosure of Interest: None declared
P1186 TREATMENT OF PREVIOUSLY UNTREATED PATIENTS WITH
CHRONIC HEPATITIS C GENOTYPE 1 (G1) INFECTION IN
GERMAN REAL - LIFE: FREQUENCY AND SEVERITY OF
HEMATOLOGICAL ALTERATIONS UNDER BOCEPREVIR TRIPLE
THERAPY COMPARED TO DUAL THERAPY
G. Teuber1,*, P. Buggisch2, H. Lohr3, H. Steffens4, M. Kraus5, C. John6,
P. Geyer7, B. Weber8, T. Witthoeft9, A. Herrmann10, M. Hoesl11,
U. Naumann12, T. Dahhan13, D. Hartmann14, B. Dreher14, M. Bilzer14
1
Gastroenterological Practice, Frankfurt, 2ifi Institute, Hamburg,
3
Gastroenterological Practice, Wiesbaden, 4Practice of Internal Medicine, Berlin,
5
Medical Department II, Klinikum Burghausen, Burghausen, 6Center of Internal
Medicine, Berlin, 7Gastroentorological Practice, Fulda, 8Medical Practice, Kassel,
9
Gastroenterological Practice, Stade, 10Friedrich-Schiller-University, Jena,
11
Gastroenterological Practice, Nurnberg, 12Center of Medicine, Berlin,
13
Gastroenterological Practice, Fellbach, 14MSD Pharma GmbH, Haar, Germany
Contact E-mail Address: manfred.bilzer@bilzer-consulting.de
INTRODUCTION: Triple therapy of chronic hepatitis C G1 infection with the
HCV protease inhibitor boceprevir is accompanied by hematological alterations
such as anemia, leukopenia and thrombopenia. Data regarding the frequency
and severity of these alterations caused by triple therapy in real-life are still
scarce and were evaluated in the present analysis by comparison of two
German real-life cohorts.
AIMS & METHODS: Data of treatment-na ve patients treated for G1 infection
(N 1873) with pegylated interferon (PegIFN) alfa-2b and ribavirin (RBV) in a
large German observational study (Online-AWB) were compared with data of
153 treatment-na ve patients from the ongoing German NOVUS observational
study who have started triple therapy with PegIFN/RBV together with boceprevir at least 8 months ago.
RESULTS: Hematologic alterations according to the WHO classification caused
by dual or triple therapy are shown in the table. Patients undergoing triple
therapy achieved a similar frequency of the most common hemoglobin (Hb)
alterations grade 1 in contrast to significantly higher frequencies of grade 2
and grade 3 Hb alterations. Hb alterations during triple therapy were managed
by RBV dose reductions in 51% while 2.5% received blood transfusions. Only
one patient was treated with erythropoietin and one patient discontinued triple
therapy because of anemia. Compared to dual therapy there was a higher frequency of alterations in leukocyte (grade 2 and grade 4) and platelet count (grade
1 and grade 3) in patients undergoing boceprevir triple therapy (table).

Hb (g/dL)
Online-AWB (N 1873)
NOVUS (N 153)
P
Leukocytes (103/mL)
Online AWB (N 1873)
NOVUS (N 153)
P
Platelets (103/ml)
Online AWB (N 1873)
Novus (N 153)
P

Grade 1

Grade 2

Grade 3

Grade 4

9.5- 5 11.0
% (N)
33.5 (628)
39.9 (61)
0.1115^
2.0 - 53.0
% (N)
42.5 (795)
39.7 (60)
0.5166^
70 -  100
% (N)
17.0 (318)
26.3 (40)
0.0037^

8.0 - 59.5
% (N)
10.7 (200)
21.6 (33)
5.0001^
1.5 - 52.0
% (N)
13.8 (258)
21.9 (33)
0.0065^
50 - 570
% (N)
5.6 (105)
7.2 (11)
0.4053^

6.5 - 58.0
% (N)
0.8 (15)
3.9 (6)
0.0035*
1.0 - 51.5
% (N)
3.5 (66)
5.3 (8)
0.2638^
25 - 550
% (N)
3.4 (64)
8.6 (13)
0.0015^

56.5
% (N)
0.1 (1)
0.7 (1)
0.1454*
51.0
% (N)
0.1 (2)
1.3 (2)
0.0300*
525
% (N)
0.6 (12)
0.7 (1)
1.0000*

^ Chi-square test, * Fishers exact test


CONCLUSION: Triple therapy with boceprevir results in a higher frequency of
hematological alterations compared to dual therapy. Most alterations are mild to
moderate. In German real-life Hb alterations are managed by RBV dose reductions without the use of erythropoietin and only few patient need blood
transfusions.
Disclosure of Interest: G. Teuber Financial support for research from: MSD, P.
Buggisch Financial support for research from: MSD, H. Lohr Financial support
for research from: MSD, H. Steffens Financial support for research from: MSD,
M. Kraus Financial support for research from: MSD, C. John Financial support
for research from: MSD, P. Geyer Financial support for research from: MSD, B.
Weber Financial support for research from: MSD, T. Witthoeft Financial support for research from: MSD, A. Herrmann Financial support for research from:
MSD, M. Hoesl Financial support for research from: MSD, U. Naumann
Financial support for research from: MSD, T. Dahhan Financial support for
research from: MSD, D. Hartmann Other: Employee of MSD, B. Dreher Other:
Employee of MSD, M. Bilzer Consultancy for: MSD
P1187 PERFORMANCE OF TRANSIENT ELASTOGRAPHY AND
SERUM BIOMARKERS AS NON-INVASIVE METHODS FOR
ASSESSMENT OF HEPATIC FIBROSIS IN CHRONIC HEPATITIS C
EGYPTIAN PATIENTS
M. Alboraie1,* on behalf of Egyptian liver fibrosis study group, M. Khairy2,
A. Elsharkawy2, M. Elsharkawy3, N. Asem4, G. Esmat2 on behalf of Egyptian
Liver Fibrosis Study Group
1
Department of Internal Medicine, Al-Azhar University, 2Department of Endemic
Medicine and Hepatology, 3Department of Clinical and Chemical Pathology,
4
Department of Public Health and Community Medicine, Cairo University, Cairo,
Egypt
Contact E-mail Address: m.alboraie@gmail.com
INTRODUCTION: Different non-Invasive methods for assessing stage of hepatic fibrosis had emerged in the last decade. Most popular methods include transient elastography and serum biomarkers panels.
AIMS & METHODS: We aimed at studying the diagnostic performance of
transient elastography and five biomarker panels (APRI, FIB-4, Forns Index,
Egy-Score and Hepa-Index) in detecting different stages of hepatic fibrosis in
chronic hepatitis C Egyptian patients. Hundred treatment na ve chronic hepatitis
C patients were enrolled. They were subjected to liver biopsy and histopathological scoring of fibrosis according to METAVIR scoring system, transient elastography (using FibroScan), APRI, FIB4, Forns Index, Egy-Score and HepaIndex. Calculations and cut off values for biomarkers panels were done according to their original publications.
RESULTS: Significant fibrosis ( F2 METAVIR) was best detected by transient
elastography followed by Forns Index, Hepa-Index, Egy-Score, FIB-4, and
APRI respectively (AUROC: 0.947, 0.806, 0.803, 0.776, 0.645 and 0.589 respectively). Advanced fibrosis (F3 METAVIR) was best detected by transient elastography followed by Egy-Score, Forns Index, FIB-4, Hepa-index and APRI
respectively (AUROC: 0.976, 0.875, 0.851, 0.828, 0.783, and 0.754). Cirrhosis was
best detected by transient elastography followed by Egy-Score, FIB-4, Forns
Index, APRI and Hepa-Index respectively (AUROC: 0.958, 0.874, 0.841,
0.827, 0.795 and 0.744).
CONCLUSION: Transient elastography had the best performance for noninvasive assessment of hepatic fibrosis in chronic hepatitis C Egyptian patients
compared to the studied serum biomarkers.
Disclosure of Interest: None declared

A457

United European Gastroenterology Journal 2(1S)


P1188 TREATMENT OF PREVIOUSLY UNTREATED PATIENTS WITH
CHRONIC HCV GENOTYPE 1 INFECTION WITH BOCEPREVIR
(BOC) IN GERMAN REAL - LIFE: BASELINE AND ON-TREATMENT
PREDICTORS OF AN EARLY VIROLOGY RESPONSE
P. Buggisch1,*, H. Lohr2, G. Teuber3, H. Steffens4, M. Kraus5, C. John4,
P. Geyer6, B. Weber7, T. Witthoft8, A. Herrmann9, M. Hoesl10, U. Naumann11,
T. Dahhan12, D. Hartmann13, B. Dreher13, M. Bilzer13
1
ifi Institute, Hamburg, 2Gastroenterological Practice, Wiesbaden,
3
Gastroenterological Practice, Frankfurt, 4Practice of Internal Medicine, Berlin,
5
Medical Department II, Klinikum Burghausen, Burghausen, 6Gastroentorological
Practice, Fulda, 7Medical Practice, Kassel, 8Gastroentorological Practice, Stade,
9
Friedrich-Schiller-University, Jena, 10Gastroentorological Practice, Nurnberg,
11
Center of Medicine, Berlin, 12Gastroentorological Practice, Fellbach, 13MSD
Pharma GmbH, Haar, Germany
Contact E-mail Address: manfred.bilzer@bilzer-consulting.de
INTRODUCTION: The achievement of early virologic response (EVR) during
triple therapy of chronic HCV genotype 1 infection with BOC has been identified
as predictor of high SVR rates of up to 90% and as predictor to shorten treatment to 24 weeks. The present interim analysis of the NOVUS observational
study was aimed to investigate EVR during BOC triple therapy in German reallife and to identify factors associated with EVR.
AIMS & METHODS: From April 2012 until January 2014, 536 patients with G1
infection were recruited in the ongoing NOVUS study by 97 practices and hospitals in Germany. Patients were treated with pegylated interferons (PegIFN) and
ribavirin (RBV) together with BOC for 24 to 44 weeks after a 4 weeks lead-in
period with PegIFN/RBV. The present interim analysis was restricted to 203
untreated patients with documented HCV-RNA levels at treatment week 8.
RESULTS: The frequency of EVR was 73%. Achievement of EVR was significantly associated with age 50 years, baseline viral load 400.000 IU/mL,
normal gamma-GT levels and ferritin levels 300 mg/L at baseline, but not
with gender, ALT levels, glucose levels, platelet count or genotype 1 subtype
(table). The significant differences above were confirmed by univariate logistic
regression analysis. When a multivariate logistic regression model was used, viral
load and gamma-GT levels at baseline were identified as independent predictors
of EVR: baseline viral load (400.000 IU/mL vs 4400.000 IU/mL): OR 2.99 (CI
1.13-7.93; p 0.027); gamma-GT (normal vs elevated): OR 2.17 (CI 1.03-4.60;
p 0.042). In an expanded model that included virologic response at the end of
the 4-week lead-in period a HCV-RNA decline 41log10 (vs 1log10) was
strongly predictive of an EVR: OR 6.63 (CI 2.88-15.26; p50.0001).

Male/ Female
Age 50/450 years
Genotype 1a/1b
BVL: /4 400.000/ IU/mL
GGT normal/ elevated
ALT normal/ elevated
Platelets /4 150/nL
Glucose /4 100 mg/dL
Ferritin /4 300 mg/L

EVR (N 148) % (n/N)

P*

76.3
78.6
69.0
88.9
81.6
78.4
69.7
69.8
71.9

0.2161
0.0202
0.8122
0.0006
0.0013
0.3539
0.7997
0.8232
0.0419

(87/114) / 68.5 (61/89)


(99/126) / 63.6 (49/77)
(49/71) / 70.7 (70/99)
(56/63) / 65.7 (92/140)
(84/103) / 60.7 (54/89)
(29/37) / 70.8 (114/161)
(23/33) / 71.9 (110/153)
(67/96) / 71.9 (23/32)
(46/64) / 47.6 (10/21)

CONCLUSION: 73% of treatment-na ve patients with HCV G1 infection undergoing triple therapy with BOC in German real-life achieve an EVR. A low baseline viral load 400.000 IU/mL, normal gamma-GT values at baseline and a
HCV-RNA decline 41log10 at the end of the 4-week lead-in period are independent predictors for an EVR.
Disclosure of Interest: P. Buggisch Financial support for research from: MSD, H.
Lohr Financial support for research from: MSD, G. Teuber Financial support
for research from: MSD, H. Steffens Financial support for research from: MSD,
M. Kraus Financial support for research from: MSD, C. John Financial support
for research from: MSD, P. Geyer Financial support for research from: MSD, B.
Weber Financial support for research from: MSD, T. Witthoft Financial support
for research from: MSD, A. Herrmann Financial support for research from:
MSD, M. Hoesl Financial support for research from: MSD, U. Naumann
Financial support for research from: MSD, T. Dahhan Financial support for
research from: MSD, D. Hartmann Other: Employee of MSD, B. Dreher Other:
Employee of MSD, M. Bilzer Consultancy for: MSD
P1189 EFFICACY AND TOLERANCE OF ANTIVIRAL COMBINATION
THERAPY (PEGYLATED INTERFERON, RIBAVIRIN AND
TELAPREVIR OR BOCEPREVIR) IN HEPATITIS C VIRUS: COHORT
STUDY OF 100 PATIENTS
1,*

P. Guillouche , I. Archambeaud , C. Garret , M. Labat , E. Andre-Garnier ,


J. Gournay1
1
IMAD, 2Laboratoire de virologie - CHU Hotel Dieu, NANTES, France
Contact E-mail Address: pauline.guillouche@chu-nantes.fr
INTRODUCTION: Since 2011, the standard of care treatment of Hepatitis C
Virus genotype 1 is a combination of pegylated interferon, ribavirin and protease
inhibitor: telaprevir or boceprevir.
AIMS & METHODS: The aim of this study was to evaluate its effectiveness and
tolerance in real life. Single center retrospective study of 100 unselected and

consecutive patients whose antiviral treatment started between March 2011 and
March 2013.
RESULTS: The median age was 53 years and 72% of the patients were men;
46% were F4 and 15% were F3. Status regarding previous treatment was: naive
30%, responder-relapser 28%, partial responder 17% and null responder 24%.
After 2, 4, 8 and 12 weeks of treatment with protease inhibitor, Hepatitis C Virus
RNA was undetectable in respectively 12%, 52%, 60% and 64% of the cases.
The overall rate of sustained virological response at week 12 (intention to treat
analysis) was 57%: 70% in the naive patients, 75% in responder-relapser, 41% in
partial responder and 33% in null responder. During the therapy, the rate of
serious adverse events was 41%. Four deaths occurred. Initial platelets count
5100.000/mm3 and age  53 years were associated with a higher risk of occurrence of serious adverse events.
CONCLUSION: The rate of sustained virological response to tritherapy in real
life is approximately 10% lower than those observed in phase III trials.
Tolerance issues are limiting the use of protease inhibitor.
Disclosure of Interest: None declared
P1190 NON-INVASIVE LIVER FIBROSIS EVALUATION IN PATIENTS
WITH CHRONIC HCV AND HBV HEPATITIS
R. Zykus1,*, L. Jonaitis1, V. Petrenkiene_1, I. Valantiene_1, L. Kupcinskas1.2
Gastroenterology, 2Institute of Digestive Diseases, Lihuanian University of Health
Sciences, Kaunas, Lithuania
Contact E-mail Address: rzykus@gmail.com

INTRODUCTION: The role of non-invasive test to assess liver fibrosis is


increasing and they are gradually introduced in clinical practice. FibroScan is
dedicated tool for liver fibrosis evaluation. Aspartate aminotransferase to platelet
ratio index (APRI) and FIB4 score are cheap and easy reproducable in daily
praxis for liver fibrosis evaluation.
AIMS & METHODS: The aim of our study was to assess correlation between
transient elastography (TE), aspartate aminotransferase to platelet ratio index
(APRI), FIB4 score and histological stage of fibrosis (F). APRI index was
assessed as (AST elevation/platelet count) x 100 and FIB4 index as age (yr) 
AST (IU/L)/(platelet count (10(9)/L)  ALT^(1/2) (IU/L)). In this prospective
study the correlations of TE, APRI and FIB4 score with fibrosis stage were
assessed in 157 chronic HCV or HBV hepatitis patients. TE, APRI and FIB4
were measured at the same day before biopsy. Interquartile range/median 520%
and success rate 460% were considered as good quality criteria during TE.
Fibrosis was evaluated using METAVIR score. Pathologist was blinded to TE,
APRI, FIB4 results. Cut-off values were established by ROC analysis.
RESULTS: We included 139 HCV, 16 HBV and 2 coinfected patients. Strong
correlation of liver stiffness R - 0.76 (p50.01) and FIB4 R 0.66 (p50.01), but
moderate of APRI R 0.59 (p5 0.01) with liver fibrosis stage were established.
For histological F4 stage TE cut-off value 12.5kPa had sensitivity 0.90 and
specificity 0.87; APRI cut-off value 1.4 had 0.87 and 0.82; FIB4 cut-off value
2.89 had 0.84 and 0.84 respetively. F3 10.7 kPa (0.89 and 0.88), 1.18 (0.80 and
0.76), 2.23(0.85 and 0.80); F2 8.5 kPa (0.79 and 0.77), 0.95 (0.74 and 0.72), 1.63
(0.80 and 0.75); F1 5.5 kPa (0.82 and 0.76), 0.54 (0.82 and 0.76), 0.98 (0.82 and
0.69). Summarized results are shown in the table below.
Fibrosis TE in kPa
APRI
FIB4
stage
(sensitivity/specificity) (sensitivity/specificity) (sensitivity/specificity)
4
43
42
41

12.5 (0.90/0.87)
10.7 (0.89/0.88)
8.5 (0.79/0.77)
5.5 (0.82/0.76)

1.4 (0.87/0.82)
1.18 (0.80/0.76)
0.95 (0.74/0.72)
0.54 (0.82/0.76)

2.89
2.23
1.63
0.98

(0.84/0.84)
(0.85/0.80)
(0.80/0.75)
(0.82/0.69)

CONCLUSION: Liver TE and FIB4 score are strongly while APRI moderately
correlated with fibrosis and accurately predicts the stage of liver fibrosis in
patients with chronic HBV and HCV hepatitis. More advanced stage of liver
fibrosis are predicted more accurately. TE is more sensitive and specific than
APRI or FIB4 for andvanced liver fibrosis and cirrhosis.
Disclosure of Interest: None declared
P1191 REGULATING B CELLS MOBILIZED BY ACUTE PHASE GRAFT
INJURY PROMOTED TUMOR RECURRENCE AFTER LIVER
TRANSPLANTATION FOR LIVER CANCER
K. Man1,*, Y. Shao1, C.X. Li1, K.T. Ng1, C.M. Lo1
1
Department of Surgery, The University of Hong Kong, Hong Kong, China
Contact E-mail Address: kwanman@hku.hk
INTRODUCTION: Orthotopic liver transplantation (OLT) has been regarded as
the best curative treatment for patients with end stage liver diseases including
advanced liver cirrhosis and acute liver failure. It is also the alternative therapy
for patients with early stage hepatocellular carcinoma (HCC). Because of the
severe shortage of grafts from brain-death donors, and the importance of
timely operation on recipients, living donor liver transplantation (LDLT)
offers the unique opportunity of early transplantation with theoretically unlimited source of liver grafts. However, a liver graft from a living donor is frequently
small-for-size for the recipient. Acute phase fatty graft injury after transplantation will exacerbate further when the graft is small-for-size. Such acute phase
liver grafts injury will trigger a series of inflammatory cascades, which will mobilize the circulating immune cells leading to cancer invasiveness.

A458

United European Gastroenterology Journal 2(1S)

AIMS & METHODS: We aim to investigate the impact of acute-phase small-forsize graft injury on mobilization of circulating regulating B cells (Bregs) in HCC
patients after liver transplantation and to explore the molecular mechanism.
There were 115 HCC recipients included in current study. The intragraft gene
expression profile and Bregs infiltration of the grafts greater (Group 1) and less
than 60% (Group 2) of standard liver weight (SLW) were detected by RT-PCR
and immunostaining. Circulating Bregs (CD19CD24hiCD38hi) were also compared together with the clinical-pathological data including the incidence of
tumor recurrence and metastasis. The direct roles of TLR4, CXCL10 and
CXCR3 on circulating Bregs mobilization were investigated in TLR4-/-,
CXCL10-/- and CXCR3-/- mice models, respectively. The association of intragraft Bregs infiltration and tumor invasiveness were also examined in a rat liver
transplantation for liver cancer model. The role of Bregs on liver tumor growth
and invasiveness were further studied in a series of in vitro and in vivo functional
experiments with the application of in vivo imaging modalities and intravital
confocal microscopy.
RESULTS: The patients were grouped into Group 1 (4 60% SLW, n 37)
and Group 2 (560% SLW, n 78). Much more patients in Group 2 developed
tumor recurrence and lung metastasis [19/78(24.4%) vs 3/37(8%), p 0.04].
Level of circulating Bregs was significantly higher in Group 2 (Week1: 7.02 vs
1.31/10^5PBMC, p 0.03; month3: 5.7 vs 1.3/10^5PBMC, p 0.03). There was
more intragraft Bregs infiltration in group 2 indicated by CD20/IL10 staining.
Intragraft gene expression of TLR4, CXCL10 and CXCR3 were significantly
higher in Group 2 at early phase after transplantation. In rat liver transplantation model, more Bregs infiltration at early phase after transplantation correlated
with late phase invasive tumor growth. Levels of circulating Bregs were significantly lower in the mice model with major hepatectomy and hepatic I/R injury
using TLR4-/-, CXCL10-/- and CXCR3-/- mice, respectively. Bregs also promoted liver cancer cell proliferation and migration in vitro, and tumor growth
in vivo.
CONCLUSION: A significantly higher population of circulating Bregs, which
are mobilized by small-for-size graft injury, may lead to a higher incidence of
tumor recurrence and metastasis after LDLT. TLR4/CXCL10/CXCR3 signaling
may play important roles on Bregs mobilization.
Disclosure of Interest: None declared
P1192 DE NOVO INFLAMMATORY BOWEL DISEASE
ORTHOTOPIC LIVER TRANSPLANTATION FOR PRIMARY
SCLEROSING CHOLANGITIS

AFTER

L. Bajer1,*, P. Drastich1, P. Wohl1, M. Benes1, J. Spicak1


1
Hepatogastroenterology, Institute for Clinical and Experimental Medicine,
Prague, Czech Republic
Contact E-mail Address: lukasbajer1@gmail.com
INTRODUCTION: For patients who develop end-stage primary sclerosing cholangitis (PSC), orthotopic liver transplantation (OLTx) is the only effective treatment currently available. PSC is commonly associated with inflammatory bowel
disease (IBD), particularly with ulcerative colitis (UC) in 60-85% cases. De novo
IBD after OLTx has been reported, the 10-year risk is estimated to be 14-30%.
De novo inflammatory bowel disease activity and impact on the recurrent PSC
and colorectal cancer (CRC) after OLTx is not yet fully clear.
AIMS & METHODS: A total of 944 liver transplants were performed in IKEM
(Czech Republic) between 1995 and 2012. We analyzed 69 consecutive patients
with PSC (50 men and 19 women) who survived more than 12 months and were
regularly followed up in our center. IBD was confirmed in 49 (71%) patients preOLTx. Except 2 patients with Crohns disease (CD) all other patients were suffering from UC. Colonoscopy was performed in all patients before OLTx and
annually after OLTx. Patients were studied over median follow up period of 82
months (range 16-228) after OLTx.
RESULTS: The course of IBD was mild or in remission in 34/49 (69.4%)
patients after OLTx. The remaining 15 patients (30.6%) were suffering from
clinically active disease. De novo IBD was confirmed in 13 patients (UC 12,
CD 1) after median of 3 years (1-8) after OLTx. Except 2 patients the course
of IBD has been described as mild. Recurrent PSC (rPSC) was confirmed in total
of 25 patients (36.2%). Risk of rPSC was higher in de novo IBD vs. pre-TX IBD
group (9/13 vs. 17/49, p5 0.05). Low-grade dysplasia (LGD) of colonic mucosa
was found in 3/49 (6.1%) patients in pre-TX IBD vs. 1/13 of de novo IBD
patients. Advanced colorectal neoplasia was confirmed just in pre-TX IBD
group, high-grade dysplasia (HGD) in 1 (2.0%) patient and colorectal cancer
(CRC) was confirmed in 3 (6.1%) patients followed by colectomy.
CONCLUSION: The course of de novo IBD after OLTx is frequently mild but
could have negative impact on recurrent PSC. Detection of dysplastic changes
supports the usefulness of regular colonoscopic evaluations.
Disclosure of Interest: None declared
P1193 THREE-DIMENSIONAL CONFIGURATION AND IMPROVED
OXYGENATION PROTECT HEPARG PROGENITOR CELL LINEDERIVED HEPATOCYTES FROM HUMAN PLASMA
CYTOTOXICITY IN THE AMC-BIOARTIFICIAL LIVER
M.Van Wenum1.2,*, R. Chamuleau2, E. Hendriks1, T.van Gulik1, R. Hoekstra1.2
1
Surgical laboratory, 2Tytgat institute for Liver and Intestinal Research, Academic
Medical Center, Amsterdam, Netherlands
Contact E-mail Address: m.vanwenum@amc.nl
INTRODUCTION: The AMC-Bioartificial Liver (BAL) is a high-capacity bioreactor that facilitates the human liver progenitor cell line HepaRG in a nonwoven polyester matrix, where cells in 3D configuration are directly oxygenated
with 40% O2. The AMC-BAL is designed to bridge patients suffering from
Acute Liver Failure (ALF) to transplantation or regeneration and has proven

to be efficacious in prolonging survival in a rat model of total liver ischemia (1).


A phase I clinical trial has been planned for 2015. During patient treatment, the
cells in the BAL are exposed to human ALF plasma. It is therefore essential to
investigate the performance of HepaRG cells in human plasma. We previously
found that exposure to rat plasma reduced hepatic transcript levels and increased
cell leakage in both monolayer (2D, 20% O2) and BAL cultures (2.3). The effect
of healthy rat plasma was comparable to ALF-rat plasma. The effect of human
plasma is, however, unknown.
AIMS & METHODS: The aim of the study was to assess human plasma cytotoxicity on HepaRG cells in monolayer and BAL culture, and to investigate the
contribution of 3D arrangement and increased oxygenation to plasma tolerance.
We compared monolayer cultures and static 3D cultures in non-woven polyester
matrices under 20% (low-O2) and 40% O2 (high-O2), to BAL cultures.
At maximal differentiation, a baseline test was performed for ammonia elimination, urea synthesis, cell leakage, lactate elimination and transcript levels of the
genes encoding hepatic nuclear factor 4a (HNF4a), enzymes involved in ammonia metabolism including urea cycle, and detoxification protein CYP3A4.
Cultures were exposed to 100% plasma antibiotics (plasma group) or to standard culture medium (control group) for 16 hours, and subsequently tested again
on the parameters mentioned above. The differences between baseline and postexposure test were compared between groups.
RESULTS: After 16 hours of plasma exposure, in BAL cultures, HNF4a and
urea cycle genes were decreased up to 50% compared to control, but CYP3A4
expression remained stable. No significant change in hepatic functionality or cell
damage was observed.
In monolayers exposed to plasma under low-O2 all hepatic transcript levels and
ammonia elimination were decreased by up to 95% compared to control.
In both the 3D configuration group and the high-O2 group, mRNA transcription
of hepatic genes was less downregulated compared to the low-O2 monolayer
group, up to 75% of the controls, but the cytotoxic effect remained stronger
than in the BAL group.
CONCLUSION: Human plasma has a detrimental effect on HepaRG liver functionality and transcript levels, when cultured in 2D with 20% O2. However,
BAL-cultured cells are significantly less susceptible to plasma toxicity compared
to monolayer cultures, and both 3D configuration and increased oxygenation
contribute to this resistance to plasma cytotoxicity. This suggests that the duration of effective BAL treatment may last at least up to 16 hours. These results
should be confirmed with human ALF plasma.
REFERENCES
1. PLoS One 2012; 7: e38778.
2. Int J Artif Organs 2012; 35: 1006-1014
3. Liver Int 2013; 33: 516-524.
Disclosure of Interest: M. Van Wenum: None declared, R. Chamuleau Other: RC
is CSO of the University spin-off company Hep-Art Medical Devices, which has
the exclusive license of the AMC bioartificial liver. However, he owns no shares
of the company., E. Hendriks: None declared, T. van Gulik: None declared, R.
Hoekstra Financial support for research from: 50% of RH salary was paid by the
University spin-off company Hep-Art Medical Devices. Funders had no role in
study design, data collection and analysis, decision to publish, or preparation of
the abstract.
P1194 DE NOVO HEPATOCELLULAR CARCINOMA IN 4 LIVER
ALLOGRAFTS
M. Ble Caso1.2,*, A. Rubin1.2, C. Vinaixa2, V. Aguilera2, S. Benlloch2, R. LopezAndujar2, M. Berenguer2, M. Prieto2
1
CiberEHD, 2Hepatology and Liver Transplantation Unit, Hospital la Fe,
Valencia, Spain
Contact E-mail Address: marina.berenguer@uv.es
INTRODUCTION: De novo hepatocellular carcinoma (HCC) in liver allografts
is rare, with only 11 cases previously published in the last 14 yrs.
AIMS & METHODS: Our hospital has performed 1906 liver transplants (LT)
from 1991 to 2012. 914 (47.9%) were due to hepatitis C virus (HCV). 67 (7.3%)
of these were re-transplanted due to HCV recurrence and graft loss without
evidence of HCC in the explant. Induction and baseline immunosuppression
was based on calcineurin inhibitor (CNI) and all patients received metylprednisolone bolus as treatment of early acute cellular rejection. The median time to
HCC was 13.5 yrs (range 8-19); the median age at diagnosis was 66 yrs (range 5874). Three patients had chronic renal failure (one had a kidney transplant).
CONCLUSION: With improved survival of LT-patients and use of older allografts, an increase in the incidence of de novo malignancies may be expected.
There are no screening guidelines in this patient population. We should be aware
of the high-risk population of cirrhotic patients with HCV-allograft recurrence
and CNI based IS.
REFERENCES
1. Sotiropoulos GC, Frilling A, Molmenti EP, et al. De novo hepatocellular
carcinoma in recurrent liver cirrhosis after liver transplantation for benign hepatic disease: is a deceased donor retransplantation justified? Transplantation 2006;
82: 1112.
2. Morita K, Taketomi A, Soejima Y, et al. De novo hepatocellular carcinoma in
a liver graft with sustained hepatitis C virus clearance after living donor liver
transplantation. Liver Transpl 2009; 15: 1412-1416.
3. Waghray A, OShea R, Pai R, et al. Hepatocellular carcinoma complicating
recurrent hepatitis C after liver transplantation. Hepatology 2013 Jun 6.
Disclosure of Interest: None declared

A459

United European Gastroenterology Journal 2(1S)


Table to abstract P1194
Table 1 Clinical features and management of 4 cases of de novo HCC in liver allografts.

Years

Diagnosis
alfa-fetoprotein
(ng/mL)

Year of LT /
aetiology

Recipient sex / Donor sex /


age at diagnosis age

Time from LT
to cirrhosis / to HCC
HCC
characteristics

2002 / HCV

Female / 72

Female / 70

7 / 10

1993 / HCV

Male / 60

Female / 51

17 / 19

1995 / HCV & Male / 74


HCC

Male / 45

2 / 17

2005 / Multiple Male / 58


HCCs &OH

Female / 68

Chronic rejec- MRI HCC 1.5 cm Elevated alfa- 203


(segment 4b)
fetoprotein
tion 1 yr
& MRI. US
posLT / 8
failed to
detect the
tumour

Diagnosis
method

MRI and CT scan: Routine US


196.2
3.6 cm (segment
8), 4.3 cm (segment 7) and 3.2
cm (segment 4)
HCC
Multicentric and dis- Highly elevated 1283.6
seminated poorly
alfa-fetoprodifferentiated
tein & MRI.
HCC. Recurrent
Routine US
HCV cirrhosis.
the previous
Peritoneal and
month failed
pulmonary
to detect the
metastases.
tumour
CT scan: 2 cm HCC Routine US
3
(segment 4)

P1195 ACUTE LIVER FAILURE OF HYPOXIC CAUSE - AN OFTEN


OVERLOOKED ENTITY
S. Carvalhana1, D. Trabulo2,*, A.R. Goncalves3, A. Valente3, R. Palma3,
P. Alexandrino3, J. Velosa1
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Gastroenterology, Hospital
de Sao Bernardo, CHS, 3Gastroenterology and Hepatology Intensive Care Unit,
Hospital de Santa Maria, CHLN, Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: Hypoxic hepatitis or acute ischemic hepatocellular injury
represents 1% of Intensive Care Units (ICU) admissions. In most cases, it is
underdiagnosed due to a reduced awareness of clinicians to its complex etiopathogenesis, and association with hypotension in only about 40 % of patients.
AIMS & METHODS: Aims: Evaluation of the causes and prognosis of acute
liver failure (ALF) in an Intensive Care Unit with particular analysis of hypoxic
etiology.
Methods: Retrospective analysis of the period between 1992-2013, all patients
admitted to the Gastroenterology and Hepatology ICU with ALF; review of the
etiology, progression and outcome (survival, liver transplantation and death).
RESULTS: 90 patients studied, mean age 42 years, 59% men. Etiology: viral 35.6 % (HBV HDV - 60.0%); toxic - 33.3% (Amanita phalloides - 30.0%);
hypoxic - 16.6%; other - 11.1%; unknown - 3.3%. Causes of hypoxic ALF were:
atrial fibrillation - 6; drepanocytosis/thalassemia - 2; cardiomyopathy - 2; epileptic seizure - 2; acute myocardial infarction - 1; cor pulmonale - 1; neuroleptic
malignant syndrome - 1.
ALF mortality was 38.8 % (35 patients): viral 54.3%; toxic 34.3%; hypoxic
8.6%. 21 patients were referred for liver transplantation (23.3%) of which
17.7% were transplanted (16 patients). The majority of transplants were due to
toxic ALF (69%) and none was performed due to hypoxic causes. Although 47
% of patients with hypoxic ALF have had inotropic support, there was a good
clinical outcome.
CONCLUSION: Hypoxia is an etiology of ALF, which in our series represented
one sixth of admissions for ALF. The prognosis is good if the diagnosis is made
early on.
Disclosure of Interest: None declared
P1196 METABOLIC RADIOTHERAPY IN CHOLANGIOCARCINOMA:
IS THIS A VALID ALTERNATIVE?
A. I. Fernandes1,*, A. Brito2, A.C. Ribeiro2, A.M. Abrantes2, M. Laranjo2,
K. Santos2, A. Goncalves3, A.B. Sarmento-Ribeiro3, J.G. Tralhao4, F. CastroSousa4, C. Sofia1, M.F. Botelho2
1
Gastroenterology, Centro Hospitalar e Universitario de Coimbra, 2Institute of
Biophysics and Biomathematics, 3Molecular Biology Department, Faculty of
Medicine of the University of Coimbra, 4Surgery A, Centro Hospitalar e
Universitario de Coimbra, Coimbra, Portugal
Contact E-mail Address: xanafmuc@hotmail.com
INTRODUCTION: The Cholangiocarcinoma (CC) is a tumour with limited
therapeutic options. The natrium-iodide symporter (NIS) mediates the uptake
of iodine by thyroid, representing a key component in the successful metabolic
radiotherapy using iodine-131 (131I) in the treatment of thyroid tumours.
Recently it has been shown that the expression of NIS is increased in CC, opening the possibility of a new therapeutic approach for this type of tumour.

Treatment

Cause of death /
survival time
after diagnosis

Sorafenib (5
months)

Dead due to liver


failure complications / 5 months

Palliative

Dead of multiorgan
failure / 2 weeks

RF & transarter- Dead of pulmonary


ial chemoemsepsis / 10 months
bolization. No
HCC
recurrence
RF
Alive / 4 months
follow up

AIMS & METHODS: The aim of this study was to evaluate the therapeutic
efficacy of 131I in a human cell line of CC, the TFK1. Kinetic studies of influx
and efflux were performed in order to determine the profile of uptake and retention of 131I by the cell line. Subsequently, the cells were subjected to different
doses of 131I in order to evaluate and characterize the effects of metabolic radiotherapy. The effect on cell survival was evaluated by clonogenic assay using the
crystal violet staining. Flow cytometry was used to assess the type of induced cell
death, the effects on the expression of BAX, BCL2 and cytochrome c, changes on
mitochondrial membrane potential, as well as the production of reactive oxygen
species and anti-oxidant defenses. To determine the possible damages in the
DNA it was also performed the comet assay. To assess the cellular expression
of NIS, immunohistochemical methods were carried out using anti-NIS
antibody.
RESULTS: Treatment with 131I induced a decrease in cell viability dependent on
the dose. The predominant type of cell death was apoptosis, and it was accompanied by a decrease in the BCL2 and increase in the BAX expressions. It also
occurred release of cytochrome c and mitochondrial membrane depolarization.
Irradiation with 131I also induced breaks in DNA. Interestingly there were no
differences in the production of intracellular peroxides, superoxide dismutase and
reduced glutathione. The immunohistochemical study revealed a strong expression of NIS in this cell line, with a predominantly membrane localization.
CONCLUSION: The 131I caused a decrease in the survival of the studied cell line
(TFK1), inducing cell death by apoptosis, through the intrinsic pathway. The 131I
appears to be a promising option for the treatment of CC, considering the
membrane expression of NIS and the type of induced cell death.
Disclosure of Interest: None declared
P1197 SERUM/BILIARY MMP9 AND TIMP1 CONCENTRATIONS IN
THE DIAGNOSIS OF CHOLANGIOCARCINOMA
A.T. Ince1,*, K. Yldz1, V. Gangarapu1, Y. Kayar1, B. Baysal1, O. Kocaman1,
A. Danalioglu1, K. Turkdogan1, H. Senturk1
1
_
Gastroenterology, Bezmialem Vakf University, Istanbul,
Turkey
Contact E-mail Address: dralince@gmail.com
INTRODUCTION: Cholangiocarcinoma is generally detected late in the course
of disease, and current diagnostic techniques often fail to differentiate benign
from malignant disease. We analyzed the roles of serum and biliary MMP9 and
TIMP1 concentrations in the diagnosis of cholangiocarcinoma.
AIMS & METHODS: The 113 patients (55 males, 58 females) included 33 diagnosed with cholangiocarcinoma (malignant group) and 80 diagnosed with choledocholithiasis (benign group). MMP9 and TIMP1 concentrations were
analyzed in serum and bile and compared in the malignant and benign groups.
RESULTS: Biliary MMP9 concentrations were significantly higher (576  209
vs. 403  140 ng/ml, p50.01) and biliary TIMP1 concentrations were significantly lower (22.44.9 vs. 29.4  6.1 ng/ml, p50.01) in the malignant than in the
benign group. In contrast, serum MMP9 and TIMP1 concentrations were
similar in the two groups. Receiver operating curve analysis revealed that the
areas under the curve of bile MMP9 and TIMP1 were significantly higher than
0.5 (p50.001). The sensitivity, specificity, positive and negative predictive values,
positive and negative likelihood ratios and accuracy were 0.94, 0.32, 0.36, 0.93,
1.40, 0.19 and 0.5 for biliary MMP9, respectively, and 0.97, 0.36, 0.39, 0.97, 1.5,
0.08 and 0.54 for biliary TIMP1, respectively (Table I).

A460

United European Gastroenterology Journal 2(1S)

Table I. Concentrations of MMP9 and TIMP1


Table to abstract P1197

Serum MMP9
(cut-off: 325 ng/
ml)
Bile MMP9 (cutoff: 350 ng/ml)
Serum TIMP1
(cut-off: 205 ng/
ml)
Bile TIMP1 (cutoff: 31 ng/ml)

Sensitivity Specificity PPV

NPV PLR

NLR Accuracy

0.7273

0.3625

0.32

0.7631 1.1408 0.7523 0.4690

0.9394

0.325

0.3647 0.9286 1.3917 0.1864 0.5044

0.9697

0.1375

0.3168 0.9167 1.1243 0.2204 0.3805

0.9697

0.3625

0.3855 0.9667 1.5211 0.0836 0.5398

CONCLUSION: Serum and biliary MMP9 and TIMP1 concentrations do not


appear to be useful in the diagnosis of cholangiocarcinoma.
REFERENCES
1- Qin XL, Wang ZR, Shi JS, et al. Utility of serum CA199 in diagnosis of
cholangiocarcinoma: in comparison with CEA. World J Gastroenterol 2004; 10:
427432.
2- Schropfer A, Kammerer U, Kapp M, et al. Expression pattern of matrix
metalloproteinases in human gynecological cancer cell lines. BMC Cancer
2010; 10: 553.
3- Leelawat K, Sakchinabut S, Narong S, et al. Detection of serum MMP-7 and
MMP-9 in cholangiocarcinoma patients: evaluation of diagnostic accuracy.
BMC Gastroenterol 2009; 9: 30.
4-Gao ZL, Zhang C, Du GY, et al. Clinical significance of changes in tumor
markers, extracellular matrix, MMP-9 and VEGF in patients with gastric carcinoma. Hepatogastroenterology 2007; 54: 1591155.
Disclosure of Interest: None declared
P1198 DEVELOPMENT OF A SWINE BENIGN BILIARY STRICTRURE
MODEL USING ENDOBILIARY RADIOFREQUENCY ABLATION
D.H. Lee1,*, S. Jeong1, Y.W. Shin1
1
Internal Medicine, Inha University School of Medicine, Incheon, Korea, Republic
Of
Contact E-mail Address: inos@inha.ac.kr
INTRODUCTION: An established and reproducible animal model of benign
biliary stricture (BBS) has been indispensable to develop new devices or methods
for endoscopic treatment of biliary stricture.
AIMS & METHODS: We studied how to make a porcine BBS model using
endobiliary radiofrequency ablation (RFA). Fourteen-month-old, female mini
pigs (Sus scrofa), each approximately 30 kg, were used. Endoscopic retrograde
cholangiography (ERC) was performed in 12 swine. The animals were allocated
to three groups (100 W, 80 W, and 60 W) according to the electrical power level
of RFA electrode. Endobiliary RFA was applied to the common bile duct for 60
seconds using by RFA probe which could be endoscopically inserted. ERC was
repeated two and four weeks respectively after the RFA to identify BBS. After
the strictures were identified, the animals were euthenized and bile duct samples
were achieved to evaluate the pathologic findings.
RESULTS: BBS were verified in all animals. Cholangitis were detected on endoscopic findings of day 14 in all the animals of 3 groups, but not significant. Bile
duct perforations occurred in 1 swine (n 1, 100%) for 100 W group, and 1 swine
(n 7, 14.3%) for 80 W group. There was no major complication (n 4, 0%) in
60 W group. All benign strictures were proven pathologically. The pathologic
findings resembled BBS in human.
CONCLUSION: The application of endobiliary RFA with 60 W-electrical power
resulted in a safe and reproducible swine model of BBS.
Disclosure of Interest: None declared

shown. The estimated incidence rate per three-year period progressively increased
from 1.33 to 1.996 to 4.99 and 6.48 per 100.000 for the periods 2002-2004, 20052007, 2008-2010 and 2011-2013 respectively. Median survival time was 7 months
[SE 1.76 95% CI 3.53-10.46]. Median survival times according to location were 3
months [SE 2.61] for intrahepatic, 6 months [SE 1.4] for Klatskin tumors and 11
months [SE 1.88] for bile duct carcinomas.
CONCLUSION: A steady incidence increase of cholangiocarcinoma cases in
Crete during the time period 2002-2013 was shown. This is probably due to
changing dietary habits since both the genetic background and other environmental factors in the island are more or less stable.
Disclosure of Interest: None declared
P1200 HELICOBACTER BILIS IS A RISK FACTOR ASSOCIATED TO
EXTRAHEPATIC BILIARY CANCER IN A MEXICAN POPULATION
A. Guitron-Cantu1, F.K. Segura-Lopez2,*, F. Aviles-Jimenez3, H. ValdezSalazar3, A. Hernandez-Guerrero4, S. Leon-Carballo5, L. Guerrero-Perez6,
J. Garcia-Correa7, G. Alfaro-Fattel8, J.G. Fox9, J. Torres3
1
Gastrointestinal Endoscopy, 2PhD Fellow, Mexican Institute of Social Security,
Torreon, 3Infectious Diseases Research Unity, Mexican Institute of Social
Security, 4Gastrointestinal Endoscopy, National Cancer Institute, Mexico City,
5
Gastrointestinal Endoscopy, ISSSTECh, Tuxtla Gutierrez, Chiapas,
6
Gastrointestinal Endoscopy, Mexican Institute of Social Security, Juarez,
Chihuahua, 7Gastrointestinal Endoscopy, Mexican Institute of Social Security,
Guadalajara, Jalisco, 8Gastrointestinal Endoscopy, Mexican Institute of Social
Security, Mexico City, Mexico, 9Medicine Comparative, MIT, Cambridge MA,
United States
Contact E-mail Address: aguitron@prodigy.net.mx
INTRODUCTION: The biliary tract cancer (include gallbladder, common bile
duct (CDB) and Vater s ampulla) is the sixth cause of death for all cancer in
Western countries with a global incidence rate of 2-6/100.000 habitants.
Approximately 178.101 new cases of gallbladder carcinoma and 142.813 deaths
were recorded in 2012. Although etiology and pathogenesis remain unclear,
genetic alterations, environmental, and infection with enterohepatic
Helicobacter spp such as H. bilis, H. hepaticus, or H. cholecystus have been
suggested as risk factors.
AIMS & METHODS: The aim of this work was to study whether H. bilis or H.
hepaticus are associated with bile duct cancer.
Multicenter, case-control study performed in 18 states of Mexico between May
2012-December 2013, included adults diagnosed with malignant stenosis of CBD
and patients with benign pathology of the bile duct matched by sex, age ( 5
years) and place of residence. The diagnosis was made by endoscopic retrograde
cholangiopancreatography (ERCP). All cases were confirmed by brush cytologyhistopathology and clinical course. Epithelial cells were obtained by scraping the
biliary ducts during ERCP and brushes were suspended in buffer solution and
frozen at -80 C until tested. DNA was extracted from brushed cells using
QIAamp DNA easy kit (Qiagen, Hilden, Germany) and quantified using
PicroGreen kit (Life technologies, Carlsbad, CA). A PCR reaction to amplify
a 207 bp fragment from the 16S rRNA gene specific for H. bilis and H. hepaticus
was performed. Differences between groups were analyzed by chi square test, and
odds ratio determined using Epidat 3.1 programme.
RESULTS: The study included 194 Mexican patients, 103 samples corresponded
to extrahepatic bile duct cancer: 66 CBD, 11 gallbladder and 26 of Vater s
ampulla. Mean age of cases was 61.8113.95 years, 41 were men and 62
women. As controls, bile duct samples were obtained from 91 patients: 64 choledocholithiasis, 6 cholecystolithiasis, 3 biliary leaking, 14 benign stenosis, 2
normal biliary duct, 1 biliary post-surgical stenosis and one choledochal cyst.
H. bilis was positive in 44 (42.78%) of the patients with extrahepatic biliary
cancer and in 19 (20.88%) of controls and difference was statistically significant
(p 0.002). Odds ratio for extrahepatic biliary cancer with H. bilis in comparison
with gallstones or another benign pathology was 2.83 (95% CI 1.49-5.32). H
hepaticus was detected in 17 (16.5%) cases, and 13 (14.28%) controls, a difference which was not significant (p 0.82)
CONCLUSION: Our results suggest that H. bilis, but not H. hepaticus might be
a risk factor to develop extrahepatic biliary cancer in Mexican population.
Disclosure of Interest: None declared

P1199 INCREASING INCIDENCE OF CHOLANGIOCARCINOMA IN


CRETE 2002-2013
V. Tzimourtos1, S. Terzoudis1, C. Georgousaki1, A. Papadopoulos1,
A. Dailiani2, D. Tsetis2, G. Paspatis3, I. Mouzas1, E. Kouroumalis1,*
1
Gastroenterology, 2Radiology, University Hospital of Crete, 3Gastroenterology,
Venizeleion Hospital, Heraklion, Greece
Contact E-mail Address: bbtzim@gmail.com
INTRODUCTION: Epidemiological data on cholangiocarcinoma in Greece is
limited. Crete has a homogeneous population and environmental factors are
uniform.
AIMS & METHODS: Patients with cholangiocarcinoma, resident on the island
of Crete, diagnosed between 2002 and 2013 in the two reference centers, were
studied. Periampullary tumors were excluded. Data were prospectively and retrospectively collected from the database of the 2 major hospitals of Crete. Crude
incidence rates are presented. The statistical analysis was performed with the
SPSS 19 software.
RESULTS: During the 12-year period a total of 89 patients (55.6% males,
median age 74 years) were diagnosed with cholangiocarcinoma. 7 of them had
cholangiocarcinoma of the intrahepatic ducts, 42 were hilar Klatskin tumors and
40 patients were diagnosed with extrahepatic ducts carcinoma. Diagnosis was
radiologically established in 91% of the cases (40% MRCP, 28% CT, 20%
ERCP, 3% PTC), while histological diagnosis was available in 8 (9%) patients.
A steady incidence increase of cholangiocarcinoma, irrespective of location, was

P1201 LONG TERM FOLLOW-UP DATA OF PATIENTS


DEFERRED CHOLECYSTECTOMY AFTER SUCCESSFUL EST

WHO

J.Y. Lee1,*, J.W. Y. Shin1, J.H. Park1, Y.H. Joo1


1
Gastroenterology, Changwon Fatima Hospital, Changwon city, Korea, Republic
Of
Contact E-mail Address: vastus1@hanafos.com
INTRODUCTION: Endoscopic sphincterotomy (EST) has been the optimal
therapy for choledocholithiasis since it was introduced in 1974. And the cholecystectomy is generally recommended after EST in cases with gall bladder stone.
But there are debates if the cholecystectomy is necessary for all of the patients,
and lots of patients defer cholecystectomy for various reasons. We studied the
natural courses of patients with gall bladder stone who deferred cholecystectomy
after EST in our clinic.
AIMS & METHODS: There were 727 patients with gall bladder stone who
received EST for CBD stone from 2004 to 2012 in Changwon Fatima
Hospital. 605 patients received cholecystectomy soon after EST, and the other
122 patients who defered operation were analyzed retrospectively by chart review
and phone calls. 43 patients were lost to follow up and 79 patients were finally
enrolled.
RESULTS: The mean age was 72.88 years and the mean follow up duration was
39.73 months. 28 patients had biliary recurrence (35.4%) and 12(15.1%) patients

United European Gastroenterology Journal 2(1S)


received emergent cholecystectomy later. All-cause death was occurred in
9(11.3%) patients. The mean interval to 1st biliary recurrence was
17.9(months) and the types of recurrence were mostly cholangitis (16 pts) followed by cholecystitis (15 pts) and uncomplicated biliary pain (3 pts). 34 patiens
(43%) defered cholecystectomy for old age, 29 patients (36.7%) defered for
personal reasons and 16 patients (20.2%) were high risk for operation. In 9
cases of death, cause of death was cancer in 4 patients and 3 patients were
died of pneumonia. There were no biliary complication related death.
CONCLUSION: There was significant biliary recurrence who had gall bladder
stone but defered cholecystectomy after receiving EST for CBD stone. Many
patients defer operation because of old age and personal reasons. They should
be warned enough about high incidence of biliary recurrence despite rare mortality of biliary complication.
Disclosure of Interest: None declared
P1202 PROTEOMIC ANALYSIS OF HUMAN BILE SAMPLES
IDENTIFIES NOVEL MARKERS FOR CHOLANGIOCARCINOMA IN
PATIENTS WITH, AS WELL AS WITHOUT, UNDERLYING
PRIMARY SCLEROSING CHOLANGITIS
K.S. Jabbar1.2,*, P. Hedenstrom1, L. Eklund1, G.C. Hansson2, R. Sadik1
1
Department of Gastroenterology and Hepatology, Sahlgrenska University
Hospital, 2Department of Medical Chemistry, Gothenburg University, Gothenburg,
Sweden
Contact E-mail Address: karolina.sjoberg@medkem.gu.se
INTRODUCTION: Cholangiocarcinoma is a cancer form that is often detected
late, resulting in poor prognosis. Its diagnosis is challenging, particularly in the
context of primary sclerosing cholangitis (PSC). The aim of this study was to
identify potential novel bile biomarkers for cholangiocarcinoma in patients with/
without PSC.
AIMS & METHODS: Bile samples were prospectively collected from 21 patients
referred for ERCP: 6 patients with a clinical diagnosis of cholangiocarcinoma (3
with and 3 without underlying PSC), 5 patients with PSC without suspicion of
cholangiocarcinoma, and 10 patients with other benign bile duct diseases.
Following delipidation, samples (60ml) were prepared by the filter aided sample
preparation (FASP) method (modified), and digested by trypsin, before analysis
by nano-LC MS/MS on a Q-Exactive instrument. Data were searched against the
UniProt/Swissprot database using the Mascot software. At least one peptide at
the 99% significance level with a score of 20 or above was required for protein
identification.
RESULTS: The on-filter digestion approach, performed, to our knowledge, for
the first time on bile, appeared to work well. Up to 758 individual protein
identifications were possible from one sample, and the total time for preparation
and analysis for all aspirates was less than a week. Interestingly, there was little
resemblance between the PSC-associated and non-PSC -associated cholangiocarcinoma samples. Several markers for non-PSC-associated cholangiocarcinoma
were identified, including EPS8L2 (3/3 non-PSC-cholangiocarcinomas, 0/18
others; p 0.0008 [Fisher s Exact test]) and SLC9A3R1 (p 0.003). Promising
markers for PSC-associated cholangiocarcinoma are PDE4DIP (Myomegalin)
(2/3 PSC-associated cholangiocarcinomas, 0/18 others; p 0.01), and ITGA6
(Integrin alpha-6) (p 0.04). Importantly, neither of the latter markers was
found in PSC patients without suspicion of cholangiocarcinoma.
Furthermore, several differences between PSC (n 8) and non-PSC (n 13)
samples were detected including the upregulation of S100P (p 0.03) and downregulation of EZR (Ezrin) (p 0.02) in PSC samples. These two proteins are
previously known to interact with each other, and S100P has been implicated
in carcinogenesis, through the activation of ERK and NFB signalling pathways.
CONCLUSION: A novel preparation method for proteomic analysis of human
bile was evaluated, and proved to be simple, fast, and generate a high number of
protein identifications. Several promising markers for PSC-associated and nonPSC-associated cholangiocarcinoma, were tentatively identified.
Disclosure of Interest: None declared
P1203 AUTOCRINE VEGF SIGNALING IN EXTRAHEPATIC BILE DUCT
CANCER: CORRELATION WITH PATIENTS PROGNOSIS AND
TUMOR CELL PROLIFERATION
Y. Zhang1,*, S. Peng1, J. Li1, M. Chen1
Division of Gastroenterology & Hepatology, The First Affiliated Hospital of Sun
Yat-Sen University, Guangzhou, China
1

INTRODUCTION: Tumor cells express vascular endothelial factor (VEGF) that


can activate VEGF receptors (VEGFRs) on or within tumor cells to promote
growth in an angiogenesis-independent fashion, however, this autocrine VEGF
pathway is not reported in extrahepatic bile duct cancer (EBDC) and the role of
autocrine VEGF pathway in cholangiocyte pathophysiology and clinical significance is yet unknown.
AIMS & METHODS: Immunohistochemistry were used to characterize the
expression of VEGF and phospho-VEGF receptors in EBDC patients. Using
EBDC cell lines, we studied the mechanism of VEGF signaling on EBDC cell
proliferation.
RESULTS: The number of VEGF-positive, pVEGFR1-positive and pVEGFR2positive cases was 40 (55.5%), 26 (36.1%) and 24 (33.3 %), respectively.
Comparison of clinicopathological characteristics and immunohistochemistry
showed that the positive expression of pVEGFR1 and pVEGFR2 significantly
correlated with the poorer survival. The positive expression of pVEFR1 was a
significant independent poor prognostic factor in EBDC. The pVEGFR1 expression was positively correlated with cell proliferation marker pErk1/2 in EBDC
tissues. In vitro, we showed that VEGF promoted phosphorylation of VEGFR1
and VEGFR2 in an autocrine fashion, which is pro-proliferative through a PLC-

A461
ERK pathway. Sorafenib treatment inhibited cell proliferation and reduced
VEGF secretion by inactivating autocrine VEGF pathway.
CONCLUSION: In EBDC, the pVEGFR1 and pVEGFR2 expression are prognostic factors of the poorer survival. The activation of autocrine VEGF signaling
promotes EBDC cell proliferation, supporting a role of autocrine VEGF signaling as potential therapeutic target for clinical treatment.
Disclosure of Interest: None declared
P1204 HISTOLOGIC EFFECT OF IN VIVO RADIOFREQUENCY
ABLATION ON BILE DUCT IN SWINE MODEL: A PRELIMINARY
EXPERIMENT
Y.W. Shin1,*, S. Jeong1, D.H. Lee1
1
Internal Medicine, Inha University School of Medicine, Incheon, Korea, Republic
Of
Contact E-mail Address: inos@inha.ac.kr
INTRODUCTION: Radiofrequency ablation (RFA) exerts heat energy on target
tissue to induce localized necrosis. It has been used for local control of liver
cancer. We recently developed RFA electrode and RF generator which can
monitor total emitted amount of heat energy in real time for endobiliary
application.
AIMS & METHODS: We evaluated histologically injury depth and whether
perforation occurs or not in bile duct according to thermal energy amount
after in vivo biliary RFA experiment of swine model. 14-month-old, female
mini pigs (Sus scrofa) were used. After laparotomy and duodenal incision, guidewire was inserted into the common bile duct (CBD) through the major duodenal
papilla. RFA electrode was passed over the guidewire, and placed in the distal
CBD. Then RFA was applied to the CBD in different total energy amount of
laser (50, 100, 150, 200, 300, and 1000 joule) with different target temperatures
(80 and 90 oC). All mini pigs were sacrificed right after the procedure and bile
duct samples were achieved to evaluate the pathologic findings.
RESULTS: Total eight mini pigs were verified for pathologic analysis. Mean
value of injury depth of the bile ducts were 50 m, 125 m, and 150 m in
50, 100, and 150 joule-group, respectively. Bile duct perforations were observed
in all 3 swine at 200 joules or more with 90 oC of target temperature.
CONCLUSION: The application of in vivo endobiliary RFA under 150 joules of
total heat energy with less than 80 oC of target temperature may result in unperforated, dose-dependent thermal injury of the bile duct.
Disclosure of Interest: None declared
P1205 LIVER RESECTION IS A BETTER SURVIVAL THAN SORAFENIB
IN HEPATOCELLULAR CARCINOMA PATIENTS IN BARCELONA
CLINIC LIVER CANCER STAGE C WITH MACRO VASCULAR
INVASION
C.-W. Lin1,*, G.-H. Lo2, C.-C. Hsu1, D.-S. Perng1, L.-R. Mo1, P.-M. Hsieh3, Y.S. Chen3
1
Division of Gastroenterology and Hepatology, Department of Medicine,, 2E-DA
Hospital/ I-SHOU University, Kaohsiung, United States, 3Department of Surgery,
E-DA Hospital/ I-SHOU University, Kaohsiung, United States
Contact E-mail Address: lincw66@gmail.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most
common malignancies, with an increasing incidence and is the third leading
cause of cancer-related mortality in the world. Liver resection remains the curative therapy for BCLC stage A. For BCLC stage C, the efficacy of sorafenib has
been demonstrated in clinical practice. However, certain patients could still benefit from liver resection than sorafenib, especially in Asian.
AIMS & METHODS: This study aims to evaluate and compare overall survival
in HCC patients in BCLC stage C with macro vascular invasion treated with liver
resection and sorafenib.
We retrospectively reviewed the medical records of 138 newly diagnosed hepatocellular carcinoma patients between 2005 and 2013 in BCLC stage C with
macro vascular invasion and Child-Pugh class A were analyzed and compared
at E-DA hospital, Taiwan.
RESULTS: Sixty-two patients (45%) were treated with surgical resection and 76
patients were treated with sorafenib (55%). The average age is 57.9 and 60.8
years old in the resection and sorafenib group, respectively. The rate of male is
78.8% and 82.6% in the resection and sorafenib group, respectively. The rate of
HBV is 56.8% and 60.2% in the resection and sorafenib group, respectively.
Median survival was 30.3 months (range 1.5-90.2 months) in resection group
compared with 7.6 months (range 1.1-15.2 months) in the sorafenib group
(p50.001). The 1-year survival rate is 67.8% and 15.6% in the resection group
and sorafenib group, respectively.
CONCLUSION: Liver resection gets a better survival than sorafenib in HCC
patients at BCLC stage C with macro vascular invasion and Child-Pugh class A.
REFERENCES
[1] Llovet JM, Burroughs A and Bruix J. Hepatocellular carcinoma. Lancet 2003;
362: 19071917.
[2] Bosch FX, Ribes J, Diaz M, et al. Primary liver cancer: worldwide incidence
and trends. Gastroenterology 2004; 127: S5S16.
Disclosure of Interest: None declared

A462
P1206 PATIENT-TARGETED
AND
MULTIDISCIPLINARY
MANAGEMENT IMPROVES SURVIVAL IN PATIENTS WITH HCC:
THE HEPATOCATT EXPERIENCE
E. Rinninella1,*, M. Montagna1, A. Saviano1, T. Di Rienzo1, M. Ciresa1,
L. Laterza1, C. Mele1, M.A. Zocco2, L. Riccardi2, M.E. Ainora1, M. Biolato1,
A. Grieco2, M. Siciliano2, E.B. Annicchiarico2, M. Pompili2, F. Giuliante3,
A.W. Avolio3, S. Agnes3, R. Iezzi4, R. Inchingolo4, A. De Gaetano4,
L. Bonomo4, F.M. Vecchio5, N. De Matthaeis6, G.L. Rapaccini6, A. Gasbarrini2
1
Universita` Cattolica del Sacro Cuore, Rome, Italy, 2Department of Medical
Sciences, 3Department of Surgical Sciences, 4Department of Radiological Sciences,
5
Department of Anatomopathology, 6Division of Internal Medicine and
Gastroenterology (CIC), Universita` Cattolica del Sacro Cuore, Rome, Italy
Contact E-mail Address: emanurinni@yahoo.it
INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth most common
and the third cause of cancer-related death in the world. Due to its complex and
heterogeneous nature, HCC could represent a real challenge for clinicians. The
overall survival rate in West countries population is 63% at 1 year, 29% at 3
years and 33% at 1 year in untreated patients.
AIMS & METHODS: The aim of our study is to analyze the impact of a multidisciplinary approach on patients survival, comparing survival of our centre
with data published in literature. Since September 2008 to September 2013,
medical records of 636 patients with primitive lesions of the liver (including
benign tumors and dysplastic nodules) were collected in the archive of our centres Multidisciplinary Group (HEPATOCATT) and were retrospectively
reviewed. For the survival analysis we selected 463 HCC patients for whom an
adequate follow-up was available. Therapeutic strategies for each patient have
been decided after collegial discussion with different specialists according to the
stage of disease, the liver damage and the patients clinical state, also adopting
BCLC international guidelines.
RESULTS: Data analysis showed an overall survival of 79% and 56% at 1 and 3
years respectively. 51% patients presented with early stage HCC (BCLC A), 27%
with BCLC B, 17% with BCLC C and 5% with end stage HCC (BCLC D). The
survival analysis according to BCLC stage showed a survival rate of 90% at 1 and
69% at 3 years for BCLC A, 78% at 1 and 52% at 3 years for BCLC B, 53% at 1 and
25% at 3 years for BCLC C, 59% at 1 and 31% at 3 years for BCLC D (p50.01).
CONCLUSION: The current study shows that a patient-targeted and multidisciplinary management of patients with HCC allows similar or slightly better
survival rates than data of literature. This was particularly evident for advanced
stages. Furthermore, our study shows a better survival rate for BCLC D than for
BCLC C stage, proving that a customized therapy of the underlying liver disease
allows even patients with advanced HCC to access potentially curative
treatments.
REFERENCES
1. Mark op den Winkel M, Nagel D, et al. Prognosis of patients with hepatocellular carcinoma. validation and ranking of established staging-systems in a large
western HCC-cohort. PLoS One 2012; 7.
2. Camma` C, Di Marco V, Cabibbo G, et al. Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH
staging systems. Aliment Pharmacol Ther 2008; 28: 62-75.
3. Jorge A. Marrero, Robert J. Fontana et al. Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology 2005;
41: 707-716.
4. Hsu CY, Hsia CY, et al. Selecting an optimal staging system for hepatocellular
carcinoma: comparison of 5 currently used prognostic models. Cancer 2010; 116:
3006-3014.
Disclosure of Interest: None declared
P1207 VASCULAR ENDOTHELIAL GROWTH FACTOR AND HYPOXIA
INDUCIBLE FACTOR IN HCC: PROGNOSTIC ROLE IN PATIENTS
UNDERGOING CONVENTIONAL AND DEB-MEDIATED
CHEMOEMBOLIZATION
G. Peserico1, G. Castelli1, C. Perini1, C. Pozzan1, V. Vanin1, A. Giacomin1,
R. Cardin1, M. Piciocchi1, D. Paccagnella2, V. Iurilli3, F. Farinati1,*
1
Policlinico Universitario di Padova, 2Ospedale SantAntonio, 3Azienda
Ospedaliera di Padova, Padova, Italy
Contact E-mail Address: fabio.farinati@unipd.it
INTRODUCTION: Transcatheter arterial chemoembolization (TACE) is the
conventional palliative treatment for HCC in the BCLC intermediate stage.
Factors interfering with effectiveness include the neo-angiogenic reaction due to
ischemia, with changes in circulating vascular endothelial growth factor (VEGF)
and hypoxia-inducible factor (HIF) levels after TACE.
AIMS & METHODS: Our study sought significant differences in neo-angiogenesis before and after conventional TACE (C-TACE), compared to DC-Beads
mediated TACE (DEB-TACE), measuring serum VEGF and HIF levels.
VEGF and HIF levels (ELISA) were determined in the sera and plasma, respectively, of 129 consecutive HCC intermediate stage patients, before TACE (t0) and
4 weeks after (t1). C-TACE was administered to the first 86 patients and DEBTACE to the next 43. Tumour vascularization was evaluated at t0 and response
to treatment at t1, based on angiography and sCT scan (mRECIST criteria).
RESULTS: VEGF levels at t0 significantly correlated with lesion size (0.005) and
number (0.004) in both C- and DEB-TACE. HIF levels at t0 significantly correlated with aetiology (0.02), in particular with HCV, and large size lesions (0.05)
both overall and in patients undergoing DEB-TACE. VEGF showed a significant
increase from t0 to t1 overall (0.002) and separately in C-TACE and DEB-TACE
(0.02). The t0-t1 variation in HIF was not significant. The two markers showed
opposite trends, with an increase in VEGF after treatment and a decrease in HIF
(chi square 0.0001). An inverse significant correlation was observed between the

United European Gastroenterology Journal 2(1S)


two markers, with high VEGF at t0 corresponding with low HIF at t1 (0.03).
VEGF t0 levels and tumour size were singled out in the Cox multivariate analysis
as independent predictors of survival, with no significant results with respect to
HIF. DEB-TACE and C-TACE effects in terms of mRECIST response to treatment did not differ, with similar severity of side effects and, finally, survival.
CONCLUSION: Our study confirms the evidence so far obtained for VEGF,
that is confirmed as an independent predictor of survival, with higher levels
identifying patients with worse prognosis. An unpredicted reduction after treatment of HIF was observed, in contrast with the few studies carried out so far,
mostly oriental, which may suffer from small sample size and an ethnicity-related
bias. The interesting correlation with viral aetiology, in particular with HCV,
should be explored further, in order to search for possible viral and cellular
molecular targets, involved in HIF-mediated carcinogenesis. The opposite behaviour of the two markers could be attributable to activation of alternative pathways, such as that involving VEGF, mediated by SP1 and PI3K/Akt, or it could
depend on different transcription sites (VEGF being preponderantly produced in
the pericancerous tissues and HIF in the tumour area). DEB-TACE and CTACE seem equally effective as regards response to treatment, side effects and,
most importantly, impact on survival.
Disclosure of Interest: None declared
P1208 ASSOCIATION OF IL-28B RS12979860 GENE POLYMORPHISM
AND HEPATOCELLULAR CARCINOMA IN PATIENTS INFECTED
WITH HCV GENOTYPE 4
A.Z. Elsamanoudy1, S.M. Abo El-Khair1, H. Abdelaziz Abdalla1, T. Besheer2,
H. Elalfy2,*, A.H. A. Metwali33
1
MEDICAL BIOCHEMISTRY, 2tropical medicine, 3INTERNAL MEDICINE,
mansoura university, mansoura, Egypt
Contact E-mail Address: elalfy_hatem66@yahoo.com
INTRODUCTION: Hepatitis C infection is a major global public health problem. Egypt has the highest prevalence of HCV worldwide with 9% countrywide
and up to 50% in certain rural areas [1] and the highest prevalence of HCV-4,
which is responsible for almost 90% of infections and is considered a major cause
of chronic hepatitis, liver cirrhosis, hepatocellular carcinoma [2]. Hepatocellular
carcinoma (HCC) is the fifth most common tumor and the third most common
cause of cancer-related deaths worldwide [3]. There are few and controversial
data available on the association between IL-28B SNPs and severity of liver
fibrosis, presence of cirrhosis or developing HCC [4].
AIMS & METHODS: The current study aimed to investigate the association
between rs12979860 SNP of IL-28B gene and HCC in Egyptian patients infected
with HCV genotype 4. This hospital-based study included 150 patients with HCV
infection that were classified into three groups: 50 patients with chronic hepatitis,
50 patients with cirrhosis, and 50 patients with hepatocellular carcinoma. The
plasma Human interleukin 28B levels, liver enzymes activities and serum levels of
total proteins, albumin, and  fetoprotein were measured, spiral computed triphasic scanning in focal hepatic lesion for documentation of HCC diagnosis
(vascular flush with rapid washout). Also, Genotyping of IL-28B rs12979860
C/T allele Polymorphism was carried out using RFLP-PCR.
RESULTS: Fifty patients (33.3%) were CC homozygous genotype, whereas, the
other 100 patients were either TT or CT. The genotype TT was more frequent in
HCC group in comparison to chronic hepatitis group. In addition, T-carriers
increase significantly in HCC group than chronic hepatitis group. Also, IL-28B
and -FP were significantly different in T-carriers than CC genotype, and in
HCC patients in comparison to either chronic hepatitis or cirrhosis patients.
CONCLUSION: This study suggests that in IL-28B rs12979860 C/T polymorphism, the T allele appears to be more prevalent in patients with end stage liver
disease (liver cirrhosis and HCC). Furthermore, chronic HCV infection with end
stage liver disease may be associated with a reduced IL-28B production. Further
research is needed to reveal the cause-effect of these polymorphisms on host
protective immunity against HCV infection.
REFERENCES
[1] Kamal SI and Nasser IA. Hepatitis C genotype 4: what we know and what we
dont yet know. Hepatology 2008; 47: 1371-1383.
[2] Abdel-Hamid M, El-Daly M, Molnegren V, et al. Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma.
Virology 2007; 88: 15261531.
[3] El-Serag HB. Hepatocellular carcinoma: recent trends in the United States.
Gastroenterology 2004; 127: S27S34.
[4] Di Marco V, Bronte F, Calvaruso V, et al. IL-28B polymorphisms influence
stage of the liver fibrosis and spontaneous or interferon-induced viral clearance
in thalassemia patients with hepatitis C virus infection. Haematologica 2011; 97:
679-686.
Disclosure of Interest: None declared
P1209 EFFICACY OF RADIO FREQUENCY ABLATION FOR ELDERLY
HEPATOCELLULAR CARCINOMA PATIENTS
S. Kamachi1,*, T. Otsuka1, Y. Kubotsu1, N. Araki1, H. Isoda1, S. Nakashita1,
T. Akiyama2, S. Kawazoe2, Y. Eguchi3, T. Mizuta1, K. Anzai1
1
Internal medicine, Division of Hepatology, Diabetes, Metabolism and
Endcrinology, Saga University Hospital, 2Internal medicine, Hepato-BiliaryPancreatology Division, Saga-Ken Medical Centre Koseikan, 3Liver disease control
and assistance task force, Saga University Hospital, Saga, Japan
Contact E-mail Address: saori.kamachi@gmail.com
INTRODUCTION: In Japan, the population of patients with hepatocellular
carcinoma (HCC) is aging, and the use of radiofrequency ablation (RFA) to
treat elderly patients with HCC is increasing. However, there are few studies

A463

United European Gastroenterology Journal 2(1S)


that compare elderly and non-elderly patients regarding the efficacy of RFA.
Therefore, we evaluated the efficacy of RFA for elderly patients with HCC.
AIMS & METHODS: Two hundred and nineteen patients with primary HCC
(tumor size  30mm and tumor number  3) treated with RFA between 2004 to
2012 were analyzed. Elderly patients (age 75 or over) accounted for 33% (73
patients) of the patients. We analyzed patient characteristics, recurrence free
survival (RFS), factors related to RFS and overall survival (OS).
RESULTS: The baseline characteristics of patients were comparable between
two groups with the exception of gender (male, 49% vs. 69%, respectively,
p50.01), ALT (median, 39IU/L vs. 45IU/L, respectively, p50.01) and the presence of diabetes mellitus (12% vs. 27%, respectively, p 0.01). The median RFS
times were 29.7 months and 29.8 months in the elderly group and non-elderly
group. The RFS rates at 1, 3, and 5 years were 80.7%, 31.8%, and 21.2% in the
elderly group compared with 76.6%, 40.0% and 29.7% in the non-elderly group,
respectively (p 0.43). The times to local recurrence (TTLR) were not significantly different between the two groups (p 0.12). In multivariate Cox analysis,
AFP420ng/ml (HR:1.84, 95%CI:1.2-2.8, p50.01) and multiple tumor
(HR:1.74, 95%CI:1.2-2.6,p 0.04) were significantly associated with recurrence.
The 5-year OS rates in the elderly group were 51%, and 72 % in the elderly and
non-elderly groups (p50.01), respectively. There were 67 and 123 patients positive for anti-hepatitis C antibodies in the elderly and non-elderly groups, respectively. In patients with HCV who received anti-viral therapy (3 elderly, 29 nonelderly), none of the elderly and seven of non-elderly patients sustained viral
response. When we restricted the analysis to patients who didnt receive antiviral therapy (64 elderly group, 94 non-elderly group), the 5-year OS rates were
not significantly different (50% and 65%, p 0.13), respectively.
CONCLUSION: Results indicated that RFA is equally effective for treating
elderly and non-elderly patients with HCC.
Disclosure of Interest: None declared
P1210 RADIOFREQUENCY ABLATION FOR THE TREATMENT OF
COLORECTAL LIVER METASTASIS: A CLINICAL OUTCOME
REPORT
S.J. C. Bellido1.1,*, J.-A. V. Bisnar1, J.G. Cervantes1
1
Institute of Digestive and Liver Diseases, St. Lukes Medical Center, Quezon City,
Philippines
Contact E-mail Address: sarahbellido@gmail.com
INTRODUCTION: The 5 year-survival rate of patients with Colorectal liver
metastases (CRLM) without treatment is 55%, with a median survival time
of 8-10 months. Radiofrequencyablation (RFA) is one of the loco-regional therapies that may be used as an adjunct to chemotherapy in treating these patients,
and improve survival.
AIMS & METHODS: Data from patients diagnosed with CRLM and treated
with RFA from 2003 to 2012 were gathered and analyzed: age, sex, number of
lesions, size of the largest lesion, the treatment regimen and the number of RFA
sessions. The overall survival rate, median survival time and the prognostic
factors that affect survival were determined using Kaplan-Meier and Cox regression analysis.
RESULTS: From the period of March 2003 up to June 2012, a total of 69 RFA
sessions were performed in 42 patients. All of the patients included underwent
chemotherapy together with RFA. Three also underwent percutaneous ethanol
injection therapy, while 1 patient also underwent liver resection. Majority of the
patients (71%) underwent only a single RFA session. Eight patients underwent
RFA twice to three times, while another 4 patients required 4 to 5 sessions of
RFA. The overall 3- and 5-year survival rates of patients with CRLM treated
with RFA were both 20.6%. There seems to be no significant difference in survival
between age groups (p 0.660), gender groups (p 0.815), number of lesions
(p 0.055), RFA treatment combinations (p 0.777), and number of RFA sessions
(p 0.141). The size (p 0.011), and the number (p 0.017) of lesions are significant predictors of survival. Median survival time is 25 and 11 months for lesions
55cm, and 45cm, respectively. Patients have a median survival time of 454, 14,
and 12 months for solitary, 2-5, and 45 lesions, respectively.
CONCLUSION: RFA in conjunction with chemotherapy improves the overall
survival rate of patients to 20.6%, and the median survival time to 26 months.
Disclosure of Interest: None declared
P1211 VALIDATION OF STAGING SYSTEMS FOR HEPATOCELLULAR
CARCINOMA: A COMPARISON OF THE BM-JIS SCORE, THE JIS
SCORE AND THE BCLC STAGING
S. Kitai1,*, M. Kudo1, N. Nishida1, N. Izumi2, M. Sakamoto3, Y. Matsuyama4,
T. Ichida5, O. Nakashima6, O. Matsui7, Y. Ku8, N. Kokudo9, M. Makuuchi10 on
behalf of Liver Cancer Study Group of Japan
1
Gastroenterology and Hepatology, Kinki University school of medicine,
Osakasayama, 2Gastroenterology and Hepatology, Musashino Red Cross Hospital,
Musashino, 3Pathology, Keio University school of medicine, 4Biostatistics, School
of Public Health, University of Tokyo, Tokyo, 5Hepatology and Gastroenterology,
Juntendo Shizuoka Hospital, Izunokuni, 6Clinical Laboratory Medicine, Kurume
University Hospital, Kurume, 7Radiology, Kanazawa University Graduate School
of Medical Science, Kanazawa, 8Surgery, Kobe University Graduate School of
Medicine, Kobe, 9Surgery, Graduate School of Medicine, University of Tokyo,
10
Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo,
Japan
Contact E-mail Address: dorapepsi@hotmail.com
INTRODUCTION: The Barcelona Clinic Liver Cancer Staging system (BCLC)
is the most widely used system and has been reported to have good stratification
ability in patients with hepatocellular carcinoma (HCC). Similarly, The Japan
Integrated Staging (JIS) score also has been reported to effectively stratify

patients with HCC. The aim of this study was to examine which staging systems
can predict the survival of patients with HCC.
However, the JIS score could not estimate malignant grade of HCC. The aim of
this study was to evaluate the performance of a new staging system: the biomarker combined JIS (bm-JIS) which includes three tumor markers: alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP and des-gamma-carboxy
prothrombin with the conventional JIS score.
AIMS & METHODS: A total of 11.531 HCC patients were included in this
retrospective study. We compared their overall survival, the stratification ability
and suitability as a prognostic model according to the BCLC staging system and
the JIS score.
RESULTS: There were significant differences between the survival curves for all
JIS scores (p 5 0.0001) and all BCLC scores (p 5 0.0001). The independent
homogenizing ability and the stratification value of the JIS score and the bm-JIS
score determined by the likelihood ratio test using the Cox proportional hazard
regression model showed the bm-JIS score to have a higher value (chi2 717.348)
than the JIS score (chi2 668.91).
CONCLUSION: The bm-JIS score showed superior stratification ability and
thus was found to be a better predictor of the prognosis than the conventional
JIS score, especially for the patients with good prognosis.
REFERENCES
1)Forner A, Llovet JM and Bruix J. Hepatocellular carcinoma. Lancet 2012; 379:
1245-1255.
2)Kudo M, Chung H, Haji S, et al. Validation of a new prognostic staging system
for hepatocellular carcinoma:the JIS score compared with the CLIP score.
Hepatology 2004; 40: 13961405.
3)Kitai S, Kudo M, Minami Y, et al. Validation of a new prognostic staging
system for hepatocellular carcinoma: a comparison of the biomarker-combined
Japan Integrated Staging Score, the conventional Japan Integrated Staging Score
and the BALAD Score. Oncology 2008; 75(Suppl. 1): 83-90.
4) Akaike H. A new look at statistical model identification. IEEE Trans Autom
Control 1974; AC-19: 716722.
Disclosure of Interest: None declared
P1212 DOWNSTAGING
THERAPY
IN
PATIENTS
INTERMEDIATE STAGE HCC (BCLC B) AS BRIDGE FOR
TRANSPLANTATION: THE HEPATOCATT EXPERIENCE

WITH

T.A. Di Rienzo1,*, V. Cesario1, M. Campanale1, G. DAngelo1, F. Barbaro1,


M. Siciliano1, B.E. Annicchiarico1, M. Pompili1, G.L. Rapaccini1, A. Grieco1,
S. Agnes1, A.W. Avolio1, A. De Gaetano1, G.B. Gasbarrini2, R. Iezzi1,
L. Bonomo1, A. Gasbarrini1 on behalf of Hepatocatt Study Group
1
Catholic University, Rome, 2Fondazione Ricerca in Medicina "Falcone e
Borsellino", Bologna, Italy
Contact E-mail Address: teresaanto@hotmail.it
INTRODUCTION: At state of the art, patients with intermediate stage HCC
(BCLC B) are suitable only of not curative treatment. Liver transplantation may
potentially cure both the tumor and the underlying liver disease, but only patients
with an early stage tumor disease (meeting Milan Criteria) could be evaluated for
inclusion in the transplant list.
AIMS & METHODS: The aim of our study is to evaluate the efficacy of downstaging therapy in order to satisfy Milan criteria, in patients with intermediate
stage of HCC (BCLC B) referred to our Center.
Since September 2010 to September 2013, among 463 HCC patients investigated
at Multidisciplinary Group for the Treatment of Hepatocellular Carcinoma of
our Center (HEPATOCATT), we retrospectively selected and reviewed medical
records of patients younger than 65 years old, with intermediate-stage HCC
(BCLC B) that underwent a downstaging treatment (liver resection, locoregional
therapy, antiangiogenic drugs and/or combined treatments) and for whom an
adequate follow-up was available. Tumor response was evaluated on 1-month
follow-up multiphasic CT based on mRECIST criteria. CT scan was also performed on 3-month follow up to evaluate the persistence of the response.
RESULTS: We selected 20 patients with intermediate-stage HCC (BCLC B). In
all patients more than one downstaging treatment have been performed (total of
41 treatments): 2 liver resections, 21 TACE, 10 PEI, 1 RFA, 7 combined treatments (5 TACE/RFA; 1 liver resection/antiangiogenic;1RFA/antiangiogenic).
On 1-month follow up CT scan, 14 out of 20 patients (70%) experienced an
effective downstaging, satisfying Milan criteria. 3-months follow up CT scan
showed a stability of disease in all patients. 9 out of 14 (64.3%) patients were
listed for OLTx. Finally, 7/20 patients (35%) underwent liver transplantation.
CONCLUSION: Our results show that an effective downstaging strategy allows
even patients with intermediate HCC (BCLC B) not suitable to liver transplantation, to access potentially curative treatments
Disclosure of Interest: None declared
P1213 TREATMENT OF HEPATOCELLULAR CARCINOMA MEETING
THE MILAN CRITERIA. RETROSPECTIVE COMPARISON OF
RADIOFREQUENCY ABLATION AND RESECTION FOR LESIONS
TREATABLE BY BOTH TECHNIQUES
Z. Sparchez1.2,*, P. Radu2, N. Al Hajjar2, C. Iancu1.2
1
University Of Medicine "Iuliu Hatieganu", 2Regional Institute Of
Gastroenterology and Hepatology "O Fodor", Cluj Napoca, Romania
Contact E-mail Address: zsparchez@yahoo.co.uk
INTRODUCTION: In patients with well-preserved hepatic function, hepatic
resection (HR) is the most appropriate and effective treatment. In the last
decade, local ablative therapies (mostly radiofrequency ablation -RFA) have
obtained good results in term of efficacy. Whether ablation of HCC eligible

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United European Gastroenterology Journal 2(1S)

also for HR provides long-term disease control comparable to resection remains


still in debate.
AIMS & METHODS: Aim. To compare the therapeutic outcome in terms of
survival and recurrence of RFA and HR in the treatment of HCC lesions within
Milan criteria treatable by both techniques.
Methods: Using inclusion and exclusion criteria, seventy-nine HCC patients treatable by both HR or RFA were included in this study. Thirty two patients were
treated by HR and 47 by RFA. In the HR group, 22 lesions were located in the
left lobe and 11 in the right lobe. In the RFA group 40 lesions were located in the
right lobe and 7 lesions in the left lobe. Mean tumor size was 31.5 /-7.55 mm in
the RFA and 32.6 /- 10 mm in the HR group. In the ARF group were included
41(88%) patients with Child Pugh A class and 6 (12%) patients were Child Pugh
B class. In the HR group were included 30 (94%) patients with Child Pugh and 2
(6%) patients with Child Pugh B class. The outcome was considered in terms of
overall survival (OS) and local recurrence rate. Survival curves were constructed
with the Kaplan-Meier method and compared by using the log-rank test.
RESULTS: Even if in the first two years the RFA group presented a better OS, in
the third year the survival rate was lower than HR (91%, 82%, and 35 % vs 81%,
65% and 57% at 1.2, and 3 years), respectively) (p 0.185). The local recurrence
was higher in the RFA group (38.2%) than in the HR group (3.1%)(p 0.001).
There was one major complications in each group (death after surgical resection)
and 1 case of haemoperitoneum after RFA.
CONCLUSION: RFA provides a better survival at 1 and 2 years than HR in
patients with HCC within Milan criteria treatable by both treatments. The survival rate at 3 years is better for HR presumable due to the lower local reccurence
rate.
Disclosure of Interest: None declared
P1214 ENDOSCOPIC RETROGRADE BILIARY DRAINAGE
OBSTRUCTIVE JAUNDICE OF UNRESECTABLE
HEPATOCELLULAR CARCINOMA: COMPARISON OF SELFEXPANDABLE METALLIC STENTS VS. PLASTIC STENTS

IN

D.K. Jang1,*, K.H. Chung1, B.S. Lee1, S.H. Lee1, J.K. Ryu1, Y.-T. Kim1
1
Department of Internal Medicine and Liver Research Institute, Seoul National
University College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: kwasay@gmail.com
INTRODUCTION: Patency of self-expandable metallic stents (SEMS) known to
be better than plastic stents (PS) in palliating malignant biliary obstruction.
However, data were scarce for the obstructive jaundice caused by hepatocellular
carcinoma (HCC). This study aimed to compare SEMS and PS in palliating
obstructive jaundice of unresectable HCC.
AIMS & METHODS: A total of 96 patients who undergone endoscopic retrograde biliary drainage (ERBD) for obstructive jaundice of unresectable HCC and
deployed either SEMS or PS successfully were included in this retrospective
analysis. Successful biliary drainage rate, complication rate, stent patency duration and patient survival were compared between SEMS and PS groups
RESULTS: Thirty-six patients were SEMS group and 60 patients were PS group.
Successful biliary drainage rate was not significantly different between SEMS
and PS (69.4% vs. 65.0%, p 0.655). Complication rate was 16.7% in SEMS
vs. 21.7% in PS (p 0.552). The median patency duration was also not significantly different between SEMS group and PS (68 day vs. 60 day, p 0.396).
Median patient survival was longer in PS group than SEMS group (123 day
vs. 48 day, p 0.005). Use of PS, lower total bilirubin level, earlier TNM
stage, successful biliary drainage, and following anticancer treatment was significantly related with longer patient survival in multivariate analysis.
CONCLUSION: SEMS was not superior to PS for palliating malignant biliary
obstruction of HCC with regard to successful drainage, patency and complications and patient survival was longer in PS group. Considering the lower cost of
PS, ERBD with PS could be a favorable option for malignant biliary obstruction
caused by HCC.
Disclosure of Interest: None declared
P1215 SURGERY OR EUS-GUIDED CHOLEDOCHODUODENOSTOMY
FOR DISTAL BILIARY CANCER PALLIATION AFTER FAILED ERCP
E.L. Artifon1,*, J.F. Loureiro1, P. Sakai1
1
university of sao paulo, sao paulo, Brazil
Contact E-mail Address: jarbasfaraco@gmail.com
INTRODUCTION: Most patients with neoplasm in the biliopancreatic junction
are diagnosed at an advanced stage. Endoscopic retrograde cholangiopancreatography (ERCP) is the method of choice for drainage of obstructed biliary tract.
However, there is a failure rate of about 10%. In such cases, alternative techniques,
such as, percutaneous transhepatic drainage and surgical drainage are applied.
AIMS & METHODS: To evaluate the technical and clinical success, quality of
life and patient survival of biliary drainage by conventional surgery and endosonography-guided technique in patients with malignant neoplasm of the biliopancreatic junction.
From April 2010 to September 2013, 32 patients with malignant neoplasm of the
biliopancreatic junction were studied. All patients included in this study had
failed biliary drainage by ERCP. Three patients were excluded due to technical
failure (failure in the construction of hepatico-jejuno anastomosis and formation
of endosonography-guided choledochoduodenal fistula). Group I comprised of
15 patients who underwent Roux-en-Y hepaticojejunostomy (HJT) and gastrojejunal bypass. Group II consisted of 14 patients who underwent endosonography-guided choledochoduodenostomy (CDT). Clinical success was assessed by
the decrease of more than 50% in total serum bilirubin in the first seven days
after the procedure. Quality of life was assessed by SF-36 questionnaire and
survival by Kaplan-Meier curve.

RESULTS: Technical success rate was 93.75% (15/16) in group I and 87.5% (14/
16) in group II (p 0.598). Clinical success occurred in 14 (93.33%) patients in
group I and 10 (71.43%) patients in group II. There was no significant statistically difference (p 0.169). The average quality of life score were statistically
equal between the techniques during follow-up (p 4 0.05 * Technical
Moment). There were statistically significant mean changes during follow-up
of functional capacity score, physical health, pain, social functioning, emotional
and mental health aspects in both techniques (p 5 0.05). The mental health score
was, on average, statistically higher in group II (CDT) at all times (p 0.035).
The median survival time of patients in group I was 82.27 days and Group II
patients was 82.36 days. Sixty percent of patients in group I died within 90 days
after the surgical procedure. On the other hand, 42.9% of the patients who
underwent CDT died in the same period. There was no statistically significant
difference in survival time between the groups (p 0.389).
CONCLUSION: Data relating to technical and clinical success, quality of life
and survival were similar in both groups and there were no statistically significant
differences.
Disclosure of Interest: None declared
P1216 APPROPRIATE THERAPEUTIC STRATEGY FOR BILIARY
STENTING USING THREADED INSIDE STENTS BASED ON THE
LOCATION OF THE MALIGNANT OBSTRUCTION
H. Hasegawa1,*, O. Inatomi1, Y. Morita1, H. Ban1, M. Shioya1, S. Bamba1,
A. Andoh1
1
Division of Gastroenterology, SHIGA UNIVERSITY OF MEDICAL
SCIENCE, Otsu, Japan
INTRODUCTION: Although the use of endoscopic biliary stents in cases of
malignant obstruction may be widespread, optimal endoscopic management
remains controversial. We retrospectively evaluated the safety and efficacy of
the placement of a threaded inside plastic stent above the sphincter of Oddi
(threaded PS) and compared the results with those of other stent types with
respect to the location of the obstruction.
AIMS & METHODS: Forty patients with malignant hilar obstructions (type IIV;
Bismuth classification) underwent endoscopic indwelling stent placements. These
cases involved the use of threaded PS, conventional PS, and uncovered metallic
stents (MS). To create a threaded PS, a nylon monofilament thread (size 3/0) was
attached to a conventional PS (Flexima, Boston Scientific) using a puncher. The
duration of patency and complications were retrospectively evaluated in each group.
The patients with malignant hilar obstructions all underwent threaded PS placement
as a salvage therapy after MS was obstructed due to tumour ingrowth. We compared the patency of MS and threaded PS in these cases. In cases with mid or lower
bile duct obstruction, the duration of patency and any complications were retrospectively evaluated in the MS and threaded PS groups.
RESULTS: All procedures were successful in each group. The median duration
of patency in the threaded PS group was significantly longer compared with the
duration in the conventional PS group (126.3 vs 42.1 days, P 0.025, Log-rank
test) and was not significantly different compared with the MS group (126.3 vs
200.3 days, P 0.76). The removal of threaded PS was simple because the
attached thread was visible in the sphincter of Oddi except in one case. The
stents did not migrate in any group. The median duration of the threaded PS
patency was 123 days compared with that of the MS patency of 163 days
(P 0.486). In patients with mid or lower bile duct obstruction, the median
duration of the threaded PS patency was significantly shorter compared with
that of the MS patency (P 5 0.03). In particular, the median patency of the
threaded PS when there was no precedent endoscopic nasal bile drainage was
significantly shorter (22 days).
CONCLUSION: The placement of threaded PS is safe and effective compared
with conventional PS for the treatment of a malignant hilar obstruction; this
procedure was not inferior to MS. In addition, the threaded PS patency was
comparable with the MS patency even when used as a salvage therapy, suggesting
that threaded PS may be useful not only for an initial therapy but also as a
salvage therapy. On the other hand, the placement of threaded PS without a
precedent ENBD was not superior to MS in cases with mid or lower bile duct
obstruction. The type of stent should be decided in terms of both the location of
the obstruction and the endoscopic therapeutic process.
Disclosure of Interest: None declared
P1217 AIR VERSUS IODINE CONTRAST CHOLANGIOGRAPHY FOR
ENDOSCOPIC BILATERAL STENT-IN-STENT PLACEMENT OF
METALLIC STENTS IN PATIENTS WITH MALIGNANT HILAR
BILIARY OBSTRUCTION
J.M. Lee1,*, S.H. Lee2, D.K. Jang2, B.S. Lee2, K.H. Chung2, J.M. Park2,
J.K. Ryu2, Y.-T. Kim2
1
Department of Internal Medicine, Myongji Hospital, Goyang, 2Department of
Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic Of
Contact E-mail Address: 01179jm@naver.com

n
w
a
r
d
h
t
i

INTRODUCTION: Endoscopic biliary drainage is one of the major palliative


treatments for unresectable malignant hilar biliary obstruction. However, postendoscopic retrograde cholangiopancreatography (ERCP) cholangitis could
occur frequently due to the inadequate drainage, especially after contrast injection into biliary tree.
AIMS & METHODS: The aim of this study was to investigate the effect of air
cholangiography on post-ERCP complications for endoscopic bilateral stent-instent (SIS) placement of self-expandable metallic stents (SEMS). This study was
included 42 patients with unresectable malignant hilar obstruction who underwent endoscopic bilateral SEMS placement using SIS technique. They were
divided into the two groups, air (n 21) or iodine contrast (n 21)

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United European Gastroenterology Journal 2(1S)


cholangiography, respectively. We retrospectively compared comprehensive clinical and laboratory data in both groups.
RESULTS: There were no significant differences in age, gender, stent type, liver
function tests, type of tumor origin, and Bismuth classification between the two
groups. Technical success was achieved for all 42 patients and functional success
rate was 95.2% (20/21) in each group. Post-ERCP complications were occurred
in 5 (23.8%) of the patients in air group and 8 (38.1%) of the patients in iodine
contrast group (P 0.317). The rate of cholangitis in air group was significantly
lower than that in iodine contrast group (4.8% vs. 33.3%, P 0.045). The difference of 30-day stent occlusion and 30-day mortality between the two groups
was not significant (P 1.000 and P 0.232, respectively).
CONCLUSION: Air cholangiography is a safe and effective method to visualize
intrahepatic bile duct with low incidence of post-ERCP cholangitis. In addition,
it could be considered for endoscopic bilateral SIS placement of SEMS in
patients with malignant hilar biliary obstruction.
Disclosure of Interest: None declared

n
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P1218 THE USEFULNESS OF NARROW-BAND IMAGING SYSTEM IN


DIAGNOSING AMPULLARY LESION
J.-S. Park1,*, D.-W. Seo1, T.J. Song1, D.H. Park1, S.S. Lee1, S.K. Lee1, M.H. Kim1
1
Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center,
Seoul, Korea, Republic Of
Contact E-mail Address: Pjsinha@naver.com
INTRODUCTION: The differentiation between ampullary tumors and benign
ampullary lesions is challenging occasionally because endoscopic findings may be
similar to each other. Narrow-band imaging system (NBI) can yield clear images
of microvessel and surface structure, and it is widely used for the diagnosis of
gastric or colonic cancer.
AIMS & METHODS: we evaluated the the usefulness of NBI for differentiating
between the ampullary tumor and other benign diseases. 29 patients with 42
ampullary lesions were retrospectively analyzed between March 2010 and
January 2011. Inclusion criteria were enlarged or protruded lesions that were
suspected ampullary tumor during duodenoscopy. Abnormal NBI images were
classified as follows: Irregular arrangement of villi; Irregular size of villi;
Disappearance of ridged villi structure; Demarcation with normal villi;
Abnormal microvasculature. The correlation between NBI images and histological findings was investigated.
RESULTS: In histological examination, there were 21 adenoma, 6 adenocarcinoma and 15 benign diseases. On NBI images, the abnormal findings according
to our classification were: Irregular arrangement of villi (50%); Irregular size of
villi (64%); Disappearance of ridged villi structure (40%); Demarcation with
normal villi (55%); Abnormal microvasculature (67%). In multivariate analysis,
irregular arrangement of villi (OR, 45.44; 95% CI, 2.87-604.34; P50.01) and
abnormal microvasculature (OR, 11.79; 95% CI, 2.24-235.67; P50.01) were
significant factors to identify ampullary tumor.
CONCLUSION: Our study suggested that Irregular arrangement of villi and
Abnormal microvasculature on NBI image would be useful for detection of
ampullary tumor.
Disclosure of Interest: None declared

Charlson comorbid score  4 were main prognostic factors with significant


difference affecting mortality rate in malignant obstructive jaundice inpatients.
Prognostic threshold  2 quite good to classify malignant obstructive jaundice
inpatients into high risk mortality population. Mortality of patients with those
significant prognostic factors can be predicted in 76.9%.
Disclosure of Interest: None declared
P1220 CLINICAL USEFULNESS OF BILE CYTOLOGY OBTAINED BY
TRANSPAPILLARY CATHETERIZATION OF THE GALLBLADDER
FOLLOWED BY RUBBING WITH A GUIDEWIRE FOR
GALLBLADDER WALL THICKENING
K. Ito1,*, S. Koshita2, Y. Kanno1, T. Ogawa1, K. Masu1, Y. Michikawa1,
Y. Iwashita1, G. Kobayashi1, Y. Noda1
1
Gastroenterology, 2SENDAI CITY MEDICAL CENTER, Sendai, Japan
Contact E-mail Address: keiito@openhp.or.jp
INTRODUCTION: Although gallbladder (GB) diseases have been increasingly
detected with the widespread use of ultrasonography, MRI, and multi-detectorrow CT, it is sometimes difficult to distinguish malignant GB diseases from
benign ones.
AIMS & METHODS: The aim of this study was to evaluate the clinical usefulness of bile cytology obtained by endoscopic transpapillary catheterization of the
gallbladder (ETCG) followed by rubbing with a guidewire for GB wall thickening. Between January 2008 and December 2013, 67 patients with GB wall thickening who underwent ETCG cytology were enrolled in this study. Fifty-five
patients underwent surgical treatment. Pathological findings of the resected specimen revealed GB cancer in 20 patients and benign GB diseases in 35 (20,
chronic cholecystitis; 11, adenomyomatosis; 2, xanthogranulomatous cholecystitis; 1, acute cholecystitis; 1, cholesterol polyp). Five patients were diagnosed as
inoperable advanced GB cancer by CT findings such as liver/lymph node metastases. The remaining seven patients were diagnosed as benign GB diseases after a
follow-up period of at least 12 months. The method of ETCG cytology was as
follows. A 5 Fr catheter with side holes was inserted into the GB over a 0.025 or
0.032-inch hydrophilic guidewire. The first aspirated bile was discarded. Fresh
exfoliated cells were obtained after washing by saline solution and rubbing the
target lesion with a guidewire. Cytology was performed by HE stain with the
cellblock method. A rating of Class IIIb or more was defined as malignancy. The
sensitivity, specificity, and accuracy of ETCG cytology were evaluated.
RESULTS: Of the 25 patients with GB cancer, 16 were defined as having malignancy by ETCG cytology (6, Class V; 6, Class IV; 4, Class IIIb). The causes of
false-negative results included insufficient material in 2 patient, inability to rub
the lesion with a guidewire in 1, and indeterminate causes in 6. Of 42 patients
without malignancy, one patient was found to be false positive by ETCG cytology (Class IIIb). Sensitivity, specificity, and accuracy of ETCG cytology were
64%, 98%, and 85%, respectively. No procedure-related complications such as
cholecystitis and cystic duct perforation occurred.
CONCLUSION: Bile cytology obtained by ETCG is a feasible and safe method
for differential diagnosis of GB wall thickening.
Disclosure of Interest: None declared
P1221 CURRENT STATUS OF ENDOSCOPIC MANAGEMENT FOR
AMPULLARY NEOPLASM

P1219 THREE-MONTH SURVIVAL OF MALIGNANT OBSTRUCTIVE


JAUNDICE PATIENTS: FACTORS AFFECTING MORTALITY
J. Kurniawan1,*, I. Hasan1, R.A. Gani1, M. Simadibrata2
1
Division of Hepatology, Department of Internal Medicine, 2Division of
Gastroenterology, Department of Internal Medicine, Faculty of Medicine
University of Indonesia/Dr. Cipto Mangunkusumo General National Hospital,
Jakarta, Indonesia
Contact E-mail Address: juferdyk@gmail.com
INTRODUCTION: Understanding any related factors affecting mortality in
malignant obstructive jaundice patients will better guide to an approriate and
optimal planning in making diagnostic approach and proper treatment for each
aetiological and relating factors thus improving survival and patients quality of
life.
AIMS & METHODS: To obtain survival and mortality-related factors of malignant obstructive jaundice patients, retrospective cohort study was conducted
with medical records of obstructive jaundice inpatients from January 2010 to
December 2013 were reviewed. Suggested mortality-related factors include age,
gender, sepsis, hypoalbumin, serum bilirubin level, serum CA 19-9 level, billiary
drainage, non ampula vater carcinoma, and comorbid factors were analyzed.
Overall survival and survival related mortality factors were measured, bivariat
and multivariat analysis was done with Cox Proportional Hazards Regression
Model to obtain Hazard Ratio (HR) of each prognostic factor. Prognostic score
from each mortality-related factor was calculated based on the last regression
model.
RESULTS: A total of 181 (106 male/75 female) patients were enrolled in this
study, with patients aged 50 years or above was 57.5%. The cox proportional
hazards model demonstrated that sepsis (HR 2.462; 95% CI 1.552 3.906),
unsuccessful / no prior billiary drainage (HR 1.604; 95% CI 0.988 2.603),
and Charlson comorbid score  4 (HR 2.476; 95% CI 1.562 3.923) were
independent prognostic factors for mortality. Patients with significant prognostic
factors had shorter survival than overall survival (median survival 14 days; 95%
CI: 9.66 18.34 vs 26 days; 95% CI: 20.82 31.19, respectively) (p 0.01). Score
 2 identified as the highest prognostic score threshold with sensitivity 68%,
specificity 75%, and AUC on ROC curve 0.769.
CONCLUSION: Patients with significant prognostic factors had shorter survival
than overall survival. Sepsis, unsuccessful / no prior billiary drainage, and

K. Ito1,*, S. Koshita1, Y. Kanno1, T. Ogawa1, K. Masu1, Y. Michikawa1,


Y. Iwashita1, G. Kobayashi1, Y. Noda1
1
Gastroenterology, SENDAI CITY MEDICAL CENTER, Sendai, Japan
Contact E-mail Address: keiito@openhp.or.jp
INTRODUCTION: Endoscopic papillectomy (EP) is performed in selected
patients with ampullary neoplasm. Accurate preoperative tumor staging is indispensable for making management decisions.
AIMS & METHODS: The aim of this study was to elucidate the current status of
endoscopic management for ampullary neoplasm. Eighty-three patients with
ampullary neoplasm (male, 51; female, 32; mean age, 68; mean tumor size, 21
mm) who underwent transpapillary intraductal US (IDUS) of the bile duct (BD)
were enrolled in this study. The indication for EP was determined based on the
following findings by IDUS: (1) no tumor infiltration into the BD or the pancreatic duct (PD) and (2) adenoma or T1 cancer. In cases of T1 cancer, additional
surgery was considered when the tumor had invaded the Oddis muscle because
of the risk of lymph node metastasis.
RESULTS: Based on the results of IDUS, EP was performed in 37 patients.
Twenty-one had adenoma and 16 had adenocarcinoma (T1, 14; T2, 2). The other
46 patients, whose tumors were contraindicated for EP by IDUS, were treated by
pylorus-preserving pancreatoduodenectomy (T1, 19; T2, 10; T3-4, 17). Of these 19
surgical cases of T1, 9 had a tumor invading the Oddis muscle and 8 had a tumor
spreading into the BD or PD. Theoretically, the remaining 2 patients could have
been treated by EP based on the histopathological findings.
In the 37 patients who underwent EP, the accuracy of IDUS in T staging was
95% (35/37). Of the two patients with T2, one underwent additional surgical
treatment, which revealed neither a residual tumor nor lymph node metastasis by
histopathological evaluation of the resected specimen. The other refused surgical
therapy and received chemotherapy without evidence of recurrence for 48
months. One patient with T1, whose tumor invaded the Oddis muscle, died in
an accident one month after EP. In one patient with T1 (tumor depth, Oddis
muscle) who refused additional surgical treatment, lung metastases were detected
by chest CT 11 months after EP without local recurrence. In the remaining 12
patients with T1 (tumor depth, mucosa), neither local recurrence nor distant
metastasis was observed. Of the 21 patients with adenoma, 4 successfully underwent argon plasma coagulation for a residual tumor. At follow-up (mean duration, 38 months; range, 1-108 months), no local recurrence was observed in the

A466
remaining patients. The sensitivity, specificity, and accuracy of determining the
indication for EP by IDUS was 89%, 96%, and 93%, respectively.
CONCLUSION: IDUS can provide useful information for determination of the
indication for EP. Detailed histological evaluation of the resected specimen and
long-term follow-up are mandatory after EP.
Disclosure of Interest: None declared
P1222 RISK FACTORS FOR INTRAHEPATIC AND EXTRAHEPATIC
CHOLANGIOCARCINOMA: A CASE-CONTROL STUDY IN JAPAN
K. Hosono1,*, K. Ishii1, Y. Fujita1, Y. Sekino1, A. Nakajima1, K. Kubota1
1
Gastroenterology, YOKOHAMA CITY UNIVERSITY SCHOOL OF
MEDICINE, Yokohama, Japan
Contact E-mail Address: hiro1017@yokohama-cu.ac.jp
INTRODUCTION: The association between diabetes, smoking, obesity, and
cholangiocarcinoma (CC) risk remain inconclusive. We evaluated the risk factors
for both intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC).
AIMS & METHODS: A case-control study in which cases were cholangiocarcinoma patients referred to Yokohama City University Hospital (YCUH) in Japan
between 2009 and 2013 and controls were healthy individuals. Controls were
randomly selected from an existing database of healthy individuals at YCUH.
Data on family history, diabetes, smoking and drinking were collected by a
retrospective review of the patients records and health examination reports or
by interview. The associations between potential factors and CC risk were
determined.
RESULTS: A total of 111 patients (23 ICC; 88 ECC) and 547 age- and sexmatched controls were enrolled. Compared with controls, ICC patients had a
higher prevalence of diabetes (34.8% vs 17.4%, p 0.04). The adjusted odds
ratio (OR) and 95% confidence intervals (CI) were 3.1 (95% CI: 1.08-9.19).
ECC patients showed significant independent associations with diabetes (OR:
2.68; 95% CI: 1.36-5.29) and smoking (OR: 2.88; 95% CI: 1.57-5.30).
CONCLUSION: These findings strongly support the positive link between diabetes and the increased risk of ICC and ECC, and smoking were associated only
with ECC.
Disclosure of Interest: None declared
P1223 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE
MANAGEMENT OF PATIENTS WITH BILIARY STRICTURES: A
CONSENSUS REPORT BASED ON CLINICAL EVIDENCE
M. Giovannini1.2,*, R. Arsenescu3, H. Bertani4, F. Caillol1, D. Carr-Locke5,
G. Costamagna6, S. I. Gan7, F.G. Gress8, O. Haluszka9, K. Ho10,
H. Neumann11, F. Prat12, R. Shah13, P. Sharma14, S. Singh15, K. Wang16
1
Institut Paoli Calmettes, Marseille, 2CHU Nantes, Nantes, France, 3Ohio State
University Medical Center, Columbus, United States, 4Nuovo Ospedale Civile
SantAgostino Estense, Modena, Italy, 5Beth Israel Medical Center, New York,
United States, 6Policlinico Agostino Gemeli, Roma, Italy, 7Virginia Mason
Medical Center, Seattle, 8N. Y Presbyterian Columbia University Medical Center,
Brooklyn, 9Temple University Hospital, Philadelphia, United States, 10National
University Hospital, Singapore, Singapore, 11Universitatsklinikum Erlangen,
Erlangen, Germany, 12Cochin, Paris, France, 13University of Colorado Hospital,
Aurora, 14VA Kansas City Medical Center, Kansas City, 15VA Boston Healthcare
System, Jamaica Plain, 16Mayo Clinic, Rochester, United States
Contact E-mail Address: giovanninim@wanadoo.fr
INTRODUCTION: Differential diagnosis of bilio-pancreatic strictures includes
cholangiocarcinoma and benign lesions. The nature of biliary tumors remains
very difficult to diagnose due to the difficulty of getting adequate tissue samples
and to the lack of histopathological evaluation. Confocal Laser Endomicroscopy
(CLE) has been shown to considerably improve the characterization of those
lesions as compared with standard modalities thanks to a sensitivity and an
NPV higher than 90%. This substantial evolution has the potential to provide
a more informed diagnosis and to impact patient management.
AIMS & METHODS: The aim of this study is to develop up-to-date evidencebased consensus statements for the diagnosis of biliary strictures.
Initial statements on the use of CLE for the characterization of indeterminate
biliary strictures were developed by a single CLE expert based on the available
clinical evidence. Those preliminary statements were edited and submitted by an
external group of 16 GI physicians using a modified Delphi approach. After two
rounds of votes based on relevant data, quality of the evidence and strength of
recommendation, statements were validated if the threshold of agreement was
higher than 75%.
RESULTS: Out of 9 proposed statements, 6 were validated and 3 rejected. CLE
can be used to evaluate biliary strictures, and the probe can be delivered via a
catheter or a cholangioscope. CLE is more accurate than ERCP with brush
cytology and/or forceps biopsy in determining malignant or benign strictures,
using established criteria. The accuracy of CLE in indeterminate biliary strictures
may be decreased by prior presence of plastic stent.
The Negative Predictive Value (NPV) of CLE is very high. The use of CLE can
assist clinical decision-making such as excluding malignancy. CLE should be
cited as a valuable tool for an increased diagnostic yield in official guidelines.
The black bands that can be seen in pCLE images have been shown to be
collagen fibrils that predictably increase in pathologic tissue.
CONCLUSION: According to the panel of 16 physicians, given its very high
accuracy, Confocal Laser Endomicroscopy has the potential to improve the
current diagnostic algorithm of biliary strictures. At centers where expertise is
available, Confocal Laser Endomicroscopy used during ERCP in the evaluation
of biliary strictures should be considered as a standard practice complementary
to conventional tissue sampling.

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: None declared
P1224 BILIARY
DRAINAGE
FOR
MALIGNANT
BILIARY
OBSTRUCTION CAUSED BY METASTATIC GASTRIC CANCER
N. Takahara1,*, H. Isayama1, H. Ishigami2, T. Hamada1, K. Miyabayashi1,
D. Mohri1, T. Sasaki1, H. Kogure1, N. Yamamoto1, Y. Nakai1, K. Hirano1,
H. Yamaguchi2, M. Tada1, J. Kitayama2, K. Koike1
1
Department of Gastroenterology, Graduate School of Medicine, 2Department of
Surgical Oncology, The University of Tokyo, Tokyo, Japan
Contact E-mail Address: naminatsu.takahara@gmail.com
INTRODUCTION: Malignant biliary obstruction (MBO) is not a rare condition
in advanced gastric cancer (AGC). However, the clinical outcome of this setting
remains unclear. Moreover, the role of biliary drainage for this setting is not fully
elucidated.
AIMS & METHODS: Between October 2004 and February 2014, 63 consecutive
AGC patients (pts) with MBO who received biliary intervention were studied
retrospectively.
RESULTS: Of 63 pts, 35 pts (%) had previous gastrectomy (B-1/B-2/RY
reconstruction 8/5/22). The primary tumor of differentiated adenocarcinoma
in 23 pts (37%) and undifferentiated in 40 pts (63%), with liver metastases in 7
pts (11%) and ascite in 30 pts (48%). Portal vein stenosis and periportal collar
sign were observed in 28 pts (44%) and 17 pts (27%), respectively. The causes of
biliary obstruction were lymph node metastases in 8 pts, peritoneal metastases in
45 pts, and direct invasion in 10 pts, with the median lengths in biliary obstruction of 25 mm. Biliary drainage was performed via ERCP in 14 pts and PTBD in
49 pts, with technical and clinical success of 100% and 86% (ERCP/
PTBD 93%/84%), respectively. Periportal collar sign, emerged as a result of
tumor infiltration to Glissons capsule, was revealed as a risk factor for unsuccessful drainage (Odds ratio 9.2 (95% CI 1.5-78.0), p 0.02). Nine complications
were developed; 5 after ERCP (2 acute pancreatitis, 2 cholecystitis, and 1 cholangitis) and 4 after PTBD (1 stent migration, 1 pneumothorax, hemobilia in 1,
and 1 pseudoaneurysm). After biliary intervention, 29 pts (46%) received systemic chemotherapy. Median survival after biliary intervention was 3.6 months.
Clinical success of biliary drainage was prognostic of survival after intervention
(4.9 vs. 1.1 months, p50.01).
CONCLUSION: Although the prognosis of AGC pts with MBO is poor, biliary
interventions should not be considered as a contraindication because of its safety
and efficay in selected pts.
Disclosure of Interest: None declared
P1225 THERAPEUTIC
ENDOSCOPIC
RETROGRADE
CHOLANGIOPANCREATOGRAPHY IN PATIENTS WITH
ALTERED GASTROINTESTINAL ANATOMY
R. Koyama1,*, T. Tamura1, Y. Koizumi1, T. Imamura1, K. Takeuchi1
gastroenterology, TORANOMON HOSPITAL, tokyo, Japan

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP)


in patients with altered gastrointestinal (GI) anatomy remains a challenging
procedure. However, the progression of techniques and devices like a Doubleballoon enteroscopes (DBEs) enables us to perform ERCP on these patients. The
aim of this study is to assess the efficacy and safety of therapeutic ERCP, especially biliary drainage for malignant biliary obstructions, in patients with surgically altered GI anatomy (patients with Billroth-I anastomosis were excluded).
AIMS & METHODS: 2239 consecutive ERCP procedures were performed at
Toranomon Hospital during a 5- year period (2009 to 2013). In these, a total of
19 patients with altered GI anatomy underwent 33 ERCPs for malignant biliary
obstruction. We retrospectively investigated: (1) the success rate of reaching
either the papilla of vater or the bilioenteric anastomosis; (2) the success rate
of cannulation to deeper parts of a biliary tract; (3) the rate of successful therapeutic ERCPs; (4) complications.
RESULTS: The mean age was 72.5 years, range 58 to 82 years; 68% were male
and 32% were female. Bile duct cancer 45.5%(n 15), pancreatic cancer
18.2%(n 6), hepatocellular carcinoma 18.2%(n 6), and lymph node metastasis from the recurrence of gastric cancer, or esophageal cancer 18.2%(n 6) were
major indications. 10 cases underwent Roux-en-Y anastomosis, 4 cases underwent Billroth-II anastomosis, 4 cases underwent biliojejunal anastomosis, and 8
cases underwent bilioduodenal anastomosis. A plastic stent and self-expanding
metal stent (SEMS) were positioned for biliary drainage in 39.4% of the cases
(13/33) and 33.3% (11/33), respectively. The results of the above investigations
were: (1)87.9% (29/33), (2)84.8% (28/33), (3)84.8% (28/33), (4)3% (1/33):
respiratory suppression. There were no cases of the therapeutic ERCPs being
stopped by an accident during this procedure. Procedure-related mortality did
not occur. There were no incidences of hemorrhage and/or perforation. The
median duration of hospitalization was 21 days (2-82 days) and 44% of patients
could be discharged within 2 weeks. The median duration of survival after therapeutic ERCPs was 80 days (16-601 days).
CONCLUSION: ERCP in patients with surgically altered GI anatomy remains a
challenging procedure. But due to using DBE or PCF, the number of the successful therapeutic ERCPs is increasing in these patients. Successful therapeutic
ERCP was achieved in 84.8%, a relatively high figure in this study. The
median duration of survival time is short, only 80 days, because the most patients
are at the end stage of their diseases. To improve the QOL of patients with
malignant biliary obstructions, therapeutic ERCP should be performed positively, even if its a case of altered GI anatomy, because its relatively safe procedure, less invasive, and possible to discharge patients earlier.

A467

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: None declared

P1228 CLINICAL
OUTCOMES
OF
ENDOSCOPIC
SNARE
PAPILLECTOMY OF DUODENAL MAJOR PAPILLARY NEOPLASM

P1226 CHARACTERIZATION
OF
CHOLANGIOCARCINOMAS:
CLINICAL AND TOPOGRAPHIC FEATURES OF A GROWING
ONCOLOGICAL REALITY
R. Coelho1,*, M. Silva1, E. Rodrigues-Pinto1, S. Lopes1, P. Pereira1, H. Cardoso1,
F. Vilas-Boas1, J. Santos-Antunes 1, J. Lopes2, F. Carneiro2, G. Macedo1
1
Gastrenterology Department, 2Pathology Department, Centro Hospitalar Sao
Joao, Oporto, Portugal
INTRODUCTION: Cholangiocarcinomas account for 3% of the malignant gastrointestinal neoplasms. The incidence of intra-hepatic cholangiocarcinomas has
increased for unknown reasons [1.2].
AIMS & METHODS: To determine the clinical and analytical characteristics,
the diagnosis approach and the treatment options for patients with cholangiocarcinoma according to its location. Retrospective analysis of patients with diagnosis of cholangiocarcinoma in the last 5 years in a tertiary referral center.
RESULTS: 89 patients (55% male) were followed for a median of 23 weeks (P2575: 8-80). There was a progressive increase in the number of cholangiocarcinoma
diagnosis since the beginning of the cohort (14 new diagnoses in 2008-2009, 31 in
2010-2011 and 44 in 2012-2013). The mortality rate at 6 months was 40.5% and
the median survival was 164 days (P25-75: 61-566). Most patients (53%) presented perihilar, 24% extrahepatic and 24% intrahepatic cholangiocarcinoma
(ICC). The median age at diagnosis was 71 years, being lower in the ICC (68
vs 74, p 0.014). The diagnosis was obtained using imaging methods in 73% of
cases, the abdominal computed tomography was the most common method
(45%). There was a statistically significant correlation between the diagnosis of
ICC and the need of histological methods to make a diagnose (p50.001). Serum
levels of G-GT, alkaline phophatase and total bilirrubin at diagnosis were lower
in ICC (p50.001). In 36% of cases there was metastatic disease at diagnosis,
being hepatic metastization the most common disease (12%). In 56% of cases
palliative treatment was decided at diagnosis and in 54% of the patients underwent surgery. Hepatectomy was the most common intervention and was performed in 20% of the cases.
CONCLUSION: ICC presents with less cholestasis at diagnosis. It is more frequent the need for a histological diagnosis in this type of cholangiocarcinoma.
An increase of the incidence of cholangiocarcinoma was verified in this cohort.
REFERENCES
1-Gores GJ, LaRusso NF, et al. Biliary tract cancers. N Engl J Med 1999; 341:
1368.
2-Vauthey JN and Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis 1994; 14: 109.
Disclosure of Interest: None declared
P1227 PREDICTIVE
FACTORS
OF
SURVIVAL
CHOLANGIOCARCINOMA: A 5-YEARS EXPERIENCE

IN

R. Coelho1,*, M. Silva1, E. Rodrigues-Pinto1, S. Lopes1, P. Pereira1, H. Cardoso1,


F. Vilas-Boas1, J. Santos-Antunes 1, J. Lopes2, F. Carneiro2, G. Macedo1
1
Gastrenterology Department, 2Centro Hospitalar Sao Joao, Oporto, Oporto,
Portugal
Contact E-mail Address: rosacoelhoabrantes@hotmail.com
INTRODUCTION: Most patients with cholagiocarcinoma present an unresectable disease at diagnosis with an extremely poor prognosis, an average five-year
survival rate of 5 to 10 percent. Those, who undergo potentially curative resection, tumor-free margins can be obtained in only less than half of the patients [12].
AIMS & METHODS: To analyze the survival of patients with cholangicarcinoma according to clinical and therapeutic options. Retrospective study of
patients with diagnosis of cholangiocarcinoma between 2008 and 2013 in a tertiary referral center. The Kaplan-Meier survival curves were used, alpha 0.05.
RESULTS: We included 71 patients (39 male) with a median age of 71 years at
diagnosis. The mortality rate during the follow-up period was 79% (37% at 3
months, 42% at 6 months and 51% at 12 months). The median survival was 44
weeks (P25-75: 8-90). A higher level of survival at 3, 6 and 12 months was
associated with chemotherapy treatment (p 0.002, p 0.001, p 0.003, respectively), lower levels of CA-19.9 (p 0.001, p 0.009, p 0.013), surgical treatment (p50.001), TNM-R0 (p 0.006, p 0.031, p 0.039) and no metastization
at diagnosis (p50.001, p 0.006, p 0.002). Survival in the first trimester was
associated with TNM-N0 (p 0.022). Survival in the first year was associated
with higher levels of albumin (p 0.032), lower levels of alkaline phosphatase
(p 0.020), younger age (p 0.038) and fewer days between the beginning of the
symptoms until the diagnosis date (p 0.029). The analysis of the Kaplan-Meier
curves showed an association between survival, absence of metastization at diagnosis (p50.001), surgical treatment (p50.001) and chemotherapy treatment
(p 0.009). In terms of survival at 3, 6 and 12 months, the therapeutic surgery
and the mestastization were associated independently in the logistic regression.
CONCLUSION: The factors that determine a greater survival are surgical treatment and chemotherapy. Absence of metastization at diagnosis seems to be
related to a medium-term survival.
REFERENCES
[1]-Burke EC, Jarnagin WR, Hochwald SN, et al. Hilar Cholangiocarcinoma:
patterns of spread, the importance of hepatic resection for curative operation,
and a presurgical clinical staging system. Ann Surg 1998; 228: 385.
[2]-Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma. A spectrum of
intrahepatic, perihilar, and distal tumors. Ann Surg 1996; 224: 463.
Disclosure of Interest: None declared

Y.D. Cho1,*, S. Cha1, P. Ahn1, T.H. Lee1, H.J. Choi1, S.H. Park1, S.J. Kim1
1
Internal Medicine, Digestive Research, Digestive Disease Center, Soonchunhyang
University, College of Medicine, seoul, Korea, Republic Of
Contact E-mail Address: ydcho@schmc.ac.kr
INTRODUCTION: The use of endoscopic snare papillectomy (ESP) for the
treatment of duodenal major papillary neoplasm was increased. However, concerns about ESP included the risks of incomplete removal.
AIMS & METHODS: The aim of this study was to evaluate the clinical outcomes of ESP and the effectivity of argon plasma coagulation (APC) for the
treatment of residual tissue.
Among the patients who received ESP for the treatment of duodenal major
papillary neoplasm from November 2005 to march 2014, 33 patients were
enrolled. These patients were followed for more than 3 months. We retrospectively reviewed the medical records of the patients.
RESULTS: Twenty eight patients had adenoma, 2 had adenocarcinoma, 1 had
carcinoid tumor, 1 had paraganglioma and 1 had inflammation. Median followup periods was 12 months (range: 3-72 months). The overall rate of en bloc
resection was 87.9% (29/33). Specimens with margin positivity after ESP were
reported in 12 patients (9 lateral margin positivity, 3 lateral and vertical margin
positivity). Among the 12 patients with margin positivity, 5 patients received
additional treatment (4 APC, 1 hot biopsy and APC) and 7 patients with grossly
no residual tissue were followed by close endoscopic surveillance with white light
and/or narrow band imaging. Among all patients, local recurrence was detected
in 4 patients (12.1%, 4/33). 3 cases (25%, 3/12) occurred in the patient with
margin positivity and 1 case (4.8%, 1/21) occurred in the patient with margin
negativity. Two patients with local recurrence were the patients who did not
receive additional treatment of lateral margin positivity. There was no local
recurrence in the patients who received APC for the treatment of residual tissue.
CONCLUSION: After ESP of duodenal major papillary neoplasm, additional
treatment of margin positivity should be considered and close endoscopic surveillance should be performed. APC may be an effective method for the treatment of residual tissue.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
PANCREAS III POSTER EXHIBITION HALL XL_____________________
P1229 MUCUS SECRETION OF PANCREATIC DUCTAL EPITHELIUM
INCREASES IN CHRONIC PANCREATITIS
A. Balazs1,*, J. Duerr2, Z. Zhou-Suckow2, J. Schatterny2, L. Tiszlavicz3,
I.B. Nemeth3, Z. Rakonczay1, M. Mall2, P. Hegyi1
1
First Department of Medicine, University of Szeged, Szeged, Hungary,
2
Department of Translational Pulmonology, Translational Lung Research Center,
University of Heidelberg, Heidelberg, Germany, 3Department of Pathology,
University of Szeged, Szeged, Hungary
Contact E-mail Address: anitabalazs@outlook.com
INTRODUCTION: Mucoprotein plug formation within the pancreatic ducts is
one of the early events of chronic pancreatitis (CP), but little is known about its
pathogenesis. Recent evidence suggests impaired ion- and fluid secretion of pancreatic ductal epithelial cells (PDEC) in CP, which together with increased mucus
secretion may alter mucus hydration and subsequently lead to plug formation.
AIMS & METHODS: We aimed to invesigate mucus secretion of PDEC in CP.
Human and mouse pancreata were investigated. Human CP tissue samples were
collected from surgically resected pancreata, whereas CP was induced by administration of 6x50mg/kg cerulein, 3 series/week for 4 weeks in mice. Morphometric
analysis of mucus was carried out by CellF software. Total RNA was isolated
from human and mouse tissue. The mRNA levels of different mucin subtypes
were analysed by quantitative RT-PCR.
RESULTS: We found that mucus volume density (Vdmuc) of human PDEC was
significantly higher in CP than in controls, in case of smaller ducts (ductal diameter 5100mm: 1.210.13nl/mm2 and 0.370.05nl/mm2, respectively).
Similarily, mouse PDEC showed significantly higher Vdmuc in CP than in controls, especially in ducts with smaller diameter (ductal diameter 580mm:
0.720.06nl/mm2 vs. 0.0050.0002nl/mm2, ductal diameter 480mm:
0.0750.020nl/mm2 vs. 0.0160.004nl/mm2). Mucin gene expression analysis
showed, that muc6 was 1000-fold upregulated in mouse and 17-fold upregulated in human CP.
CONCLUSION: There is a substantial mucus hypersecretion in CP localized to
the small ducts. Obstruction of the small ducts by mucus in CP may contribute to
the pathogenesis of the disease. Supported by EPC Travel Fellowship.
Disclosure of Interest: None declared
P1230 IMPACT OF ETHANOL ON METABOLIC ACTIVITY OF HUMAN
PANCREATIC STELLATE CELLS
V. Cesna1, L. Venclauskas1, S. Trumbeckaite2, R. Baniene2, A. Gulbinas1,*,
G. Barauskas1
1
Department of Surgery, Lithuanian university of health sciences hospital,
2
Neuroscience institute, Lithuanian university of health sciences, Kaunas, Lithuania
Contact E-mail Address: c.vaidas@yahoo.com
INTRODUCTION: Alcohol consumption is the leading cause (70-90%) of
chronic pancreatitis, which is known to be one of the major factors for pancreatic
cancer pathogenesis. Pancreatic stellate cells (PSC) are known to play a key role
in pathogenesis of chronic pancreatitis. It is known, that ethanol activates PSC

A468
migration to pathological site of the pancreas. The effect of ethanol on PSC
energy metabolism is unknown. The aim of our study is to investigate PSC
growth change and energy metabolism under exposure to different alcohol
concentrations.
AIMS & METHODS: Human PSC were extracted from pancreatic tissue
obtained during pancreatic surgery. PSC were cultivated in Petri dishes in
DMEM and F-12 media, containing 20% FBS with addition of PenicillinStreptomycin. Immunofluorescence assay using beta-actin as primary antibody
was performed for differentiation PSC from fibroblasts. Crystal violet test was
performed using control cell group, 0.1%, 0.5% and 1% ethanol concentration.
MTT assay was carried out to determine different alcohol concentration impact
on the PSC viability. Oxygen consumption of PSCs was measured oxygraphically in cell media by using Oroboros-2K oxygraph (respiratory subtrates
glutamatemalate).
RESULTS: Cultivated cells were beta-actin positive indicating presence of PSC,
but not fibroblasts. Evaluating alcohol impact to the cell phenotype, we observed
0.5% alcohol induced cells were bigger compared to control. 0.1% and 1%
ethanol concentration forced cell shrinking. MTT assay revealed that the best
cell proliferation was achieved in PSC under pretreatment with 0.5% ethanol.
Pretreatment of cells with 0.5% ethanol increased oxygen consumption by 34%
as compared to control, i.e. activated energy metabolism, while low ethanol
concentration (0.1%) had no effect. However, higher concentrations (1%) of
ethanol decreased the pancreatic stellate cells respiration rate by 15% and 37%
as compared to control and to 0.5% ethanol group, respectively. The 2.4-dinitrophenol uncoupled respiration rate was also found to be diminished (by 22%)
after pretreatment with higher concentration (1%) of ethanol. Lower concentrations of ethanol (0.1-0.5%) had no effect on this parameter.
CONCLUSION: 0.5% ethanol concentration is the best PSCs promoter in the
matter of growth and oxygen consumption, while other investigated concentrations seem to have opposite effect. Further studies are necessary to investigate the
ways to reduce the activity of ethanol affected PSCs.
Disclosure of Interest: None declared
P1231 CIGARETTE SMOKE EXTRACT INHIBITS CFTR ACTIVITY AND
PANCREATIC DUCTAL FLUID SECRETION IN GUINEA PIG
K. Toth1, A. Schnur1, J. Maleth1, D. Csupor2, V. Venglovecz3,*, E. Gal1,
Z.J. Rakonczay1, P. Hegyi1
1
1st Department of Medicine, University of Szeged, 2Department of
Pharmacognosy, University of Szeged, 3Department of Pharmacology and
Pharmacotherapy, University of Szeged, Szeged, Hungary
Contact E-mail Address: dr.krisztinatoth@gmail.com
INTRODUCTION: Smoking represents an independent risk factor for the development of chronic pancreatitis, however, the pathomechanism remains
unknown. Secretion of fluid and bicarbonate plays a crucial role in maintaining
the integrity of the gland.
AIMS & METHODS: The aim of this study was to investigate the effects of
cigarette smoke extract (CSE) on pancreatic ductal fluid secretion and on cystic
fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity.
Intra/interlobular pancreatic ducts were isolated from guinea pig pancreas.
Basal and forskolin stimulated fluid secretion were measured by videomicroscopy, whereas, CFTR currents were detected by whole cell configuration of
the patch clamp technique. CSE was prepared by smoking of 3 cigarettes into
40ml distilled water by a smoking machine and 10x (21mg/ml), 40x (5.25mg/ml)
and 400x (0.5mg/ml) dilution of the extract were studied.
RESULTS: Administration of 5mM forskolin activated CFTR currents by 10-15fold in magnitude. 15 min administration of 0.5, 5.25 and 21 mg/ml CSE inhibited
the currents by 44%, 64.6% and 79.4%, respectively (n 2-4). Concerning the
fluid secretion, the basal volume of isolated intact pancreatic ducts in bicarbonate-free solution was considered to be 1.0. Administration of 25mM bicarbonate increased the relative luminal volume up to 1.570.02 (n 7).
Administration of 5 mM forskolin further increased the luminal volume to
1.870.1 (n 16). Simultaneous administration of 21mg/ml CSE decreased
fluid secretion by 24% (1.420.06; n 12).
CONCLUSION: CSE inhibits pancreatic ductal fluid secretion and the activity
of the CFTR which may play role in the smoke-induced pancreatic damage.
This study was supported by OTKA, MTA and NFU/TAMOP.
Disclosure of Interest: None declared
P1232 THE CONTRASTING EFFECT OF URSODEOXYCHOLATE AND
CHENODEOXYCHOLATE ON PANCREATIC DUCTAL EPITHELIAL
CELLS
M. Katona1,*, P. Hegyi1, Z. Rakonczay Jr1, M. Jozsef1, R. Zsolt2, V. Viktoria3
1
First Department of Medicine, 2Department of Pathology, 3Department of
Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
Contact E-mail Address: mate.katona@gmail.com
INTRODUCTION: We have recently shown that chenodeoxycholate (CDC) in
high concentration strongly inhibited ion transporters through the destruction of
mitochondrial function in intact guinea pig pancreatic ducts. Since ursodeoxycholic acid (UDC) is known to protect the mitochondria against hydrophobic
bile acids and have antiapoptotic effect, we investigated whether UDC is able to
prevent the CDC-induced cell damage.
AIMS & METHODS: Intra-interlobular ducts were isolated from guinea pig
pancreas. Ducts were then pretreated with UDC (0.1 mM and 0.5mM) for 5 h
and 24 h and changes in intracellular Ca2concentration [Ca2]i, ATP level
[ATP]i, pH [pH]i, mitochondrial permeability transition pore (MPTP) opening
were measured by microfluorometry. Mitochondrial transmembrane potential
(MTP) was studied by confocal microscopy. Morphological changes of

United European Gastroenterology Journal 2(1S)


mitochondria were investigated by transmission electron microscopy.
Expressions of bile acid transporters were studied by reverse transcriptase PCR
(RT-PCR).
RESULTS: 5 h pretreatment with 0.1 or 0.5 mM UDC and 24 h pretreatment
with 0.1 mM UDC did not significantly influence the effect of 1 mM CDC on
duct cells. However, 24 h pretreatment with 0.5 mM UDC significantly reduced
the rate of ATP depletion, mitochondrial injury, MPTP opening and the decrease
of MTP induced by 1 mM CDC. In addition, 0.5 mM UDC prevented the
inhibitory effect of CDC on the acid-base transporters, however, had no effect
on the CDC-induced calcium signaling. mRNA expression of Slc10A1 and A2
was detected in the ducts by RT-PCR.
CONCLUSION: Our results indicate that protection of mitochondria with UDC
administration may represent a novel option against bile acid-induced ductal
injury.
This study was supported by
Hungarian National Development Agency grants (TAMOP-4.2.2. A-11/1/
KONV-2012-0035,
TAMOP-4.2.2-A-11/1/KONV-2012-0052,
TAMOP-4.2.2. A-11/1/KONV-2012-0073, TAMOP-4.2.2./B-10/1-2010-0012,
TAMOP
4.2.4. A/2-11-1-2012-0001 National Excellence Program) and the Hungarian
Scientific Research
Fund (OTKA NF105758, NF100677, K109756)
Disclosure of Interest: None declared
P1233 GLUCAGON-POSITIVE ISLET CELLS CAN BE POSSIBLE
SOURCE OF PANCREATIC ACINAR TISSUE REGENERATION IN
COPPER-DEFICIENT MODEL
A. Abdulkhakova1, A. Galyavieva1, A. Trondin1, G. Pevnev2, M. Mavlikeev2,
A. Gumerova2, S. Abdulkhakov1.2,*, A. Kiyasov1.2
1
Kazan State Medical University, 2Kazan (Volga region) Federal University,
Kazan, Russian Federation
Contact E-mail Address: sayarabdul@yandex.ru
INTRODUCTION: Liver and pancreas are supposed to have the common
origin. There were publications by Rao et al. (1989) showing the possible appearance of hepatocyte-like cells in pancreas in copper-deficient diet model of pancreatic injury however the mechanisms of pancreatic regeneration in this model
werent described.
AIMS & METHODS: The aim of our work was to find out the possible sources
of pancreatic tissue restoration in copper-deficient model of pancreatic injury. 24
white Wistar male rats (80-100 g weight) were maintained on copper-deficient
diet (MP Biomedicals, USA) containing a relatively non-toxic copper-chelating
agent, triethylenetetramine tetrahydrochloride (Tokyo Chemical Industry Co.,
Ltd, Japan) in final concentration of 0.6 % w/w and had unlimited access to
water for 8 weeks, and then returned to normal rat chow for another 8 weeks
(recovery phase). Control group animals were maintained on normal rat chow
for the whole duration of experiment. Groups of 3 animals each were killed after
4, 6, and 8 weeks of copper-deficient diet and 4, 6, and 8 weeks after they
returned to normal rat chow. Histological sections of pancreas were stained
immunohistochemically using antibodies to insulin and glucagon.
RESULTS: After 4 weeks of copper-deficient diet we observed the signs of
pancreatic acinar tissue injury, after 6 and 8 weeks of diet only few ducts and
pancreatic islets were still present along with the almost total loss of acinar tissue.
The same picture was observed 2 and 4 weeks after animals were returned to
normal rat chow. Partial recovery of pancreatic acinar tissue was observed only
at 6 and 8 weeks of recovery phase. In control group glucagon-positive cells were
located predominantly on the periphery of pancreatic islets while insulin-positive
cells occupied most central part of the islet. Staining with antibodies to glucagon
after 2 and 4 weeks of copper-deficient diet revealed positive cells on the periphery of the islets; however therere some totally glucagon-positive islets as well as
some separate glucagon-positive cells within the destroyed acinar tissue. Later on
(6 and 8 weeks of copper-deficient diet and 2 and 4 weeks of recovery phase) few
small totally glucagon-positive islets along with the larger islets with intense
glucagon-positive staining on periphery and weaker staining in the central part
of the islet were observed. Pancreatic acinar tissue seemed to be partially restored
around the remaining/newly formed islets after 6 and 8 weeks of return to normal
rat chow. Staining with antibodies to insulin was positive only in central parts of
the islets at all terms of the experiment.
CONCLUSION: So we suppose that glucagon-positive progenitor cells can be
probably the source of pancreatic islets and acinar cells restoration.
Disclosure of Interest: None declared
P1234 DIFFERENTIAL EFFECTS OF THE CENTRAL AND PERIPHERAL
ADMINISTRATION OF OPIOIDS IN EXPERIMENTAL ACUTE
PANCREATITIS IN RATS
B. Kui1,*, Z. Balla1, E.S. Kormanyos1, B. Ivanyi2, T. Wittmann1, P. Hegyi1,
A. Szabo3, G. Horvath4, T. Takacs1, Z.J. Rakonczay1
1
First Department of Medicine, 2Department of Pathology, 3Institute of Surgical
Research, 4Department of Physiology, University of Szeged, Szeged, Hungary
Contact E-mail Address: k.kubali@gmail.com
INTRODUCTION: Acute pancreatitis (AP) is often associated with severe pain,
which causes discomfort and worsens the prognosis of the disease. Major analgetics (opioids) attenuate the pain associated with AP, but there are no experimental studies that investigated the effects and possible administration methods of
analgesia on the severity of AP.
AIMS & METHODS: AP was induced by intraperitoneal (i.p.) administration of
3 g/kg L-ornithine in SPRD rats. Intrathecal (i.t.) catheter was implanted one

United European Gastroenterology Journal 2(1S)


week before AP induction. 0.1-1 mg/kg i.p. or 0.01-0.03 mg/kg i.t. buprenorphine
(or physiological saline) was administered one hour before AP induction. Control
rats were injected i.p. or i.t. with physiological saline or buprenorphine one hour
before the i.p. administration of physiological saline instead of L-ornithine. The
animals were sacrificed after 24 hours. Laboratory (serum amylase activity, pancreatic dry/wet weight ratio) and histological (necrosis, oedema, inflammatory
cell infiltration) parameters were measured.
RESULTS: I.p. and i.t. treatment with buprenorphine did not influence laboratory and histological parameters in the control group. In the AP groups, all of
measured parameters were significantly elevated compared to control groups.
Pretreatment of AP rats with i.p. administered buprenorphine significantly
increased, whereas i.t. administration of the analgetic reduced all of the measured
parameters compared to the AP groups pretreated with saline.
CONCLUSION: The different routes of opioid administration have varying
effects on the pathogenesis of AP. Central administration of buprenorphine
seems to have beneficial effects on the severity of experimental AP, however
peripherally given opioids worsen the severity of the disease.
Sponsors: TAMOP: 4.2.2. A-11/1/KONV-2012-0035, 4.2.2-A-11/1/KONV-20120052, 4.2.2. A-11/1/KONV-2012-0073, OTKA: NF105758, NF100677, K101116,
Hungarian Academy of Sciences BO 00174/10/5
Disclosure of Interest: None declared
P1235 REVISION OF THE L-ARGININE-INDUCED EXPERIMENTAL
PANCREATITIS MODEL IN MICE
E.S. Kormanyos1,*, B. Kui1, Z. Balla1, B. Ivanyi2, T. Wittmann1, P. Hegyi1,
T. Takacs1, Z. Rakonczay Jr1
1
First Department of Medicine, 2Department of Pathology, University of Szeged,
Szeged, Hungary
INTRODUCTION: The pathogenesis of acute pancreatitis (AP) remains
unknown and it has no adequate therapy. To investigate the pathomechanism,
we rely on animal models such as L-arginine-induced AP, which is becoming
increasingly popular. However, we found only mild inflammation in Balb/c and
high mortality in FVB/n and C57BL/6 mouse strains with the originally published method (2x4 g/kg, 8% L-arginine).
AIMS & METHODS: We aimed to establish a basic amino acid-induced AP
model with acceptable morbidity and mortality rate. AP was induced with different doses (2x4, 3x3, 4x2.5 g/kg) and concentrations (0-10%) of intraperitoneal
L-arginine administration in Balb/c, FVB/n and C57BL/6 mice. Serum amylase-,
pancreatic myeloperoxidase activity and oedema, necrosis, leukocyte infiltration
were measured to determine AP severity. Our findings are represented as effectivity rate (ER number of mice with AP/all treated mice).
RESULTS: In L-arginine treated groups, all parameters were significantly elevated compared to the control group. In all three strains, the injection with 3x3
or 4x2.5 g/kg L-arginine caused similar AP severity with lower mortality vs the
2x4 g/kg dose. In Balb/c mice, 10% L-arginine injection resulted in moderate
morbidity and low mortality (ER 90%). In FVB/n strain 5% L-arginine caused
low mortality with severe AP (ER 90%), while 10% L-arginine caused greater
mortality (ER 25%). C57BL/6 mice developed mild disease with low mortality
due to 5% L-arginine (ER 90%), however, disease severity and mortality were
higher in case of 10% L-arginine administration (ER 35%).
CONCLUSION: Mouse strains show different sensitivities to L-arginine and a
fine borderline appears between effective and lethal doses and concentrations.
Sponsors: TAMOP: 4.2.2. A-11/1/KONV-2012-0035, 4.2.2-A-11/1/KONV-20120052, 4.2.2. A-11/1/KONV-2012-0073; OTKA: NF105758, NF100677, K101116.
Disclosure of Interest: None declared
P1236 THE EFFECTS OF HMG-COA REDUCTASE INHIBITOR ON
LIPOPOLYSACCHARIDE INDUCED ACTIVATION OF
PANCREATIC STELLATE CELLS
H.S. Lee1,*, J.M. Lee1, J.J. Hyun1, H.J. Kim1, J.S. Kim1, C.D. Kim1
1
Internal Medicine, Korea University College of Medicine, Seoul, Korea, Republic
Of
Contact E-mail Address: hslee60@korea.ac.kr
INTRODUCTION: Pancreatic stellate cell (PSC) plays a crucial role in pancreatic fibrogenesis in chronic pancreatitis. Increased gut permeability has been
described in acute and chronic pancreatitis with the effect of bacterial translocation across the mucosal barrier. Bacterial components such as lipopolysaccharide
(LPS) may reach the bloodstream and pancreas. Islet cell dysfunction also develops during acute exacerbating stage and end stage of chronic pancreatitis.
However little is known about the effect of LPS and hyperglycemia on PSC.
AIMS & METHODS: Aims: To investigate the effects of LPS and hyperglycemia
on PSC activation and effects of simvastatin on LPS induced PSC activation.
Materials and Method: Primary cultures of rat PSCs were exposed to various
concentrations of glucose and LPS with/without simvastatin. Quantification of
proliferation was performed by Brd-U assay. PSC activation was assessed by
expression of -SMA and extracellular signal-regulated kinase (ERK) using
Western blot.
RESULTS: Results: LPS induced activation and proliferation of PSC. However,
glucose did not affect PSC proliferation. The proliferative effect of LPS on PSC
was not affected by glucose concentration in culture media. Simvastatin inhibited
LPS induced activation and proliferation of PSC. The proliferative effect of LPS
was mediated by activation of Erk 1/2 pathway which was effectively inhibited by
simvastatin.
CONCLUSION: Conclusion: This study shows that LPS is one of the activating
factors toward PSC. Endotoxemia which is frequently encountered in the clinical
settings of acute and chronic pancreatitis may act as a triggering factor for

A469
initiating and persisting pancreatic fibrosis. Simvastain could be a therapeutic
agent for preventing pancreatic fibrosis.
Disclosure of Interest: None declared
P1237 THE ROLE OF HEAT SHOCK PROTEIN 70 IN PANCREATIC
STELLATE CELLS
J.J. Hyun1,*, J.M. Lee1, H.J. Kim1, J.S. Kim1, H.S. Lee1, C.D. Kim1
1
Internal Medicine, Korea University College of Medicine, Seoul, Korea, Republic
Of
Contact E-mail Address: sean4h@korea.ac.kr
INTRODUCTION: The role of heat shock protein 70 (hsp70) in acinar cells
(acute pancreatitis) and ductal cells (pancreatic cancer) has been extensively
studied. However, the role of hsp70 in pancreatic stellate cell (PSC), an important
cell responsible for desmoplastic reaction, is less well understood.
AIMS & METHODS: Aims: To investigate the role of hsp70 in PSC activation
and proliferation.
Materials and Methods: PSCs were incubated at 42 C for 2hr and recovered at
37 C for 24hr in order to induce hsp70 expression. Cultured PSCs were treated
with heat, PDGF, TGF-, and LPS to measure -SMA and hsp70 expression by
Western blotting. Cell proliferation was measured by BrdU assay. Simvastatin
and quercetin were used in order to inhibit PSC proliferation and hsp70 expression, respectively.
RESULTS: Overexpression of hsp70 did not affect cytokine induced -SMA
expression. Hsp70 expression was significantly increased with PDGF and to a
moderate degree with LPS, but not with TGF-. Similarly, PSC proliferation was
also significantly increased by PDGF and to a lesser degree by LPS, but TGF-
did not induce PSC proliferation. Simvastatin suppressed hsp70 expression and
PSC proliferation induced by heat or PDGF. Quercetin completely inhibited
PDGF-induced hsp70 expression and cell proliferation and partly inhibited
heat-induced effects. However, heat preconditioning which induces hsp70 expression had no additional effect on PDGF induced cell proliferation.
CONCLUSION: Hsp70 expression was closely related to cell proliferation in
PSCs. Inhibition of hsp70 expression abolished or decreased the effect of
PDGF and heat on cell proliferation. Therefore, modulation of hsp70 expression
could be an effective therapeutic target for inhibition of pancreatic fibrosis.
Disclosure of Interest: None declared
P1238 GRANULOCYTE COLONY-STIMULATING FACTOR REDUCES
FIBROSIS IN A MOUSE MODEL OF CHRONIC PANCREATITIS
W.-R. Lin1,*, T.-H. Yen2, S.-N. Lim3, M.-D. Perng4, M.-Y. Su1, C.-T. Yeh5, C.T. Chiu1
1
Gastroenterology, 2Nephrology, 3Neurology, Linkou Chang Gung Memorial
Hospital, Taoyuan, 4Institute of Molecular Medicine, National Tsing Hua
University, Hsinchu, 5Liver Research Unit, Linkou Chang Gung Memorial
Hospital, Taoyuan, Taiwan, Province of China
Contact E-mail Address: victor.wr.lin@gmail.com
INTRODUCTION: Chronic pancreatitis (CP) is a necroinflammatory process
resulting in extensive fibrosis and loss of both exocrine and endocrine function.
Granulocyte colony-stimulating factor (G-CSF), a hematopoietic stem cell mobilizer, has been shown an anti-fibrotic effect in liver partial through the enhancement of bone marrow (BM) cells into fibrotic liver1. In this study, we aim to test
the effect of G-CSF on fibrosis in a mouse model of CP.
AIMS & METHODS: The BM from male green fluorescent protein transgenic
C57Bl/6J mice was transplanted into irradiated female C57Bl/6J mice. CP was
induced by consecutive caerulein injection (50ug/kg/day, two days a week) for 6
weeks. Mice were then treated with G-CSF (200ug/kg/day, 5 day a week) or
normal saline for 1 week, and sacrificed at week 7 or week 9 after first caerulein
injection. Pancreatic histology, collagen expression, myofibroblast and BM cells
were evaluated to determine the effect of G-CSF in caerulein-induced CP.
RESULTS: The fibrosis was observed in the pancreatic tissues from mice with
caerulein injection. The fibrosis was not induced by G-CSF alone. The degree of
fibrosis and collagen were significantly decreased in the pancreas from mice with
caerulein and G-CSF sacrificed at week 9, while there was no change observed at
week 7. The number of myofibroblast in the pancreatic tissue was not changed
between mice with or without G-CSF. However, the proportion of BM cells was
significantly increased in the mice with G-CSF, suggesting a potential anti-fibrotic role of BM cells stimulated by G-CSF.
CONCLUSION: G-CSF administration contributes to the regression of pancreatic fibrosis at least partially through the enhanced migration of BM cells.
REFERENCES
1. Higashiyama R, Inagaki Y, Hong YY, et al. Bone marrow-derived cells
express matrix metalloproteinases and contribute to regression of liver fibrosis
in mice. Hepatology 2007; 45: 213-222.
Disclosure of Interest: None declared

A470
P1239 THE NOVEL KYNURENIN ANALOGUE SZR-72 IS BENEFICIAL
IN ACUTE PANCREATITIS IN RATS
Z. Balla1,*, B. Kui1, E.S. Kormanyos1, B. Ivanyi2, L. Vecsei3, F. Fulop4,
G. Varga5, T. Takacs1, T. Wittmann1, P. Hegyi1, Z. Rakonczay Jr1
1
First Department of Medicine, 2Department of Pathology, 3Department of
Neurology, 4Institute of Pharmaceutical Chemistry, 5Institute of Surgical
Research, University of Szeged, Hungary, Szeged, Hungary
Contact E-mail Address: ballatanar@gmail.com
INTRODUCTION: The pathogenesis of acute pancreatitis (AP) is not well
understood and the disease has no specific therapy. There is evidence that the
L-kynurenic acid analogue SZR-72 has immune modulator roles in several
inflammatory diseases. Therefore, we investigated its effects on experimental AP.
AIMS & METHODS: In the AP groups, male SPRD rats were injected intraperitoneally (i.p.) with 3 g/kg L-ornithine 1 hour after the administration of
physiological saline (PS) or 30-300 mg/kg SZR-72 (n 6-8). Control animals
were injected i.p. with PS instead of L-ornithine and with 30-300 mg/kg SZR72 or PS 1 hour afterwards (n 6-8). Animals were sacrificed at 24 hours.
Laboratory [serum amylase activity, pancreatic myeloperoxidase (MPO) activity,
pancreatic dry/wet weight ratio (DW/WW)] and histological (necrosis, oedema,
inflammatory cell infiltration) parameters were measured to evaluate disease
severity.
RESULTS: The administration of 30-300 mg/kg SZR-72 did not influence serum
amylase and pancreatic MPO activities, pancreatic DW/WW and histological
parameters in the control groups. However, the injection of rats with L-ornithine
significantly increased all parameters vs. the control groups. Pre-treatment of AP
rats with 30 mg/kg SZR-72 did not have affect on disease severity. However, all
measured laboratory and histological parameters were significantly reduced in
AP animals in response to treatment with 300 mg/kg SZR-72.
CONCLUSION: Our experiments showed that SZR-72 has a dose-dependent
effect on L-ornithine-induced AP. The administration of 300 mg/kg SZR-72
significantly ameliorated the severity of AP in rats. Further investigations are
needed to determine the pathomechanism of SZR-72 action.
This study was supported by TAMOP-4.2.2. A-11/1/KONV-2012-0035,
TAMOP-4.2.2-A-11/1/KONV-2012-0052 TAMOP-4.2.2. A-11/1/KONV-20120073, NF105758, NF100677, K101116, BO00174/10/5.
REFERENCES
Disclosure of Interest: None declared
P1240 IS TIMING OF EARLY ENDOSCOPIC INTERVENTION IN
ACUTE BILIARY PANCREATITIS IMPORTANT?
A. Sayilir1,*, B. Odemis1, E. Parlak1, S. Disibeyaz1, Y. Beyazit1, N. Sasmaz1
Gastroenterology, TURKIYE YUKSEK IHTISAS TEACHING AND
RESEARCH HOSPI, ANKARA, Turkey
Contact E-mail Address: drabdurrahim@gmail.com

United European Gastroenterology Journal 2(1S)


in both groups. The only deaths were observed in 2 (3.3%) patients in the 24hour group.
Table 1. Comparison of disease severity between groups according to different
scoring systems
First 24 hours group 24-72 hours group
n 32 (%)
n 27 (%)
p-value
Ranson score
2 mild
3-5 moderate
mGPS
2 mild
42 severe
CTSI*
0-3
4-6
7-10
Organ failure**
At least one organ
Hypotension
Acute renal failure
Respiratory failure
24-48. hour CRP, mg/L
Length of hospital stay, days

25 (78.1)
7 (21.9)

22 (81.5)
5 (18.5)

0.750

25 (78.1)
7 (21.9)

21 (77.8)
6 (22.2)

0.974

24 (92.3)
1 (3.8)
1 (3.8)

12 (85.7)
1 (7.1)
1 (7.1)

0.803

7 (21.9)
2 (6.3)
3 (9.4)
2 (6.3)
59.95 (3.36-268
5 (3-12)

6 (22.2)
1 (3.7)
4 (14.8)
2 (7.4)
114.5 (6.26-271)
7 (3-30)

0.974
0.565
0.403
0.627
0.242
0.122

MGPS, modified Glasgow prognostic score;CTSI, computerized tomography


severity index; *calculated for 26 patients in the 24-hour group and for 14
patients in the 24-72 hour group, CRP, C-reactive protein,**based on Atlanta
criteria
CONCLUSION: In our study, we could not demonstrate any added benefit of
ERCP performed within 24 hours comparing with 24-72 hours of the onset of
symptoms with regards to local and systemic complications of ABP. Undertaking
early endoscopic intervention, however, increases the likelihood of detecting an
impacted stone at the papilla, the delayed management of which may increase the
risk for cholangitis. Early ERCP in patients with ABP is effective and safe, and
may be recommended in the presence of cholangitis and persistent biliary
obstruction.
Disclosure of Interest: None declared

INTRODUCTION: The exact role and optimal timing for endoscopic retrograde
cholangiopancreaticography (ERCP) for the management of acute biliary pancreatitis (ABP) remains a controversial topic.
AIMS & METHODS: The main aim of this study was to investigate any benefits
early ERCP intervention may have in preventing the development of local and
systemic complications due to ABP. Patients presenting to Turkiye Yuksek
_
Ihtisas
Teaching and Research Hospital (TYIH) between 1 January 2010 and
31 August 2011 with ABP, who underwent ERCP within 72 hours of the onset of
symptoms were screened, and eligible patients were enrolled in the study. Patients
were divided into 2 groups based on timing of ERCP (24 hour group: ERCP
performed within 24 hours; 24-72 hour group: ERCP performed 24-72 hours
after onset of symptoms), and comparisons between both groups were made in
terms of patient characteristics, severity of pancreatitis, and local/systemic
complications.
RESULTS: A total of 59 patients were included in the final analysis, for 32 of
which ERCP was performed in the first 24 hours, while in the remaining 27
patients endoscopic intervention was undertaken 24-72 hours after the onset of
symptoms. There was no difference between the 24 hour and 24-72 hour groups
with regards to biliary stone detection rate (84.4% vs. 71.4% p 0.196).
However, impacted stones at the papilla were observed more frequently in the
24-hour group compared to the 24-72 hour group (50% vs. 11.1%; p 0.006).
Severity of pancreatitis, rate of pancreatitis-related complications, computed
tomography severity index scores and durations of hospital stay were similar

P1241 PREDICTIVE FACTORS FOR, AND INCIDENCE


ADMISSIONS OF PATIENTS WITH ACUTE AND CHRONIC
PANCREATITIS

OF

RE-

A.A. Aghdassi1,*, T. Suchsland2, K. Kuhn2, P. Simon1, J. Mayerle1, S. Flea2,


M.M. Lerch1
1
Department of Medicine A, University Medicine Greifswald, 2Department of
Health Care Management, University of Greifswald, Greifswald, Germany
Contact E-mail Address: aghdassi@uni-greifswald.de
INTRODUCTION: While factors like older age and greater severity of the initial
disease cannot be influenced to reduce the readmission rate for pancreatitis,
variables like alcohol-, tobacco- and substance abuse should be addressed in
outpatient programs to reduce disease recurrence and readmission rate for
pancreatitis.
To study positive and negative predictive factors for hospital readmissions of
patients after in-hospital treatment for pancreatitis.
AIMS & METHODS: Data from patient records and reimbursement information of the years 2006 2011 were evaluated for 606 hospital admissions for
pancreatitis (373 patients). 973 patient variables, 611 secondary diagnoses, and
295 different procedures (OPS) were assessed by bivariate and multivariate
analysis.
RESULTS: The readmission rate of pancreatitis patients during the first 30 days
after discharge was 15 %, over the entire study period 29 %. The best predictors
for readmission were, when present during the initial episode, concomitant liver
disease (OR 12.8; C31.5-111), a suspected tumor of the pancreas (OR 10; C31.192), alcohol- (OR 5.4; C32-13), tobacco- or substance-abuse or mental illness.
Patients with pseudocyst formation or who had undergone contrast enhanced CT
were also more frequently readmitted. Lower than average readmission rates
were found when pancreatitis was treated in connection with decompensated
diabetes or gallstone disease.
CONCLUSION: While factors like older age and greater severity of the initial
disease cannot be influenced to reduce the readmission rate for pancreatitis,
variables like alcohol-, tobacco- and substance abuse should be addressed in
outpatient programs to reduce disease recurrence and readmission rate for
pancreatitis.
Disclosure of Interest: None declared

A471

United European Gastroenterology Journal 2(1S)


P1242 VALUE OF DIFFERENT PROGNOSTIC SYSTEMS AND
BIOLOGICAL MARKERS FOR PREDICTING SEVERITY OF ACUTE
PANCREATITIS ACCORDING TO THE REVISED ATLANTA
CLASSIFICATION
H. Yoon1,*, J.H. Cho1, K.J. Lee2, H.M. Kim2, Y.J. Kim1, Y.S. Kim1
Internal Medicine, Gachon University Gil Medical Center, Incheon, 2Internal
Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea, Republic
Of
Contact E-mail Address: hwa9620@naver.com
1

INTRODUCTION: Early identification of patients at risk for severe acute pancreatitis (SAP) is an essential step to guide an intensive care and to improve
outcomes.
AIMS & METHODS: Because the severity of acute pancreatitis (AP) was reclassified, we aimed to compare the prognostic value of various predictors including
procalcitonin (PCT), C-reactive protein (CRP), CT severity index (CTSI), and
complex scoring systems (BISAP, Ransons, APACHE-II score) according to
revised Atlanta classification. Between March 2010 and September 2013, 152
patients with AP were prospectively enrolled. CRP and PCT were obtained on
admission, and various scoring systems including Ransons, APACHE-II, BISAP
and CTSI were calculated.
RESULTS: There were 152 patients with AP (mean age 51.3  18.5, 63.2 %
male), of which 45 patients (30%) was classified as moderately SAP and 17
patients (11%) SAP. In patients with moderately severe to SAP, PCT (on admission, 4 0.5 ng/ml, AUC 0.61, CI 0.51-0.70), CRP 2d (24 hours after admission,
410 mg/dl, AUC 0.64 CI 0.55-0.67) BISAP (score 3, AUC 0.60, CI 0.510.70),
Ransons (score 3, AUC 0.65, CI 0.560.76), APACHE-II (score 8, AUC
0.61, CI 0.520.70), and CTSI (score 3, AUC 0.79, CI 0.720.87) were significant predictors compared to mild AP. Multivariate analysis showed that
CTSI (sensitivity 63%, specificity 84%, OR 11.5, CI 4.7-27.8, p50.01),
APACHE-II (sensitivity 32%, specificity 88%, OR 3.7, CI 1.2-11.6, p 0.028),
and CRP 2d (sensitivity 39%, specificity 90%, OR 4.6, CI 1.6-13.6, p50.01) were
strongly related to moderately severe and SAP. In patients with SAP compared
with mild to moderately SAP, PCT (AUC 0.79, CI 0.67-0.92), BISAP (AUC 0.66,
CI 0.500.82), Ransons (AUC 0.76, CI 0.650.88), and APACHE-II (AUC
0.72, CI 0.570.86) were significant predictors. On multivariate analysis using
them, PCT (sensitivity 75%, specificity 82%, OR 5.8, CI 1.4-24.2, p 0.015) was
only strongly associated with SAP.
CONCLUSION: According to revised Atlanta classification, various biological
and structural scoring system had different prognostic value for predicting severity of AP. In patients with SAP, the best efficiency in the early prediction would
be achieved by the measurements of PCT. However, in case of moderately to
severe AP, CTSI, APACHE-II and CRP 2d act as a valuable predictors for
severity of them.
REFERENCES
1. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis2012: revision of the Atlanta classification and definitions by international
consensus. Gut 2013; 62: 102-111.
2. Otsuki M, Takeda K, Matsuno S, et al. Criteria for the diagnosis and severity
stratification of acute pancreatitis. World J Gastroenterol 2013; 19: 5798-5805.
3. Nawaz H, Mounzer R, Yadav D, et al. Revised Atlanta and determinantbased classification: application in a prospective cohort of acute pancreatitis
patients. Am J Gastroenterol 2013; 108: 1911-1917.
Disclosure of Interest: None declared
P1243 COMPLEX
TREATMENT
OF
INTRAABDOMINAL
HYPERTENSION IN PATIENTS WITH ACUTE PANCREATITIS
I. Kolosovich1,*, V. Teplyi1, A. Lutsiv1, A. Kolosovych1
1
Surgery Department #2, O. Bohomolets National Medical University, Kyiv,
Ukraine
Contact E-mail Address: kolosovich_igor@mail.ru
INTRODUCTION: Abdominal compartment syndrome (ACS) is a serious problem in acute inflammatory diseases of the abdominal cavity. Causing severe
changes in organs and tissues, this pathology is responsible for the up to 42%
lethality (1). Acute pancreatitis (AP) occupies a special place among acute
abdominal pathology. In case of wide-spread pancreatic and peripancreatic
necrosis it can cause development of life-threatening complications, among
which special subject of the interest is severe intra-abdominal hypertension
(IAH)(2).
AIMS & METHODS: The purpose of this study was to use antiflatulents in
complex treatment of IAH in patients with AP to prevent the development of
ACS. We observed 35 patients with AP, in whom IAH of varying severity
(according to classification of J. M. Burch et al.,1996) was identified at admission. Males were 21 (60%), females 14 (40%). Age of the patients ranged from
24 to 58 years, averaging 38.61.2 years. We monitored intra-abdominal pressure (IAP) by measuring the bladder pressure (BP). First grade of IAH was
detected in 12 patients (34.3%), second grade in 18 (51.4%), third grade in
5 (14.3%). With the help of ultrasonography liquid in omental bursa was found
in all patients, in 13 of them fluid in the abdominal cavity (enzymatic peritonitis). Complex conservative treatment of the 15 patients with AP (42.9%) corresponded to guidelines from the World Society of the ACS: insertion of
nasogastric tube; prokinetic agents; intraabdominal catheter drainage (3
patients), epidural block; antisecretory and detoxification therapy and early enteral nutrition (Group 1). In 20 patients (57.1%) antiflatulent (50 Espumisan
emulsion droplets in the probe for enteral feeding thrice daily) was added to
diminish IAH (Group 2).
RESULTS: Complex conservative treatment in 60% of group 1 patients normalized bowel function (decreased bloating and flatulence, spontaneous defecation)

during a week period. Monitoring of BP demonstrated significant decrease of


IAP in 8 of them (53.3%): in 5 of the 7 patients (71.4%) with first grade IAH, 2 of
6 patients (33.3%) with II grade IAH and one of the two patients (50%) with
IAH of III grade. Additional use of Espumisan emulsion allowed restoration of
bowel function in similar terms in 90% of patients in group 2. In latter group
normalization of IAP was achieved in 17 people (85%): in all 6 patients with first
grade IAH, in 9 of 11 patients (81.8%) with second grade IAH and in 2 of 3
patients (66.7%) with third grade IAH (p50.05). Conservative measures did not
permit to normalize the IAP in 2 patients of every group whom then decompressive laparotomy was performed.
CONCLUSION: Complex conservative treatment of IAH including antiflatulents in patients with AP effectively normalizes bowel function, and thus
decreases IAP in significantly more patients (85.0% versus 53.3% in the control
group). The majority of patients could be avoided from the development of ACS.
REFERENCES
1. De Keulenaer BL, et al. Nonoperative management of intra-abdominal hypertension and abdominal compartment syndrome: evolving concepts. Am Surg
2011; 77(Suppl. 1): 34-41.
2. Pupelis G, et al. Increased intra-abdominal pressure an important risk factor
of early organ dysfunction in severe acute pancreatitis. Zentralbl Chir 2002; 127:
982-986.
Disclosure of Interest: None declared
P1244 RISK FACTORS FOR INFECTION AFTER ENDOSCOPIC
ULTRASONOGRAPHY-GUIDED DRAINAGE OF SPECIFIC TYPES
OF PANCREATIC AND PERI-PANCREATIC FLUID COLLECTIONS
J. Guo1,*, S. Sun1
Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang,
China
Contact E-mail Address: guojt@sj-hospital.org
1

INTRODUCTION: Endoscopic ultrasonography (EUS)-guided drainage is a


widely-used treatment modality for specific types of pancreatic and peri-pancreatic fluid collections (PFCs). The complication of infection have been reported. It
is recommended that the infection rate should be assessed by measuring risk
factors.
AIMS & METHODS: Aims: The objectives were to measure whether the risk of
infection after endoscopic ultrasound guided drainage was associated with (1)
patient-related factors and (2) procedure-related factors.
Methods: A total of 83 patients were eligible for inclusion in this study from
September 2005 through November 2012. EUS-guided drainage was performed
in all patients. The complication of infection was observed. The data on patientrelated factors, and procedure-related factors were collected. Patient-related factors mainly included age, sex, etiology of PFCs, location of the cyst, cyst diameter, and so on. Procedure-related factors mainly included approach of EUSguided drainage and stent diameter. Separate multivariate logistic regression
models for all EUS-guided drainage were carried out.
RESULTS: Complete EUS-guided drainage was achieved in all patients (100%).
A definitive diagnosis of infection after EUS-guided drainage was made in seven
patients. All seven patients had a history of acute pancreatitis, and the cyst
diameters were all 4 15 cm. Three patients suffered from diabetes mellitus.
CONCLUSION: Acute pancreatitis and cyst diameter were the relevant independent risk factors for infection after EUS-guided drainage. Furthermore, cyst
diameter was an independent risk factor for infection. Additional stent placement
or using double flanged metal stents may be useful to avoid infection.
REFERENCES
1. Baron TH, Harewood GC, Morgan DE, et al. Outcome differences after
endoscopic drainage of pancreatic necrosis, acute pancreatic pseudocysts, and
chronic pancreatic pseudocysts. Gastrointest Endosc 2002; 56: 717.
2 Cahen D, Rauws E, Fockens P, et al. Endoscopic drainage of pancreatic
pseudocysts: long-term outcome and procedural factors associated with safe
and successful treatment. Endoscopy 2005; 37: 977-983.
3 Rotman SR and Kahaleh M. Pancreatic fluid collection drainage by endoscopic
ultrasound: new perspective. Endosc Ultrasound 2012; 1: 61-68.
4 Akshintala VS, Saxena P, Zaheer A, et al. A comparative evaluation of outcomes of endoscopic versus percutaneous drainage for symptomatic pancreatic
pseudocysts. Gastrointest Endosc 2013 Dec 4.
Disclosure of Interest: None declared
P1245 THE EFFECT OF ASPIRIN USE ON SEVERITY OF ACUTE
PANCREATITIS IN HOSPITALIZED PATIENTS
N. Poowanawittayakom1,*, M. Flicker1
1
Internal Medicine, Advocate Illinois Masonic Medical Center, Chicago, United
States
Contact E-mail Address: nongnoochmd@gmail.com
INTRODUCTION: Acute pancreatitis is a common gastrointestinal disease
often seen in daily practice. Although the precise mechanism of pancreatitis is
still not fully understood, it is believed that the inflammatory response via phospholipase A2, cyclogenase, and neutrophils plays a role. Aspirin is a commonly
used NSAID, most notably prescribed for cardiovascular diseases such as stroke,
myocardial infarction, and select groups of patients with atrial fibrillation. The
aim of this study was to examine the effect of aspirin use on the severity of acute
pancreatitis.
AIMS & METHODS: A total of 135 patients with the diagnosis of acute pancreatitis were included in this retrospective study. Relevant clinical data were
collected. Patients were divided into two groups according to aspirin use or
non-use and the severity of acute pancreatitis was compared. Severe pancreatitis
was defined as a Ranson score at any time  3. Appropriate descriptive statistics

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United European Gastroenterology Journal 2(1S)

and statistical tests were performed. Statistical significance was defined as a p


value 5 0.05.
RESULTS: The cohort consisted of 58% (78 of 135) men with a mean (SD) age
of 50 (18) years. Of the 135 patients, 4 (2.96%) had gallstone pancreatitis, 4
(2.96%) had alcoholic pancreatitis, and 127 (94.07%) had pancreatitis of
unknown etiology. Median (interquartile range) Ranson score on admission
and 48 hours afterwards were 2 (1.3) and 1 (0.2), respectively. On admission,
there was no statistically significant difference in aspirin user group and nonaspirin user group between the mild-to-moderate acute pancreatitis group and
the severe acute pancreatitis group (Table 1). Likewise, at 48 hours after admission, the percentage of patients with aspirin use was not statistically different
(p 0.678) between the two severity groups as shown on Table 2. Multivariable
regression analysis showed that female gender was the only independent variable
associated with a higher severity of pancreatitis (p 0.046)
CONCLUSION: This pilot study demonstrates that aspirin use has no effect on
decreasing the severity of acute pancreatitis. Female gender was associated with a
higher severity of acute pancreatitis in the first 48 hours after admission. This
association has never been identified in prior studies. Obesity, however, which
has previously been found to be associated with a higher severity of pancreatitis
was not identified as a predictor for the severity of acute pancreatitis in this
study.
Disclosure of Interest: None declared

or metastatic state was diagnosed and if at least one cycle of chemotherapy was
given. Survival was assessed until February 2014.
RESULTS: 107 patients met the inclusion criteria. Of the 74 patients in the
historical control group 62 patients received Gemicitabine, 6 Gemcitabine combined with Erlotinib, 5 Gemcitabine combined with Oxalipaltin and one 5Fluoruracil as the first line chemotherapy. Of the 33 patients diagnosed between
2011 and July 2013, 15 patients received FOLFIRINOX, 17 Gemcitabine and
one patient Oxaliplatin as the first line chemo therapy. 45 out of the 74 patients in
the historical control group died and 29 were lost to follow-up. 12 out of the 33
patients in the group diagnosed from 2011 died, 10 were lost to follow-up and 11
were alive until February 2014. Mean of combined time of survival and lost to
follow-up revealed 9.2 months (95% CI, 7.4 to 11.0) in the historical control
group and 12.7 months (95% CI, 9.8 to 15.6) in the group diagnosed from 2011.
Estimated mean survival using Kaplan-Meier was 14.2 months (95% CI, 10.4 to
17.9) in the historical control group and 20.1 months (95% CI, 16.1 to 24.1) in
the group diagnosed from 2011. Comparison of the survival curves between the
two groups using the log-rank test showed p 0.005.
CONCLUSION: This retrospective study presents a marked improvement in
survival of patients diagnosed with locally advanced or metastatic adenocarcinoma of the pancreas in a community-based hospital during the past three years.
A possible contributing reason is the use of new polychemotherapies.
Disclosure of Interest: None declared

P1246 MEAN PLATELET VOLUME AND OTHER INFLAMMATORY


MARKERS IN PATIENTS WITH ACUTE PANCREATITIS

P1248 EXOCRINE PANCREATIC INSUFFICIENCY IN PATIENTS WITH


PANCREATIC OR PERI-AMPULLARY CANCER: A SYSTEMATIC
REVIEW

Y. Okuturlar1,*, A. Soylu2, O. Harmankaya1, S. Cakmak2, H. Ozkan1,


B. Oztosun1, I. Utku1, S. Sayilan2, U. Ure1, B.A. Kumbasar1
1
Internal Medicine, 2Gastroenterology, Bakirkoy Dr Sadi Konuk Research and
Training Hospital, Istanbul, Turkey
INTRODUCTION: Acute pancreatitis (AP) induced by different etiological factors is a pancreatic inflammation which is caused by the activation of pancreatic
enzymes. The pancreas can usually heal itself without any local and systemic
complications. No single laboratory markers are pathognomonic for AP. Mean
platelet volume (MPV) has been investigated as an indicator of inflammation and
related in several inflammatory diseases. In our study, we aimed to investigate the
relationship between white blood cells (WBC) and C-reactive protein (CRP)
which are the indicators of AP inflammation and MPV.
AIMS & METHODS: All the data from the 84 (male/female: 51/33) patients
diagnosed by non-biliary acute pancreatitis (NBAP) were evaluated. The patients
included in this study were diagnosed by clinically, laboratory methods (three
times increase in amylase and lipase) and imaging. The symptoms of the patients
at the first visit, the findings of the laboratory results and imaging were compared
with the values at the time of discharge. The levels of MPV, WBC and CRP of
the NBAP patients were compared with the control group (male/female: 53/47) at
the first admission and discharge.
RESULTS: The mean age was 50.0217.69 years and 41.1110.46 years for
NBAP and control group, respectively and there was no age and gender significant difference between groups (p40.05). WBC levels of the NBAP group at
onset (12.485.93/mm3x103) and remission (7.542.4/mm3x103) were higher
than the control group (6.431.49/mm3x103) (p 0.0001 for both groups).
MPV levels of the NBAP group at onset (8.071.07 fL) and remission
(8.551.05 fL) were lower than the control group (8.990.94 fL) (p 0.0001;
p 0.003). The mean CRP value was 10.4610.39 mg/dl at onset; however it
dropped to the value of 3.484.96 mg/dl at remission. CRP values of onset and
remission were higher than the control group (0.470.66 mg/dl) (p 0.0001 in
both groups) (Table 1). When the cut-off value of MPV was taken smaller than 8
fL in the ROC analysis, the sensitivity and specificity were found 54.7% and
86.8%, respectively (AUC: 0.74, p50.001).
CONCLUSION: In NBAP patients, the WBC and CRP values were higher at the
initial phase of the disease than the healing phase. The MPV value was low at the
first examination in which the inflammation was high; it was higher in the healing
phase of the disease. In NBAP patients, the increase in MPV values during the
healing phase shows that there is a decrease in the inflammation and the remission phase has started.
Disclosure of Interest: None declared
P1247 MARKED
IMPROVEMENT
IN
PANCREATIC
SURVIVAL A SINGLE CENTER EXPERIENCE

CANCER

A. Hann1,*, W. Bohle1, W. Zoller1


Department of Internal Medicine and Gastroenterology, Katharinenhospital,
Stuttgart, Germany
Contact E-mail Address: a.hann@klinikum-stuttgart.de
1

INTRODUCTION: Pancreatic cancer has a poor prognosis with a 5-year survival rate of less than 5%. Most patients are diagnosed in a locally advanced or
metastatic state. Chemotherapy regiments have changed since the introduction of
survival prolonging polychemotherapies like FOLFIRINOX (5-Fluoruracil,
Oxaliplatin, Irinotecan and Leucovorin). In this retrospective study we analyzed
the overall survival of patients diagnosed with locally advanced or metastatic
pancreatic adenocarcinoma who were treated at our community-based hospital
during the past ten years. We compared patients diagnosed with pancreatic
cancer before (historical control) and after the introduction of FOLFIRINOX
in 2011.
AIMS & METHODS: We retrospectively identified patients with pancreatic
cancer who were treated at our hospital from 2011 to July 2013 by our cancer
center registry. Patients treated in the years 2003 to 2010 (historical control) were
identified using the diagnosis-related group C25 (malignant neoplasm of pancreas). Patients were included if pancreatic adenocarcinoma in a locally advanced

D.S. J. Tseng1,*, H.C. van Santvoort1, I.H. Borel Rinkes1, I.Q. Molenaar1
Dept. of Surgery, University Medical Center Utrecht, Utrecht, Netherlands

INTRODUCTION: Exocrine pancreatic insufficiency may occur due to loss of


pancreatic parenchyma or obstruction of the pancreatic duct. This may occur in
pancreatic or peri-ampullary cancer, both before and after resection. The prevalence and natural course of exocrine pancreatic insufficiency in these patients
has not been thoroughly studied.
AIMS & METHODS: The aim of this study was to determine the prevalence of
exocrine pancreatic insufficiency in patients with pancreatic or peri-ampullary
cancer.
We systematically reviewed the literature published up to February 20th 2014,
according to the PRISMA guidelines. We included studies reporting on exocrine
pancreatic insufficiency in patients with pancreatic or peri-ampullary cancer.
Studies reporting on exocrine pancreatic insufficiency due to other causes and
focusing solely on a diagnostic test were excluded. Data on baseline characteristics, type of pancreatic resection, diagnostic test for exocrine pancreatic insufficiency and occurrence of exocrine pancreatic insufficiency were extracted.
Prevalence of exocrine pancreatic insufficiency was calculated from these data.
RESULTS: After screening 3203 articles, 9 observational cohort (4 prospective, 5
retrospective) studies were included on a total of 664 patients. Of these patients
333 (50%) underwent pancreatoduodenectomy, 23 (3%) total pancreatectomy,
114 (17%) distal pancreatectomy and 194 (33%) no resection due to locally
advanced pancreatic cancer. Median preoperative prevalence of exocrine pancreatic insufficiency was 44% (range 42-67%) before pancreatoduodenectomy;
20% (16-67%) before distal pancreatectomy; 63% before total pancreatectomy;
and 50% in unresectable patients. The median prevalence of exocrine pancreatic
insufficiency at least 6 months postoperative was 84% (36-100%) after pancreatoduodenectomy; 67-80% after distal pancreatectomy; and 100% after total
pancreatectomy.
CONCLUSION: Exocrine pancreatic insufficiency is frequently seen in patients
before resection for pancreatic or peri-ampullary cancer. The prevalence
increases markedly following resection.
Disclosure of Interest: None declared
P1249 FACTORS ASSOCIATED WITH ABDOMINAL DISSEMINATION
OF PANCREATIC CANCER: RETROSPECTIVE ANALYSIS OF
SURGICAL PATHOLOGY FINDINGS
H. Taguchi1,*, S. Hashimoto1, M. Numata1, J. Nakazawa1, S. Arima1, Y. Nasu1,
F. Sasaki1, S. Kanmura1, H. Setoyama1, H. Kurahara2, Y. Mataki2,
K. Maemura2, M. Higashi3, A. Ido1
1
Digestive and Life-style related Disease, 2Department of Surgical Oncology and
Digestive Surgery, Field of Oncology, 3Department of Human Pathology, Field of
Oncology, Kagoshima University Graduate School of Medical and Dental Sciences,
Kagoshima, Japan
Contact E-mail Address: tag@m2.kufm.kagoshima-u.ac.jp
INTRODUCTION: In pancreatic cancer, abdominal dissemination is one of the
most important determinants of prognosis. To date, there have been few studies
on which surgical findings are relevant to abdominal dissemination, so we retrospectively analyzed patients who underwent surgery for pancreatic cancer.
AIMS & METHODS: We included 145 patients who underwent surgery for
pancreatic cancer at our institution between January 2006 and October 2013 in
this study. The patients were divided into 2 groups based on whether abdominal
dissemination was found during surgery. Abdominal dissemination was defined
as the existence of disseminated nodules on the peritoneum or the surface of the
liver and confirmed pathologically. We analyzed the 2 groups with respect to
patient characteristics, cancer stage, washing cytology results, tumor location
[head of pancreas (Ph) / uncinate process of pancreas (UP) or body of pancreas
(Pb) / tail of pancreas (Pt)], vascular invasion [portal vein or its branches (PV
invasion), superior mesenteric artery, celiac artery, or their branches (arterial
invasion)], and whether preoperative endoscopic ultrasonography-guided fine
needle biopsy (EUS-FNA) was performed.

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United European Gastroenterology Journal 2(1S)


RESULTS: Fourteen patients had abdominal dissemination (dissemination
group), and 131 patients did not (non-dissemination group). In patients background, the number of diagnostic laparoscopic procedures was significantly
higher in the dissemination group than in the non-dissemination group
(p50.001), and there were significant differences in the 2 groups in cancer
stage (p50.001). Univariate analysis revealed that the number of positive washing cytology results, tumor located in Pb/Pt, PV invasion, and arterial invasion
were significantly higher in the dissemination group than in the non-dissemination group (p50.001, p 0.002, p 0.035, and p 0.012, respectively). The
number of EUS-FNA procedures was similar in the 2 groups (p 0.208).
Multivariate analysis revealed that more patients in the dissemination group
had positive washing cytology compared to the non-dissemination group
(p50.001), and more patients in the dissemination group tended to have arterial
invasion compared to the non-dissemination group (p 0.059).
CONCLUSION: We observed a significant relationship between abdominal dissemination and positive washing cytology. Arterial invasion may also be relevant
to abdominal dissemination in pancreatic cancer.
Disclosure of Interest: None declared
P1250 SERUM CA 19-9 AS SCREENING TEST FOR PANCREATIC
CANCER IN NEW ONSET DIABETIC PATIENTS
J.S. Kim1,*, J.W. Choe1, H.J. Kim1, M.K. Joo1, J.-J. Park1, Y.-T. Bak1
1
Korea University Guro Hospital, Internal Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: hjkimmd@korea.ac.kr
INTRODUCTION: Patients with diabetes newly detected within 2 years have
higher risk of pancreatic cancer than general population. The need of screening is
suggested and CA19-9 is the only available biomarker for pancreatic cancer,
however it is unknown in these patient.
AIMS & METHODS: The aim of this study was to evaluate the usefulness of CA
19-9 as a screening test for pancreatic cancer in the new onset diabetes patients.
We retrospectively reviewed medical records of 9.584 patients with new onset (5
2yrs) diabetes from January 2004 to January 2013. Independent t-test, Kai square
test, and ROC curve analysis were used to identify clinical features and usefulness
of CA 19-9 as a screening test in diabetic patients.
RESULTS: Total 1465 patients were analyzed (male; female 877;588, mean age
was 62.1 yrs). Total 40 cases of pancreatic cancer (2.7%) were occurred but 1.425
patients did not show pancreatic cancer. Their mean age was 58.2 and 62.3
respectively (p 0.019). 279 patients were CA 19-9 high group and 1186 patients
were low group. There was no significant difference in basal characteristics
between two groups. In high group, 9.7% (27/279) developed pancreatic cancer
and only 1% (13/1186) in low group. Compared with low group, a significant risk
of pancreatic cancer was observed in CA19-9 high group (p50.001). Pancreatic
cancer patients with new onset diabetes showed higher CA 19-9 level than noncancer patients (1744 vs. 33U/mL, P50.01). When setting CA 19-9 cut off value
as 37.05U/mL, sensitivity was 67.5% and specificity was 83.1%.
CONCLUSION: CA 19-9 is suggested as a screening test for pancreatic cancer in
newly diagnosed diabetic patient.
REFERENCES
Mizuno S, Nakai Y, Isayama H, et al. Risk factors and early signs of pancreatic
cancer in diabetes: screening strategy based on diabetes onset age. J Gastroenterol
2013; 48: 238-246.
Disclosure of Interest: None declared
P1251 OUTCOME OF PANCREATECTOMY
ARTERIAL RESECTION

WITH

ASSOCIATED

J. PERINEL1,*, M.E. BECHWATY1, P.J. VALETTE2, P. FEUGIER3,


M. ADHAM1
1
Hepato-Biliary and Pancreatic Surgery, 2Digestive Radiology, 3Vascular Surgery,
Edouard Herriot hospital, Lyon, France
Contact E-mail Address: julie.perinel@chu-lyon.fr
INTRODUCTION: Pancreatic cancer is a leading cause of death in Europe with
more than 100 000 deaths in 2012. Surgery remains the only curative option.
Whereas extended surgery with venous resection have been demonstrated to be
safe and may contribute to improvement of patient survival, arterial resection
remains a controversy because of a high related morbidity.
AIMS & METHODS: Retrospective review of prospectively collected data on 18
patients who had pancreatectomy for malignant tumor with arterial resection
between October 2008 and september 2013 at our institution. The main end
point was postoperative outcome and secondarily the need for new interventional
procedure.
RESULTS: The most common type of resection was total pancreatectomy (TP)
in 10 cases, followed by pancreaticoduodenectomy (PD) in 8 cases and distal
pancreatectomy in 2 cases. There were 15 arterial resection: 3 celiac trunk, 6
superior mesenteric and 9 hepatic artery. In 10 cases, resections were planned.
Unplanned arterial resection was done in 8 cases, 3 because of intraoperative
arterial injury and 5 because of tumour adhesions discovered intraoperatively. 2
patients had grade  IIIb post operative complications including 1 pancreatic
fistula. 4 patients required an interventional procedure, 3 were interventional
radiology and 1 had surgery. Hospital and 30 day mortality was 0%.
Mortality at 90 days occurred in one patient. Fifteen patient had pancreatic
duct adenocarcinoma (pT3 14, pT2 1; R1 7), and 3 patients had neuroendocrine carcinoma (pT3N 2, pT1N 1; R1 0). In case of adenocarcinoma
(n 15), overall survival and disease free survival was respectively 24 months
[2.6-63.5] and 14.3 months [2.6-61.2]. 10 patients had distant metastasis, 2 aptients had local recurrence.
CONCLUSION: In selected patients and after eventually neoadjuvant chemotherapy, pancreatectomy with arterial resection is associated to low

morbidity. Overall survival and disease free survival are acceptable. In case of
arterial resection, surgery is more radical with high rate of R0 and low rate of
local recurrence.
REFERENCES
1. Tani M, Kawai M, Hirono S, et al. A pancreaticoduodenectomy is acceptable
for periampullary tumors in the elderly, even in patients over 80 years of age. J
Hepatobiliary Pancreat Surg 2009; 16: 675680
2. Menon KV, Al-Mukhtar A, Aldouri A, et al. Outcomes after major hepatectomy in elderly patients. J Am Coll Surg 2006; 203: 677683.
3. Turrini O, Paye F, Bachellier P, et al. Pancreatectomy for adenocarcinoma in
elderly patients: postoperative outcomes and long term results: a study of the
French Surgical Association. Eur J Surg Oncol [Internet] 2013; 39: 171178.
4. Scurtu R, Bachellier P, Oussoultzoglou E, et al. Outcome after pancreaticoduodenectomy for cancer in elderly patients. J Gastrointest Surg 2006; 10: 813
822.
5. Tani M, Kawai M, Hirono S, et al. A pancreaticoduodenectomy is acceptable
for periampullary tumors in the elderly, even in patients over 80 years of age. J
Hepatobiliary Pancreat Surg 2009; 16: 67580
Disclosure of Interest: None declared
P1252 ENDOSCOPIC
ULTRASOUND-GUIDED
FINE-NEEDLE
ASPIRATION OF SOLID PANCREATIC MASSES: IMPACT ON
MANAGEMENT STRATEGY
L.C. Lourenco1,*, A. Oliveira1, C.G. Rodrigues1, D. Horta1, J. Reis1,
J.M. Pontes1, J.R. Deus1
1
Servico de Gastrenterologia, Hospital Prof. Dr. Fernando Fonseca, Amadora,
Portugal
Contact E-mail Address: luisclourenco@gmail.com
INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) is a safe and accurate technique for diagnosing pancreatic cancer.
However, few studies investigated its impact for management of these patients.
AIMS & METHODS: AIM: To investigate the diagnostic yield and the impact
of EUS-FNA in the management of solid pancreatic masses. METHODS: All
patients who underwent EUS-FNA for a solid pancreatic mass between June 1st
2011 and December 31st 2013 were included. Aspirates were placed onto glass
slides for cytological examination and microbiopsies were fixed for histology.
The impact on clinical management was analysed prospectively according to
different endpoints, such as its impact on indications for chemotherapy, surgery
or appropriate follow-up modality.
RESULTS: Forty-five patients were included; two procedures were considered
failures. A final diagnosis was obtained in 43 patients. The sensitivity, specificity
and accuracy of combined cytology and histology for the diagnosis of malignant
or potentially-malignant tumours were 89.2%, 100% and 90.7%, respectively.
The sensitivity and accuracy of cytology alone were significantly higher than
those of histology alone (p50.05). There were no complications related to the
procedure. By intention-to-diagnose analysis, EUS-FNA directly influenced the
management strategy in 33 of 45 patients (77%).
CONCLUSION: In patients with pancreatic mass and suspected malignancy,
EUS-FNA provides an accurate diagnosis in approximately 90% of cases.
EUS-FNA can directly influence the management in three-fourths of patients.
Disclosure of Interest: None declared
P1253 DIAGNOSTIC ACCURACY OF ENDOSCOPIC ULTRASOUNDGUIDED FINE-NEEDLE ASPIRATION FOR PANCREATIC SOLID
LESIONS CYTOLOGICAL PREPARATIONS VERSUS CELL BLOCK
SECTIONS
L. Elvas1,*, D. Brito1, R. Carvalho1, M. Areia1, S. Alves1, S. Saraiva1,
J.M. Pontes1, A.T. Cadime1
1
Gastroenterology, Portuguese Institute of Oncology of Coimbra, Coimbra,
Portugal
Contact E-mail Address: luisandreelvas@gmail.com
INTRODUCTION: Endoscopic ultrasound (EUS) enables imaging of the pancreas with high resolution; however, it is not enough to distinguish between
benign and malignant lesions. EUS-guided fine-needle aspiration (EUS-FNA)
allows obtaining a tissue sample from pancreatic lesions for cytological or histological diagnosis.
AIMS & METHODS: The aim was to evaluate the diagnostic accuracy of EUSFNA for solid pancreatic lesions, comparing the cytological preparations and cell
block sections. We performed a retrospective study of EUS-FNA procedures for
pancreatic solid lesions performed between January 2006 and December 2013.
The diagnosis was established with cytology alone, cell block alone or both. Final
diagnosis was based on clinical and imaging follow-up and/or surgical pathology.
RESULTS: Eighty-six EUS-FNA were performed in 84 patients (46 men; mean
age 63  11 years), using a 22-gauge needle. Median number of needle passes per
procedure was 3. More than half of the lesions (56%) were located in the pancreatic head and median lesion size was 30mm [11-103]. Tissue samples were
collected for both cytological preparations and cell block sections in 75 procedures (87%). Sensitivity, specificity and accuracy were 84%, 62% and 80%,
respectively, for cytology alone, and 81%, 100% and 83% for cell blocks
alone. EUS-FNA results that relied on both techniques had 90% sensitivity,
83% specificity and 89% accuracy.
Cytology revealed 5 malignancies not diagnosed on cell blocks, while cell blocks
revealed 7 malignancies not diagnosed by cytology. There were 3 procedurerelated minor complications (3.5%) but there was no mortality associated with
the technique.
CONCLUSION: Our study revealed that EUS-FNA is a safe procedure with a
high diagnostic accuracy for pancreatic solid lesions. Combination of cytological

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preparations and cell block sections improved EUS-FNA accuracy, showing that
collecting tissue samples for both techniques should be tried in every procedure.
Disclosure of Interest: None declared
P1254 FEEDING PATIENTS WITH GASTRIC OUTLET OBSTRUCTION
UNDERGOING PANCREATODUODENECTOMY: ROUTINE TUBE
FEEDING VERSUS EARLY ORAL FEEDING
A. Gerritsen1.2, R.A. Wennink1,*, I.Q. Molenaar1, I.H. Borel Rinkes1,
D.J. Gouma2, O.R. Busch2, M.G. Besselink2
1
Department of Surgery, University Medical Center Utrecht, Utrecht, 2Department
of Surgery, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: rooswennink@gmail.com
INTRODUCTION: Early oral feeding is nowadays considered the optimal routine feeding strategy after pancreatoduodenectomy (PD). However, 33-45% of
patients develop delayed gastric emptying (DGE) after PD, usually requiring
nutritional support. It is suggested that patients with preoperative symptoms
of gastric outlet obstruction (GOO) have such a high risk of developing DGE
that GOO represents one of the few remaining indications for routine postoperative tube feeding.
AIMS & METHODS: The aim of this study was to determine the association
between preoperative GOO and postoperative DGE. We also compared routine
postoperative tube feeding with early oral feeding in patients with GOO undergoing PD.
A multicentre retrospective cohort study was performed in all consecutive
patients undergoing PD in two tertiary referral centres between 2010 and 2013.
GOO was defined as two or more of the following preoperative symptoms:
nausea, vomiting, loss of appetite, dysphagia, or postprandial complaints
(abdominal pain, early satiation, or bloating). Patients with GOO were categorized into two groups based on the applied feeding strategy: routine postoperative
tube feeding or protocolized early oral feeding (with on-demand tube feeding).
Primary outcome was the time to resumption of an adequate oral intake.
RESULTS: Of 421 patients undergoing PD, 61 (15%) suffered from preoperative
symptoms of GOO. DGE developed in 26 of 61 (42%) patients with GOO versus
113 of 360 (31%) patients without GOO (p 0.08). Of 61 patients with GOO, 15
patients (25%) received routine tube feeding and 46 (75%) early oral feeding.
Time to resumption of adequate oral intake (11 (4-69) vs.14 (7-11) days,
p 0.80), incidence of DGE (40% vs. 43%, p 0.81) and length of hospital
stay (17 (7-67) versus 14 (4-46) days, p 0.19) did not differ between the two
feeding strategies. Of the patients receiving early oral feeding, 24 of 46 (52%)
patients with GOO ultimately needed postoperative tube placement as compared
to 112 of 297 patients (37%) without GOO (p 0.06).
CONCLUSION: In this retrospective study, the risk of DGE and need for postoperative tube placement tended to be slightly increased in patients with GOO,
but outcomes were comparable between routine tube feeding and early oral
feeding. Since almost half of patients with GOO tolerate early oral feeding,
routine tube feeding may not be indicated in these patients.
Disclosure of Interest: None declared
P1255 IRREVERSIBLE ELECTROPORATION IN LOCALLY ADVANCED
PANCREATIC CANCER: A SYSTEMATIC REVIEW
S. Rombouts1,*, S. Fegrachi1, H. V. Santvoort1, M. Besselink2, R.
V. Hillegersberg1, Q. Molenaar1
1
SURGERY, University Medical Center Utrecht, UTRECHT, 2Surgery,
Academic Medical Center Amsterdam, Amsterdam, Netherlands
Contact E-mail Address: S. J. E. Rombouts@umcutrecht.nl
INTRODUCTION: Ablative techniques are being explored as a new treatment
option for locally advanced pancreatic cancer (LAPC). Unlike radiofrequency
ablation, irreversible electroporation (IRE) is a non-thermal ablation technology
and might preserve vascular and ductal structures.
AIMS & METHODS: The aim of this study was to evaluate the safety and
potential benefits of IRE in patients with LAPC.
A systematic search was performed in PubMed, Embase and Cochrane Library
for English articles published until March 2014 and subsequently reviewed
according to PRISMA guidelines. Included were clinical studies reporting on
outcomes of IRE in LAPC. Exclusion criteria were: 1) studies that did not
report morbidity and mortality; 2) case reports; 3) conference abstracts.
Baseline characteristics as well as study characteristics were extracted.
Outcomes expressed as morbidity, mortality and overall survival were extracted
from the articles.
RESULTS: After screening 143 studies, 4 clinical studies were included. These
studies involving 176 patients, reported overall morbidity of 21-59%, IRErelated morbidity of 7-18.8%, and mortality of 0-3%. The IRE-related complications consisted of pancreatic fistula, portal vein thrombosis, duodenal leak and
acute pancreatitis with reported rates of up to 3.7%, 7.4%, 7.4% and 7.1%
respectively. Only one clinical study (n 139) reported median survival of 20.2
months.
CONCLUSION: IRE for LAPC seems feasible and safe based on clinical studies.
However, the number of complications does not seem improved in comparison
with RFA, except for pancreatic fistula. A large prospective, preferably randomized study should establish whether morbidity, overall survival and quality of
life are improved by IRE as compared to alternative established treatments.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1256 INTRAABDOMINAL DRAIN VERSUS
PANCREATIC RESECTION: A META-ANALYSIS

NO

DRAIN

FOR

U. Nitsche1,*, T.C. Muller1, C. Spath1, L. Cresswell2, K.-P. Janssen1,


D. Wilhelm1, J. Kleeff1
1
Department of Surgery, 2Institute of Statistics and Epidemilogy, Klinikum rechts
der Isar, TU Munchen, Munich, Germany
Contact E-mail Address: ulrich.nitsche@tum.de
INTRODUCTION: Routine placement of intraabdominal drains has been challenged for distinct abdominal surgical procedures. Studies for abdominal drains
after pancreatic resections are inconsistent. The aim of this meta-analysis was to
investigate morbidity and mortality of patients with and without abdominal
drains after pancreatic resections.
AIMS & METHODS: According to the PRISMA guidelines, a literature search
of medical data bases was performed for eligible studies reporting on patients
with any kind of pancreatic resection, and comparing a group with abdominal
drainage to a group without abdominal drainage. The quality of studies was
assessed according to MINORS and STROBE criteria. Morbidity, mortality,
and the length of hospital stay were compared by random effects models.
RESULTS: Overall, eight studies with 2.773 patients were included in this metaanalysis. Patients without intraabdominal drainage had a significant reduced rate
of any kind of complications (p50.001). However, no significant differences
were detected when separated into minor complications, major complications,
pancreatic fistulas, intraabdominal abscesses, need for radiological interventions,
need for re-operations, postoperative mortality, and length of in-hospital stay.
Study heterogeneity made the results difficult to interpret.
CONCLUSION: The meta-analysis of the current literature does not allow explicit recommendations for or against the routine placement of intraabdominal
drains after pancreatic resections. At least, omitting drains seems not to increase
the rate of complications and should be considered for unproblematic pancreatic
resections. Systematic review registration number CRD42014007497. No
funding.
Disclosure of Interest: None declared
P1258 HEPATIC METASTASES OF GASTROENTEROPANCREATIC
NEUROENDOCRINE TUMORS: A 17-YEAR SINGLE CENTER
PROSPECTIVE STUDY
M.P. Spampatti1,*, S. Massironi2, R.E. Rossi1, C. Ciafardini1, M. Galeazzi1,
D. Conte1, M. Peracchi1
1
Department of Medical, Surgical and Transplant Pathophysiology, University of
Milan, 2Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca Granda
Ospedale Maggiore Policlinico, Milan, Italy
Contact E-mail Address: matilde.spampatti@gmail.com
INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP NET)
with hepatic metastases (HM) have a poorer prognosis in comparison with localized GEP NET.
AIMS & METHODS: Primary endpoints of the study are overall survival from
the diagnosis of liver metastases (OS), progression-free survival (PFS) and treatment effectiveness. Among 186 consecutive patients with diagnosed GEP NET
from 1995 to 2012, 74 had HM. Prognostic factors and survival times of GEP
NET with HM with different treatments were calculated using Kaplan-Meier
method and regression analysis.
RESULTS: Median OS (range) was 96 (3-201) months. Prognostic factors for OS
were grading, presence of extrahepatic disease (EHD) and treatment (p50.0001).
Ten patients (14%) achieved complete remission, 18 (24%) partial remission, 18
(24%) stable disease, and 28 (38%) progression of disease. Among responsive
patients median PFS was 84 (4-180) months. Prognostic factors for PFS were
grading and presence of EHD (p50.001). Five- and 10-year survival rate were
86% and 71% for radical surgery (RS), 82% and 58% for palliative surgery (PS)
with radioreceptor therapy (RT), 58% and 37% for PS and medical treatment
(MT), and 23% and 8% for MT alone.
CONCLUSION: Overall survival of GEP NET with HM resulted high, as
described from other authors. Interestingly, we found that OS and PFS of
patients treated with RS are similar to those of patients treated with PS and
RT. Main prognostic factors for GEP NETs with HM are grading and EHD.
REFERENCES
1)Panzuto F, et al. Advanced digestive neuroendocrine tumors: metastatic pattern is an independent factor affecting clinical outcome. Pancreas 2014; 43: 212218.
2) Rossi RE, at al. Treatment of liver metastases in patients with digestive neuroendocrine tumors. J Gastrointest Surg 2012; 16: 1981-1992.
3) Ter-Minassian M, et al. Clinical presentation, recurrence, and survival in
patients with neuroendocrine tumors: results from a prospective institutional
database. Endocr Relat Cancer 2013; 20: 187-196.
Disclosure of Interest: None declared

A475

United European Gastroenterology Journal 2(1S)


P1259 DIABETES, SMOKING, ALCOHOL AND FAMILY HISTORY OF
CANCER AS RISK FACTORS FOR SPORADIC PANCREATIC
NEUROENDOCRINE TUMORS: A SYSTEMATIC REVIEW AND
META-ANALYSIS
S.-P. Haugvik1.2,*, P. Hedenstrom3, E. Korsth2, R. Valente4, A. Hayes5,
D. Siuka6, P. Maisonneuve7, I.P. Gladhaug1.2, B. Lindkvist3, G. Capurso4
1
Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital,
2
Institute of Clinical Medicine, University of Oslo, Oslo, Norway, 3Unit of
Gastroenterology, Department of Medicine, Sahlgrenska University Hospital,
Gothenburg, Sweden, 4Digestive and Liver Diseasee Unit, II Medical School,
University of "La Sapienza", S. Andrea Hospital, Rome, Italy, 5Department of
General Surgery, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom,
6
Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana,
Slovenia, 7Division of Epidemiology and Biostatistics, European Institute of
Oncology, Milan, Italy
Contact E-mail Address: svhaug@ous-hf.no
INTRODUCTION: The identification of environmental risk factors for sporadic
pancreatic neuroendocrine tumors (PNETs) may suggest mechanisms of pathogenesis and allow the identification of groups at high risk of disease.
AIMS & METHODS: The aim of this systematic review was to assess if diabetes,
smoking, alcohol and/or a family history of cancer are risk factors for sporadic
PNETs. MEDLINE and abstracts from the ENETS and NANETS were
searched for studies published until October 2013. Eligible studies were selected
according to the PRISMA statement.
RESULTS: Four studies were included (study accrual period 2000-10) in a metaanalysis, involving 518 (range, 160-196) cases and 1805 (range, 233-924) controls.
All studies were case-control studies and described regional cohorts. The pooled
and adjusted OR was 3.512 (95% CI 2.188-5.638; p0.001) with a history of
diabetes, 1.401 (95% CI 1.082-1.814; p 0.011) with a history of ever smoking,
1.371 (95% CI 0.986-1.906; p 0.061) with a history of heavy smoking, 1.397
(95% CI 1.075-1.816; p 0.013) with a history of ever alcohol consumption,
3.206 (95% CI 2.038-5.043; p0.001) with a history of heavy alcohol consumption, and 2.160 (95% CI 1.639-2.847; p0.001) with a first degree family history
of cancer. There was some heterogeneity in the results that was most apparent
with regard to the risk of heavy smoking and heavy drinking.
CONCLUSION: Diabetes, smoking, alcohol and first degree family history of
cancer are associated with an increased risk of developing sporadic PNET. There
is a need for larger international case-control studies with homogenous study
populations to draw definitive conclusions with regard to heavy smoking and
heavy drinking and other potential risk factors for sporadic PNETs.
Disclosure of Interest: None declared
P1260 THE ROLES OF EUS-FNA AND 68GA-SOMATOSTATIN
ANALOGUES PET/CT IN PATIENTS WITH PANCREATIC
LESION(S) IDENTIFIED BY COMPUTED TOMOGRAPHY AND
SUSPECTED TO BE NEUROENDOCRINE TUMORS
V. Iori1,*, M. Sollini2, R. Zecchini1, P. Pattacini3, G. Carlinfante4, A. Frasoldati5,
P. Cecinato1, T. Cassetti1, R. Sassatelli1, V. Annibale2, L. Camellini1
1
Gastroenterology and Endoscopy Unit, 2Nuclear Medicine Unit, 3Radiology Unit,
4
Pathology Unit, 5Endocrinology Unit, Santa Maria Hospital,Reggio Emilia,
reggio emilia, Italy
Contact E-mail Address: lorenzo.camellini@asmn.re.it
INTRODUCTION: Pancreatic neuroendocrine tumors (PNETs) are diagnosed
by multidetector computed tomography (MDCT) with increasing frequency: the
roles of EUS-FNA and PET/CT in the diagnostic algorithm of these lesions has
not been established yet.
AIMS & METHODS: We aimed to investigate the role of EUS-FNA and PET/
CT in the evaluation of pancreatic lesions suspected to be PNETs, on the basis of
MDCT. We retrieved from our institution databases all patients, who underwent
both EUS-FNA and PET from Jan 2007 to Mar 2014, for diagnosis and staging
of pancreatic lesions identified by MDCT. Only patients having a MDCT suspected for PNET, were considered in the analysis. We compared 1) the accuracies
of EUS-FNA and PET in confirming the diagnosis of PNET and 2) the detection
rates of MDCT and PET for suspected secondary lesions. The reference standard
for the diagnosis of PNET was histology or cytology (confirmed by at least 6
month follow-up - mean 30 months).
RESULTS: 34 patients were identified (lesions diameter: 27 mm;8-98). The final
diagnoses were: PNET (n 31; G1 20; G2 10; G3 1); duct cells pancreatic
carcinoma (1) and clear cell carcinoma metastases (2).
Table 1 shows results of the methods, according to the diagnosis:

EUS-FNA
EUS-FNA (overall)
MDCT
PET/CT

pathological lymph node, neither distant site metastases in 26 patients affected


by PNET; PET identified a suspected secondary metastasis in one of these
patients, but at a retrospective review of the MDCT findings the lesion was
confirmed as visible, but missed during initial evaluation. MDCT diagnosed
secondary lesions in 2 patients and these diagnoses were confirmed by PET/
CT. In the other 3 patient the results of MDCT were doubtful; in all of them
PET/CT identified secondary lesions, but these findings were later found to be
false positive diagnoses in 2/3.
CONCLUSION: Although the majority of PNET identified by MDCT resulted
positive using PET/CT, EUS-FNA remains necessary to confirm suspected
PNET. In patients affected by PNET, in whom MDCT suggests the presence
of secondary lesions, PET/CT may be useful providing additional clinical information. On the other hand, the probability of diagnosing secondary lesions by
PET/CT in patients, without secondary lesions at MDCT is low.
Disclosure of Interest: None declared
P1261 DNMT1 OVEREXPRESSION IS A PREDICTIVE FACTOR FOR
RECURRENCE OF PANCREATIC NEUROENDOCRINE NEOPLASM
Y. Hamada1,*, Y. Nakayama2, K. Maeshiro3
Pathology, FUKUOKA UNIVERSITY, 2Laboratory Medicine, National Medical
Center, Fukuoka, 3Surgery, St. Maria Hospital, Kurume, Japan
Contact E-mail Address: yhamada@fukuoka-u.ac.jp
1

INTRODUCTION: Endoscopic ultrasound is used for precise preoperative evaluation of pancreatic neuroendocrine neoplasm. Endoscopic ultrasound-guided
fine-needle aspiration provides safe, highly accurate cytologic confirmation.
However, in contrast to adenocarcinomas, the degree of nuclear pleomorphism
and architectural pattern do not correlate well with prognosis. It is desirable to
find biomarkers that detect the malignant potential without morphological cytological changes. DNA methylation is important in transcriptional regulation,
chromatin remodeling and genomic stability. DNA hypomethylation and regional DNA hypermethylation are commonly observed in various tumours, including pancreatic cancer, even in precancerous states, which lack obvious cytological
atypia.
We investigated epigenetic alterations and clinicopathologic features of pancreatic neuroendocrine neoplasms using immunohistochemistry.
AIMS & METHODS: A case-control study of 38 patients with pancreatic endocrine neoplasm who underwent pancreatic resection and one case obtained from
autopsy. The observation period was 3 to 192 months. We analysed correlations
between clinicopathologic factors and immunohistochemical stains of DNMT1.
DNMT1 was detected in nuclei of lymphocytes (positive control) and tumour
cells. To discriminate definitely positive cases from cases, if more than 5% of cells
in a sample exhibited nuclear staining the sample was considered to show immunoreactivity. Correlations between the incidence of DNMT1 immunoreactivity
and recurrence were analysed using a chi-square test. A p-value 50.05 was
considered significant.
RESULTS: There were nine males and 30 females, including 23 cases of nonfunctioning neoplasms, nine of insulinoma, three of serotonin-producing neoplasms, two of gastrinomas, one of ACTH-producing neoplasm, one of VIPproducing neoplasm, and two of microadenomas. Multiple endocrine neoplasia
type 1, invasive ductal adenocarcinoma of the pancreas, and gastric cancer were
seen in each case. Tumour size was 1044 mm. From 2010 WHO classifications,
76% of tumours were G1, 20% were G2, and 4% were G3. From 2000 classifications, 30 patients had well-differentiated endocrine neoplasms and nine had welldifferentiated endocrine carcinomas. One patient died from liver metastasis 9
years after surgery. Six patients were alive with liver metastasis and had undergone chemotherapy. In one case, liver metastasis occurred 15 years after surgical
resection. The remaining 17 cases were alive without recurrence. DNMT1 protein
overexpression was significantly associated with liver metastasis (p50.0006).
There was one case with metastasis 15 years after surgery and DNMT1 tested
positive in the resected primary specimen.
CONCLUSION: Increased DNMT1 expression correlated to the metastatic
potential of pancreatic endocrine neoplasm.
REFERENCES
Pancreatic FNA in 1000 cases: Usefulness of EUS-guided fine needle aspiration
(EUS-FNA), EUS-guided FNA, Puli, Bemstein, Hooper.
Zee S, Hochwald S, Conlon KC, et al. Pleomorphic pancreatic neuroendocrine
neoplasms: a variant commonly confused with adenocarcinoma. Am J Surg
Pathol 2005; 29: 1194-1200.
Jones PA and Baylin SB. The fundamental role of epigenetics events in cancer.
Nat Rev Genet 2002; 3: 415-428.
Disclosure of Interest: None declared

True
positive

True
negative

False
positive

False
negative

WEDNESDAY, OCTOBER 22, 2014


ENDOSCOPY AND IMAGING III
XL_____________________

28
30
31
27

3
3
0
0

0
0
3
3

3
1
0
4

P1262 USE OF THE GLASGOW BLATCHFORD SCORING SYSTEM FOR


EVALUATION OF UPPER GASTROINTESTINAL BLEED IN AN
IRISH POPULATION; CAN WE PUSH THE GB SCORE TO TWO FOR
DISCHARGE AND FOLLOW UP ENDOSCOPY AS AN OUTPATIENT

In patients with clear cell metastases PET/CT showed a high tracer uptake, while
only a faint uptake was found in the patient with duct cell carcinoma. EUS-FNA
results were inconclusive in 3 patients; in 2 of them the diagnosis of PNET was
confirmed by performing EUS-FNA again. In 5 patients with PNET, EUS and/
or PET/TC identified additionally primary lesions. MDCT did not show any

POSTER

EXHIBITION

9:0014:00
HALL

P.K. Maheshwari1,*, H. Yousif2, C. Kiat1, N. Idrees3, C. Goulding1


1
gastroenterology, GUH, Galway, 2MWRH Limerick, limerick, Ireland, 3gastroenterology, MWRH Limerick, limerick, Ireland
Contact E-mail Address: rathipardeep@hotmail.com
INTRODUCTION: Upper Gastrointestinal bleed (UGI Bleed) is very common
cause for presentation to the emergency department often leading to unnecessary
admission and prolonged length of stay, whilst awaiting in-patient endoscopy

A476

United European Gastroenterology Journal 2(1S)

AIMS & METHODS: To validate GBS in our population and to determine if


those with GBS up to two can be managed with outpatient OGD
This was a prospective single-centre observational study of patients presented to
our centre between December 2012 to June 2013. We recruited those with a
working diagnosis of upper gastrointestinal bleeding (UGIB) including those
who were discharged from the emergency department (ED) for outpatient
OGD. Patients younger than 18 years of age and those who did not give consent
were excluded. Data collections include patients demographics, GBS, hospital
admissions, OGD findings (normal or abnormal). Analyses were performed to
determine the correlation between GBS and OGD findings (using the Forrest
Classification) emphasizing on those with GBS score up to two
RESULTS: Seventy out of 93 patients who presented during the recruitment
period had an OGD performed. The mean age of patients was 62.6 years and
53 patients were males (57.0%). The mean GBS was 6.2. Forty-six patients had a
normal OGD and their mean GBS was 3.5.
11 had Forrest Classification III, 3 had Forrest IIc, 1 had Forrest IIb, 2 had
Forrest IIa, 4 had Forrest Ib and 3 had Forrest 1a. 14 patients were re-admitted
within four weeks but none for UGIB. There is a statistically significant correlation between the GBS and Forrest Classification in our cohort (r 0.431, p-value
50.001). Four patients with variceal bleed were included in the abnormal OGD
group as well. Thirty four patients have GBS of 0 to 2 (0 15, 1 12, 2 7)
and all have normal OGD findings.
Ten of the twenty three not having OGD, had GBS score of zero, Three had
score 1 and Two had GBS score 2. Patients with score zero and one were discharged from the emergency department for follow OGD but they never returned
back to the endoscopy or represented to the hospital within 4 weeks with any
symptoms of upper GI bleed. Three of the patients were very unwell with other
co morbidities and they had GBS score of more than 8; in that case looking after
physicians decided not to go for the OGD. Five of the patients had GBS score of
more than 6 but their OGD record was not available in the notes as they may
have endoscopy in the operation theater under surgical team.
CONCLUSION: Our study validates the GBS as per previous studies and suggests that we can push the score up to two at which it is safe to discharge and
offer out-patient endoscopy.
Disclosure of Interest: None declared
P1263 PROBE
BASED
CONFOCAL
ENDOMICROSCOPY
DETERMINE THE EXTENT OF MYOTOMY DURING PERORAL
ENDOSCOPIC MYOTOMY

TO

P.W. Chiu1,*, J.C. Wu2, F.K. Chan2, J.Y. Lau1


1
Department of Surgery, 2Department of Medicine & Therapeutics, THE
CHINESE UNIVERSITY OF HONG KONG, Hong Kong, China
Contact E-mail Address: philipchiu@surgery.cuhk.edu.hk
INTRODUCTION: Peroral endoscopic myotomy (POEM) achieved myotomy
for treatment of achalasia through submucosal tunnel. The determination of
extent of myotomy depends on preoperative high resolution manometry and
endoscopic measurement. Endoscopic observation of the inner circular muscles
showed a difference in appearance between the tight lower esophageal sphincter
(LES) and normal muscle fibres. This study aimed to determine the criteria for
observation through probe based confocal endomicroscopy (pCLE) in determining the pathological extent of LES during POEM.
AIMS & METHODS: This is a prospective clinical trial on the use of probe based
confocal endomicroscopy to determine the extent of pathological LES. Prospective
patients who underwent POEM for treatment of achalasia were recruited. After
development of the submucosal tunnel from 15cm above gastroesophageal junction
(GEJ) to 5cm below, the pCLE was applied to observe for changes at 2cm intervals
from 10cm above to 5cm below GEJ. The criteria for changes during confocal
endomicroscopy in pathological LES included 1. Non-distinct vasculature; 2. No
visible normal muscular fibres; 3. Increased cellularity; 4. Presence of thick dark
bands. The patients received intravenous fluorescin 2 minutes before the observation.
The pCLE was performed using a catheter type confocal probe (Cellvizio MKT) with
a diameter of 2.0mm. All the procedures were video recorded for reassessment.
RESULTS: Four patients who underwent POEM for treatment of Achalasia
received pCLE for determination of the extent of pathological LES. The mean
operative time for POEM was 94.1 mins, and the mean duration for confocal
observation at 8 different levels was 10.4 minutes. All the features employed for
distinction between pathological LES and normal inner circular muscles were
observed for all patients with Achalasia after development of submucosal tunnel.
The corresponding length of abnormal pCLE findings was generally longer than
that reported in preoperative manometry.

Age / gender
Abnormal pCLE
Preop Abnormal LES
Preop LES pressure
IRP4s

Patient 1

Patient 2

Patient 3

Patient 4

75/M
40 45cm
44 47 cm
60 70 mmHg
48.6mmHg

M/78
39 42cm
40 42cm
8 12mmHg
-

F/76
38 45cm
41 44cm
26 32mmHg
21.6mmHg

F/62
37 45cm
42 46cm
30 40 mmHg
17.8mmHg

CONCLUSION: In this preliminary study, we were able to establish preliminary


criteria to differentiate between pathological LES and normal inner circular
muscle fibres during POEM. These changes shall serve as guidance to determine
the extent of myotomy during POEM.
REFERENCES
1. Chiu PW, Wu JC, Teoh AY, et al. Peroral endoscopic myotomy for treatment
of achalasia: from bench to bedside. Gastrointest Endosc 2013; 77: 29-38.
Disclosure of Interest: None declared

P1264 ENDOSCOPIC
MUCOSAL RESECTION
OF SPORADIC
DUODENAL POLYPS IS ASSOCIATED WITH A HIGH RISK OF
COMPLICATIONS
P. Martens1,*, I. Demedts1, S.Van Gool2, H. Willekens1, R. Bisschops1
1
GASTROENTEROLOGY, UZ LEUVEN, Leuven, 2GASTROENTEROLOGY,
AZ Turnhout, Turnhout, Belgium
Contact E-mail Address: pieter.1.martens@uzleuven.be
INTRODUCTION: Endoscopic mucosal resection (EMR) is an established technique for the treatment of early neoplastic lesions in the colon, esophagus and the
stomach. Sporadic duodenal adenomas (SDA) are a rare finding on endoscopy.
Little data is available about the safety and efficacy of EMR for SDA in larger
case series.
AIMS & METHODS: The aim of this study is to report our experience with
regard to the safety and efficacy of duodenal EMR for SDA.
Methods: Prospectively collected data of fifty nine patients (31 men, 28 female,
mean age 61) referred for duodenal EMR to our center between 2006 and 2013,
were analyzed. Only duodenal polyps were included in the study. Data regarding
polyp size, location, endoscopic morphology, EMR technique, procedure time,
complications, pathology result and periodical follow up were recorded. All
patients underwent day after endoscopy to detect and treat delayed bleeding.
RESULTS: Seventy-one duodenal EMRs were performed in fifty nine patients
during the study period. The median polyp size was 15mm (range 7-40 mm). The
success rate of complete endoscopic removal after a single EMR was 83%.
Complete remission was achieved with 2 and 3 EMRs in 9 and 3 patients respectively. Complications occurred in 26% of the procedures. We encountered 10
cases of early bleeding (54 hours after EMR) and 10 cases of delayed bleeding
(44 hours after EMR) with need of additional hemostatic measures, transfusion
or radiological intervention and admission to intensive care. In one patient a
small perforation could be managed conservatively with clips. No patients were
referred for rescue surgery. Except for 2 neuro-endocrine tumors, all lesions were
adenomas with low grade dysplasia in 82% and high grade dysplasia in 18%.
Long term histological follow up (median: 18 months, range 12-50 months) was
available in 30 patients, complete histologic remission was achieved in 25 patients
(83%). Five patients revealed histologic arguments of residual adenomatous
tissue, all showing low grade dysplasia. No tumor related deaths were reported.
CONCLUSION: This study is one of the largest available series confirming the
efficacy of EMR for SDA. Duodenal EMR is efficient (83%) in achieving long
term complete histological remission. However morbidity (26%) seems higher for
duodenal EMR as compared to EMR in other location within the gastrointestinal tract and in comparison to other smaller series. Our systematic approach of
day after follow-up endoscopy could contribute to the higher morbidity rate with
detection of late bleeding.
Disclosure of Interest: P. Martens: None declared, I. Demedts: None declared, S.
Van Gool: None declared, H. Willekens: None declared, R. Bisschops Financial
support for research from: Covidien, Ipsen, Pentax, Lecture fee(s) from:
Covidien, Pentax, Fujifilm, Olympus, Consultancy for: Covidien
P1265 ENDOSCOPIC RESECTION OF DUODENAL ADENOMASCOMPARISON OF SAFETY AND EFFICACY BETWEEN SPORADIC
ADENOMAS AND ADENOMAS IN FAP
P. Mundre1,*, B. Rembacken1, A. Rehman1, L. smith1
1
Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK, Leeds,
United Kingdom
Contact E-mail Address: bj.rembacken@ntlworld.com
INTRODUCTION: Although there is a low risk of malignant conversion of
duodenal polyps in FAP, EMR is often considered. However, few studies have
looked at the safety and efficacy of EMR. We compared the outcome of duodenal EMRs in patients with FAP vs sporadic adenomas. To our knowledge, this is
the largest series of duodenal EMRs that is published so far (1)
AIMS & METHODS: We looked at Clinical records of all patients who underwent endoscopic resections for duodenal adenomas at Leeds in a 10 year period.
RESULTS: A total of 49 sporadic adenomas were resected (in 51 patients) and 44
FAP related (in 22 patients). Most lesions appeared either sessile (43) or flat
elevated (48). The average size of the FAP related polyps was 16.9mm vs.
20.7mm in sporadic lesions. Most were removed by standard EMR (n 82)
rather than the strip biopsy technique (n 9). Two procedures failed and no
follow-up data was available after the resection of 2 sporadic polyps.
The final histology of the lesions were; TALGD (76), TAHGD (13), adenocarcinoma (2) and 2 polyps were not retrieved. In 11 lesions, there was a change
in the histological grade after resection.
There were 4 perforations (4.3%), 3 were managed surgically. 12 patients (13%)
were readmitted with significant late GI bleeding and 8 patients required endoscopic therapy and transfusion.
There was no significant difference in the success rates in the two groups (19/44
vs 32/49) p value 0.94). However, the resection of polyps 2cm were significantly
more likely to be associated with a complication (7/59 vs. 8/19 p 0.02). There
was no difference in the risk of complications with the polyp location, ASA
status, Spigelman score or patient age.
Amongst the FAP polyps, polyps420 mm were significantly more likely to have
local recurrence (3/6 vs 3/31 p value 0.04). There was no difference in the chances
of success of the resection with the growth pattern, the location of the polyp or
the Spigelman score.
CONCLUSION: Duodenal EMR is hazardous, particularly when lesions 2cm or
larger are resected. However, there was no significant difference in the hazards or
success rates between the two groups. Most FAP patients had further neoplasia

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United European Gastroenterology Journal 2(1S)


on follow up, but this is due to the fact that many of the adenomas were not
resected /treated in the first sitting.
REFERENCES
1. Basford P and Bhandari P. Endoscopic management of nonampullary duodenal polyps. Therap Adv Gastroenterol 2012; 5: 127138.
Disclosure of Interest: None declared
P1266 WHAT IS THE OPTIMAL TIME TO DO ENDOSCOPY IN ACUTE
CAUSTIC INGESTION?
R. kochhar1,*, P.K. Siddapa1, U. Dutta1, S.K. Sinha1
Gastroenterology, Postgraduate Institute of Medical Education and Research
(PGIMER), Chandigarh, India
Contact E-mail Address: dr_kochhar@hotmail.com

RESULTS: There was no significant difference in mean age (64 vs. 66 years) and
gender distribution (41% vs. 50% male) between patients undergoing WLE and
BLI. WLE and BLI could detect gastric polyp, erosion, ulcer, intestinal metaplasia (IM) and advanced gastric cancer (Table 1). BLI provided a trend of better
focal gastric lesions detection when compared to WLE (52% vs. 41%, p 0.082).
All IM lesions were detected only by BLI, whereas WLE did not detect any IM.
These five cases of IM were classificed as 0_IIa at 80% and 0_IIb at 20%.
However, no early gastric cancer was detected in this study.
Table 1

INTRODUCTION: Early (524 h) upper GI endoscopy (UGIE) is used to prognosticate mucosal injury after caustic ingestion.
AIMS & METHODS: To evaluate the usefulness of day 5 UGIE over day 1
UGIE in prediction of cicatrisation and other outcomes after acute caustic
ingestion.
Consecutive adult patients of caustic ingestion seen by us between 2009-2013
were subjected to upper GI endoscopy after informed consent within 24 hours
and on fifth day of caustic ingestion. Upper GI mucosal changes were graded
using Zargars classification. Patients with changes of grade IIa were classified
as mild and those with IIb were classified as severe. Patients were regularly
followed up for development of complications. Management of cicatrisation
included endoscopic dilatation followed by surgery if the former failed.
Comparison was made between day 1 and 5 endoscopy changes for development
of cicatrisation and complications.
RESULTS: A total of 63 patients had presented to us within 24 h of caustic
ingestion of who 51(mean age 3213.3yrs, 31 males) had day 1 and day 5 UGIE.
Acid intake was seen in 43(84.3%), alkali in 6(11.8%) and unknown substance in
2(3.9%). The cause of caustic intake was suicidal in 24(47.1%), accidental in
20(39.2%) and unknown in 7(13.7%). Esophageal stricture developed in
12(23.5%) and antro-pyloric stricture developed in 18(35.3%) patients. 1(2%)
patient died, emergency surgery was done in 1(2%) patient and definitive surgery
for cicatrisation was done in 7(13.7%) patients. 42 (82.3%) patients recovered on
conservative management requiring only dilatation in those with cicatrisation.
Endoscopic grading on day 1 significantly overestimated severity of mucosal
changes compared to day 5 grading (table.1). Endoscopic grading on day 1 overestimated esophageal injury severity by 23.5% compared to day 5 grading.
Endoscopic grading on day 1 overestimated gastric injury severity by 29.4%
compared to day 5 grding. Day 5 endoscopic grading of esophageal injury correlated with stricture formation (p 0.019) better than day 1 endoscopic grading
(p 0.287). For gastric injury both day 1(p 0.005) and day 5 (p 0.000) endoscopic grading correlated with gastric cicatrisation. Day 5 endoscopic grading
correlated better with need for surgery and recovery as compared to day 1
endoscopic grading (p50.05).
Table 1: Endoscopic grading on day 1 and day 5

Esophagus day1(n 51)


Esophagus day5(n 51)
Stomach day 1(n 51)
Stomach day5(n 49)

Mild changes
grade IIa

Severe changes
grade IIb

19(37.3%)
31(60.8%)
11(21.6%)
25(51%)

32(62.7%)
20(39.2%)
40(78.4%)
24(49%)

Day 1 vs day 5
(significance)

p 0.008
p 0.006

CONCLUSION: Endoscopic assessment on day 1 significantly overestimates the


grade of injury. Endoscopic grading of injury on day 5 is a better predictor of
esophageal and gastric cicatrisation and need for surgery. We suggest that relook
endoscopy on day 5 should be done in all patients of caustic ingestion.
Disclosure of Interest: None declared
P1267 A RANDOMIZED CONTROLLED TRIAL OF WHITE LIGHT
ENDOSCOPY VERSUS BLUE LASER IMAGING ENDOSCOPY FOR
THE DETECTION OF FOCAL GASTRIC LESIONS; A PRELIMINARY
REPORT
R. Pittayanon1.2,*, R. Rerknimitr1
1
Medicine, Chulalongkorn University, 2Medicine, King Chulalongkorn Memorial
Hospital, Bangkok, Thailand
Contact E-mail Address: rapat125@gmail.com
INTRODUCTION: White light endoscopy (WLE) may miss subtle mucosal
changes of stomach. Blue laser imaging (BLI) (Fujifilm Co., Japan) is a novel
bright illumination with high definition resolution diagnostic tool that may
improve mucosal surface contrast and facilitate visualization of mucosal details.
AIMS & METHODS: To evaluate the detection rate of focal gastric lesions
between WLE and BLI system. From November 2013 to March 2014, 110
patients were recruited (55 in each). Inclusion criteria: 1) aged 4 50 years undergoing UGI endoscopy with indications; for instant, chronic dyspepsia, unexplained weight loss, iron deficiency anemia, etc. Exclusion criteria: 1) presence
of active gastrointestinal bleeding; 2) presence of coagulopathy; 3) past history of
partial gastrectomy. Patients were randomized to either WLE or BLI. The presences of focal gastric lesions, the morphology based on the Paris classification
and real-time diagnosis were recorded. All lesions were biopsied for histological
confirmation. The difference in the detection rate of focal lesion was analysed.

WLE
BLI

Gastric
polyp

Gastric
erosion

Ulcer

Intestinal
Metaplasia (IM)

Advanced
gastric cancer

Total

7
6

9
8

4
9

0
5

2
1

22
29

CONCLUSION: WLE and BLI are both potentially a promising tool for detection of subtle focal gastric lesions. However, BLI may have more advantage than
WLE on detecting IM lesion. Additional cases should be recruited to determine
the usefulness of BLI.
Disclosure of Interest: None declared
P1268 PUSH-METHOD
PERCUTANEOUS
ENDOSCOPIC
GASTROSTOMY (PEG) FOR HEAD AND NECK (H&N) CANCER
PATIENTS; OUR EXPERIENCE AT A LARGE
GASTROENTEROLOGY UNIT
R. Sinha1,*, H. Taha1, D. Oliver1
1
Endoscopy Unit, South Tees NHS Foundation Trust, Middlesbrough, United
Kingdom
Contact E-mail Address: rohits78@gmail.com
INTRODUCTION: Nutritional support via gastrostomy is advocated in H&N
cancer patients undergoing chemo-radiotherapy treatment.
These may be inserted either endoscopically (PEG) or radiologically (RIG;
Radiologically Inserted gastrostomy). PEGs may be performed using a pull or
push (Seldinger) method. BSG guidelines 2010[1] specify that push-PEG technique should be preferred where cure is the intention of treatment for H&N cancer
to avoid risk of tumour seeding[2]. We have adopted this method and describe
our experience at a large gastroenterology centre of using push-PEGs for this
purpose.
AIMS & METHODS: The aim of this study was to audit safety and success rates
of push-inserted PEGs for H&N cancer patients. We retrospectively audited caserecords of all patients receiving push-inserted PEG procedures between January
2012 to December 2013
RESULTS: Push-PEGs were successfully placed in 95% (53/56) patients. Mean
age was 57.2 years; male:female ratio 36:17. Preprocedure antibiotics were used in
98% (52/53) patients. 84% (46/55) received a combination of midazolam (mean
dose 2.8mg) and fentanyl (mean dose 52.5mcg); rest 16% received single sedative
(midazolam). Discomfort scores[3] were recorded as 65% (33/51) comfortable
during the procedure and 35% had mild discomfort. 30-day mortality was
3.8% (2/52). Major complications occurred in 2 patients (3.8%): misplaced
suture in the peritoneal cavity requiring laparotomy retrieval; suture-tension
induced gastric perforation 3 days post-procedure in an obese patient. No gastrostomy site metastases were observed. Minor complications occurred in 2
patients (3.8%); balloon rupture resulting in dislodged PEG and skin hematoma
after day1 post-procedure. Our complication rates were lower than published
4.8%[4]. Three patients required RIG, having failed intubation due to stricturing
disease.
CONCLUSION: Push method PEG is safe, useful and a viable alternative to
RIG with high success rate in H&N cancer patients. RIG or surgically placed
gastrostomies should be reserved as second-line approach. We aim to provide
push-PEG for all H&N cancer by 2015 by education and training,compared to
62.2% (56/90). We reflect that obesity leading to suture-tension may be a risk
factor for major complication.
REFERENCES
1. BSG Guidelines on the provision of a percutaneously placed enteral tube
feeding service, 2010. British Society of Gastroenterology. Gut 2010; 59: 15921605.
2. Cruz I, et al. Incidence of abdominal wall metastasis complicating PEG tube
placement in untreated head and neck cancer. Gastrointest Endosc 2005; 62: 708711.
3. BSG Guidelines on Safety and Sedation during Endoscopic Procedures, 2003.
British Society of Gastroenterology.
4. Maple JT, et al. Direct percutaneous endoscopic jejunostomy:outcomes in 307
consecutive attempts. Am J Gastroenterol 2005; 100: 2681-2688.
Disclosure of Interest: None declared
P1269 EFFICACY AND SAFETY OF ENDOSCOPIC
RESECTION OF NONAMPULLARY DUODENAL POLYPS

MUCOSAL

R. Combes1,*, Y. Duny2, P. Bauret1


1
Hepato-gastroenterology Department, CHU Montpellier, 2INSERM,
Montpellier, France
Contact E-mail Address: roman.combes@hotmail.fr
INTRODUCTION: Endoscopic mucosal resection (EMR) of nonampullary duodenal (NAD) polyps is an alternative to surgical treatment. The literature is quite
poor about this subject and series often includes small sized populations.

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United European Gastroenterology Journal 2(1S)

AIMS & METHODS: This study aimed to evaluate efficacy and safety of EMR
for NAD polyps. This is a retrospective cohort analysis of all consecutive patients
referred between 2002 and 2013 for management of NAD polyps at a tertiarycare center by a single practitioner.
RESULTS: Between 2002 and 2013, 61 NAD polyps have been resected in 53
patients (22 females, 31 males). The mean age was 64.5 years (34.5-91.5). The
mean polyp size was 23.4 /- 14.1mm of wich 8.2% (n 5) 510mm, 50.8%
(n 31) between 10 and 20mm and 41% (n 25) 420mm.
Of 53 patients who underwent attempted endoscopic resection, complete resection was achieved in 52 cases (98.1%), during a single session in 48 patients
(90.4%) and with double or triple sessions in 5 patients (9.6%). En bloc resection
was performed for 36 polyps (59%) and piece meal resection for 25 polyps (41%).
37 of resected areas were closed by endoclips (60.7%) but closure failed or was
incomplete in 8 cases (21.6%).
Histological findings revealed 50 adenomas (15 tubulars and 35 tubulovillous or
villous with high degree of dysplasia in 5 (10%) of them), 11 non adenomatous
lesions (5 Brunners gland hyperplasias, 1 Brunners gland hamartoma, 1 gangliocytic paraganglioma, 1 lipoma, 1 neuroendocrine tumor, 1 inflammatory
fibro d polyp and 1 ectopic pancreas).
Complications occured in 11 patients (20.8%): 8 haemorrhages (15.1%) of which
a lethal one, with surgery needed in 2 cases, and 3 perforations (5.7%). In multivariate analysis, the only predictive factor of complication was the failure of
resected area closure by clip (OR 7.2; IC 95 [1.3-39.6]).
5 recurrences (17.2%) have been observed among 29 patients diagnosed with
adenoma who benefitted from a follow-up (mean follow-up: 23.4 months). All
recurrences were successfuully treated by EMR.
CONCLUSION: EMR of NAD polyps is an effective therapy but with significant morbi-mortality rate. However, in most of cases, complications have been
successfully treated by medical or endoscopic therapies. Long term endoscopic
follow-up is needed in adenomas with a recurrence rate of 17.2%.
Disclosure of Interest: None declared
P1270 ENDOSCOPIC SUBMUCOSAL DISSECTION CAN TRANSFORM
THE MANAGEMENT OF PATIENTS WITH UPPER
GASTROINTESTINAL SUBMUCOSAL TUMOURS: RESULTS FROM
A UK SERIES
R. Bhattacharyya1,*, G. Longcroft-wheaton2, P. Bhandari1 on behalf of
Portsmouth, UK
1
Gastroenterology, 2Portsmouth Hospitals NHS Trust, Portsmouth, United
Kingdom
Contact E-mail Address: rupam.bhattacharyya@gmail.com
INTRODUCTION: It is very difficult to establish an accurate diagnosis for
upper GI submucosal tumours. Biopsy during endoscopy cannot go deep
enough. EUS is unable to give a tissue diagnosis. The risks of surgical resection
are higher than the benefits as the lesion may very well be benign. As a result
most of these patients keep having endoscopic surveillance as possible GISTs.
AIMS & METHODS: A retrospective cohort study of patients undergoing ESD
for upper GI submucosal tumours. They were all referred to us as possible GISTs
that were found to be growing in size on surveillance. ESD was carried out in all
these cases. As these lesions are mostly bulky, gravity and patient positioning
were utilized as traction during ESD to achieve deroofing and enucleation of
these tumours. Any complications were recorded. Endoscopic follow up was
performed to assess for incomplete resection or recurrence.
RESULTS: 21 submucosal lesions were resected by ESD between 2007 and 2013.
7 were oesophageal, 10 gastric and 4 duodenal. Sizes ranged from 10 to 35mm.
Endoscopic clearance was achieved in all cases. Histology showed a wide range of
diagnoses, mostly benign (table). There was 1 complication; a microperforation
which was identified and clipped intraprocedurally, giving a complication rate of
4.7%. On follow up, there was 1 recurrence (recurrence rate 4.7%) which was
managed endoscopically. 1 patient had surgery as the ESD specimen showed a
synovial sarcoma. Endoscopic cure rate was 95.2%.
Table: Histological diagnosis of submucosal tumours resected by ESD
Diagnosis

number

Granular cell tumour


GIST
Leiomyoma, lipoma
Pancreatic acinar tissue
Carcinoid
Inflammatory fibroid polyp
Hyperplastic polyp
Synovial sarcoma
Gangliocytic paraganglioma

3
2
22
1
6
1
1
1
1

CONCLUSION: ESD is a safe and novel, minimal access therapeutic technique


which has the potential to transform management of submucosal tumours.
Patients go from the uncertainty of having repeated endoscopies for an unknown
diagnosis, to having it completely removed and cured in the vast majority, without the need for continuing endoscopies. In the remaining cases, ESD specimens
provide an accurate histological diagnosis based on which definite management
plans can be made.
Disclosure of Interest: None declared

P1271 PER-ORAL
ENDOSCOPIC
MYOTOMY
(POEM)
ACHALASIA CARDIA, CASE SERIES FROM SINGLE TERTIARY
CARE CENTRE

FOR

S. Davavala1,*, A. Bapaye1, N. Dubale1, S. Date1, V. Thorat1


Department of digestive diseases and Endoscopy, Deenanath Mangeshkar
Hospital and Research Centre, Pune, Pune, India
Contact E-mail Address: amolbapaye@gmail.com
1

INTRODUCTION: Treatment for achalasia cardia includes endoscopic (balloon


dilatation/botulinum injection) or surgical Hellers myotomy. Per-oral endoscopic myotomy (POEM) is an upcoming modality. This study reports preliminary results of POEM in patients suffering from achalasia cardia.
AIMS & METHODS: Patients with achalasia cardia confirmed on endoscopy
(EGD), high-resolution manometry (HRM) and barium swallow and undergoing
POEM were included. Associated co-morbidities & previous treatments for achalasia were recorded. Eckhardt dysphagia score was recorded before the procedure. Procedure time, technical success and complications were noted. Follow up
was by EGD, with or without HRM and post procedure Eckhardt score at 4
weeks.
RESULTS: 20 patients were enrolled, Male: Female (1:1). Achalasia Type: I 4,
II 12, III nil, Not Done - 4. Significant comorbidities: 6 / 20(30%).
Categories: na ve patients (n-10), previous therapies Hellers myotomy (n-2),
botulinum injection (n-1) and Balloon dilatation (n-6). Mean symptom duration: 24-420 weeks. Mean pre- procedure Eckhardt score 6.5; mean LES pressure 43.3mmHg (Range 17 -74 mmHg). Mean procedure duration (minutes)
was 187.5 (60 330), clinical success in all (100%) and no complications encountered. Technical difficulties occurred in 4 / 20 (20%) patients. Follow up (mean 6
months) mean Eckhardt score was 1.5 (p 0.001) and mean LES pressure 12.8
(p 0.018). Relief in dysphagia was in all patients (100%) and occasional heartburn in 8 / 20 (40%).
CONCLUSION: POEM is safe and effective treatment for achalasia cardia. It is
effective in treating na ve, previously treated patients and also in those with
comorbid illness that may preclude surgical treatment.
Disclosure of Interest: None declared
P1272 FACTORS RELATED TO NON-CURATIVE ENDOSCOPIC
SUBMUCOSAL DISSECTION FOR UNDIFFERENTIATED-TYPE
EARLY GASTRIC CANCER
S. Abe1,*, C. Sato1, I. Oda1, M. Sekiguchi1, G. Mori1, S. Nonaka1, H. Suzuki1,
S. Yoshinaga1, H. Taniguchi2, S. Sekine2, R. Kushima2, Y. Saito1
1
Endoscopy Division, 2Pathology Division, National Cancer Center Hospital,
Tokyo, Japan
Contact E-mail Address: seabe@ncc.go.jp
INTRODUCTION: Intramucosal undifferentiated-type (UD-type) early gastric
cancer (EGC)  2cm without ulceration has been treated by endoscopic submucosal dissection (ESD) as an investigational treatment. However, it is difficult to
estimate the depth of invasion in UD-type EGC compared with differentiatedtype. In addition, tumor margin is indistinct in some UD-type EGCs extending
along the proliferative zone in the middle layer of the mucosa, leaving normal
ducts covering the superficial epithelium.
AIMS & METHODS: This study aimed to evaluate factors related to non-curative ESD of UD-type EGC. 137 consecutive UD-type EGCs in 127 patients who
underwent ESD met the inclusion criteria: i) they had a poorly differentiated
adenocarcinoma or signet ring cell carcinoma histologically proven by preoperative biopsy, ii) the cancer was intramucosal and appeared on endoscopy to be  2
cm and without ulceration, iii) they had had no prior endoscopic treatment or
surgery of the upper gastrointestinal tract. This study assessed short-term outcomes of ESD, factors related to non-curative ESD and width of tumor extension
along the mucosal proliferative zone in 0-IIc lesions. Curative resection of ESD
for UD-type EGC was defined as the presence of an intramucosal cancer  2 cm
without ulceration or lymphovascular invasion and with clear lateral and vertical
margins on histological assessment.
RESULTS: Of 137 lesions, en bloc resection was achieved in 99.3% and R0
resection 94.2%. The median procedure time was 65 (10-300) minutes. Delayed
bleeding, perforation and delayed perforation rates were 2.9%, 2.9% and 0.7%,
respectively. Macroscopic types (0-IIc/0-IIa or 0-IIaIIc/0-IIb) were 133/3/1.
Median tumor size was 11mm (1-45). Pure sig morphology was identified in
58.4% and por including with other component in 41.6%. Curative resection
was 70.1% and was significantly higher with pure sig than por (81.3%/52.6%,
p50.0001). Main causes of non-curative ESD in all patients were submucosal
invasion (16.8%)
(minute
submucosa 5500m/deeper
submucosa
500m 8.0%/8.8%), tumor size 4 20mm (12.4%) and ulceration (7.3%)
(with overlapping, shown in table). Submucosal invasion and resected tumor
size 420mm were significantly more common in por than in pure sig (29.8%/
7.5%, p50.001 and 19.3%/10.0%, p 0.009). 43 lesions (31.4%) were preoperatively underestimated by more than 5mm in size. 75% (6/8) of the lesion which
were preoperatively diagnosed as 20mm in size were over 20mm. Extension along
the proliferative zone was found in 74 of 133 0-IIc lesions (55.6%) and median
width of extension was 980m (0-11650m). Increasing lesion size was associated
with more extension along the proliferative zone (preoperative tumor size and
median width of extension: 1-5mm/6-10mm/11-15mm/16-20mm 490m /
960m /1040m /1960m).

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United European Gastroenterology Journal 2(1S)

CONCLUSION: Careful preoperative assessment is needed for UD-type EGC,


especially if tumor size is near 20mm.
Disclosure of Interest: None declared

were both of non circumferential short segment (53cm) BE without intestinal


metaplasia. No patients had oesophageal cancer at follow up OGD.
CONCLUSION: In this study, the pick-up rate of cancer or BE at follow-up
OGD assessment in patients with Grade C or D oesophagitis is very low (0.3%).
Those in whom BE is diagnosed at follow up endoscopy, had preceding grade D
oesophagitis and BE is short segment and without intestinal metaplasia. This
pick up rate of BE is much lower than that reported if all patients with symptoms
of GORD were endoscoped suggesting that the presence of severe oesophagitis is
not a marker for detection of BE. From this study, we concluded the practice of
endoscopic follow-up in patients with severe oesophagitis adds to higher healthcare costs without improving patient outcomes. OGD is a valuable diagnostic
tool and for endoscopy services to be effective it is essential that it is not overloaded with inappropriate referrals. If our findings are replicated at other centres
then guidelines on follow up OGD in oesophagitis should be re-visited.
Disclosure of Interest: None declared

P1273 HOW TO PREDICT DELAYED BLEEDING AFTER ESD FOR


GASTRIC NEOPLASMS?

P1275 ODYNOPHAGIA AND ITS YIELD ON UPPER GI ENDOSCOPY - A


SYMPTOM WORTH ASKING ABOUT

S.H. Kim1,*, Y.K. Cho1, J.B. kim1, T.K. kim1, S.B. Ahn1, B.K. Son1, Y.J. Jo1,
Y.S. Park1
1
Department Of Internal Medicine, Eulji univerity, seoul, Korea, Republic Of
Contact E-mail Address: shkim@eulji.ac.kr

S. Subramaniam1.1,*, G. Goodchild1, K. Besherdas1


Department of Gastroenterology, Barnet & Chase Farm Hospitals NHS Trust,
London, United Kingdom
Contact E-mail Address: sharmila.subramaniam@nhs.net

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a major treatment option for gastric neoplasms. However, ESD causes Post-ESD delayed
bleeding (PEDB), one of the significant complication. Few studies showed that
risk factor of PEDB is large artificial ulcer. Known as ESD induced ulcer is
different from Peptic ulcer disease healing mechanism. Major healing mechanism
is muscle contraction. For preventing the PEDB, prophylactic coagulation
during the ESD was performed. So, we want to probe the effect of prophylactic
coagulation induced thermal injury to the delayed ESD bleeding. The primary
end point of this study is the relations between the post dissection coagulation
time (PDCT) and delayed post ESD bleeding.
AIMS & METHODS: A total of 288 lesions diagnosed with early gastric neoplasms and treated by ESD from March 2005 to February 2013 in Eulji Hospital,
retrospectively. PEDB was defined as the time of the bleeding after 24hrs: early
PEDB, and late PEDB. Also the lesion was categorized non bleeding visible
vessel, oozing bleeding and spurting bleeding. We analyzed associations between
bleeding and the following factors of the characteristics of the patients and the
lesions: age, sex, pathology, macroscopic findings (elevated, flat and depressed
lesion), location, size of the resected lesion, duration time of the procedure, the
type of the resection methods; enbloc or piecemeal resection, and fibrosis or not.
Also, we measured the PDCT.
RESULTS: PEDB which is in 3.0% lesions (16/288). Delayed bleeding which
oozing and spurting bleeding is only 1.5% (9/288). The male sex (P50.001),
piecemeal resection was risk factor of delayed bleeding (p 0.025). Compared
with non bleeding group, larger resected size (4.26/3.50(cm), p 0.02), and
delayed procedure time (96.62/58.24(min), P5 0.001) to be risk factors for
delayed bleeding. And the PDCT was longer delayed bleeding group, but there
are not significant (9.86/7.33(min) p 0.19). The location and macroscopic finding, pathology and fibrosis were not significant also.
CONCLUSION: This study demonstrated risk factors for PEDB. The male sex,
piecemeal resection, large resected size and delayed procedure time are increase
PEDB risk. However, we dont clarify the relationship between PDCT as thermal
injury variable and PEDB because of small volume size of study.
Disclosure of Interest: None declared

INTRODUCTION: Odynophagia can be defined as a painful sensation in the


oesophageal region that occurs in relation to swallowing. Unlike dysphagia,
which has historically been an alarm symptom or warning sign of oesophageal
cancer, odynophagia is not classified as an alarm symptom and does not form
part of the suspected upper gastrointestinal (GI) cancer referral form in the UK.
Endoscopy is the gold standard imaging modality for the diagnosis of mucosal
lesions in the oesophagus. However, there is no clear data regarding the findings
at endoscopy in patients scoped for odynophagia. Mucosal abnormalities even in
the presence of typical symptoms of gastro-oesophageal reflux disease, namely
heartburn and regurgitation are absent in up to 70%.
AIMS & METHODS: We hypothesise that the presence of odynophagia has a
high predictive value of mucosal abnormality at endoscopy and aimed to assess
the findings at endoscopy for patients scoped for odynophagia.
A retrospective analysis of all patients who underwent upper GI endoscopy for
odynophagia as a primary symptom over an 8-year period (2005-2013) within an
NHS Trust in north London was performed. Data was obtained from the
Unisoft Endoscopy reporting software. The findings at endoscopy in patients
with odynophagia were scrutinized.
RESULTS: 50 patients were endoscoped for odynophagia during the study
period. 34 of 50 patients (68%) had oesophageal mucosal lesions (4 Barretts
mucosa, 2 candida oesophagitis, 14 reflux oesophagitis, 6 malignant tumour, 5
oesophageal stricture, 3 oesophageal ulcers). 12% (6 of 50) had oesophageal
cancer. A further 10 had hiatus hernia, 1 had a motility disorder and 1 had
oesophageal diverticulum.
CONCLUSION: From this study, 68% of patients endoscoped for odynophagia
have a positive endoscopic mucosal abnormality. Odynophagia as a symptom
has a high sensitivity for abnormal endoscopy. 12% of patients endoscoped for
odynophagia had oesophageal cancer. This prevalence is similar to the diagnosis
of cancer in patients referred on the two week wait upper GI cancer referral
form. We recommend the symptom of odynophagia be classified as an alarm
symptom and those presenting with odynophagia all undergo upper GI endoscopy to define the exact mucosal abnormality and exclude oesophageal cancer.
Disclosure of Interest: None declared

P1274 LIMITED VALUE FOR FOLLOW UP ENDOSCOPY IN SEVERE


OESOPHAGITIS: FINDINGS FROM A LARGE LONDON DISTRICT
GENERAL HOSPITAL

P1276 EVALUATION OF SAFETY OF ENDOSCOPIC BIOPSY FOR


GASTRIC LESIONS IN ACCORDANCE WITH THE REVISED
JAPAN GASTROENTEROLOGICAL ENDOSCOPY SOCIETY
GUIDELINES FOR GASTROENTEROLOGICAL ENDOSCOPY IN
PATIENTS UNDERGOING ANTITHROMBOTIC TREATMENT

Submucosal invasion (SM1/SM2)


42cm in size
Ulceration
Lympho-vascular invasion
Positive lateral/vertical margin
Piecemeal resection

23(11/12)
17
10
4
5/4
1

16.8% (8.0%/8.8%)
12.4%
7.3%
2.9%
3.6%/2.9%
0.7%

S. Subramaniam1,*, G. Goodchild1, K. Besherdas1


1
Department of Gastroenterology, Barnet & Chase Farm Hospitals NHS Trust,
London, United Kingdom
Contact E-mail Address: sharmila.subramaniam@nhs.net
INTRODUCTION: The American Society of Gastrointestinal Endoscopy
recommends the practice of endoscopic follow-up for patients with gastro-oesophageal reflux disease (GORD) with oesophagitis after adequate medical therapy
has achieved mucosal healing, specifically to exclude masquerading Barretts
oesophagus (BE) or underlying cancer. Historically, follow-up oesophagogastro-duodenoscopy (OGD) for patients with GORD with oesophagitis was
reserved for patients whose symptoms failed to respond to medical therapy,
those who had severe oesophagitis or an oesophageal ulcer, or for those who
needed additional biopsies to clarify a diagnosis. It could be argued that repeat
OGD is not necessary as it gives a low yield in cancer and BE detection especially
if initial appearance is benign and not indicative of BE.
AIMS & METHODS: The aim of this study was to assess the findings in patients
who underwent a follow-up OGD for severe oesophagitis.
A single centre (large district general hospital), retrospective analysis of patients
diagnosed with severe oesophagitis (Los Angeles classification Grade C or D)
who subsequently underwent follow-up OGD over 8 years from 2005 was performed. Data was obtained using the GI Audit tool from the Unisoft endoscopy
reporting system. Patients were assessed for the presence of cancer or BE at
repeat OGD.
RESULTS: 76 patients with severe oesophagitis (31 grade D oesophagitis, 45
grade C oesophagitis) were included in the study. At follow up OGD, findings
were: normal in 43, grade A oesophagitis in 18, grade B oesophagitis in 12, BE in
3. Of the 3 patients with BE on review, all had Grade D oesophagitis at initial
OGD, one had appearance of BE macroscopically at initial OGD and the other 2

S. Tounou1.2,*, Y. Morita2, T. Hosono2


1
Gastroenterology, Teikyo University Chiba Medical Center, Ichihara-City,
2
Gastroenterology, Shin-Tokyo Hospital, Matsudo-City, Japan
Contact E-mail Address: s-tounou@med.teikyo-u.ac.jp
INTRODUCTION: Guidelines for gastroenterological endoscopy in patients
undergoing antithrombotic treatment published by Japan Gastroenterological
Endoscopy Society has been revised recently. In the revised guidelines, endoscopic biopsy is allowed without interruption of antithrombotic agents but
hemorrhagic risk of endoscopic biopsy for gastric lesions in the patients with
continuous use of antithrombotic agents has not been evaluated. We investigated
whether bleeding caused by biopsy is more likely to occur in patients with continuous use of antithrombotic agents.
AIMS & METHODS: The aim of this study is to evaluate a risk of bleeding
caused by endoscopic biopsy for gastric lesions with continuous use of antithrombotic agents (ATA) in accordance with the revised Japanese guidelines.
Subjects were 4197 gastric biopsies in 2059 patients between January 2012 and
December 2013. Subjects were classified into three groups according to the status
of administration of ATA. Multivariate analysis was performed to identify independent risk factors associated with biopsy-caused bleeding which needed endoscopic hemostasis.
RESULTS: Patients were classified into three groups; those who had not taken
antithrombotic agents (no ATA group: 3253 biopsies), those who had stopped
these agents completely (stop ATA group: 266 biopsies), and those who had
received and continued antithrombotic agents (ATA group: 678 biopsies).
Endoscopic hemostasis was performed in 5 biopsies in the no ATA group
(0.15%), 9 biopsies in the stop ATA group (3.38%, P50.001, compared with

A480
no ATA group) and 3 biopsies in the ATA group (0.44%, p 0.15, compared
with no ATA group). In multivariate analysis using logistic regression analysis,
ATA use (P50.001, RR 3.61), and biopsy from upper third region of the stomach (P 0.001, RR 5.53) were risk factors for biopsy-caused bleeding but
continuous use of ATA did not increase additional hemorrhagic risk even in
continuous use of multiple ATA.
CONCLUSION: Use of antithrombotic agents increased risk of bleeding caused
by biopsy for gastric lesions but continuous use of antithrombotic agents did not
increase additional hemorrhagic risk. Interruption of antithrombotic agents is
not necessary even in the use of multiple antithrombotic agents in the endoscopic
biopsy for gastric lesion. This study was performed in a single center, and further
studies in multiple centers are necessary.
REFERENCES
1. Fujimoto K, Fujishiro M, Kato M, et al. Guidelines for gastroenterological
endoscopy in patients undergoing antithrombotic treatment. Digestive Endoscopy
2014; 26: 1-14.
2. Ono S, Fujishiro M, Kodashima S, et al. Evaluation of safety of endoscopic
biopsy without cessation of antithrombotic agents in Japan. J Gastroenterol 2012;
47: 770-774.
3. Iwastuka K, Gotoda T, Kusano C, et al. Clinical management of esophagogastroduodenoscopy by clinicians under the former guidelines of the Japan
Gastroenterological Endoscopy Society for patients taking anticoagulant and
antiplatelet medications. Gastric Cancer. Epub ahead of print 8 January 2014.
Disclosure of Interest: None declared
P1277 ENDOSCOPIC DISTINCT FINDINGS OF DIFFERENTIATEDUNDIFFERENTIATED MIXED TYPE EARLY GASTRIC CANCER
WITH CONVENTIONAL ENDOSCOPY: COMPARISON WITH PURE
DIFFERENTIATED AND UNDIFFERENTIATED TYPES
S. Yoshinaga1,*, I. Oda1, H. Takamaru1, S. Abe1, S. Nonaka1, H. Suzuki1,
Y. Saito1, H. Katai2, S. Sekine3, H. Taniguchi3, R. Kushima3
1
Endoscopy Division, 2Gastric Surgery Division, 3Pathology Division, National
Cancer Center Hospital, Tokyo, Japan
Contact E-mail Address: shiyoshi@ncc.go.jp
INTRODUCTION: Mixed type early gastric adenocarcinomas, which have both
differentiated and undifferentiated histopathological component, have been
reported to have higher incidence of lymph node metastasis than pure differentiated or undifferentiated types. The endoscopic features to distinguish mixed
type early gastric cancer from other subtypes have not been previously described.
AIMS & METHODS: We reviewed endoscopic findings of 1230 early gastric
adenocarcinomas that were resected in the National Cancer Center Tokyo
between January 2011 and December 2012. The following cases were excluded:
lesions located at the esophago-gastric junction, specimens from patients who
had received chemotherapy within 1 year before resection, cancers located in the
remnant stomach after previous gastrectomy and specimens suspected to be
recurrent cancers after previous endoscopic resection. After excluding, total of
1047 lesions were evaluated finally. Endoscopic findings that were evaluated
include location in the stomach, relationship with atrophic mucosa, color, clarity
of demarcation with surrounding mucosa and endoscopic morphology of the
lesions. Histopathological findings were evaluated size, depth, presence/absence
of an ulcer and evidence of venous/lymphatic invasion. Histopathologically,
these lesions were divided into 3 subtype; pure differentiated type, pure undifferentiated type and mixed type.
RESULTS: One thousand and forty seven lesions were consisted of 156 mixed
type, 738 differentiated type and 153 undifferentiated type. When compared to
differentiated type early gastric cancer, mixed type is more commonly located in
the middle third of the stomach (odds ratio 1.636, 95% C. I. 1.077-2.487),
located in the atrophic border area or the unatrophic area (odds ratio 4.237,
95% C. I. 2.330-7.705), 0-IIc type in Paris classification (odds ratio 4.282,
95% C. I. 2.515-7.289), larger than 20mm (odds ratio 4.226, 95% C.
I. 2.703-6.608), have ulcerative findings (odds ratio 1.868, 95% C.
I. 1.146-3.043) and have submucosal invasion (odds ratio 3.237, 95% C.
I. 2.042-5.131) in multivariate analysis. In comparison to undifferentiated
type early cancer, mixed type is more commonly located in the atrophic area
(odds ratio 1.839, 95% C. I. 1.062-3.183), reddish colored (odds
ratio 4.966, 95% C. I. 2.595-9.504), and have submucosal invasion (odds
ratio 1.935, 95% C. I. 1.121-3.341). Histopathologically, mixed type cancers
have a higher incidence of lymphatic invasion than the other subtypes in univariate analysis (p-value 5 0.001).
CONCLUSION: Mixed type early gastric cancers have distinct endoscopic
findings.
Disclosure of Interest: None declared
P1278 USEFULNESS OF LAPAROSCOPIC AND ENDOSCOPIC
COOPERATIVE SURGERY FOR GASTRIC SUBMUCOSAL
TUMORS, INCLUDING ESOPHAGOGASTRIC JUNCTION TUMORS
S. Hoteya1,*, S. Haruta1, H. Shinohra1, M. Kaise1, Y. Kuribayashi1,
H. Udagawa1
1
Gastroenterology, Toranomon Hospital, Tokyo, Japan
INTRODUCTION: A preoperative histopathological diagnosis of gastric submucosal tumor (gSMT) is not only difficult with a regular biopsy, but it often
cannot be obtained even by endoscopic ultrasound/fine-needle aspiration (EUSFNA). In most gSMT cases, treatment indications are determined on the basis of
macroscopic signs visible on diagnostic imaging such as EUS or computed tomography, including growth in size over time or surface ulceration, and a definitive
diagnosis is only reached after surgical resection. Recently, however, the use of
endoscopic submucosal dissection (ESD) for gSMT and the development of

United European Gastroenterology Journal 2(1S)


laparoscopic and endoscopic cooperative surgery (LECS) have enabled either
preservation of the stomach or minimization of the extent of partial resection,
and an increasing number of hospitals are introducing it as less invasive, more
reliable treatment. In this study, the outcomes following the recent introduction
of LECS for gSMT are presented. We evaluated the feasibility and safety of the
LECS for SMTs located at the esophagogastric junction (EGJ), compared with
non-EGJ SMTs.
AIMS & METHODS: Treatment for gSMT at our hospital broadly follows the
algorithm given in the clinical practice guidelines for gastrointestinal stromal
tumor (GIST), in which lesions are classified as those for which surgery is absolutely indicated, those for which it is relatively indicated (including endoscopic
surgery), and those that should be monitored. Among those lesions for which
surgery is relatively indicated, LECS is indicated for lesions that have an intragastric growth pattern, or for which fundusectomy can be avoided despite an
extragastric growth pattern. We retrospectively evaluated the outcome of LECS
performed in 29 gSMTs, including 6 EGJ SMTs.
RESULTS: Partial gastric resection was performed for 29 patients in our hospital
using LECS between its introduction in February 2011 and February 2014. The
mean tumor diameter was 31.2 mm (12-72 mm), with a R0 resection rate of
100%, with no postoperative complications of suture rupture, obstruction, or
stasis occurring in any patient. On pathology, the tumors were GIST in 20 cases
(low 19, high 1), myoma in 5, aberrant pancreas in 2, schwannoma in 1, and
cavernous hemangioma in 1. Endoscopic confirmation of the EGJ enabled the
extent of resection to be minimized and the stomach to be preserved, And fundusectomy was successfully avoided in all 6 patients in whom tumors were within
2 cm of the cardia. Although there were significantly differences in tumor size
and resected specimen size between EGJ SMTs and non-EGJ SMTs, there were
no significant differences in outcomes of LECS procedure.
CONCLUSION: LECS for gSMT is easily performed through cooperation
between experts in endoscopy and laparoscopy, with good results. LECS is a
low-invasive treatment that is both organ-preserving and curative, especially for
EGJ SMTs.
Disclosure of Interest: None declared
P1279 THE EFFICACY OF CARBON DIOXIDE INSUFFLATION IN
UPPER GASTROINTESTINAL TRACT ENDOSCOPIC
SUBMUCOSAL DISSECTION: A RANDOMIZED, DOUBLE-BLIND,
CONTROLLED PROSPECTIVE STUDY
S.Y. Kim1,*, J.W. Chung1, D.K. Park1, K.A. Kwon1, K.O. Kim1, Y.J. Kim1
1
Department of Gastroenterology, Gachon University, Gil Medical Center,
Incheon, Korea, Republic Of
INTRODUCTION: Recently, endoscopic submucosal dissection (ESD) is one of
important treatment modality for gastrointestinal tract neoplasm. ESD is performed with using air insufflations, and is associated with abdominal discomfort.
It is well recognized that carbon dioxide (CO2) is absorbed quickly in the body
than air. CO2 insufflation is expected to be reduces abdominal discomfort and
pain after ESD.
AIMS & METHODS: This prospective study was designed to assess the efficacy
of CO2 insufflation instead of air insufflation during upper gastrointestinal tract
(esophagus: 1, stomach: 53) ESD. From May 2012 to April 2014, a total of 54
consecutive patients were randomly assigned to CO2 insufflation (CO2 group,
n 26) or air insufflation (Air group, n 28). Abdominal pain after ESD was
chronologically recorded on visual analogue system (VAS) score. Also, we
recorded of both group that change of abdominal circumference, the amounts
of sedatives, and complication rates.
RESULTS: Baseline patient characteristics (age, gender, tumor size, tumor location, tumor histology) were not different in both groups. The mean procedure
time was 54.6 minutes in the CO2 group and 57.5 minutes in the Air group, with
no statistically significant difference between both groups. Abdominal pain on
VAS in the CO2 group vs. Air group was 0.0 vs. 0.3 before the ESD (p 0.210),
3.4 vs. 4.6 one hour after the ESD (p 0.131), 2.7 vs. 3.8 three hours after the
ESD (p 0.141), 1.7 vs. 3.3 six hours after the ESD (p 0.015), and 0.8 vs. 2.3
one day after the ESD (p 0.002). In the CO2 group, the abdominal pain on
VAS (six hours after the ESD & one day after the ESD) was significantly lower
than that of the Air group. The abdominal circumference change in CO2 group
shows less variation than in Air group. However, there was no statistical difference between them (0.89 cm vs. 1.42 cm, p 0.422). The amounts of sedative
drugs did not differ between the groups (p 0.17). Complication rates were not
statistically different between both groups (CO2 group: 19.2%, 5/26; Air group:
28.6%, 8/28) (p 0.53).
CONCLUSION: The amounts of sedatives or complication rates, there were no
differences in the two groups. However, CO2 insufflation during upper gastrointestinal tract ESD is less painful for patients than air insufflation.
REFERENCES
Prolonged carbon dioxide insufflation under general anesthesia for endoscopic
submucosal dissection. Endoscopy 2010; 42: 10211029.
Safety of carbon dioxide insufflation for upper gastrointestinal tract endoscopic
treatment of patients under deep sedation. Surg Endosc 2010; 24: 16381645.
A prospective, randomized, double-blind, controlled trial on the efficacy of
carbon dioxide insufflation in gastric endoscopic submucosal dissection.
Endoscopy 2013; 45: 335341.
Effectiveness of CO2-insufflated endoscopic submucosal dissection with the duodenal balloon occlusion method for early esophageal or gastric cancer: a randomized case control prospective study. BMC Gastroenterology 2012; 12: 37.
A pilot study to assess the safety and efficacy of carbon dioxide insufflation
during colorectal endoscopic submucosal dissection with the patient under conscious sedation. Gastrointest Endosc 2007; 65.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1280 LIMITATIONS OF ESD FOR EARLY GASTRIC CANCER:
RETROSPECTIVE ANALYSIS OF FACTORS RELATED TO
POSITIVE VERTICAL MARGINS
T. Maehata1,*, O. Goto2, R. Morita1, M. Suzuki1, Y. Sato1, S. Ishigooka1, S.I. Ozawa1, K. Hosoya1, Y. Matsuo1, M. Yamashita1, H. Yamamoto1,
H. Yasuda1, F. Itoh1
1
Gastroenterology and Hepatology, St. Marianna Univercity School of Medicine,
Kawasaki, 2Division of Research and Development for Minimally Invasive
Treatment, Keio University School of Medicine, Tokyo, Japan
Contact E-mail Address: t2maehata@marianna-u.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) for early gastric
cancer is widely used and contributes greatly to the preservation of gastric function. In clinical practice, however, for cases not indicated for ESD, we occasionally encounter treatments such as diagnostic ESD that are considered
overindications. Some cases have incomplete resection because of positive vertical margins and deviate from the rule that tumors should be completely resected
en bloc. In this study, we examined the limitations of ESD (conditions of lesions
worthy of full-thickness resection) by identifying the clinicopathological factors
involved in positive vertical margins (pVM1) among cases of early gastric cancer
resected using ESD.
AIMS & METHODS: A total of 653 lesions of early gastric cancer resected en
bloc with ESD at two institutions prior to 2013 were categorized into the pVM1
and pVM0 groups. Factors that influenced pVM1 were extracted by univariate
analysis of factors such as patient background (age, sex) and pathological background (site, tumor diameter, macroscopic type, ulcerative findings, pathological
invasion depth, degree of differentiation, and vascular invasion) followed by
multivariate analysis of those factors.
RESULTS: The pVM1 group included 24 lesions (3.5%). On univariate analysis,
tumor diameter (p 5 0.0001), pathological invasion depth (pT1b; p 5 0.0001),
and degree of differentiation (p 0.007) had a significant effect on pVM1. On
multivariate analysis of those factors, pT1b was the only factor that had a significant effect on pVM1. The pVM1 rates in pT1a and pT1b lesions were 0.055%
and 19.6% (p 5 0.0001), respectively, and the diagnostic rate of invasion depth
was 92.5% overall and 97% and 84.6% in M-SM1 and SM2, respectively.
CONCLUSION: Submucosal (SM) invasion depth had a significant effect on
pVM1. When SM invasive cancer is suspected prior to surgery, full-thickness
resection, which is more reliable, is desirable for cT1b gastric cancer not only
because of possible lymph node metastasis but also because of the high possibility
of incomplete resection when ESD is performed for the primary tumor. The
future development of function-preserving or reductive surgeries that bridge
the gap between ESD and standard surgery in such cases of potentially invasive
gastric cancer is desired.
Disclosure of Interest: None declared
P1281 CONVENTIONAL ENDOSCOPY USING NON-EXTENSION
SIGN AS A DIAGNOSTIC MARKER IS SUPERIOR TO
ENDOSCOPIC ULTRASONOGRAPHY (EUS) FOR DIAGNOSING
DEPTH OF INVASION IN EARLY GASTRIC CANCER
T. Nagahama1,*, K. Otsu1, K. Yao2, K. Imamura1, T. Matsui1, A. Iwashita3
1
Department of Gastroenterology, 2Department of Endoscopy, 3Department of
Pathology, Fukuoka University Chikushi Hospital, Chikushino, Japan
INTRODUCTION: Precise diagnosis of depth of invasion is important for deciding upon the proper treatment for early gastric cancer. The authors previously
investigated the possibility of diagnosing depth of invasion with conventional
endoscopy using non-extension sign as a diagnostic marker, and reported
that the diagnostic sensitivity, specificity and accuracy for submucosal massive
invasion (SM2, 500 micrometers and over) by cancer were 89.7%, 97.7%, 96.6%,
respectively [1]. However, it is not clear whether conventional endoscopy is superior to endoscopic ultrasonography (EUS) with regard to discriminating submucosal massively invasive cancer (SM2, 500 micrometers and over) from mucosal
cancer (M)/submucosal micro-invasive cancer (SM1, less than 500 micrometers).
The present study aimed to compare the diagnostic performance of conventional
endoscopy and EUS for SM2 early gastric cancer.
AIMS & METHODS: Consecutive early gastric cancer lesions, in which both
preoperative conventional endoscopy and EUS were conducted, were included in
the study among 863 lesions (704 patients) treated with endoscopic or surgical
resection in our hospital between 2005 and 2012. Lesions were excluded if a
definitive diagnosis could not be made through histopathological examination
of resected specimens. During conventional endoscopy and EUS, the depth of
invasion was diagnosed as M/SM1 or SM2 and immediately recorded into a
database. Non-extension sign was determined as positive when one of the
following two findings is detected according to the conventional endoscopic
findings: (i) massive surround elevation; or (ii) mucosal convergence with elevation [1]. The non-extension sign relate to the increased thickness and rigidity
caused by massive submucosal invasion by the cancer. In order to obtain reproducible findings, the stomach was insufflated with a large volume of air to detect
non-extensibility. Diagnostic criteria for SM2 were positivity for non-extension
sign on conventional endoscopy and a rupture in the 2nd layer 2 with a tumor
echo in the 3rd layer on EUS. Lesions negative for these findings were diagnosed
as M/SM1. Histopathological examination was used as the gold standard for
diagnosing depth of invasion.
RESULTS: A total of 341 early gastric cancer lesions (M/SM1:SM2 284:57)
were included in this study. The following results were obtained for the diagnosis
of SM2 with conventional endoscopy vs. EUS: sensitivity, 89.5% (95% confidence interval [CI]: 81.597.4%) vs. 68.4% (95%CI: 56.380.5%) [p50.05, chisquare test]; specificity, 99.3% (98.3100%) vs. 83.5% (79.187.8%) [p50.0001];
and diagnostic accuracy, 98.4% (9699.3%) vs. 80.9% (76.885.1%) [p50.0001].

A481
CONCLUSION: Conventional endoscopy using non-extension sign showed
superior diagnostic performance compared to EUS for the diagnosis of SM2
early gastric cancer. The diagnosis of depth of invasion in early gastric cancer
by this conventional endoscopy method has the potential to omit EUS.
REFERENCES
[1] Nagahama T, et al. United Eur Gastroenterol J 2013; 1(Suppl. 1): A44
Disclosure of Interest: None declared
P1282 THE STUDY OF LONG TERM OUTCOMES UTILIZING TISSUEENGINEERED CELL SHEET TRANSPLANTATION FOR THE
PREVENTION OF OESOPHAGEAL STRICTURE
T. Ohki1.2,*, M. Yamato2, M. Ota1, R. Takagi2, M. Kondo2, N. Kanai2,
T. Okano2, M. Yamamoto1
1
Department of Surgery, Institute of Gastroenterology, Tokyo Womens Medical
University, 2Institute of Advanced Biomedical Engineering and Science, Tokyo
Womens Medical University, Tokyo, Japan
Contact E-mail Address: ohki@ige.twmu.ac.jp
INTRODUCTION: We reported a regenerative medical approach to prevent
oesophageal stricture after endoscopic submucosal dissection (ESD) using
tissue-engineered oral mucosal epithelial cell sheets in a short term. In this
study, long-term outcome has not yet been determined.
AIMS & METHODS: The aim of our study is to reveal the long-term outcome
of cell sheet transplantation. Epithelial cells, isolated from the patients own oral
mucosal tissue, were cultured for 16 days using temperature-responsive culture
dishes. Then, the autologous cell sheets were endoscopically transplanted onto
the bed of the oesophageal ulcer after endoscopic mucosal resection (EMR) and
ESD. Results of 10 patients who underwent endoscopic transplantation of oral
mucosal epithelial cell sheets from April 2008 through September 2010 were
recoded. We analyzed the outcome, the cause, and the endoscopic findings.
RESULTS: All patients were being followed-up. No stricture was detected in any
of the patients. The average period of observation was 1.600 days. One patient
was deceased because of pancreatic cancer. One patient underwent chemo-radio
therapy for farther treatment. One patient underwent surgery due to metastasis
of lymph nodes. Only the lymph nodes were dissected, the oesophagus remained
intact. From the endoscopic findings: Melanosis was found at the transplanted
site in a patient. Strong iodine staining was shown at the transplanted site in a
patient.
CONCLUSION: Transplantation of cell sheets has been proven to be a safe
method. No patients showed any controlled oesophageal stricture. This study
was only an exploratory research, further studies which involve prospective randomized control studies will be needed.
REFERENCES
(1) Ohki T, et al. Regenerative medicine: Tissue-engineered cell sheet for the
prevention of postendoscopic submucosal dissection esophageal stricture.
Gastrointest Endosc Clin North Am, 2014.
(2) Ohki T, et al. Prevention of esophageal stricture after endoscopic submucosal
dissection using tissue-engineered cell sheets. Gastroenterology, 2012, 143.3: 582588. e2.
(3) Ohki T, et al. Application of cell sheet technology for esophageal endoscopic
submucosal dissection. Tech Gastrointest Endosc 2011; 13: 105-109.
(4) Ohki T, et al. Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a
canine model. Gut 2006; 55: 1704-1710.
Disclosure of Interest: T. Ohki: None declared, M. Yamato: None declared, M.
Ota: None declared, R. Takagi: None declared, M. Kondo: None declared, N.
Kanai: None declared, T. Okano Financial support for research from: Teruo
Okano is a founder and director of the board of CellSeed Inc., a cell sheet
regenerative medicine company in Japan, licensing technologies and patents
from Tokyo Womens Medical University related to this presentation. The presentator is also a stake holder of the company listed at JASDAQ (Code: JQG
7776), M. Yamamoto: None declared
P1283 LONG-TERM OUTCOMES OF NON-CURATIVE ESD FOR EARLY
GASTRIC CANCER: A MULTICENTER RETROSPECTIVE STUDY BY
THE OSAKA GUT FORUM
T. Yamada1.2,*, T. Nishida2.3, M. Kato2, S. Kitamura4, M. Komori5, N. Kawai6,
K. Yamamoto3, M. Nakahara7, S. Egawa8, F. Nakanishi9, A. Nishihara10,
A. Mukai11, H. Iijima2, M. Tsujii2, E. Mita1, T. Takehara2
1
Department of Gastroenterology and Hepatology, Osaka National Hospital,
Osaka, 2Department of Gastroenterology and Hepatology, Osaka University
Graduate School of Medicine, Suita, 3Department of Gastroenterology, Toyonaka
Municipal Hospital, Toyonaka, 4Department of Gastroenterology, Sakai
Municipal Hospital, 5Department of Gastroenterology, Osaka Rosai Hospital,
Sakai, 6Department of Gastroenterology, Osaka Police Hospital, Osaka,
7
Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, 8Department
of Gastroenterology, Kansai Rosai Hospital, Amagasaki, 9Department of
Gastroenterology, Osaka Minami Medical Center, Kawachi-Nagano,
10
Department of Gastroenterology, Minoh City Hospital, Minoh, 11Department of
Gastroenterology, Sumitomo Hospital, Osaka, Japan
Contact E-mail Address: yamada@onh.go.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) is currently
becoming the major treatment for early gastric cancer (EGC) without risk of
lymph node (LN) metastasis. ESD showed better results to remove EGC with
relatively high resection rate and low local recurrence rate. On the other hand,
when the endoscopic resection (ER) is non-curative, surgical treatment is
required. Some patients, however, do not undergo surgery after non-curative

A482
ER, because of their comorbidity, refusal of surgery, and so on. Long-term
follow-up data and prognosis factors are needed for the case of non-curative ER.
AIMS & METHODS: The aim of this study is to investigate long-term outcome
and evaluate the factors related to prognosis of non-curative ER. This is a retrospective study in consecutive patients with EGC underwent ESD from March
2003 to November 2010 in 10 institutes in the Osaka Gut Forum. We defined
curative resection as the lesions meeting expanded criteria with R0 resection.
Expanded criteria is following; 1) specified mucosal cancer without ulcer findings
irrespective of tumor size, 2) mucosal cancer without ulcers 3 cm diameter or
smaller, and 3) minute submucosal invasive cancer 3 cm diameter or smaller. We
studied the overall and relapse-free survival rate using KaplanMeier methods,
and the prognosis factors using Coxs regression model.
RESULTS: We treated 1468 patients with EGC by gastric ESD. Of them, 174
patients (174 lesions) resulted in non-curative resection. One hundred seven
patients were underwent surgical treatment and 67 patients were observed.
These patients had median age of 72 years (mean, 71.2 years; range, 39-90
years), and a male/female ratio of 132:42. Seventy-two lesions were mucosal
cancer and 102 lesions were submucosal cancer. Median follow-up period was
58.5 months. There was one gastric cancer-related death in the case of surgical
treatment. The 5-year overall survival rate and relapse-free survival rate were
91% and 86%, respectively, and were not significantly different between surgical
and non-surgical groups. The most important factor related to relapse-free survival was age (hazard-ratio: 3.37), followed by lymphatic-vascular invasion
(2.90), and depth of tumor (2.45).
CONCLUSION: The patients with non-curative endoscopic resection for EGC
generally require additional surgery to avoid recurrence. This study, however,
showed no significant advantage of surgery within at least 5 years after ER, even
though selection bias can exist. There may be no merit of an additional operation
in the patients without lymphatic-vascular invasion.
Disclosure of Interest: None declared
P1284 MULTICENTER, PROSPECTIVE TRIAL OF MAGNIFYING
ENDOSCOPY WITH NARROW BAND IMAGING FOR STAGE
DIAGNOSIS OF SUPERFICIAL ESOPHAGEAL CANCER
T. Yamada1,*, T. Shimura2.3, M. Ebi2, T. Mizushima4, K. Itoh5, H. Tsukamoto2,
K. Tsuchida6, Y. Hirata7, K. Murakami8, H. Kanie1, S. Nomura1, H. Iwasaki4,
M. Kitagawa5, S. Takahashi9, T. Joh2
1
Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital,
2
Department of Gastroenterology and Metabolism, Nagoya City University
Graduate School of Medical Sciences, Nagoya, Japan, 3Boston Childrens Hospital
and Harvard Medical School, Boston, United States, 4Gifu Prefectural Tajimi
Hospital, Tajimi, 5Nagoya City East Medical Center, 6Nagoya City West Medical
Center, Nagoya, 7Kasugai Municipal Hospital, Kasugai, 8Nagoya Memorial
Hospital, 9Department of Experimental Pathology and Tumor Biology, Nagoya
City University Graduate School of Medical Sciences, Nagoya, Japan
Contact E-mail Address: tshimura@med.nagoya-cu.ac.jp
INTRODUCTION: Among superficial esophageal squamous cell carcinoma
(SESCC), cancer invading within the epithelium and the lamina propria
mucosa (T1a-EP/LPM) is considered as the indication of endoscopic resection,
while surgical resection or chemoradiotherapy is recommended for cancer invading beyond the muscularis mucosa (T1a-MM). Many retrospective studies have
reported that magnifying endoscopy with narrow band imaging (ME-NBI) can
predict invasion depth of SESCC well. However, the true additional effect of
ME-NBI on white light imaging (WLI) for diagnosis of invasion depth is unclear
because of a lack of prospective data. Thus, a prospective study of ME-NBI was
conducted in the present study.
AIMS & METHODS: Patients with SESCC were prospectively enrolled from 7
Japanese institutions. Enrolled patients received primary WLI followed by MENBI and the report of primary WLI was completed before the start of ME-NBI
by an assistant. Diagnoses of invasion depth by each tool were divided into T1aEP/LPM and T1a-MM and then collated with the final pathological diagnosis
by an independent pathologist blinded to the clinical data. All endoscopists
attended the consensus meeting and were trained before the trial to standardize
diagnosis among examiners, and this trial was started after achievement of a
mean k value 0.6 among all participating examiners. The primary end point
was diagnostic accuracy for invasion depth.
RESULTS: In total, 55 patients with SESCC were enrolled from June 2011 to
October 2013, and the results of WLI and ME-NBI were finally analyzed for a
total of 49 lesions. Forty one patients underwent endoscopic submucosal dissection and 8 patients did esophagectomy as the initial treatment. Final pathological
diagnosis of invasion depth was T1a-EP/LPM in 31 lesions and T1a-MM in 18
lesions. The accuracy of invasion depth in WLI and ME-NBI was 71.4% and
67.3% (P 0.661), respectively. Sensitivity for T1a-MM was 61.1% in both
WLI and ME-NBI (P 1.000), and specificity for T1a-MM was 77.4% in WLI
and 67.7% in ME-NBI (P 0.393). Moreover, we will present other data of
subset analyses in this meeting.
CONCLUSION: ME-NBI did not demonstrate the additional effect on WLI for
diagnosis of invasion depth of SESCC. Further development of diagnostic tool is
hopeful in the future.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1285 A NOVEL SELF-ASSEMBLED PEPTIDE SOLUTION
PREVENTION OF POST PROCEDURE BLEEDING AND
PROMOTING ULCER HEALING AFTER ENDOSCOPIC
SUBMUCOSAL DISSECTION FOR GASTRIC LESIONS

FOR

T. Uraoka1.2,*, O. Goto2, J. Horii2, Y. Ochiai2, A. Fujimoto2, K. Takabayashi1,


Y. Kawahara3, K. Hori4, S. Matsuda5, Y. Kitagawa5, N. Yahagi2
1
Department of Gastroenterology, Tokyo Medical Center, 2Division of Research
and Development for Minimally Invasive Treatment, Cancer Center, School of
Medicine, Keio University, Tokyo, 3Department of Endoscopy, Okayama
University Hospital, 4Department of Gastroenterology and Hepatology, Okayama
University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,
Okayama, 5Department of Surgery, School of Medicine, Keio University, Tokyo,
Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) can remove early
stage gastric epithelial neoplasms en bloc those that are large, with scarring,
however, post-ESD bleeding has been reported in 4-7% of patients. Gastric
ESD-induced ulcer is generally treated with proton pump inhibitor (PPI) for at
least 8 weeks after ESD. Recently, a self-assembled peptide solution, which has a
function as an extracellular matrix scaffold material to replace collagen has been
developed.
AIMS & METHODS: The aim of this clinical trial was to assess the safety and
efficacy of a novel self-assembled peptide solution for ESD-induced ulcers.
Consecutive patients who underwent gastric ESDs enrolled in this study.
Patients receiving antithrombotic therapy were included, but such medications
were no longer being administered prior to the procedures. Cases with perforation and coagulopathy (INR43) despite anticoagulation management after
heparin bridge therapy (HBT) were excluded. For every 1 cm of tumor, 1 mm3
of fully-synthetic peptide solution that self-assembles at physiological pH and
forms a gel comprising a network of nanofibers (PuraMatrixTM; 3-D Matrix,
Ltd) was applied to the ESD-induced ulcer using a catheter immediately after the
procedure. Single dose PPI was administered for 8 weeks beginning the morning
of the procedure. Ulcer stages were evaluated by endoscopy as active, healing or
scarring at 1, 4 and 8 weeks after ESDs. The primary endpoint was the rate of
post-ESD bleeding. The secondary endpoints include the transitional rate to
healing and scarring stages of gastric ESD-induced ulcers according to the
Sakita-Miwa classification.
RESULTS: Of 47 patients recruited, 45 patients with 51 lesions were enrolled for
outcome analysis and 2 patients were excluded due to 1 perforations and 1 with
coagulopathy. Fourteen patients (31%) were previously on antithrombotic therapy including 5 (11%) requiring HBTs. The mean size of resected specimen was
4016mm. The rate of post-ESD bleeding was 2.0% (1/51, 95%CI, 0.03 to 10.3).
A post-ESD bleeding was successfully managed endoscopically without needed
blood transfusion. Transitional rate to healing stage at 1 week was 96%. Follow
up endoscopies demonstrated scaring stage in 17% and 98% at 4 and 8 weeks
respectively. There were no adverse effects related with PuraMatrix use.
CONCLUSION: The use of this novel self-assembled peptide solution may help
reduce post-ESD bleeding rate and promote ulcer healing. Further studies are
needed to fully evaluate its efficacy. (UMIN Clinical Trials Registry: 000011548)
Disclosure of Interest: None declared
P1286 FEASIBILITY OF IN VIVO ENDOCYTOSCOPY IN THE
DIAGNOSIS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA:
A MULTICENTER STUDY
T. Iizuka1,*, S. Morita2, K. Goda3, K. Kaneko4, M. Kaise1, M. Kato5, H. Inoue6,
S. Kodashima7, Y. Niwa8, R. Miyahara9, J. Aida10, Y. Nakanishi11,
K. Takubo10, Y. Ohkura12, M. Ikegami13, A. ochiai14, T. Shimoda15,
K. Yoshimura16, M. Muto17
1
Gastroenterology, TORANOMON HOSPITYAL, Tokyo, 2Gastroenterology,
Graduate School of Medicine, Kyoto University, Kyoto, 3Endoscopy, The Jikei
University School of Medicine, Tokyo, 4Gastroenterology and Endosocpy, National
cancer Center Hospital East, Chiba, 5Endoscopy, Hokkaido University Hospital,
Hokkaido, 6Digestive Disease Center, Showa University Northern Yokohama
Hospital, Yokohama, 7Gastroenterology, Graduate School of Medicine, The
University of Tokyo, Tokyo, 8Endoscopy, Aichi Cancer Center Hospital,
9
Gastroenterology and Hepatology, Nagoya University, Graduate School of
Medicine, Aichi, 10Research Team for Geriatric Pathology, Tokyo Metropolitan
Institute of Gerontology, Tokyo, Japan, 11Pathology, Indiana University,
Bloomington, United States, 12Pathology, Kyorin University Hospital,
13
Pathology, The Jikei University School of Medicine, Tokyo, 14Pathology,
Research Center for Innovative Oncology, National Cancer Center Hospital East,
Chiba, 15Diagnostic pathology, Clinical Laboratory Division, National Cancer
Center Hospital, Tokyo, 16Center for Clinical Research, Kobe University Hospital,
Kobe, 17Department of therapeutic oncology, Graduate School of Medicine, Kyoto
University, Kyoto, Japan
Contact E-mail Address: t-iizuka@toranomon.gr.jp
INTRODUCTION: The endocytoscopy system (ECS) enables observation of cell
nuclei and real-time microscopic diagnosis. High-quality in vivo imaging and
accurate diagnosis of ECS images are essential for the practical application of
this modality.
AIMS & METHODS: This study sought to determine the diagnostic visualization capabilities of in vivo ECS in superficial esophageal squamous cell carcinoma (SCC) and to reveal the diagnostic accuracy of pathologists. Patients with
superficial esophageal SCC or high-grade intraepithelial neoplasia (HGIN) larger
than 10 mm were targeted. Endoscopists selected 3 ECS images each of cancerous
and non-cancerous lesions in each patient, and central pathologists verified both
sets of images and the corresponding parts in the specimens. The ECS images
were randomly assigned in each case and subsequently evaluated by 5

United European Gastroenterology Journal 2(1S)


pathologists blinded to individual cases. Diagnostic criteria were cellular or structural atypia, specifically nuclear enlargement, anisokaryosis, high nuclear density, and intercellular boundary. The primary endpoint was the diagnostic rate of
cancerous lesions on ECS images determined by the pathologists (sensitivity).
The secondary endpoints were the inter-observer agreement among the 5 pathologists (multi-rater  coefficient), the percentage of ECS images useful for diagnosis, and the diagnostic rate of non-cancerous lesions (specificity). Using a
prototype integrated endocytoscope, ECS diagnosis was made based on that
previously reported by Inoue et al. that defined ECA13 as a non-cancerous
lesion and ECA45 as a cancerous lesion.
RESULTS: Between May 2011 and January 2012, 72 patients were registered at 9
medical facilities. After excluding patients who declined to participate or patients
without an available specimen, 68 patients were enrolled. Mean tumor diameter
was 22.5 mm (range, 1060 mm). Fifty-five lesions were squamous cell carcinomas and 13 were HGIN. The diagnostic sensitivity and specificity were 88%
(95% CI, 77.294.5) and 100% (95% CI, 94.5100), respectively. The multirater  coefficient was 0.88 (95% CI, 0.800.96). In addition, 96% (95% CI,
87.699.1) of the ECS images were suitable for diagnosis.
CONCLUSION: In vivo ECS images provided high visualization, with high
sensitivity and high specificity in the diagnosis of esophageal squamous cell
carcinoma by pathologists. Given the high inter- observer agreement, ECS
appears to be useful for the real-time endoscopic histological diagnosis of esophageal squamous cell carcinoma.
Disclosure of Interest: None declared
P1287 LONG TERM OUTCOMES OF ENDOSCOPIC RESECTION FOR
SUPERFICIAL PHARYNGEAL CARCINOMAS AND EFFICACY OF
DOUBLE SCOPE ESD
T. Yoshio1,*, T. Tsuchida1, A. Ishiyama1, T. Hiraswa1, Y. Yamamoto1,
J. Fujisaki1
1
Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer
Reserch, Tokyo, Japan
Contact E-mail Address: toshiyuki.yoshio@jfcr.or.jp
INTRODUCTION: For recent advance in image enhanced endoscopy, such as
Narrow Band Imaging (NBI), we have more frequent opportunities for early
detection of superficial pharyngeal cancer (SPC). Endoscopic resection has
been proposed as a safe and effective treatment for SPC. We previously reported
endoscopic submucosal dissection (ESD) yielded higher rate of complete resection, and lower rate of local recurrence compared with endoscopic mucosal
resection (EMR). But ESD was more time consuming and more frequently complicated by laryngeal edema.
AIMS & METHODS: This study includes consecutive 113 patients treated by
endoscopic resection for SPC from October 2006 to December 2013 in one
referral cancer center. We treated SPC in first period by EMR, in second
period by conventional ESD (cESD) and in recent period by double scope
ESD (dsESD), in which we use second thin endoscopy for good counter traction.
We compared outcome of these three methods for short term outcome, and we
also showed long term outcome after endoscopic resection for SPC.
RESULTS: A total of 166 SPCs in 113 patients (Male: 100, Female: 13) were
treated by endoscopic resection (EMR: 55, cESD: 32, dsESD: 79). The size of
tumor was 18mm in average, which invaded to CIS/SEP/MP 108/57/1 respectively. All lesions were diagnosed squamous cell carcinoma. In dsESD, the procedure time was shortened compared to cESD (82 min vs 111 min, p50.05)
although the rate of laryngeal edema was not decreased (16% vs 9%). It may
be because we treat more complicated cases recently. En bloc resection rate and
complete resection rate for EMR, cESD and dsESD were 38%, 91%, 97%
(p50.01) and 29%, 63%, 84% (p50.01), respectively. Local recurrence was
detected in 3 cases after EMR and in 1 case after cESD. We treated by reEMR in 2 cases, by RT in 1 case and by surgery in 1 case. LN metastasis was
detected in 2 patients who were treated by surgical neck dissection. All the
salvage treatment was successfully performed. For long time outcome with
median followup period of 30 months (range 2-86 months), the overall survival
rate at 5 years was 88% (95%CI, 82-94), no patient died of SPC. The cumulative
development rate of multiple cancers in pharyngeal mucosal sites at 5 years was
27% (95%CI, 18-35). The pharynx was preserved in almost all the patients except
for one case who had surgery for local recurrence.
CONCLUSION: Here we showed dsESD was a superior method in treating
SPC, for achieving both en bloc and complete resection and reducing the procedure time. Endoscopic resection for SPC is organ preserving with no loss of
function and effective treatment with curative intent.
Disclosure of Interest: None declared
P1288 THE USEFULNESS AND COST-EFFECTIVENESS OF NONTARGETED GASTRIC BIOPSIES: ARE WE TOO FORWARD WITH
THE FORCEPS?
V. Gibson1,*, S. Needham1, M. Nayar1, N. Thompson1
1
Newcastle Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
Contact E-mail Address: gibsonvm@doctors.org.uk
INTRODUCTION: There are no agreed guidelines on indications for endoscopic
gastric biopsies. Taking and reporting gastric biopsies is costly, and there is a
shortage of trained pathologists in the UK. We investigated whether non-targeted gastric biopsies contributed to cost-effective and best patient management.
AIMS & METHODS: We retrospectively analyzed all endoscopic gastric biopsies taken across two teaching hospital sites in a 3-month period, 2/1/13-31/3/13;
details were obtained from our histopathology database. For each set of biopsies
taken we accessed our endoscopy database for patient demographics, reason for
endoscopy, appearance of gastric mucosa, Urease-based Helicobacter test

A483
(UBHT) result if obtained, and the grade of endoscopist (Consultant,
Registrar or Nurse Specialist). The electronic patient medical record was
reviewed to assess whether the biopsy changed the patients diagnosis or
management.
A targeted biopsy was defined as the presence at OGD of a polyp, ulcer or other
lesion documented in the report. Non-targeted biopsy was any other appearance,
including gastritis. The cost of biopsy included histopathology manpower and
processing costs. We looked separately at the cost of UBHT testing plus forceps
use.
RESULTS: During the 3-month period 2.265 OGDs were performed. 408
patients had gastric biopsies taken, resulting in 419 biopsy sets (some had multiple endoscopies), an overall biopsy rate of 18.5%. The age range was 18-97 years
(median 63 years). 22% of endoscopists were consultants, 33% registrars and
45% nurse specialists. Of the 419 biopsies, 43% were targeted (n 181) and 57%
were non-targeted (n 238).
Of the non-targeted biopsies, 0.8% (n 2) revealed an adenocarcinoma, both
these biopsies being from the same man who was under surveillance for a strong
family history of gastric carcinoma. 70% (n 168) showed a form of gastritis,
16% (n 37) showed H.pylori, and 13% (n 31) had normal histology. Of the
non-targeted biopsies, 94% (n 223) had no change to their diagnosis or management based on histology. 1% (n 2) had a gastrectomy, which was the one
man under surveillance, 3% (n 8) had eradication therapy based on histology
as UBHT was not performed, and 2% (n 6) had recommendation to GP to give
eradication therapy if not already given, as result of the UBHT test was unclear.
The cost of processing each biopsy set was 103.51. The annual cost of nontargeted biopsies where result did not change the management (n 223) was
92.330. This compared to 6.90 for each UBHT which would amount to only
6.154 per annum, creating an annual potential saving of 86.177.
CONCLUSION: The majority of non-targeted gastric biopsies did not contribute to patient management. Limiting non-targeted gastric biopsies could save
significant resources, as well as contributing to patient safety by limiting unnecessary biopsies.
Disclosure of Interest: None declared
P1289 A PILOT STUDY ON THE ENDOMICROSCOPIC ASSESSMENT
OF TUMOR EXTENSION IN BARRETTS ESOPHAGUSASSOCIATED NEOPLASIA PRIOR TO ENDOSCOPIC RESECTION
W. Dolak1,*, I. Mesteri2, R. Asari3, M. Preusser4, B. Tribl1, F. Wrba2,
S.F. Schoppmann3, M. Hejna4, M. Trauner1, M. Hafner1, A. Puspok1
1
Gastroenterology and Hepatology, 2Clinical Institute of Pathology, 3Surgery,
4
Oncology, MEDICAL UNIVERSITY OF VIENNA, Vienna, Austria
Contact E-mail Address: werner.dolak@meduniwien.ac.at
INTRODUCTION: Barretts esophagus (BE)-associated neoplasia can be treated by endoscopy, but accurate assessment of neoplastic lesions in BE is
challenging.
AIMS & METHODS: This study aimed to investigate the role of confocal laser
endomicroscopy (CLE) as an adjunct in the endoscopic treatment of BE-associated neoplasia by assessing lateral and sub-squamous tumor extension (SSTE).
In the context of a prospective single arm clinical pilot trial patients referred for
endoscopic resection of BE-associated neoplasia (high grade dysplasia and esophageal adenocarcinoma) underwent high-definition white light endoscopy with
narrow band imaging (NBI), followed by CLE-mapping of suspected neoplastic
lesions prior to endoscopic mucosal resection (EMR) or endoscopic submucosal
resection (ESD) depending on lesion size and anticipated histology.
RESULTS: In 7/38 (18%) patients CLE revealed additional neoplastic tissue as
compared to prior white light and NBI two concomitant lesions, two cases of
lateral tumor extension within the Barretts epithelium and three cases of previously undetected SSTE. Overall, en-bloc resection (tumor-free lateral margin)
was achieved in 28/34 neoplastic lesions (82%) and complete resection (tumorfree lateral and basal margins) in 21/34 neoplastic lesions (62%).
CONCLUSION: CLE-assisted endoscopic resection of BE-associated neoplasia
was safe and effective in this study, proved by a high additional diagnostic yield
of CLE (including visualization of occult SSTE) and a favorable en-bloc resection rate. The clinical value of CLE for assisting endoscopic therapy of BEassociated neoplasia deserves further evaluation in randomized controlled trials.
Disclosure of Interest: None declared
P1290 DIFFERENCE IN ENDOSCOPIC VACUUM-ASSISTED CLOSURE
(E-VAC) AND ESOPHAGEAL STENTING IN POSTSURGICAL
GASTROESOPHAGEAL LEAKAGE
Y.S. Jeong1,*, Y.S. Park1, J.Y. Lee1, Y.J. Choi1, Y.H. Kwon1, J.J. Hwang1,
K.C. Yoon1, A. Lee1, H.J. Lee1, H. Yoon1, C.M. Shin1, N. Kim1, D.H. Lee1
1
Internal medicine, Seoul National University Bundang Hospital, Seongnam,
Korea, Republic Of
Contact E-mail Address: nadapk@naver.com
INTRODUCTION: After esophagectomy or proximal gastrectomy, the reported
incidence of esophageal leakage ranges from 5% to almost 30%.
Gastroesophageal leakage increases morbidity and mortality rates, and several
treatments are used to control leakage such as approximation with endoclipping,
injection with tissue adhesive agents of histoacryl or fibrin glue, and endoscopic
implantation with self-expendable metal stents (SEMS). But these treatments
included endoluminal esophageal stent always could not be successful. E-VAC
therapy has recently been reported as an effective treatment modality for postsurgical anastomotic leakage.
AIMS & METHODS: The aims of this study are to show the relative differences
therapy of between esophageal stenting and E-VAC in treating postsurgical gastroesophageal leakage.

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United European Gastroenterology Journal 2(1S)

From 2006 to 2014, 13 patients treated with postsurgical gastroesophageal leakage in one medical center were evaluated (Male: Female 11: 2). Mean age were
71.4  5 years in E-VAC group and 63.1  6 years in stenting group. Among the
patients, 7 patients were treated by E-VAC. It has been proceeded endoscopically
placing drainage tube armed with size-adjusted sponge in the necrotic cavities,
and then applied continuous suction of mean pressure 125 mmHg. We changed
sponges and drain twice a week. On the other hand, 6 patients were treated by
covered SEMS. In stenting group, we removed the stent after 6 to 8 weeks
because of difficulty to remove stent due to tissue hyperplasia. The followings
were compared: clinical success rate, recurrence, mean closure time and mean
hospital stay.
RESULTS: The 7 patients treated with E-VAC were all treated successfully. Of
the 6 patients treated with stenting, 5 patients of them were treated successfully.
However, one patient in stenting group died of cancer progression without control of leakage by stenting. One patient in the stenting group after 69 days and
one patient in the E-VAC group after 63 days recurred. They were treated with
same method. Mean closure time was 17.8  17 days in E-VAC group and 16.8 
14 days in stenting group. Mean hospital stay were 33  30 days in E-VAC group
and 50.5  29 days in stenting group.
Table 1. Postsurgical gastroesophageal leakage treated by endoscopic vacuum
closure (E-VAC) and esophageal stenting: characteristics and treatment in 13
patients.

Age (year), mean  SD


Male / Female
Clinical Success Rate
Closure Time, mean  SD
Hospital Stay, mean  SD

E-VAC Group

Stenting Group

71.4  5
5/2
100 %
17.8  17
33  30

63.1  6
6/0
83 %
16.8  14
50.5  29

CONCLUSION: E-VAC therapy might be effective treatment option for postsurgical gastroesophageal leakage.
Disclosure of Interest: None declared
P1291 PROPER MUSCLE LAYER DAMAGE AFFECTS
HEALING AFTER GASTRIC ENDOSCOPIC SUBMUCOSAL
DISSECTION

ULCER

Y. Horikawa1,*, H. Mizutamari1, N. Mimori1, Y. Kato1, K. Shimazu1,


S. Ohkubo1
1
Gastroenterology, HIRAKA GENERAL HOSPITAL, Yokote city, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) is the established
therapy for superficial gastrointestinal neoplasms. As the larger ulcers associated
with ESD, management of artificial ulcers has become more important.
However, the relationship between ulcer healing factors and treatment is still
unclear.
AIMS & METHODS: We aimed to evaluate the ESD-related artificial ulcer
reduction ratio at 4 weeks to assess the factor associating with ulcer healing
after ESD that may lead to optimal treatments.
Between January 2009 and December 2013, a total of 375 lesions fulfilled the
expanded criteria for ESD. After exclusion, 328 lesions were divided into two
groups based on the ulcer reduction rate and analyzed: Group A, rate 590% and
Group B, rate 90%. These two groups were compared based on clinicopathological / endoscopic features, concomitant drugs, and treatments.
RESULTS: The ulcer reduction rate was significantly correlated with factors
related to the ESD procedure, i.e., procedure time, submucosal fibrosis, and
exposure of the proper muscle layer, in univariate analysis. Multivariate logistic
regression analysis showed that submucosal fibrosis (F2) (p 0.03; OR, 16.46;
95% CI, 1.31206.73) and exposure of the proper muscle layer (p 0.01; OR,
4.27; 95% CI, 2.048.92) were statistically significant predictors of delayed
healing.
CONCLUSION: This single-center retrospective study indicated that ESDinduced artificial ulcer healing was affected by submucosal fibrosis and exposure
of the proper muscle layer, which induced damage to the contraction of the
muscle layer.
Disclosure of Interest: None declared
P1292 LENS COATING WITH LIQUID CERAMICS IS USEFUL TO
MAINTAIN GOOD VISIBILITY FOR TRANSNASAL SMALLCALIBER ESOPHAGOGASTRODUODENOSCOPY
Y. Komazawa1,*, M. Yuki1, M. Kusunoki1, Y. Kobayashi1, S. Nakashima1,
T. Shizuku1
1
Izumo-city General Medical Center, Izumo, Japan
INTRODUCTION: Unsedated transnasal small-caliber esophagogastroduodenoscopy (TN-EGD) is used to examine the upper gastrointestinal tract and its
feasibility as compared to conventional transoral EGD has been shown.
However, a well-known limitation encountered with TN-EGD is poor image
quality as compared to conventional endoscopy due to the small size of the
CCD, while insufficient lens cleansing is related its small caliber water jet
nozzle. Poor visibility may affect endoscopic diagnostic accuracy, thus maintenance of good visibility is very important. Liquid ceramics coating is known to be
an effective means to keep glasses or lenses clean because of its hydrophilic
characteristic. Using a randomized prospective double-blind trial, we evaluated
the efficacy of lens coating with liquid ceramics for TN-EGD.

AIMS & METHODS: Basic in vitro (Study I) and randomized prospective clinical (Study II) studies were performed. Two groups of small-caliber endoscopes,
with and without ceramics coating (C- and N-group, respectively), were prepared. For lens coating, we applied a very small quantity of liquid ceramics
onto the lens, then completely wiped it off with gauze.
Study I: Endoscopic lenses in the C- and N-groups were soiled with lard oil and
washed using a lens cleansing procedure that consisted of air and subsequent
washing solution from the endoscopic jet nozzle, then photographs of a test chart
were obtained with them. Image quality was judged by 3 experts who had no
knowledge of grouping.
Study II: We randomly assigned 115 patients who underwent TN-EGD to the Cand N-groups. TN-EGD procedures were performed by 3 expert endoscopists,
who judged the level of endoscopic visibility using a 5-grade visual analogue scale
after TN-EGD. This study was approved by the ethics committee of Izomo City
General Medical Center. Written informed consent was obtained from all
participants.
RESULTS: In Study I, photographic image quality was significantly better in the
C-group as compared to the N-group (P50.05). In Study II, the level of endoscopic visibility in the C-group was also significantly superior (P50.05).
CONCLUSION: For EGD with transnasal small-caliber endoscopy, lens coating
with liquid ceramics may be useful to maintain a good visual condition and
improve diagnostic accuracy.
Disclosure of Interest: None declared
P1293 THE EFFIECTIVENESS OF CHROMOENDOSCOPIC METHOD
USING AN ACETIC ACIDINDIGOCARMINE MIXTURE FOR
SUPERFICIAL FLAT-TYPE (0-IIB) EARLY GASTRIC CANCERS
Y. Kawahara1,*, H. Okada1, S. Kawano1, K. Hori1, T. Tsuzuki2, M. Kita2,
H. Kanzaki2, Y. Kohno2, K. Miura2, K. Yamamoto2
1
Department of Endoscopy, 2Department of gastroenterology and hepatology,
Okayama University, Okayama, Japan
Contact E-mail Address: yoshirok@md.okayama-u.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been established as a standard treatment for early gastric cancer (EGC) in Japan. The
advantage of ESD is that it enables the en-block resection of large lesions, thereby
allowing the accurate pathological evaluation of the resected lesions and avoidance of recurrence after piecemeal resection. Therefore, it is important to accurately determine the extent of gastric cancer invasion and resect the cancer.
However, in superficial flat-type gastric cancer (0-IIb type), it is often difficult
to determine the extent of tumor invasion.
AIMS & METHODS: We previously reported the effectiveness of chromoendoscopic method using an acetic acidindigo carmine mixture (AIM) in one hundred gastric cancer cases. The aim of the present study was to estimate the
accuracy of this chromoendoscopic method using an acetic acidindigo carmine
mixture (AIM) in superficial flat-type cases.
Studied were 112 flat-type EGC lesions. EGC were initially observed by white
light (WL) after which indigo carmine (IC) solution was sprinkled onto the
gastric mucosa. Images by WL and IC observation were recorded by a digital
filing system. After washing away IC solution with water, AIM solution was
sprinkled onto the gastric mucosa and images were recorded. Margin lines of
EGC determined by each observation were drawn on recorded images by graphic
software for comparison with resected specimens. First, diagnostic accuracy of
the endoscopic images with each modality was independently evaluated with
regard to the recognition of the entire contact border around the lesions by
two endoscopists who have extensive experience in the diagnosis and management of EGC. Second, the agreements between the endoscopic views with efficient modality were evaluated and, finally, the evaluations of the two
endoscopists were compared and, in case of any conflicts in the findings, an
agreement was reached through discussion, and margin lines of EGC determined
by each observation were drawn on the recorded images by graphic software.
After lines were similarly drawn on images of resected specimens, the extent of
the lesions was compared with that determined by endoscopic images.
RESULTS: We found that AIM chromoendoscopy enabled us to achieve a very
clear enhanced visualization of flat-type EGC lesions. Diagnostic accuracy of
WL, IC, and AIM observations were 23.0%(n 26), 54%(n 60) and
82%(n 92), respectively. No adverse events occurred with the AIM method.
Diagnostic accuracy of AIM observation was significantly higher than that by
WL observation (P 5 0.0001) and IC observation (P 5 0.0001).
CONCLUSION: We can achieve clearer visualization of the tumor extent by the
AIM chromoendoscopy than by the IC method.
Disclosure of Interest: None declared
P1294 THE
RESULT
OF
GLASGOW-BLATCHFORD
COMPARED TO OTHER SYSTEMS IN ACUTE UPPER
GASTROINTESTINAL BLEEDING

SCORE

Y.S. Shin1,*, D.H. Kang1, H.W. Kim1, C.W. Choi1, S.B. Park1, B.J. Song1,
S.J. Kim1, Y.Y. Choi1, D.K. Kang1, H.K. Lim1, S.K. Oh1, H.S. Nam1
1
Division of Gastroenterology, Department of Internal Medicine, School of
Medicine Pusan National University, Pusan National University Yangsan Hospital,
Yangsan-si, Korea, Republic Of
Contact E-mail Address: shadam@naver.com
INTRODUCTION: Upper gastrointestinal bleeding has been a major cause of
hospital admission and mortality throughout the world. Therefore prediction of
the risk in the patients with acute upper gastrointestinal bleeding (AUGIB) is
important subject. Several scoring systems have been used to identify patients
with acute upper gastrointestinal bleeding who are at a high risk. GlasgowBlatchford score (GBS) predicts the need for medical intervention (such as

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United European Gastroenterology Journal 2(1S)


blood transfusion or endoscopy) by using the results of blood tests and vital sign.
Rockall score (RS) is calculated by endoscopic finding, age, comorbidity, vital
sign and used to predict outcome. But this scoring system has disadvantage of
complicated calculation.
Recently AIMS65 is the simple risk scoring system that identified five factors
such as serum albumin, international normalized ratio, altered mental status,
systolic blood pressure and age. We studied retrospectively the usefulness of
these scoring systems and compared these systems. We hope that our study
will help for assessing the need for clinical intervention, re-bleeding and death
in cases of AUGIB.
AIMS & METHODS: We found 384 patients who underwent urgent endoscopy
due to UGIB from December 2008 to August 2013 at Pusan national university
Yangsan Hospital. Of these patients, 223 patients were satisfied with UGIB and
included in this study. All 223 patients were assessed by GBS, RS and AIMS65.
At the same time the patients who needed the clinical intervention or died inhospital within 30 days were defined as unfavorable outcome patients. Then the
result of each scoring system was compared with clinical outcome.
RESULTS: Overall in-hospital mortality was 2.2% (5/223). In our total 223
patients, 43.9% (98/223) were classfied as unfavorable outcome patients. The
re-bleeding rate was shown as 9.4% (21/223). Compared to these scoring
system, there was little significant difference in predicting the need of therapeutic
intervention and death. But GBS was significantly elevated in unfavorable outcome patients (p 0.0119). Also GBS was superior to the other scores for predicting the need for packed red blood cell transfusions (p 0.0134).
CONCLUSION: In acute upper gastrointestinal bleeding, GBS, RS and AIMS65
scoring system can predict need for intervention and unfavorable clinical outcome in AUGIB. GBS was more advantageous to the prediction of blood transfusion. On the other hand, these systems were similar to predict clinical outcome.
Disclosure of Interest: None declared
P1295 EVALUATION OF SAFETY OF ENDOSCOPIC SUBMUCOSAL
DISSECTION WITHOUT CESSATION OF ANTITHROMBOTIC
AGENTS
Y. Mashimo1,*, K. Shudou1, S. Arai1, R. Shomei1
Gastroenterology, Saitama Medical University International Medical Center,
Hidaka-shi, Japan
Contact E-mail Address: ymashimo@saitama-med.ac.jp
1

INTRODUCTION: New guidelines for gastroenterological endoscopy considering the associated risk of thrombosis were revised in 2012, by the Japan
Gastroenterological Endoscopy Society. The new edition of the guidelines
includes discussions of gastroenterological hemorrhage associated with continuation of antithrombotic therapy, as well as thromboembolism associated with
withdrawal of antithrombotic therapy. Therefore, we aimed to assess the feasibility of endoscopic submucosal dissection (ESD) without cessation of antithrombotic agents.
AIMS & METHODS: This was a retrospective study from a single institution.
This study enrolled 330 neoplasms (47 esophageal neoplasms, 161 gastric neoplasms and 122 colorectal neoplasms) in 310 patient who had ESD from April
2013 to May 2014. 75 patients who were receiving antithrombotic agents because
of their high-risk status for a thromboembolic event (after implantation of coronary stent, after valve replacement, or a previous history of thromboembolic
event or heart failure due to atrial fibrillation) were involved. We evaluated the
rate of post-ESD severe bleeding complications (overt hematemesis/hematochezia, a drop of hemoglobin42g/dL from baseline, or requirement of endoscopic
hemostasis, and/or transfusion).
RESULTS: Of 310 patients, 58 took antiplatelet agent, among whom 13 continued aspirin, 4 replaced with heparin. 26 took anticoagulant agent, among
whom 22 replaced with heparin. Of 310 patients, 9 took antiplatelet agent and
anticoagulant agent in combination therapy. This 9 cases was performed ESD
with continued aspirin under replacement of heparin. Post-ESD bleeding
occurred in 4 subjects (1.2%) including 2 from the continued aspirin group, 1
from the withdrawal antiplatelet agent group who had a renal dysfunction, and 1
from the no-antithrombotic agents group who was big specimen diameter.
Univariate analysis revealed antiplatelet therapy (OR 13.69, 95%CI: 1.24348.24, p 0.0036) was associated with post-ESD bleeding, but continued aspirin
(OR 8.00, 95%CI: 0.49-247.40, p 0.059) was not statistically significant. All
post-ESD bleeding cases were treated successfully by endoscopic hemostasis.
Emergency surgery was not required in any of the cases. Blood transfusion
was needed in 1 patient (0.3%). Among 75 subject who had antithrombotic
therapy, 2 developed acute cerebral infection (2.6%) including 1 from the continued aspirin group, 1 from the withdrawal antiplatelet agent group. No event
occur in the anticoagulant group replaced with heparin.
CONCLUSION: ESD without cessation of antithrombotic agents, can be acceptable if performed carefully for patients with antiplatelet therapy.
REFERENCES
Fujimoto K, Fujishiro M et al. Guidelines for gastroenterological endoscopy in
patients undergoing antithorombotic treatment. Dig Endosc 2014; 26: 1-14.
Disclosure of Interest: None declared

P1296 DETECTION OF COLONIC POLYPOID LESIONS BY PET OR


PET-CT IN PHYSICAL CHECK-UP POPULATIONS
S. Park1,*
1
Center for Health Promotion, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: semi2010.park@samsung.com
INTRODUCTION: A 18-Fluorodeoxyglucose positron emission tomography
(FDG-PET) or PET-computed tomography (PET-CT) is used clinically detect
malignant lesions. The efficacy of PET or PET-CT comparing colonoscopy to
detect colonic polypoid lesions including premalignant adenomas and colon cancers is not well defined in large number of populations.
AIMS & METHODS: The aim of this study is to evaluate the efficacy of PET or
PET-CT comparing standard colonoscopy to detect colonic polypoid lesions in
physical check-up examinees.
Methods: A total of 4063 persons with synchronous evaluation of PET or PETCT with colonoscopy were enrolled between 2003 and 2010 for the physical
checkup at our single health promotion center.
RESULTS: Colonoscopy with biopsy confirmed the adenomas and cancers in
1212 of 4063 examinees. The focal FDG uptake by PET or PET-CT showed in 19
examinees of positive colonoscopic findings. Sensitivity, specificity, positive predictive value, and negative predictive value to detect colonic polypoid lesions
including adenomas and cancers by PET or PET-CT comparing with standard
colonoscopy were 1.6%, 99%, 82%, and 70%, respectively. The sensitivity of
PET or PET-CT according to the adenoma size was increased (1.7% for 1-10mm,
3.3% for 11-20mm, 40% for 420mm). A total of 8 patients had high grade
dysplasia (n 1), rectal neuroendocrine tumors (n 5) or colon cancers (n 3).
Among them, only 1 patient with 5cm sized advanced colon cancer showed
FDG-PET uptake.
CONCLUSION: In physical check-up examinees, a PET or PET-CT comparing
with conventional colonoscopy did not detect colonic advanced adenomas, rectal
neuroendocrine tumor (rectal carcinoid) or early colon cancers smaller than 1 cm.
Therefore, detection of colonic polypoid lesions except advanced colon cancers
by PET or PET-CT was insufficient in physical check-up populations.
REFERENCES
1. Weston BR, et al., Ability of integrated positron emission and computed
tomography to detect significant colonic pathology: the experience of a tertiary
cancer center. Cancer 2010; 116: 1454-1461.
2. Friedland S, et al. 18-Fluorodeoxyglucose positron emission tomography has
limited sensitivity for colonic adenoma and early stage colon cancer. Gastrointest
Endosc 2005; 61: 395-400.
3. van Kouwen MC, et al. 2-(18F)-Fluoro-2-Deoxy-D-Glucose positron emission
tomography detects clinical relevant adenomas of the colon: a prospective study.
J Clin Oncol 2005; 23: 3713-3717.
Disclosure of Interest: None declared
P1297 WATER EXCHANGE ATTENUATES REAL-TIME INSERTION
PAIN AND POTENTIALLY ENHANCES COST SAVINGS BY
PROMOTING COMPLETION OF UNSEDATED COLONOSCOPY
S. Cadoni1,*, S. Sanna2, P. Gallittu1, M. Argiolas2, V. Fanari2, M.L. Porcedda2,
M. Erriu3, F.W. Leung4
1
Digestive Endoscopy Unit, P. O. S. Barbara, Iglesias (CI), 2Digestive Endoscopy
Unit, P. O. N. S. di Bonaria, S. Gavino Monerale (SV), 3Department of Surgery,
University of Cagliari, Cagliari, Italy, 4Gastroenterology, Veterans Affairs, Los
Angeles, United States
Contact E-mail Address: cadonisergio@gmail.com
INTRODUCTION: We tested the hypothesis that water exchange (WE) produces significantly lower insertion pain scores than air insufflation (AI) and
water immersion (WI).
AIMS & METHODS: A 2-center RCT stratified enrolment of diagnostic and
screening patients given on-demand sedation. Primary outcome: real-time maximum insertion pain recorded by an unblinded observer. Before discharge
patients reported recalled pain to a blinded observer and guessed the method
used.
RESULTS: 576 patients were randomized to AI (n 193), WI (n 197), WE
(n 186). Patients correct guesses were 533%. Table 1 shows the primary outcome and recalled pain (Visual analogue scale: 0 none, 10 worst).
Comparison of primary outcome and recalled pain in unsedated patients
(Pearson correlation 0.6, p5.0005) confirmed its validation. Uniquely, WE has
no significant investigator differences in mean pain score during insertion
(p5.48), and lower standard deviation. Recalled pain did not reveal differences
in the three groups. Individual colonoscopists real-time pain scores, however,
were susceptible to type II errors due to small numbers. Since adoption of WE,
85% of colonoscopies are unsedated. Immediate return to routine activities
after successful unsedated colonoscopy was feasible. Estimates of resources
saved on-site: patients, E 2.074; nursing time E 3.121; pharmacy expenses, E
194. At home, patients E 89.731. Table 1: Investigators real-time and recalled
pain, mean (95% CI). M, maximum; R, recalled; CI, confidence interval; SD,
standard deviation. 6, ANOVA.

A486

United European Gastroenterology Journal 2(1S)

Table to abstract P1297


Investigators Pain WE
1

M
R

M
R

M
R

M
R

M
R

M
R

Within group,
P value6 (SD)

WI

AI

P 6

2.2 (1.6-2.8)
4.8 (4.0-5.6)
5.5 (4.8-6.2)
50.0005
1.9 (1.4-2.4)
3.3 (2.4-4.1)
3.9 (3.2-4.6)
50.0005
n 46
n 40
n 47
3.0 (2.3-3.7)
3.5 (2.7-4.2)
4.3 (3.8-5.2)
0.048
2.2 (1.7-2.8)
2.8 (2.1-3.5)
2.8 (2.0-3.6)
0.386
n 46
n 43
n 48
2.3 (1.0-3.6)
2.3 (1.0-3.6)
4.0 (2.9-5.1)
0.096
0.5 (0.4-1.4)
0.1 (0.1-0.3)
0.5 (0.1-1.0)
0.486
n 14
n 19
n 13
2.2 (0.8-3.6)
2.3 (1.6-2.9)
2.8 (2.0-3.5)
0.574
0.2 (0.1-0.6)
0.1 (0.1-0.3)
0.2 (0.1-0.4)
0.766
n 28
n 12
n 29
2.9 (1.8-4.0)
3.7 (2.3-5.1)
3.5 (2.2-4.8)
0.699
0.7 (0.1-1.5)
0.8 (0.1-1.6)
0.3 (0.1-0.8)
0.509
n 13
n 16
n 20
2.4 (1.6-3.2)
2.6 (1.5-3.7)
3.4 (2.4-4.5)
0.255
0.2 (0.1-0.4)
0.2 (0.1-0.4)
0.6 (0.1-1.2)
0.066
n 23
n 20
n 33
M 0.48 (2.1)
M 50.0005 (2.6) M 50.0005 (2.7)
R 50.0005 (1.7) R 50.0005 (2.3) R 50.0005 (2.5)

CONCLUSION: This head-to-head comparison shows WE to have the lowest


real-time insertion pain score, high repeatability and reproducibility by endoscopists with otherwise significantly different pain scores during insertion when
using AI or WI. WE equalizes differences in method-related real-time pain
among investigators. Promotion of the unsedated option lessens the burden of
sedation on patients on-site and at home. Direct (nursing staff time) and indirect
(patients) cost savings appear to be plausible. (NCT01781650, 01780818)
Disclosure of Interest: None declared
P1298 SHOULD PATIENTS WITH RECTAL BLEEDING HAVING A
FLEXIBLE SIGMOIDOSCOPY COME FULLY PREPARED FOR A
COLONOSCOPY?
S. Subramaniam1,*, K. Besherdas1
1
Department of Gastroenterology, Barnet & Chase Farm Hospitals NHS Trust,
London, United Kingdom
Contact E-mail Address: sharmila.subramaniam@nhs.net
INTRODUCTION: The vast majority of patients referred for investigation of
rectal bleeding have benign anal disease or proctitis. Flexible sigmoidoscopy (FS)
has been widely used for the investigation of patients with rectal bleeding with
same day single phospho-soda enema preparation prior to the examination.
However, conversion to full colonoscopy is warranted if adenomatous polyps
or colon cancer is detected to exclude synchronous lesions. We hypothesise that
as the patients age at presentation of rectal bleeding increases, the prevalence of
adenomatous polyps and colon cancer increases and thereby the requirement for
evaluation of the entire colon. If this is established then we should recommend
that patients undergoing FS for rectal bleeding should be scoped with full bowel
preparation and converted to a colonoscopy if polyp or cancer is detected at the
time of FS.
AIMS & METHODS: The aim of the study was to assess the diagnostic yield of
FS in detecting colon cancer/polyp in patients of different ages presenting with
rectal bleeding. A single centre, retrospective analysis of patients with rectal
bleeding investigated with FS in a district general hospital from north London
was performed. The patients were identified using the Unisoft Endoscopy reporting software over a period from June 2006 to March 2014. Data obtained during
the study period was scrutinised for diagnosis and whether further full colonic
imaging was indicated as judged by diagnosis of colon cancer or adenomatous
polyp.
RESULTS: 1406 FS were performed in the study period. The table below demonstrates the findings at FS in patients with rectal bleeding according to age category. 25% of patients over 45 years of age have a cancer or polyp diagnosed that
requires further full colonic imaging.
Age (years)
Number of procedures
Normal
Normal (%)
Cancer
Cancer (%)
Polyp
Polyp (%)
Other benign cause eg
colitis/haemorrhoids
Other benign cause (%)

545
224
90
40
0
0
27
12
91

445
1179
308
26
67
5
220
19
677

455
944
223
23
64
7
192
20
554

465
666
126
19
56
9
144
22
419

475
404
72
18
40
10
85
21
237

485
144
34
24
12
8
21
15
89

495
12
3
25
0
0
2
17
7

40

57

59

63

58

62

58

CONCLUSION: 25% of patients over 45 years of age undergoing FS for rectal


bleeding have a colon cancer or polyp diagnosed that require further colonic
imaging. Preparing all patients for a full colonoscopy at the time of attendance
for FS and conversion to colonoscopy if a polyp or cancer is detected would save
reattendance in 25% of patients over the age of 45 for rectal bleeding. The
prevalence of polyps and cancer however is low in patients under 45 years of
age and these patients could continue to have FS with enema preparation just
prior to the procedure.
Disclosure of Interest: None declared
P1299 IS THE LOCATION OF THE POLYP IN THE COLON A RISK
FACTOR FOR THE OCCURRENCE OF COMPLICATIONS
FOLLOWING ENDOSCOPIC MUCOSAL RESECTION?
S. Khater1,*, M. Barret1, G. Rahmi1, G. Malamut1, E. Samaha1, L. Abbes1,
J.M. Canard1, C. Cellier1
1
Hopital Europeen Georges Pompidou, paris, France
INTRODUCTION: Endoscopic mucosal resection (EMR) is a commonly used
technique to remove colorectal polyps. Complications such as bleeding and perforation can occur, with rates reported reaching 10% in some series. Some risk
factors for the occurrence of these complications have been identified in the
literature, such as the size of the polyp, its shape (flat or sessile), the presence
of comorbid conditions and the use of antiplatelet and anticoagulant drugs.
Some studies also found that the location of the polyp can be a risk factor.
AIMS & METHODS: The aim of this study is to determine if the location of the
polyp in the colon is a risk factor for the occurrence of complications after EMR
of supracentimetric polyps. Clinical and endoscopic data were collected by retrospective methods for all patients who underwent endoscopic resection of polyps
of one centimeter or more from January 2001 to march 2013 at the Georges
Pompidou European Hospital in Paris. A univariate and a multivariate analysis
were used to identify risk factors for the development of complications.
RESULTS: 378 polyps were resected in 263 patients (mean age: 65.2 years [2992], 57.9% of men). The mean size of the polyps was 17.2 mm. 67.2% were
sessile, 20.9% flat and 11.9% pedunculated. Polyps were located in the right
colon (proximal to the left colic flexure) in 62.4% of cases and in the left
colon and rectum in 37.6% of cases. Endoscopic clip placement after EMR
was performed in 53.7% of cases. 7.9% of patients were taking anticoagulant
drugs and 19.8% were taking antiplatelet therapy. Complications after EMR
occurred in 7.6% (29/378) of cases; there was 4 perforations (1.1%) and 25
hemorrhage (6.6%). The clinical outcome was favorable with conservative or
endoscopic treatment in 96.5% of cases; only one patient had a surgery following
a perforation. No death occurred. A complication was observed in 8.4% (20/236)
and 6.3% (9/142) of cases following polyp resection in the right colon and the left
colon, respectively (p 0.6). A perforation occurred in 1.3% (3/236) and 0.7%
(1/142) in the right and in the left colon respectively (p 1). The rate of bleeding
after EMR was 7.2% (17/236) in the right colon and 5.6% (8/142) in the left
colon (p 0.6), respectively. The univariate and the multivariate analysis showed
that the only factor that was significantly associated with the occurrence of
complications following EMR was the use of anticoagulant drugs (p50.0001).
However, the location of the polyp, its size, its shape, the use of clips, the age of
the patient or the use of antiplatelet drugs were not predictive factors for
complications.
CONCLUSION: In this study, the location of the polyp in the right or left colon
doesnt seem to be a risk factor for the occurrence of complications following
EMR of supracentimetric polyps.
Disclosure of Interest: None declared
P1300 THE UTILITY OF ENDOCYTOSCOPY, WHICH CAN PROVIDE
ADDITIONAL DIAGNOSTIC VALUE TO MAGNIFYING
CHROMOENDOSCOPY FOR PREDICTING A MASSIVELY
INVASIVE COLORECTAL CANCER: A RETROSPECTIVE
COMPARATIVE STUDY
S.-E. Kudo1,*, S. Kataoka1, Y. Mori1, K. Wakamura1, Y. Kouyama1, Y.S. Ogawa1, K. Igarashi1, M. Kutsukawa1, K.-I. Takeda1, K. I. Ichimasa1,
M. Misawa1, T. Kudo1, T. Hayashi1, H. Miyachi1, H. Inoue1
1
Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama-shi,
Japan
Contact E-mail Address: shinichikataok@hotmail.com
INTRODUCTION: Magnifying chromoendoscopy (MC) is a Japanese standard
diagnostic method for endoscopically predicting a massively invasive submucosal
colorectal cancer (SMm) which has the possibility of metastasis[1]. Recently
developed ultra-magnifying (450-fold) endoscopy endocytoscopy (EC) was
also reported to be useful for predicting SMm.[2]
AIMS & METHODS: The aim was to assess the additional value of EC to MC
for diagnosing colorectal lesions. Consecutive lesions which were resected after
colonoscopical examination with use of EC were enrolled in this retrospective
study between May 2005 and March 2013 in Showa University Northern
Yokohama Hospital. Advanced-type lesions were excluded from the analysis.
At colonoscopy, the on-site endoscopists diagnosed each lesion on the basis of
MCEC findings after assessing it on the basis of MC findings alone. The
diagnostic abilities of MCEC were compared to those of MC alone with reference to the histopathology of the resected specimens. As main outcome measure,
the diagnostic abilities of predicting both neoplastic change and SMm were
evaluated according to Kudos pit pattern classification[1] and the EC
classification[2].
RESULTS: Overall, 524 patients with 578 specimens were available for analysis.
Of them, there were 71 non-neoplastic lesions,279 dysplasias, 15 slightly invasive
submucosal cancers, and 94 SMms. The main results were shown in the table.

A487

United European Gastroenterology Journal 2(1S)


Table to abstract P1300

Diagnostic ability of predicting.neoplastic change


Sensitivity
Specificity
Accuracy
deeper than SMm
Sensitivity
Specificity
Accuracy

P1302 FEASIBILITY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL


DISSECTION FOR LARGE COLORECTAL TUMORS
MC alone

MCEC

Pvalue
(McNemarstest)

93.0%
97.4%
96.9%

93.0%
96.8%
96.4%

1.000
0.343
0.032

75.5%
97.9%
94.3%

81.0%
99.2%
96.4%

0.070
0.041
0.002

CONCLUSION: Though MC alone has feasible diagnostic ability for predicting


both neoplastic change and SMm, observation with EC can provide additional
diagnostic value to MC for predicting SMm with substantial reliability.
REFERENCES
[1]Kudo S, et al. J Clin Pathol 1994; 47: 880-885.
[2]Kudo S, et al. Endoscopy 2011; 43: 869-875.
Disclosure of Interest: None declared
P1301 COMPARISON BETWEEN CONVENTIONAL SCOPES AND
SHORT TYPE DOUBLE BALLOON ENDOSCOPES WHEN USING
ESD FOR THE TUMOR LOCATED IN THE PROXIMAL COLON
S. Katsuki1,*, T. Fujita1, K. Takanashi1, E. Waga1, K. Kitaoka1, Y. Komatsu 1,
H. Ohta2, Y. Sato3
1
Center of Gastroenterology, OTARU EKISAIKAI HOSPITAL, Otaru,
2
Gastroenterology, Sapporo Orthopedics and cardiovascular Hospital, 3Fourth
Department of internal Medicine, Sapporo Medical University School of medicine,
Sapporo, Japan
Contact E-mail Address: sinichi-katuki@otaru-ekisaikai.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) method for the
colorectal neoplasm has been spread all over the world in recent years.
However there arent so many medical facilities where the method is carried
out completely.
There are 4 reasons - First, there are a lot of various shapes of colons. Second, the
colon wall is very thin. Third, the feces in the colon contain much bacteria.
Fourth, sometimes there are adhesion or malformation in the patients colon.
Furthermore once perforation arises, there is a possibility of emergency open
surgery. Moreover, with the tumor in the proximal colon, ESD method becomes
more difficult. In order to solve those difficulties, we basically employ short type
DBE.
AIMS & METHODS: Our purpose was to evaluate the efficacy and safety of
ESD by using short type DBE for the tumor located in the proximal colon in a
prospective, randomized trial.
We treated the tumor located in the proximal colon using two types of scopes, the
Conventional Scopes (CS) and Double Balloon Endoscopes (DBE). CS we used
were EC450RD5M (Fujifilm Co., Tokyo, Japan), and PCF-Q260JL/I (Olympus
Co., Tokyo, Japan) and DBE we used was EC450BI5 or EN530BI (Fujifilm Co.,
Tokyo, Japan).
The period of the evaluation was from Nov.2012 to Mar.2014.
We divided 70 cases into two groups: Group A (treated by CS), and Group B
(treated by DBE). We examined the reaching time, the treatment time, the completing rate, the negative rate of cut end (lateral and vertical), the average hospitalization, the average cost and the perforation rate.
RESULTS: There were 32 cases in Group A and 38 cases in Group B. The
number of ESD in the Group A were 32 lesions and Group B were 40 lesions.
The reaching time to the cecum were 8.43.9 min. in the Group A and 5.32.2
min. in the Group B. The treatment time were 41.314.4 min. in the Group A
and 26.29.1 min. in the Group B. The negative rate of cut end (lateral and
vertical) were 87.5% (28/32) in the Group A and 100% (40/40) in the Group B.
The perforation rate was 3.1% (1/32) in the Group A and no cases in the
Group B.
The average cost were 591.7 EUR. in the Group A and 657.7 EUR. in the Group
B (converted by EUR.-JPY. as of April 19th)
CONCLUSION: The cost spent on DBE is slightly more expensive than that
spent on CS. However, given the low rate of perforation, the shortened time
spent on ESD, and the accuracy of en-block resection, ESD by using DBE is
beneficial for the patients who have the tumor in his or her proximal colon.
Disclosure of Interest: S. Katsuki: None, T. Fujita: None, K. Takanashi: None, E.
Waga: None, K. Kitaoka: None, Y. Komatsu: None, H. Ohta: None, Y. Sato:
None

S. Tanaka1,*, T. Toyonaga1, Y. Ohara2, T. Yoshizaki1, F. Kawara1, T. Ishida2,


N. Hoshi2, Y. Morita2, T. Azuma2
1
Department of Endoscopy, Kobe University Hospital, 2Division of
Gastroenterology, Department of Internal Medicine, Graduate School of Medicine,
Kobe University, Kobe, Japan
Contact E-mail Address: tanakas@med.kobe-u.ac.jp
INTRODUCTION: Recently, endoscopic submucosal dissection (ESD) has been
applied for superficial colorectal neoplasms and the number of publications
about it has been increasing, but little is known about the outcomes of colorectal
ESD for the lesions over 50 mm.
AIMS & METHODS: In this study, we evaluated the feasibility and safety of
colorectal ESD for the lesions over 50 mm compared to the lesions less than 50
mm. A total of 674 superficial colorectal neoplasms in 629 patients treated by
ESD at Kobe University Hospital from July 2008 to July 2013 were included in
the analysis. Among these lesions, 28 residual or local recurrent lesions after
previous treatment were excluded, as result, 646 lesions were analyzed for this
study. Resected lesions were divided into two groups, large lesion group (tumor
size 50 mm) and small lesion group (tumor size 550 mm).
RESULTS: Of 646 lesions included in this study, 530 lesions were classified into
the small lesion group and 116 were into the large lesion group. The median
operation time (range) in the large lesion group was 109 (37-596) minutes, and it
was 55 (6-248) minutes in the small lesion group. Median procedure speed (range)
in the large lesion group was 0.28 (0.06-0.83) cm2/minutes, and it was 0.19 (0.040.83) cm2/minutes in the small lesion group. The en bloc resection rate and the
curative resection rate in the small lesion group was 98.7% and 96.0%, and those
were 95.7% and 91.4% in the large lesion group, respectively. In terms of adverse
events, perforation, muscle damage and postoperative bleeding occurred at similar frequency in both groups. To investigate further, the outcome of ESD
depends on the part of the bowel (rectum, left colon and right colon) was analyzed. The median operation time was significantly longer in the large lesion
group and the median procedure speed was significantly faster in the large
lesion group in all bowel parts. The en bloc resection rate and the curative
resection rate were not significantly different between two groups in either locations. In terms of adverse events, significant differences were not found in either
locations.
CONCLUSION: ESD on colorectal lesions over 50 mm takes longer operation
time, however, it is resected time effectively without increasing the risk of adverse
events compared to smaller lesions by ESD.
Disclosure of Interest: None declared
P1303 ENDOSCOPIC DIAGNOSIS AND CLINICAL MANAGEMENT OF
SESSILE SERRATED ADENOMA/POLYP
S. Ishigooka1,*, S.-I. Ozawa1, Y. Matsuo1, K. Hosoya1, M. Yamashita1, Y. Sato1,
T. Maehata1, H. Yasuda1, F. Itoh1
1
Gastroenterology and Hepatology, St. Marianna University School of Medicine,
Kawasaki, Japan
Contact E-mail Address: s2 ishigouoka@marianna-u.ac.jp
INTRODUCTION: Sessile serrated adenoma/polyp (SSA/Ps) are known to be
precursors of sporadic cancers (CRCs) with microsatellite instability (MSI).
Consequently, colonoscopic identification of SSA/Ps has important implications
for preventing CRCs. Although we reported evaluation of magnifying colonoscopy in the diagnosis of serrated polyps (World J gastroenterol 2012 August 28;
18 (32)), accurate endoscopic diagnosis is often difficult.
AIMS & METHODS: Our aim is the establishment of more accurate diagnostic
criteria and examination of the clinical management for the present.
This study examined 191 serrated lesions excised in our hospital as suspected
serrated lesions after magnified observation between January 2008 and March
2014. Patient characteristics (sex, age), conventional colonoscopic findings (location, size, morphology, color, mucin) and magnified colonoscopic findings (pit
pattern diagnosis) were compared with histopathological diagnosis. Surface
microstructures were analyzed using magnifying endoscopy.
RESULTS: Lesions comprised 57 HPs (29.8%) and 134 SSA/Ps (70.2%: complicated with cancer in 8 cases).
Conventional colonoscopy showed that SSA/Ps were characterized by existence
in the right side of colon [P 5 0.001], flat-elevated lesion [P 5 0.001], normalcolored or pale in color of mucosa [P 5 0.001], and with large amounts of mucin
[P 5 0.001]. Magnified colonoscopy showed the type II-open shaped (type II-O)
pit pattern as characteristic of SSA/Ps [PPV 92.4%, specificity 86%]. All cancer
cases were observed only in female. Cancer was also present in 8 lesions, in all of
which a type III or IV or V pit pattern was also present within the same lesion.
CONCLUSION: In our study, we have understood to be able diagnose as SSA/
P, which indicated both flat shaped and type II-O pit pattern, and SSA/Ps which
had malignant potential indicated another pit patterns other than type II-O pit
pattern. Consequently, we should consider excise not only large lesions, also
lesions that have Type II-O pit pattern including the Type III, IV, V pit pattern.
Disclosure of Interest: None declared

A488
P1304 CLINICOPATHOLOGICAL
CHARACTERISTICS
LATERALLY SPREADING TUMORS WITH SKIRT

United European Gastroenterology Journal 2(1S)


OF

S. Osera1,*, H. Ikematsu1, T. Kadota1, M. Imajoh1, T. Kato1, H. Morimoto1,


T. Odagaki1, Y. Oono1, T. Yano1, K. Kaneko1
1
Department of Gastroenterology, Endoscopy Division, National Cancer Center
Hospital East, Kashiwa, Chiba, Japan
Contact E-mail Address: shou0122@hotmail.com
INTRODUCTION: Many laterally spreading tumors (LST) are detected in the
rectum while the frequency of hyperplasia is high and there are few conventional
small adenoma lesions. A hardly elevated, flat lesion with wide pits has been
often observed at the margin of LST. This lesion has been termed skirt. We
have reported that LST with skirt were located in the rectum, however, the
clinicopathological characteristics of LST with skirt have not been clarified.
AIMS & METHODS: The aim of this retrospective study was to clarify the
clinicopathological characteristics of LST with skirt. Between February 2006
and December 2013, a total of 986 LST in 806 consecutive patients were resected
endoscopically or surgically in our hospital. LST were macroscopically classified
into the following three groups: granular-homogeneous type (LST-GH), granular-nodular mixed type (LST-GM) and non-granular type (LST-NG). The location was divided into two regions: rectum (from upper rectum to lower rectum)
and colon (from cecum to recto-sigmoid colon). The skirt was defined by three
findings: 1) spreading at the margin of LST, 2) presenting as a hardly elevated
lesion, and 3) presenting with wide-shape pits. We assessed the clinicopathological characteristics such as age, gender, location, size, macroscopic type of LST,
histopathological findings. We also assessed the endoscopic findings of skirt
regarding the characteristics of pit in tumor surface using chromoendoscopy
with indigo carmine dye or crystal violet dye, and the characteristics of microvessels by magnifying narrow band imaging (NBI) endoscopy.
RESULTS: Of the 986 LST, skirt was identified in the peripheral region of 34
LST (3.4%). All LST with skirt were attaching LST-GM. Of the 34 LST with
skirt, 25 LST (74%) were located in the rectum and 9 LST (26%) were located in
the colon (4 in cecum, 3 in sigmoid colon, and 2 in recto-sigmoid colon). The
mean sizes of LST with skirt and LST without skirt were 46.5  19.3 mm and
30.0  16.8 mm. While carcinoma components were found in 27 lesions (80%) of
LST with skirt, 437 lesions (46%) of LST without skirt were carcinoma.
Significant differences were seen in the location (p 5 0.001), the size of tumor
(p 5 0.001) and the frequency of carcinoma (p 5 0.001) between LST with skirt
and LST without skirt. In contrast, there were no significant differences in age
and gender. Of the 34 LST with skirt, 26 were available for the histopathological
analysis of region of skirt and all were diagnosed as low-grade dysplasia. With
regard to the endoscopic findings at the surface of skirt, 29 (85%) showed coral
reef-like appearance pit (which was often visible in ulcerative colitis) and the
others showed type II like or type IIIL like pit pattern. As for the surface
microvessels of the skirt surface, all regions could not be detected as meshed
capillary vessels showing feature of lo-grade dysplasia, and were identified as
capillary pattern type I.
CONCLUSION: Significant characteristics of LST with skirt were more frequent
in rectal LST-GM lesions, larger tumor size, and high frequency of cancers
compared to LST without skirt. In the portion of skirt, there was dissociation
between endoscopic and histological findings.
Disclosure of Interest: None declared
P1305 COLONIC
PREPARATION
BEFORE
COLONOSCOPY:
EVALUATION OF A NEW METHOD WITH INTRACOLONIC
INFUSION OF WATER COMPARED TO CLASSICAL
ADMINISTRATION OF PEG
S. Adrien1,*, H. Jerome1, S. Sebastian1, D. Michel1, G. Gerard1
1
CHU Strasbourg, Strasbourg, France
Contact E-mail Address: adrien.sportes@free.fr
INTRODUCTION: Bowel cleansing before colonoscopy is currently based upon
lavage solutions of polyethylene glycol (PEG) or NaP with large amounts of
fluids ingested in a split manner. This prospective randomized study compared
a PEG protocol with a new method of bowel cleansing based upon infusion of
water into the colon at low pressure (Angel of Water, Lifestream, Austin, TX),
named hereafter the Prepsystem.
AIMS & METHODS: The device for water infusion is made of a reservoir of
water maintained at 37 C. The patient is installed on an adapted seat allowing
easy evacuation of water and faeces. Water is infused by gravity through a
cannula, into the rectum. Patients with an indication of colonoscopy and no
history of colorectal surgery or IBD were randomly assigned to PEG preparation
(2L PEG in the evening before and 2L in the morning of colonoscopy) or the
Prepsystem. All patients followed a low residue diet for 5 days. In the Prepsystem
group, sennosides (Pursennide 80 mg, Novartis, Rueil Malmaison, France) were
administered in the evening before and patients underwent 2 cleansing cycles, by
infusion of 35L tap water each, about one hour before the colonoscopy. Quality
of bowel cleansing was assessed with the Boston score by an endoscopist blinded
to the preparation type. Boston scores in both groups were compared with a nonparametric test, with a signifcance level of 5%.
RESULTS: 100 patients were included (62 males, 5913 y.). Main indications for
colonoscopy were colorectal cancer screening (n 57) and abdominal pain with
recent change in bowel habits (n 32). 50 patients received the Prepsystem and
50 the PEG protocol. Groups were comparable for age, sex and colonoscopy
indication. 6 patients were excluded from the analysis after an incomplete colonoscopy for anatomical reasons, preventing calculation of the Boston score: 4 in
the Prepsystem and two in the PEG groups. Consequently, 46 and 48 patients
were analysed in the Prepsystem and PEG groups respectively. The median
Boston score was 7 in both groups, without statistical difference. In the

Prepsystem group, the colonoscopy was not completed up to the caecum in 2


patients because of poor cleansing. Mild mucosal tears induced by the cannula
were observed in the rectum in 5 patients of the Prepsystem group. Mean duration of the colonoscopy was not different in the Prepsystem (193 min) and the
PEG (221 min) groups. Blood electrolytes were not significantly modified after
bowel cleansing in both groups. Patient satisfaction was good to excellent in all
cases in the Prepsystem group.
CONCLUSION: The Prepsystem water infusion protocol appeared as effective
as the split PEG protocol for bowel cleansing before colonoscopy. Patient tolerance of the Prepsystem was good. Further studies should evaluate the benefit of
this protocol in patients with contraindications or poor tolerance to PEG cleansing or in ambulatory patients.
Disclosure of Interest: None declared
P1306 COLONOSCOPIC WITHDRAWAL TIME IS BELOW THE
RECOMMENDED 6 MINUTES IN UNOBSERVED ENDOSCOPISTS
AND SIGNIFICANTLY INCREASES UNDER MONITORING
S. Vavricka1,*, L. Degen2, R. Rechner1, L. Biedermann1, G. Rogler1, M. Manz3,
C. Beglinger2, E. Safroneeva4, A. Schoepfer5
1
University Hospital Zurich, Zurich, 2University Hospital Basel, 3Claraspital
Basel, Basel, 4University of Bern, Bern, 5University Hospital Lausanne / CHUV,
Lausanne, Switzerland
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: Six minutes are recommended as the minimum withdrawal
time for screening colonoscopy. However, there is a lack of data regarding the
question how well this recommendation is followed by gastroenterologists unaware of being monitored in daily practice.
AIMS & METHODS: We aimed to assess first the withdrawal times in endoscopists unaware of being monitored, second if they would change the withdrawal
time when knowing to be monitored (with subsequent increase in adenoma
detection rate), and third, whether they could subjectively guess their withdrawal
times. Seven experienced gastroenterologists performed 558 screening colonoscopies in a tertiary referral centre. Colon retraction times were first measured without and then with the gastroenterologists knowledge of being monitored.
RESULTS: The mean withdrawal time in endoscopists unaware of being monitored was 4.7  1.6 min (range 1-13 min) without colonic intervention and 7.1 
3.9 min (range 2-25 min) with colonic intervention. In endoscopists aware of their
being monitored the withdrawal time without intervention rose to 8.1  2.8 min
and with intervention to 9.3  3.9 min (p 5 0.001 when compared to the withdrawal times unaware of being monitored). Adenoma detection rate increased
significantly (p 0.001) in endoscopists aware of being monitored. The subjective
estimate of withdrawal time with and without intervention was comparable to the
measured withdrawal time (7.7  2.7 vs. 8.1  2.8 min, p 0.180; 9.3  3.9 vs. 9.2
 4.3 min, p 0.796).
CONCLUSION: Colonic withdrawal time in unmonitored gastroenterologists is
shorter than recommended and increases when being monitored. Adenoma
detection rate increases in monitored endoscopists. Endoscopists are good in
guessing the measured withdrawal time. Withdrawal time should be monitored
using a watch in the endoscopy room.
Disclosure of Interest: None declared
P1307 USEFULNESS OF AN ENDOSCOPE WEIGHT-REDUCING AID
DURING GASTROSCOPY AND COLONOSCOPY
T. Fujii1,*
Gastroenterology, TF CLINIC, Tokyo, Japan
Contact E-mail Address: tfclinic@khaki.plala.or.jp
1

INTRODUCTION: In recent years, as the diagnostic/therapeutic endoscopic


procedures continue to increase in numbers, the left-arm/-shoulder burden continues to increase for the endoscopists performing these procedures, resulting in
their overuse injuries (upper extremity biomechanical overload).
AIMS & METHODS: To help relieve the biomechanical overload associated
with endoscopic procedures. Following installment of an infusion rail, an infusion runner system, and an infusion stand from the ceiling, a highly retractable
Teflon tube was connected to the infusion stand with its lower end clipped to an
endoscope, so that the endoscope could be left hanging from the system. With
this device weight-reducing aid, the infusion rail and the Teflon tube gave greater
freedom to endoscopist movement during endoscopy. The endoscopes available
at the clinic (GIF-XP260, GIF-Q260, PCF-Q240ZI, and CF-H260AZI;
Olympus) were compared in a diagnostic setting, with the endoscope connectors
attached to each system, for weight as well as for force exerted on each device,
with or without the weight-reducing aid.
RESULTS: The weight of each device with/without the weight-reducing aid was
0.66 kg/1.17 kg (0.56) for GIF-XP260, 0.8 kg/1.3 kg (0.62) for GIF-Q260, 0.96
kg/1.49 kg (0.64) for PCF-Q240ZI, and 0.97kg/1.58kg [0.61) for CF-H260AZI,
respectively. The force exerted on each device with/without the weight-reducing
aid was 6.46 Newton (N)/11.46 N (0.56) for GIF-XP260, 7.84 N/12.74 N (0.62)
for GIF-Q260, 9.4 N/14.6 N (0.64) for PCF-Q240ZI, and 9.5 N/15.48 N (0.61)
for CF-H260AZI, respectively.
CONCLUSION: An endoscope weight-reducing aid was developed. Endoscope
weight reductions with this aid may not only help decrease the physical burden
on the endoscopist performing endoscopic procedures but allow him/her to maintain concentration during prolonged diagnostic/therapeutic procedures, thus
leading to better diagnostic yield and clinical outcome.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1308 STENOSIS AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION
FOR LARGE COLORECTAL TUMORS
T. Hayashi1,*, S.-E. Kudo1, T. Ishigaki1, N. Toyoshima1, Y. Yagawa1,
Y. Maeda1, Y. Mori1, M. Misawa1, K. Wakamura1, A. Katagiri1, H. Miyachi1,
E. Hidaka1, F. Ishida1
1
Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
HOSPITAL, Yokohama, Japan
Contact E-mail Address: take09043946487@yahoo.co.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) provides a high
rate of curative resection for large superficial neoplasms, as it allows en-bloc
resection. It allows relatively large tumors to be included as candidates for endoscopic resection in place of surgical resection. Resection of large tumors would
leave large ulcers at the site of ESD, and a large size of the defect after ESD can
influence the healing progress. Consequently, post-ESD stenosis is a major complication in stomach and esophagus. A circumferential extent of the mucosal
defect (CEMD) of =3/4 was found as a major risk factor for postoperative
stricture. On the other hand, the situation might be different in the colorectum.
AIMS & METHODS: The aim of this study is to investigate the risk factor of
post ESD stenosis in the colorectum. From September 2003 to October 2013, 619
consecutive superficial colorectal tumors were treated by ESD. Among them, 34
cases in which CEMD was 3/4 or more, were thoroughly investigated. Only one
case was whole circumferential resection. CEMD was classified endoscopically as
being 3/4-9/10 or 9/10 5 just after the ESD procedure. Post-ESD stenosis was
diagnosed when a standard 11.5mm diameter colonoscope could not be negotiated through the colonic segment at the site of ESD. Follow-up endoscopy was
performed 4 to 6 months later. If patients had any different clinical symptoms
from those prior to the ESD, endoscopy was performed in order to check for
post-ESD stenosis.
RESULTS: Post-ESD stenosis didnt occur in 585 cases which CEMD was under
3/4. In 34 cases in which CEMD was 3/4 or more, postoperative stricture developed in 3 of them. Two cases were controlled only by a few sessions of endoscopic balloon dilatation. The other which was whole circumferential resection
case from lower rectum to dentate line required steroidal suppository and Finger
bougienage as daily regimen for 90 days and three sessions of endoscopic balloon
dilatation. There was significant difference in CEMD but no significant difference in circumferential and longitudinal diameter of the resected specimen and
procedure time between presence and absence of postoperative stricture groups.
CONCLUSION: Post-ESD stenosis didnt occur among cases with a CEMD of
less than 9/10. Even in cases that developed postoperative stricture, the symptoms could be controlled by a few sessions of endoscopic balloon dilatation and
conservative treatment. Thus, we concluded that near and whole circumferential
resection is acceptable for lesions of the colorectum.
Disclosure of Interest: None declared
P1309 ENDOSCOPIC EXAMINATION OF GASTROINTESTINAL
LESIONS ASSOCIATED WITH MICROANGIOPATHY CAUSED BY
IMMUNOSUPPRESSANTS
T. Yamaguchi1,*, M. Ito2, J.-I. Haruta1, M. Doisaki1, T. Ishikawa1, T. Yama1
1
Gastroenterology, 2Pathology, Japanese Red Cross Nagoya First Hospital,
Nagoya, Japan
Contact E-mail Address: yamaguchi@nagoya-1st.jrc.or.jp
INTRODUCTION: There is a concern within the scientific community that
many iatrogenic diseases will increase and diversify as a result of the diversification and increasingly widespread use of immunosuppressants (calcineurin inhibitors). Patients often experience lower gastrointestinal tract symptoms such as
diarrhoea, melena and lower abdominal pain after allogeneic hematopoietic stem
cell transplantation (allo-HSCT). The cause is often attributed to transplantation
associated microangiopathy (TAM); however, the differentiation of this from
gastrointestinal graft-versus-host disease (GVHD) is difficult, which may lead
to patients being mistakenly treated for severe gastrointestinal GVHD.
AIMS & METHODS: We performed lower gastrointestinal endoscopies in
patients experiencing post-transplantation abdominal pain to investigate the
effectiveness of this procedure. The subjects were 101 patients selected from a
group of 824 patients who underwent allo-HSCT at this medical facility during
the 16-year period from 1998 to 2013 because of leukemia, myelodysplastic syndrome, malignant lymphoma, or aplastic anemia. The selected patients had all
experienced abdominal symptoms such as diarrhoea, abdominal discomfort and
abdominal pain within 6 months of the procedure, had undergone lower gastrointestinal endoscopy and histopathological examination and had been diagnosed
with TAM based on the presence of microangiopathy with ischemic (non-inflammatory) crypt loss in mucosa of the biopsy specimens.
RESULTS: (1) The major findings obtained from the endoscopic examination of
TAM were edema, rubefaction, coarse mucosa, inflammation, ulcers and mucosal loss. (2) Endoscopic examination enabled the identification of findings in
100% of the cases, with the highest percentage of findings concentrated in the
ascending colon, sigmoid colon and rectum. (3) Pathological diagnosis revealed
that the number of severe cases had been decreasing in recent years and that a
small percentage of cases were complicated with GVHD or cytomegalovirus
(CMV) infection. (4) A correlation was observed between the endoscopic severity
and the histologic severity of TAM. (5) Magnification endoscopy allowed for the
accurate diagnosis of TAM, including its severity and stage.
CONCLUSION: The results of the present study showed that active use of
endoscopy for gastrointestinal symptoms following allo-HSCT allows the clinical
picture of TAM to be elucidated and is useful in determining subsequent treatment strategies.
Disclosure of Interest: None declared

A489
P1310 COMPARING
STANDARD
COLONOSCOPY
WITH
ENDORINGSTM COLONOSCOPY: A RANDOMIZED,
MULTICENTER TANDEM COLONOSCOPY STUDY INTERIM
RESULTS OF THE CLEVER STUDY
V.K. Dik1, I. Gralnek2,3, O. Segol4, A. Suissa2,3, L. Moons1, M. Segev5,
T. Belderbos1,*, D. Rex6, P. Siersema1
1
Dept. of Gastroenterology & Hepatology, University Medical Center Utrecht,
Utrecht, Netherlands, 2Dept. of Gastroenterology, Rambam Health Care Campus,
3
GI Endoscopy Unit, Elisha Hospital, 4Dept. of Gastroenterology, Lady Davis
Carmel Medical Center, Haifa, 5EndoAid Ltd., Caesarea, Israel, 6Dept. of
Medicine, Division of Gastroenterology and Hepatology, Indiana University
Hospital, Indianapolis, United States
Contact E-mail Address: i_gralnek@rambam.health.gov.il
INTRODUCTION: Adenoma miss rates during colonoscopy have become
widely acknowledged. This is primarily due to inadequate visualization of the
proximal aspects of colonic folds and flexures. EndoRingsTM (EndoAid Ltd.,
Caesarea, Israel) is a silicone rubber device, that is fitted onto the distal end of
the colonoscope. Its flexible circular wings engage and mechanically stretch colonic folds during withdrawal.
AIMS & METHODS: In this multicenter tandem colonoscopy study, we compared adenoma miss rates (per lesion analysis) between standard colonoscopy
(SC) and colonoscopy using EndoRingsTM (EC). Secondary aims were to compare polyp miss rates, cecal intubation time, withdrawal time and total procedure
time. Subjects referred for screening, surveillance or diagnostic colonoscopy were
randomly assigned to undergo EC followed by SC or SC followed by EC.
Both colonoscopies were performed on the same day by the same endoscopist.
Polyps detected during the first procedure were immediately removed.
Diminutive (1-2 mm), rectal polyps with hyperplastic appearance were not
removed. The study sample size was calculated with a two-group chi-square
test with 80% power and 0.05 two-sided significance level. Based on an expected
adenoma miss rate of 35% with SC and 10% with EC, an expected mean number
of adenomas per subject of 0.75 and a 10% drop-out rate, a total sample size of
126 subjects will be required.
RESULTS: To date, 96 subjects have been enrolled After excluding 8 subjects
due inability to reach the cecum or other protocol violations, 88 subjects (59%
male, mean age 58  9 years) remained for analysis. Indications for colonoscopy
were screening n 25 (28%), surveillance n 26 (30%) and diagnostic evaluation
n 37 (42%). Forty three subjects were randomly assigned to undergo EC first
followed by SC and 43 subjects to undergo SC first followed by EC. In the study
group, 43 adenomas were detected during first pass with EC and 7 additional
adenomas during the second procedure with SC. In the control group, 14 adenomas were detected during the first pass colonoscopy with SC and 14 additional
adenomas during the second procedure with EC. The adenoma miss rate (14%)
in subjects undergoing EC first was statistically significantly (p 0.001) lower
compared to subjects who underwent SC first (50%). Similar results were found
for polyp miss rates, i.e. 11% for EC and 59% for SC (p50.001). The adenoma
detection rate was statistically significantly (p 0.01) higher with EC (51%) when
compared to SC (24%). Mean cecal intubation times (9.4 min. vs. 8.3 min.,
p 0.15) and withdrawal times (7.3 min. vs. 6.9 min., p 0.12) were not significantly different between EC and SC. Mean total procedure time was longer
(p50.001) with EC (21.9 min.) compared to SC (17.8 min.) due to removal of
more polyps.
CONCLUSION: The interim results of this study (inclusion of all patients
expected in June 2014) demonstrate that colonoscopy with EndoRingsTM results
in significantly lower adenoma and polyp miss rates than standard colonoscopy.
Disclosure of Interest: V. Dik: None declared, I. Gralnek Consultancy for:
EndoAid Ltd., O. Segol Consultancy for: EndoAid Ltd., A. Suissa: None
declared, L. Moons: None declared, M. Segev Other: Employee of EndoAid
Ltd., T. Belderbos: None declared, D. Rex Consultancy for: EndoAid Ltd., P.
Siersema Consultancy for: EndoAid Ltd.
P1311 COMPARISON OF CECUM INTUBATION AND ADENOMA
DETECTION BETWEEN HOSPITALS CAN PROVIDE INCENTIVES
TO IMPROVE QUALITY OF COLONOSCOPY
T.D. Belderbos1,*, E.J. Grobbee2, M.G. van Oijen1, M.A. Meijssen3,
R.J. Ouwendijk4, T.J. Tang5, F. ter Borg6, P.van Der Schaar7, D.M. Le Fevre8,
M. Stouten9, O.van Der Galien8, T.J. Hiemstra8, W.H. de Vos3, P.C. ter Borg4,
M.C. Spaander2, M.G. van Oijen1, L.M. Moons1, E.J. Kuipers2, P.D. Siersema1
1
Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht,
2
Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam,
3
Gastroenterology and Hepatology, Isala Hospital, Zwolle, 4Gastroenterology and
Hepatology, Ikazia Hospital, Rotterdam, 5Gastroenterology and Hepatology,
IJselland Hospital, Capelle aan den IJssel, 6Gastroenterology and Hepatology,
Deventer Hospital, Deventer, 7Gastroenterology and Hepatology, Sint Antonius
Hospital, Nieuwegein, 8Achmea Health Care, Leiden, 9Gupta Strategists,
Ophemert, Netherlands
Contact E-mail Address: t.d.g.belderbos@umcutrecht.nl
INTRODUCTION: Cecum intubation rate (CIR) and adenoma detection rate
(ADR) are used as quality indicators for colonoscopy. Both parameters are easy
to measure and have been found to be negatively associated with the occurrence
of post-colonoscopy colorectal cancer (CRC). Comparing CIR and ADR
between hospitals could provide useful incentives for quality improvement if
possible inter-hospital differences depend at least to some extent on modifiable
institutional and procedural factors.
AIMS & METHODS: The aim of this study was to compare the quality of
routine colonoscopy between seven hospitals in the Netherlands to determine
to what extent possible differences in CIR and ADR could be attributed to

A490
procedural- and hospital-related factors. We prospectively registered all colonoscopies performed between November 2012 and January 2013 in two academic
and five general hospitals in the Netherlands. Colonoscopies in patients with
inflammatory bowel disease (IBD) or hereditary CRC syndromes were excluded.
To correct for casemix variation, we performed adjusted multivariate analyses
for age, gender, ASA score and indication.
RESULTS: A total of 3,129 patients were included (54% female; mean age
5915 years). The majority of procedures (90%) were performed in adequately
prepared colons, defined as a Boston Bowel Preparation Scale (BBPS) score 6.
Mean CIR was 95% and ranged from 89% to 99% between hospitals (p50.01).
In multivariate analysis, independent predictors for CIR were BBPS 6 (odds
ratio (OR) 23.3, 95%CI 13.5-40.1), and hospital (p50.01), with ORs ranging
from 1.1 to 9.7 (largest hospital as reference). Mean ADR was 32% and varied
between hospitals, ranging from 23% to 43% (p50.01). Nurse endoscopists and
fellows detected adenomas more frequently than gastroenterologists (36% and
34% vs. 30%, p50.01), but this difference was not significant in multivariate
analysis (p 0.21). Independent predictors for ADR were a BBPS 6 (OR 1.8,
95%CI 1.3-2.5), use of conscious sedation (1.7, 95%CI 1.1-2.6), cecum intubation (OR 2.0, 95%CI 1.3-3.0) and hospital (p50.01) with ORs ranging from 0.5
to 1.4 (largest hospital as reference). We combined the CIR and ADR per hospital in a scatter plot, providing an overview that can be used by hospitals to
drive quality improvements.
CONCLUSION: Differences in quality of colonoscopy between hospitals can be
depicted using CIR and ADR. As both CIR and ADR are affected by modifiable
institutional and procedural factors that are independent of casemix, a comparison between hospitals can help improving quality of colonoscopy.
Disclosure of Interest: None declared
P1312 THE GOLDEN RETRIEVER STUDY: IMPROVING POLYP
RETRIEVAL RATES BY PROVIDING COMPETITIVE FEEDBACK
T.D. Belderbos1,*, M.G. van Oijen1, L.M. Moons1, P.D. Siersema1
1
Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht,
Netherlands
INTRODUCTION: Colonoscopy surveillance is an essential part of screening
programs aiming to prevent colorectal cancer. Recommendations on the adequate surveillance interval for patients with one or more colorectal polyps are
predominantly based on the presence and grade of neoplasia found after histopathological evaluation. Therefore, it is important that resected colorectal
polyps, especially right-sided lesions, are retrieved for histology. The internationally accepted standard for polyp retrieval rate is 90%.
AIMS & METHODS: The primary aim of this study was to evaluate the effect of
education and competitive feedback on the overall polyp retrieval rate. The
secondary aim was to investigate the association between polyp size or location
and non-retrieval. We included consecutive colonoscopies in a single center
between April 1, 2013 and April 1, 2014. Patients with inflammatory bowel
disease or familial colorectal cancer syndromes were excluded for analysis. All
gastroenterologists and trainees performing colonoscopy were educated on the
importance of polyp retrieval and techniques to improve retrieval 6 months after
the start of the study (end of September 2013). Then, the polyp retrieval competition was started by publicly providing feedback on the retrieval rate of all endoscopists and the monthly best performers (or golden retrievers). We compared
overall retrieval rates during six months prior to and after October 1, 2013.
RESULTS: Overall polyp retrieval rate improved from 88.6% (466/526) to 93.2%
(923/990) when comparing consecutive colonoscopies performed in 6 months before
and during the polyp retrieval competition (p 0.002). Non-retrieval occurred significantly more often in polyps 5 mm compared to polyps 45 mm (11.1% vs.
1.7%, p 0.005). The retrieval rate of left-sided polyps was higher compared to
right-sided polyps during the 6 months previous to the competition (92.6% vs.
84.1%, p 0.003), but this difference was not significant anymore when the 6
months of competition were also taken into account (92.5% vs 91.1%, p 0.334).
CONCLUSION: A simple intervention to improve awareness and dedication is
able to increase both overall and right-sided polyp retrieval rates in order to meet
the international standard of 90%.
Disclosure of Interest: None declared
P1313 EFFICACY AND TOLERABILITY OF SODIUM PHOSPHATE
TABLETS AND POLYETHYLENE GLYCOL SOLUTION IN BOWEL
PREPARATION FOR COLONOSCOPY: A PROSPECTIVE STUDY
T. Tashima1,*, K. Ohata1, M. Takita1, Y. Matsuyama1, Y. Minato1, K. Nonaka1,
N. Matsuhashi1
1
Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan
INTRODUCTION: As the result of the increment of colorectal cancer, the
importance of high quality screening colonoscopy has been rapidly increasing.
Polyethylene glycol (PEG) solution and sodium phosphate (NaP) solution are
effective for colon cleansing before colonoscopy. However, large volume and
unpleasant taste reduce tolerability and acceptability. Recently, NaP tablet has
been developed to improve patient compliance and tolerability.
AIMS & METHODS: The aim of this study was comparing the efficacy and
tolerability of the two different preparations. We have performed prospective
cohort study to compare the efficacy of bowel preparation and patients acceptance between NaP tablets and PEG during May 2011 and February 2013. We
assigned patient randomly to two groups. Group A (n 250) received NaP
before colonoscopy. Group B (n 250) received PEG before procedure. We
analyzed the effectiveness of bowel preparation by endoscopists scoring based
on the grading system and patient acceptance by patients questionnaire. In the
grading system, we classified the cleansing grade into 5 categories, and defined
the favorable and effective cleansing group as grade 1 and 2.

United European Gastroenterology Journal 2(1S)


RESULTS: 440 patients (217 NaP; 223 PEG) completed the study preparation
and patients questionnaire prior to colonoscopy. There were statistically no
significant differences in (gender (p 0.87), age (p 0.37), height (p 0.64)
and weight (p 0.12)) between the two groups. Effectiveness of bowel preparation was significantly higher in Group A (88.0% vs 80.7%, p 0.035). There
were no significant differences in acceptance between the two groups (A; 81.9%,
B; 78.6%, p50.05). Among 133 patients who have experienced both NaP tablets
and PEG, (57.1%), (25.6%), and patients (17.3%) preferred NaP tablets, PEG,
and either of the two in future colonoscopy. There was no severe adverse event
through this study in both groups.
CONCLUSION: In conclusion, NaP tablets preparation is easy to take, well
tolerated, and more preferred by patients than PEG.
Disclosure of Interest: None declared
P1314 PATHOLOGICAL FEATURES OF LATERALLY SPREADING
TUMOR OF THE COLORECTUM; REFERENCES AMONG
SUBTYPES AND SUBMUCOSAL INVASION
T. Ishigaki1,*, S.-E. Kudo1, H. Miyachi1, T. Hayashi1, Y. Kouyama1, Y. Maeda1,
K. Ichimasa1, H. Nakamura1, Y. Yagawa1, N. Toyoshima1, Y. Mori1,
M. Masashi1, T. Kudo1, T. Hisayuki1, K. Wakamura1, A. Katagiri1, E. Hidaka1,
F. Ishida1, S. Hamatani1
1
Digestive Disease Center, Showa University Northern Yokohama Hospital,
Yokohama City, Japan
INTRODUCTION: Laterally spreading tumors (LSTs) are usually good indication for endoscopic treatment because they are rather benign in spite of their
large diameter. There are four subtypes in LSTs; granular type [homogeneous
type (H) / nodular mixed type (M)], and non-granular type [flat-elevated type (F)
/ pseudo-depressed type (PD)]. Their pathological features are different among
subtypes.
AIMS & METHODS: The aim of this study is to evaluate the pathologial
features of LSTs focusing on their subtypes and submucosal (SM) invasion. In
a retrospective review of the colonoscopy database (Apr 2001 to Dec 2013) at our
institution, we selected cases of colorectal neoplasms based on the following
criteria; endoscopically diagnosed cases of LSTs that underwent subsequent
endoscopic or surgical resection. We evaluated pathological features (size, rate
of SM invasion) according to LSTs subtypes. Furthermore, we examined the
LSTs with SM invasion which treated from Apr 2010 to Dec 2013 focusing on
their locus of SM invasion. For analysis, we used chi-square test and one way
ANOVA post hoc test for statistical analysis.
RESULTS: A total of 2226 LSTs were eligible for inclusion. The main results are
shown in the table. As the three types of LST(G(M)/NG(F)/NG(PD)) became
larger, the ratio of submucosal invasion became higher. But LST-G(H) showed
low rate of that even when they were large in diameter. LST-NG(PD) had higher
ratio of submucosal invasion (45.1%; 102/226) than the other types (P50.01).
LSTs with SM invasion which treated from Apr 2010 to Dec 2013 were 104
lesions. The locus of SM invasion at LST-G(M) was almost (78.8%; 21/27)
under nodule. In LST-NG(PD), SM invasion was tend to occur multifocally
(45.2%; 14/31) compared with the other type (12.3%; 9/73) (P50.01).

N
Size (mm)
Rate of SM
invasion (%)

Total

LST-G(H) LST-G(M) LST-NG(F) LST-NG(PD) P-value

2226
25.115.9
12.7
(282/2226)

573
26.316.8
0.7
(4/573)

450
37.420.4
17.6
(79/450)

977
19.79.8
9.9
(97/977)

226
21.38.8
45.1
(102/226)

P50.01
P50.01

CONCLUSION: Pathological features of LSTs are different among subtypes. To


understand the way of SM invasion in LSTs is useful to choise the appropriate
treatment method.
Disclosure of Interest: None declared
P1315 DISTINCT CLINICOPATHOLOGICAL AND MOLECULAR
FEATURES OF LATERALLY SPREADING TUMORS IN THE
COLORECTUM
T. Kihara1,*, Y. Kubota1, K. Konishi1, H. Nozawa1, A. Katagiri1, Y. Yano1,
M. Tojo1, K. Shinmura1, K. Konda1, T. Tagawa1, F. Yanagisawa1, K. Iijima1,
H. Yoshida1
1
Division of Gastroenterology, Department of Medicine, Showa University School
of Medicine, Tokyo, Japan
Contact E-mail Address: toshikiha@yahoo.co.jp
INTRODUCTION: Colorectal flat-elevated neoplasms can be classified into
small-flat adenoma and laterally spreading tumor (LST). LSTs are subcategorized into granular-type LST (LST-G) and nongranular-type LST (LST-NG).
LSTs tend to extend laterally and circumferentially rather than vertically along
the colonic wall and seem be found at an early stage tumor such as adenoma.
However, LSTs with large nodules or depressions tend to invade the submucosa.
These observations suggest that there may be biological differences between LSTGs and LST-NGs.
AIMS & METHODS: We examined the clinicopathological and molecular features of 24 granular-type laterally spreading tumors (LST-Gs) and 57 nongranular-type LSTs (LST-NGs) that were resected endoscopically at Showa University
Hospital from July 2007 through December 2011. We investigated the frequency
of KRAS and BRAF mutations, and DNA methylation of seven genes or
sequences (MINT1, MINT2, MINT31, p16, MLH1, SFRP1 and ESR1) by pyrosequencing. We also examined the methylation level of SFRP1 and ESR1 in

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United European Gastroenterology Journal 2(1S)


normal adjacent mucosa. A tumor was considered to be CpG island methylator
phenotype (CIMP) -positive if 2 or more CIMP markers (MINT1, MINT2,
MINT31, p16 and MLH1) were methylated.
RESULTS: We observed significant differences in the tumor size (30 mm vs. 15
mm), the frequency of KRAS mutation (75%, 18/24 vs. 5%, 3/57) and CIMP
(35%, 8/23 vs. 5%, 3/57,) between LST-Gs and LST-NGs (P 5 0.001). The
frequency of TP53 mutation tended to be higher in LST-NGs than LST-Gs
(14%, 8/57 vs. 0%, 0/24, P 0.05). However, we found no significant differences
in the frequency of BRAF mutation between two groups. For LST-NGs, the
histological grade was increased with an increase in the tumor size. The frequency
of Dukes A cancer was significantly higher in tumors larger than 20 mm or equal
than tumors less than 20 mm in size (P 5 0.05). In contrast, LST-G showed no
correlation of a size-dependent increase in the histological grade. No significant
differences in the frequency of KRAS mutation and CIMP in LST-Gs and LSTNGs were observed by tumor size. Although the methylation levels were relatively low, we observed SFRP1 and ESR1 methylation in normal adjacent
mucosa as well as tumor tissues of LST-G and LST-NGs (median methylation
density: SFRP1 methylation, 18% and 22%; ESR1 methylation, 19% and 20%,
respectively).
CONCLUSION: Our results suggest that different molecular mechanisms may
exist in these subtypes of colorectal flat-type neoplasms. Furthermore, SFRP1
and ESR1 methylation in normal adjacent mucosa might be associated with field
effects defined by epigenetic changes as early events predisposing to laterally
spreading manner of LSTs.
Disclosure of Interest: None declared
P1316 IMPROVING THE QUALITY OF COLONOSCOPY BOWEL
PREPARATION USING A SMART PHONE APPLICATION
V. Lorenzo-Zuniga1,2,*, V. Moreno-de-Vega1, J. Boix1
Gastroenterology, Hospital Universitari Germans Trias i Pujol/CIBERehd,
2
CIBERehd, Badalona, Spain
1

INTRODUCTION: Bowel preparation for colonoscopy is a complex undertaking, involving diet modifications and laxative choice according to patient needs.
An adequate level of cleansing is critical for the efficacy and the quality of
colonoscopy. Bowel preparation is inadequate in an up to 30% of patients undergoing colonoscopy, and has been associated with patient characteristics, previous
failure to adequately prepare colon and noncompliance with cleansing instructions. Education of patients before colonoscopy is very important to ensure
compliance. Early data have shown a significant improvement in bowel preparation quality in patients who used the smart phone application (SPA). Therefore,
we created a novel SPA aimed to increased bowel preparation quality and patient
satisfaction, using different educational tools.
AIMS & METHODS: To determine whether SPA could improve proper bowel
preparation in patients undergoing colonoscopy, and to evaluate the effect of
SPA on patient satisfaction.
We performed a randomized, double-blind, pilot study with two parallel arms
from January to April 2014. Outpatients submitted for colonoscopy, owners of a
smart phone and able to manage a SPA, were included. We enrolled 194 consecutive patients (104 female, 90 male, age range 26-75 yrs) that were randomnly
allocated by nurse assistant to one of the following bowel preparation protocols:
a) SPA Group (n 95): patients downloaded this free SPA onto their smart
phone. The app provides to patients timed alerts and explains the procedure
providing tips, examples of low fiber diet, and educational video to explain
how to prepare the purgative solution; and b) Control Group (n 99): written
instructions for bowel preparation, with visual aids explaining the procedure and
how to prepare the solution, was given to each patient. All procedures were
performed in afternoon time, and patients received the same purgative regimen
(2-L PEG solution plus ascorbic acid), in a full-dose same-day regimen. The
study was powered to detect an improvement in quality of bowel preparation
using the Herefield Cleansing Scale (HCS) scale. To evaluate the effect of SPA on
patient satisfaction were assessed with a specific questionnaire at time of the
colonoscopy. Patients were asked if they used the application and their satisfaction with the app. Endoscopists were blinded to the actual treatment given to
each patient and to the answers. Results are expressed as median (CI 95%)
RESULTS: There was no significant difference in the HCS scores in both regimens (17.003.11 in the SPA group vs 16.213.60 in the control group;
p 0.188); however, the use of SPA was superior to written instructions in overall successful cleansing (100% vs 90.9%; p 0.003.) (HCS scores A or B), with
specifically better cleansing in the right colon (p 0.016) and in the transverse
colon (p 0.040), respectively. Patient-reported tolerability and the overall
experience with the prescribed bowel preparation was significantly higher for
the SPA group than for the control group (p50.001).
CONCLUSION: Successful cleansing and patient acceptability with the use of
SPA were superior to written instructions in outpatients submitted for colonoscopy prepared 2-L PEG solution plus ascorbic acid.
Disclosure of Interest: None declared

P1317 ENDOSCOPIC MUCOSAL RESECTION FOR PARIS TYPE 0-I S


AND TYPE 0-II SUPERFICIAL COLORECTAL NEOPLASIA
V. Boyko1,*
1
Endoscopy, Clinical Hospital Pheophania, Kyiv, Ukraine
Contact E-mail Address: boyko_doc@mail.ru
INTRODUCTION: Endoscopic mucosal resection (EMR) is an endoscopic technique developed for removal of sessile or flat neoplasms confined to the superficial layers of colorectal mucosa. EMR can provide effective cure for Paris type
Is and type II colorectal neoplasia and node-negative early cancer, avoiding the
need of surgical resection.
AIMS & METHODS: 186 colorectal neoplasm in 142 patients were removed by
EMR between January 2012 and November 2013. All patients previously underwent total colonoscopy by EC590ZW/L (Fujinon, Japan) or CF-160L
(Olympus, Japan) endoscopes. Resection included following stages: (1)
guided local or total chromoscopy by 0.5% indigo carmine solution, (2) mucosal
examination of pit-pattern, (3) submucosal injection of fluid, (4) snare mucosectomy, (5) estimation of results, (6) clip closure of defect when feasible.
RESULTS: EMR were performed in total of 186 colorectal neoplasia: 152 Paris
type II and 34 Paris type Is. Neoplasia lesions size ranged from 3-39 mm (mean
size 17.8 mm). Mean resection time was 11.8 min (range 1-38 min).
Mucosectomies were performed in total of 152 non-polypoid lesions with 91
(59.9%) right colonic, 39 (25.6%) left colonic and 22 (14.5%) identified rectal
lesions. Histology confirmed adenoma (tubular, tubulo-villous, villous) in 94,
adenoma with LGD in 29, adenoma with HGD in 20, and intramucosal Ca in
9 lesions respectively. The majority of lesions - 90 (59.2%) were lesions of type 0IIa, 8 (5.3%) type 0-IIb, 2 (1.3%) type 0-IIc, 30 (19.7%) type 0-IIac or 0-IIca,
and 22 (14.5%) - Lateraly Spreading Tumor.
Mucosectomies were performed in 34 polypoid lesions (Is) with 12 (35.3%) right
colonic, 14 (41.2%) left colonic and 8 (23.5%) identified rectal lesions. Histology
confirmed adenoma (tubular, tubulo-villous, villous) in 25, adenoma with LGD
in 5, adenoma with HGD in 2, and intramucosal Ca in 2 lesions respectively. The
majority of lesions - 30 (88.3%) were lesions of type 0-Is, 4 (11.7%) type 0-IsIIc.
En-block resection was performed in 172 (92.5%) cases, resection by several
fragments in 14 cases (7.5 %). All removed in parts lesions were over 20 mm
in size. Three patients experienced an episode of delayed bleeding. No perforation were seen. In two patients we found relapses of neoplasia (after 1y). 21 cases
of dysplasia and 8 cases of adenocarcinoma were revealed in 36 neoplasms with
0-IIp component. With the absence of 0-IIc component (150 neoplasms) dysplasia was observed in 35 cases and adenocarcinoma in 3 cases.
CONCLUSION: Endoscopic management EMR is a safe and effective treatment for Paris type Is and type II of colorectal neoplasia and may be an alternative to surgery in selected patients. Presence of 0-IIc focus significantly
correlates to the presence of dysplasia or adenocarcinoma.
Disclosure of Interest: None declared
P1318 THE MANAGEMENT OF DIMINUTIVE ADENOMATOUS POLYP
USING PIT PATTERN CLASSIFICATION
Y. Maeda1,*, S.-E. Kudo1, K. Wakamura1, H. Miyachi1, A. Yamauchi1,
Y. Ogawa1, K. Igarashi1, M. Misawa1, Y. Mori1, N. Ogata1, T. Kudo1,
K. Kodama1, T. Hayashi1, A. Katagiri1, M. Kaga1, F. Ishida1
1
Digestive Disease Center, Showa University Northern Yokohama Hospital,
Yokohama, Japan
Contact E-mail Address: yasharumaeda610@hotmail.com
INTRODUCTION: It is now available to estimate histological feature of colorectal lesions using magnifying chromo-endoscopy (pit pattern classification). In
regard to diminutive (55mm) adenomatous polyps (DAP), it has been reported
that the prevalence of advanced histological features was low1). However diminutive invasive cancer has been found. We basically permit to left untreat and
follow up DAP with type IIIL pit pattern and resect ones with type IIIs, IV or
V in routine colonoscopy.
AIMS & METHODS: The aim of this retrospective study was to assess our
management DAP using pit pattern classification. Objective was the patients
who were performed total colonoscopy between April 2000 and December
2012 in Showa University Northern Yokohama Hospital. Inclusion criteria
was defined as follows; 1: all polyps were performed magnifying chromo-endoscopy. 2: all adenomatous polyps of 45mm were removed or no adenomatous
polyp was detected at initial colonoscopy. 3: followed up colonoscopy was examined43 years after initial colonoscopy. Patients who had a history of familial
adenomatous polyposis, hereditary non-polyposis, advanced colorectal cancer or
inflammatory bowel disease were excluded. They were divided into three groups
according to the finding and treatment at initial colonoscopy as follows; Group
A: No neoplastic polyp was detected. Group B: All neoplastic polyps including
DAP were resected. Group C: DAP with type IIIL pit pattern were left untreated.
The groups were compared in cumulative incidence of index lesion (=10mm, or
high grade dysplasia) or invasive cancer at follow-up colonoscopy.
RESULTS: A total of 4550 patients were enrolled in our study. 1565 patients
classified into Group A, 2021 in Group B, 964 in Group C. Index lesion was
detected in 18 patients (1.2%) in Group A, 145 (7.2%) in Group B, and 64
(6.7%) in Group C, respectively. Invasive cancer was detected in 10 patients
(6.3%) in Group A, 10 (4.9%) in Group B, and 4 (4.1%) in Group C, respectively. There were not significant differences in incidence of invasive cancer
among three groups. In regard to incidence of index lesion, Group A was significant lower than Group B and Group C. There was no significant difference
between Group B and Group C.
CONCLUSION: Removing DAP with type IIIL pit pattern did not decrease an
incidence of index lesion and invasive cancer, significantly. DAP with type IIIL
pit pattern could be allow to left untreat and follow up.

A492
REFERENCES
1) Gupta N, Bansal A, Rao D, et al. Gastrointest Endosc 2012; 75: 1022-1030.
Disclosure of Interest: None declared
P1319 EVALUATION OF COLORECTAL TUMOUR HYPOXIA BY
AUTOFLUORESCENCE IMAGING WITH A HIGH-PERFORMANCE
CMOS IMAGER
Y. Kominami1,*, S. Yoshida1, R. Miyaki2, Y. Sanomura1, S. Oka1, S. Tanaka1,
M.-W. Seo3, K. Kagawa3, S. Kawahito3, H. Arimoto4, K. Yamada5,
K. Chayama2
1
Department of Endoscopy and Medicine, Graduate School of Biomedical and
Health Science, 2Department of Gastroenterology and Metabolism, Graduate
School of Biomedical and Health Science, HIROSHIMA UNIVERSITY,
Hiroshima, 3Research Institute of Electronics, SHIZUOKA UNIVERSITY,
Shizuoka, 4National Institude of Advanced Industrial Science and Technology,
Tsukuba, 5Graduate School of Medicine, Division of Health Sciences, OSAKA
UNIVERSITY, Osaka, Japan
Contact E-mail Address: yoshida7@hiroshima-u.ac.jp
INTRODUCTION: Autofluorescence is the natural emission of light by biological structures such as nicotinamide adenine dinucleotide (NADH) and flavins.
NADH is increased in tumour cells because of anaerobic glycolysis. Recent
report that the dual-wavelength excitation method is useful technique for the
detection of early colonic tumours, reveals that the precise measurement of
NADH fluorescence intensity as a method for visualizing colonic tumours with
cooling EM-CCD1).
AIMS & METHODS: The aim of this study is to evaluate colorectal tumour
hypoxia by autofluorescence imaging with a high-performance CMOS imager
that needs no cooling.
Study samples were 91 colorectal tumour specimens obtained by endoscopic
resection in our department between October 2012 and February 2014 (12 sessile
serrated adenoma/polyp (SSA/P), 40 adenoma and 39 mucosal adenocarcinoma
(M-ca) specimens). The resected specimens were irradiated with excitation lights
of 365 nm and 405 nm, and autofluorescence images were obtained with a highperformance CMOS imager with band pass (47525nm) and long pass filters
(450 nm). Ratio images (F365ex/F405ex, band pass filter images (bp images)
and long pass filter images (lp images)) were created for evaluation of lesion
brightness (High, Iso or Low) compared with the brightness of normal mucosa.
RESULTS: In bp images, to evaluate the brightness of the lesion in all case is
that High group is 84.6% (77/91), Iso group is 8.8% (8/91) and Low group is
6.6% (6/91). Histologic SSA/P was depicted on a total of 12 bp images, with
66.7% (n 8) falling into the High group, 8.33% (n 1) falling into the Iso
group and 25.0% (n 3) falling into the Low group; adenoma/M-ca was
depicted on a total of 79 bp images, with 87.3% (n 69) falling into the High
group, 8.86% (n 7) falling into the Iso group and 3.80% (n 3) falling into the
Low group.
In lp images, to evaluate the brightness of the lesion in all case is that High group
is 70.3% (64/91), Iso group is 19.8% (18/91) and Low group is 9.9% (9/91).
Histologic SSA/P was depicted on a total of 12 lp images, with 33.3% (n 4)
falling into the High group, 33.3% (n 4) falling into the Iso group and 33.3%
(n 4) falling into the Low group; adenoma/M-ca was depicted on a total of 79
lp images, with 75.9% (n 60) falling into the High group, 17.7% (n 14) falling
into the Iso group and 6.33% (n 5) falling into the Low group.
CONCLUSION: Our results show that autofluorescence images obtained with a
high-performance CMOS imager may be useful for clinical detection and functional diagnosis of colon tumours.
REFERENCES
Imaizumi K, Harada Y, Wakabayashi N, et al. Dual-wavelength excitation of
mucosal autofluorescence for precise detection of diminutive colonic adenomas.
Gastrointest Endosc 2012; 75: 110-117.
Disclosure of Interest: None declared
P1320 CLINICAL COURSE AFTER CIRCUMFERENTIAL AND SUBCIRCUMFERENTIAL RECTAL ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR LARGE RECTAL NEOPLASMS
Y. Ohara1,*, T. Toyonaga2, S. Tanaka2, T. Yoshizaki2, F. Kawara2, T. Ishida1,
N. Hoshi1, Y. Morita1, E. Umegaki1, T. Azuma1
1
Division of Gastroenterology, Department of Internal Medicine, Graduate School
of Medicine, Kobe University, 2Department of Endoscopy, Kobe University
Hospital, Kobe, Japan
Contact E-mail Address: yosy29april@gmail.com
INTRODUCTION: Recently, the techniques of endoscopic submucosal dissection (ESD) have been improved, and rectal circumferential and sub-circumferential ESD has been often performed. In esophageal ESD, several clinical studies
reported that resection of more than three-quarter circumference is closely
related to esophageal stricture after ESD. However, little is known about clinical
course after ESD for wide spreading rectal neoplasms.
AIMS & METHODS: The aim of this study is to clarify clinical course of
patients who underwent circumferential and sub-circumferential rectal ESD.
Fifty nine rectal neoplasms in 59 patients which required more than three-quarter
circumferential resection at our hospital and an affiliated hospital from April
2005 to December 2013 were included in the analysis.
RESULTS: Of 59 lesions in this study, 48 lesions were morphologically classified
as lateral spreading tumor (LST) granular type, 2 were LST non-granular type, 2
were 0-IIa, and 7 were 0-I. The median specimen and tumor size were 85 (ranging
43-254) cm and 72 (12-245) cm, respectively. The median procedure time was 139
(33-596) minutes. In terms of the range of submucosal defects that resulted from
ESD treatments, 6 lesions required circumferential dissection, 5 lesions required

United European Gastroenterology Journal 2(1S)


more than 11/12 (eleven-twelfth), and 48 lesions required three-quarter to 11/12
circumferential dissection. Perforation and postoperative bleeding occurred in
one case each, however, both could be treated conservatively. To prevent postoperative rectal strictures, steroids were injected into ulcer floor after ESD in 5
cases, steroid suppositories were administered in 3 cases, and oral steroids were
administered in one case. There were 9 cases of non-curative resection due to
deep invasion or lymphatic/venous invasion, and, 7 cases underwent additional
surgery. Fifty two cases, excluding 7 surgical cases, were followed up by colonoscopy to evaluate the rectal strictures after ESD. Four surgical treatment cases
were also evaluated for strictures by follow-up colonoscopy and/or by surgical
specimens. Of these total 56 cases, strictures occurred in 7 cases (13%). All cases
were the lesions which required resection of more than 11/12 circumference, and
some cases did not receive steroid treatment. Endoscopic balloon dilation (EBD)
was performed to treat the stricture, and it was successfully improved in all cases.
CONCLUSION: Our data shows that less than 11/12 circumferential rectal
resection never causes stricture. Only more than 11/12 circumferential rectal
resection has a risk of developing stricture after ESD, however, it could be
treated by the combination of steroid therapy and EBD, or EBD alone.
Because ESD is less invasive and can preserve anal function compared to surgical
resection, indication of ESD for large rectal neoplasms which needs more than
three-quarter circumferential resection could be effective and beneficial.
Disclosure of Interest: None declared
P1321 EVALUATION FOR THE DIAGNOSTIC PERFORMANCE OF
TRADITIONAL SERRATED ADENOMA USING MAGNIFYING
CHROMOENDOSCOPY
Y. Sato1,*, T. Sakamoto1, H. Sasaki1, Y. Matusyama1, T. Yokota1,
J. Nakamura1, H. Takamaru1, M. Yamada1, Y. Otake1, T. Nakajima1,
T. Matsuda1, Y. Saito1
1
Endoscopy division, National Cancer Center Hospital, tokyo, Japan
INTRODUCTION: Serrated neoplastic pathway has been proposed in recent
years as a new oncogenic pathway for development of colorectal carcinoma.
Traditional serrated adenoma (TSA) is focused of attention as one type of precursor lesion. We use magnifying chromoendoscopy for diagnosis about colorectal lesions, Type III H pit-pattern (fernlike pit-pattern) and IV H pit-pattern
(pinecone pit-pattern) are used for diagnosis of TSA.
AIMS & METHODS: The aim of this investigation was to evaluate the diagnostic performance using magnifying chromoendoscopy (MCE) in identifying
TSA. We analyzed a total of 50 histologically proven TSA and a total of 150
non TSA lesions that underwent endoscopic resection at a single tertiary hospital
between January 2007 and June 2013. For each lesion images taken by conventional white light endoscopy and magnified indigo carmine spraying were
reviewed by five experienced and five non-experienced colonoscopists. A diagnosis of TSA or non-TSA was made on a six-point scale of confidence.
Diagnostic performance was evaluated using Receiver Operating Characteristic
(ROC) analysis based on calculation of the Area Under the Curve (AUC).
RESULTS: AUC was 0.91 for correctly diagnosis TSA or non TSA with MCE
for all reviewers. AUC was 0.95 in experienced group and 0.85 in non-experienced group, respectively (P50.001). The lesions was diagnosed correctly with
high confidence in 89% of the experienced group and in 57% of the non-experienced group (P50.001). AUC was 0.95 which diagnosed with high confidence
versus 0.75 which diagnosed with low confidence in experienced group, and 0.87
versus 0.67 in non-experienced group. In both groups, diagnostic performance
was significantly higher when diagnosed with high confidence (P50.001).
Interobserver agreement for diagnosis of TSA was 0.72 (kappa value) in experienced group and 0.42 (kappa value) in non-experienced group.
CONCLUSION: The performance of MCE for diagnosis of TSA was highly
accurate when the experienced group diagnosed with high confidence.
Interobserver agreement was good results in experienced group. In non-experienced group, the diagnostic performance was still high. With education and
experience in recognizing the typical findings of TSA a high diagnostic accuracy
can be achieved.
REFERENCES
JASS JR, et al. Histopathology 2000; 37: 295-301.
Makinen MJ, et al. J Pathol 2001; 193: 286-294.
Hawkins NJ, et al. Pathology 2002; 34: 548-555.
Disclosure of Interest: None declared
P1322 ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR
COLORECTAL TUMOR BECAME SAFE AND CURATIVE
PROCEDURE AS COMPARED WITH EMR AND PIECEMEAL EMR
Y. Tamegai1,*, T. Kishihara1, H. Ishikawa1, K. Okamoto1, A. Chino1,
M. Igarashi1
1
Endoscopy Division, Cancer Institute Hospital, Tokyo, Japan
Contact E-mail Address: yoshiro.tamegai@jfcr.or.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) technique has
made it possible to perform one-piece resection of colorectal tumors regardless
of lesion size and location. However, ESD has been regarded as a procedure with
the high risk complication than endoscopic mucosal resection (EMR) and piecemeal EMR. In this study, we compared the safety and curability between these
endoscopic treatments.
AIMS & METHODS: ESD was performed for 766 cases of tumor in 760 patients
(male: female 449:311; mean age, 65.7 years) including 8 withdrawal cases. In
same periods, we experienced 4.870 EMR cases and 507 cases with piecemeal
EMR. We compared the incidence of perforation and residual/local recurrence
between ESD, EMR, and piecemeal EMR.

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United European Gastroenterology Journal 2(1S)


RESULTS: We completed ESD procedure on 758 of 766 colorectal tumors (84
lesions in the caecum, 129 in the ascending colon, 142 in the transverse colon, 33
in the descending colon, 180 in the sigmoid colon and 190 in the rectum), and
other 8 cases were abandoned endoscopic treatment due to severe degree fibrosis
relating deep SM cancer invasion and screen-like fibrosis. The average lesion size
was 34.0mm (range: 5-170 mm), and 11 lesions were larger than 100 mm in
diameter. The average operation time was 74.2 minutes (range, 7-480 min).
The incidence of perforation was 0.25% (12/4.870) with EMR, 0.59% (3/507)
with EPMR, and 0.13% (1/766) with ESD including 8 withdrawal cases. This
result revealed that ESD has become a very safe procedure than the EMR and
piecemeal EMR technique. The incidence of residual/local recurrence was 0.49%
(24/4.870) with EMR, 5.33% (27/507) with piecemeal EMR, and 0.13% (1/758)
with ESD excluding 8 withdrawal cases. Thus, although there is no significant
difference in the incidence of perforation between these endoscopic procedures,
the rate of residual/local recurrence after piecemeal EMR was significantly higher
(p50.001) than after EMR and ESD. The possibility to completing ESD for
colorectal tumor sometime depends on the existence of fibrosis in submucosal
layer rather than the size and location. Among 766 ESD cases, 190 cases were
accompanied by SM fibrosis. Among 190 cases with SM fibrosis, of which 59
cases were considered related to cancer invasion and 131 cases were unrelated. En
bloc resection rate of the tumor without fibrosis was 97.6% (562/576), and the
tumor was accompanied with fibrosis in 84.7% (161/190). We experienced only
one case of perforation (0.13%), which was accompanied by fibrosis. From the
view point of safety and curability, use of the ESD procedure is thought to be
limited for this group at high risk of perforation and recurrence. For the above
mentioned reasons, we have developed laparoscopy endoscopy cooperative surgery (LECS) in order to perform an one-piece resection of tumor, which was
difficult to complete ESD due to firm fibrosis in submucosal layer. And we have
achieved one-piece resection for 4 cases by using LECS procedure successfully.
CONCLUSION: ESD for colorectal tumors became safe and curative procedure
owing to the progress of endoscopic technique and devices as compared with
EMR and piecemeal EMR. And we have established LECS procedure in order to
overcome the limitation (high risk of perforation due to wide and firm fibrosis in
SM layer) of ESD procedure.
Disclosure of Interest: None declared
P1323 COMPARISON OF EFFICACY BETWEEN COLONIC SELFEXPANDING METALLIC STENTS AND TRANSANAL TUBE FOR
PALLIATION OR AS A BRIDGE TO ELECTIVE OPERATION IN
MALIGNANT LARGE BOWEL OBSTRUCTION
Y. Ito1,*, N. Ogasawara1, H. Noda1, Y. Tamura1, A. Shimozato1, Y. Kondo1,
Y. Hijikata1, M. Sasaki1, K. Kasugai1
1
Aichi Medical University School of Medicine, Nagakute, Japan
INTRODUCTION: Acute colorectal obstruction often accompanies advanced
colorectal cancer and requires urgent surgical treatment. Approximately 30%
of patients present with acute obstruction, which represents a surgical emergency
associated with mortality and morbidity rates higher than when surgery is performed in elective conditions. To avoid major postoperative complications such
as anastomotic leakage with septic multiple organ failure resulting in high morbidity and mortality, most surgeons advocate two-step surgery. However, various
methods for performing one-step surgery have been reported including intraoperative colonic lavage, preoperative small bowel and colonic decompression and
lavage with a long nasointestinal tube, decompression with self-expandable metal
stent (SEMS) and decompression with a transanal drainage tube (TDT).
However, each of these methods still presents unsolved problems or difficulties
with regard to efficacy, safety and technical aspects. In particular, the efficacy
and safety between SEMS and TDT placement as a bridge to elective surgery or
definitive palliation is debated. This study aimed to evaluate the outcomes of
patients with colorectal obstruction treated using different strategies.
AIMS & METHODS: Fifty eight patients with colorectal obstruction caused by
advanced colon cancers were studied between January 2009 and January 2014.
Twenty three patients underwent SEMS as a bridge to elective surgery (n 11) or
for definitive palliation (n 12). On the other hand 35 patients underwent TDT
as a bridge to elective surgery (n 33) or for definitive palliation (n 2). Colonic
obstruction was identified as the cause of the mechanical ileus by computed
tomography (CT) scan in all patients. The site of the obstruction was the
rectum for 27 patients, the sigmoid colon for 25 patients, the descending colon
for 5 patients and the transverse colon for 1 patient. The histologic diagnosis was
confirmed by endoscopic biopsy at SEMS or TDT placement, or by examination
of the operation specimen.
RESULTS: Placement of SEMS was technically successful in 92.3 % and clinically successful in 100 % of the technically successful cases. Placement of TDT
was technically successful in 85.7 % and clinically successful in 93.5 % of the
technically successful cases. The short-term complication was perforation in 1
patient of SEMS group and 1 patient of TDT group. However, there were no
complications such as migration, occlusion, colon bleeding and abdominal pain
in both groups. The rates of clinically efficacy and complication were not significantly different between the two groups. The median postoperative hospital
stay was 18.8 days in SEMS group versus 38.9 days in TDT group (P50.001).
The in-hospital mortality rates in SEMS group and TDT group were 7.7 % and
11.4%, respectively. The mean procedure time was significantly shorter for
SEMS than for TDT (33.9 minutes vs. 46.0 minutes; P50.05).
CONCLUSION: SEMS achieved a high rate of clinical success and a low rate of
complications. In case of colorectal obstruction, SEMS as a bridge to elective
operation or definitive palliation should be considered as the treatment for
patients given the significant advantages for outcomes compared with TDT.
REFERENCES
Disclosure of Interest: None declared

P1324 PROS AND CONS OF UNSEDATED COLONOSCOPY WITH


WATER INFUSION PERFORMED BY EXPERIENCED
COLONOSCOPISTS
S. Lee1, Y. Yang1,*, G. Song1, A. Jiang1
1
digestive department, the first affiliated hospital of Harbin medical university,
Harbin, China
Contact E-mail Address: Dr.yangylin@163.com
INTRODUCTION: Recently, lots of papers has indicated that colonoscopy with
water infusion in lieu of air insufflation can relieve unsedated patients abdominal
pain, facilitate colonoscopic performance and increase the rate of successful cecal
intubation, et al, especially for trainees. However, non-difficult colonoscopy
performed by experienced colonoscopists is still unclear.
AIMS & METHODS: The aim of this study was to identify if the advantages
above could be achieved by our endoscopists with great total experience.
Method:This study was conducted at 1st hospital of Harbin medical University
from August 2013 through December 2013. A total of 800 patients were randomized to undergo unsedated colonoscopy with either water infusion or air insufflation. Two experienced colonoscopists who had performed at least 10000
standard air insufflation colonoscopies, attained a 95% completion rate and
spent no more than 10min in intubating on average conducted these procedures.
Cecal intubation times, intent-to-treat (ITT) cecal intubation rates and abdominal pain scores evaluated by visual analogue scale (VAS) were documented in the
water infusion group (WIG) compared with the air insufflation group (AIG).
RESULTS: Cecal intubation time in WIG was significantly longer ((273 159s)
than that in AIG (246s 146s). ITT cecal intubation rate in WIG was about
97%, significantly higher when compared with AIG(93%). Median pain scores in
WIG and AIG were 3 and 5, respectively (p50.01).
CONCLUSION: Although colonoscopy with water method seemed time-consuming for experts, it could still increase successful cecal intubation rate, improve
colonoscopistsperformances and effectively relieve patients abdominal pain at
non-difficult colonoscopy. For unsedated colonoscopy conducted by experienced
colonoscopists, it was superior to traditional colonoscopy with air insufflation.
REFERENCES
[1]Boijsen E. Inactive malignant endocrine tumors of the pancreas. Radiologe
1975; 15: 177-182.
[2] Fischer LS, Lumsden A and Leung FX. Water exchange method for colonoscopy:learning curve of an experienced colonoscopist in a U. S.community
practice setting. J Interv Gastroenterol 2012; 2: 128-132.
[3] Radaelli F, Paggi S, Amato A, et al. Warm water infusion versus air insufflation for unsedated colonoscopy:a randomized, controlled trial. Gastrointest
Endosc 2010; 72: 701-709.
[4] Leung FW. A hypothesis-generating review of the water method for difficult
colonoscopy. Scand J Gastroenterol 2011; 46: 517-521.
Disclosure of Interest: None declared
P1325 WATER METHOD FOR DIFFICULT
RANDOMIZED CONTROLLED TRIAL

COLONOSCOPY:

D. Xu1, Y. Yang1,*, G. Shang1, J. Lee1


1
gastroenterology, the 1st affiliated hospital of Harbin Medical University, Harbin,
China
Contact E-mail Address: dr.yangylin@163.com
INTRODUCTION: The femle patients with a lower BMI and abdominal-pelvic
surgery history always suffer more abdominal pain during unsedated colonoscopy, even effect cecal intubation rate and insertion time. Recently years,
some research revealed the water method could reduce abdominal pain during
insertion time. But, without research about water method colonoscopy on femle
patients with a lower BMI and abdominal-pelvic surgery history (difficult
colonoscopy).
AIMS & METHODS: To perform a randomized, controlled trial comparing
water infusion in lieu of air insufflation (study method) and air insufflation
(conventional method) in unsedated difficult colonoscopy. One hundred outpatients with difficult colonoscopy that were defined as femle, with a lower BMI
and abdominal-pelvic surgery history were randomized divided into a water
infusion group (water group) and a traditional air insufflation group (air
group). The cecal intubation rate, abdominal pain scores, cecal intubation time
and the rate of patients refuse to reapt the unsedated colonoscopy were compared
between the water group and the air group.
RESULTS: There was no significant difference in the age and body mass index
(BMI) between the water group and the air group. The abdominal pain score of
the water group was significantly lower than that of the air group (P50.05). The
rate of patients refuse to repeat the unsedated colonoscopy of water group
(8.1%) was significantly lower than that of the air group (29.79%, P50.05).
There was no significant difference in the cecal intubation rate and cecal intubation time between the water group and the air group.
CONCLUSION: Water infusion method instead of air insufflation can reduce
the abdominal pain and improve the acceptability of unsedated colonoscopy.
Disclosure of Interest: None declared
P1326 EFFECTIVENESS OF SURGICEL (FIBRILLAR) IN PATIENTS
WITH COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION
Y.S. Myung1,*, B.M. Ko1, J.P. Han1, H.J. Jung1, M.S. Lee1
1
Digestive Disease Center and Research Institute, Department of Internal Medicine
Soonchunhyang University College of Medicine, Bucheon, Korea, Republic Of
Contact E-mail Address: 88037@schmc.ac.kr

A494
INTRODUCTION: Because the invasive procedure of colorectal endoscopic
submucosal dissection (ESD) entails a extensive mucosal defect and submucosal
exposure, the procedure may have a substantial risk of complications including
delayed bleeding, perforation and bacteremia and/or endotoxemia. Therefore,
these complications was increasing the duration of hospital day.
AIMS & METHODS: The aim of our study is to investigate whether Surgicel
would be effective in reducing complications after colorectal ESD.
Between 2011 and 2013, 72 consecutive patients who underwent a colorectal ESD
by one skilled endoscopists were enrolled. After the colorectal epithelial neoplasm removed, surgicel was sprayed onto the submucosal surface using the
wet type of application in some cases. We evaluated tumor type, location, size,
histology, procedure time, hospital stay and associated complications for both
the surgicel groups (Group A) and non- surgicel groups (Group B). For assessing inflammatory reaction, white blood cells and body temperature were
monitored.
RESULTS: Of the 72 patients, two patients with microperforation were
excluded. Of the total 70 patients, 35 cases (50.0%) underwent the surgicel
application. During follow-up period, rebleeding occurred in 0 (0% in Group
A) patient and 2 (5.7% in Group B) patients. The fever (437.7) was 1 (2.9%) and
8 (22.9%) patients, respectively (p 0.028) and the leukocytosis (410.000 cells/
L3) was 5 (14.3%) and 11 (31.4%) patients, respectively (p 0.088). The inflammatory reaction (fever or leukocytosis) was 6 (17.1%) and 13 (37.1%), respectively (p 0.060). Blood cultures were obtained in five patients with high fever
(4 38 C) and were positive in three of these patients (60%). The isolated microorganism was coagulase-negative Staphylococcus in two patients, and
Streptococcus species in one patient. The mean hospitalization period was 5.14
and 5.97 days, respectively (p 0.016). The Group (surgicel Vs non-surgicel,
p 0.034, odds ratio (OR) 10.074 (1.18685.570) was identified as independent
predictor for fever by multivariated analysis.
CONCLUSION: Surgicel application after Colorectal ESD may be effective
method to reduce complications and mean hospitalization period. Therefore,
Surgicel application may be considered to be a valuable clinical methods.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1328 DIAGNOSIS OF COLORECTAL SERRATED POLYPS USING
ENDOCYTOSCOPY
Y. Ogawa1,*, S.-E. Kudo1, M. Kutsukawa1, Y. Mori1, K. Wakamura1,
K. Ichimasa1, M. Misawa1, T. Kudo1, Y. Wada1, T. Hayashi1, A. Katagiri1,
H. Miyachi1, F. Ishida1, S. Hamatani1, H. Inoue2
1
Digestive Disease Center, Showa Univercity Northern Yokohama Hospital,
Yokohama, 2Digestive Disease Center, Showa Univercity Koto Toyosu Hospital,
Tokyo, Japan
Contact E-mail Address: sunny.onet@gmail.com
INTRODUCTION: Recently, serrated polyps have gathered much interests as
the precursor lesions to colorectal cancers which follow the serrated pathway
different from adenoma carcinoma sequence.
Accurate endoscopic criteria to differentiate the family of serrated polyps including hyperplastic polyps (HPs), sessile serrated adenoma/polyps (SSA/Ps), and
traditional serrated adenomas (TSAs) are needed.
AIMS & METHODS: The aim was to investigate the endocytoscopic features of
serrated polyps focusing on elements of the shape of lumens and nuclei.
A total of 590 colorectal lesions were observed with Endocytoscopy (EC, XCFQ260EC1, CF-Y0020I, Olympus, Tokyo, Japan), and resected endoscopically or
surgically in our Center from May 2005 to October 2013. Of these, 83 serrated
lesions were analyzed. 39 lesions were HPs, 24 lesions were SSA/Ps, and 20
lesions were TSAs.
In the EC images, the shapes of lumens were divided into straight, star-like, oval,
serrated and villous, while the shapes of nuclei were classified into small round
and fusiform.
The study protocol was approved by the ethics committee of Showa University
Northern Yokohama Hospital (No.1302-01). Informed consent was obtained
from all patients before collection of the specimens. This study was registered
in UMIN Clinical Trials Registry (UMIN000007850).
RESULTS: The results are shown in the table below.
lumen

P1327 RISK OF BLEEDING AFTER ENDOSCOPIC SUBMUCOSAL


DISSECTION FOR COLORECTAL NEOPLASIAS IN PATIENTS
WITH CONTINUED USE OF LOW DOSE ASPIRIN
Y. Ninomiya1,*, S. Tanaka1, S. Oka1, S. Nishiyama2, Y. Tamaru2, N. Asayama2,
K. Shigita2, N. Hayashi2, Y. Sanomura1, K. Chayama2
1
Department of Endoscopy, 2Department of Gastroenterology and Metabolism,
Hiroshima University Hospital, Hiroshima, Japan
Contact E-mail Address: ikuyayimonin@live.jp
INTRODUCTION: Low-dose aspirin (LDA), which prevents platelet aggregation, is prescribed to pharmacologically prevent cardiovascular disease. Japan
Gastroenterological Endoscopy Society guideline recommends non-interruption
of LDA perioperatively for patients undergoing endoscopic submucosal dissection (ESD) of colorectal neoplasias (CRNs); however, no studies have confirmed
the efficacy of this practice.
AIMS & METHODS: To retrospectively confirm the validity of non-interruption of LDA in patients undergoing ESD for CRN. Four hundred and ninetyfour patients with 494 CRNs who were resected by ESD at our institution
between August 2008 and December 2013 were included in this study. The
patients were classified into three groups: Group A, those in whom LDA use
was interrupted perioperatively (11 patients treated between August 2008 and
November 2010); Group B, those in whom LDA use was continued perioperatively (24 patients treated between December 2010 and December 2013); and
Group C, those who did not take any anti-thrombogenic agents (440 patients
treated between August 2008 and December 2013). For each group, we investigated the bleeding rate after ESD and compared the rates among the three
groups in location, tumor size, and pathological diagnosis. We defined bleeding
after ESD as a hemoglobin level decreased by 42.0 g/dL and identified it in
those in whom bleeding points were identified by emergency endoscopy for
melena after treatment as previously reported. There was no difference in clinicopathological backgrounds among the three groups.
RESULTS: The bleeding rates after ESD were 18% (2/11) in Group A, 21% (5/
24) in Group B, and 8% (34/440) in Group C, respectively. There was no significant difference in bleeding rate between Groups A and B; however, that of
Group B was significantly higher than that of Group C (p 5 0.01). Bleeding after
ESD occurred in the colon in 13% (1/8), 18% (3/17), and 4% (12/271) of patients
and in the rectum in 33% (1/3), 29% (2/7), and 13% (22/169) of patients in
Groups A, B, and C, respectively. Bleeding occurred in 0% (0/2), 33% (1/3),
and 11% (6/53) of patients with tumor size 520 mm, and in 22% (2/9), 19% (4/
21), and 7% (28/387) of patients with tumor size=20 mm in Groups A, B, and C,
respectively. Bleeding occurred in 0% (0/5), 0% (0/10), and 8% (14/173) of
patients with adenoma, in 33% (1/3), 38% (3/8), and 9% (15/173) of patients
with Tis carcinoma, and in 33% (1/3), 18% (2/11), and 5% (5/94) of patients with
T1 carcinoma in Groups A, B, and C, respectively. There were no differences in
these variables among the three groups. No patients suffered from ischemic
events during the perioperative period.
CONCLUSION: Our data indicate that the continued use of LDA increased the
risk of bleeding after ESD compared to its non-use; however, outcomes did not
differ significantly when LDA use was perioperatively interrupted or continued
in patients with LDA use.
Disclosure of Interest: None declared

straght star-like oval

nuclei
serrated villous fusiform small round

HP (%)
6 (15.4) 31 (79.5) 2 (5.1) 0
SSA/P(%) 0
6 (15)
18 (85) 0
TSA (%) 0
0
0
7 (35)

0
37 (94.9) 2 (5.1)
0
21 (87.5) 3 (12.5)
13 (65) 0
20 (100)

Presence of oval lumens was for diagnosing SSA/Ps (p 5 0.05), and presence of starlike lumens was for diagnosing HPs (p 50.05). Presence of fusiform nuclei and
serrated or villous lumens were significant elements for diagnosing TSA (p 5 0.05).
CONCLUSION: Endocytoscopic diagnosis focusing on the shape of lumens and
nuclei would be useful for the differentiation of serrated polyps.
REFERENCES
Kutsukawa M, Kudo SE, Ikehara N, et al. Gastrointest Endosc 2014; 79: 648-656.
Disclosure of Interest: None declared
P1329 QUANTITATIVE IMAGE ANALYSIS OF THE LUMINAL AREA
FOR HYPERPLASTIC POLYPS AND SESSILE SERRATED
ADENOMA / POLYPS WITH ENDOCYTOSCOPY
Y. Ogawa1,*, S.-E. Kudo1, M. Kutsukawa1, Y. Mori1, K. Wakamura1,
K. Ichimasa1, Y. Kouyama1, M. Misawa1, T. Kudo1, Y. Wada1, T. Hayashi1,
A. Katagiri1, H. Miyachi1, F. Ishida1, S. Hamatani1, H. Inoue2
1
Digestive Disease Center, Showa Univercity Northern Yokohama Hospital,
Yokohama, 2Digestive Disease Center, Showa Univercity Koto Toyosu Hospital,
Tokyo, Japan
Contact E-mail Address: sunny.onet@gmail.com
INTRODUCTION: Sessile serrated adenoma/polyps (SSA/Ps) are known to be
precursors of CRCs. Kimura et al reported that the Type II open pit pattern
(Type II-O) was specific to SSA/Ps. [1] Type II-O were wider and more rounded
in shape, reflecting dilatation of the crypts. But there are no reports which
measured the actual value of the dilatation. Actually we investigated luminal
area by using Endocytoscopy (EC).
AIMS & METHODS: The aim was to determine the threshold of the area that
differentiate SSA/Ps from Hyperplastic polyps (HPs) using EC.
A total of 247 lesions were observed with a single CCD integrated type
Endocytoscopy (CF-Y0020I, Olympus, TOKYO, Japan), and resected endoscopically or surgically in our Center from August 2010 to December 2012. Of these,
19 HPs and 8 SSA/Ps were included. For each lesion we selected one image which
showed the widest lumen, then measured the average area of the contiguous three
lumens, using Image J software (NIH, Bethesda, MD). We analyzed the specific
threshold of the areas.
RESULTS: The average luminal area of SSA/Ps was 9323.34208.1m2, while
that of HPs was 2565.11556.9m2. As assessed by ROC analysis, the luminal
areas threshold of = 6676.3m2 was found with moderate accuracy (sensitivity
87.5% and specificity 94.7%, AUC 0.875).
CONCLUSION: This analysis of the luminal area has been revealed to be useful
for SSAPs diagnosis.
Endocytoscopy is a promising diagnostic tool not only for neoplastic lesions but
also for serrated lesions.
This approach could be adopted to computer-aided diagnosis.
REFERENCES
1) Kimura T, Yamamoto E, Yamano HO, et al. Am J Gastroenterol 2012; 107:
460-469.

A495

United European Gastroenterology Journal 2(1S)


Disclosure of Interest: None declared
P1330 COMPARISON OF BIPOLAR RADIOFREQUENCY CUTTING
AND MONO POLAR CUTTING FOR ENDOSCOPIC SUBMUCOSAL
DISSECTION (ESD) IN A PORCINE MODEL
Z.P. Tsiamoulos1,*, P. Sibbons2, C. Hancock3, A. Polecina4, B.P. Saunders4
1
Wolfson Unit for Endoscopy, St Marks Hospital/Academic Institute, 2Division of
surgical science, Northwick Park Institute for Medical Research, London,
3
Department of Physics, University of Bangor, Bangor, 4Wolfson unit for
Endoscopy, St Marks Hospital and Academic Institute, London, United Kingdom
INTRODUCTION: Current endoscopic knives utilise mono-polar energy (transmitted from the device across the bowel wall to the return plate) to incise the
mucosa, dissect the submucosa and coagulate bleeding vessels. Monopolar
devices have proven efficacy but remain technically challenging to use with the
risk of major complications (perforation/bleeding).
AIMS & METHODS: A new bipolar endoscopic device (energy localised to the
device tip) Speedboat-RS2, Creo Medical Ltd, UK was compared to a standard mono-polar endoscopic device (Flush-knife-BT, Fujifilm, Japan) for endoscopic submucosal dissection (ESD) in the porcine colon. The Speedboat-RS2
blade delivers bipolar radio frequency (RF-400KHz) cutting and microwave
coagulation (5.8GHz) for hemostasis, and contains a retractable needle for submucosal injection/tissue irrigation. It also has an insulated hull to prevent thermal injury to the underlying muscle layer. ESD was performed and video
recorded on 5 consecutive 60kg pigs. The following parameters were measured:
time taken to complete resection, complications encountered and histological
assessment. Two animals were recovered for one week and four animals for
four weeks.
RESULTS: Ten consecutive resections were performed in the colorectum (2 per
animal), 5 with Speedboat-RS2 and 5 with Flushknife-BT. Median time for
Speedboat RS2 to complete a resection was 44 min, range (33-58 min) using
RF cutting 30W, voltage circa 300Vrms and for Flushknife-BT was 52min,
range (28-67min) using monopolar cutting for mucosal incision (80W) and for
submucosal dissection, monopolar forced coagulation 30W. Median flap size
(longest diameter) for Speedboat RS2 was 36.8mm, range (30-42mm) and for
Flushknife was 43mm, range (35-55mm). Microwave coagulation was applied for
either minor bleeding or visible vessels on 25 occasions (mean energy 7.5W) with
Speedboad-RS2. Monopolar coagulation was applied 14 times with Flushknife,
mean energy 30W. The Hemostatic Coagrasper was used 7 times to control
arteriolar bleeding during Speedboat RS2 dissection when microwave was not
sufficient and only once during Flushknife-RS2 dissection. Endoclips were placed
to treat deep muscle injury in the resection base on 10 occasions in the Flushknife resections (15clips placed) and on 3 occasions (3 clips) for the SpeedboatRS2 resections. There was only one study perforation - Flushknife-BT group,
where urgent peritoneal decompression was required and the resection was abandoned. Histology (Speedboat-RS2 resections) showed an intact muscle layer in
four resection bases and in one there was slight muscle alteration but muscle cell
viability was retained. The muscle layer was absent in two Flushknife-BT resection bases and moderately altered in one.
CONCLUSION: Compared to Flush knife-BT ESD colonic resections (monopolar) the Speedboat-RS2 was associated with less muscle injury and need for
endoscopic clipping. However Speedboat-RS2 resections produced more intraprocedural bleeding requiring the haemostatic forceps.
Disclosure of Interest: Z. Tsiamoulos Consultancy for: Creo Medical Ltd, P.
Sibbons Consultancy for: Creo Medical Ltd, C. Hancock Shareholder of: Creo
Medical Ltd, A. Polecina: None declared, B. Saunders Consultancy for: Creo
Medical Ltd.
P1331 SINGLE CENTRE PILOT EVALUATING THE
ENDOCUFF-VISION IN SCREENING COLONOSCOPY

USE

OF

The total number of procedures where Endocuff-vision has been utilized was in
65 occasions (BPS-21, STG-30, AH-14) with similar CIR rates but increased
post-Endocuff ADR.
Post-Endocuff performance:
BPS: CIR-100%/ADR-78%
STG: CIR-98%/ADR-74%
AH: CIR-97%/ADR-77%
The mean ADR with the aid of Endocuff was calculated to be 76%.
On 8 patients the Endocuff-vision was electively removed from the scope due to
insertion difficulties through fixed sigmoid colonic segments secondary to severe
diverticular disease. There were no adverse events reported during the trial evaluation period.
CONCLUSION: In this small pilot study, use of the Endocuff-vision appeared to
improve the average ADR. There were no complications from the use of the cuff
although it was electively removed in 8 cases with severe sigmoid colon diverticulosis. Further randomized evaluation of this simple novel device is warranted.
Disclosure of Interest: None declared
P1332 ENDOSCOPIC
SNARE
PAPILLECTOMY
(ESP)
AMPULLARY TUMOURS: SAFETY AND OUTCOMES FROM A
SINGLE CENTRE TERTIARY CENTRE

FOR

N. Dubale1,*, A. Bapaye1, S.K. Davavala2


Department of digestive diseases and Endoscopy, Deenanath Mangeshkar
Hospital and Research Centre, Pune, Pune, 2 Department of digestive diseases and
Endoscopy, Deenanath Mangeshkar Hospital and Research Centre, Pune,
Mumbai, India
Contact E-mail Address: amolbapaye@gmail.com
1

INTRODUCTION: Tumors of duodenal papillae may be malignant or premalignant. Endoscopic snare papillectomy (ESP) may be a minimally invasive solution to treat these lesions. This retrospective single centre study evaluates the
safety and outcome of ESP for ampullary tumors.
AIMS & METHODS: Patients with ampullary tumors treated with ESP during
6-years (Feb 2007 to Jan 2013) identified from ERCP database. All underwent
pre-ESP EUS and relevant imaging to confirm localized disease and suitability
for procedure.
ESP was performed using a diathermy snare followed by biliary and pancreatic
stenting - removed at 4 6 weeks with base biopsies for residual tumor. Patients
with histology adenocarcinoma were counseled for either close follow-up or
surgical resection & with benign histology were followed up. Follow up done
at 3, 6, 12, 18, and 24 months, yearly thereafter.
RESULTS: 36 patients underwent ESP, mean age 63 years (33 83), males 23.
Mean tumor diameter was 18mm (7 37). Complications - 2 bleeds (managed
endoascopically), one delayed biliary stenosis (underwent stenting) and one fatal
pancreatitis after biopsy.
Histopathology: adenocarcinoma 20 (56%), adenoma 15 (41%), NET 1.
Margin positive 7 (19.4%) adenocarcinoma 4 (20%), adenoma 3 (20%).
Mean follow up 13.6 months (1 58).
4 (11%) lost to follow up 2 each in carcinoma and adenoma group.
Adenoma group no recurrence at mean 12-month (3 36) 10 (67%), recurrence 3 (treated by APC), NET 3-month no recurrence.
CONCLUSION: ESP for ampullary tumors is effective and safe. It can be curative for most ampullary adenomas. ESP for localized adenocarcinoma may be
potentially curative in 4 50% patients and may obviate need for major surgery.
Negative resection margin status may be a predictor of improved ESP outcomes.
Disclosure of Interest: None declared
P1333 SECONDARY BILIARY STONES
ORTHOTOPIC LIVER TRANSPLANTATION

IN

PATIENTS

WITH

Z.P. Tsiamoulos1,*, K. Patel1, R. Misra1, N. Suzuki1, A. Haycock1, S. ThomasGibson1, B.P. Saunders1


1
Wolfson Unit for Endoscopy, St Marks Hospital/Academic Institute, London,
United Kingdom

I. Parzanese1, D. Conte1, R. Penagini1, P. Cantu`1,*


1
Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca` Granda, Maggiore
Policlinico Hospital, Department of Medical-Surgical Pathophysiology and
Transplants, Universita` degli Studi, Milan, Italy
Contact E-mail Address: paolo.cantu@policlinico.mi.it

INTRODUCTION: Although colonoscopy is considered the optimal procedure


for bowel cancer screening, it remains an imperfect tool for cancer prevention,
due to missed adenomas and early cancers. Optimal imaging modalities, innovative scopes and accessories (cap-assisted colonoscopy) have attempted to decrease
the adenoma miss rate. Adenoma detection rates (ADR) have been shown to be a
key performance indicator of quality colonoscopy.
AIMS & METHODS: Endocuff-vision is a simple accessory mounted at the end
of the scope with a proximal row of 6mm length soft plastic, finger-like projections. During scope insertion, these projections invert towards the shaft of the
tube and during withdrawal they evert to hold back the colonic folds augmenting
the forward endoscopic views. ADRs were recorded for screening colonoscopy
procedures before and after introduction of Endocuff-vision.
RESULTS: To date, three screening endoscopists (BPS, STG, AH) have used the
Endocuff-vision as part of a clinical evaluation process (at the discretion of each
endoscopist) from August 2013 until February 2014. From our local Bowel
Cancer Screening Program database, the figures of the caecal intubation rate
(CIR) and the ADR in 135 screening colonoscopies during April 2013 to July
2013 (BPS-45, STG-42, AH-48) before Endo-cuff were retrieved:
Pre-Endocuff performance:
BPS: CIR-100%/ADR-62%
STG: CIR-97%/ADR-40%
AH: CIR-97%/ADR- 54%
Prior to the introduction of the Endocuff-vision, the mean CIR was 98% and the
mean ADR was calculated to be 52%.

INTRODUCTION: Secondary biliary stones have been known as a relevant


complication after orthotopic liver transplantation (OLT) and may be associated
with liver dysfunction. Endoscopic retrograde cholangiopancreatography
(ERCP) represents the reference standard for the therapy of biliary stones.
Data on the efficacy of ERCP in the treatment of post-OLT biliary stone are
scanty.
AIMS & METHODS: To report the rate of secondary biliary stones after OLT,
to investigate the possible triggering factors and to describe treatment in our
Academic Centre.
From January 2000 to December 2013, 539 patients underwent OLT for HCV
(#209) and non-HCV cirrhosis (#330). Among them, 78 OLT-patients (15%)
were evaluated for biliary complications (choledoco-choledocal anastomotic
stricture, biliary stones, hepatico-jejuno anastomotic stricture, hilary ischemic
stricture, biliary leak, sphincter of Oddi dysfunction) on the basis of symptoms,
alterations of liver tests (LTs) and non invasive imaging tests (abdominal ultrasound/magnetic resonance cholangiopancreatography). Presence of biliary stones
was confirmed by ERCP. Patients with biliary stones during biliary stent
exchange to treat anastomotic stricture or leak were excluded.
Comparison between OLT patients with or without biliary stones was done
(using Chi-square test) in the view of etiology of cirrhosis (HCV vs non HCV),
age, immunosuppressive therapy, use of ursodeoxycholic acid and associated
ABS.
RESULTS: Overall 11 patients (10 male, 42-62 y.o.) on 539 (2%) post-OLT
patients with secondary biliary stones were found. They had undergone OLT

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United European Gastroenterology Journal 2(1S)

for HCV, HCV and ETOH, HBV and Wilsons disease associated cirrhosis (# 5,
2, 3 and one respectively). Median timing from OLT was 31 (3-182) mos.
Alteration of LTs and symptoms were present in all patients (jaundice in five,
abdominal pain in four or both in other two). Median stone diameter was 10 (525) mm. In eight patients (73%) stones were multiple and in nine (82%) found
above the anastomosis. De novo ABS was found in four patients and recurrence
of ABS was found in five at a median time of 20 mos after the end of
endotherapy.
In this series 32 ERCPs (1-7/patient) were performed to treat biliary stones.
Three patients required multistenting to progressively dilate a recurrent ABS
and to access stones above it. Seven perendoscopic, six extracorporeal shock
waves and two percutaneous laser lithotripsies were used in four patients, all
of them presenting with multiple and large biliary stones associated with recurrent ABS. One patient underwent hepatico-jejuno anastomosis to treat tight and
angulated ABS and biliary stones as well. Overall, successful removal of biliary
stones was achieved in 9 patients (82%) and ongoing in the remaining two. The
presence of secondary biliary stones was significantly associated with the presence of ABS (p50.001) and not associated to the other factors analyzed.
CONCLUSION: Symptomatic secondary biliary stones have been found in 2%
of all OLT patients which represents 14% of biliary complications in our series.
Recurrence of ABS could play a role as marker of presence of multiple and large
biliary stones. Successful treatment of this condition needs a multidisciplinary
approach, including multisession endotherapies.
Disclosure of Interest: None declared
P1334 EFFICACY AND SAFETY OF DEEP BILIARY ACCESS WITH
GUIDEWIRE CONTROLLED BY THE ENDOSCOPIST COMPARED
TO CONTRAST INJECTION AND GUIDEWIRE MANIPULATION BY
THE ASSISTANT: SINGLE VS. TWO-OPERATOR CANNULATION
TECHNIQUE
R. Di Mitri1,*, F. Mocciaro1, C. Luigiano2, M. Giunta3, C. Linea3, V. Peri3,
M. Di Pisa3, V. Caravello1, G.M. Pecoraro1, L.M. Montalbano3, C. Virgilio2
1
Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli
Hospital, Palermo, 2Gastroenterology Unit, ARNAS Garibaldi Hospital, Catania,
3
Gastroenterology Unit, Villa Sofia - V. Cervello Hospital, Palermo, Italy
Contact E-mail Address: fmocciaro@gmail.com
INTRODUCTION: Cannulation with a sphincterotome is an efficient technique
to gain biliary access in endoscopic retrograde cholangiopancreatography
(ERCP). Contrast injection and two-operator guidewire cannulation technique
requires experience and precise coordination between the operators. The shortwire system allowed the endoscopist to manage the guidewire and the endoscope
independently (single-operator technique).
AIMS & METHODS: We compared single-operator cannulation technique with
two-operator technique collecting data of all consecutive na ve patients (pts) that
underwent ERCP in 3 referral centres (2 used the single-operator technique and 1
the two-operator technique). Data on demographics, final diagnosis, cannulation, non-intentionally pancreatic cannulation, stents placement and complications were evaluated.
RESULTS: 80 pts (male 46 [58%], mean age 69.916.4 yrs) were evaluated
retrospectively in a 1 to 3 ratio (1 from two-operator group vs. 3 from singleoperator group). Indications for ERCP were: choledocholithiasis in 46 pts
(57.5%), pancreatic carcinoma in 15 (18.7%), cholangiocarcinoma in 12
(15%), oddi dysfunction in 3 (3.8%), benign strictures in 2 (2.5%), ampulloma
in 1 (1.4%), biliary leakage in (1.4%). Successful biliary cannulation was
achieved in 69/80 pts (86%) without difference between the two groups (81 vs.
75%, p ns). Cannulation time was 2.811.71 min. (2.72 vs. 3.11, p ns). In
biliary cannulation failure: 9/11 achieved a complete biliary drainage after precut
papillotomy and 2/11 after EUS-rendez-vous. Non-intentionally guidewire pancreatic cannulation was 7 vs. 30% in the single and two-operator group respectively (p 0.006; OR 0.16, 95%CI 0.04-0.67) without difference of post-ERCP
pancreatitis. Peri/intradiverticular papilla was reported in 14% of pts without
difference in terms of cannulation failure or complications between the two
groups. No differences concerning plastic or metallic stents placement were
observed. Ten/80 pts (13%) experienced a complication (12% in single and
15% in two-operator group, p ns): 5 pancreatitis/hyperamylasemia, 4 bleeding,
1 perforation. All complications resolved after medical or endoscopic therapy.
CONCLUSION: Our study shows that the single-operator cannulation technique offers the same efficacy and safety compared to the two-operator technique
but with lower risk of non-intentionally pancreatic cannulation.
Disclosure of Interest: None declared
P1335 FACTORS INFLUENCING THE SUCCESS OF ERCP
TREATMENT OF BILIARY ANASTOMOTIC STRICTURES IN
PATIENTS AFTER LIVER TRANSPLANTATION

IN

S. Francesco Vadala di Prampero1,*, G. Faleschini1, M. Bulajic1,2, N. Panic3,


L. Mario Zoratti1, M. Marino1, M. Zilli1
1
Department of Gastroenterology and Digestive Endoscopy, Academic Center
Santa Maria della Misericordia, Udine, Italy, 2Faculty of Medicine, University
of Belgrade, 3Digestive Endoscopy Unit, University Clinic "Dr Dragisa Misovic",
Belgrade, Serbia
Contact E-mail Address: nikola.panicmail@gmail.com
INTRODUCTION: Biliary anastomotic stricture (BAS) represents the most frequent biliary complication following liver transplantation (LT).
AIMS & METHODS: The aim of the study was to identify epidemiological,
clinical and endoscopic factors influencing appearance and resolution of BAS
in patients undergoing ERCP. We included 171 consecutive liver transplanted
recipients recruited in University Hospital of Udine, Italy from 2004 to 2010 with

at least one year of follow-up. All patients with clinical or radiologic suspicion of
obstructive jaundice and cholestasis underwent ERCP. The ERCP treatment
implied biliary sphyncterotomy followed by stricture dilation and placement of
at least one plastic stent, exchangeable every 3-6 months until the final stricture
resolution.
RESULTS: During post-operative follow-up 40 patients developed BAS. They
underwent median number of 3 ERCP per patient. The median number of 1
stents was inserted per procedure and median period until stricture resolution
was 9 months. Stricture resolution was obtained in 83%. The use of Kehr T tube
(12/23 Vs 28/148, p50.01) and use of cyclosporine as immunosuppressive therapy (18/54 Vs 22/117, p50.05) were significantly more frequent among patients
who developed BAS. We identified use of Kehr T tube (O. R. 5.46, p50.01) and
male gender of donor (O. R. 2.61, p50.01) as an independent predictors of BAS
development. The elevated number of repeated ERCP (OR 0.659; 95% CI 0.5220.832; p 0.000), combined stenting with dilation (OR 0.197; 95% CI 0.0740.525; p 0.001), increasing number of inserted stents per procedure (OR
0.896; 95% CI 0.782-1.026; p 0.112) and longer period of warm ischemia
(OR 0.966; 95% CI 0.938-0.995; p 0.023) were associated with successful endoscopic treatment. On the contrary, longer period of stent in place (OR 1.034; 95%
CI 1.005-1.064; p 0.021), elevated MELD score (OR 1.104; 95% CI 1.0351.178; p 0.003), elevated Child-Pugh score (OR 1.679; 95% CI 1.089-2.591;
p 0.019) and high pre-transplantation bilirubin values (OR 1.104; 95% CI
1.007-1.210; p 0.035) were associated with endoscopic treatment failure.
CONCLUSION: Detailed clinical assessment and skilled endoscopic team is
necessary in order to achieve the successful endoscopic treatment of BAS.
Understanding clinical and endoscopic risk factors may help in predicting of
more appropriate regimen of treatment of patients undergoing ERCP for BAS
post-LT.
Disclosure of Interest: None declared
P1336 MANAGEMENT AND OUTCOMES OF ERCP-RELATED
PERFORATIONS: EXPERIENCE OF THE LAST 6 YEARS IN THE
SINGLE INSTITUTION
S. Budzinskiy1,*, S. Shapovaliantc1, E. Fedorov1, G. Konuhov1
1
Moscow University Hospital 31, Russian National Research Medical University
n/a N. I. Pirogov, Moscow, Russian Federation
Contact E-mail Address: konuhov_gv@rambler.ru
INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP)
and endoscopic papillotomy (EPT), being relatively minimally invasive, nevertheless have their own morbidity, the most feared of which is periduodenal
perforation, and mortality. The management of ERCP-related perforations
remains controversial: some patients requiring immediate surgery, some endoscopy treatment and others only conservative management.
AIMS & METHODS: The aim of the study was to determine the incidence,
predisposing factors, management approaches and clinical outcomes of ERCPrelated perforations. Patients were evaluated according to ERCP indication,
clinical presentation, diagnostic methods, time to diagnosis and treatment, type
of injury, management, length of hospital stay, and clinical outcome.
RESULTS: In our hospital ERCP&EPT have been launched in 1977 and at the
moment experience equals 13937 cases. For the last 6 years - from 01.2008 till
04.2014 - a total 2788 ERCPs were performed in our department. Perforations
were diagnosed in 13 (0.48%) patients. There were 3 males and 10 females. The
age ranged from 55 to 83, mean age 62.710.3 years. Perforation developed after
EPT in 11 pts.; after catheterization with a guide wire in 1; after insertion of an
endoscope in 1 pt. Perforation was confirmed immediately during endoscopy in 7
pts.; per ERCP in 3 pts.; using plain abdominal X-ray or upper abdominal CT
scan in 3 pts. Conservative management was employed in 3 (23%) pts., which
was successful in all of them. Surgical treatment was carried out in 4 (31%) pts.; 3
of them received surgery within 2 to 5 hours after perforation, the rest one was
operated at 8 days after perforation. Two pts. from surgical group died from
intra-abdominal abscess and multiple organ failure (mortality rate 50%). Six pts.
were managed by endoscopic interventions: by endoclipping - 3, by endoclipping
and plastic biliary stenting - 2, by inserting full-covered metal stent and endoclipping - 1. Five pts. recovered without additional complications and their postoperative period was uneventful. One pt. died (16.6%) from abdominal sepsis
and multiple organ failure after salvage surgery due to failed endoscopic treatment (biliary stenting with plastic prosthesis and clipping of the perforation). The
lengths of hospital stay in conservative, endoscopic and surgical groups were
12.2; 12.3 and 31.6 days, respectively. The overall mortality rate after ERCPrelated perforations was 23.1% (3 of 13 pts.).
CONCLUSION: Although rare, ERCP-related perforations are serious complications that may end fatally. Early recognition and appropriate intervention is
the only way to avert a fatal outcome. Early diagnosis can be established by
prompt intraoperative identification using endoscopic visualization, ERCP,
abdominal X-ray and postoperative CT scan. The choice of the management
approach should be individualized, depending on endoscopic and radiological
findings, the features of perforation type and the clinical picture. Endoscopic
clips and biliary stenting should be considered aside from surgical intervention.
Based on our experience delay in intervention, surgery treatment and salvage
surgery after failed endoscopic management contributed to a longer hospital
stay and bad outcomes.
Disclosure of Interest: None declared

A497

United European Gastroenterology Journal 2(1S)


P1337 COMPLICATIONS
ARISING
AFTER
ENDOSCOPIC
RETROGRADE CHOLANGIOPANCREATOGRAPY PLASTIC STENT
INSERTION
S. Chetcuti Zammit1,*, D. Muscat2, J. Ellul Pirotta2, V. Said Pullicino2,
J. Pocock1
1
Gastroenterology, 2Medicine, Mater Dei Hospital, Msida, Malta
Contact E-mail Address: stf_che@yahoo.com
INTRODUCTION: This is a retrospective study looking at possible complications arising after plastic biliary stenting at Endoscopic Retrograde
Cholangiopancreatograpy (ERCP). Biliary stenting is performed to relieve biliary
obstruction in patients with benign or malignant biliary strictures and in patients
with choledocholithiasis if complete common bile duct (CBD) stone clearance is
not achieved at ERCP. More than 90% of stents used were 12 cm 10 Fr plastic
stents. Patients with cholelithiasis and benign strictures usually undergo elective
stent change at 3-4 months while patients stented for malignancy undergo restenting after onset of complications.
For the purposes of the study, biliary sepsis was defined as: fever, right upper
quadrant pain and jaundice requiring intravenous antibiotics and hospitalization.
Stent failure was defined as recurrent obstructive jaundice with biliary hypertension confirmed on CT scan or MRCP but without signs of sepsis.
AIMS & METHODS: All patients who underwent an ERCP between 2009 and
2012 at our hospital were included in this study. Patients were then followed up
until 2013 to determine complication rates.
RESULTS: 552 ERCPs were carried out in 420 patients as 96 patients (22.9%)
underwent an ERCP more than once. Of these 229 (n 552 41.4%) patients had a
stent inserted, and another 63 (n 552 11.4%) patients underwent a change of stent.
148 patients (n 292; 50.7%) underwent stent insertion due to a malignant stricture. 24 of these patients underwent a change of stent. Stents were inserted in 35
patients (n 292; 12.0%) with underlying benign strictures. 109 patients (n 292;
37.3%) had a stent inserted due to incomplete CBD stone clearance.
On follow up 62 patients (n 292; 21.2%) required hospitalization after undergoing their first stent insertion or a change of stent due to biliary sepsis or stent
failure. The average time span between stent insertion and readmission due to
complications was 232 days. Complications related to sepsis and stent failure
were commonest beyond 6 months across all groups. None of the patients experienced problems related to stent migration. Complication rates were similar in all
3 groups.
Number of months after stent insertion
Reason for
stent insertion

46

Benign stricture

4
(3.66%)
6
(4.06%)

2
(5.71%)
0

Choledocholithiasis

2
(5.71%)
4
(3.66%)
3
(2.03%)

2
(5.71%)
1
(0.92%)
0

3
(8.57%)
9
(8.26%)
10
(6.76%)

Malignant stricture

3
(2.75%)
2
(1.35%)

3
(2.03%)

2
(1.83%)
6
(4.06%)

Table 1: Number of patients admitted with complications within months from


ERCP stenting.
CONCLUSION: Leaving a plastic stent for 6 months appears to be safe and does
not seem to result in a disproportionate increase in the rate of biliary sepsis or
stent failure.
Disclosure of Interest: None declared
P1338 SERUM LIPASE LEVEL THRESHOLD 5 10N AT H4 PREDICTS
THE ABSENCE OF POST-ERCP PANCREATITIS OCCURRENCE
AND ALLOWS EARLY ORAL REFEEDING
R. Alhameedi1, A. Di Fiore1, M. Antonietti1, I. Iwanicki-Caron1, A. Gangloff1,
P. Michel1, P. Ducrotte1, S. Lecleire1,*
1
Gastroenterology, University Hospital of Rouen, Rouen, France
Contact E-mail Address: stephane.lecleire@chu-rouen.fr
INTRODUCTION: Acute pancreatitis is a common complication of endoscopic
retrograde cholangio-pancreatography (ERCP), varying from 2 to 20 % in the
literature. Although several predictors of post-ERCP pancreatitis (PEP) have
been described, there is to date no reliable method for predicting its occurrence
with a good accuracy. Besides, post-ERCP early refeeding remains discussed
among physician endoscopists.
AIMS & METHODS: The aim of the study was to test whether the serum lipase
level at H4 after ERCP would: 1) predict the occurrence of PEP; 2) allow an early
refeeding.
Patients and Methods. All patients who underwent ERCP between January 2013
and January 2014 were included in this prospective study, with the exception of
patients who had acute pancreatitis before ERCP. Serum lipase level was routinely controlled after the endoscopic procedure at H4, to define patients at low
risk of pancreatitis (5 10N), and patients at high risk of pancreatitis (4 10N).
Threshold of lipasemia upper 10N at H4 was chosen in order to determine the
prediction of post- ERCP pancreatitis. This threshold was strongly suggested to
be relevant for the prediction of PEP in a previous prospective study of 272
patients (1). When lipase was 5 10N and in the absence of abdominal pain,
the patients received an oral feeding on the evening of the same day with a calory
intake of less than 800 Cal. Patients with lipase 4 10N with or without abdominal pain remained fasting overnight. The sensitivity (Se), specificity (Sp) and
positive (PPV) and negative predictive values (NPV) of the lipase for predicting

a PEP at H4 were calculated. The occurrence of abdominal pain occurring after


early refeefing was noted.
RESULTS: Among the 175 consecutive patients, five patients were excluded
because they had pancreatitis before ERCP. Data from 170 patients were analyzed. The average age of patients was 70 years, 92 women and 78 men. ERCP
was performed for gallstones in the common bile duct (n 103) or a tumor
compressing the CBD (n 67). The rate of PEP was 10.6%. There was a significant correlation between the value of the serum lipase level at H4 and the
occurrence of PEP (p 5 0.0001, Fishers exact test). PEP were mild on CT scan
(Balthazar stages A to C) except from one severe acute pancreatitis (Balthazar D,
0.6%). The Se, Sp, PPV and NPV of serum lipase level at for predicting PEP were
respectively 100 %, 95%, 77% and 100 %. No patient who underwent early postERCP oral refeeding showed any pain nor complications. The mortality was 0%.
Patients who benefited from early oral refeeding did not show any sign of pancreatitis in postprandial peroid.
CONCLUSION: The dosage of serum lipase level at H4 is a simple, fast and
effective method for predicting the occurrence of PEP and identifying patients
who may benefit from early oral refeeding after ERCP and early discharge after
procedure. None of the patients with a serum lipae level 5 10N at H4 developed
PEP. Early oral refeeding in patients with serum lipase level 5 10 N at H4 did
not induce PEP.
REFERENCES
(1) Duclos A, et al. Predictive factors of post-ERCP pancreatitis: a prospective
multicentre study. Oral presentation UEGW 2010.
Disclosure of Interest: R. Alhameedi: no conflict, A. Di Fiore: no conflict, M.
Antonietti: no conflict, I. Iwanicki-Caron: no conflict, A. Gangloff: no conflict,
P. Michel: no conflict, P. Ducrotte: no conflict, S. Lecleire: no conflict.
P1339 MULTICENTER STUDY ON THE OUTCOMES OF ERCP USING
A CAP-FITTED FORWARD-VIEWING ENDOSCOPE IN PATIENTS
WITH BILLROTH II GASTRECTOMY
T.J. Song1,*, S.S. Lee1, J.S. Choi2, H.J. Kim3, J.W. Jang4, J.W. Kim5,
D.H. Park1, D.W. Seo1, S.K. Lee1, M.-H. Kim1
1
Ulsan University College of Medicine, Asan Medical Center, Seoul, 2Inje
University Busan Paik Hospital, Busan, 3Gyeongsang College of Medicine, Jinju,
4
Eulgi University College of Medicine, Daejeon, 5Inje University Ilsan Paik
Hospital, Koyang, Korea, Republic Of
Contact E-mail Address: medi01@naver.com
INTRODUCTION: In patients with Billroth II gastrectomy, ERCP has often
been performed using a cap-fitted forward-viewing endoscope because of technical difficulty and risk of adverse events in the use of duodenoscope. This study
was aimed to investigate the outcomes and the risk factors of adverse events of
ERCP using a cap-fitted forward-viewing endoscope in patients with Billroth II
gastrectomy as a multicenter study.
AIMS & METHODS: Between August 2008 and May 2013, we retrospectively
reviewed the data on the ERCP using a cap-fitted forward-viewing endoscope in
patients who had undergone Billroth II gastrectomy. During the study periods,
123 patients were enrolled at five tertiary referral centers in South Korea.
RESULTS: The indications of ERCP were common bile duct (CBD) stone in
80.5% (99/123), CBD stricture in 9.8% (12/123), CBD cancer in 1.6% (2/123)
and others in 8.1% (10/123). Successful ERCP could be achieved in 82.1% (101/
123). The reasons of failed ERCP were failure of entry to ampulla in 13 patients,
failure of cannulation in five patients and the others in four patients. Mean size
and number of CBD stones was 10.83.9mm and 1.781.1, respectively. For the
complete removal of CBD stones, mechanical lithotripsy was required in 17.8%
(15/84) of patients. Endoscopic papillary balloon dilatation was performed in
68.2 % (84/123) of patients. In these patients, the mean CBD diameter was
15.23.9mm and the mean balloon size and mean ballooning time was
10.11.4mm and 63.427.4sec. Adverse events occurred in 24.3% (30/123),
including asymptomatic hyperamylasemia in 15.4% (19/123), post-ERCP pancreatitis in 7.3% (9/123), bowel perforation in 1.6% (2/123). The large stone
more than 20mm was the significant risk factors for adverse events (odds ratio
15.5).
CONCLUSION: In patients with Billroth II gastrectomy, the ERCP using a capfitted forward-viewing endoscope may be a useful method. Nevertheless, the
significant rate of adverse events cannot be ignored, suggesting the need for
taking precautions.
Disclosure of Interest: None declared
P1340 EFFICACY AND SAFETY OF ENDOSCOPIC PAPILLARY LARGE
BALLOON DILATION FOR DIFFICULT STONES IN HIGH ELDERLY
PATIENTS
T. Tsuchiya1,*, T. Itoi1, A. Sofuni1, F. Itokawa1, S. Tsuji1, K. Ishii1, I. Nobuhito1,
K. Kamada1, J. Umeda1, R. Tanaka1, R. Tonozuka1, M. Honjyo1, S. Mukai1,
M. Fujita1, F. Moriyasu1
1
Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
Contact E-mail Address: tsuchiya@tokyo-med.ac.jp
INTRODUCTION: Minimally invasive interventions for choledocholithiasis are
preferable in elderly patients because they tend to have multiple underlying disorders or a decreased activity of daily living. Endoscopic sphincterotomy and
endoscopic papillary balloon dilation have been recognized as first-line treatments for choledocholithiasis excluding difficult cases such as large stones or
multiple stones. Recently, the safety and efficacy of endoscopic papillary large
balloon dilation (EPLBD) for difficult choledocholithiasis cases have been
reported. However, there was a few reports for elderly patients.
AIMS & METHODS: To investigate whether EPLBD can be safety and effectively performed in high elderly patients. The medical records of 204 patients who

A498
underwent EPLBD from November 2006 to August 2013 were analyzed retrospectively. The patients were divided into 2 groups: Group A (85 years); Group
B (585 years). The criteria of EPLBD was the patients with large or multiple
CBD stones; 13 mm or more in the shortest dimension (i.e., the shortest dimension of the largest stone) or multiple (3) bile duct stones with the smallest stone
410 mm in the shortest dimension.
RESULTS: Number of patients are 57 and 147 in Group A and B. The average
age are 89.9 (85-102) and 73.2 (31-84) years old in Group A and B, respectively.
The patients in Group A had more prevalence of periampullary diverticulum
than those in Group B (54.4% vs 36.7 %, p 0.02). However, there was no
significant difference in the success rates in the first session (96.5 vs 95.3 %,
p 0.99) and in the final success rates (100 % in both groups) between Group
A and Group B. The adverse event rates (3.5 vs 3.4 %, p 0.70) and recurrence
rates of choledocholithiasis (12.3 vs 10.2 %, p 0.67) were not significantly
different. Post-EPLBD pancreatitis (moderate) was observed in 1 patient in
Group A. Perforation developed in 1 patient in Group A and none in Group
B. In Group B, mild hemorrhage without a transfusion developed in 4 patient,
and acute cholangitis in 1 patients.
CONCLUSION: This study suggested that EPLBD procedure for high elderly
patients was safe and effective for difficult stones.
Disclosure of Interest: None declared
P1341 PROGNOSTIC FACTORS OF RESPONSE TO ENDOSCOPIC
TREATMENT IN PAINFUL CHRONIC PANCREATITIS RETROSPECTIVE OBSERVATIONAL STUDY
M. Maria Alina1, T. Marcel1,*
Department of Gastroenterology, 3rd Medical Clinic, Cluj Napoca, Romania, Cluj
Napoca, Romania
Contact E-mail Address: alina_mandrutiu@yahoo.com
1

INTRODUCTION: Patients with chronic pancreatitis often present with severe


abdominal pain, resistant to common analgesics. There is no etiological therapy
for chronic pancreatitis. The goal of the endoscopic treatment of painful chronic
pancreatitis is to drain the pancreatic duct, reduce the frequency and severity of
pain and resolve local complications of the disease. Few data are available on the
long term efficacy of endoscopic treatement.
AIMS & METHODS: The aim: to evaluate the endoscopic treatment efficacy
and the prognostic factors of long-term response treatment in patients with
painful chronic pancreatitis. All the patients with painful chronic pancreatitis
who underwent ERCP or endoscopic treatment in the last 5 years at a single
tertiary referral endoscopy center were retrospectively identified from the hospital database. The inclusion criteria were: the pancreatic pain and dilated pancreatic duct. Demographics data regarding the clinical history, the endoscopic
procedures and the patients follow-up were collected from the medical charts and
analyzed. All the patients were called to obtain updated clinical informations.
RESULTS: We included 132 patients (109M,23F, mean age 52, predominant
etiology ethanolic). At enrollment, the pancreatography showed:minimal
changes of the pancreatic ducts in 10 patients, pancreatic duct stones in 30
patients, pancreatic pseudocyst in 24 patients and 29 patients had chronic pancreatitis related biliary strictures. A total of 375 procedure were performed
(mean3/patient). In 25 patients the sphincterotomy was the only procedure
required. 2 patients needed ESWL. Pancreatic stone extractions were performed
in 39 patients. Pancreatic plastic stenting were performed in 49 patients among
which 34 patients required many long term stenting. The pseudocyst have been
drained transpapillary (11 patients), transmural (9 patients) and EUS (4
patients). During the follow-up, a part of patients (10 patients) developed a
biliary stricture. The biliary decompression was performed by CBD plastic stenting (22 patients), multiple plastic stents (8 patients), SEMS (2 patients). In
90.16% cases the procedures was successful, in 9.8% failed and the patients
underwent surgical drainage. Mean follow up after treatment is 24 months.
About 90% of patients had substantial improvement of symptoms after endoscopical treatment, including frequency and severity of pain attack. Pain disappeared completely in 56% patients during follow-up. The pseudocysts was
successfully drained and did not reappeared during follow-up in 95% cases.
The hospitalization admission rate in patients with severe chronic pancreatitis
was higher (mean5/patient) compared to those patients with minimal pancreatic
changes (mean3.6/patient). No differences were found regarding the number of
hospital admission between the patients with pancreatic stones and the patients
without pancreatic duct stones. Success of endotherapy in chronic pancreatitis
with minimal changes was 94.12% vs. 89.8% in patients with pancreatic duct
strictures. None of the patients younger than 40 years required surgical drainage
and the success rate in patients older than 40 years was 87%.
CONCLUSION: We consider that in painful chronic pancreatitis the minimal
endoscopic treatment is sufficient. Due to the increased risk of complications and
higher costs, additional endoscopic treatment and surgical intervention should be
reserved for cases with no response to the minimal endoscopic treatment.
Disclosure of Interest: None declared
P1342 ASSESSING ENDOSCOPIC SKILLS DURING ERCP TRAINING
A ROMANIAN TERTIARY CENTER EXPERIENCE
T.A. Pop1,2,*, M. Tantau1,2
1
Gastroenterology, Regional Institute for Gastroenterology and Hepatology "Prof.
Dr. O. Fodor", 2Gastroenterology, UNIVERSITY OF MEDICINE AND
PHARMACY I. HATIEGANU, Cluj-Napoca, Romania
INTRODUCTION: The current Romanian endoscopy teaching system confronts with several problems including lack of targeted courses for practical
skills development. Also, clear criteria for assessing ERCP procedures and the
ability to develop and carry out patient management plans are not defined.

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: Our aim was to analyze the ERCP learning curve and to
assess the development of endoscopic competence.
From January 2011 - May 2013, 4 trainees in our center entered the ERCP
training program. The training consisted of modules of 100 cases each. The
CBD cannulation in patients with non-altered anatomy and the rate of complications were prospectively recorded for every trainee after every module fulfillment.
Trainee success rates were compared to those of the trainer.
RESULTS: Trainees performed 1041 examinations. Each did an average of 251
examinations (range, 109 to 396). The CBD median cannulation rate improved
significantly from first module (100 procedures - 54.57%) to 2nd module (200
procedure) (79.33%, P 5 .048). The 3rd module was completed only by 2 trainees
who reached a 82.5 CBD cannulation rate. The rate of complications decreased
form 14.67% (first 100 ERCPs) to 8.72% (200 ERCPs) and 6.01% (300 ERCPs),
respectively.
CONCLUSION: The success rate for deep biliary cannulation should be assessed
in every ERCP trainee. A success rate of at least 80% for deep biliary cannulation should become a threshold for ERCP competence programs.
Disclosure of Interest: None declared
P1343 RISK FACTORS FOR BLEEDING AFTER ENDOSCOPIC
SPHINCTEROTOMY IN COMPARISON WITH ENDOSCOPIC
PAPILLARY BALLOON DILATION FOR THE PATIENTS WITH
ANTIPLATELET THERAPY
T. Arizumi1,*, N. Toda1, K. Saito2, T. Yamada1, M. Yamagami1, K. Kojima1,
T. Ohki1, M. Seki1, K. Tagawa1
1
Gastroenterology, Mitsui Memorial Hospital, 2Department of Gastoenterology,
Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
Contact E-mail Address: arizut-tky@umin.ac.jp
INTRODUCTION: In Japan, endoscopic papillary balloon dilation (EPBD) is
classified as low risk procedure of bleeding, and considered endoscopic sphincterotomy (EST) as high risk. EPBD can be performed for the patient with antiplatelet therapy. But Japan Gastroenterological Endoscopy Soaciety Guideline
do not recommend to perform EST for the patient with antiplatelet therapy,
except for the patient with aspirin monotherapy. This study aimed to evaluate
risk factors of bleeding after such endoscopic procedures for the patient with
antiplatelet therapy.
AIMS & METHODS: Consecutive patients received EST or EPBD with antiplatelet therapy were retrospectively studied. A total of 118 patients (EST 85,
EPBD 33) who were received such endoscopic procedure (Jan 2009 to Dec.2013)
were enrolled. Univariate and multivariate analyses to identify risk factors for
bleeding were performed using a proportional hazards model.
RESULTS: In EST group (25 female, 60 male, mean age 77.0), the number of
patients taking with aspirin, ticlopidine, clopidogrel, other antiplatelet agent,
dual agents were 70, 9, 16, 12, 21, respectively. In EPBD group (7 female, 26
male, mean age 76.8), the number of patients were 25, 3, 4, 5, 4, respectively.
Perforation did not occur in both groups. Pancreatitis was significantly frequent
in EPBD group (EST 2/85 2.4% vs EPBD 4/33 12.1%, p 0.042). Bleeding
occurred with 3 patients in EST group (3.5%), but did not occurred in EPBD
group. There was not significant change. The details of patients with bleeding
were 2 patients taking with aspirin and ticlopidine, 1 patient with clopidgrel
monotherapy. All patient with bleeding took thienopyridine compound.
Univariate analysis revealed that ticlopidine therapy (2/9 p 0.0163), tienopyridine compound therapy (3/25 p 0.0058), and dual antiplatelet therapy (2/21
p 0.0031) were risk factors of bleeding after EST for patient with antiplatelet
therapy. But by multivariate analysis, none of them were significant.
CONCLUSION: In this study, taking tienopyridine compound and taking ticlopidine, dual antiplatelet therapy were proved to be not statistically significant
risk factors for bleeding after EST, but showed increase trend. EPBD may be
considered alternative procedure to EST instead of the high incidence of pancreatitis associated with EPBD.
Disclosure of Interest: None declared
P1344 ENDOSCOPIC
RETROGRADE
CHOLANGIOPANCREATOGRAPHY IN BILLROTH II PATIENTS
A SINGLE CENTRE EXPERIENCE
V. Costa Santos1,*, N. Nunes1, F. Avila1, P. Massinha1, R. Liberal1, A.C. Rego1,
J.R. Pereira1, N. Paz1, M.A. Duarte1
1
Gastrenterologia, Hospital do Divino Esprito Santo de Ponta Delgada, Ponta
Delgada, Portugal
Contact E-mail Address: vera@multi.pt
INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP)
in patients submitted to a previously gastrectomy with a Billroth II reconstruction is technically challenging, with success rates ranging from 50 to 90 %.
AIMS & METHODS: In this study we aimed to analyse ERCPs performed in
Billroth II patients, addressing techniques and accessories used, difficulties
found, success rate and complications.
Medical and endoscopic records of Billroth II patients submitted to ERCP between
January 2011 and December 2013 at our institution were retrospectively reviewed.
RESULTS: A total of 15 ERCPs performed in 12 patients (9 male and 3 female,
mean age 71 years, range 51-88 years) were included in the analysis.
A duodenoscope was used in 12 procedures (3 of which with a guidewire previously placed in the afferent loop), a paediatric colonoscope in 2 and an endoscope in 1 procedure.
Afferent loop intubation was achieved in all patients. In one patient, papilla was
not reached due to duodenal stenosis. Precut was used for biliary cannulation in 9
ERCPs (60%). Of these, 3 were performed in a previously placed Wirsung stent,
and 2 were followed by dilation without sphincterotomy.

United European Gastroenterology Journal 2(1S)


ERCP was successful at first attempt in 9 procedures. Inability to perform selective cannulation in 5 cases and the presence of a duodenal stenosis in 1 prevented
the completion of ERCP in the remaining cases. A second ERCP was performed
in 3 patients, successful in all of them. The overall success rate was 80%.
One ERCP was interrupted due to patient hemodynamic instability and in
another patient there was a self-limited papilla bleeding after dilation. No perforation was recorded.
CONCLUSION: ERCP is effective and safe in Billroth II patients. The choice of
the most appropriate technique in each case seems to be the best way to increase
the success rate in these patients and to avoid complications.
Disclosure of Interest: None declared
P1345 PROSPECTIVE EVALUATION OF ERCP PERFORMANCE
RESULTS OF A NATIONWIDE QUALITY REGISTRY
V.E. Ekkelenkamp1,*, R.A. de Man1, F. ter Borg2, P.C. J. ter Borg3, M.J. Bruno1,
M.J. M. Groenen4, A.J. P. van Tilburg5, E.A. J. Rauws6, A.D. Koch1
1
Gastroenterology and Hepatology, Erasmus MC University Medical Center,
Rotterdam, 2Gastroenterology and Hepatology, Deventer Hospital, Deventer,
3
Gastroenterology and Hepatology, Ikazia Hospital, Rotterdam, 4Gastroenterology
and Hepatology, Rijnstate Hospital, Arnhem, 5Gastroenterology and Hepatology,
Sint Franciscus Gasthuis, Rotterdam, 6Gastroenterology and Hepatology,
Academic Medical Center, Amsterdam, Netherlands
INTRODUCTION: Despite significant interest by health authorities, patient
organizations and insurance companies, data on procedural outcome and quality
of ERCP in general and academic practice are sparse. The aim of this study was
to assess procedural outcome of ERCP within a large prospective registry in the
Netherlands and to evaluate associations between endoscopist-related factors
and procedural outcome.
AIMS & METHODS: All endoscopists performing ERCP in the Netherlands
were invited to register their ERCPs over a one-year period using the Rotterdam
Assessment Form for ERCP (RAF-E). Primary outcome measure was procedural success. A priori difficulty level of the procedure was classified according
to Schutz. Baseline characteristics of the endoscopist, e.g. previous experience,
were recorded at study entry. Regression analysis was performed to identify
predictors of procedural outcome.
RESULTS: A total of 8575 ERCPs was registered by 171 endoscopists from 61
centers. This entails about 50% of all ERCPs performed in that period nationwide.
Overall procedural success was 85.8%. An intact papillary anatomy was present in
5106 patients (59.5%): procedural success in this subset of patients was 83.4% versus
89.4% after sphincterotomy (p50.001). Regression analysis through Generalized
Estimating Equations identified degree of difficulty (p50.001), intact papillary
anatomy (p50.001), and previous ERCP failure (p50.001) to be independently
associated with procedural failure. Yearly volume of ERCPs (p50.01) and trainee
involvement (p50.05) were independently associated with success.
CONCLUSION: Our nationwide prospective RAF-E registry proved to be a
valuable tool to gain insight in procedural outcome of ERCPs. The overall
procedural success rate for ERCP was 85.8%. Factors predictive of outcome
include Schutz classification (degree of difficulty), papillary anatomy, previous
ERCP failure, ERCP volume, and trainee involvement.
Disclosure of Interest: None declared
P1346 HIGH RATE OF DEEP SEDATION WITH A COMBINATION OF
MIDAZOLAM AND FENTANIL IN A CONSECUTIVE SERIES OF
PATIENTS UNDERGOING UPPER EUS
N. Pagano1,*, L.H. Eusebi1, C. Luigiano2, G. Rando3, R.M. Zagari1, F. Bazzoli1
1
Gastroenterology and Endoscopy Unit, Policlinico S. Orsola, University of
Bologna, Bologna, 2Gastroenterology Unit, ARNAS Garibaldi, Catania, 3UOC
Chirurgia e diagnostica endoscopica, Az. ospedaliera S. Salvatore, LAquila, Italy
INTRODUCTION: A good level of sedation increases outcomes and safety in
interventional endoscopic procedures. With benzodiazepines and morphinic
based protocols a high frequency of deep sedation has been reported. This is
our experience with a midazolam/fentanil based protocol of sedation in patients
undergoing upper digestive endoscopic ultrasonography (EUS) with particular
attention to the level of sedation.
AIMS & METHODS: We retrospectively analyzed data on sedation in all patients
undergoing EUS, collected prospectively from March to October 2013. Demographic
data, indication, type of procedure, data on technique, ASA score, dosage of drugs,
outcomes and complications were collected. Patients were sedated with a combination
of 1-2 mcg/Kg of fentanil and 0.05 mg/Kg of midazolam as initial bolus. Repeated
boluses of 1 mg of midazolam every 5 minutes were then administered based on
patients response. Sp02, blood pressure, heart rate and respiratory movements
were continuously monitorized during the procedure. OASS score was calculated
every 5 minutes. Patients were discharged when the score was 4 5. We evaluated
patients and endoscopist satisfation on a scale from 0 to 10 after the procedure.
RESULTS: During the observation period, 320 upper EUS procedures were
performed. 178 patients were males, mean age was 65 (range 25-89), 280 outpatients (88%). There were 22 ASA IV patients (7%), 98 ASA III patients (31%)
and 200 ASA I and II patients (62%). In 96 cases a FNA was performed (30%).
The mean duration of procedures was 25 minutes (range 5-45). The mean dose of
midazolam was 8.5 mg (range 2-15) and the mean dose of fentanil was 95 mcg
(range 0-200). In 125 procedures (39%) the mean OASS was 5 2 (deep sedation),
in 149 (46%) was between 2 and 4 (moderate sedation), in 46 (15%) 4 4 (mild
sedation). We reported 20 minor desaturation events (Sp02 590% but 4 85%
for more than 10 seconds) that responded promptly to increase in oxygen flux.
One patient required bag-mask ventilation for 2 minutes. In this case the procedure was completed after rescue maneuvers. The mean recovery time was 65

A499
minutes (range 45 to 90). The patients and endoscopist mean statisfation was
8.5 (range 6-10) and 7.3 (range 6-9).
CONCLUSION: In our series, midazolam and fentanil based sedation allowed
the execution of all upper EUS with a good safety profile. The doses needed to
obtain a good compliance resulted in a consistent rate of deep sedation in our
experience.
Disclosure of Interest: None declared
P1347 HIGHER CA 19-9 LEVELS ARE RELATED WITH HIGHER
DIAGNOSTIC YIELD OF EUS-FNA IN PANCREATIC
ADENOCARCINOMA
R. Barosa1,*, P.P. Marques2, L.R. Ramos2, P. Figueiredo2, T. Meira2, J. Freitas2
1
Gastroenterology, 2Hospital Garcia de Orta, Almada, Portugal
Contact E-mail Address: a.rita.b@gmail.com
INTRODUCTION: Endoscopic ultrasonography guided fine needle aspiration
(EUS-FNA) sensitivity and accuracy described in literature is 60-90% and 6095%, respectively. Size and type of needle, multiple passes and on-site cytopathology assessment increases diagnostic accuracy. Serologic CA 19-9 correlates
with pancreatic adenocarcinoma stage.
AIMS & METHODS: To assess the relationship between CA 19-9 and diagnostic yield of EUS-FNA. Retrospective analysis of 293 patients with pancreatic
mass diagnosed between January 2009 and May 2013. A total of 87 patients
underwenting first EUS-FNA were included. Two groups were analyzed: cytology diagnostic of adenocarcinoma (group 1) and inconclusive cytology (group 2).
Median expression of CA 19-9 was compared and CA19-9 was analyzed as
dichotomous variable (1000 or 5 1000 U/L). Mann-Whitney and Qui-square
tests were used for groups comparison.
RESULTS: FNA was suggestive of adenocarcinoma in 69 patients (mean age 70
years, 49% male) and inconclusive in 18 patients (mean age 67 years, 56% male).
EUS-FNA sensitivity for adenocarcinoma diagnosis was 73%. The median CA
19-9 in group 1 was 1000 U/L (range 0-48462 U/L) and in group 2 was 196 U/L
(range 0-7685 U/L), p 0.04. In the subgroup with CA 19-9 1000 U/L, 7.9% of
all EUS-FNA were inconclusive vs. 30.6% when CA 19-9 51000 U/L
(p 0.009).
CONCLUSION: To the best of our knowledge this is the first study assessing the
relationship between CA 19-9 levels and EUS-FNA diagnostic yield. Patients
with first EUS-FNA diagnostic for adenocarcinoma have higher levels of CA
19-9. When using a cut- off 1000 U/L cytology is less often inconclusive.
Disclosure of Interest: None declared
P1348 A PROSPECTIVE COMPARISON OF 22-GAUGE FLEXIBLE
NEEDLE AND SIDE PORT NEEDLE IN EUS-FNA FOR
PANCREATIC MASSES
S. Koyama1,*, H. Imazu1, H. Arakawa1, S. Koido2, K. Kanazawa1, N. Mori1,
M. Chiba1, H. Toyoizumi1, N. Shimamoto1, T.L. Ang3, H. Tajiri2
1
Department of Endoscopy, 2Division of Gastroenterology and Hepatology,
Department of Internal Medicine, The Jikei University School of Medicine, Tokyo,
Japan, 3Department of Gastroenterology and Hepatology, Changi General
Hospital, Singapore, Singapore
Contact E-mail Address: himazu21@aol.com
INTRODUCTION: Two different needles; a cobalt chromium needle with an
end port alone to enhance flexibility (ExpectTM: flexible needle, Boston Scientific)
and a stainless steel needle with both side and end ports (EzShot2: side port
needle, Olympus Medical Systems), have been developed to improve the diagnostic yield of EUS-FNA.
AIMS & METHODS: The aim of this study was to compare the performance of
the 22-gauge flexible needle and side port needle in EUS-FNA for pancreatic
masses. Fifty-two consecutive patients who underwent EUS-FNA for pancreatic
masses were prospectively enrolled in this study from January 2013. EUS-FNA
was performed for each mass using both with randomization of puncture
sequence. Then, differences of diagnostic accuracy was evaluated, as well as,
the score of adequateness of obtained specimens for cytological evaluation,
needle visibility and ease of puncture (0: poor, 1: good, 2: excellent) 1).
RESULTS: A total of 86 punctures (43 with the flexible needle and 43 with the
side port needle) were analyzed in 42 patients with pancreatic masses. The final
diagnosis based on results of EUS-FNA, surgery and clinical course were pancreatic carcinoma in 32 patients, chronic pancreatitis in 6 and autoimmune pancreatitis in 5. The pancreatic mass was located in the head of pancreas in 25
patients, the body in 11, and the tail in 7. Sensitivity, specificity and accuracy
with the overall, flexible needle and side port needle for detecting pancreatic
carcinoma were 93.5/100/95.2%, 83.9/100/88.1%, and 77.4/100/83.3%, respectively (N. S). Although the score of visibility of both needles was similar (1.9 vs.
1.86, p 0.4), the score of adequateness of specimens of flexible needle was
significantly higher than that of side port needle (1.88 vs. 1.69, p 0.039). In
addition, there was no significant difference in the score of adequateness of
specimens obtained from masses of the pancreatic head and body/tail with the
flexible needle (1.87 vs. 1.89), while the score of adequateness for specimens
obtained from pancreatic head masses with the side port needle was significantly
lower than that for pancreatic body/tail masses (1.57 vs. 1.83, p 0.02). The
score of ease of puncture of flexible needle was significantly higher than that
of side port needle (1.88 vs. 1.38, p50.001).
CONCLUSION: The flexible and side port needles have similar overall diagnostic yield, when EUS-FNA is performed for pancreatic masses. However, the
flexible needle was superior in the adequateness of obtained specimens, especially
from pancreatic head lesions, because puncture is significantly easier. Therefore,

A500
the exploitation of new needle should probably be focused on enhancement of
puncture performance.
REFERENCES
1) Imazu H et al. A prospective comparison of EUS guided FNA using 22-gauge
and 25-gauge needles. Gastroenterol Res Prac 2009.
Disclosure of Interest: None declared
P1349 REVIEW OF 114 ENDOSCOPIC ULTRASOUND-GUIDED
CYSTGASTROTOMIES FOR PANCREATIC PSEUDOCYST IN TWO
LONDON TEACHING HOSPITALS
S.F. Sze1,*, M.G. Keane1, S. Murray1, G.J. Johnson1, M.H. Chapman1,
G.J. Webster1, D. Thorburn2, S.P. Pereira1
1
Division of GI Services, University College London Hospital, 2Royal Free
Hospital, London, United Kingdom
Contact E-mail Address: alexsze@yahoo.com
INTRODUCTION: With the advancement of interventional endoscopic ultrasound (EUS), EUS-guided cystgastrostomy is now regarded as a good alternative
to surgical or percutaneous drainage in the management of pancreatic fluid
collections. This procedure was performed in University College London
Hospital (UCLH) since 1998 and was started in Royal Free Hospital (RFH),
London from 2009 when the two services were combined.
AIMS & METHODS: This is a retrospective review of all EUS-guided cystgastrostomies performed in UCLH from 1998 to 2013 (16-year period) and RFH
from 2009 to 2013 (5-year period). Case details including demographics, indications, procedure method and outcome were retreived from patient record database and endoscopy reporting tool, which were then reviewed and analyzed.
RESULTS: A total of 114 EUS-guided cystgastrostomies were identified, with 80
performed at UCLH and 34 at RFH. The male-to-female ratio was 1.5:1 and the
median age was 55 years (range 23-85). The median onset of pancreatitis before
drainage was 6 months (range 1-120). The most common causes of pancreatitis
were gallstones (44.7%), idiopathic (23.7%), alcohol (20.2%), and post-ERCP
(3.5%). The pseudocyst was usually located over the pancreatic body (45.6%) or
head (14.9%). Indications for drainage included abdominal pain (40.4%),
increasing pseudocyst size (35.1%), both pain and increasing size (3.51%),
infected pseudocyst (14%) or luminal or biliary obstruction (5.3%). 87.7% of
patients had only one pseudocyst. The median maximum diameter of the pseudocyst was 97.5mm (range 42-200). Nine patients had received previous percutaneous drainage while one patient had previous surgical drainage.
Bulge sign was reported in 28 cases (24.6%). The routes of puncture were via
body (64%), antrum (13.2%), fundus (7.9%) and duodenum (6.1%). A cystotome was used in 71.1% of cases. The median length of follow-up was 13 months
(range 1-138). The procedure was technically successful in 86% (98/114); drainage failed in fourteen cases (12.3%) and in two cases the pseudocyst was aspirated to dryness without stent insertion. Among those technically successful
cases, a pseudocyst recurred in 13.3% (13/98) cases and one pseudocyst persisted
despite drainage. Those with recurrence were managed conservatively (7/13), by
repeat EUS-guided cystgastrostomy (3/13), by surgical drainage (2/13) or percutaneous drainage (1/13). Complications occured in 8.8% (10/114) including three
cases of pneumoperitoneum which required laparotomy, one oesophageal perforation, four gastrointestinal bleeding (two required blood transfusion), one
pneumothorax and one aspiration pneumonia. The median length of hospital
stay was 7 days (range 0-174). The 30-day mortality was zero.
CONCLUSION: EUS-guided cystgastrostomy is increasingly employed in the
management of pancreatic fluid collections. This large series demonstrated comparable rates of technical success, recurrence and reintervention to those reported
by other groups. In comparison to surgical cystgastrostomy, rates of technical
success appear to be similar but with lower complication rates and shorter hospital stays. Further studies are needed to define clear pathways for use of interventional EUS in the management of pancreatic fluid collections.
Disclosure of Interest: None declared
P1350 A NEW NEEDLE PLATFORM FOR EUS-GUIDED FNA: A
PROSPECTIVE RANDOMIZED CLINICAL TRIAL COMPARING
THE 22G NEEDLE AND THE 25G NEEDLE
S. Carrara1,*, M. Jovani1, A. Anderloni1, D. Rahal2, L. Di Tomasso2,
D. Federico2, A. Repici1
1
Endoscopy Unit; Department of Gastroenterology, 2Pathology Unit, Humanitas
Research Hospital, Milan, Italy
INTRODUCTION: EUS-FNA is safe and effective in obtaining samples from
the GI masses and lymphnodes. Available needles include 25G, 22G and 19G. A
recently developed needle platform allows for interchangeability of all needle
sizes through a universal delivery system (BNX system, Beacon Endoscopic,
Newton, MA).
AIMS & METHODS: The primary endpoint of this prospective, randomized,
trial was to compare the performance of 25G and 22G needle by evaluating the
adequacy of the aspirated obtained from solid lesions. Secondary aims were the
ease of needle pass, needle malfunctions, n of passes, n of crossovers to the
other needle size, major complications.
Consecutive patients referred for EUS-FNA for solid masses were randomized to
the 25G or to the 22G needle arm. Inclusion criteria: EUS appearance of a solid
lesions, age 418 yrs, informed consent. Crossover to the other size of needle was
allowed when the endoscopist experienced difficulties in puncturing the mass, or
when the material was not adequate after 3 passes.
RESULTS: Eighty-two patients were enrolled from Aug 2013 to Apr 2014 (50 M,
32F), mean age 67 years (range 29-87). Sixty pancreatic masses, 17 lymphnodes
and 5 parietal lesions were biopsied. Forty-one patients were randomized to the
25G needle arm: in 8 cases (19.5%) a crossover to the 22G was asked by the

United European Gastroenterology Journal 2(1S)


pathologist in order to obtain more material for immunohistochemistry (neuroendocrine tumors or lymph-nodes). Forty patients were randomized to the 22G
needle arm: in 9 cases (22%) a crossover to the 25G was done because of the
hardness of the tumor. The mean of needle passes was 2.2 (1.08 SD) per lesion.
In 37 cases the aspirate was both smeared for cytological examination and put
into formalin for histology. Final diagnosis was confirmed by surgical resection
or radiological follow up. Overall adequacy was 86%. In 11 cases the aspirated
was inadequate: 1 adenocarcinoma, 3 lymphnodes (1 sarcoidosis, 2 colliquative
nodes), 1 GIST, 1 pseudosolid pancreatic mass, 1 suspected groove pancreatitis, 1
IPMN, 1 tumor involving the hepatic hylum, 2 hypervascularized pancreatic
lesions. In patients with adequate specimen the sensitivity and accuracy were
95% and 91% for the 22G needle and 97% and 97% for the 25G needle, respectively. In 5 cases a resistance to 22G needle advance was felt by the endosonographer. No major complications were observed.
CONCLUSION: The BNX-platform is accurate for the diagnosis of solid
masses, with results comparable to those of the literature and with no significant
difference between the performance of the 22G and 25G needle. Nearly one
fourth of all procedures may require crossover with a higher adequacy rate.
Disclosure of Interest: None declared
P1351 CHARACTERIZATION OF FLUID COLLECTIONS USING
QUANTIFICATION OF SOLID DEBRIS IN ACUTE PANCREATITIS
- A COMPARATIVE STUDY OF EUS VS. CT FOR PREDICTION OF
INTERVENTION
S. Appasani1,*, J. Basha1, M. Manrai1, P. Siddappa1, T.D. Yadav2, V. Gupta2,
A. Gulati3, N. Khandelwal3, S.K. Sinha1, R. Kochhar1
1
Gastroenterology, 2Surgery, 3Radiology, PGIMER, Chandigarh, India
Contact E-mail Address: drasreekanth@gmail.com
INTRODUCTION: Computed tomography (CT) is the commonest imaging
modality used to detect fluid collections in acute pancreatitis. However CT
poorly differentiates solid necrotic debris from liquid component, which plays
an important role in planning intervention and predicting outcome.
AIMS & METHODS: To evaluate the role of CT and EUS in defining the
morphological characteristics of pancreatic fluid collections along with quantification of the solid debris and evaluate their predictability for intervention and
outcome.
Consecutive patients of acute pancreatitis with fluid collections detected on
CECT, between January-October, 2013 were evaluated further by EUS using
Pentax and Olympus linear echoendoscopes. Morphological characteristics of
fluid collections (based on revised Atlanta) i.e. nature of collection, location,
size and the amount of solid debris, were correlated for need of intervention
and final outcome using CT and EUS. The amount of solid debris was graded
as minimal (510%), moderate (10-50%) and profound (450%) and compared
between various types of collections. CECT images were analysed by 2 experienced radiologists and EUS images were analysed by 2 independent
endosonologists.
RESULTS: 50 patients (mean age-41.8411.7 years, 44% males) of acute pancreatitis with fluid collections were analysed. 61 fluid collections were detected in
these 50 patients, 11 of which were distant collections and could be demonstrable
only on CT and remaining 50 were pancreatic/peri-pancreatic collections which
could be analysed using both on CT & EUS. 18 (36%) had acute necrotic collections (ANC), 29 (58%) had walled off necrosis (WON) and 3 (6%) had pseudocysts. The mean size of fluid collections on CT was significantly more than on
EUS (9.3 vs. 7.7 cm, p50.001). Solid debris was detected in 46 (92%) patients
using EUS while only 16 (32%) patients could be identified with CT (p50.001).
On EUS, minimal solid debris was noted in 11 (22%), moderate solid debris in 23
(46%) and profound solid debris in 16 (32%). 72% of ANCs labelled on CT had
profound solid debris and 30% of pseudocysts labelled on CT had moderate solid
debris, all of whom were managed conservatively. Amongst WONs labelled on
CT, 8 (27.5%) had minimal solid debris who could be managed conservatively;
18 (62%) had moderate solid debris, 7 (38%) of whom required intervention (4percutaneous; 3-endoscopic drainage) and 3 (10.3%) had profound solid debris,
all (100%) of whom required intervention (2-endoscopic necrosectomy; 1-percutaneous drainage) (p50.001).
CONCLUSION: EUS is a better modality than CT in detecting solid debris in
pancreatic fluid collections. As the fluid collections evolve from ANC into WON
the solid debris decreases making EUS the preferred modality for follow up of
fluid collections. EUS quantification of solid debris can be used as a guide for
selecting the treatment modality.
Disclosure of Interest: None declared
P1352 EFFICACY OF ENDOSCOPIC ULTRASONOGRAPHY
TREATMENT OF EARLY GASTRIC CANCER
1,*

FOR
1

S.J. Kim , D.H. Kang , H.W. Kim , C.W. Choi , S.B. Park , B.J. Song ,
Y.Y. Choi1, Y.S. Shin1, D.K. Kang1, H.K. Lim1
Division of Gastroenterology, Department of Internal Medicine, School of
Medicine Pusan National University, Pusan National University Yangsan Hospital,
Yangsan-si, Korea, Republic Of
Contact E-mail Address: shadam@naver.com
1

INTRODUCTION: Endoscopic ultrasonograpy (EUS) is thought to be the most


reliable preoperative method for evaluation of depth of invasion. Findings on
endoscopy can also predict the depth of tumor invasion.
AIMS & METHODS: The aim of this study was to evaluate the accuracy of EUS
for depth of invasion and to compare the accuracy of EUS with that of conventional endoscopy (CE) to predict suitable candidates for endoscopic submucosal
dissection (ESD) according to standard and expanded indication.

A501

United European Gastroenterology Journal 2(1S)


Between May 2009 and May 2013, 300 patients were underwent EUS and curative treatment for early gastric cancer (EGC). We reviewed the medical and
compared preoperative CE and EUS staging with the pathological staging
results.
RESULTS: The overall accuracy of CE and EUS to evaluate the invasion depth
of EGC were 73.3% versus 76.5% (p 0.209). Large size, submucosal invasion,
radial EUS were associated with accuracy of EUS. The accuracy of CE and EUS
to identify proper candidate of ESD were 98.8%, 89.9 (p 0.568) in standard
indication and 60.0%, 71.8% in EUS (p 0.0064). Undifferentiated histology
(100% and 66.7%, p 0.007) or invasion depth confined to the mucosa
(80.3% and 63.6%, p 0.033) were associated with higher accuracy of EUS to
select the proper candidates according to expanded ESD indication compared
with CE.
CONCLUSION: EUS staging could be helpful to decide the optimal treatment
according to expanded indication. Especially, lesion with undifferentiated histology should be carefully considered prior to ESD by pretreatment EUS staging.
Disclosure of Interest: None declared
P1353 USEFULNESS
AND
SAFETY
OF
ULTRASONOGRAPHY-GUIDED DRAINAGE FOR
POSTOPERATIVE PANCREATIC FISTULAS

ENDOSCOPIC

T. Osoegawa1,*, E. Ihara1, K. Nakamura1, H. Kubo1, A. Aso 1, Y. Niina1,


N. Sawamura1, M. Hijioka1, H. Igarashi 1, T. Ito1, M. Tanaka2, R. Takayanagi1
1
Medicine and Bioregulatory Science, 2Department of Surgery and Oncology,
Graduate School of Medical Sciences, Kyushu University, fukuoka, Japan
INTRODUCTION: Endoscopic ultrasonography (EUS)-guided drainage has
recently been shown to be useful for treating walled-off pancreatic necrosis
(WOPN), a late complication of necrotizing pancreatitis that consists of loculated
fluid collections with necrotic material. With this development in mind, we
became interested in determining if EUS-guided drainage is also useful for treating postoperative pancreatic fistula (POPF). Hence, the objective of this study
was to examine the usefulness and safety of EUS-guided drainage for POPF.
AIMS & METHODS: A total of 37 patients who had undergone EUS-guided
drainage for treatment of POPF or WOPN between December 2002 and March
2013 were enrolled in this retrospective study. We reviewed the success rates of
the procedures, rates of lesion size reduction, treatment success rates, and complication rates associated with EUS-guided drainage. By comparing the resultant
data for EUS-guided drainage of the two conditions (POPF and WOPN), we
were able to determine the usefulness and safety of EUS-guided drainage for
POPF.
RESULTS: EUS-guided drainage was performed in 14 patients with POPF and
in 23 patients with WOPN. There were no significant differences in the clinical
characteristicsincluding sex, age, and lesion sizeof the patients in the POPF
and WOPN groups who underwent EUS-guided drainage. The procedures
required for EUS-guided drainage included aspiration in three cases, an external
fistula in one case, internal fistulas in four cases, and external and internal fistulas
in six cases in the POPF group, but no endoscopic necrosectomy. The corresponding numbers for the WOPN group were aspiration in five cases, external
fistulas in three cases, internal fistulas in three cases, external and internal fistulas
in seven cases, and endoscopic necrosectomy in three cases. The successful procedures, reduced lesion size, and successful treatment rates were 100 %, 100 %,
and 93 %, respectively, in the POPF group and 91.3 %, 78.2 %, and 71.4 %,
respectively, in the WOPN group. The reduced lesion size and treatment success
rates were significantly higher in the POPF group than in the WOPN group. No
complications occurred in the POPF group, whereas four patients in the WOPN
group suffered such complications as perforative peritonitis and procedurerelated bleeding. In all, 26 (13 POPF, 13 WOPN) of 37 patients were followed
up for a mean of 22  4.2 months. There were no recurrences in the POPF group,
whereas three patients in the WOPN group did have a recurrence.
CONCLUSION: EUS-guided drainage is a useful treatment not only for WOPN
but also for POPF. Comparing the usefulness and safety of EUS-guided drainage
in patients with POPF using the same parameters as those used to assess its use in
those with WOPN indicated that EUS-guided transmural drainage can be a good
option for treating POPF.
Disclosure of Interest: None declared
P1354 CLINICAL IMPACT OF LIQUID-BASED OR CELL BLOCK
PREPARATION OF RESIDUAL MATERIAL AFTER ANALYSIS OF
CYTOLOGICAL SMEARS IN ENDOSCOPIC ULTRASOUNDGUIDED FINE-NEEDLE ASPIRATION
1,*

W. Kappelle , M. Van Oijen , P. Siersema , F. Vleggaar


Gastroenterology and hepatology, UMC Utrecht, Utrecht, Netherlands
Contact E-mail Address: w.f.w.kappelle@umcutrecht.nl
1

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) is an accurate technique to biopsy lymph nodes and masses for cytological
analysis. Residual material, being residue aspirate or an extra aspiration after
preparation of cytological smears or residual tissue, can be used for liquid-based
or cell block preparation, which may be useful when smears are inadequate and/
or immunohistochemistry is required. For liquid-based preparation, residual
material is placed in hemolytic solution and then placed on a slide, resulting in
a thin layer of cells. For cell block preparation, residual material is clustered,
embedded in a fixative and then cut, enabling analysis of tissue particles that are
too thick to be analysed with cytological smears. The diagnostic value of these
additional tests is unclear. We hypothesised that analysis of residual material is a
valuable addition to EUS-FNA.
AIMS & METHODS: The aim of this study was to evaluate the additional
diagnostic yield of liquid-based or cell block prepared residual material after

routine cytological smear analysis in EUS-FNA procedures. EUS-FNA procedures between 2002 and 2013 were identified using a single center endoscopy
database. Diagnostic yield and accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytological smears and
smears combined with residual material were calculated and compared using onesided testing. Diagnostic yield was defined as the proportion in which the pathologist could make a diagnosis. Diagnostic accuracy was defined as the proportion
in which the diagnosis of the pathologist was in line with the final diagnosis based
on a histologal biopsy, surgical resection or clinical outcome.
RESULTS: In total, 510 cases were identified. EUS-FNA was successful in 482
cases (95%), on-site evaluation was available in 448 (93%). A total of 580 sites
were targeted, a lymph node was targeted 444 times (77%) and a mass 136 times
(23%). The most frequently aspirated sites were the subcarina (n 264, 46%),
pancreas (n 64, 11%) and aortopulmonary window (n 64, 11%). Residual
material was available in 216 cases (45%), which directly benefited the diagnosis
in 30 cases (14%). In 11 cases (37%), it led to the diagnosis, in 4 cases (13%) it
enabled differentiation in origin of the tumour and in 15 cases (50%) immunohistochemistry was useful to determine the origin of the tumour. In cases with
residual material available and using the cytological smears only for analysis vs.
combining this with analysis of residual material, the diagnostic yield was 88%
vs. 88% (p 0.5), diagnostic accuracy 82% vs. 92% (p 0.01), sensitivity 79%
vs. 90% (p 0.01), specificity 97% vs. 97% (p 0.5), PPV 99% vs. 99% (0.44)
and NPV 55% vs. 72% (p 0.03). Number needed to test with regard to residual
material was 7.2.
CONCLUSION: Additional analysis of liquid-based or cell block prepared residual material after analysis of cytological smears benefits diagnostic accuracy,
sensitivity and NPV in EUS-FNA procedures. Future studies are warranted to
establish whether adding the analysis of residual material is indeed cost-effective.
Disclosure of Interest: None declared
P1355 ROLE OF ENDOSONOGRAPHY IN DETECTING GASTRIC
MALIGNANCIES
Y. Valerieva1,*, B. Golemanov1, P. Gecov2, I. terziev3, Y. Asenov4,
B. Vladimirov1
1
Clinical Centre of Gastroenterology, 2Department of Medical Imaging,
3
Department of Pathology, 4Clinic of Surgery, University Hospital "Queen Joanna
-ISUL" Sofia, Bulgaria, Sofia, Bulgaria
Contact E-mail Address: yana_valerieva@abv.bg
INTRODUCTION: Assessing the role of endoscopic ultrasound (EUS) examination in the diagnosis of non-typical or malignancy suspected stomach lesions
found in conventional upper endoscopy.
AIMS & METHODS: Twenty eight patients (64.3% male, 35.7% female) at
mean age 5518 years with endoscopy findings of stomach ulcers (25%),
polyps (21.4%), polypoid mucosal changes (35.7%) or enlarged folds (17.9%)
were evaluated by linear EUS in our centre following conventional forceps biopsies. According to the endosonographic features of the lesions: homogeneity,
thickening or loss of wall stratification, lesion margins, presence of necrotic
areas and lymph nodes, they were classified as EUS benign and EUS malignant.
Biopsy results were also subdivided into two groups benign (gastritis, adenoma,
hyperplastic and fundic gland polyp) or malignant (carcinoma, lymphoma) and
compared to EUS groups. All lesions signed as malignant were further evaluated
by computer tomography, second look biopsies and/or laparoscopy/laparotomy.
RESULTS: Patients evaluation resulted in the following groups: EUS benign
42.9%, EUS malignant 57.1%; biopsy benign 67.9%, biopsy malignant 32.1%.
When comparing EUS and biopsy groups we found that EUS features of malignancy were present in 7 cases (43.8%) with benign histology results, while all
EUS benign lesions corresponded to benign histology (p 0.002). The mismatch
cases were further evaluated resulting in change of diagnosis in all patients of this
group from benign to malignant. In the malignant EUS groups, the predominant
EUS features were: presence of lymph nodes (87.5% vs. 12.5%, p 0.005), loss
of wall stratification (93.8% vs. 6.3%, p50.001) and lesion heterogeneity (87.5%
vs. 12.5%, p50.001).
CONCLUSION: Endosonography of stomach lesions is a reliable method for
neoplasm detection. Even in patients with negative conventional biopsy histology
result certain EUS features are indicative for malignancy and can lead to the final
diagnosis.
Disclosure of Interest: None declared
P1356 CONTRAST-ENHANCED ENDOSCOPIC ULTRASONOGRAPHY
CAN PREDICT A HIGHER MALIGNANT POTENTIAL OF
GASTROINTESTINAL STROMAL TUMORS BY VISUALIZING
LARGE NEWLY FORMED VESSELS
Y. Yamashita1,*, K. Ueda1, Y. Kawazi1, T. Tamura1, M. Itonaga1, H. Maeda1,
T. Maekita1, M. Iguchi1, H. Tamai1, J. Kato1, M. Ichinose1
1
Second Department of Internal Medicine, Wakayama Medical University,
Wakayama, Japan
Contact E-mail Address: yasunobu@wakayama-med.ac.jp
INTRODUCTION: Contrast-enhanced endoscopic ultrasonography (CE-EUS)
is a new imaging modality for detecting intratumoral vessels in real time.
AIMS & METHODS: The aim of this study was to elucidate the histological and
clinical implications of detection on CE-EUS of intratumoral vessels in gastrointestinal stromal tumors (GISTs). A total of 13 patients, each having a GIST,
and all of whom were referred for surgery, underwent presurgical CE-EUS. Final
diagnoses were made by pathologic examination of resected specimens. The
GIST malignancy potential, assessed according to the modified Fletcher risk
classification system, and the histological degree of angiogenesis were compared
to the presence or absence of intratumoral vessels on CE-EUS.

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United European Gastroenterology Journal 2(1S)

RESULTS: Intratumoral vessels were observed on CE-EUS in 6 patients, but not


in the remaining 7. Of the 6 tumors with intratumoral vessels, 5 (83%) were
intermediate- or high-risk GISTs, and all negative cases were categorized as
very low risk or low risk. Presence of intratumoral vessels on CE-EUS was
significantly correlated with a higher-risk classification (according to the modified Fletcher classification system) (P 0.005). All GISTs with the visualized
vessels with CE-EUS incorporated vessels more than 500 m in histology. The
large intratumoral vessels of the 5 intermediate- or high-risk GISTs lacked elastic
fibers, suggesting that they were neovascular in nature. These higher-risk tumors
were also found, by immunohistochemical analysis, to have high expression of
vascular endothelial growth factor.
CONCLUSION: Intratumoral vessels observed in GISTs on CE-EUS are large
vessels, by histological examination, and are correlated with higher malignant
potential.
Disclosure of Interest: None declared
P1357 THE ACCURACY OF ENDOSCOPIC ULTRASONOGRAPHY IN
DIFFERENTIATING OF T1M AND T1SM ESOPHAGEAL
SQUAMOUS CELL CARCINOMA
Y.-Y. Chu1,*, J.-M. Lien1, M.-S. Lee1, C.-J. Lin1, C.-T. Chiu1, S.-C. Ng2
Gastroenterology, 2Internal Medicine, CHANG GUNG MEMORIAL
HOSPITAL, Taipei, Taiwan, Province of China
Contact E-mail Address: chu2235@yahoo.com

INTRODUCTION: According to TNM classification of esophageal cancer, the T1


stage is subdivided into mucosa (T1m) and submucosa (T1sm). Endoscopic submucosal dissection (ESD) is a newly developed skill to complete resection gastrointestinal (GI) tract early cancer. The limitation of ESD is cancer invasion to submucosal
layer and increasing the risk of lymph node metastasis (20-28%), therefore, the
accurate T1 stage subdivision of esophageal cancer prior to ESD is essential.
Endoscopic ultrasound (EUS) is a useful examination for detecting the T stage of
GI tract cancer, the reported accuracy of different T stage are around 70-90%,
however, there are few published data on the detail discrimination of EUS among
each subdivision T1m or T1sm of esophageal cancer. The aim of this study is to
evaluate the accuracy of T1 stage subdivision of esophageal cancer by higher
frequency EUS probe.
AIMS & METHODS: From April 2009 to March 2014, there are 1125 patients
diagnosed with esophageal cancer, further stage with EUS, computered tomography and PET-CT. The EUS examination is performed with miniprobe (UM2R, 12 MHz, UM-3R, 20 MHz; Olympus Optical Co. Ltd., Tokyo, Japan) and
water immersion method.
The enrolled criteria of this study: 1. esophageal squamous cell carcinoma was
proved by biopsy result. 2. T1m or T1sm stage diagnosed by EUS. 3. Further
treatment with ESD or radical surgery. All EUS-T stage results were correlated
with final pathological T stage.
RESULTS: There were 134 patients with T1 stage of esophageal squamous cell
carcinoma by EUS, and 73 patients received further ESD (33) or surgical esophagectomy (40). All lesions were confirmed as T1 on pathology, EUS stage of T1m in
55 patients and 45 (82%) were confirmed as T1m on pathology; of the 18 T1sm on
EUS and12 (67%) were confirmed as T1sm. Positive predictive value of EUS for
T1m was 82%, negative predictive value was 67%, sensitivity 88%, specificity 55%.
CONCLUSION: EUS demonstrated median degree of accuracy for distinguishing between stages T1m and T1sm of esophageal squamous cell carcinoma. Even
with high frequency miniprobe, peritumoral inflammation or submucosal fibrosis
causes some difficulties in differentiating mucosal from submucosal lesions, and
develops more advanced EUS device is needed. EUS remains a valuable tool
when endoscopic treatment is considered.
Disclosure of Interest: None declared
P1358 EUS
GUIDED
CARDIAC
APRROACH-EUS
TRANSESOPHAGEAL PERICARDIOCENTESIS

GUIDED

Y. Hashimoto1,*, I. Kazuaki2
Gastrointestinal Oncology/Endosocpy, National Cancer Research Center East
Hospital, Kashiwa, 2Gastroenterology, Showa Univeristy Fujigaoka Hospital,
Yokohama, Japan
Contact E-mail Address: yusuke.h914@gmail.com
1

INTRODUCTION: EUS-guided intervention has been established for diagnostic


and therapeutic procedures in gastroenterology. Echocardiographic-guided pericardiocentesis is the preferred initial procedure for the diagnosis and treatment of
pericardial effusion. Pericardial effusion is rarely located in the posterior side of
pericardial sac, which makes it difficult for cardiologist to perform
Echocardiographic-guided pericardiocentesis through the subxiphoid route.
Cardiac intervention using EUS- guided transesophageal approach might be
anatomically practical but has still been experimental.
AIMS & METHODS: AIM: These clinical cases are to show our experience of
EUS guided-transesophageal pericardiocentesis successfully and safely.
METHODS: Three patients who failed echo-cardiography guided diagnostic pericardiocentesis were offered EUS-guided approach. Informed consent was obtained.
Diagnostic EUS-pericardiocentesis was performed with sedation of meperidine and
midazolam. EUS guided transesophageal puncture using 22G needle was performed into the pericardial effusion. The fluid was fully aspirated for evaluation
of tumor makers, cytology and culture. Patients were carefully monitored during
and after the procedure and given third generation cephalosporins.
RESULTS: EUS-guided pericardiocentesis performed in 3 patients in hemodynamic stable condition (Male 2, Average 69 year old). The puncture was via
lower portion of the esophagus. The average procedure time is 10minutes. The
median fluid amount was 15ml. EUS guided aspiration confirmed non-diagnostic

in 2 patients and tubeculosis in 1 patients. No early or late complications: no


infection, arrythmia, heart failure and/or bleeding.
CONCLUSION: EUS guided transesophageal approach to pericardiocentesis
was successful in the limited cases. The cases must be applied to the procedure
only if echocardiographic pericardiocentesis fails.
Disclosure of Interest: None declared
P1359 GUIDE-WIRE ASSISTED INSERTION OF AN ULTRATHIN
ENDOSCOPE INTO THE PROXIMAL JEJUNUM: A NOVEL
TECHNIQUE
A. Mori1, T. Yumura1,*, H. Hachiya1, S. Ito1, S. Hayashi1, N. Ohashi1
1
Ichinomiya Nishi Hospital Gastroenterology, Ichinomiya, Japan
Contact E-mail Address: a-mori@anzu.or.jp
INTRODUCTION: Insertion into the proximal jejunum with conventional esophagogastroduodenoscopy (EGD) by push technique is difficult. The reasons for
difficulty are that an endoscope bends in the stomach and the distal end of an
endoscope has less flexibility for advancement. Although the flexible ultrathin
endoscope (UTE) has the drawback of easily bending in the stomach, when
inserting the stiff guide-wire through the biopsy channel, the bending of the
UTE in the stomach is avoided. Using these characteristics of the UTE, we
made it possible to insert the UTE assisting with a balloon and a super stiff
guide-wire into the common bile duct (Endoscopy 2012; 44). Recently, we have
developed a novel technique which inserts the UTE assisting with only a super
stiff guide-wire into the proximal jejunum. We report here the method and the
feasibility of this technique.
AIMS & METHODS: 20 consecutive patients were evaluated in a preliminary
prospective feasibility study. 16 patients were suspected of the distal duodenal
and proximal jejunum diseases (7 strictures, 4 obscure gastrointestinal bleedings,
2 tumors and 3 others) and 4 patients needed injection of enteral feeding from the
distal duodenal and proximal jejunum. All unsedated patients underwent this
procedure via transnasal route. After observing the upper gastrointestinal tract
with the UTE (EG580NW, FujiFilm, Tokyo, Japan), we inserted a guide wire
(Amplatz superstiff 0.035) using the biopsy channel of the UTE until about 20 cm
distal end of the UTE to maintain the stiffness of the UTE to avoid the bending
in the stomach. This facilitated insertion of the UTE into the proximal jejunum
and made it possible to perform not only EGD but also jejunoscopy at the same
time (ultrathin esophagogastroduodenojejunoscopy: UT-EGDJ). We assessed
the success rate, procedure time and usefulness in diagnosis. Successful UTEGDJ was defined as the fluoroscopically-confirmed advancement of the UTE
beyond the duodeno-jejunal angle.
RESULTS: UT-EGDJ was performed successfully in 19/20 patients (95%). We
failed to complete UT-EGDJ in only one patient who had a huge abdominal
aortic aneurysma placed the stent graft in. The median (interquartile range) time
to reach the proximal jejunum was 300 (240-327) seconds. This procedure
revealed 3 SMA syndromes, one small intestinal adenoma with bleeding and
one lupus enteritis. No significant clinical complications related to UT-EGDJ.
CONCLUSION: UT-EGDJ appears to be sufficiently feasible and may be available for a screening of the deep duodenum and proximal jejunum as a bridge to
balloon small intestinal endoscopy.
Disclosure of Interest: None declared
P1360 EFFECTIVENESS OF ENDOSCOPIC ULTRASONOGRAPHY
DURING DOUBLE BALLOON ENTEROSCOPY FOR SUSPECTED
SMALL BOWEL TUMORS
A. Murino1,*, M. Nakamura1, T. Yamamura 2, A. Nagura 2, T. Yoshimura 1,
A. Nakano 1, H. Oshima 1, J. Sato1, K. Furukawa 1, K. Funasaka 2, E. Ohno 1,
R. Miyahara 1, H. Kawashima 1, O. Watanabe 1, Y. Hirooka 2, T. Ando1,
H. Goto1
1
Department of Gastroenterology and Hepatology, Nagoya University Graduate
School of Medicine, 2Department of Endoscopy, Nagoya University Hospital,
Nagoya, Japan
Contact E-mail Address: albertomurino@yahoo.it
INTRODUCTION: Endoscopic Ultrasonography (EUS) performed during
Double Balloon Enteroscopy (DBE) was firstly reported in 2006. The combination of these two techniques allows the endoscopists to evaluate extraluminal
small bowel (SB) lesions previously considered inaccessible. Despite appearing
a promising diagnostic technique, his employment is still limited and his usefulness is not widely assessed.
AIMS & METHODS: The aim of this retrospective study was to evaluate the
diagnostic rate of EUS during DBE for suspected small bowel tumors (SBT) and
its usefulness for characterization of sub mucosal tumors (SMT) in a large cohort
of patients. The secondary endpoint was to compare, for the first time, DBE and
EUS with computerised tomography (CT) and small bowel capsule endoscopy
(SBCE).
Patients with a suspected SBT, who underwent EUS-DBE in our Institution
between 2007 and December 2013, were retrospectively reviewed. Demographic
datas, clinical, endoscopic and radiological findings, therapeutical management,
final diagnosis and follow-up were considered. DBE, EUS, SBCE and CT diagnostic rate and concordance among the 4 procedures analysed.
RESULTS: Sixty-one patients with suspected SBT were included in the study (38
male, 54 years old). DBE and EUS were performed in all patients, CE in 29 and
CT in 56. SBT were diagnosed in 46 patients, 30 were SMT while the remnant 16
SBT involved the mucosa. DBE and EUS diagnosed SBT in 44 (96%) and 43
(93%) patients respectively. In particular a correct characterization of SMT was
obtained by DBE and EUS in 8 (27%) and 20 (67%) patients respectively
(p 0.0014). GIST (8), carcinoid (1), metastasis (3), haemangioma (3) were successfully diagnosed in all case by EUS while the characterization of SB pancreatic

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United European Gastroenterology Journal 2(1S)


rest (3/8), lymphangioma (1/4) and lipoma (0/2) was limited. In addition CE
detected 10 SB tumors out of 19 (53%) and CT 34 out of 44 (77%). SBT
diagnosis concordance rates among the procedures were the following: DBEEUS 91% (42/46), DBE-CE 53% (10/19), DBE-CT 73% (32/44), EUS-CE
47% (9/19) EUS-CT 68% (30/44), CE-CT 42% (8/19).
CONCLUSION: Our results suggest that EUS performed during DBE is a useful
technique for SBT diagnosis and in particular for SMT characterization.
Therefore we recommend integrating EUS to DBE practice to establish a certain
diagnosis, in order to provide the most appropriate medical management.
Disclosure of Interest: A. Murino Financial support for research from: Takeda
Foundation, M. Nakamura: None declared, T. Yamamura: None declared, A.
Nagura: None declared, T. Yoshimura: None declared, A. Nakano: None
declared, H. Oshima: None declared, J. Sato: None declared, K. Furukawa:
None declared, K. Funasaka: None declared, E. Ohno: None declared, R.
Miyahara: None declared, H. Kawashima: None declared, O. Watanabe: None
declared, Y. Hirooka: None declared, T. Ando: None declared, H. Goto: None
declared
P1361 GAY INDEX IN ROUTE SELECTION FOR SINGLE-BALLOON
ENTEROSCOPY AFTER POSITIVE FINDINGS IN CAPSULE
ENDOSCOPY
C. Fernandes1,*, R. Pinho1, A. Rodrigues1, T. Pinto-Pais1, I. Ribeiro1, J. Silva1,
A. Ponte1, J. Carvalho1
1
Gastroenterology, C. HOSPITALAR VILA NOVA GAIA, V N Gaia, Portugal
INTRODUCTION: After positive findings in capsule enteroscopy, deviceassisted enteroscopy route is not always evident. Gay et al1 developed an index
to predict the correct route for device-assisted enteroscopy after a positive capsule enteroscopy (if transit time until the finding 4 0.75 of orocecal time anal
route). Recently, Li et al.2 proposed another ndex (if transit time between
pylorus and the finding 40.6 of small bowel transit anal route).
AIMS & METHODS: To evaluate Gay ndex ability to predict the correct route
for single balloon enteroscopy after positive findings in capsule enteroscopy. To
compare Gay index with Li index.
A single-center retrospective study evaluated patients with positive findings on
capsule enteroscopy that were subsequently submitted to a single balloon enteroscopy. Considered the period between January 2010 and September 2013. Single
balloon enteroscopy route selected accordingly to Gay index. Comparison with
Li index.
RESULTS: 49 patients (female gender 57.1%; mean age 66.7 years) were evaluated. Angioectasias (n:20) and bleeding without an identified source (n:17) were
the most important capsule enteroscopy positive findings. Accordingly to Gay
index, oral route was selected in 69.4% (n:34) of the cases. The single-ballon
enteroscopy goal was not fulfilled in 12.2% (n:6). Nevertheless, in 5 cases the goal
was not achieved for reasons not related to the distance (fixed angulation: 3;
technical issues 1; stenotic ileo-colic anastomosis: 1). In one case it was attempted
the alternative route, without success. Gay index and Li index were concordant in
98% (n:48) of the cases.
CONCLUSION: In our study 1) the single-balloon enteroscopy goal was
achieved in most of the patients; 2) Gay index revealed a good ability to predict
the single-balloon enteroscopy route; 3) Li index and Gay index revealed a
similar ability to predict the correct insertion route.
REFERENCES
1- Endoscopy 2006; 38: 49-58.
2 - Endoscopy 2009; 41: 762-766.
Disclosure of Interest: None declared
P1362 CELIAC DISEASE AND DOUBLE-BALLOON ENTEROSCOPY:
WHAT CAN WE ACHIEVE? THE EXPERIENCE OF TWO
EUROPEAN TERTIARY REFERRAL CENTERS
C. Tomba1,2,*, L. Elli2, R. Sidhu3, F. Branchi1, M. Locatelli1, L. Roncoroni2,
D. Conte1,2, M.T. Bardella2, P. Mooney3, D. Sanders3
1
Universita` degli Studi di Milano, 2Center for the Prevention and Diagnosis of
Celiac Disease Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca
Granda Ospedale Maggiore Policlinico, Milan, Italy, 3Gastroenterology and Liver
Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom
Contact E-mail Address: tomba.carolina@gmail.com
INTRODUCTION: The indications for and efficacy of device-assisted enteroscopy is not standardised in celiac disease (CD).
AIMS & METHODS: We present the largest study to date to evaluate the
clinical role of double-balloon enteroscopy (DBE) in complicated CD. DBE
findings in CD patients with suspected small bowel complications were retrospectively evaluated in two tertiary referral centers (Milan and Sheffield).
Demographic data of the studied cohort were compared with a database of
1000 non complicated CD patients.
RESULTS: Findings from 14 oral and seven anal DBE in 19 CD cases (11 males
p 0.003 vs control database) were reviewed. Mean age at CD diagnosis (3919
vs 2718) and at small bowel evaluation (4915 vs 3813) was significantly
higher in the DBE group compared to controls (p50.001). Indications for
DBE were the follow up of known refractory coeliac disease (RCD) (#7), suspicion of small bowel complications due to gastrointestinal symptoms (#4), severe
iron deficiency anemia (#6) and long standing poor dietary adherence (#2). All
DBE were performed after small bowel capsule endoscopy, except for one case.
Three patients from the known RCD group had evidence of TCR gamma monoclonality on biopsy (type 2 RCD). One of these patients had jejunal ulceration
whilst the other 2 cases had areas with small white raised patches. A further RCD
case had evidence of jejunal ulceration however biopsies didnt show any evidence of TCR gamma monoclonality. Patchy small bowel atrophy was observed

in all the non adherent patients and in 2 patients with persistent gastrointestinal
symptoms who had only been on a gluten free diet for a short time. Two jejunal
adenocarcinomas and an ileal neuroendocrine tumour were detected. All 3 of
these patients presented with iron deficiency anaemia. A therapeutical approach
was planned in 30% of patients after DBE. No events were detected at follow up
(18 months; 5-55).
CONCLUSION: This is the largest international DBE outcomes study in CD
patients. DBE could be useful in selected CD cases to exclude/confirm malignant
or premalignant conditions, possibly associated even with minor mucosal lesions.
Evaluation of non-responsive/refractory symptoms by DBE was associated with
older patients and a higher proportion of males than an uncomplicated CD
population. Studies are needed to understand the clinical relevance of the small
bowel endoscopic features and to optimise DBE indications.
REFERENCES
Hadithi M, Al-toma A, Oudejans J, et al. The value of double-balloon enteroscopy in patients with refractory celiac disease. Am J Gastroenterol 2007; 102:
987-996.
Flieger D, Keller R, May A, et al. Capsule endoscopy in gastrointestinal lymphomas. Endoscopy 2005; 37: 1174-1180.
Cellier C, Green PH, Collin P, et al. ICCE consensus for celiac disease.
Endoscopy 2005; 37: 1055-1059.
Disclosure of Interest: None declared
P1363 THE SIGNIFICANCE AND BENEFIT OF THE COMPLEX
ENTEROSCOPY IN PATIENTS WITH SMALL BOWEL NEOPLASIA
E. Ivanova1,*, E. Fedorov1, D. Seleznev1, E. Tikhomirova1, E. Polukhina1
1
MOSCOW UNIVERSITY HOSPITAL 31, Moscow, Russian Federation
Contact E-mail Address: katendo@yandex.ru
INTRODUCTION: Diagnosis of small bowel tumor can be a very challenging.
Videocapsule endoscopy (VCE) and balloon-assisted enteroscopy (BAE) have
their own specific limitations.
AIMS & METHODS: To estimate the benefits of combined use of VCE and
BAE in diagnosis and treatment of small bowel tumors. From II. 2007 until
IV.2014 VCE followed by BAE were performed in 43 pts. (m-18, f-25, mean
age 4513.9 yrs., range 18-73) with strongly suspected small bowel neoplasia.
Small bowel tumors have been detected in 31 (72.0%) pts. (m-14, f -17, mean age
4214.5 yrs., range 18-70). Obscure GI bleeding was an indication for VCE in 19
(61.3%) of them. The insertion route for BAE was determined according to the
site of the suspected lesions detected by VCE. For precise diagnosis and tumor
evaluation we performed sonde-EUS through the enteroscope in 13 (41.9%) pts.
with intestinal neoplasia.
RESULTS: According to VCE data tumor was suspected in 30 (96.7%) pts.
while BAE detected the neoplastic lesions in 29 (93.5%) pts. (plus in 2 pts.
with negative BAE weve performed laparoscopy and revealed tumors with extraorganic growth). BAE-EUS in 13 pts. provided detailed and useful information
about the echogenicity, its echo-structure and the layer of origin of the tumor
that helped to determine the treatment policy and method of tumor removal.
Histologically the tumors were defined as neuroendocrine tumors in 6 (19.3%)
pts., GIST in 4 (12.9%) pts., adenocarcinoma in 2 (6.4%) pts., lymphoma in 1
(3.2%) pt., Peutz-Jeghers hamartomas in 8 (25.8%) pts., hyperplastic polyps in 4
(12.9%) pts., tubular adenoma in 2 (6.4%) pts., cavernous haemangioma in 2
(6.4%), angiofibrolipoma in 1 (3.2%), lymphangioma in 1 (3.2%) pt. Intestinal
tumors mainly localized in jejunum in 16 (51.6%) pts. and in ileum 8 (25.8%) pts.
and in 7 (22.6%) pts. with Peutz-Jeghers syndrome (5) and neuroendocrine
tumors (2) the lesions extended segmental in jejunum and ileum. Conservative
specific treatment was applied in 1 (3.2%) patient with B-cell lymphoma as well
as endoscopic haemostasis by APC during BAE because of tumor bleeding.
Endoscopic treatment (polyp removal) was performed in 11 (35.5%) pts.:
EMR (1) and polypectomy (10). Surgery was performed in 18 (58.1%) pts.
Diagnostic accuracy

VCE

BAE

VCEBAE

Sensitivity
Specificity

96.6%
77.0%

93.3%
92.3%

100%
92.3%

CONCLUSION: Complex enteroscopy (VCEBAE) provides all the benefits of


gradual, proper and accurate diagnosis of small bowel tumors as well as possibilities of conservative/endoscopic treatment through the endoscope in 38.7%
patients. Combination of VCE and BAE demonstrates a higher effectiveness in
the diagnosis of small bowel neoplasia than its separate usage.
Disclosure of Interest: None declared
P1364 A PROSPECTIVE COHORT STUDY EVALUATING NAVIAID AB A NOVEL PLATFORM FOR DEEP SMALL BOWEL ENTEROSCOPY
H. Neumann1,*, K. Monkemuller2, G.E. Tontini1,3, M. Grauer1,4, M. Vieth5,
L.C. Fry2, M.F. Neurath1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany,
2
University of Alabama at Birmingham, Birmingham, United States, 3IRCCS
Policlinico San Donato, San Donato Milanese, Italy, 4Klinikum Neumarkt,
Neumarkt, 5Klinikum Bayreuth, Bayreuth, Germany
INTRODUCTION: Endoscopic visualization of the small-bowel is facilitated by
device-assisted enteroscopy. Deep small-bowel intubation mostly requires a significant amount of time, involved a prolonged learning curve, and coopers often
two assistance. Notable, it has been shown that more than 75% of lesions within
the small bowel are located in the proximal jejunum.

A504
AIMS & METHODS: To evaluate the feasibility, usability, and safety of a novel
platform for deep small bowel enteroscopy featuring the very recently introduced
NaviAid AB device. This was a prospective, single-center pilot and feasibility
study. Patients underwent deep small bowel enteroscopy featuring the newly
introduced NaviAid AB device for evaluation of obscure gastrointestinal bleeding, suspicious small-bowel Crohns disease, celiac disease, familial adenomatous
polyposis or abdominal pain. Study end points included successful deep small
bowel enteroscopy, time to evaluate the small bowel, success of therapeutic interventions, adverse events, and endoscopists subjective evaluation of NaviAid AB.
RESULTS: Overall, 23 patients, aged 19 - 77 years were prospectively included.
Enteroscopy was feasible in all cases. Mean time to prepare the system was 2
minutes (Range 2-5 minutes). The estimated small bowel intubation depth was
200 cm (Range 90-280 cm) past the ligament of Treitz. Average time of the
procedure was measured as 14 minutes (Range 13-18 minutes). Findings included
small bowel Crohns disease, small bowel diverticulosis, NSAID enteropathy,
celiac disease, small bowel polyps and angiovascular malformations. No procedure related complications occurred.
CONCLUSION: The newly introduced NaviAid AB device allows safe and fast
on demand deep enteroscopy. Approaching the deep jejunum could be achieved
within only 14 minutes. The device allows stable positioning of the scope for
therapeutic interventions. Therefore, the new NaviAid AB device could become
an additional device to explore the small bowel. Future studies should now focus
on the learning curve and if even total enteroscopy is feasible.
Disclosure of Interest: None declared
P1365 UTILITY OF DOUBLE BALLOON ENTEROSCOPY IN PATIENTS
WITH SURGICALLY ALTERED BOWEL ANATOMY AFTER
OBESITY SURGERY
J. Velazquez1,2,*, M. Skinner2, S. Peter2, K. Monkemuller2
1
ENDOSCOPY, UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO,
MEXICO, Mexico, 2ENDOSCOPY, UNIVERSITY OF ALABAMA,
Birmingham, United States
Contact E-mail Address: jacovelazquez@gmail.com
INTRODUCTION: Endoscopic investigation of the gastrointestinal (GI) luminal and pancreatobiliary tracts in patients with surgically-altered GI anatomy
after bariatric surgery is challenging and often impossible. The advent of balloonassisted enteroscopy (BAE) has increased our ability to navigate through the
surgically altered bowel. Despite the existence of BAE since more than a
decade there is few data available on it potential utility for evaluation postobesity-surgery patients.
AIMS & METHODS: To evaluate the diagnostic yield, success and complications rates of double-balloon enteroscopy (DBE) in consecutive patients with GI
problems necessitating endoscopic evaluation.
Materials and Methods: Single-center, observational, cohort study of consecutive
patients with post-obesity-surgery undergoing DBE during a 12-months period.
Patients demographics, procedure indications, findings, endoscopic interventions, and post-procedural recovery data were recorded.
RESULTS: A total of 265 DBE were performed at our institution during the 12months study period. Thirty-three patients (12.1%) with post-obesity surgery
were evaluated using DBE. The most common indication for DBE was obscure
GI bleeding (OGIB) (n 12), followed by DBE-ERCP (n 11), and evaluation
of and abdominal pain (n 10). The excluded stomach could be reached in 90%
of patients. The overall diagnostic yield of DBE-ERCP was 65% (stones, n 4,
sphincter stenosis, n 3, bile leak, n 2, bile duct stricture, n 1). The yield of
DBE for abdominal pain was 20% (n 2: gastric erosions, gastro-gastric fistula)
and DBE for OGIB 75%. Of the 12 patients with OGIB, 9 had active bleeding at
the time of DBE. In all but one case, the bleeding was occurring at the site of the
anastomosis, whether that be hepaticojejunal, jejunojejunal, or gastrojejunal. Of
these patients 5 patients had arteriovenous malformations at the anastomotic
site, 5 had ulcers or erosions, and 2 were bleeding secondary to Dieulafoys
lesions. A total of one complication (3%) was observed (small bowel perforation
after application of argon plasma coagulation to the jejunojejunal anastomosis).
CONCLUSION: DBE is a feasible and relatively safe technique to evaluate the
small intestines, stomach and biliary tract and associated with reasonably high
diagnostic yield in patients with surgically altered bowel anatomy in the setting of
bariatric surgery.
REFERENCES
1. Chahal P, Baron TH, Topazian MD, et al. Endoscopic retrograde cholangiopancreatography in post Whipple patients. Endoscopy 2006; 38: 1241-1245.
2. Neumann H, Fry LC, Meyer F, et al. Endoscopic retrograde cholangiopancreatography using the single balloon enteroscope technique in patients with
Roux-en-Y anastomosis. Digestion 2009; 80: 52-57.
3. Cho S, Kamalaporn P, Kandel G, et al. Short double-balloon enteroscope for
endoscopic retrograde cholangiopancreatography in patients with a surgically
altered upper gastrointestinal tract. Can J Gastroenterol 2011; 25: 615-619.
4. Monkemuller K and Jovanovic I. Endoscopic and retrograde cholangiographic appearance of hepaticojejunostomy strictures: A practical classification.
World J Gastrointest Endosc 2011; 3: 213-219.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1366 LABORATORY PREDICTORS OF HYPERAMYLASEMIA AND
HYPERLIPASEMIA AFTER DOUBLE BALLOON ENTEROSCOPY
M. Kopacova1, J. Bures1,*, S. Rejchrt1, J. Bartova1, T. Soukup1, J. Toms1,
J. Vavrova2, I. Tacheci1
1
2nd Dpt of Internal Medicine - Gastroenterology, 2Institute of Clinical
Biochemistry and Diagnostics, Charles University and University Teaching
Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
Contact E-mail Address: marcela.kopacova@fnhk.cz
INTRODUCTION: The causal mechanism of acute pancreatitis after oral double
balloon enteroscopy (DBE) is still uncertain. The most probable cause seems to
be a mechanical straining of the endoscope with an over-tube on the pancreas.
Hyperamylasemia and hyperlipasemia after DBE are frequent and usually
asymptomatic. They do not represent the immediate risk factor of acute pancreatitis. The aim of this prospective study was to investigate several laboratory
markers to predict patients in a higher risk of hyperamylasemia and hyperlipasemia and/or possible DBE-associated acute pancreatitis.
AIMS & METHODS: A total 38 patients (18 men and 20 women, mean age 51
years) with 44 DBEs and 30 matched healthy controls with no endoscopy entered
the study. Following laboratory markers were investigated before, 4 hours and 24
hours after DBE and once in controls: serum hs-CRP, prokalcitonin, total S100
protein, cathepsin B, SPINK1, lactoferrin, E-selectin, alfa-1-antitrypsin, malondialdehyde, amylase and lipase. The mean time of DBE was 80 min. (range 20
210 min.), the mean number of push-and-pull cycles was 14 (range 1 41). We
have not recorded any DBE-associated acute pancreatitis in this series.
RESULTS: Serum amylase and lipase rose significantly with the maximum 4
hours after DBE, with increased abnormal values in 31/44 (70%) of serum amylase and 29/44 (66%) of serum lipase (p 5 0.001 and p 5 0.001). Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to
healthy controls and patients values before DBE (p 0.018 and p 0.031).
There was a statistically significant, but clinically irrelevant, difference in malondialdehyde between males and females 4 hours after DBE (0.330.20 vs.
0.200.13 mmol/L; p 0.012). No other gender-associated difference was
recorded. There was a trend for an association between number of push-andpull cycles in DBE and procalcitonin (r -0.384; p 0.011) and urine amylase
(r 0.313; p 0.043) 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin (r 0.358; p 0.021), cathepsin (r 0.362; p 0.020) and hs-CRP
(r 0.358; p 0.021); and between E-selectin and malondialdehyde (r 0.364;
p 0.019) 4 hours after DBE. Either serum amylase or lipase 4 hours after
DBE did not correlate with any markers before DBE.
CONCLUSION: Our current results support our previous hypothesis that endoscope-induced mechanical straining during DBE is the most important factor
responsible for the increase of amylase and lipase or even for progression to
acute pancreatitis. We found no laboratory predictive markers that would identify in advance those patients in a higher risk.
Disclosure of Interest: None declared
P1367 EFFICACY OF SINGLE-BALLOON ENTEROSCOPY
TREATMENT OF THE STENOSIS IN SMALL INTESTINE

FOR

N. Ogata1,*, K. Ohtsuka1,2, S. Hayashi1, K. Kodama1, S.-E. Kudo1


Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
HOSPITAL, Yokohama, 2Endoscopy unit, TOKYO MEDICAL and DENTAL
UNIVERSITY HOSPITAL, Tokyo, Japan
Contact E-mail Address: n.ogata@hotmail.co.jp
1

INTRODUCTION: Before the progress of balloon-assisted enteroscopy (BAE)


and wireless capsule endoscopy, the stenoses of the small intestine were detected
by CT or radiological enteroclysis. They were often difficult to diagnose, and
surgery was selected for diagnostic therapy. BAE has enabled to make diagnosis
and treat small intestinal lesions. We evaluated the efficacy of single-balloon
enteroscopy (SBE) for treatment of small intestinal stenosis.
AIMS & METHODS: A total of 632 cases of SBE were performed between
September 2005 and December 2013 at our center, and 62 stenotic cases of the
small intestine detected by SBE were enrolled in the study. Stenosis was defined as
difficulty in penetrating the enteroscope or sliding tube. Endoscopic balloon dilation
(EBD) was performed to the suitable cases of benign stenosis. The indications of
EBD were as follows: Abenign stenoses with the length being less than or equal to
5cm, Bstrictures without deep ulcers, fistulas, or abscesses, and Cstenoses without
sharp angle. Adopted cases were divided into two groups: CD group with stenoses
caused by Crohns disesase, and non CD group with benign stenoses caused by
other factors. We assessed the first EBD success rate, restenotic rate, duration until
restenosis, cumulative surgical free rate and occurrence of complications.
RESULTS: The causes of the stenosis cases included 23 Crohns disease (CD,
37.1%), 4 postoperative stenosis (6.5%), 4 ischemic enteritis (6.5%), 6 adenocarcinoma (9.7%), 4 cases of invasion of small intestine from other carcinoma
(6.5%), 6 malignant lymphoma (9.7%), 5 other cases (8.1%), and 10 cases of
unknown etiology (16.1%). Of the 62 cases, 24 were suitable for EBD therapy,
and 15 cases were included in the CD group while 9 cases (2 ischemic enteritis, 2
postsurgical stenoses, and 5 others) were in the non CD group. The first EBD
successful rate was 100% for each. Eight of the 15 CD cases had restenosis, while
restenosis occurred in one of nine non CD cases. The two groups had a significantly different restenotic rate (P50.05). Duration until occurrence of restenosis
was 10.91.9 months on average. The cumulative surgical free rate after EBD
was 87.5% (21/24), and the observation period was almost 4 years. One case had
a post-EBD bleeding, but perforation or other complications did not occur.
CONCLUSION: EBD was performed safely in most cases. The result suggests it
is necessary to consider periodical SBE for stenotic lesions in the small intestine,
especially in CD cases. There is a possibility that surgery can be avoided by doing
EBD in cases of small intestinal stenoses.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1368 USEFULNESS OF CAPSULE ENDOSCOPY IN THE DIAGNOSIS
OF OVERT OBSCURE GASTROINTESTINAL BLEEDING
COMPARED WITH BALLOON-ASSISTED ENTEROSCOPY
R. Sawada1,*, T. Kato22, D. Ide1, E. Hayashi1, T. Iwasaki1, N. Komoike1,
M. Saruta1, S. Arihiro1, N. Tamai2, M. Matsuoka1, S. Saito2, H. Tajiri1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
2
Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
INTRODUCTION: Although overt obscure gastrointestinal bleeding (OGIB) is
difficult to diagnose, capsule endoscopy (CE) and balloon-assisted enteroscopy
(BAE) are very effective approaches that are essential to the control of small
intestinal bleeding. CE in particular is a very simple and convenient technique for
overt OGIB. Despite great progress, few cases could not be detected using CE.
Here we checked the detection and lack of detection rates of CE and BAE.
AIMS & METHODS: Between April 2005 and June 2013, a total of 364 patients
had both CE and BAE (239 men, 125 women; mean age, 60 years) in our institute; of these, 155 had overt OGIB. When the diagnosis of overt OGIB using CE
(Pillcam SB2; Given Imaging) was first made, BAE (single-balloon enteroscopy;
Olympus Medical Systems) was checked for the diagnosis and treatment. If
lesions were suspected in the small intestine by another modality, BAE was
used despite negative CE findings. CE was checked independently by at least
two doctors. BAE was performed using an oral or anal approach according to
the CE results. Prior to checking small intestinal lesions with CE and BAE,
esophagogastroduodenoscopy and total colonoscopy were both performed to
confirm a lack of gastrointestinal bleeding except in the small intestine.
RESULTS: CE findings of 155 overt OGIB cases included: angiectasia, 30%;
erosion/ulcer, 28%; carcinoma, 7%; and Crohns disease, 1%. Active bleeding
was observed in 47 of 155 patients (30%) using CE, and all cases were confirmed
using BAE. A total of 39 (83%) of 47 cases were diagnosed by BAE, and some
cases such as angiectasia were simultaneously treated with BAE. However, 17
(17%) of the 47 cases could not be diagnosed using BAE. Of the 155 cases of
overt OGIB, 108 (70%) could not be detected by bleeding points using CE, but
five (3.2%) cases were diagnosed using another modality such as scintigraphy or
BAE. They were three cases of Meckels diverticulum, one case of jejunal sarcoma, and one case of angiectasia of the ileum. CE images of these patients were
not consistent with lesions, so the diagnoses could not be made by CE only.
CONCLUSION: CE is very useful for the detection and diagnosis of overt
OGIB. However, some cases could not be detected in the present study.
Therefore, even if bleeding points cannot be detected by CE and bleeding
occurs repeatedly, another modality such as BAE should be applied.
Disclosure of Interest: None declared
P1369 FACTORS INFLUENCING CECAL INTUBATION TIME DURING
RETROGRADE SINGLE-BALLOON ENTEROSCOPY: IS IT THE
SAME AS THAT DURING COLONOSCOPY?
T.-M. Ou1, P.-J. Chen1, W.-K. Chang1, T.-Y. Hsieh1, T.-Y. Huang1,*
1
Internal Medicine, TRI-SERVICE GENERAL HOSPITAL, Taipei, Taiwan,
Province of China
Contact E-mail Address: teinyu.chun@msa.hinet.net
INTRODUCTION: The retrograde technique for single-balloon enteroscopy
(SBE) seems to be more difficult than the antegrade technique because of the
need to pass through the colon. The predisposing factors for prolonged cecal
intubation time (CIT) during colonoscopy have been well identified. However,
the factors influencing CIT during retrograde SBE have not been addressed.
AIMS & METHODS: The aim of this study was to determine the factors influencing CIT during retrograde SBE. We investigated patients who underwent
retrograde SBE at a medical center from January 2011 to March 2014. The
medical charts and SBE reports were reviewed. The patients characteristics
and procedure-associated data were recorded: age, sex, body mass index
(BMI), indication, history of surgery, bowel preparation, CIT, total procedure
time, endoscopic findings, and endoscopic interventions. These data were analyzed with univariate analysis as well as multivariate logistic regression analysis
to identify the possible predisposing factors.
RESULTS: The median CIT was 17.4 minutes. With univariate analysis, there
was no statistical difference in age, sex, BMI, or history of abdominal surgery,
except for bowel preparation (P 0.022). Multivariate logistic regression analysis
showed that bowel preparation (odds ratio 7.80, 95% confidence interval 2.76
22.02; P 5 0.001) and previous history of pelvic surgery (odds ratio 0.26, 95%
confidence interval 0.700.97; P 0.045) were the independent predisposing factors for prolonged CIT during retrograde SBE.
CONCLUSION: Bowel preparation and previous history of pelvic surgery were
the independent predisposing factors for prolonged CIT during retrograde SBE.
Disclosure of Interest: None declared
P1370 SMALL BOWEL AND COLONIC MUCOSAL HEALING IN
CROHNS DISEASE - A PILOT STUDY WITH PILLCAM COLON 2
FOR ENTIRE GASTROINTESTINAL CAPSULE ENDOSCOPY
P. Boal Carvalho1,2,*, B. Rosa1,2, F. Dias de Castro1,2, M.J. Moreira1,2,
J. Cotter1,2
1
Life and Health Sciences Research Institute (ICVS), School of Health Sciences,
University of Minho, 2Gastrenterology, Centro Hospitalar do Alto Ave, Guimaraes,
Portugal
INTRODUCTION: In Crohns Disease (CD), both small bowel and colonic
mucosa are affected in almost half the patients. PillCam COLON2 Capsule
(PCC2) allows for the non-invasive evaluation of the entire gastrointestinal tract.

A505
AIMS & METHODS: Our aim was to evaluate mucosal healing in patients with
both small bowel and colon distribution of CD using PCC2.
We included patients with non-stricturing non-penetrating small bowel plus colonic CD in corticosteroid-free remission (Harvey-Bradshaw Index 5 5); patients
had been submitted to ileocolonoscopy (identifying active CD lesions such as
ulcers, erosions and spontaneous bleeding) and small bowel capsule endoscopy
(with Lewis Score assessment) at diagnosis.
After  1 year of follow-up, patients underwent entire gastrointestinal tract
evaluation with PCC2, which was reviewed by an independent researcher,
blinded to both the initial endoscopic results and current CD therapy. Primary
endpoint: to assess mucosal healing in small bowel and colon mucosa, defined as
a Lewis Score (LS) 5 135 and no active CD lesions in the colon.
RESULTS: Twelve patients were included, 7 male; mean age was 32 (18-50)
years, mean follow-up was 38 (12-62) months. At diagnosis, most patients
(n 8, 66.7%) presented with segmental CD lesions in ileocolonoscopy; moderate to severe activity (LS790) was observed during SBCE in 7 patients (58.3%),
while 5 (41.7%) presented with mild activity (LS 135-790). Two patients were
treated with combination immunossupression therapy (anti-TNF and
azathioprine), 8 with azathioprine in monotherapy and 2 with messalazine. We
are currently recalling patients for PCC2.
Six patients already completed the procedure: the entire gastrointestinal tract was
observed in all of them. Small bowel mucosal healing (LS5135) occurred in 3
patients (50%) patients - 2 of them, with a LS790 at diagnosis, treated with
azathioprine in monotherapy, and the other one, with previous LS 135-790, was
treated with messalazine. Two patients maintained moderate to severe activity in
the small bowel despite treatment with azathioprine, and another one, also under
azathioprine monotherapy, was shown to have intensified inflammatory activity
(mild activity at diagnosis and moderate to severe activity in the small bowel
observed with PCC2).
Mucosal healing of the colonic mucosa was observed in 3 patients (50%), two of
them treated with azathioprine, and the remainder with messalazine; 2 patients
maintained a segmental pattern of colon CD, and in one patient, treated with
azathioprine, CD lesions throughout the entire colonic mucosa persisted during
follow-up.
CONCLUSION: With this pilot study, in a population of patients with both
small bowel and colonic Crohns Disease, we have shown that endoscopy of the
entire gastrointestinal tract with PCC2 is feasible and safe, allowing for mucosal
inflammatory activity assessment in patients in clinical remission, evaluating
mucosal healing as a surrogate of treatment efficacy.
Disclosure of Interest: None declared
P1371 VIRTUAL
CHROMOENDOSCOPY
IMPROVES
THE
DIAGNOSTIC YIELD OF SMALL BOWEL CAPSULE ENDOSCOPY
IN OBSCURE GASTROINTESTINAL BLEEDING
P. Boal Carvalho1,*, J. Magalhaes1, F. Dias de Castro1, T. Curdia Goncalves1,
B. Rosa1, M.J. Moreira1, J. Cotter1,2
1
Gastrenterology, Centro Hospitalar do Alto Ave, 2Life and Health Sciences
Research Institute (ICVS), School of Health Sciences, University of Minho,
Guimaraes, Portugal
Contact E-mail Address: Pedro.n.carvalho@gmail.com
INTRODUCTION: Small bowel capsule endoscopy (SBCE) represents the initial
form of investigation for obscure gastrointestinal bleeding (OGIB). FICE mode
is a virtual chromoendoscopy technique designed to enhance focal lesions during
endoscopic procedures.
AIMS & METHODS: Our objective was to compare and analyze the differences
in diagnostic yield using both FICE 1 and conventional SBCE imaging.
Included 60 consecutive patients referred to SBCE for OGIB. Every SBCE exam
was independently reviewed by four researchers using conventional imaging and
FICE 1, and afterwards compared by an independent researcher for consensus
report.
Diagnostic yield was defined as the presence of at least one small bowel lesion
with high bleeding potential (P2), such as angioectasia, ulcer or tumor, after the
exclusion of false positive results.
Statistical analysis of the data was performed with SPSS v21.0, using the
McNemar test for categorical variables and paired-samples T-test for continuous
variables.
RESULTS: SBCE diagnostic yield using FICE 1 was significantly higher than
conventional imaging (58.3 vs 41.7 %, p 0.021). Using FICE 1 we additionally
found a superior number of P2 lesions (74 vs 44, p 0.003), particularly angioectasias (54 vs 26, p 0.002). No differences were observed regarding the number
of ulcers (17 vs 15, p 0.568) or tumors (3 vs 3, p 1.000) when comparing FICE
1 with conventional imaging.
CONCLUSION: FICE 1 viewing during small bowel capsule endoscopy for
obscure gastrointestinal bleeding was significantly superior to conventional imaging, resulting in a 16% improvement in diagnostic yield. Potentially bleeding
lesions were more often observed when using FICE 1, in particular angioectasias.
Our results support the generalization of this technique while reviewing small
bowel capsule endoscopy for obscure gastrointestinal bleeding.
Disclosure of Interest: None declared

A506
P1372 ACTIVE SMALL BOWEL BLEEDING: EARLIER DETECTION,
EARLIER REACTION
P. Boal Carvalho1,*, B. Rosa1, J. Cotter1,2
Gastrenterology, Centro Hospitalar do Alto Ave, 2Life and Health Sciences
Research Institute (ICVS), School of Health Sciences, University of Minho,
Guimaraes, Portugal
Contact E-mail Address: Pedro.n.carvalho@gmail.com
1

INTRODUCTION: Obscure gastrointestinal bleeding (OGIB) is the leading indication for small bowel capsule endoscopy (SBCE). Despite being present in only
a minority of patients undergoing SBCE, early detection of active bleeding allows
for treatment adjustments and prognostic improvement.
AIMS & METHODS: We aimed to ascertain whether some clinical and analytical patient characteristics would correlate with active bleeding in the small
bowel observed during capsule endoscopy.
Unicentric retrospective study comprising all patients submitted to SBCE for
OGIB over 6 years. The following variables were analyzed: age, gender, comorbidities (hypertension, chronic kidney disease, diabetes mellitus, ischemic heart
disease), antiplatelet and anticoagulant drug use, and the need for hospital
admission. Both active bleeding and potentially bleeding lesions in the small
bowel were assessed during SBCE. Statistical analysis was performed with
SPSS 21.0, and a p value 5 0.05 was considered significant.
RESULTS: Among the 244 patient included, potentially bleeding lesions were
found in 65 (26.6%), while active bleeding on SBCE was observed in 21 patients
(8.6%). Small bowel hemorrhage was significantly more frequent among patients
presenting with visible gastrointestinal bleeding (19 versus 7%, p 0.008). Elder
patients (72 versus 60 years p 0.003), hospitalized patients (17 versus 7%,
p 0.034) and those with ischemic heart disease (16 versus 5%, p 0.007) displayed significantly more often small bowel active bleeding. Only 1% of the
patients with no comorbidities was found to have active bleeding during
SBCE, compared to 14% among patients with 2 or more comorbidities
(p 0.007). Antithrombotic drugs were not associated with an increased risk
for small bowel active bleeding.
CONCLUSION: Small bowel active bleeding was significantly more frequent in
patients presenting with visible OGIB. Advanced age, the need for hospital
admission and comorbidities, particularly ischemic heart disease, were associated
with an increased prevalence of active bleeding during SBCE. In such patients,
carrying out small bowel capsule endoscopy early on is of prime importance as to
swiftly detect and treat the observed lesions.
Disclosure of Interest: None declared
P1373 DELIVERING A CAPSULE ENDOSCOPY SERVICE TO A WIDE
GEOGRAPHICAL AREA THE SOUTH TYNESIDE EXPERIENCE
R. Bevan1,2,*, C. Davison1,2, S. Dunn1,2, F. Butt1, S. Panter1,2
SOUTH TYNESIDE DISTRICT HOSPITAL, South Shields, 2NREG,
Newcastle, United Kingdom
1

INTRODUCTION: Video capsule endoscopy (VCE) is an increasingly utilised


small bowel investigation. Not all hospital sites offer it; patients may need to
travel to have the procedure performed. It involves several appointments; assessment prior to the procedure, patency capsule (PC) procedure, follow up radiology, & the VCE procedure itself.
In the Northern region of England, 2 centres offer an established VCE service,
with a 3rd service recently commissioned. Despite efforts to develop services in
the most appropriate localities, the referral area to these centres is large with
potential journey times of over 2 hours.
South Tyneside District Hospital (STDH) started performing VCE in 2006, and
began a telephone assessment service in 2010. Referrals are received from across
the Northern region, frequently extending as far as Cumbria, North Yorkshire
and South Teeside, and occasionally from further afield (Scotland, the
Midlands). Prior to the telephone service, patients were admitted for assessment,
PC (if appropriate, based on clinical information and patient informed choice),
bowel prep, and VCE procedure equating on average 1-3 nights in hospital.
AIMS & METHODS: We describe the patient pathways before and after the
telephone service began, and evaluate the service up to January 2014. Average
patient stay was calculated, bed days saved and cost differences described using
NHS costings for elective stays in hospital.
RESULTS: The telephone service started in August 2010. Two 30-minute slots
are allocated each week to the service, and are reserved for patients from outside
the local area.
A nurse consultant conducts the telephone consultation. Those requiring PC are
sent the device to their home to take unsupervised, or may attend their local
hospital to be observed. They attend STDH the following day for a scan /AXR/localised CT abdomen. They either stay locally overnight for VCE the
following day, or return home with a future plan for VCE. Alternatively, they
are admitted to STDH, and VCE administered the following day. If not requiring
PC, bowel preparation, consent forms and instructions are sent to the patient,
with the patient attending STDH for VCE to be delivered. Patients can be
admitted to STDH for inpatient preparation if required.
1164 VCE procedures have been performed at STDH. From 525 referrals from
outside STDH, 205 telephone assessment appointments have been utilised.
The highest number of telephone assessments have come from hospitals in
Cumbria: 77 referrals from Carlisle, and 52 from Whitehaven; 73 and 111
miles from STDH respectively. Saving each patient one return journey by
using the telephone service has reduced patient journeys by almost 23,000
miles. An elective inpatient bed costs 225 per night. A telephone service appointment is charged at 23.69. PC device and VCE device costs are the same in both
pathways. Therefore, making a conservative estimate of cost savings (assuming

United European Gastroenterology Journal 2(1S)


all telephone service patients have reduced their inpatient stay by one night),
38,000 has been saved by this service in 4 years.
CONCLUSION: A telephone assessment clinic for patients distant to the VCE
centre has been well utilised at STDH. This has reduced the inpatient stay
required for VCE investigation, reducing costs, the impact on the gastroenterology inpatient service, and travel burden on patients.
Disclosure of Interest: R. Bevan: None declared, C. Davison: None declared, S.
Dunn Financial support for research from: Aquilant Endoscopy, F. Butt: None
declared, S. Panter: None declared
P1374 CAPSULE ENDOSCOPY: DIAGNOSTIC ACCURACY OF LEWIS
SCORE IN PATIENTS WITH SUSPECTED CROHNS DISEASE
S. Monteiro1,*, P. Boal Carvalho 1, F. Dias de Castro 1, J. Magalhaes 1,
J. Firmino Machado2, M.J. Moreira1, B. Rosa1, J. Cotter1,3
1
Gastroenterology, 2Centro Hospitalar do Alto Ave, Guimaraes, 3Instituto de
Investigacao em Ciencias da Vida e da Saude, Universidade do Minho, Braga/
Guimaraes, Portugal
Contact E-mail Address: sara.s.o.monteiro@gmail.com
INTRODUCTION: Small bowel capsule endoscopy (SBCE) has assumed an
increasing importance in the diagnosis of Crohns Disease (CD). The Lewis
Score (LS) aims to standardize the quantification of inflammatory activity
detected in the small bowel mucosa.
AIMS & METHODS: The aim of this study was to evaluate the diagnostic
accuracy of the LS in patients undergoing SBCE for suspected CD. We performed a retrospective single-center study including 95 patients who underwent
SBCE for suspected CD between September 2006 and February 2013, with at
least 12 months of follow-up after the capsule. Patients were divided in 2 groups
according to the criteria of the International Conference on Capsule Endoscopy
(ICCE) for the definition of suspected CD. Group 1: 37 patients not fulfilling
ICCE criteria; Group 2: 58 patients with  2 ICCE criteria. Inflammatory activity on SBCE was objectively assessed by determining the LS. The diagnosis of
CD during follow-up was based on a combination of clinical, analytical, endoscopic, histological and imaging elements.
RESULTS: SBCE detected significant inflammatory activity (LS  135) in 46
patients (48.4%), 7 patients from group 1 (18.9%) and 39 patients from group 2
(67.2%) (p 5 0.001).
The diagnosis of CD was established in 38 patients (40%): 8 patients (21.6%)
from Group 1, 30 patients from Group 2 (51.7%) (p 0.003), 34 patients with LS
 135 (73.9%) and 4 patients with LS 5 135 (8.2%) (p 5 0.001). The LS  135
had an overall diagnostic accuracy of 83.2 %. The LS Sensitivity, Specificity,
Positive Predictive Value and Negative Predictive Value for the diagnosis of CD
were 89.5%, 78.9%, 73.9% and 91.8%, respectively.
CONCLUSION: The application of LS  135 as the cut-off value for the presence of significant inflammatory activity in patients undergoing SBCE for suspected CD may be useful to establish the diagnosis. In patients with LS 5 135,
the probability of having CD confirmed on follow-up is low.
Disclosure of Interest: None declared
P1375 IS IT WORTH REPEATING PREVIOUSLY UNREMARKABLE SB2
CAPSULES WITH THE NEW SB3?
S. Dunn1,*, R. Bevan1, L. Neilson1, R. Dunn1, C. Davison1, F. Butt1, S. Panter1
1
South Tyneside NHS Foundation Trust, South Shields, United Kingdom
Contact E-mail Address: simon.panter@stft.nhs.uk
INTRODUCTION: Small bowel capsule endoscopy (SBCE) has become a valuable tool for investigating the small bowel and technology is rapidly advancing.
One of the most recent devices available for capsule endoscopy (Pillcam SB3,
Given Imaging) has improved image resolution and a variable frame rate. The
aim of this work is to address whether these innovations lead to increased mucosal visualisation and diagnostic yield in clinical practice and therefore whether a
repeat SB3 capsule should be considered in those patients with an equivocal SB2
result.
AIMS & METHODS: A review was undertaken of the last 100 Pillcam SB2
capsules and the first 100 Pillcam SB3 capsules to be performed at South
Tyneside District Hospital (14/01/13 - 13/03/14). Visualisation of the ampulla
was used as a surrogate marker of mucosal visualisation and diagnostic yield was
assessed by reviewing the reports. Statistical significance was calculated using
Fishers exact test.
RESULTS: Results are summarised in the table below. The ampulla was visualised in 14% of SB2 capsules and 14% of SB3 capsules (p40.05). 44% of SB2
capsules were abnormal and SB3 capsules were abnormal in 60% of cases
(p50.05)
Capsule type

Number

Ampulla seen (%)

Pathology found (%)

SB2
SB3
p value

100
100

14 (14%)
14 (14%)
1.0000

44 (44%)
60 (60%)
0.0335

CONCLUSION: It is recognised that the views obtained by SBCE can be compromised in the duodenum due to rapid transit and variable frame rates hope
to address this by capturing more images when the capsule is moving quicker. We
showed no statistically significant difference in ampullary visualisation between
the SB2 and SB3 capsules. However the overall yield of pathology from SB3
capsules was significantly higher than that in SB2 capsules. Given the overall

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United European Gastroenterology Journal 2(1S)


increased yield of pathology it may be beneficial to repeat an SB3 capsule in
someone with a previously equivocal SB2 result.
REFERENCES
1. Koulaouzidis A, Rondonotti E and Karargyris A. Small-bowel capsule endoscopy: a ten-point contemporary review. World J Gastroenterol 2013; 19 (24):
3726-2840.
Disclosure of Interest: S. Dunn Financial support for research from: Aquilant
Endoscopy, R. Bevan Financial support for research from: Aquilant Endoscopy,
L. Neilson: None declared, R. Dunn: None declared, C. Davison: None declared,
F. Butt: None declared, S. Panter: None declared
P1376 IS THERE A ROLE FOR URGENT SMALL BOWEL VIDEO
CAPSULE ENDOSCOPY?
S. Dunn1,*, F. Butt1, R. Bevan1, C. Davison1, S. Panter1
1
South Tyneside NHS Foundation Trust, South Shields, United Kingdom
Contact E-mail Address: simon.panter@stft.nhs.uk
INTRODUCTION: Capsule endoscopy has become a valuable modality for
imaging the small bowel and has been suggested as a useful diagnostic tool in
the emergency diagnosis of overt occult GI bleeding when used in the appropriate
context1. Diagnostic yield (DY) is known to be greatest if the study is performed
as soon as possible after the bleeding episode2. This is not possible in centres
without a capsule endoscopy service who therefore refer for urgent studies.
Presently the DY of urgent small bowel video capsule endoscopy (SBCVE) is
unclear. This work aims to assess the DY of urgent SBVCE in a district general
hospital acting as a tertiary referral centre for SBVCE.
AIMS & METHODS: All referral letters since 2008 were reviewed. Referrals
were classified as urgent if the referrer had indicated a degree of urgency or if
the team at South Tyneside felt the SBVCE should be done urgently. DY was
assessed by reviewing the capsule endoscopy reports and then relating the findings to the indication. Considered as positive findings were active bleeding,
angiodysplasias, ulcers, strictures, tumours, villous atrophy and polyps.
RESULTS: 127 studies were identified from reviewing the referral letters (1164).
Of these 60 were requested as urgent, 24 were expedited and 43 were changed to
urgent by the capsule endoscopy team. 57 of the 127 capsules had a significant
finding (45%). The table below summarises the results. Active bleeding was
defined as patients having melaena or ongoing transfusion requirements.
Abnormal imaging was defined as a CT or MRI showing potentially abnormal
small bowel. Diarrhoea only and weight loss only were indications where the
referrer was not querying the possibility of Crohns disease.
Indication

Number

Significant?

?Active bleeding
?Crohns disease
Abnormal imaging
Anaemia
Crohns assessment
Diarrhoea only
Weight loss only
Other
Total

47
12
14
27
5
3
11
8
127

37.01%
9.45%
11.02%
21.26%
3.94%
2.36%
8.66%
6.30%
100.00%

25
3
5
16
2
1
3
2
57

53.19%
25.00%
35.71%
59.26%
40.00%
33.33%
27.27%
25.00%

CONCLUSION: The most common indication for an urgent capsule was the suspicion of active bleeding and more than half of these SBVCEs showed a bleeding
point. Urgent investigations for anaemia also had a high yield of positive findings.
Other indications with more than 10 urgent studies performed did not show an
appreciable yield. Our data adds weight to the argument that capsule endoscopy
may be a useful test in active occult GI bleeding while also suggesting it may play a
role in the assessment of severe anaemia in the absence of overt GI bleeding. Such
patients should be referred for urgent assessment to maximise diagnostic yield.
REFERENCES
1. Despott E. Is there a role for emergency small bowel capsule endoscopy in the
investigation and management of severe obscure-overt gastrointestinal bleeding?
Ann Gastroenterol 2013; 26: 178-179.
2. Panazzio et al. Outcome of patients with obscure gastrointestinal bleeding
after capsule endoscopy: report of 100 consecutive cases. Gastroenterology
2004; 126: 643-653.
Disclosure of Interest: S. Dunn Financial support for research from: Aquilant
Endoscopy, F. Butt: None declared, R. Bevan Financial support for research
from: Aquilant Endoscopy, C. Davison: None declared, S. Panter: None declared

AIMS & METHODS: We aimed to assess PHE in patients with liver cirrhosis
(LC) using capsule endoscopy (CE) and investigated factors that may predict its
presence, including PSs.
One hundred and thirty-four consecutive patients with LC (78 males and 56
females), with a mean age of 66.7 years (range: 2788 years) who underwent
CE at our hospital between February 2009 and September 2013, comprised the
study population. All had undergone dynamic computed tomography (CT) and
esophagogastroduodenoscopy before CE examination. The frequencies and types
of PHE lesions were investigated. The distribution of the lesions was also determined. Moreover, the relationships between PHE and the patients clinical characteristics, which included age, sex, liver function, etiology of cirrhosis, PSs,
ascites, hepatocellular carcinoma, splenomegaly, portal thrombosis, esophageal
varices (EVs), gastric varices, and portal hypertensive gastropathy (PHG), were
examined. PSs were evaluated using dynamic CT during the portal venous phase
and coronal CT imagery. Left gastric veins, short gastric veins, posterior gastric
veins, paraesophageal veins, splenorenal shunts, and paraumbilical veins with
diameters greater than 3 mm were defined as PSs. Comparisons were performed
using Students t-test for quantitative data and the chi-square test for categorical
data. All tests were 2-sided, and a P value 5 0.05 was considered statistically
significant. The impacts of the clinical variables on PHE were estimated by
calculating the odds ratios (OR) and the 95% confidence intervals (95% CI)
using logistic regression analyses.
RESULTS: PHE was found in 91 (68%) patients, and 70 (52%) patients had
erythema, 25 (19%) had erosions, 24 (18%) had angioectasia, 18 (13%) had
villous edema, and 10 (7%) had varices. Most lesions were located in the jejunum. The clinical characteristics associated with the presence of PHE were a
Child-Pugh grade of B or C (P 0.0058), and the presence of PSs (P 5
0.0001), ascites (P 0.0017), portal thrombosis (P 0.016), EVs (P 0.0017),
and PHG (P 0.0029). The other factors had no significant relation with the
presence of PHE. Subsequent multivariate analysis determined that the presence
of PSs was an independent predictor of PHE (OR: 3.15; 95% CI: 1.277.95). The
shunt types significantly associated with PHE on univariate analysis were the left
gastric vein (P 0.00068), the paraesophageal vein (P 0.029), and splenorenal
shunts (P 0.03). Subsequent multivariate analysis determined that left gastric
vein (OR: 5.31; 95% CI: 1.9717.0) and splenorenal shunts (OR: 4.26; 95% CI:
1.2919.4) were independent predictors of PHE.
CONCLUSION: PSs appear to reliably predict the presence of PHE.
Furthermore, CE should be considered in patients with LC accompanied by
PSs, especially left gastric vein and splenorenal shunts.
Disclosure of Interest: None declared
P1378 THE FACTOR OF IMPROVEMENT THE DIAGNOSTIC YIELD OF
THE CAPSULE ENDOSCOPE IN OBSCURE GASTROINTESTINAL
BLEEDING WITH NEGATIVE SMALL BOWEL COMPUTED
TOMOGRAPHY
Y.S. Lee1,*, J.-O. Kim1, W.C. Lee1, S.R. Jeon1, H.G. Kim1, T.H. Lee1, J.H. Cho1, Y. Jung1, B.M. Ko1, J.Y. Cho1, J.S. Lee1, M.S. Lee1
1
Internal Medicine, Institute for Digestive Research, Digestive Disease Center,
Division of Gastroenterology, Department of Internal Medicine, College of
Medicine, Soonchunhyang University, Seoul, South Korea, Seoul, Korea, Republic
Of
INTRODUCTION: Capsule endoscopy (CE) is currently recommended as firstline study in the evaluation of obscure gastrointestinal bleeding (OGIB), some
consider small bowel computed tomography (SBCT) as a complementary test to
CE
AIMS & METHODS: AIMS: This study evaluated the factors of improvement
the diagnostic yield of CE in patients with OGIB and negative SBCT.
METHODS: We reviewed the medical records related to forty one patients with
OGIB who was performed SBCT and CE from July 2007 to February 2013,
focusing our attention with negative SBCT. SBCT is defined including enteral
phase with or without neutral enteric contrast material. We evaluated forty one
patients with negative SBCT and analyzed the detection rate of CE obscure
bleeding focus. Cases were divided into two groups; first group who had diagnostic finding of CE (n 26) and second group who had non-diagnostic finding
of CE (n 15). The two groups were compared retrospectively.
RESULTS: Twenty six of 41 (63.4%) CE studies had diagnostic results. Mucosal
lesions (75.6%) were the most common findings, followed by nonspecific findings
(17.1%) and tumorous lesions (2.4%). In comparison between patients with and
without diagnostic CE finding, mucosal lesion (Odds 21.660, CI 2.269-206.755;
p 0.008) and using of neutral enteric contrast material before SBCT (Odds
15.828, CI 1.005-249.350; p 0.050) were significant factor for diagnostic CE
finding.
CONCLUSION: In the patients with OGIB and negative SBCT, using of neutral
enteric contrast material before SBCT is possible to improve the diagnostic yield
of the CE
Disclosure of Interest: None declared

P1377 MAJOR
PREDICTORS
OF
PORTAL
HYPERTENSIVE
ENTEROPATHY IN PATIENTS WITH LIVER CIRRHOSIS
T. Aoyama1,*, S. Oka2, H. Aikata1, A. Igawa1, M. Nakano1, N. Naeshiro1,
S. Yoshida2, S. Tanaka2, K. Chayama1
1
Department of Gastroenterology and Metabolism, Graduate School of Biomedical
Sciences, Hiroshima University, 2Department of Endoscopy, Hiroshima University
Hospital, Hiroshima, Japan
INTRODUCTION: Since portal hypertensive enteropathy (PHE) has been
acknowledged as a source of bleeding, predicting its presence has become more
important. However, few previously published reports discuss factors that predict
its presence in the context of portosystemic shunts (PSs).

P1379 SELF-EXPANDABLE METAL STENTS IN THE MANAGEMENT


OF BENIGN ESOPHAGEAL DISEASES
P. Magalhaes-Costa1,*, T. Bana1, D. Serra1, L. Matos1, C. Chagas1
Gastrenterology, Hospital Egas Moniz - Centro Hospitalar Lisboa Ocidental,
Lisboa, Portugal
Contact E-mail Address: pmagalhaescosta@gmail.com
1

INTRODUCTION: The use of self-expandable metal stents in the esophagus for


the management of benign disease has grown immensely over the last decade.
Fully covered self-expandable metal stents (FCSEMS) are considered a viable
alternative to serial bougienage and endoscopic dilation in the management of

A508
refractory benign esophageal strictures. The use of SEMS, particulary partially
covered (PCSEMS), in the treatment of anastomotic esophageal leaks or fistulas
is a valid and efficacious resource in order to restore the gastrointestinal function,
resume oral nutrition and avoiding a, potencially costly, surgical re-intervention.
AIMS & METHODS: The primary aim of this retrospective study was to determine the efficacy and safety, in our institution (Jan 2008 - Feb 2013), of
FCSEMS for refractory benign esophageal strictures and SEMS (mainly
PCSEMS) in the management of anastomotic esophageal leaks/fistulas.
RESULTS: A total of 14 patients underwent SEMS placement for benign esophageal conditions. 8 patients for refractory esophageal stricture and 6 for postsurgery leak/fistula. In the stricture group, 19 FCSEMS were used (patient/stent
ratio: 2.4) and in the post-surgery group, 13 SEMS were needed (patient/stent
ratio: 2.0). Regarding the etiology, stricture group: post-surgery (n 3), radiation-induced (n 2), caustic (n 1) and peptic (n 1). In the anastomotic esophageal leak/fistula group, the most common procedure was a laparoscopic
gastric sleeve (n 4) and gastric bypass (n 2). In 50% of the cases, 2 stents
were deployed in the same session. In the stricture group, the preferred stents
were the Wallflex@ Boston Scientific (n 11) and the Hanarostent@ M. I. Tech
(n 5). The stent body diameter ranged from 18 and 23mm. In the post-surgery
group, the preferred stent was the partially covered Ultraflex@ Boston Scientific
(n 5), Wallflex@ Boston Scientific (n 4) and Evolution@ Cook Medical
(n 3). In this group, the use of PCSEMS dominated (n 10; 77%). The
mean stent body diameter was 25mm and length 125mm. The technical immediate success rate was 79% (15/19) and 100% (6/6) for the stricture and postsurgery groups, respectively. Global stent migration rate, for the stricture
group, was 63% (12/19). No migration events were reported in the post-surgery
group. Stent occlusion by tissue hyperplasia occurred more in the stricture group
(3 events vs 1 event). All the stents were removed successfully, including those
who migrated, and no procedure nor stent-related complications were reported.
Clinically, at the end of the study, in the stricture group, 3 out of 8 patients (38%)
remain symptom-free and their stricture was deemed solved, another 3 out of 8
patients (38%) had a temporary clinical benefit but remain dependent of endoscopic dilation and 2 cases (25%) demanded an invasive procedure. In the leak/
fistula group, complete resolution was achieved in 83% (5/6).
CONCLUSION: Althought far from being the perfect solution for refractory
benign esophageal strictures, FCSEMS appear to be a valid and safe option in
their management. Their clinical success is moderate (38%) but migration rates
seem to remain a frequent issue (63%). On the other hand, the use of PCSEMS in
the management of anastomotic esophageal leaks or fistulas seems to hold a high
clinical success rate (83%) without complications or migration events.
Disclosure of Interest: P. Magalhaes-Costa: None declared, T. Bana: None
declared, D. Serra Consultancy for: Wilson Cook, L. Matos Consultancy for:
Gilead, Merck Sharp & Dohme, Janssen, C. Chagas Lecture fee(s) from: Abbvie.
P1380 GASTRIC OUTLET OBSTRUCTION TREATMENT WITH
ENDOSCOPIC PLACEMENT OF SELF-EXPANDING METAL
STENT: DATA FROM A LARGE SERIES OF PATIENTS TREATED IN
A TERTIARY REFERRAL HOSPITAL FOR PALLIATIVE CARE
R. Di Mitri1,*, F. Mocciaro1, G.M. Pecoraro1
Gastroenterology and EndoscopyUnit, A. R. N. A. S. Civico-Di CristinaBenfratelliHospital, Palermo, Italy
Contact E-mail Address: fmocciaro@gmail.com
1

INTRODUCTION: Gastric outlet obstruction (GOO) can occur in several different GI malignant conditions (intrinsic or extrinsic) that can be treated with
endoscopic placement of self-expanding metal stents (SEMS). In non operable
patients SEMS placement ensure a prompt oral intake with less morbidity and
shorter hospital stay compared to surgical jejunostomy. Clinical success rate is
similar between surgical and endoscopic treatment (around 90%).
AIMS & METHODS: The aims of this study are to evaluate the efficacy and
safety of SEMS placement in a large consecutive series of patients with malignant
inoperable gastroduodenal obstruction. From March 2007 to March 2014 we
collected data on all consecutive patients treated with SEMS placement
(Wallflex Enteral by Boston Scientific) due to malignant GOO. Baseline gastric
outlet obstruction scoring system (GOOSS) score was recorded (0 no oral
intake; 1 liquid diet; 2 soft solid diet; 3 low residue or normal diet).
Stents were deployed under fluoroscopic and endoscopic guidance after traversing the stricture with a catheter/guidewire. If needed, balloon dilation was performed before stent placement. Technical and clinical success, and adverse events
were recorded.
RESULTS: 63 patients (42 male [67%]), with a mean age of 69.612.7 year, were
treated: 34 had pancreatic head cancer (54%), 13 antro-bulbar cancer (21%), 7
gallbladder cancer/cholangiocarcinoma (11%), 4 retroperitoneal sarcoma (6%),
3 peritoneal carcinomatosis (5%), 2 duodenal obstruction due to colon cancer
(3%). Thirty-one of these patients had biliary involvement too (49%) treated
with biliary SEMS placement. Baseline GOOS score was: 0 in 27 patients
(43%), 1 in 23 (36%), 2 in 10 (16%), 3 in 3 (5%). Technical success was achieved
in all patients with a satisfactory oral feeding after 24-42 hours. Median lenght of
SEMS was 9 cm (range 6-12). At 1 month the median GOOSS score improved
from 1 [range 0 -3] to 2 [range 2-3]. In patients with both biliary and duodenal
obstruction the double stenting allowed significant improvement in oral feeding
and bilirubin levels reduction (at least 50% of the baseline value). None complications related to the SEMS placement were recorded. Stent occlusion due to
ingrowth occurred in 3 patients (5%). The median hospital stay was 4 days (range
3-8) with a median survival time of 7 months (range 3-9). All deaths were due to
the natural course of underlying malignancy.
CONCLUSION: Endoscopic management of gastroduodenal obstruction with
SEMS placement is the treatment of choice in advanced unresectable gastroenteric neoplasm. It is a safe procedure and it enhances patients quality of life.

United European Gastroenterology Journal 2(1S)


In advanced diseases or in frail patients palliative surgery should be considered
only in case of endoscopic failure.
Disclosure of Interest: None declared
P1381 EFFICACY OF THE OVER-THE-SCOPE CLIP (OTSC) IN THE
MANAGEMENT OF IATROGENIC GASTROINTESTINAL
PERFORATIONS
S. Khater1,*, G. Rahmi1, E. Samaha1, L. Abbes1, M. Barret1, M. Georgia1,
C. Cellier1
1
Hopital Europeen Georges Pompidou, Paris, France
Contact E-mail Address: sherine_khater@hotmail.com
INTRODUCTION: Perforation is a rare but serious complication of endoscopic
procedures. The over-the-scope clip (OTSC, Ovesco, Tuebingen, Germany) is a
novel endoscopic tool used in the non surgical management of gastrointestinal
perforations. However, data from clinical use are still limited.
AIMS & METHODS: The aim of this study is to evaluate the efficacy and safety
of this clip in closure of iatrogenic perforations occurring during diagnostic and
therapeutic endoscopies. We conducted a monocentric retrospective study. From
June 2011 to September 2013, eight consecutive patients (mean age: 72 years [4393], 7 women) had an acute iatrogenic perforation treated with an OTSC.
RESULTS: The perforation was located in the sigmoid in five patients, the
duodenum in two patients and the cardia in one patient. The mean size of the
perforation was 11.8 mm [10-20]. Endoscopic repair was performed by using a
single OTSC. The twin grasper was used in 50% of the cases to approximate the
edges of perforation. Complete sealing of the perforation was achieved with
OTSC in all patients. An exsufflation of the pneumoperitoneum using an 18gauge needle was performed in two patients. An abdominal CT scanner was done
in the following 48 hours in five patients and showed a pneumoperitoneum without leakage. The overall clinical success rate was 75% (6/8 patients). One patient
required surgical intervention although the clip had completely sealed the perforation because of the presence of a localized peritonitis with fever and abdominal pain. An adverse event occurred in one patient in whom the OTSC
placement in the sigmoid was complicated by right ureteral obstruction; this
patient had to undergo surgery in order to perform a ureteral resection and
anastomosis and remove the clip.
CONCLUSION: OTSC is effective for endoluminal closure of iatrogenic gastrointestinal perforations, with a complete sealing of the perforation in 100% of
cases. Complications can occur but are exceptional.
Disclosure of Interest: None declared
P1382 USE OF BARIATRIC SELF-EXPANDABLE METAL STENTS FOR
THE TREATMENT OF STAPLE LINE LEAKAGE FOLLOWING
LAPAROSCOPIC SLEEVE GASTRECTOMY- CASE SERIES
S. Fishman1,*, S. Mati1, Z. Halpern1, E. Santo1
1
Gastroenterology, Sourasky Medical Center Tel Aviv, Tel Aviv, Israel
Contact E-mail Address: sigalf@tlvmc.gov.il
INTRODUCTION: Laparoscopic sleeve gastrectomy is gaining popularity as a
treatment for obesity. This procedure is prone to some complications, including
staple line leak, sleeve stricture and bleeding. Several therapeutic approaches
have been suggested for leaks but limited data is available regarding the safety
and efficacy of each technique.
AIMS & METHODS: Describe a single tertiary center experience using bariatric
designed, self-expandable metallic stents (BSEMS) for the treatment of postoperative leaks.
We reviewed the medical records and imaging studies of consecutive patients
diagnosed with staple line leakage between June 2012 and December 2013 and
treated with BSEMS.
Either the Hanaro stent (MI-Tech, Seoul, Korea) with a length of 18-24cm or the
Niti-S stent (Teawoong, Seoul, Korea) with a length of 18 or 23 cm were used.
RESULTS: Twenty six patients were referred to our clinic and treated with
BSEMS. The average treatment duration was 28 days. Success, defined as avoiding further surgical intervention, removal of external drain tubes, weaning off
TPN and resuming oral diet was achieved in 65%. A higher rate of 81% was
reached when excluding 5 patients in which the stent was removed less than 2
weeks after insertion.
In 8 patients endoscopic fistule closure was achieved and in 7 patients reposition
was needed due to migration.
Severe adverse event were noted in 5 patients that mandated early removal: 4
patients with severe intolerance and 1 patient with severe upper gastrointestinal
bleeding. Minor AE were universal, including discomfort and ulceration.
CONCLUSION: BSEMS is a safe and effective treatment for staple line leak
following LSG.
Disclosure of Interest: None declared
P1383 EFFICACY OF A WALLFLEX ENTERAL STENT
MALIGNANT GASTRIC OUTLET OBSTRUCTION DURING
CHEMOTHERAPY

FOR

T. Yoshii1,*, M. Asayama1, H. Hara1, K. Yamaguchi1


1
Gastroenterology, Saitama Cancer Center, Kitaadachi-gun, Japan
Contact E-mail Address: takako_y@cancer-c.pref.saitama.jp
INTRODUCTION: Gastric outlet obstruction (GOO) occurs due to different
gastroenteral malignancy. It causes nausea, deficient oral intake, resulting in a
low quality of life. The newly available enteral WallFlex stent (Boston Scentific)
has been reported to be useful to improvement of these troublesome symptoms.
It might benefit survival, improving not only nutrition but also the compliance to

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United European Gastroenterology Journal 2(1S)


the chemotherapy of the patients. To date, this matter has not been fully
evaluated.
AIMS & METHODS: The aim of this study is to investigate the efficacy of
enteral WallFlex stent for malignant gastric outlet obstruction (GOO) during
chemotherapy of unresectable gastroenteral malignancy. Twenty-one consecutive
patients with symptomatic malignant GOO who were treated with a WallFlex
stent between September 2011 and January 2014 at our hospital were analyzed
retrospectively. All the patients gave the written informed consent. We evaluated
the following clinical outcomes: the improvement of oral intake, the timing of
stent insertion during the cancer treatment progress, and the survival after stent
insertion. A four-point GOO scoring system (0-3) was used to estimate oral
intake. We also analyzed the complications. The statistical analysis was performed by Kaplan-Meier method in April 2014.
RESULTS: Among 21 patients, median age was 69 years (43-77), and 15 were male.
Sixteen patients had pyloric stenosis, 3 had stenosis of bulbs, and 2 had stenosis of
more anal side of duodenum. Seventeen patients had stenosis due to primary tumor,
and others due to extraductal compression by the pancreatic or biliary cancer.
Sixteen patients had gastric cancer, 1 had duodenal cancer, and 4 had pancreatic
or biliary cancer. Almost all patients had the GOO score of 0 before insertion. Of
them, improved score of more than 2 points was achieved in 16 patients (76%). The
improvement was achieved within 2 days after treatment on average. Seven patients
were released from the total parenteral nutrition. Median survival time after the
stent insertion was 96 days (95%CI, 96-155). Seven patients underwent the treatment as the initial step of clinical course, and 14 as the sequential course among the
chemotherapy. Fifteen patients could continue the chemotherapy after the insertion
(71%). The survival time was not significantly different with or without the therapy
before the insertion [initial insertion vs after chemotherapy: 82 days (95%CI, 46117) vs. 96 days (95%CI, 22-169), p 0.85]. However, the survival time of the
patients who could continue the chemotherapy after stent insertion was significantly
longer compared with the other group [150 days (95%CI, 59-240) vs 40 days (1267),p 0.0022]. Although there was no statistical significance, the patients who
could continue the chemotherapy showed the trend wherein GOO score after the
treatment was improved. Five patients experienced tumor in-growth and were successfully treated by stent in stent. In these cases, median time to tumor in-growth was
116 days (95%CI, 96-135). No life-threatening complication or treatment-related
death occurred within 30 days.
CONCLUSION: Placement of enteral WallFlex stent for malignant GOO could
benefit survival other than improvement of oral intake, supporting the compliance of chemotherapy. Further research should be continued.
Disclosure of Interest: None declared
P1384 COMPLICATIONS OF ENDOSCOPIC DILATATION
ESOPHAGEAL STENOSIS AFTER ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR SUPERFICIAL ESOPHAGEAL CANCER

FOR

Y. Kishida1,*, N. Kakushima1, M. Tanaka1, K. Takizawa1, N. Kawata1,


Y. Tanaka1, K. Igarashi1, S. Sugimoto1, M. Yoshida1, K. Shinjo1, K. Imai1,
K. Hotta1, H. Matsubayashi1, H. Ono1
1
Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
Contact E-mail Address: y.kishida@scchr.jp
INTRODUCTION: Esophageal stenosis is a major problem after performing
endoscopic submucosal dissection (ESD) for large superficial esophageal
cancer. Endoscopic dilatation (ED) is useful for benign strictures caused by
reflux esophagitis or anastomotic stenosis after esophagectomy. However, little
is known about the incidence of complications of ED for stenosis caused by
esophageal ESD.
AIMS & METHODS: Between September 2002 and December 2012, a total of
111 patients underwent ED for stenosis after esophageal ESD. Among these
patients, we retrospectively assessed the following factors; age, sex, use of antithrombotics, location of lesion, circumferential extent of mucosal defect after ESD,
diameter of the specimen resected by ESD, number of ED sessions, period from
ESD to starting ED, treatment duration of ED, and complications. Since ED is
considered as a high-risk procedure for bleeding in the Japanese guideline [1],
antithrombotics were generally discontinued a minimum days before ED.
RESULTS: The patient population included 90 men and 21 women. The median
age was 69 years old. Among them, 19 patients (17%) had daily usage of antithrombotics. The major location of the lesions was the middle or lower thoracic
esophagus (81/111, 73%). The mucosal defect was larger than 3/4 circumferential
extent in 75 patients (68%), and the median diameter of the resected specimen
was 50 mm (range 23-106mm). A total of 1250 ED sessions were performed, and
the median number of ED sessions per patient was 17 (range 1-70). The first ED
session was performed a median of 13 days (range 1-154 days) after ESD, and the
median treatment duration was 86 days (range 1-1079 days).
The incidence of bleeding was 0.9% (1/111) per patient, 0.1% (1/1250) per session. The only case of bleeding occurred in the middle thoracic esophagus with a
mucosal defect less than 1/2 of circumference. This patient did not take daily
antithrombotics. Bleeding occurred at the first time of ED session which was
performed 23 days after ESD. The bleeding was stopped endoscopically without
the need of blood transfusion. The incidence of perforation was 4.5% (5/111) per
patient, 0.4% (5/1250) per procedure.
The location of the lesion among these five patients was upper/middle/lower/
abdominal esophagus 1/2/1/1, respectively. The mucosal defect was 1/2-3/4 / 3/4semicircular / whole circumference 1/2/2, respectively. Perforation occurred at a
median of second time of ED session (range 2-9), and a median of 18 days (range
8-29) after ESD The median treatment duration of ED among these five patients
was 190 days which was longer compared to that of the whole population. Four
patients recovered by conservative treatment but there was one fatal case that
developed pyogenic spondylitis after 26 times of ED.

CONCLUSION: The incidence of bleeding caused by ED for esophageal stenosis


after ESD was small. Relevant risk of perforation should be considered for
patients requiring multiple sessions of ED.
REFERENCES
[1] Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc 2014; 26: 1-14.
Disclosure of Interest: None declared
P1385 INCIDENCE OF BLEEDING AND PERFORATION CAUSED BY
ENDOSCOPIC DILATATION FOR GASTRIC STENOSIS AFTER
ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC
CANCER
Y. Kishida1,*, N. Kakushima1, M. Tanaka1, K. Takizawa1, N. Kawata1,
Y. Tanaka1, K. Igarashi1, S. Sugimoto1, M. Yoshida1, K. Shinjo1, K. Imai1,
K. Hotta1, H. Matsubayashi1, H. Ono1
1
Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
Contact E-mail Address: y.kishida@scchr.jp
INTRODUCTION: Gastric stenosis is a major problem after performing endoscopic submucosal dissection (ESD) for large superficial gastric cancer.
Endoscopic dilatation (ED) is a safe and useful treatment for benign strictures
caused by postoperative anastomotic stenosis or peptic ulcer disease. However,
little is known about the incidence of bleeding and perforation caused by ED for
gastric stenosis after ESD.
AIMS & METHODS: Between September 2002 and December 2012, a total of
64 patients underwent ED using a wire-guided balloon dilator for stenosis after
gastric ESD. Among these patients, we retrospectively assessed the following
factors; age, sex, use of antithrombotics, location of the lesion, circumferential
extent of mucosal defect after ESD, diameter of the specimen resected by ESD,
number of ED sessions, period from ESD to starting ED, treatment duration of
ED, and complications of bleeding and perforation. Since ED is considered as a
high-risk procedure for bleeding in the Japanese guideline [1], antithrombotics
were generally discontinued a minimum days before ED.
RESULTS: The patient population included 48 men and 18 women. The median
age was 75 years old. Among them, 19 patients (30%) had daily usage of antithrombotics. Lesions were located in the upper part of the stomach in 38% (24/64),
lower part in 58% (37/64). The mucosal defect was larger than 3/4 circumferential extent in 46 patients (72%), the median diameter of the resected specimen was
66 mm (range 27-147 mm). A total of 341 ED sessions were performed, and the
median number of ED sessions per patient was four (range 1-25). The first ED
session was performed a median of 28 days (range 9-90) after ESD, and the
median treatment duration was 30 days [1-282].
The incidence of bleeding was 3% (2/64) per patient, 0.6% (2/341) per session.
One patient who continued taking antithrombotics because of concomitant disease required blood transfusion. The incidence of perforation was 8% (5/64) per
patient, 1.5% (5/341) per procedure. All five cases of perforation occured in the
lower stomach, and the mucosal defects were larger than 3/4 circumference.
Among them, two patients underwent surgery.
There was no significant increase in the incidence of complication among patients
taking antithrombotics when they were discontinued before ED.
CONCLUSION: The incidence of bleeding and perforation caused by ED for
gastric stenosis after ESD was small.
REFERENCES
[1] Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc 2014; 26: 1-14.
Disclosure of Interest: None declared
P1386 COMPARISON OF ENDOSCOPIC COLORECTAL STENT AS A
BRIDGE TO SURGERY AND CURATIVE SURGERY ONLY IN THE
MANAGEMENT OF ACUTE MALIGNANT OBSTRUCTION
Y.Y. Choi1,*, D.H. Kang1, H.W. Kim1, C.W. Choi1, S.J. Kim1, S.B. Park1,
B.J. Song1, Y.S. Shin1, D.K. Kang1, H.K. Lim1, J.J. Goo1
1
Division of Gastroenterology, Department of Internal Medicine, School of
Medicine Pusan National University, Pusan National University Yangsan Hospital,
Yangsan-si, Korea, Republic Of
Contact E-mail Address: shadam@naver.com
INTRODUCTION: Recently, the use of endoscopic colorectal stenting for palliation or as a bridge to surgery in acute malignant colorectal obstruction has
increased. However, there are many questions whether endoscopic colorectal
stenting as a brige to surgery is really useful for obstructive colorectal cancer,
according to the results of recently pulblished studies.
AIMS & METHODS: The aim of this study was to compare the outcomes
between operation after colorectal stenting and surgery only for curative purpose
in patients with colorectal obstruction.
100 patients who were treated for obstructive colorectal cancer between
May 2009 and May 2013 were enrolled. We reviewed the medical records retrospectively. 37 patients underwent endoscopic colorectal stent as a bridge to curative surgery (stent group). 40 patients underwent a curative operation without
colorectal stent (surgery only group). Primary outcomes included the stoma rate
and the length of hospital stay after surgery, postoperative complication including in-hospital mortality and the emergency and open surgery rate. Secondary
outcomes included the technical success rate of stent insertion and symptom
improvement rate after stenting, complication during procedure.
RESULTS: The stoma rate was 27.0% (10/37) in stent group versus 45.0% (18/
40) in surgery only group (p 0.10). The median postoperative hospital stay was
12.35.8 versus 12.27.4 days (p 0.92). The postoperative complication rate
was 8.1% (3/37) versus 10.0% (4/40) (p 1.00). In-hospital death happened two
case (5.4%, 2/37) in stent group and one case in surgery only group (p 0.60). 7

A510
patients (18.9%) in stent group and 11 patient (27.5%) in surgery group underwent emergency surgery (p 0.37). Open surgery rate was 32.4% (12/37) versus
40.0% (16/40), respectively (p 0.49). Subgroup analysis showed that emergency
surgery rate of stent group who had successful stent insertion was significantly
lower compared to surgery only group (6.7%, p50.01). The overall success rate
of colorectal stent insertion for malignant colorectal obstruction was 88.7% (77/
86). The success rate of stent as a bridge to curative surgery was 81.1% (30/37).
Failure of the guidewire passage through lesions occurred in 5 patients (13.5%).
Perforation during procedure occurred in 2 patients (5.4%). All patients who
were performed stent insertion successfully, achieved symptom improvement.
CONCLUSION: The role of endoscopic colorectal stenting for bridging procedure before surgery is limited in the management of acute malignant obstruction.
When the patients have high risks of complications of emergency surgery, stent
can be considered as alternative approach to emergency surgery.
Disclosure of Interest: None declared
P1387 OUTCOMES OF STENT-IN-STENT TECHNIQUE FOR PRIMARYFAILURE AND RECURRENCE OF SYMPTOMS IN MALIGNANT
COLORECTAL OBSTRUCTION CASES WITH SELF-EXPANDABLE
METALLIC STENTS
Y. Ota1,*, S. Yoshida2, H. Isayama1, T. Sasaki1, A. Narita1, T. Shimpoh1,
T. Hamada1, A. Yamada1, N. Takahara1, H. Kogure1, N. Yamamoto1,
Y. Nakai1, Y. Hirata1, K. Koike1
1
Gastroenterology, 2Endoscopy and Endoscopic Surgery, The University of Tokyo,
Tokyo, Japan
Contact E-mail Address: u_mix0042008@hotmail.co.jp
INTRODUCTION: Self-expandable metallic stents (SEMS) placement was
widely accepted procedure for malignant colorectal obstruction (MCRO), however, we sometimes encounter the primary failure or recurrence of colorectal
obstruction (RCRO) after SEMS placement. In these cases, additional SEMS
insertion through the previous SEMS, so-called stent-in-stent (SIS) technique,
was effective, but was not well reported.
AIMS & METHODS: To estimate the safety and efficacy of SIS technique for
MCRO, we retrospectively reviewed the clinical records. Between Mar. 2006 to
Apr. 2014, 104 patients underwent endoscopic SEMS placement for MCRO.
Primary SEMS failure was defined as un-resolved symptom of MCRO and
RCRO as the recurrence of colorectal obstructive symptoms after SEMS placement. Technical success was defined as deployment of the stent across the entire
length of the stricture on the first attempt. Clinical success was defined as a
resolution of symptoms and radiological relief of the obstruction within 24 h,
confirmed by radiographic observation. To pass the stricture in the previous
SEMS, a hydrophilic biliary guidewire was promoted in a J-turn shaped by
way of prevention for passing through the SEMSs mesh. We excluded the
obstruction at the different locations.
RESULTS: Primary stent failure and RCRO occurred in 2 and 21 patients,
retrospectively. The causes of primary stent failure were insufficient expansion
(0) and remaining stricture with too-short SEMS because of underestimation of
stricture length (2). Those of RCRO were kinking at the stent edge (8), tumor in/
overgrowth (10) and stool impaction (3). Four patients underwent surgical intervention (bypass operation 1, colostomy 3), stent-in-stent placements were
performed for 15 patients. We used covered (5) and uncovered (10) stents. The
obstructions were located at rectum (5), sigmoid colon (4), splenic flexure (3),
descending colon (1), and transverse colon (1) and cecum (1). Six patients had
colorectal cancer. The remaining 9 patients had extra-colonic obstruction by
following malignancies; pancreatic cancer (4), stomach cancer (2), ovarian
cancer (2) and gallbladder cancer (1). Technical success was 100%, and clinical
success was 86.7% (13/15). The median duration of secondary stent patency and
survival was 161 (1-234) days and 122 (24-487) days, respectively. There was no
severe adverse event. Long-term clinical failure occurred in 9 of 15 patients,
attributed to re-occlusion of SEMS. Of these patients, tertiary SEMS placements
were attempted for 4 patients, technical success was 100%, and clinical success
was 50% (2/4). One patient underwent colostomy because of immediate perforation at 1 day after last stent insertion. Of the remaining 6 patients without tertiary
stent insertion, four patients received palliative surgery and 2 patients were managed with total parenteral nutrition through a central venous catheter.
CONCLUSION: Stent-in-stent placement for primary failure and RCRO
showed high technical and clinical success rate without any serious complications
for both colonic and extra-colonic obstruction. We should carefully assess effectiveness of tertiary SEMS placement.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
SURGERY III POSTER EXHIBITION HALL XL_____________________
P1388 THE USEFULNESS OF A CLOSURE OF ULCER FOR THE
PREVENTION OF DELAYED PERFORATION AND BLEEDING
AFTER DUODENAL ESD
A. Takahashi1,*, T. Oyama1
Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan
Contact E-mail Address: aurevoireurope@yahoo.co.jp
1

INTRODUCTION: Duodenal ESD is difficult, because of narrow cavity, thin


wall and poor maneuverability. And complication rate such as delayed bleeding
and perforation is higher than that of gastric ESD. We tried the closure of ESD
ulcer by clip for the prevention of delayed perforation and bleeding.
AIMS & METHODS: The aim of this study is to investigate the usefulness of a
closure of ESD ulcer by clip for the prevention of delayed perforation and
bleeding after duodenal ESD.

United European Gastroenterology Journal 2(1S)


68 patients who had duodenal tubular adenoma or adenocarcinoma treated by
ESD from May 2001 to December 2013 were enrolled into this retrospective
study. The patients were divided into 2 groups, one was followed up without
closure (non-closure group), the other was closure group. EZ clip made by
Olympus (HX-610-090L) was used for the closure. Second look endoscopy was
performed on 2 to 5 days after ESD to check delayed bleeding and perforation.
Characteristics of the lesions were as follows. Bulbs / 2nd portion / 3rd portion
was 1/3/0 in non-closure group and 0/57/7 in closure group. The median diameter
of resected specimen was 25 (23 - 30) mm and 17 (10 - 44) mm, respectively (P:
0.0239). The median diameter of lesion was 17 (13 - 22) mm and 9 (2 - 34) mm,
respectively (P: 0.018). The oral intake of anticoagulant drug and under artificial
dialysis were 0, 5 and 0, 2, respectively.
RESULTS: 1. The delayed bleeding rate was 50% (2/4) in non-closure group and
5% (3/64) in closure group. There was significant difference (P :0.0248). Three
patients who had the delayed bleeding in closure group had risk of bleeding such
as oral intake of anticoagulant drug, hemodialysis and diabetes mellitus.
2. The delayed perforation rate was 25% (1/4) in non-closure group and 0% (0/
64) in closure group (P: 0.06).
3. The successful rate of the closure was 98% (63/64). The mean number of clips
was 8.7 (range 4 to 17). The ESD ulcer of only one patient could not be closed by
clips. Therefore, ENPD and ENBD was performed to prevent complications.
And, the patient was fine without any complications such as delayed perforation
and bleeding.
CONCLUSION: The incidence of delayed bleeding or perforation after duodenal ESD is high. However, the closure of ESD ulcer by clip is useful for the
prevention of delayed perforation and bleeding after duodenal ESD.
Disclosure of Interest: None declared
P1389 TRANSORAL
DIVERTICULO-ESOPHAGOSTOMY
TREATMENT OF ZENKER DIVERTICULUM

AS

A. Melis1,*, M. Ceolin2, U. Fumagalli2, L. Barbieri2, U. Elmore1, R. Rosati1


1
Chirurgia Gastroenterologica, Ospedale San Raffaele, Milano, 2Chirurgia
Generale e Mini-Invasiva, Humanitas Research Hospital, Rozzano (MI), Italy
Contact E-mail Address: melis.alessandra@hsr.it
INTRODUCTION: Transoral diverticulo-esophagostomy (TDE) is a modern
treatment for Zenker diverticula (ZD) with low morbidity rate and high rate of
symptom improvement. Residual or recurrent symptoms may impair patients
QoL and may request retreatment. Aim of this study is to analyze mode of
presentation, diagnosis and treatment details of patients (pts) submitted to
TDE who needed retreatment.
AIMS & METHODS: From March 1998 to September 2013, 96 out of 101
candidates, pts were submitted to TDE. TDE was performed with linear stapler
with modified anvil (Endo GIA 30, 3.5) in all patients and, since 2009 (44 cases),
with placement of two stay sutures on the septum to increase the length of
section. All patients underwent FU at 1 month with barium swallow, whenever
symptoms occurred by endoscopy and manometry, and at the time of this
analysis.
RESULTS: Oropharyngeal dysphagia occurred in 83/96 pts; regurgitation, inhalation, throat lump were also recorded. Complications were: 4 dental lesions, 2
perforation treated conservatively, 1 bleeding. Two bleeding from the stapled line
required endoscopic hemostasis. Twenty pts complained persistent symptoms
due to residual spur or recurrent diverticulum: in 3/20 stay sutures were used;
15/20 pts (with a residual spur 5 2 cm) were treated with flexible endoscopy with
further treatment required in 2 cases; in 5/20 pts with a spur longer than 2 cm
second TDE (4 pts) or open diverticulectomy (1 pt) were performed. Mean
interval between TDE and retreatment was 7 months. After retreatment 4/20
patients complained mild symptoms. At a median FU of 42 months symptoms
disappeared globally in 94% of patients.
CONCLUSION: Transoral treatment of ZD shows good results in terms of
symptom reduction and patients satisfaction. In few cases results were optimized
by complementary treatment. The use of stay sutures allows to obtain better
results.
Disclosure of Interest: None declared
P1390 TUMOR
STROMA
RATIO
(TSR)
IN
ESOPHAGEAL
ADENOCARCINOMA BIOPSIES IN THE PREDICTION OF
RESPONSE TO NEOADJUVANT THERAPY AND OVERALL
SURVIVAL
C. Hetterschijt1, S. Lagarde1, R. Blom1, M. Anderegg1,*, H.van Laarhoven2,
S. Meijer3, S. Gisbertz1, M.van Berge Henegouwen1
1
Surgery, 2Medical Oncology, 3Pathology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: s.m.lagarde@amc.uva.nl
INTRODUCTION: The incidence of esophageal carcinoma has been rising over
the past decades. Surgical resection remains an important part of curative treatment. Several studies have demonstrated a survival benefit for patients receiving
neoadjuvant therapy compared to patients that underwent surgical resection
alone. Identification of non responders at an early stage could prevent patients
from the toxicity of neoadjuvant therapy and avoid a possible fatal delay in the
performance of potentially curative surgery. Tumor stroma ratio (TSR) in primary tumor biopsies taken before neoadjuvant therapy and surgery proved to be
a prognostic factor for patients survival. The aim of this study was to evaluate
the prognostic value of the TSR in biopsies of esophageal adenocarcinomas
taken before neoadjuvant therapy and surgery, in correlation to the response
to neoadjuvant therapy prior to esophagectomy. In addition the correlation of
the tumor stroma ratio with overall survival was evaluated.

A511

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: In a retrospective study, we selected 141 patients with
esophageal adenocarcinoma who underwent neoadjuvant chemoradiotherapy
prior to esophageal resection between 2004 and 2011. The haematoxylin-eosin
(H&E) stained sections of the tumor biopsies were reanalysed. TSR was scored as
TSR low (5 50% carcinoma) or TSR high (4 50% carcinoma). Response to
neoadjuvant therapy was determined in the resected specimen based on the
tumor regression grade (TRG). The chi-square and Fishers exact tests were
used to evaluate the correlation of TSR with TRG. Survival was calculated
from the date of surgery using the KaplanMeier method.
RESULTS: 141 patients were analysed. 55 (39%) patients were defined as
responders (TRG 1 and 2) and 86 (61%) as non-responders (TRG 3 and 4).
Estimation of the TSR was performed successfully in all the tumors (100%).
104 (74%) patients were classified as TSR high and 37 (26%) patients as TSR
low. The correlation of TSR with TRG was not significant (p 0.537). The
correlation of TSR with overall survival was not significant (p 0.793).
CONCLUSION: Our results suggest that the TSR in biopsies of esophageal
adenocarcinomas does not have a prognostic value in correlation to the response
to neoadjuvant therapy prior to esophagectomy. Moreover, according to our
results TSR is not a prognostic characteristic for overall survival.
Disclosure of Interest: None declared
P1391 OCCUPATIONAL STATUS AFTER ESOPHAGECTOMY FOR
CANCER
E. Pinto1,*, M. Scarpa1, F. Cavallin1, R. Alfieri1, M. Cagol1, L.M. Saadeh1,
S. Mantoan1, C. Castoro1
1
Oncological Surgery, Veneto Institute of Oncology, Padova, Italy
Contact E-mail Address: eleonora.pinto@ioveneto.it
INTRODUCTION: In the last decade, work participation of cancer survivors
has received growing attention worldwide and cancer survivors are at risk for job
loss, unemployment and social and work disability. Cancer survivors who are
unable to resume a former job face the risk of a financial loss.
AIMS & METHODS: The purpose of the current study was to evaluate the
impact of esophagectomy for cancer on patients occupation. We also evaluated
the association between the job condition and perceived quality of life at one year
after esophagectomy.
We retrospectively evaluated all consecutive patients referring to our department
between 2009 and 2012 for esophageal cancer. Inclusion criteria was esophagectomy for cancer. Patients not suitable for work (due to psychiatric disease or
tetraplegia) and patients with missing information about their job were excluded.
Working condition at diagnosis, at one month before surgery and at one year
after surgery was collected. Patients and tumor characteristics along with
therapeutic strategies were also collected. Quality of life was evaluated at
diagnosis and at one year after surgery using Financial Difficulties (FI), Social
Functioning (SF), Role Functioning (RF) and Global health status (QL2) scores
of EORTC QLQ-C30 questionnaire.
RESULTS: Fifty-one active workers and 29 retirees underwent surgical resection
for esophageal cancer.
At diagnosis, retirees had slightly lower FI score than active workers (9.015.1
vs. 18.927.8, p 0.07), whereas self-employed subjects had slightly higher RF
(93.612.8 vs. 78.531.3, p 0.05) and QL2 (80.117.2 vs. 65.623.6, p 0.06)
than employees.
At one year after surgery, 64% active workers were still in labor force whereas
36% quit their job; SF score (92.913.1 vs. 86.717.3, p 0.34), FI score
(14.326.2 vs. 22.726.7, p 0.47), RF score (71.428.4 vs. 86.722.6,
p 0.15) and QL2 score (67.918.3 vs. 73.022.1, p 0.58) were similar between
the two groups.
CONCLUSION: Retirees reported less financial concerns than active workers at
cancer diagnosis. A considerable number of patients quit their job after esophagectomy for cancer. Adequate welfare strategy should be implemented for esophageal cancer survivors.
REFERENCES
[1] Vigen C, Bernstein L and Wu AH. Occupational physical activity and risk of
adenocarcinomas of the esophagus and stomach. Int J Cancer 2006; 118: 1004
1009.
[2] Jacobs M, et al. Meta-analysis shows clinically relevant and long-lasting
deterioration in health-related quality of life after esophageal cancer surgery.
Qual Life Res 2014; 23: 1155-1176.
[3] Parent M-E, El-Zein M, Rousseau M-C, et al. Night work and the risk of
cancer among men. Am J Epidemiol 2012. DOI: 10.1093/aje/kws318.
[4] De Boer A, Taskila T, Ojajarvi A, et al. Cancer survivors and unemployment
A meta-analyses and meta-regression. JAMA 2009; 7: 753762.
[5] Al-Dakkak I and Khadra M. Socio-economic status and upper aerodigestive
tract cancer. Evid Based Dent 2011; 12: 87-88.
Disclosure of Interest: None declared
P1392 OMENTECTOMY IN GASTRIC CANCER
PROSPECTIVE COHORT STUDY IN 100 PATIENTS

SURGERY:

E.J. Jongerius1, D. Boerma2, K.A. Seldenrijk3, S.L. Meijer4, J.J. Scheepers5,


F. Smedts6, S.M. Lagarde1, O. Balague Pons7, M. I.van Berge Henegouwen1,
J.W. van Sandick8, S.S. Gisbertz1,*
1
surgery, Academic Medical Center, Amsterdam, 2surgery, 3pathology, St.
Antonius Hospital, Nieuwegein, 4pathology, Academic Medical Center,
Amsterdam, 5surgery, 6pathology, Reinier de Graaf Gasthuis, Delft, 7pathology,
8
surgery, Netherlands Cancer Institute, Amsterdam, Netherlands
Contact E-mail Address: s.s.gisbertz@amc.nl
INTRODUCTION: There is no evidence for a complete omentectomy as part of
a radical gastrectomy with a modified D2 lymphadenectomy in potentially

curative gastric cancer. In this study we prospectively evaluated the presence of


metastases in the greater omentum in potentially curative radical gastrectomy for
gastric cancer patients.
AIMS & METHODS: In this multicenter prospective cohort trial 100 consecutive patients with gastric cancer underwent a (sub) total gastrectomy with complete en-bloc omentectomy and a modified D2 lymphadenectomy. After resection
of the specimen, the omentum was separated from the stomach distal to the
gastro-epiploic vessels and separately sent for pathological examination. The
primary endpoint was the presence of metastases in the greater omentum.
RESULTS: In 5 of 100 patients (5.0%) metastases were detected in the greater
omentum (2 patients with omental lymph node metastases, 3 patients with omental tumor deposits). These patients had pT4N1M1, pT4N1M0, ypT4N1M0,
ypT3N0M1, ypT3N3M0 disease. In all 5 patients with omental metastases, the
resection was irradical (R1) at the proximal (n 3) or distal (n 2) resection
margin. Two patients were operated for linitis plastica and 3 had a proximal
gastric tumor. In 3 patients the tumor expanded in the esophagus, in 2 in the
duodenum.
CONCLUSION: Metastases in the greater omentum are infrequent. It seems that
there are factors demonstrable that coincide with the presence of metastases in
the greater omentum. In all patients with omental metastases an irradical resection was performed. This study suggests that omentectomy could possibly be
omitted in some gastrectomy for gastric cancer patients. However, identification
of these patients, safety and true benefit of omentum preservation needs further
investigation in a randomized controlled trial.
Disclosure of Interest: None declared
P1394 PREDICTIVE FACTORS FOR CHOOSING MINIMALLY
INVASIVE SURGERY IN PATIENTS WITH ADVANCED GASTRIC
CANCER
C.A. Dutei1, I.A. Sburlan2,*, B. Berbescu3, B. Trandafir3, A. Cazan2,
G. Comanescu2, M. Ispas2, M. Barbu2, S. Tudor4, I. Lupescu5, M. Manuc2,
M.M. Diculescu6, C. Vasilescu4
1
Gastroenterology, Fundeni Clinical Institute, 2Gastroenterology, Clinical Institute
Fundeni, 3Gastroenterology, University of Medicine and Pharmacy "Carol Davila",
4
General Surgery, 5Radiology, 6Gastroentrology, Clinical Institute Fundeni,
Bucharest, Romania
Contact E-mail Address: dutei.catalin@yahoo.com
INTRODUCTION: The most important part of advanced gastric cancer surgical
treatment consists of either open surgery or minimally invasive surgical procedures, both techniques being under current evaluation for the clinical impact and
prognosis of each patient. According to various parameters which can be
revealed by pre-procedure imaging and endoscopy, the minimally invasive surgery is generally preferred. However, there are certain cases in the evolution of
advanced gastric cancer when the results indicate the necessity to switch to open
surgery due to safety and better outcome reasons.
AIMS & METHODS: We retrospectively evaluated 187 patients known with
advanced gastric cancer, whom were operated on between 2008 and 2014 in
the Surgery Department of Clinical Institute Fundeni. The patients were divided
into 2 groups according to the type of surgery performed: either open or minimally invasive surgery. We analysed the following parameters obtained by upper
endoscopy: location of cancer, aspect, extension, involvement of pylorus and
cardia, presence of haemorrhage; and tomographic imaging: metastasis, peritoneal carcinomatosis, lymph node involvement, surpassing the gastric wall, invasion of cardia, pylorus, duodenum and great vessels, presence of ascites. The
obtained data were processed in Prism5 programme for statistical analysis
using chi-square test.
RESULTS: Following statistical analysis we retain that 66% were male patients;
73% were operated by open surgery. A statistical significant p value (50.05) was
obtained for Bormann classification type 2 relevant for a clear indication of open
surgery (p 0.0091), while type 3 could be managed by minimally invasive techniques (p 0.0003). Non-involvement of cardia and pylorus was an indicator for
the minimally invasive surgery with a p-value of 0.0037 and 0.00259, respectively
(endoscopic parameters). Regarding the results from computer-tomography, minimally invasive surgery was used in the absence of the following parameters: great
intra-abdominal vessel involvement (p 0.0177), cardia invasion (p 0.0067), surpassing of gastric wall (p 0.019) and the presence of metastasis (p 0.05).
CONCLUSION: The minimally invasive surgery of gastric cancer has gained
increased interest among surgeons. It should be considered in the majority of
cases, except when there is a sum of indicators such as local invasion (cardia,
pylorus, great vessels, gastric wall), metastatic disease, lymph nodes involvement
and Borrmann 2 lesions in which open surgery is rather recommended. Type 1
and 4 Borrmann lesions and active haemorrhage did not show a precise
correlation.
Disclosure of Interest: None declared
P1395 CARDIOPULMONARY
COMPLICATIONS
AFTER
ESOPHAGECTOMY FOR CANCER: PREOPERATIVE PREDICTION
OF RISK FACTORS
L.M. Saadeh1, M. Scarpa1,*, A. Banzato2, A. Bianchi2, M.R. Marchi3,
R. Alfieri1, M. Cagol1, G. Noaro1, E. Pinto1, F. Cavallin1, C. Castoro1
1
Surgical Oncology Unit, 2Cardio-Oncology Unit, Veneto Oncological Institute
(IOV-IRCSS), 3Respiratory Pathophysiology Division, University-City Hospital
of Padua, Padova, Italy
Contact E-mail Address: luca.saadeh@gmail.com
INTRODUCTION: The esophagectomy for cancer is still burdened by many
complications. Simple, easy-to-use clinical predictors of cardiopulmonary complications may help in preventing and managing these events.

A512
AIMS & METHODS: This study aimed at identify predictive factors of cardiac
and pulmonary post-operative complications before patients undergo surgery in
order to improve the outcome and shorten the hospital stay. Every patients
underwent a cardiologic evaluation with echocardiography, ECG with further
stress-test when required and pulmonary evaluation with function tests. The
cardiologic parameters considered were the QT corrected interval, the E/A
ratio, the diastolic volume of the left ventricle, the presence of mitral and/or
tricuspid valves insufficiency, the ejection fraction and the evidence of myocardial asynergy at the cardiac US. The pulmonary function tests considered the
observed/theoretical ratio in vital capacity (VC), forced expiratory volume in one
second (FEV1), total lung capacity (TLC), transfer coefficient for carbon monoxide (KCO), FEV1/VC, RV/TLC. Logistic regression analysis was used.
RESULTS: In our center, 212 patients underwent esophagectomy for cancer
from 2008 to 2013. Cardiologic complications were reported in 14 patients
(6.6%): 7 arrhythmias with no hemodynamic instability (3.3%), 1 cardiac tamponade (0.5%), 4 myocardial infarctions (1.9%). Pulmonary complications were
observed in 20 patients (9.4%): 19 pleural effusion (9%) and one acute respiratory distress syndrome (0.5%). Overall cardiac complications were predicted only
by the presence of myocardial asynergy at cardiac US [OR 6.41 (95% CI 1.8422.36), p 0.003] that also predicted cardiac arrhythmias [OR 6.08 (95%
CI 1.07-34.32), p 0.041]. Pulmonary complications were predicted by the presence of myocardial asynergy at the cardiac US (p 0.018), male sex (p 0.046),
reduced observed/theoretical ratio in: TLC (p 0.019), KCO (p 0.039) RV/
TLC (p 0.007), VC (p 0.008). At the multivariate analysis the reduced
observed/theoretical ratio in KCO resulted to be the only independent predictor
of pulmonary complication [OR 0.94 (95% CI 0.91-0.98), p 0.009].
CONCLUSION: Cardiac and pulmonary complications after esophagectomy
can be predicted by simple, repeatable and low cost tests. Therefore, studying
every patient with cardiac US and pulmonary function tests should become part
of the path to esophagectomy in order to adopt preventive medical therapy
before and/or after surgery, to improve the outcome and to reduce the hospital
stay with a cost-effectiveness benefit.
Disclosure of Interest: None declared
P1396 DINAMICS OF ENDOSCOPIC AND HISTOPATHOLOGICAL
CHANGES OF THE MUCOUS AND SMOOTH ESOPHAGEAL
MUSCLE AFTER SURGICAL TREATMENT ACHALASIA
P.D. Fomin1,*, A. Kurbanov1
1
Surgery, National medical university named after A. A. Bogomoletz, Kiev,
Ukraine
Contact E-mail Address: peter_fomin@mail.ru
INTRODUCTION: Achalasia is associated with functional esophageal obstruction. Food stasis can predispose for esophagitis. For surgical treatment of achalasia there is important to study and compare in the dynamics in the long term of
the endoscopic data with structural and morphological changes of the mucous
membrane and smooth muscle of the esophagus and the incidence of esophagitis.
AIMS & METHODS: To investigate the correlation between endoscopic data and
morphological changes of the mucous, incidence and severity of esophagitis in
achalasia patients after surgical treatment with Heller-Dor or Heller-Toupet procedures. Before surgery on endoscopy biopsy specimens of mucous were sampled
just above and at the zone of gastro-esophageal junction and the pieces of smooth
esophageal muscle were taken above esophageal incision and at the zone of gastroesophageal junction after myotomy. We performed routine histological sections
and electron-microscopic studies of muscle biopsies. The macroscopic esophagitis
graded according the Los Angeles classification (grades AD) and histology was
graded into grade 1-3. In the long term after surgery patients were seen in 1, 2, 4, 7,
10 and 17 years with upper GI endoscopy and inspection of the presence macroscopic esophagitis, three to four biopsy specimens were sampled just above and at
the zone of gastro-esophageal junction for investigation.
RESULTS: Before surgical treatment 51 patients with achalasia had according
radiological examination stage I - 3, stage II -5, stage III 32 and stage IV 11
pts. Endoscopic sings of esophagitis A 22 (43, 2%), B 15 (29, 4%), C 9 (17,
6%), D 5 (9, 8%) and histology grade I 27 (52, 9%), II 18 (35, 3%) and III 6 (11, 8%). The association between endoscopic food stasis and histological
inflammation was significant. The ultrastructural alterations in the smooth
muscle of all patients included muscle filament disarray, mottling of the fibre
density in myocytes, thick and long cytoplasmic dense bodies, long dense plaques, and relatively few nexus junctions. In achalasia, the smooth muscle cells
exhibited nuclear and cytoplasmic inclusions. The changes are most commonly
seen between the narrowed and dilated segment of the esophagus but at the
narrowed area of gastro-esophageal junction there was a striking loss of small
nerve fibres and reduced numbers of granules in the remaining fibres. All patients
were followed for mean values of 9.4 years (range: 122). The average number of
endoscopies with biopsy sample sets per patient was 5 (range: 117). 19 (37, 3%)
patients had no histological signs of esophagitis throughout follow-up, 32 (62,
7%) had esophagitis grade I 29 (90, 6%) and grade II 3 (9, 4%). Specialized
intestinal metaplasia was found in 5 patients. The association between endoscopic food stasis and histological inflammation was significant. The association
between the severity of clinical signs evaluated by a modified symptom score as
the sum of the scores for dysphagia, regurgitation and chest pain with endoscopic
signs of esophagitis and histological inflammation was poor.
CONCLUSION: Results of our studies evidence that in the long term after
surgical treatment of esophageal achalasia with antiflux fundoplication is a considerable improvement of clinical symptoms, endoscopic sings and histological
evidence of esophagitis. The dynamics of improvement depends on the duration
and disease stage.
Disclosure of Interest: P. Fomin Financial support for research from: no, Lecture
fee(s) from: no, Consultancy for: no, Shareholder of: no, Directorship (s) for: no,
Other: no,: no, A. Kurbanov: None declared

United European Gastroenterology Journal 2(1S)


P1397 THE IMPACT OF LYMPH NODE METASTASIS NEAR THE
CELIAC TRUNK IN PATIENTS WITH CANCER OF THE DISTAL
ESOPHAGUS OR GASTRO-ESOPHAGEAL JUNCTION
S. Lagarde1, M. Anderegg1,*, S. Gisbertz1, S. Meijer2, M. Hulshof3, J. Bergman4,
H.van Laarhoven5, M.van Berge Henegouwen1
1
Surgery, 2Pathology, 3Radiation Oncology, 4Gastroenterology, 5Medical
Oncology, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: s.m.lagarde@amc.uva.nl
INTRODUCTION: The present TNM staging system (7th edition, 2010) does
not take into account the location of truncal nodes metastasis after neoadjuvant
therapy. Therefore the aim of the present study is to identify the incidence and
prognostic significance of celiac trunk metastasis in patients who underwent
neoadjuvant chemo (radiation) therapy followed by an esophagectomy.
AIMS & METHODS: Between March 1994 and September 2013 a total of 462
consecutive patients with cancer of the mid-to-distal esophagus or gastroesophageal junction (GEJ) who underwent potentially curative esophageal resection
after neoadjuvant chemotherapy (N 88, 19%) or chemoradiotherapy
(N 374 (81%) were included.
RESULTS: 71 (15.4%) patients had positive truncal nodes in the resection specimen. Metastases to these nodes occurred more frequent in male patients with
adenocarcinoma and in GEJ tumors. Pretreatment staging was significantly more
advanced. While the number of resected nodes was comparable, a worse
Mandard score, a higher yT and yN stage and a worse grade of differentiation
were significantly related to truncal node metastases. Patients with positive truncal nodes had a worse median disease free survival (11months vs 65 months). In
multivariate analysis, yN stage as well as positive truncal nodes were independently associated with a worse survival. Only 22 (31%) of 71 patients with
positive truncal nodes were identified preoperatively with EUS or CT. 37 patients
had suspicious truncal nodes on EUS or CT, but metastases in the pathology
specimen were absent.
CONCLUSION: In the present study, it is demonstrated that positive truncal
nodes are associated with advanced tumor stages and are an independent factor
for worse survival. It seems that celiac nodal involvement is a marker for
widespread microscopic disease that may later become evident, since patients
with positive truncal nodes in the resection specimen have a dismal prognosis.
Future studies need to investigate to what extent truncal node status should
influence surgical decision making.
Disclosure of Interest: None declared
P1398 RELATIONSHIP BETWEEN RIGHT GASTROEPIPLOIC ARTERY
LYMPH NODE DISSECTION AND PYLORUS-PRESERVING
GASTRECTOMY BASED ON THE SENTINEL LYMPH NODE BASIN
THEORY
T. Ono1,*, H. Takeuchi1, R. Nakamura1, T. Takahashi1, N. Wada1,
H. Kawakubo1, Y. Saikawa1, T. Omori1, Y. Kitagawa1
1
digestive surgery, Keio University, shinjuku ku, Japan
INTRODUCTION: Pylorus preservation decreases weight, prevents the dumping syndrome, and prevents bile reflux and gallstone formation.
Postoperative quality of life (QOL) is often the most important concern for
patients with early gastric cancer; therefore, pylorus-preserving surgery has an
important clinical significance.
In the present study, we identified the involvement of certain lymph nodes as
sentinel nodes (SNs) using the Sentinel Lymph Node Basin theory to ensure
appropriate lymph node dissection during pylorus-preserving gastrectomy
(PPG) in patients with middle-third early gastric cancer.
AIMS & METHODS: Totally, 283 patients with middle-third gastric cancer who
underwent PPG from 2002 to 2013 were included. The inclusion criteria were as
follows: no previous treatment, tumor size 5 4 cm, single tumor, cT1N0 disease.
Informed consent was obtained from all patients.
We evaluated the lymphatic flow in all patients to identify the involvement of
lymph nodes 4d and 6 as sentinel nodes (SNs). PPG was then performed on the
basis of this detection.
RESULTS: Lymph node 6 was identified as an SN in 27 of the 283 patients, with
a detection rate of 7.1%, 5.9%, 22%, and 7.1% in the lesser curvature, greater
curvature, anterior wall, and posterior wall, respectively, while the detection rate
for lymph nodes 6 and 4d as SNs was 16%, 84%, 72%, and 44%, respectively, in
these regions.
Our findings showed that lymph nodes 6 and 4d were less frequently involved as
SNs in patients with lesser curvature lesions, with lymph node 6 being directly
involved without the involvement of lymph node 4d.
On the other hand, the frequency of detection of lymph node 6 as an SN was high
in patients with greater curvature lesions; furthermore, it was always associated
with the involvement of lymph node 4d.
Anterior wall lesions exhibited the highest frequency of lymph node 6 involvement as an SN.
CONCLUSION: The probability of lymph node 6 involvement as an SN was
9.5% in patients with middle-third early gastric cancer. Therefore, lymph node 6
dissection should be mandatory during PPG in these patients.
Disclosure of Interest: None declared

A513

United European Gastroenterology Journal 2(1S)


P1399 THE USEFULNESS OF SEDATION USING A COMBINATION OF
PROPOFOL AND DEXMEDETOMIDINE HYDROCHLORIDE
UNDER THE CONTINUOUS AIRWAY TONE MONITORING WITH A
PROPRIETARY MICROPHONE IN THE ESOPHAGEAL ESD
T. Nonaka1,*, M. Matsuura1, K. Kanoshima1, Y. Inoh1, H. Iida1, M. Inamori2,
A. Nakajima1
1
Department of Gastroenterology and Hepatology, Yokohama City University
School of Medicine, 2Office of Postgraduate Medical Education, Yokohama City
University Hospital, Yokohama, Japan
INTRODUCTION: The esophageal endoscopic submucosal dissection (ESD) is
known to be technically more difficult and riskier about intraoperative complication than gastric ESD due to the narrow space and the thin wall of the esophagus.
Although proper sedation is essential for successful esophageal ESD, it is sometimes difficult to achieve stable sedation with midazolam or other benzodiazepines alone. Recently, introduction of new sedatives such as propofol and
dexmedetomidine hydrochloride on ESD are expected to be useful agents.
There are few reports investigating the effects of such sedatives on ESD performance and complications.
AIMS & METHODS: Objective: We started new sedation using a combination
of propofol and dexmetomidine under the continuous airway tone monitoring
with a proprietary microphone in the esophageal ESD since August 2013. The
study was conducted to investigate the safety and efficacy of our new sedation.
Subjects: The present study included consecutive 35 patients undergone esophageal ESD before and after introducing the new sedation on August 2013, in
which 20 patients were sedated either with midazolam or other benzodiazepines
alone (Conventional group) just before introducing the new sedation between
July 2012 and August 2013, and 15 patients were sedated with a combination of
propofol and dexmetomidine (New group) between August 2013 and April 2014.
Outcome Measurements: The clinical characteristics (age, sex, body mass index,
alcohol consumption and underlying disease) was collected. Minimum value of
systolic blood pressure (sBP), minimum value of blood oxygen saturation (SpO2),
and the degree of body movement leading to the interruption of maneuver during
ESD were compared between the groups. The clinical characteristics (age,
gender, body mass index, alcohol consumption and underlying disease) was collected. We consequently compared the following outcome of ESD between the
groups: procedural time, en block resection rate, resected lesion size and incidence of complications (massive bleeding or perforation).
RESULTS: There was no significant difference between the two groups in the
clinical characteristics. Minimum value of sBP (mmHg) in the New group was
lower than in the Conventional group (82.27  16.77 vs 102.10  19.30,
p 0.002). Minimum value of SpO2 (%) in the New group was higher than in
the Conventional group (97.13  2.07 vs 94.15  2.41, p 0.001). Regarding
ESD performance, there was no statistically significant difference in en block
resection rate, maximum diameter of specimen and incidence of complications
during ESD between the two groups. However, the mean procedural time (min)
in the New group was significantly shorter than in the Conventional group
(105.13  43.48 vs 134.95  45.58, p 0.013).
CONCLUSION: The continuous airway tone monitoring with a proprietary
microphone may provide the prevention of respiratory suppression by earlier
detection of apnea, glossoptosis and laryngeal spasm. Sedation using a combination of propofol and dexmedetomidine hydrochloride under the continuous
airway tone monitoring with a proprietary microphone can improve procedural
time without respiratory suppression in the esophageal ESD.
Disclosure of Interest: None declared
P1400 NEW METHOD OF LAPAROSCOPY ASSISTED ENDOSCOPIC
FULL-THICKNESS RESECTION WITH SILICON AND
POLYGLYCOLIC ACID SHEETS IN PORCINE MODEL
T. Itoh1,*, H. Kitakata1, S. Kinami2, K. Kawaura1, K. Hamada1, S. Azukisawa1,
R. Itoh1, T. Kosaka1
1
Dept. of Gastroenterological Endoscopy, 2Dept. Surgical Oncology,
KANAZAWA MEDICAL UNIVERSITY, Uchinada, Japan
INTRODUCTION: It is reported that the sentinel node concept is valid in cases
of early gastric cancer using lymphatic basin dissection method. It means that
dissection of the lymph nodes outside the basins may be avoided when the
sentinel nodes were negative for metastasis. We have previously shown the
safety and benefits of endoscopic full-thickness resection (EFTR) in in vivo porcine models. Furthermore, we initiated a clinical study of EFTR in patients with
submucosal invasive gastric cancer who were diagnosed as negative for lymph
node metastasis by laparoscopic sentinel lymph node biopsy. With this technique,
the lesion can be resected with an appropriate surgical margin, since the resection
is performed while confirming the lesion. On the other hand, it has some disadvantages, such as loss of endoscopic view caused by collapse of the stomach
and intra-peritoneal infection by outflow of gastric juice. Thus, we tried new
method of covering the serosa of stomach with silicon sheet and polyglycolic
acid felt to prevent collapse of the stomach and outflow of gastric juice.
AIMS & METHODS: Three domestic pigs were used for LA-EFTR. Under
general anesthesia, virtual lesions measuring 2 to 3 cm in diameter were set in
various positions of the stomach. Silicon sheet and polyglycolic acid (PGA) felt
(Neoveil ) were put on the serosa of the virtual lesion and pasted with fibrinogen, thrombin solution. Then, full-thickness incision was performed by IT knife.
RESULTS: By covering the serosa with PGA felt, endoscopic view was kept
during EFTR without collapse of the stomach. The felt was detached from the
stomach by laparoscopic forceps after EFTR and removed through oral cavity.
CONCLUSION: This method prevents the collapse of the stomach and enables
endoscopic resection with stable endoscopic view. EFTR may be a useful surgical

treatment as the extent of resection is limited to the minimum necessary and the
remnant gastric volume is preserved.
Disclosure of Interest: None declared
P1401 MODIFIED INTRODUCER METHOD FOR PERCUTANEOUS
ENDOSCOPIC GASTROSTOMY (PEG) DOES NOT NEED
ADMINISTRATION OF SYSTEMIC PROPHYLACTIC ANTIBIOTICS
- A PROSPECTIVE, RANDOMISED, DOUBLE-BLIND STUDY
Y. Adachi1,*, K. Akino1, H. Mita1, T. Kikuchi1, K. Yamashita2, Y. Arimura2,
T. Endo1
1
Sapporo Shirakaba-dai Hospital, 2First Department of Internal Medicine,
Sapporo Medical University, Sapporo, Japan
INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is the most
common method of enteral nutrition in patients who require long-term tube
feeding. According meta-analysis, administration of systemic prophylactic antibiotics for PEG tube placement reduces peristomal infection. However, several
recent developments of its procedure and instruments, the risk of infection having
been reduced. We want to assess necessity of systemic antibiotic prophylaxis for a
new modified introducer method PEG.
AIMS & METHODS: A prospective, randomised, double-blind trial. A total of
278 patients undergoing PEG were assessed for inclusion. Ninety-one patients
with an indication for PEG who gave informed consent to participate were
randomized. Forty-six patients received prophylactic ampicillin (sulbactam
sodium/ampicillin sodium) and 45 patients received a placebo. Introducer
method for PEG using Kangaroo-II Seldinger PEG kit was performed.
Primary outcome was the occurrence of clinically evident wound infection
within 3 and 7 days after insertion of the PEG catheter. Secondary outcomes
were fever and any infection within 3 and 7 days after PEG.
RESULTS: There were not significant difference between 2 groups in all parameters, including wound infection within 3 and 7 days, any fever within 3 and 7
days, any infection witin 3 and 7 days, and successive rate of finising antibiotics.
CONCLUSION: The new modified introducer method PEG might not needed
for systemic antibiotic prophylaxis.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


IBD III POSTER EXHIBITION HALL XL_____________________

9:0014:00

P1402 A MICROFLUIDIC BASED CHIP MODEL FOR THE STUDY OF


INTESTINAL MUCOSA BIOPSIES
M. Jacobsen1,2, J. Greenman3, A. Dawson3,*, S. Indrelid4, C. Dyer3
1
Medicine, Ostfold Hospital Trust, Fredrikstad, 2Internal medicine, University of
Oslo, Oslo, Norway, 3Biology, University of Hull, Hull, United Kingdom, 4IKBM,
University of life sciences, As, Norway
Contact E-mail Address: mjacobse@online.no
INTRODUCTION: Biopsy tissue has advantages over animal- and single cell
models as both the original disease mechanisms and the cell-matrix interactions
are maintained. Several authors have developed chip-based model for tissue
culture (1,2),
AIMS & METHODS: The chip was produced in-house of glass and PDMS with
a 2mm3 biopsy chamber. Microfluidic channels (200m) flushed the biopsy with
DMEM in separate flows to the epithelial and the basolateral surface. A syringe
pump established the flow (120lmin-1) and the effluents from both sides were
collected for analyses. The use of microfluidic channels ensured spatial and temporal regulation of solute concentration essential for the control of biomimetic
processes To ensure that the epithelial and the basolateral flow did not mix,
phenol red was added to the fluid on the epithelial side and the effluents examined with a photometer.
With proper consent from the ethics boards (UK) and after written patients
consent, biopsies were taken from patient with IBD. To investigate tissue survival, the tissue was processed for histology (HE) at start, at 24, 48 and 72 hours.
Furthermore, the biopsies were treated with Triton-X 100 at the same time-points
and the release of LDH was measured. The acute phase protein SA-100 was
measured in the effluent from tissue with macroscopic, inflammatory changes
and compared to normal looking tissue.
RESULTS: Photometry of the effluents demonstrated that the media did not
mix. Histology (HE) demonstrated that the epithelial layer was intact after 72
hours. Application of the Triton-X buffer sharply increased the LDH in the
effluent on both sides. S-100A was significantly higher in IBD than in effluents
from the non-IBD biopsies. This relationship was maintained up to 50 hours.
Staining with Ki-67 demonstrated proliferating cells in the crypts even at
50hours.
CONCLUSION: We have established a dual channel, chip method for tissue
culture that ensure tissue viability and maintain inflammatory characteristics
for more than 50 hours.
Three-dimensional culture models with intact cell-cell and cell-matrix connections have several advantages over single cell models. Our goal is to develop
this model to study individual disease mechanisms and therapy responses in
IBD. Our dual flow model may enable us to study the influence of luminal
metabolites on the colonic mucosa.
REFERENCES:
1. Hattersley SM, Dyers CE, Greenman J, et al. A microfluidic device for tissue
biopsy culture and interrogation. Lab Chip 2008; 8: 1842-1846.
2. Webster A, Greenman J and Haswell S. Development of microfluidic devices
for biomedical and clinical application. J Chem Technol Biotechnol 2010; 17: 136142.
Disclosure of Interest: None declared

A514

United European Gastroenterology Journal 2(1S)

P1403 THE EFFECT OF THE ANTI-TNFA ADALIMUMAB ON THE


LEVELS OF ANGIOGENIC FACTORS IN MUCOSAL CULTURES
FROM PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD)
P.M. Linares1,*, M.E. Fernandez Contreras1, A. Algaba2, M. Chaparro1,
I. Guerra2, F. Bermejo2, J.P. Gisbert1
1
Gastroenterology, Hospital Universitario de La Princesa, IP and CIBEREHD,
2
Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain
INTRODUCTION: Effectiveness of adalimumab (ADA) treatment could be
related to the modification of different angiogenic proteins, including VEGF,
Ang1, Ang2 and their receptor Tie2.
AIMS & METHODS: The aim of this study was to compare the concentrations
of several angiogenic factors in colonic mucosa culture supernatant (MCS) in
patients with IBD and matched controls and to analyze their modifications with
the in vitro ADA addition to the culture.
Prospective study in patients with IBD and non-IBD controls that underwent
endoscopy. Duplicates of colonic mucosa samples from affected and non-affected
mucosa from each IBD patient were obtained for comparison. Both were washed
and then cultured at 37 C in 5% CO2 medium under shaking for 24hours. In one
duplicate, ADA was added up to a final concentration of 10mg/mL prior to
culture. MCS levels in AP were determined by ELISA. Endoscopic ulcerative
colitis (UC) and Crohns disease (CD) activity was ascertained by Mayo subscore and SES-CD indexes, respectively.
RESULTS: 28 patients with IBD (16 UC, 12 CD) and 21 controls were included.
Mean age was 4116 years, and 61% were women. The mean disease duration
was 77 years. According to endoscopic activity, 36% of patient had quiescent,
32% mild, 28% moderate, and 4% severe activity. All angiogenic factors mean
levels in MCS were higher in affected than in non-affected MCS; VEGFA
(19.118.7 vs. 8.710.5 pg/mL/mg) and Ang2 (21.315.7 vs 11.88.9 pg/mL/
mg) (p50.05). There were no differences in MCS depending on endoscopic
activity. Levels of VEGFA, Ang1 and Ang2 from the affected, and VEGFA
and Tie2 from the non-affected mucosa, were lower when cultured with ADA
than without it (table 1). In UC patients, VEGFA and Ang1, and all angiogenic
factors MCS mean levels were lower in the affected-mucosa and non-affected
mucosa, and in the non-affected mucosa when cultured with ADA, respectively.
In contrast, in CD patients, there were no differences in MCS angiogenic factors
levels and the addition of ADA to the culture.
Table 1. Levels of angiogenic factors in MCS from IBD patients after culture.

VEGFA
Ang1
Ang2
Tie2

Affected mucosa

Affected mucosa ADA

p-value

19.118.7
15.78.8
21.315.7
12.05.5

14.614.5
12.26.2
19.413.1
12.416.1

0.003
0.021
0.021
0.911

Concentrations are expressed in pg/mL per mg of tissue.


CONCLUSION: ADA might downregulate the production of angiogenic factors
in MCS. ADA addition to mucosal cultures affects angiogenic factors levels in
samples from patients with UC differently than in patients from CD.
Disclosure of Interest: P. M. Linares Financial support for research from: Abbvie
grant, M. E. Fernandez Contreras: None declared, A. Algaba: None declared, M.
Chaparro Other: Dra. M Chaparro has served as a speaker and has received
research funding from MSD and Abbvie., I. Guerra: None declared, F. Bermejo:
None declared, J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker, a
consultant and advisory member for, and has received research funding from
MSD and Abbvie.
P1404 EFFECT
OF
CHONDROITIN
SULPHATE
ON
INFLAMMATORY MEDIATORS AND DISEASE ACTIVITY IN
PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD)

62% of patients were under mesalazine, 5% with sulfasalazine, 22% with thiopurines, and 3% with methotrexate. There was only one patient (with UC) that
had a flare during follow-up (6th m visit). The incidence rate of relapse was 3.4%
per patient-year of follow-up. That figure is lower than the relapse rate previously
reported for IBD patients. 12 UC and 11 CD patients completed the 12 m followup. In all patients with IBD, mean serum VEGFA levels were higher after 12
months of CS treatment (799 pg/mL) as compared to baseline (492 pg/mL)
(P50.05). Further differences regarding the other studied pro-inflammatory
markers were not found. At 12th m, the OA joint pain had improved in all but
four patients (from 5.9 to 3.0) (P50.01). 43% of patients suffered adverse events,
but only 5% were related to the drug.
CONCLUSION: The incidence of IBD relapse in patients under chondroitin
sulphate treatment was lower than the generally reported. This treatment
might modulate VEGFA serum levels, but it is not associated with modifications
in the concentrations of the other studied pro-inflammatory mediators.
Chondroitin sulphate decreases pain related to OA in patients with IBD.
Disclosure of Interest: P. M. Linares: None declared, M. Chaparro Other: Dra. M
Chaparro has served as a speaker and has received research funding from MSD
and Abbvie., A. Algaba: None declared, M. Roman: None declared, I. Moreno
Arza: None declared, F. Abad Santos: None declared, D. Ochoa: None declared,
I. Guerra: None declared, F. Bermejo: None declared, J. P. Gisbert Other: Dr. P.
Gisbert has served as a speaker, a consultant and advisory member for, and has
received research funding from MSD and Abbvie.
P1405 INTERLEUKIN-17A
HOMODIMER
REDUCES
INFLAMMATORY CYTOKINE PRODUCTION BY
INFLAMMATORY BOWEL DISEASE MUCOSA CULTURED EX
VIVO

PRO-

P. Biancheri1,*, A. Di Sabatino2, R. Curciarello1, P. Giuffrida2, F. Ammoscato1,


G.R. Corazza2, J.O. Lindsay3, T.T. MacDonald1
1
Centre for Immunology and Infectious Disease, Barts and The London School of
Medicine and Dentistry, London, United Kingdom, 2First Department of Medicine,
Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy,
3
Centre for Digestive Diseases, Barts and The London School of Medicine and
Dentistry, London, United Kingdom
Contact E-mail Address: paolo.biancheri@gmail.com
INTRODUCTION: Interleukin (IL)-17A, which is up-regulated in inflammatory
bowel disease (IBD) mucosal lesions, and IL-17F are normally present as IL17AA and IL-17FF homodimers and may occasionally form IL-17A/F heterodimers. The role of each IL-17 dimer in IBD is currently unknown.
AIMS & METHODS: Here we studied the effects of IL-17AA, IL-17FF and IL17-A/F in ulcerative colitis (UC) and Crohns disease (CD) mucosa. Inflamed
colonic biopsies from 17 IBD patients (6 UC and 11 CD) were cultured ex vivo
for 24 hours with IL-17AA, IL-17FF or IL-17A/F (1 ng/ml). Mucosal myofibroblasts isolated from the inflamed colon of 4 CD and 4 UC patients were cultured
for 24 hours with tumor necrosis factor (TNF)-alpha 20 ng/ml or with increasing
concentrations (1-100 ng/ml) of IL-17AA, IL-17FF or IL-17A/F. IL-6 and IL-8
were measured in culture supernatants by ELISA.
RESULTS: IL-17AA, but not IL-17FF, significantly reduced both IL-6 and IL-8
production by inflamed IBD biopsies cultured ex vivo, whereas IL-17A/F
decreased IL-8 release by IBD mucosa. No difference was observed between
CD and UC. Neither IL-17AA, nor IL-17FF, nor IL-17A/F exerted any effect
on IL-6 and IL-8 production by IBD myofibroblasts. As expected, TNF-alpha
stimulation significantly increased IL-6 and IL-8 production by both CD and UC
myofibroblasts in vitro. No difference was observed between CD and UC
myofibroblasts.
CONCLUSION: IL-17AA exerts an anti-inflammatory action on inflamed IBD
biopsies cultured ex vivo. The action of IL-17AA is not mediated by myofibroblasts, therefore further studies are underway to ascertain which cell type is the
main target of IL-17AA in IBD mucosa.
Disclosure of Interest: None declared

PRO-

P.M. Linares1,*, M. Chaparro1, A. Algaba2, M. Roman3, I. Moreno Arza3,


F. Abad Santos3, D. Ochoa3, I. Guerra2, F. Bermejo2, J.P. Gisbert1
1
Gastroenterology, Hospital Universitario de La Princesa, IP and CIBEREHD,
2
Gastroenterology, Hospital Universitario de Fuenlabrada, 3Clinical
Pharmacology, Hospital Universitario de La Princesa, IP and CIBEREHD,
Madrid, Spain
INTRODUCTION: Chondroitin sulphate, a glycosaminoglycan that modulates
NF-B, might modulate several pro-inflammatory proteins involved in the
pathogenesis of IBD.
AIMS & METHODS: The aim of our study was to evaluate the incidence rate of
relapse in patients with IBD under chondroitin sulphate treatment and its effect
on the concentrations of diverse pro-inflammatory mediators in serum and urine.
Prospective observational 12-month (m) follow-up study in patients with IBD in
remission for at least 6 m, starting chondroitin sulphate treatment (Condrosan,
CS Bio-ActiveTM, Bioiberica S. A., Barcelona, Spain) for osteoarthritis (OA)
(dose: 800 mg o.d.). Visits were as follows: Baseline, 3rd, 6th, 9th and 12th m.
CDAI and modified Truelove-Witts clinical indexes were calculated for Crohns
disease (CD) and ulcerative colitis (UC) respectively. C-reactive protein (CRP),
orosomucoid, and erythrocyte sedimentation rate (ESR) were also determined.
Levels of VEGFA, VEGFC, FGF2, HGF, Ang1, Ang2, TGF, TNF, IL1, -6,
-12, -17, -23, ICAM1, VCAM1, MMP3 and PGE2 were quantified by ELISA.
OA joint pain was evaluated by a visual analogue scale (VAS).
RESULTS: 37 patients with IBD (19 UC, 18 CD) were included. Mean age was
59.8 years, and 70% were women. The mean disease duration was 12.7 years.

P1406 THE ROLE OF NADPH OXIDASE IN THE PATHOGENESIS OF


COLON INFLAMMATION IN MICE
R. Ramonaite1,*, J. Skieceviciene1, J. Kupcinskas1, V. Borutaite2, L. Kupcinskas1
Institute for Digestive Research, 2Institute for Neurosciences, Lithuanian
University of Health Sciences, Kaunas, Lithuania
Contact E-mail Address: rimaramonaite@gmail.com
1

INTRODUCTION: Reactive oxygen species (ROS) induced oxidative stress is


one of most important etiological factor involved in the inflammation [1-2]. The
key producers of ROS in the cells are NADPH oxidase enzymes. Several studies
have shown that epithelial NADPH oxidase might be responsible for normal
immune response to antigens in the gut [1,3]. On the other hand, little is
known about the molecular pathways controlling ROS production via
NADPH oxidase enzymes in the primary intestinal epithelial cells during
inflammation.
AIMS & METHODS: AIM: To investigate the role of NADPH oxidase in colon
epithelial cells in pathogenesis of acute and chronic colon inflammation using
mice dextran sulphate sodium (DSS) colitis model.
METHODS: BALB/c mice were divided into three groups: 8 mice with acute
DSS colitis (3.5% DSS solution; 7 days), 8 mice with chronic DSS colitis (3.5 %
DSS solution for 5 days water for 6 days; 4 cycles; total: 44 days) and 12 mice
without DSS supplementation as control group. The primary colonic epithelial
cells were isolated using chelation method. The cells were cultivated in the presence of mediators (lipopolysaccharide (LPS), apocynin or diphenyleneiodonium). Viability of cells was assessed by fluorescent microscopy. Production of
reactive oxygen species (ROS) by the cells was measured fluorimetrically using

United European Gastroenterology Journal 2(1S)


Amplex Red. Production of tumour necrosis factor- alpha (TNF- ) by the
colonic epithelial cells was analysed by ELISA. Nox1 gene expression was
assessed by real-time (RT) PCR.
RESULTS: Our study showed that TNF- level was increased in unstimulated
primary colonic cells both in the acute and chronic DSS colitis groups, whereas
decreased viability, increased ROS production, and expression of Nox1 was
characteristic only for chronic DSS colitis mice when compared to the controls.
The stimulation by LPS increased ROS generation via NADPH oxidase and
decreased cell viability in mice with acute DSS colitis. Treatment with
NADPH oxidase inhibitors increased cell viability decreased the levels of ROS
and TNF-  in the LPS-treated cells isolated from mice of both acute and chronic
DSS colitis groups.
CONCLUSION: Our study revealed the importance of NADPH oxidase in
pathogenesis of acute and chronic colon inflammation. Moreover, the treatment
with NADPH oxidase inhibitors had a protective effect against pro-inflammatory action of LPS in mice colonic epithelium cells during DSS colitis.
REFERENCES
1. Bedard K and Krause KH. The NOX family of ROS-generating NADPH
oxidases: physiology and pathophysiology. Physiol Rev 200; 87: 245-313.
2. Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev
Immunol 2004; 4: 181-189.
3. Rokutan K, Kawahara T, Kuwano Y, et al. Nox enzymes and oxidative stress
in the immunopathology of the gastrointestinal tract. Semin Immunopathol 2008;
30: 315-327.
Disclosure of Interest: None declared
P1407 ROLE OF ADENOSINE A2B RECEPTORS IN THE CONTROL OF
INFLAMMATION, FIBROSIS AND MOTILITY IN EXPERIMENTAL
COLITIS
R. Colucci1,*, M. Fornai1, N. Bernardini1, C. Pellegrini1, D. Sacco1, B. Cso`ka2,
C. Segnani1, C. Ippolito1, G. Hasko`2, C. Blandizzi1, L. Antonioli1,2
1
Clin. Exp. Medicine, Univ. Pisa, Pisa, Italy, 2Center for Immunity and
Inflammation, Rutgers-New Jersey Medical School, Newark, United States
Contact E-mail Address: r.colucci@med.unipi.it
INTRODUCTION: The adenosine system is emerging as a pathway involved in
the regulation of balance between tissue repair and fibrosis. However, the role of
adenosine in the pathophysiology of gut fibrotic remodelling has been scarcely
investigated.
AIMS & METHODS: This study evaluated the role of adenosine A2B receptors
on inflammation, pro-fibrotic TGF-beta/SMAD signalling and motility in
experimental colitis. Colitis was induced in rats by intrarectal 2,4-dinitrobenzenesulfonic acid (DNBS). After 6 days, systemic [body and spleen weight] and
tissue inflammatory parameters [macroscopic and microscopic damage, myeloperoxidase (MPO)] were assessed. Three days before colitis assessment, animals
were treated daily with BAY606583 (BAY, A2B agonist, 2 mg/kg) or MRS1754
(MRS, A2B antagonist, 1 mg/kg) by i.p. route. At sacrifice, molecular factors
involved in fibrosis (collagen I and III, fibronectin, TGF-beta, phosphorylated
SMAD2) were analyzed by western blot. Collagen fibers (Sirius red) and elastic
fibers (orcein) were examined by histochemistry. Colonic longitudinal muscle
strips were suspended in organ baths (Krebs solution with NK 1, 2 and 3 receptor
antagonists, guanethidine, L-NAME) to record atropine-sensitive cholinergic
motor activity. Contractions were evoked either by electrical stimulation or by
carbachol in the presence of tetrodotoxin.
RESULTS: DNBS-induced inflammation was associated with a decrease in body
weight and increase in spleen weight, tissue MPO as well as macroscopic and
microscopic alterations. Western blot revealed an increased expression of collagen I and III, fibronectin, TGF-beta and pSMAD2, as compared with controls.
Histochemistry confirmed an increment of collagen deposition and a loss of
elastic fibers. In functional assays, both electrically-evoked and carbacholinduced contractions were reduced, as compared with controls. In the setting
of colitis, treatment with MRS counteracted the inflammatory indexes, while
not affecting the molecular parameters related with fibrotic remodelling. By
contrast, the administration of BAY failed to modify both systemic and tissue
inflammatory indexes. However, BAY increased the expression of collagen I and
fibronectin, while downregulating the TGF-beta/pSMAD2 pathway. With
regard for motility, the altered motor patterns associated with colitis were not
affected by BAY, while they were partly normalized by MRS.
CONCLUSION: DNBS-induced colitis is associated with colonic fibrotic remodelling and altered excitatory motility. In this setting, the pharmacological activation of A2B receptors did not modify the inflammatory indexes and abnormal
patterns of cholinergic motility, while it increased the fibrotic remodelling
through molecular pathways independent of TGF-beta signalling. By contrast,
the pharmacological blockade of A2B receptors counteracted bowel inflammation and improved colonic dysmotility, without affecting fibrotic remodelling.
Overall, these findings suggest a marginal role of endogenously activated A2B
adenosine receptors in the pathogenesis of fibrosis associated with bowel
inflammation.
Disclosure of Interest: None declared

A515
P1408 HUMAN ALPHA-DEFENSIN 6 REGULATED BY BOTH ATOH1
AND BETA-CATENIN MIGHT BE THE PATHOGENESIS OF
CROHNS DISEASE
R. Hayashi1,*, K. Tsuchiya2, S. Hibiya1, K. Fukushima1, N. Horita1, E. Okada1,
A. Araki1, K. Ohtsuka1, M. Watanabe1
1
Gastroenterology and Hepatology, 2Advanced Therapeutics for Gastrointestinal
Diseases, Tokyo Medical and Dental University, Tokyo, Japan
Contact E-mail Address: rhayashi.gast@tmd.ac.jp
INTRODUCTION: Antimicrobial mucosal barrier dysfunction, including the
reduction of Human alpha-Defensin (HD) 5, is one of the most crucial pathogenesis of Crohns disease (CD). Human Paneth cells produce two -defensin
peptides, which called HD5 and HD6. Recently, it has been reported that HD6
promotes mucosal innate immunity through self-assembled peptide nanonets
whereas HD5 has the antimicrobial activity. The transcriptional regulation of
HD6 has not been elucidated. Moreover the association of HD6 expression with
CD also remains unknown.
AIMS & METHODS: We therefore aimed to elucidate the transcriptional regulation of HD6 and the pathogenesis of CD by HD6 expression.
For the analysis of the transcriptional regulation of HD6, We transgened Atoh1
into colon cancer cell line; SW480 by lentivirus infection. The expression of HD6
was assessed by quantitative RT-PCR and immunofluorescence. The transcriptional activity of HD6 promoter was assessed by the luciferase reporter assay.
For the analysis of the HD6 expression in CD, non-inflamed jejunum biopsy
specimens of 8 CD patients and 9 healthy controls using double balloon enteroscopy (DBE) were assessed.
RESULTS: HD6 was significantly increased by Atoh1 expression in SW480
whereas other antimicrobial peptides such as HD5, Lysozyme and phospholipase
A2 were not changed. Atoh1 also enhanced the transcriptional activity of HD6
promoter. We found that HD6 promoter within 200-bp from ATG contains a
transcription factor (TCF) binding site and four E-box binding site. The deletion
of each binding sites revealed that not only TCF4/-catenin protein complex but
also Atoh1 is indispensable for HD6 expression. Moreover, ChIP assay showed
that Atoh1 directly binds to the promoter region of HD6.
Finally, we assessed the pathogenesis of CD by HD6 expression. The microarray
using mapping biopsy of whole small intestine in CD patient showed that almost
inflammatory related genes were not shown in jejunum, suggesting that the pathogenesis before the onset of CD might remain in jejunum. The expression of Atoh1
and secretory cell markers (HD5, HD6, MUC2 and CgA) in jejunum of CD patients
were significantly lower than that of healthy controls. Moreover, HD6 positive
Paneth cells of CD patients were significantly lower than that of healthy controls.
CONCLUSION: Both TCF4/-catenin protein and Atoh1 are essential to
express HD6 in different from HD5. The decrease of HD6 in small intestine
might cause mucosal barrier dysfunction suggesting that HD6 might be one of
the pathogenesis of CD.
Disclosure of Interest: None declared
P1409 DIVERSITY OF ADHERED MICROBIAL COMMUNITIES IN
COLON MUCOSAL BIOPSIES OF CROHN PATIENTS BY 16S
RRNA GENE PYROSEQUENCING, EVIDENCES FOR TWO MAIN
DISTINCT GROUPS
D. Ginard1, S. Khorrami1,*, R. Vidal2, M. Mora3, R. Munoz3, M. Hermoso2,
S. D az3, A. Cifuentes3, A. Orfila3, R. Rosello-Mora3
1
Gastroenterology. Palma Health Research Institute, Son Espases Hospital, Palma
de Mallorca, Spain, 2Institute of Biomedical Sciences, Faculty of Medicine,
Universidad de Chile, Santiago de Chile, Chile, 3Department of Ecology and
Marine Resources, Institut Mediterrani dEstudis Avancats (IMEDEA; CSICUIB), Esporles, Spain
INTRODUCTION: The human gut microbiota participates actively in the host
homeostasis and plays an important role in Crohns disease (CD) pathogenesis.
Microbial diversity measures based on environmental 16S rRNA genes had permitted the recognition of the vast diversity of yet uncultured microorganisms in
environmental samples. Next Generation Sequencing (NSG) techniques produce
thousands of sequences, and had been thoroughly used to reveal diversity in
environmental samples with identifications based on clustering sequences into
Operational Phylogenetic Units (OPUs).
AIMS & METHODS: We aimed to study the microbiota adhered in the gut
mucosa of CD patients and compare with healthy controls by means of a highthroughput NGS approach. Mucosal biopsies of 13 CD and 7 healthy controls
submitted to colonoscopy for medical indications were recruited between Augost
2011 and March 2012. Demographics and clinical characteristics (disease localization, inflammatory activity, behavior, medication and surgical history) were also
collected. Biopsies were immediately placed in sterile tubes and stored at -80 C for
DNA/RNA extraction. The mucosal adhered microbiota was studied by high
quality deep-sequencing of 16S rRNA gene amplicons. High quality sequences
(mean 500 nuc) were applied to OPUs identification approach based on clustering
sequences. The Balearic Islands Ethical committee approved the study.
RESULTS: CD samples showed a mean of 83 (16) OPUs, whereas HC samples
showed a mean of 101 (19). Two major groups of CD patients with different
mirobiomes could be discriminated. Both groups presented a common trend
mainly exhibited as depletion in members of the class Clostridia. In addition,
CD1 showed enhanced presence of co-colonizing Bacteroidetes as a result of the
disappearance of Firmicutes; whereas CD2 seemed to exhibit an opportunistic
colonization of the mucosa by members of Proteobacteria.
CONCLUSION: CD patients exhibited consistently lower microbiota diversity
than controls. CD may include different pathological disorders resulting in different adhered microbial profiles with a similar inflammatory end process.
Simple amplification tests checking the presence or absence of F. prausnitzii

A516

United European Gastroenterology Journal 2(1S)

and the relative abundances of Firmicutes, Bacteroidetes and Proteobacteria


could serve as diagnosis of both major CD groups found here and may help in
the recognition of the genetic or metabolic disorders that conduct to the CD
phenotypes.
Disclosure of Interest: None declared
P1410 THE ROLE FOR THE CYTOKINES INTERLEUKIN-22 AND
INTERLEUKIN-17A AND PATHOGEN-ASSOCIATED MOLECULAR
PATTERNS DURING THE PATHOGENESIS OF CROHNS DISEASE
ASSOCIATED PERIANAL FISTULAS
S.M. Frei1,*, A. Furst2, E. Jehle3, M. Fried1,4, G. Rogler1,4, M. Scharl1,4
1
Gastroenterology and Hepatology, University Hospital Zurich, Zurich,
Switzerland, 2Surgery, Caritas-Krankenhaus St. Josef, Regensburg, 3Surgery,
Oberschwaben-Klinik, Ravensburg, Germany, 4Zurich Center for Integrative
Human Physiology, University Zurich, Zurich, Switzerland
Contact E-mail Address: sandra.frei@usz.ch
INTRODUCTION: Intestinal and perianal fistulas represent an important complication of Crohns disease (CD). Therapeutic outcome using conventional
drugs such as antibiotics, immunosuppressive agents and biologics is poor and
surgical intervention is often required. Chronic inflammation, failure of the
intestinal barrier function and a bacterial imbalance may contribute to the induction of epithelial-mesenchymal transition (EMT) and the consequent formation
of fistula tracts. Tumor necrosis factor alpha (TNF-), transforming growth
factor beta (TGF-) and interleukin (IL)-13 synergistically contribute to the
migration and invasiveness of intestinal epithelial cells (IECs). The underlying
extracellular matrix is broken down to enable IECs to invade.
AIMS & METHODS: Human perianal fistula tissue was investigated for the IL22 receptor subtype RA1 and IL-17A using immunohistochemical procedures.
Multicellular three-dimensional HT-29 IEC constructs were exposed to MDP
(100 ng/ml) or IL-22 (50 ng/ml) for one, five and seven days and assessed microscopically as well as on a molecular level. Monolayer IECs were challenged to IL22, IL-17A (100 ng/ml), TGF- (100 ng/ml) or a combination of IL-22 plus TGF or IL-17A plus TGF-.
Here, we investigated the impact of the Th17 and/or innate lymphoid cell derived
cytokines interleukin (IL)-22 and IL-17A and pathogen-associated molecular
patters (PAMPs) such as muramyldipeptide (MDP) on the induction of EMT.
RESULTS: After exposure to MDP for seven days, the spheroids lost the welldefined globular shape and the epithelial cells separated indicating the onset of
EMT. This was not seen in untreated control spheroids. In accordance with these
microscopic findings, MDP treated spheroids up-regulated mRNA levels of
EMT-related genes, including SNAIL1 (p 5 0.05), TGF- (p 5 0.05) and IL13 (p 5 0.05) after treatment for seven days. In contrast to MDP, IL-22 did not
induce EMT in spheroids. When IECs were co-treated with IL-22 and TGF-,
the effects of TGF- were abrogated, but a further enhanced mRNA expression
of 6-Integrin (p 5 0.001) was observed. A similar pattern was found for the cotreatment with IL-17A and TGF-; TGF- induced up-regulation of SNAIL1 (p
5 0.05) and IL-13 (p 5 0.01) was abolished and the reduced E-Cadherin (p 5
0.05) levels were restored. Interestingly, we observed a strong staining signal for
IL-22RA1 and IL-17A in fistula tissue of non-smoking CD patients whereas
smokers revealed almost no expression of the indicated proteins.
CONCLUSION: Here, we demonstrate that PAMPs might contribute to the
onset of EMT and therefore to the development of CD fistulas. The observed
effects for the cytokines are indicative for an antagonistic effect of IL-22 and IL17A on TGF-b. We therefore hypothesize that IL-22 and IL-17A might exert
protective effects in the pathogenesis of CD-associated fistulas. There are some
tremendous differences in the protein expression between smokers and non-smokers, indicating an altered immune response during fistula pathogenesis. In summary, our data suggest that bacterial pathogens likely impact the pathogenesis of
CD-associated fistulas and the nicotine status might impact the response to
fistula development.
Disclosure of Interest: None declared
P1411 ACTIVE
CROHN
DISEASE
TRYPTOPHAN DEFICIENCY

IS

ASSOCIATED

WITH

S. Nikolaus1, N. Al- Massad1, J. Bethge1, G. Waetzig2, P. Rosenstiel3,


R. Junker4, F. Thieme4, S. Schreiber1,*
1
1st. Med. Department, University Hospital Schleswig-Holstein, Campus Kiel,
2
Conaris Research Institute AG, 3Institut fur Klinische Molekularbiologie,
Christian-Albrechts-Universitat Kiel, 4Institut fur Klinische Chemie, University
Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Contact E-mail Address: s.nikolaus@mucosa.de
INTRODUCTION: Malnutrition leads to intestinal inflammation and diarrhoea. In recent studies we have identified ACE2 as a key regulator of dietary
amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis which can be directly regulated by the dietary amino
acid tryptophan (TRP) (1). Moreover, B0AT1, the colonic TRP transporter, is
downregulated in IBD mucosa (1). In an ongoing study we have investigated the
role of TRP in a consecutive series of patients with IBD (n 445, UC.n 165,
CD:n 280) and controls (healthy controls and disease specificity controls 125). More than 200 patients were seen twice and are not included in
the basic statistics.
AIMS & METHODS: Patients with IBD were recruited consecutively from an
outpatient setting, controls comprise healthy blood donors and disease specificity
controls (patients with suspected IBD, in whom the diagnosis of IBD was not
confirmed). A serum sample was prospectively obtained during a three months,
ongoing sampling campaign to assess TRP levels. Patients were clinically characterized and TRP levels were related in an exploratory analysis to clinically

characteristics, age, severity of disease, gender, BMI, smoking status CRP and
duration of disease. A forward and backward logistic regression was performed.
RESULTS: TRP levels in patients with IBD were significantly lower
(P50.00001) than in controls (UC: p 0.028, CD: p510E-8) (Fig.1). Levels
were lower in CD patients lower than in UC (P50.0001). In a first analysis of
258 patients a clear relationship of low TRP levels was seen with high disease
activity (p 0.0077 for UC and p 0.0070 in CD). Female individuals had lower
TRP levels than male individuals, both in controls (p 0.0097) and patients
(p 0.0006). TRP levels were correlated with BMI (p 0.015 in controls and
P50.0001 in patients). The examination of TRP and smoking status was heavily
confounded by the uneven distribution of smokers (n 8 (10.3%) in UC, n 67
(36-5%) in CD, P50.0001). No correlation of TRP levels and age or duration of
disease could be found.
CONCLUSION: Tryptophane deficiency appears to be an important, novel
mechanism in IBD. It appears likely that low TRP levels in serum reflect a
reduced availability of TRP metabolites on the mucosal surface or an increased
local consumption through the inflammatory process. In analogy to murine
models TRP deficiency could cause the microbial changes seen in IBD and
promote the rise of a colitogenic flora. While it high TRP exposure is poorly
tolerated in the GI tract, a controlled delivery formulation of TRP derivatives
with low toxicity is under clinical development for the use in IBD.
REFERENCES
(1) Hashimoto T, et al. Nature 2012.
Supported by a grant from CONARIS Research Institute AG
Disclosure of Interest: S. Nikolaus Financial support for research from: Conaris
Research Institute AG, N. Al- Massad Financial support for research from:
Conaris Research Institute AG, J. Bethge Financial support for research from:
Conaris Research Institute AG, G. Waetzig: None declared, P. Rosenstiel
Financial support for research from: Conaris Research Institute AG, R.
Junker Financial support for research from: Conaris Research Institute AG, F.
Thieme Financial support for research from: Conaris Research Institute AG, S.
Schreiber Financial support for research from: Conaris Research Institute AG
P1412 THE EXPRESSION OF MYOSIN LIGHT CHAIN
INDUCED BY NK-KB ACTIVATION IS INVOLVED IN THE
DEVELOPMENT OF COLITIS-ASSOCIATED CANCER

KINASE

N. Jose1,*, T. Nagaishi1, T. Watabe1, A. Tokai1, M. Suzuki1, M. Yamazaki2,


M. Watanabe1
1
Gastroenterology, Tokyo Medical and Dental University, 2Obstetrics and
Gynecology, Nihon University School of Medicine, Tokyo, Japan
INTRODUCTION: It has been suggested that prolonged inflammatory bowel
disease may promote carcinogenesis in the epithelia. Myosin light chain kinase
(MLCK) has been reported to be essential to the permeability of epithelial barrier
in the context of colitis, however its role in the development of colitis-associated
cancer (CAC) is still unknown.
AIMS & METHODS: The aim of this study was to examine the effects of NF-kB
activation and MLCK expression in the setting of CAC. Wild type C57BL/6 mice
were pre-treated with azoxymethane and then three times with dextran sodium
sulfate to induce a model of CAC.
RESULTS: Semi-quantitative polymerase chain reaction (qPCR) revealed that
inflammatory cytokines such as IL-1b, IL-6 and MIP-2, which are known to be
associated with tumor growth, were up-regulated in the inflamed colonic lamina
propria. Western blotting (WB) showed slight up-regulation of MLCK in the
colonic epithelia in association with the phosphorylation of IkBa and p65. NFkB and MLCK were further up-regulated in the tumor tissues compared to the
non-tumor areas, as well as up-regulation of the specific receptor for tumor
necrosis factor (TNF) assessed by qPCR and WB. Immunohistochemistry
(IHC) and transmission electron microscopy (TEM) showed that MLCK inhibitor, ML-7, treatment prevented the disruption of epithelial tight junctions. IHC
and TEM also showed that anti-TNF mAb, MP6-XT22, treatment restored the
disrupted tight junctions and suppressed tumor development.
CONCLUSION: Our studies suggest that permeability of epithelial layer in the
inflamed tissues is associated with MLCK up-regulation and susceptibility to
inflammatory cytokines that potentially promote CAC growth.
Disclosure of Interest: None declared
P1413 SERUM REG3ALPHA LEVELS IN CROHNS DISEASE PATIENTS
UNDERGOING IMMUNOABLATION AND AUTOLOGOUS
HEMOPOETIC STEM CELL TRANSPLANTATION IN THE ASTIC
TRIAL
T. Greuter1,*, S. Lang1, C.J. Hawkey2, G. Rogler1, L. Biedermann1 on behalf of
the ASTIC Trial group
1
Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich,
Switzerland, 2Nottingham Digestive Diseases Centre, Nottingham, United
Kingdom
Contact E-mail Address: thomas.greuter@usz.ch
INTRODUCTION: Regenerating islet-derived 3-alpha (REG3) has been shown
to be a promising biomarker with remarkable specificity for lower gastrointestinal Graft versus Host Disease (GvHD) after allogeneic stem cell transplantation,
allowing better risk stratification of patients and the prediction of non-relapse
mortality (1). GvHD shares many similarities (histological features and genetic
risk factors) with Crohns disease (CD). We aimed to investigate the role of
serum REG3 as a diagnostic and prognostic biomarker in CD patients undergoing autologous hemopoetic stem cell transplantation (HSCT) in the multicenter ASTIC trial.
AIMS & METHODS: Stored serum samples from the ASTIC trial were analyzed
using a commercially available ELISA-kit to measure serum REG3 levels (Ab-

United European Gastroenterology Journal 2(1S)


Match Assembly Human PAP1 kit, MBL International Cooperation, Catalog
Number 5323). Clinical, laboratory and endoscopic data was available from the
ASTIC trial. Serum REG3 levels were correlated with clinical (Crohns disease
activity index (CDAI), harvey bradshaw index (HBI)) and endoscopic disease
activity (CDEIS) as well as overall outcome 1 year after HSCT, which was
assessed by changes in CDAI and CDEIS, and by clinical (CDAI150) or endoscopic remission (CDEIS54), respectively.
RESULTS: As of January 2014, 132 serum samples were available from 37 of the
45 ASTIC trial participants. Mean concentration of serum REG3 was 101.8 ng/
ml (95% CI 22.6-258.3). No significant elevation of serum REG3 levels was
found among patients with moderate or severe symptoms compared to patients
in clinical remission (106.3 vs. 91.4, p 0.289) and no correlation of REG3 to
CDAI was identified within the group of symptomatic patients. Nonetheless,
patients with moderate to severe endoscopic disease activity (CDEIS49)
showed slightly although not significantly elevated REG3 levels compared to
patients in endoscopic remission (95.4 vs. 52.4, p 0.052). Baseline REG3 of
patients without clinical or endoscopic remission 1 year after HSCT was not
elevated compared to patients in remission after HSCT (63.1 vs. 66.9,
p 0.947, and 68.4 vs. 59.2, p 0.796, respectively). Changes in CDAI or
CDEIS after HSCT did not show any correlation with REG3 levels at study
enrolment.
CONCLUSION: We did not observe a correlation of serum REG3 levels with
Crohns disease activity except for a trend regarding endoscopic disease activity
scores. In contrast to the findings in GvHD after allogeneic HSCT baseline
REG3alpha did not have any prognostic value for clinical and endoscopic outcome 1 year after HSCT. Given the divergent findings compared to GvHD (1),
we conclude that REG3 is not a promising diagnostic and predictive biomarker
in CD patients undergoing autologous HSCT.
REFERENCES
1. Ferrara JL, Harris AC, Greenson JK, et al. Regenerating islet-derived 3-alpha
is a biomarker of gastrointestinal graft-versus-host disease. Blood 2011; 118:
6702-6708.
Disclosure of Interest: None declared
P1414 THE IMPORTANCE OF INTESTINAL EOTAXIN-1 - EOSINOPHIL
AXIS IN INFLAMMATORY BOWEL DISEASE, RESULTS OF A
PROSPECTIVE OBSERVATIONAL STUDY
T. Adar1,*, S. Shteingart1, A. Ben-Yaacov1, A.B.-G. Shitrit1, S. Shmorak1,
F. Vernea2, E. Goldin1
1
Digestive Diseases Institute, 2Department of Pathology, Shaare Zedek Medical
Center, Jerusalem, Israel
Contact E-mail Address: adartom@szmc.org.il
INTRODUCTION: Eotaxin-1 is a potent eosinophil chemoatractant which is
considered a major contributor to tissue eosinophilia. Elevated tissue Eotaxin1 has been previously reported in Ulcerative colitis (UC) patients. Simultaneous
serum and tissue sampling from intestinal biopsies can be used to demonstrate
the effect of tissue vs. serum Eotaxin-1 levels on tissue eosinophila in patients
with UC or Crohns disease (CD).
AIMS & METHODS: To evaluate serum and tissue levels of Eotaxin-1 in
patients with Crohns disease (CD) and Ulcerative colitis (UC) compared with
healthy controls.
METHODS: Serum samples and intestinal biopsies were obtained from consenting patients with known CD or UC or healthy individuals undergoing screening
colonoscopy. Biopsies were used for quantitative assessment of tissue Eotaxin-1
levels and for histological evaluation of tissue eosinophlia as measured by average eosinophil count per high power field (HPF), by a blinded pathologist. These
parameters were than compared between the patients, which were sub-grouped
according to diagnosis and disease activity.
RESULTS: Intestinal biopsies were obtained from 60 patients (10 controls, 15
active UC, 10 UC in remission, 16 CD active and 9 CD in remission). Mean
tissue Eotaxin-1 levels were 34.02 pg/mg protein in control group compared
to159.79 and 219.62 pg/mg protein in active UC and active CD respectively
(p50.001 for both) and compared to 106.13 and 97.78 pg/mg protein in UC
and CD in remission (p 0.06 and 0.07 respectively). Tissue Eotaxin-1 levels in
active CD were significantly elevated compared with non active CD patients
(p50.05).
No significant difference was noted in serum Eotaxin-1 levels in neither CD nor
UC patients, regardless of disease activity.
In healthy control, a strong correlation was found between tissue and serum
eotaxin-1 levels (r 0.75, p 0.01). A weak correlation was found in CD and
UC patients.
Tissue but not serum eotaxin-1 levels correlated tissue eosinophilia in active UC
patients only (r 0.63, p 0.01).
CONCLUSION: This study demonstrates elevated tissue Eotaxin-1 levels as a
hallmark of both UC and CD, especially in active disease. The increase in tissue
but not in serum eotaxin-1 levels suggests its importance as a local mediator of
mucosal inflammation.
The correlation between tissue eotaxin-1 and tissue eosinophila in active disease,
marks its central role in mediating local inflammation, and also suggests that its
role in the pathogenesis of CD is not restricted to eosinophils recruitment.
DISCLOSURE: The study was funded in part by Immune Pharma.
- Relevant financial disclosure: Tomer Adar Immune Pharma, Eran Goldin
Immune Pharma.
Disclosure of Interest: T. Adar Financial support for research from: Synageva,
Lecture fee(s) from: Shire, Consultancy for: Janssen, Other: Boston Scientific,
Immune Pharma, S. Shteingart: None declared, A. Ben-Yaacov: None declared,
A. Shitrit: None declared, S. Shmorak: None declared, F. Vernea: None declared,
E. Goldin Consultancy for: Immune Pharma, Bioline Rx Ltd.

A517
P1415 COMPARATIVE BEHAVIOUR OF MACROPHAGES ISOLATED
FROM PATIENTS WITH CROHNS DISEASE OR ULCERATIVE
COLITIS AND CONTROLS IN RESPONSE TO ADHERENTINVASIVE OR NON-PATHOGENIC E. COLI INFECTION
V. Emilie1,2,*, A. Buisson1,2, M. Goutte1,2, L. Ouchchane3, J.-P. Hugot4, A. De
Vallee2, M.-A. Bringer2, G. Bommelaer1,2, A. Darfeuille-Michaud2
1
Department of Hepato-Gastroenterology, University Hospital Estaing of
Clermont-Ferrand, 2UMR 1071 Inserm/Universite dAuvergne, 3CHU ClermontFerrand, Pole Sante Publique, CNRS, ISIT, UMR6284, Clermont-Ferrand,
4
UMR843, INSERM, Assistance Publique Hopitaux de Paris et Universite, Paris
Diderot, Paris, France
INTRODUCTION: Ileal lesions of 36.4% of Crohns disease (CD) patients are
colonized by pathogenic adherent-invasive Escherichia coli (AIEC), able to highly
replicate in mature phagolysosomes within cultured macrophages. The aim of
this study was to assess whether macrophages from CD patients showed impaired
ability to control intracellular bacteria replication and pro-inflammatory cytokine expression in response to pathogenic AIEC or non-pathogenic E. coli
infection.
AIMS & METHODS: Human peripheral blood monocyte-derived macrophages
were obtained from CD patients, ulcerative colitis (UC) patients and controls. All
patients and controls were genotyped for the main coding mutations in NOD2
and for ATG16L1. Following in vitro infection with AIEC reference strain LF82
or non-pathogenic E. coli K-12 levels of intracellular bacteria at 1h and 10 h postinfection was assessed by using gentamicin protection assay. IL-6, IL-8, and
tumour necrosis factor alpha (TNF-) cytokine levels were evaluated at 10h
post-infection by ELISA. The effect of neutralization of TNF- on the number
of intracellular AIEC LF82 bacteria were analysed in CD macrophages untreated
or not with Infliximab at 1 g/ml.
RESULTS: A higher number of AIEC bacteria than non-pathogenic E. coli is
internalized within macrophages whatever cell origin. The intracellular AIEC
replicate rate was the highest in macrophages from CD patients. This was not
observed when macrophages were infected with non-pathogenic E. coli. In our
cohort of CD patients, only macrophages heterozygous for a NOD2 polymorphism were found and they did not show significant difference in their ability to
control AIEC intracellular replication. Concerning ATG16L1 polymorphism,
high levels of intracellular AIEC bacteria were observed in AIEC-infected macrophages homozygous for ATG16L1 (T300A). AIEC infection of macrophages
induced the secretion of IL-6, IL-8 and TNF- at levels higher than infection
with the non-pathogenic E. coli whatever cell origin. The levels of IL-6 cytokine
secreted were higher with AIEC-infected macrophages from CD patients. A
positive correlation was observed between the number of intracellular AIEC
bacteria at 10 h post-infection and the level of TNF- secreted by infected CD
macrophages. In contrast no significant difference in TNF- or IL-6 secretion
was observed between non-pathogenic E. coli-infected macrophages from CD
and UC patients or from controls. Infliximab have not effect on the control of
intracellular bacterial replication within macrophages.
CONCLUSION: Human peripheral blood monocyte-derived macrophages from
CD patients compared to those of UC patients or controls showed specific
characteristics in response to AIEC infection but not to non-pathogenic E. coli
challenge including load of intracellular bacteria and secretion of pro-inflammatory TNF- and IL-6 cytokines.
Disclosure of Interest: None declared
P1416 A PROSPECTIVE STUDY OF CIGARETTE SMOKING AND THE
RISK OF CROHNS DISEASE
V. Andersen1,2,* on behalf of EPIC-IBD Study Investigators
1
Organ Center, SHS Aabenraa, Aabenraa, 2Institute of Regional Health Research,
University of Southern Denmark, Odense, Denmark
INTRODUCTION: Prospective studies on smoking and the risk of Crohns
disease (CD) in the general population are limited.
AIMS & METHODS: We aimed to conduct a cohort study of both men and
women investigating smoking and the development of CD in the EPIC-IBD
Study. In total 401,326 participants, aged 30-74 years, were recruited from 12
regions in 8 countries in Europe between 1991 and 1998. Baseline questionnaires
recorded data on smoking status and the number of cigarettes. The cohort was
monitored until at least June 2004 to identify participants who developed CD.
Each case was matched with four controls (age at recruitment, gender, centre and
recruitment date) and odds ratios (ORs) calculated using conditional logistic
regression.
RESULTS: In total, 110 participants developed incident CD (73% women, mean
age at diagnosis 55.7, SD 11.1 years) after a median follow-up of 5.4 years
(range 1.5-14.3 years). Current smoking at recruitment was associated with an
increased odds of CD (OR 1.95, 95% CI 1.14-3.34) compared to non-smoking, but not former smoking (1.23, 95% CI 0.71-2.12). There was some evidence of a dose-response with an increasing number of cigarettes (P trend 1.28,
95% CI 0.96-1.63, p 0.05), with for those smoking 420/day reporting an
OR 2.34 (95% CI 0.90-6.12, p 0.08). Similarly also for a duration effect
with an association with current smoking at the time of recruitment for those
diagnoses more than 5 years after recruitment (OR 2.13, 95% CI 1.09-4.17),
but none for those diagnosed within 5 years of recruitment. Ileal disease only was
associated with smoking (OR 3.02 95% CI 1.11-8.20), but not colonic involvement only (OR 1.02, 95% CI 0.35-2.98).
CONCLUSION: The positive associations with smoking help to confer a causal
link with CD due to the prospective collection of data and some evidence of a
dose response. Further work should elucidate the biological mechanisms for
these associations.
Disclosure of Interest: V. Andersen Consultancy for: Janssen & Merck.

A518
P1417 DISTURBED
PARACELLULAR
MOVEMENT
PHOSPHATIDYLCHOLINE TO INTESTINAL MUCUS
PREDISPOSES THE DEVELOPMENT OF ULCERATIVE COLITIS

United European Gastroenterology Journal 2(1S)


OF

W. Stremmel1,*, S. Staffer1, M. Schneider2, H. Gan-Schreier1, W. Chamulitrat1,


A. Gauss1, H. Wolburg3, M. Bach4, T. Efferth2
1
Department of Internal Medicine IV, University Clinics of Heidelberg,
Heidelberg, 2Dept. of Pharmaceutical Biology, Insitute of Pharmacy and
Biochemistry, Mainz, 3Dept. of Pathology and Neuropathology, University
Medical School of Tuebingen, Tuebingen, 4Dept. of Physics, Kirchhoff Institute of
Physica, Heidelberg, Germany
Contact E-mail Address: wolfgang.stremmel@med.uni-heidelberg.de
INTRODUCTION: Phosphatidylcholine (PC) in intestinal mucus establishes a
hydrophobic barrier against the colonic microbiota. In ulcerative colitis (UC)
intrinsic low mucus PC concentration may result from disturbed PC translocation into mucus.
AIMS & METHODS: Elucidation of the mechanism of PC translocation across
the mucosa and its disturbance in UC. Apical PC translocation was examined in
CaCo2 cells plated on transwell tissue culture dishes under various conditions.
Mucus PC recovery was also evaluated in genetic UC mice models with intestinal
deletion of kindlin1 and 2 as well as in mucosa specimens of patients with UC,
Crohns disease and controls.
RESULTS: In intestinal mucosa derived CaCo2 cells we demonstrate that out of
various phospholipids only PC translocates via paracellular movement across
lateral tight junctions (TJ) to the apical (mucus) compartment driven by stepwise
negative charge generation from TJ to mucins. Driving force is CFTR mediated
HCO3 secretion and binding to membrane localized mucin3. The efficacy of
apical PC movement increases from 4.7  0.6 % to 8.0  0.9 % in presence of
mucin1 or 2. PC is basally presented as complex with apolipoprotein which itself
is not apically translocated. In in vivo mouse models with disrupted TJ (intestinally deleted kindlin1 and 2), apical PC secretion into the ileal lumen is by 470 %
reduced with consequent low mucus PC concentration. It preceded the development of ulcerative colitis. This was prevented by therapeutic supplementation of
orally applied PC. Finally, mucosa specimens of patients with ulcerative colitis
revealed disturbed TJ with suppression of paracellular luminal PC movement
determined by immunofluorescence microscopy.
CONCLUSION: Disturbance of the TJ barrier results in impaired apical PC
secretion and, thus, loss of hydrophobic protection which is of pathogenetic
relevance for development of ulcerative colitis.
Disclosure of Interest: None declared
P1418 MULTIGENE ANALYSIS UNVEILS HELPER T CELL-RELATED
GENES EXPRESSION IN INTESTINAL MUCOSA THAT
CORRELATES WITH ENDOSCOPIC SEVERITY IN ULCERATIVE
COLITIS
Y. Iboshi1,2,*, K. Nakamura2, N. Harada1,3, M. Nakamuta1,3, T. Iwasa2,
K. Fukaura2, E. Ihara2, R. Takayanagi2
1
Clinical Research Center, Kyushu Medical Center, 2Department of Medicine and
Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University,
3
Department of Gastroenterology, Kyushu Medical Center, Fukuoka, Japan
Contact E-mail Address: yoichiroiboshi@gmail.com
INTRODUCTION: Helper T cells (Th) and their related cytokines have validated roles in mediating gut inflammation in inflammatory bowel diseases such
as ulcerative colitis (UC). Although anti-TNF therapy has been shown highly
effective in a subset of patients with UC, specific anti-cytokine therapy according
to tissue cytokine expression may still be warranted. Efforts to date to examine
the relation between mucosal expression of immune mediators and disease severity in UC have yielded inconsistent and inconclusive results, possibly partly due
to the common practice of single-marker analyses that are insensitive to the
interaction of different molecules and are susceptible to large between-sample
variation. We hypothesized that joint expression of important immune molecules, which is unidentifiable by univariate analysis, may significantly correlate
with disease severity, as we have previously reported a similar method for differentiating UC from Crohns disease (reference 1).
AIMS & METHODS: 47 patients with UC underwent colonoscopy and were
assessed with Rachmilewitz endoscopic index (REI), which quantifies mucosal
damage. Biopsy samples were obtained from inflamed (REI 3-12, n 40) and
noninflamed (REI53, n 47) colonic mucosae and examined for mRNA expression of cytokines and transcription factors related to Th1 (IFN-, IL-12p35, IL12p40, T-bet, and TNF-), Th2 (IL-4, IL-13, IL-33, and GATA3), Th17 (IL17A, IL-17F, IL-23p19, IL-21, IL-22, IL-6, and RORC) and regulatory T cells
(TGF- and Foxp3) by quantitative PCR. Univariate and multivariate analyses
were performed to identify expression pattern that paralleled the endoscopic
severity.
RESULTS: Although 16 of 18 targets were upregulated in inflamed mucosae
compared with noninflamed mucosae, none of the targets examined was univariately correlated with REI in the inflamed mucosae, which showed large expression variation between samples. Multiple regression analysis with stepwise
selection, however, identified a significant expression pattern predictive of REI
(p 0.0009, RSq 0.443, RMSE 2.0104), consisting of IL-17A, IL-17F, IL-21,
IL-22 and Foxp3. In this model IL-17A (positive, p 0.0002) and IL-17F (negative, P50.0001) were the most influential parameters in predicting REI, where
IL-21 (negative, p 0.0139) and IL-22 (positive, p 0.0105) were also significant
parameters. A simplified version of this model, IL17A/IL-17F ratio, substantially
correlated with REI ( 0.5186, p 0.0006). Markers such as IL-13, IFN-,
TNF- and etc. did not serve as significant parameters in any useful REI-predictive model.

CONCLUSION: IL-17A/IL-17F expression ratio in inflamed mucosae significantly paralleled the endoscopic severity in UC. Our findings indicate that IL17A and IL-17F might have different roles in mucosal inflammation and that
they might be of equal or even higher importance to other key inflammatory
mediators in exacerbation of UC.
REFERENCES
1) Iboshi Y, et al. Multigene analysis unveils distinctive expression profiles of
helper T-cell-related genes in the intestinal mucosa that discriminate between
ulcerative colitis and Crohns disease. Inflamm Bowel Dis 2014.
Disclosure of Interest: None declared
P1419 IS HOSPITALIZATION PREDICTING THE DISEASE COURSE IN
CROHNS DISEASE? PREVALENCE AND PREDICTORS OF
HOSPITALIZATION AND RE-HOSPITALIZATION IN CROHNS
DISEASE IN A POPULATION BASED INCEPTION COHORT
BETWEEN 2000-2012
P.A. Golovics1,*, M. Mandel1, B.D. Lovasz1, Z. Vegh1, I. Szita2, L.S. Kiss1,
M. Balogh3, A. Mohas1, B. Szilagyi1, T. Pandur2, L. Lakatos2, P.L. Lakatos1
1
1st Department of Medicine, Semmelweis University, Budapest, 2Department of
Medicine, Csolnoky F. Province Hospital, Veszprem, 3Department of Medicine,
Grof Eszterhazy Hospital, Papa, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: Limited data are available on the hospitalization rates in
population-based studies.
AIMS & METHODS: Since this is a very important outcome measure, the aim
of this study was to analyze prospectively if early hospitalization is associated
with the later disease course as well as to determine the prevalence and predictors
of hospitalization and re-hospitalization in a population based inception cohort
in the Veszprem province database between 2000 and 2012. Data of 304 incident
CD patients diagnosed between January 1, 2000 and December 31, 2010 were
analyzed (mean age at diagnosis: 32.2; SD: 15.4 years). Both in- and outpatient
records were collected and comprehensively reviewed.
RESULTS: Probabilities of first hospitalization and first re-hospitalization were
54.9%, 72% 76% and 22.8%, 34%, 52.3% after 1, 2 and 5 years of follow-up in
Kaplan-Meier analysis. Main reasons for hospitalization in the first year were
diagnostic procedures (48.5%), IBD related surgery (29.9%) and disease activity
(14.3%). Non-inflammatory disease behavior at diagnosis (HR: 1.41, 95%CI:
1.41-1.89, p 0.02) was the only factor significantly associated with time to
hospitalization while both non-inflammatory disease behavior at diagnosis
(HR: 1.92, 95%CI: 1.35-2.74, p50.001) and disease behavior change (HR:
1.89, 95%CI: 1.27-2.81, p 0.002) were associated with time to first re-hospitalization in multiple Cox-regression analysis. Early hospitalization (within the
year of diagnosis) was associated with age at onset (p 0.002), non-inflammatory
disease behavior at diagnosis (OR: 2.67, p50.001), internal fistulizing disease
(OR: 2.02, p 0.04) and it was predictive for need for immunosuppressives (OR:
1.74, p 0.018) and need for surgery/multiple surgeries (OR: 2.63, p 0.018 and
OR: 2.54, p 0.005) during the disease course.
CONCLUSION: Early hospitalization was associated with clinically significant
outcomes (need for immunosuppressives and surgery). Hospitalization and rehospitalization rates are still high in this population-based cohort. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive
factors for both hospitalization and re-hospitalization.
Disclosure of Interest: None declared
P1420 HOSPITALIZATION RATE BEFORE AND AFTER ANTI-TNF
THERAPY: HOSPITALIZATION RATES ARE ASSOCIATED WITH
TIME TO ANTI-TNF THERAPY
P.A. Golovics1,*, A. Balint2, M. Mandel1, Z. Vegh1, A. Mohas1, B. Szilagyi1,
A. Szabo1, Z. Kurti1, L.S. Kiss1, K.B. Gecse1, B.D. Lovasz1, K. Farkas2,
T. Molnar2, P.L. Lakatos1
1
1st Department of Medicine, Semmelweis University, Budapest, 21st Department
of Medicine, University of Szeged, Szeged, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: Hospitalization is an important outcome measure and a
major driver of costs in patients with IBD.
AIMS & METHODS: Our aim was to analyze prospectively the prevalence and
predictors of hospitalization and re-hospitalization before and after anti-TNF
therapy. Data of 194 consecutive IBD (152 CD, 42 UC) patients were analyzed
(male/female: 88/106, median age at diagnosis: 24.0, IQR: 19-30 years, duration:
8, IQR: 8-12.5 years) in whom anti-TNF therapy was started after January 1,
2009. Total follow-up was 1874 patient-years and 474 patient-years with antiTNF exposure. Both in- and outpatient records were collected and comprehensively reviewed.
RESULTS: The hospitalization rate in the 2 years preceding anti-TNF therapy
was significantly higher compared to the hospitalization rate during anti-TNF
therapy (61.6/100 patient-years vs. 43.2/100 anti-TNF exposed patient-years,
OR: 0.64, 95%CI 0.43-0.95, p 0.03). The risk for hospitalization decreased
only in CD (OR: 0.57, 95%CI 0.36-0.90, p 0.02), but not UC In addition,
there was an association with disease duration, the risk of hospitalization
decreased in CD patients with early (within 3-years from diagnosis, p50.001),
but late anti-TNFs exposure. In a logistic regression analysis complicated disease
behavior (p 0.03) concomitant AZA (p 0.02) use but not anti-TNF type,
gender, perianal disease or previous surgeries were associated with the risk of
hospitalization during anti-TNF therapy.
CONCLUSION: Hospitalization rate decreased significantly in this referral CD
but not UC cohort after the introduction of anti-TNF therapy and it was

A519

United European Gastroenterology Journal 2(1S)


associated to time to anti-TNF therapy. Complicated disease phenotype and
concomitant AZA use were additional factors defining the risk of hospitalization.
Disclosure of Interest: None declared
P1421 PREVALENCE OF DYSLIPIDEMIA IN INFLAMMATORY BOWEL
DISEASE
S.R. Fernandes1,*, P. Sousa1, M. Moura1, L.A. Correia1, P. Moura Santos1,
A. Valente1, A.R. Goncalves1, C. Baldaia1, J. Velosa1
1
Gastrenterologia e Hepatologia, Hospital Santa Maria - Centro Hospitalar Lisboa
Norte, Lisboa, Portugal
Contact E-mail Address: Samuelrmfernandes@gmail.com
INTRODUCTION: The risk of venous thromboembolic events in inflammatory
bowel disease (IBD) is increased (relative risk 2.5). However, the incidence of
cardiovascular and cerebrovascular events is only modestly elevated (relative risk
1.19). In this subgroup, a disorder of lipid metabolism mediated by pro-inflammatory cytokines may trigger an accelerated atherogenic process.
AIMS & METHODS: To determine the prevalence of dyslipidemia in IBD. We
retrospectively analysed patients with Crohns disease (CD) and Ulcerative
Colitis (UC) and determined the lipid profile [total cholesterol (TC), triglycerides
(Tg), LDL-cholesterol (LDL) and HDL cholesterol (HDL)], endoscopic activity
and comorbidities [chronic kidney disease (CKD) and alteration of glucose metabolism (AGM)]. Dyslipidemia was defined by TC4 190 mg/dl, Tg4 160 mg/dl,
LDL4115 mg/dL and HDL5 40/45 mg/dl (men/women) and CKD and AGM
by 2 consecutive values of creatinine4 1.0 mg/dl and/or glucose4 100 mg/dl. We
used samples from several portuguese Dyslipidemia prevalence studies
(VALSIM, BECEL and ALTO-MAR - 34522 individuals) as a control group.
RESULTS: We evaluated 478 patients, 282 women (59 %), mean age 44.0
years16.2 years with CD (67.6 %) and UC (32.4 %). The prevalence of CKD
and AGM was 23.4% and 23.7%. We assessed mean levels of TC (176.4  41.8
mg/dl), Tg (111.1  58.0 mg/dl), LDL (97.9  35.3 mg/dL) and HDL (54.6 
18.3 mg/dl). In UC, TC and LDL were higher and Tg were lower compared to
CD (p50.02). The overall prevalence of dyslipidemia among patients was 58.6%
(61.9% in UC and 57.0% in CD). Endoscopic activity was associated with higher
Tg and lower LDL levels. Only HDL levels were significantly lower compared to
the control group (27.3 % versus 12.8%).
CONCLUSION: In our series, despite a high prevalence of dyslipidemia, levels
did not reach the high values reported in the control group. However, the prevalence of HDL-dyslipidaemia was significantly higher. In IBD the pro-inflammatory state is associated with increased phospholipase A2 and decreased
lipoprotein lipase activity, both implicated in decreased levels of HDL. Given
the recognized anti-inflammatory and anti-atherogenic role of HDL, their compromise may have na influence on the progression of IBD.
Disclosure of Interest: None declared
P1422 INCREASE OF INFLAMMATORY BOWEL DISEASE INCIDENCE
IN TEENAGERS IN A PROSPECTIVE POPULATION-BASED STUDY
DURING A 21-YEAR PERIOD (1988-2008)
S. Ghione1,*, H. Sarter2, L. Armengol-Debeir3, M. Fumery4, G. Savoye3,
D. Ley1, C. Spyckerelle5, O. Mouterde6, D. Djeddi7, L. Dauchet2, J.F. Colombel8, L. Peyrin-Biroulet9, D. Turck1, C. Gower-Rousseau2,2 on behalf
of Epimad Group
1
Paediatric Clinic, 2Epidemiology, UNIVERSITY AND HOSPITAL LILLE,
Lille, 3Gastroenterology, UNIVERSITY AND HOSPITAL, Rouen,
4
Gastroenterology, UNIVERSITY AND HOSPITAL, Amiens, 5Paediatric Clinic,
Catholic University, Lille, 6Paediatric Clinic, UNIVERSITY AND HOSPITAL,
Rouen, 7Paediatric Clinic, UNIVERSITY AND HOSPITAL, Amiens, France,
8
Gastroenterology, Mount Sinai Hospital, New York City, United States,
9
Gastroenterology, UNIVERSITY AND HOSPITAL, Nancy, France
Contact E-mail Address: corinne.gower@gmail.com
INTRODUCTION: Few data are available on recent temporal trends in the
incidence of paediatric-onset inflammatory bowel disease (IBD) in industrialized
countries.
AIMS & METHODS: The aim of this study was to assess the change in incidence
and location at diagnosis of paediatric-onset IBD during a 21-year period.
Patients & Methods: Paediatric-onset IBD was defined by an age at diagnosis
 17 years. Data at diagnosis were extracted from the population-based IBD
study in Northern France (Epimad Registry) between 1988 and 2008. Age groups
and digestive location at IBD diagnosis were defined according to the Paris (1)
classification with age: 510 yrs or  10 yrs and location as follows: 1) for CD:
pure small bowel involvement (L1); pure colonic involvement (L2) or ileocolonic
involvement (L3); 2) for UC: proctitis (E1); left sided colitis (E2); extensive colitis
(E3); pancolitis (E4).
RESULTS: During this 21-year period, 1147 incident paediatric-onset IBD cases
were recorded (8% of all IBD) including 846 CD, 271 UC and 30 IBD unclassified (IBDU) cases. Median age at diagnosis was not significantly different in CD
(14.5 years [Q1 11.9-Q3 16.1]) and UC (14.1 years [11.0-16.0]) and did not
change over time. There was significantly more males in CD than in UC (53.4%
vs 45.0%; p 0.02). Median time between onset of symptoms and IBD diagnosis
was stable over time at 3 months [1-6]. Mean incidence was 4.0/105 for IBD as a
whole (3.0 for CD, 0.9 for UC and 0.1 for IBDU). During this 21-year period a
dramatic increase of both CD and UC incidences was observed in teenagers [1016 years]: for CD from 4.3 in 1988-90 to 9.6/105 in 2006-2008 (123%; p510-3)
and for UC, from 1.6 to 2.9/105 (81%; p510-3) in both genders. Digestive
location did not change over time in both CD and UC; for CD L1 12.2%,
L2 14.5% and L3 73.3% and for UC E1 31.1%, E2 25.4%, E3 10.5%
and E4 33%.

CONCLUSION: In this large population-based study the incidence of both CD


and UC dramatically increased in teenagers during a 21-year period without
modification of neither age, location at diagnosis nor time between onset of
symptoms and diagnosis. This suggests that a strong environmental factor predisposing to IBD is at work in this population.
REFERENCES
(1) Levine et al. Inflamm Bowel Dis 2011.
Disclosure of Interest: S. Ghione: None declared, H. Sarter: None declared, L.
Armengol-Debeir: None declared, M. Fumery: None declared, G. Savoye: None
declared, D. Ley: None declared, C. Spyckerelle: None declared, O. Mouterde:
None declared, D. Djeddi: None declared, L. Dauchet: None declared, J.-F.
Colombel: None declared, L. Peyrin-Biroulet: None declared, D. Turck: None
declared, C. Gower-Rousseau Lecture fee(s) from: MSD, Ferring.
P1423 OBESITY INFLUENCES THE COURSE OF CROHNS DISEASESINGLE CENTRE RETROSPECTIVE ANALYSIS
S. V. Venkatachalapathy1,*, V.E. Sayer1, G. Nicola1, A. Salerno1, P. Dubois1,
G. Chung-Faye1, B.H. Hayee1
1
Gastroenterology, Kings College Hospital, London, United Kingdom
Contact E-mail Address: s.venkatachalapathy@nhs.net
INTRODUCTION: Despite the widespread perception of Crohns disease (CD)
as a wasting disorder there is a well-recognised sub-population of obese patients
with the disease (1). Notwithstanding the possibility of a pathogenic link, obesity
may influence the severity and phenotype of CD.
AIMS & METHODS: We conducted a retrospective analysis of our Institutions
electronic patient record to stratify and compare CD patients by body mass index
(BMI) at diagnosis, with regard to their disease characteristics, medication use
and outcomes. Smoking status recorded on the hospital database was validated
by survey with general practitioners. All statistical analysis was conducted using
GraphPad Prism 6.0. Mann-Whittney U test and Kruskal-Wallis with Dunn
post-test were used when the data was not normally distributed. Fisher-exact
test was used for contigency tables, one way ANOVA and t-test if the data
was normally distributed.
RESULTS: Reliable data was available for 282 patients with CD (130 female,
age 43.6  14.3y). At diagnosis, BMI 35 was recorded in n 20 (7.09%), 30 in
43 (15.2%), 25-29.9 in 68 (24.1%), 24.9-18 in 144 (51.06%) and 518 in 7 (2.4%).
The proportion of smokers did not differ significantly in each group. Patients
with BMI430 were older (p50.0001) compared to the other groups. Rates of
operative intervention per patient year were slightly higher in BMI30 group
compared to the normal BMI group (0.08 vs 0.04, p 0.007). The median time to
surgery was significantly shorter in BMI35 (11.5 months) and BMI 30
(18months) compared to the other groups (p 0.053). The median time to
anti- TNF therapy in the morbidly obese group and the obese groups were
11.5 and 14 months respectively compared to 48 months in BMI 29.9-25.36
months in the normal BMI, and 12 months in BMI518 group respectively
(p 0.008). Other comparators are shown in the table below.
Table: Disease characteristics across different BMI groups.
Disease
Characteristics

BMI 35 BMI30

Average age
Female: Male

49.212.1 51.413.1 47.613.1


14:6
23:20
35:33

39.713.1
82:62

42.221.1 50.0001
5:2
0.001

Ileal disease
Colonic disease
Ileo colonic disease
B1 inflammatory
B2 stricturing
B3 fistulizing

8/20
3/20
9/20
11/18
6/18
1/18

37/128
29/128
62/128
72/128
33/128
23/128

2/7
2/7
3/7
3/6
3/6
0/6

10/63
32/63
21/63
7/60
32/60
21/60

Normal
BMI 29.9-25 BMI 24.9-18 BMI 518 P value

28/66
16/66
23/66
40/68
18/68
10/68

0.08

0.61

CONCLUSION: Obesity is a common phenomenon in this representative cohort


of patients with CD with 22.3% having BMI430 nearing the national average
of 26%. Obesity is associated with slightly increased operative intervention per
patient year. Our data also imply a more aggressive inflammatory phenotype in
terms of requiring surgery and biologic therapy significantly earlier in the natural
history of disease.
REFERENCES
Long MD, Crandall WV, Leibowitz IH, et al. Prevalence and epidemiology of
overweight and obesity in children with inflammatory bowel disease. Inflamm
Bowel Dis 2010 Dec 17.
Disclosure of Interest: None declared
P1424 VITAMIN D INFLUENCES HEALTH RELATED QUALITY OF
LIFE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES
T. Hlavaty1,*, A. Krajcovicova1, T. Koller1, J. Toth1, M. Nevidanska1,
M. Huorka1, J. Payer2
1
Dept. Gastroenterology and Hepatology, 2University hospital Bratislava,
Bratislava, Slovakia
Contact E-mail Address: tibor.hlavaty2@gmail.com
INTRODUCTION: Several lines of evidence indicate that vitamin D (VD) plays
an important role in the pathogenesis of inflammatory bowel diseases (IBD).
AIMS & METHODS: We investigated the effect of VD concentrations and VD
supplementation on health related quality of life in Crohns disease (CD) and
ulcerative colitis (UC) patients. A cohort of 220 IBD patients (141 CD and 79
UC) was followed-up at a tertiary IBD centre. A subgroup of the cohort (n 26)

A520
took VD supplements for 43 months. Health related quality of life was assessed
using the short IBD questionnaire (sIBDQ). VD serum concentration and sIBDQ
score were assessed during summer/autumn period and winter/spring period.
RESULTS: During summer/autumn and winter/spring period, 28% and 42% of
IBD patients were VD-deficient (520 ng/ml), respectively. In winter/spring
period, there was a significant correlation between sIBDQ score and VD serum
concentration in UC patients (r 0.35, p 0.02), with a trend towards significance in CD patients (r 0.17, p 0.06). In winter/spring period, VD-insufficient
patients (530 ng/ml) had a significantly lower mean sIBDQ score than VDsufficient patients; this was true of both UC (48.32.3 vs. 56.73.4, p 0.04)
and CD (55.71.25 vs. 60.82.14, p 0.04) patients. In all analysed scenarios
(UC/CD, summer/autumn period and winter/spring period), health related quality of life was the highest in patients with VD serum concentrations of 5059 ng/
ml. Supplementation with a median of 800 IU/day VD day did not influence VD
serum concentration nor the sIBDQ score.
CONCLUSION: VD serum concentration correlated with health related quality
of life in UC and CD patients during winter/spring period. Supplementation with
currently recommended doses of VD did not influence health related quality of
life.
Disclosure of Interest: None declared
P1425 SMOKING AND USE OF ANTIBIOTICS DURING PREGNANCY
ARE RISK FACTORS FOR INFLAMMATORY BOWEL DISEASE
T.M. Blomster1,*, O.-P. Koivurova1, R. Koskela1, K.-H. Herzig2, J. Auvinen3,
S. Niemela1, M. Koiranen3, S. Keinanen-Kiukaanniemi3, J. Ronkainen4
1
Department of Internal Medicine, Institute of Clinical Medicine, University of
Oulu, 2 Division of Physiology and Biocenter of Oulu Faculty of Medicine, Institute
of Biomedicine, University of Oulu, 3Institute of Health Sciences, University of
Oulu, Oulu, 4Primary Health Care Center, Tornio, Finland
Contact E-mail Address: timo.blomster@ppshp.fi
INTRODUCTION: The pathogenesis of inflammatory bowel disease (IBD) is
unclear. Environmental factors in combination with genetic predisposition may
play a role. The aim of this study was to analyse prenatal risk factors for IBD in a
well described birth cohort from Northern Finland.
AIMS & METHODS: The prospectively collected Northern Finland Birth
Cohort 1966 (NFBC 1966) is a longitudinal research program to promote
health and well-being of the population (http://www.oulu.fi/nfbc/). The population is comprised of mothers living in the two northernmost provinces of
Finland, Oulu and Lapland with expected dates of delivery between Jan 1st Dec 31st, 1966 (12 068 mothers, 12 231 children, 96.3% of all births during 1966
in that area). Information about family history, social relationships, environment, mothers health habits and clinical parameters were collected from antenatal clinics, hospital registers and by postal questionnaires. Between years 2012
and 2014, at the age of 46 years, a large health examination was performed
including both questionnaires and clinical examination, including questions
about physicians diagnosis of IBD. 6852 subjects (66%) answered for the
postal questionnaires. Data were analyzed by chi square test, Fishers exact test
and counting relative risks (RR).
RESULTS: Data were available from 6685 individuals, of whom 175 (2.6%)
reported physicians diagnosis of IBD, 88/2957 male and 87/3553 women.
Maternal age, gestation age, gestation weight, maternal comorbidities, parity,
number of siblings, household farm animals or pets, living in an urban area
and social class were not associated with IBD of children until 46 years of age.
However, consumption of antibiotics during pregnancy [(23/549 vs. 140/5375)
RR 1.6 (1.0-2.4), p 0.041], smoking during pregnancy [continued, 37/892 RR
1.7 (1.2-2.5) vs. stopped, 8/406 RR 0.7 (0.4-1.5) vs. never smoked 128/5247 RR
0.7 (0.5-1.0), p 0.0033] and living in the most northern part of Finland [above
the Arctic Circle 19/419 RR 1.7 (1.1-2.8) vs. southern Lapland 45/1943 RR 0.8
(0.6-1.1) vs. Oulu district 111/4148 RR 1.0 (0.7-1.3), p 0.0188] were associated
with IBD.
CONCLUSION: Smoking and consumption of antibiotics during pregnancy and
mothers living above the Arctic Circle were risk factors for IBD until the age of
46.
Disclosure of Interest: None declared
P1426 CLINICAL AND ENDOSCOPIC FEATURES OF RESPONDERS
AND NON-RESPONDERS TO THERAPEUTIC DEPLETION OF
MYELOID LINEAGE LEUCOCYTES IN PATIENTS WITH
ULCERATIVE COLITIS: WHY THIS NON-PHARMACOLOGICAL
TREATMENT OPTION IS FAVOURED BY PATIENTS?
T. Tanaka1,1,*, S. Sugiyama1, H. Goishi 1, T. Kajihara1, M. Akagi 1, T. Miura1
1
Department of Gastroenterology, Akitsu Prefectural Hospital, Hiroshima, Japan
INTRODUCTION: Patients with active inflammatory bowel disease have elevated and activated myeloid lineage leucocytes, notably the CD14 ()CD16 ()
monocyte phenotype, which is a major source of tumour necrosis factor- (Belge
KU, et al. J Immunol 2002). Hence selective depletion of these leucocytes by
granulocyte/monocyte adsorption (GMA) with an Adacolumn is expected to
alleviate inflammation and promote remission or at least enhance drug efficacy.
However, studies in ulcerative colitis (UC) reported contrasting efficacy outcomes, from an 85% (Cohen RD. Gastroenterology 2005) to a statistically insignificant level (Sands, et al. Gastroenterology 2008). Patients demographic
variables in the aforementioned studies were very different.
AIMS & METHODS: In 143 consecutive UC patients, we were interested to
identify clinical and endoscopic features, which could mark a patient as a responder or otherwise as a non-responder to GMA. Seventy-three patients were steroid
naive, and 70 were steroid dependent. Patients received up to an 11 GMA sessions over 10 weeks. At entry and week 12, patients were clinically and

United European Gastroenterology Journal 2(1S)


endoscopically evaluated according to Rachmilewitz, allowing each patient to
serve as her or his own control. Clinical activity index (CAI) 4 at week 12
was defined as response to GMA. Additionally, biopsies from colonoscopically
detectable inflamed mucosa were processed to see the impact of GMA on leucocytes within the mucosa.
RESULTS: At entry the average CAI was 12.8, range 10-17. Ninety-two of the
143 patients (64.3%) responded to GMA, 52 of 73 steroid na ve patients (71.2%)
and 40 of 70 steroid dependent patients (57.1%). On average remission was
sustained for 8.6 months in steroid na ve patients and for 10.4 months in steroid
dependent cohort. Upon relapse, the majority of patients responded well to a
second course of GMA. Over 1200 biopsies were processed. Infiltrating leucocytes were overwhelmingly neutrophils and monocytes/macrophages. GMA was
associated with a marked reduction of infiltrating leucocytes. Patients who had
extensive deep UC lesions together with near total loss of the mucosal tissue at
the affected sites were identified as non-responders. Patients with the first UC
episode were identified as the best responders (100%) followed by steroid naive
patients. Additionally, a short duration of active UC prior to GMA marked a
patient as a likely responder. No GMA related serious adverse event was
observed.
CONCLUSION: Depleting elevated myeloid lineage leucocytes by GMA should
have significant efficacy in patients with UC, but before the disease has become
very severe with deep ulcers and extensive loss of the mucosal tissue, and when
the disease does not respond well to pharmacological interventions. Most notably, first episode and steroid na ve cases respond well to GMA and attain a
favourable future clinical course by avoiding medications like corticosteroids
from the start. Likewise, GMA should be applied immediately after a relapse.
Generally, GMA is very much favoured by patients for its safety profile and for
being a non-drug therapeutic intervention. Accordingly, patient compliance is
always good.
Disclosure of Interest: None declared
P1427 THE RISK OF SKIN CANCER IN PATIENTS TREATED FOR
INFLAMMATORY BOWEL DISEASES IN THE PROVINCE OF
QUEBEC
U. Kopylov1,*, M. Vutcovici2, A. Kezouh2, L. Azoulay2, E.G. Seidman1,
A. Bitton1, W. Afif1
1
Gastroenterology, McGill University Health Center, 2Centre for Clinical
Epidemiology, Lady Davis Institute for Medical Research, Jewish General
Hospital, Montreal, Canada
Contact E-mail Address: ukopylov@gmail.com
INTRODUCTION: Treatment of inflammatory bowel disease (IBD) with immunosuppressive medications has been associated with an increased risk of developing melanoma and non-melanoma skin cancer.
AIMS & METHODS: The aim of this study was to evaluate the risk of melanoma and non-melanoma skin cancer (NMSC) associated with immunomodulator and anti-TNF- medications in IBD patients. Using provincial health
insurance databases (RAMQ/MedECHO), a nested-case control analysis was
conducted within a cohort of patients diagnosed with IBD (Crohns disease
[CD] or ulcerative colitis [UC]) between 1996 and 2009. Cohort entry was defined
as the date when patients met a strict IBD definition (i.e. at least one hospitalization with a primary diagnosis of Crohns disease (CD) or ulcerative colitis (UC)
or four physician claims with the CD or UC diagnosis within a two-year period).
Patients were excluded if they had a diagnosis of any cancer prior to cohort entry
or within the first year from the inclusion, and if they had less than 1 year of
prescription coverage prior to inclusion in the cohort. Cases were patients newlydiagnosed with melanoma and NMSC during follow-up. For each case, up to 10
controls were randomly selected and matched on age, sex, and duration of disease. Conditional logistic regression was used to estimate odds ratios (ORs) with
95% confidence intervals (CIs) of melanoma and NMSC associated with ever use
of immunomodulators and anti-TNF-alpha- medications. Secondary analyses
considered duration of exposure and stratification by IBD type (CD vs UC). The
models were adjusted for history of IBD-related hospitalizations.
RESULTS: A total of 41,176 IBD patients were identified in the RAMQ/
MedECHO database; 19582 patients were eligible for inclusion in the study.
The mean age at inclusion was 42.5  19.3 years and 45.4% of the patients
were male. The mean duration of follow-up was 5.63.3 years and CD was
the primary diagnosis in 60.2% of the cases. Immunomodulators were utilized
in 25.4%, and anti-TNF- medications in 2% of the patients. A total of 102 cases
of melanoma were identified in the cohort. Neither immunomodulators (OR:
1.38, 95% CI- 0.82-2.31), nor anti-TNF-  medications (OR: 6.28, 95% CI0.59-60.79) were associated with an increased risk of melanoma. A total of 474
cases of NSMC were identified. Treatment with immunomodulators for  3
years was associated with a significantly increased risk of NSMC (OR: 1.78,
95% CI- 1.25-2.54) and this increased risk was seen in both CD and UC patients.
No cases of NMSC occurred in patients exclusively exposed to anti-TNF-
medications.
CONCLUSION: In a large provincial IBD cohort, treatment with immunomodulators for 3 years was associated with an increased risk of non-melanoma
skin cancer. No association was demonstrated between the risk of melanoma and
immunomodulator medications. Although no association between melanoma
and NMSC with anti-TNF- medications was identified, no firm conclusions
can be made given the small number of patients on these medications in the
cohort.
Disclosure of Interest: U. Kopylov: None declared, M. Vutcovici: None declared,
A. Kezouh: None declared, L. Azoulay: None declared, E. Seidman Other:
Speaker Bureau- Given Imaging, A. Bitton Other: Consultant, Advisory
Board: AbbVie, Janssen, Shire, Warner Chilcott, Takeda, Speaker: AbbVie,
Janssen, Shire, Warner Chilcott, Aptalis , W. Afif Other: Advisory Board
Member: Janssen Pharma and Abbvie.

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United European Gastroenterology Journal 2(1S)


P1428 INCIDENCE
AND
INITIAL
DISEASE
COURSE
INFLAMMATORY BOWEL DISEASES IN 2011 IN EUROPE AND
AUSTRALIA: RESULTS OF THE 2011 ECCO-EPICOM INCEPTION
COHORT

OF

Z. Vegh1,2,*, J. Burisch3, N. Pedersen3, I. Kaimakliotis4, D. Duricova5,


M. Bortlik5, S. Avnstrm6, K. Kofod Vinding6, J. Olsen7, K.R. Nielsen7,
K.H. Katsanos8, E. V. Tsianos8, L. Lakatos1, D. Schwartz9, S. Odes9,
G. Lupinacci10, A. De Padova11, L. Jonaitis12, L. Kupcinskas12, S. Turcan13,
O. Tighineanu14, I. Mihu14, L.F. Barros15, F. Magro16, D. Lazar17, A. Goldis17,
A. Fernandez18, V. Hernandez19, O. Niewiadomski20, S. Bell20, E. Langholz21,
P. Munkholm3, P.L. Lakatos2 on behalf of EpiCom group
1
Csolnoky Ferenc Hospital, Veszprem, 2Semmelweis University, Budapest,
Hungary, 3Herlev University Hospital, Copenhagen, Denmark, 4Private practice,
Nicosia, Cyprus, 5Charles University, Prague, Czech Republic, 6Amager Hospital,
Amager, Denmark, 7The National Hospital of the Faroe Islands, Torshavn, Faroe
Islands, 8University of Ioannina, Ioannina, Greece, 9Soroka Medical Center and
Ben-Gurion University of the Negev, Beer Sheva, Israel, 10Ospedale Maggiore di
Crema, Crema, 11Ospedale Morgagni -Pierantoni, Forli, Italy, 12Lithuanian
University of Health Sciences, Kaunas, Lithuania, 13State University of Medicine
and Pharmacy, 14Centre of Mother and Child, Chisinau, Moldova, Republic of,
15
Hospital de Vale de Sousa, 16Hospital de Sao Joao, Porto, Portugal, 17University
of Medicine Victor Babes, Timisoara, Romania, 18POVISA Hospital,
19
Complexo Hospitalario Universitario de Vigo, Vigo, Spain, 20St Vincents
Hospital, Melbourne, Victoria, Australia, 21Gentofte Hospital, Copenhagen,
Denmark
Contact E-mail Address: veghzsuzsi@gmail.com
INTRODUCTION: The aim of the present study was to validate the IBD
(inflammatory bowel diseases) incidence reported in the 2010 ECCO-EpiCom
(European Crohns and Colitis Organization - Epidemiological Committee)
inception cohort1 by including a second independent inception cohort from participating centers in 2011 and an Australian centre to investigate whether there is
a difference in the incidence of IBD between Eastern and Western European
countries and Australia.
AIMS & METHODS: Fourteen centers from 5 Eastern and 9 Western European
countries and one center from Australia participated in the ECCO-EpiCom 2011
inception cohort. Patients data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the web-based
EpiCom database, www.ecco-epicom.eu.
RESULTS: A total of 711 adult patients were diagnosed during the inclusion
year 2011, 178 (25%) from Eastern, 461 (65%) from Western Europe and 72
(10%) from Australia; 259 (37%) patients were diagnosed with Crohns disease,
380 (53%) with ulcerative colitis and 72 (10%) with IBD unclassified. The mean
annual incidence rate for IBD was 11.3/100,000 in Eastern Europe, 14.0/100,000
in Western Europe and 30.3/100,000 in Australia. Significantly more patients
were diagnosed with complicated disease at diagnosis in Eastern Europe compared to Western Europe (51% vs. 37%, p 0.03).
CONCLUSION: Incidence rates, disease phenotype and initial treatment characteristics in the 2011 ECCO-EpiCom cohort were not significantly different
from that reported in the 2010 cohort.
REFERENCES
1 Burisch J, Pedersen N, Cukovic-Cavka S, et al. East-West gradient in the
incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort. Gut 2013: 1-10.
Disclosure of Interest: None declared
P1429 EVALUATION
OF
ELECTROCARDIOGRAPHIC
ABNORMALITIES AND HEART RATE VARIABILITY IN
INFLAMMATORY BOWEL DISEASE PATIENTS WITH HOLTER
ECG
O. Yurekli1,*, S. Sar2, C. Sar3, S. Buyukask2, S. Sivri3, A.N. Aslan3,
A. Demirezer Bolat2, F.E. Akn2, O. Ersoy2
1
GAstroenterology, 2Ankara Ataturk Research and Teaching hospital, ankara,
Turkey, 3Cardiology, Ankara Ataturk Research and Teaching hospital, ankara,
Turkey
Contact E-mail Address: oykutayfur78@yahoo.com
INTRODUCTION: Electrocardiographic (ECG) abnormalities have been
described in inflammatory bowel disease (IBD) patients. Underlying chronic
inflammation, medicines used, nutritional deficiencies can cause many rhythm
disorders. Most commonly encountered rhythm disorders are atrial fibrillation
than less commonly supraventricular tachycardia, ventricular tachycardia and
atrioventricular block. Previous studies mostly used 12 lead normal surface
ECG and many rhythm disorders that can be detected only by holter ECG
were probably missed. This may caused underestimation of the prevalence of
arrhythmia in inflammatory disease patients.
AIMS & METHODS: 67 IBD patients aging between 18-65 years referring to
gastroenterology clinic between October 2013-March 2014 were included in this
study. Patients with previous history of coronary heart disease, patients with
heart failure or cardiac valve disease were excluded. Patients with thyroid hormone abnormalities were also excluded from the study. Physical examination and
baseline echocardiography were performed to search for evidence of organic
heart disease in cardiology clinic. Patients who do not have evidence of organic
heart disease were monitored by Holter ECG for 24 hours and results were
analyzed by using special computer software programs.
RESULTS: Of 67 patients 64.2 % were male. Mean age was 42.67 12.8 years;
mean body mass index was 25.14.39 kg /m2. 14 patients (20.9%) had Crohns
disease. 53 patients suffered from ulcerative colitis. Mean time from disease
diagnosis was 3.573.43 years. Only 12% of the patients had hypertension

while 17.9 % had diabetes. 35.8 % of the patients had active bowel disease at
the time of evaluation. Mean heart rate of the patients were 75.89.3beats/ min.
Arrhythmia was detected in 55.1 % of the patients. Mean number of supraventricular extrasystoles were 47.4217 and mean number of ventricular extrasystoles was 17.447.6. Patients with active IBD had higher minimum heart rate
(p 0.03) and significantly lower SD5, AVG, SDTF and SDVLF values. These
values are parameters used to calculate heart rate variability by the help of special
computer software programs. (p values: 0.01, 0.02, 0.03, 0.03 respectively).
Comparison of holter parameters between ulcerative colitis and Crohns disease
patients were also performed. SDANN5 (standard deviation of 5 min mean
values of RR) was found significantly lower in ulcerative colitis patients (120.3
38.4 vs 145.3 41.3, p:0.04)
CONCLUSION: Heart rate variability (HRV) was found to be significantly
decreased and minimum heart rate was found to be significantly increased in
active inflammatory bowel disease patients. Furthermore HRV was found to be
significantly lower in ulcerative colitis patients than in Crohns disease patients.
Decreases in HRV have been reported in many cardiologic and noncardiologic
diseases. In this study active IBD patients and patients with UC were found to
have autonomic dysfunction which is known to be associated with increased
cardiac morbidity and mortality. Various symptomatic and asymptomatic
rhythm disorders were detected by 24-hour holter suggesting that physicians
should be cautious about rhythm abnormalities in follow-up of these patients.
Disclosure of Interest: None declared
P1430 MULTI-COUNTRY,
CROSS-SECTIONAL
STUDY
TO
DETERMINE PATIENT-SPECIFIC AND GENERAL BELIEFS
TOWARDS MEDICATION AND THEIR TREATMENT ADHERENCE
TO SELECTED SYSTEMIC THERAPIES IN 6 CHRONIC IMMUNEMEDIATED INFLAMMATORY DISEASES (ALIGN)
P. Michetti1,*, J. Weinman2, U. Mrowietz3, J. Smolen4, D. Schremmer5,
N. Tundia6, N. Selenko-Gebauer7
1
La Source-Beaulieu, Lausanne, Switzerland, 2Kings Coll, London, United
Kingdom, 3Univ Schleswig-Holstein, Kiel, Germany, 4Med Univ, Vienna, Austria,
5
GKM, Munich, Germany, 6AbbVie, N. Chicago, United States, 7AbbVie, Zurich,
Switzerland
INTRODUCTION: Adherence to therapy is critical to achieve and sustain optimal outcomes in patients (pts) with immune-mediated inflammatory disease
(IMID). Pts beliefs about the necessity of treatment and potential adverse effects
could strongly influence adherence.
AIMS & METHODS: ALIGN was a multi-country cross-sectional study exploring pts beliefs, concerns, attitudes and adherence toward TNF inhibitors (TNFi)
and conventional therapies used alone or in combination across multiple IMIDs.
Adults age 18 y with rheumatoid arthritis (RA), ankylosing spondylitis (AS),
psoriatic arthritis (PsA), Crohns disease (CD), ulcerative colitis (UC) or psoriasis (PsO), receiving conventional therapy and/or disease-modifying antirheumatic drugs (including TNFi), were recruited. Pts completed validated
questionnaires, e.g., the Beliefs about Medicines Questionnaire (BMQ) and
short Morisky Medication Adherence Scale (MMAS-4). BMQ scores, MMAS4 scores and pts attitudes toward their medications are presented.
RESULTS: 7197 pts in 33 countries met eligibility criteria. Pts had RA (27.5%),
AS (11.3%), PsA (8.9%), CD (17.3%), UC (8.8%) or PsO (26.2%). Mean age
was 47.5 y (range, CD 38.0; RA 54.8). Mean disease duration was 11.7 y
(range, UC 8.1; PsO 18.7). The largest proportion of pts received conventional therapies (40.3%), followed by TNFi mono- (32.0%) and combination
therapy (27.7%). An attitudinal analysis of BMQ necessity and concern scores
revealed that most pts were either accepting (high necessity/low concern) or
ambivalent (high necessity/high concern) toward their medication irrespective
of disease or treatment. Adherence across diseases was generally higher in pts
receiving TNFi with or without conventional therapy (range of mean MMAS-4
scores, 3.4 3.7; 01 low, 23 medium, 4 high adherence), vs pts receiving
conventional mono- (2.6 3.3) or combination therapy (2.8 3.4). Across treatments, high adherence according to MMAS-4 was consistently lower for
ambivalent pts (46.1% 69.0%) vs accepting pts (55.8% 77.6%) according
to combined BMQ scores (Table).
Table. N (%) of Patients Accepting and Ambivalent Toward Their Medications
Who Were Adherent.
TNFi Conventional Combination
Therapy, n (%)

Monotherapy, n (%)
Conventional

TNFi

Conventional

TNFi

Accepting Ambivalent Accepting Ambivalent Accepting Ambivalent Accepting Ambivalent


(n 1347) (n 1151) (n 1251) (n 834) (n 900) (n 739) (n 1031) (n 786)
751 (55.8) 531 (46.1)
P50.0001

919 (73.5) 504 (60.4)


P50.0001

550 (61.1) 374 (50.6)


P50.0001

800 (77.6) 542 (69.0)


P50.0001

CONCLUSION: Compared with accepting pts, ambivalent pts appeared to


be less often highly adherent (MMAS-4 score 4), which could negatively affect
treatment efficacy. The high percentage of ambivalent pts reveals the need to
better explore concerns about medication and address erroneous beliefs regarding benefit-risk of treatments.
Disclosure of Interest: P. Michetti Financial support for research from: MSD AG
Switzerland, Lecture fee(s) from: MSD, UCB, Abbott, Consultancy for: MSD,
AbbVie, Abbott, UCB, Delenex, Vifor, Other: Expert testimony: Takeda Canada
(2005); Other: ECCO governing board membership and UEG Future Trends
Committee., J. Weinman Other: Employee: Atlantis Healthcare, U. Mrowietz

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United European Gastroenterology Journal 2(1S)

Financial support for research from: Abbott /AbbVie, Almirall-Hermal, Amgen,


BASF, Biogen Idec, Celgene, Centocor, Eli Lilly, Forward Pharma, Galderma,
Janssen, Leo Pharma, Medac, MSD, Miltenyi Biotech, Novartis, Pfizer, Teva,
VBL, Xenoport, Lecture fee(s) from: Abbott /AbbVie, Almirall-Hermal, Amgen,
BASF, Biogen Idec, Celgene, Centocor, Eli Lilly, Forward Pharma, Galderma,
Janssen, Leo Pharma, Medac, MSD, Miltenyi Biotech, Novartis, Pfizer, Teva,
VBL, Xenoport, Consultancy for: Abbott /AbbVie, Almirall-Hermal, Amgen,
BASF, Biogen Idec, Celgene, Centocor, Eli Lilly, Forward Pharma, Galderma,
Janssen, Leo Pharma, Medac, MSD, Miltenyi Biotech, Novartis, Pfizer, Teva,
VBL, Xenoport, J. Smolen Financial support for research from: Abbott/AbbVie,
D. Schremmer Other: Employee: GKM Gesellschaft fuer Therapieforschung
mbH., N. Tundia Shareholder of: AbbVie, Other: Employees: AbbVie, N.
Selenko-Gebauer Shareholder of: AbbVie, Other: Employees: AbbVie.
P1431 THE EFFECT OF INCREASING BODY MASS INDEX ON
CLINICAL OUTCOMES IN PATIENTS WITH CROHNS DISEASE
TREATED WITH INFLIXIMAB
P. Brown1,*, L. Warren2, T. Clark2, G. Dowson2, J. Hamlin2, V. Subramanian1
1
Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, St James
University hopsital, Universityof Leeds, 2Gastroenterology, St James University
Hospital, Leeds Teaching Hospital NHS Trust, Leeds, Leeds, United Kingdom
Contact E-mail Address: v.subramanian@leeds.ac.uk
INTRODUCTION: The incidence of obesity is increasing worldwide and there is
growing evidence that obesity is associated with low-grade background intestinal inflammation. The role of obesity in progressive inflammatory conditions
needs to be assessed and there is very little known about the effect of obesity on
outcomes in severe Crohns disease. Recent data seems to suggest that obesity is
associated with diminished responsiveness to biological agents in patients with
IBD (ref).
AIMS & METHODS: We aimed to examine the influence of obesity as measured
by BMI on the response to Infliximab in CD. A retrospective analysis was
performed on all patients identified from our CD registry, receiving Infliximab
for severe Crohns disease. The main variable of interest was BMI, assessed using
categorical and continuous scales. The outcomes of interest were 1) IBD related
flare (defined as increase in dose or steroid use or need for IBD related hospitalization or surgery), 2. Any IBD related surgery and 3) IBD related resectional
surgery. Kaplan Meier (KM) curves were used to compare survival curves for
each outcome of interest stratified according to the BMI strata (WHO criteria).
Additionally variables of interest were entered into a stepwise multivariate logistic regression analysis for each outcome of interest.
RESULTS: Overall, 388 (87.8%) patients met our predefined inclusion criteria,
with mean BMI of 24.1kg/m2 (/- 5.1). 22.2 % were classed overweight (BMI 2529.9) and 11.9% as obese (BMI 430). 232 (60.6%) patients had an IBD related
flare during mean follow-up of 33.5months (/-30.9). Of these 82 (21.4%)
required CD-related surgery, of which 39 (10.2%) required CD-related bowel
resection surgery. Being categorised as overweight (BMI: 25.0-29.9kg/m2)
increased the risk of a clinical flare (adjusted HR: 1.7, p 0.045) compared to
normal BMI (18.5-24.9kg/m2). However the risk of surgery (both all IBD-related
and resection surgery alone) decreased per unit increase of BMI on a continuous
scale (adjusted HR: 0.924, P5 0.001). Female sex increased the likelihood of CDrelated bowel resection surgery (adjusted HR: 3.5, p 0.001) as did disease phenotype (adjusted HR structuring or penetrating versus non-stricturing and nonpenetrating: 4.0, P50.001). KM curves did not show any differences in rates of
any of the outcomes of interest for the different BMI strata (based on the WHO
criteria), (log rank test p50.05).
CONCLUSION: In patients with severe CD on Infliximab, being classed as
overweight increased the risk of having an IBD related flare. This may however
reflect the variability in definition of an IBD related flare as this outcome
occurred in 60% of patients. Increasing BMI was associated with a decreased
risk of IBD related resectional surgery. The reasons for this could include better
nutritional reserve in these patients and physician reluctance to operate on
patients with higher BMI. The role of obesity in outcomes in CD needs further
validation in large prospective studies.
REFERENCES
Harper JW, Sinanan MN and Zisman TL. Increased body mass index is associated with earlier time to loss of response to infliximab in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19: 2118-2124.
Disclosure of Interest: None declared
P1432 PSYCHOMETRIC EVALUATION OF THE SIGNS
SYMPTOMS MODULES OF THE ULCERATIVE COLITIS
PATIENT-REPORTED OUTCOMES MEASURE (UC-PRO/SS)

AND

P.D. Higgins1,*, G. Harding2, D.L. Patrick3, D. Revicki2, W.-H. Chen2,


G. Globe4, H.N. Viswanathan4, K. Fitzgerald5, S. Trease5, D. Borie4,
B.G. Ortmeier4, N.K. Leidy2
1
University of Michigan Health System School of Public Health, Ann Arbor, MI,
2
Evidera, Bethesda, MD, 3University of Washington, Seattle, WA, 4Amgen Inc.,
Thousand Oaks, CA, 5Genentech Inc., South San Francisco, CA, United States
INTRODUCTION: The Ulcerative Colitis Patient-Reported Outcomes Signs
and Symptoms (UC-PRO/SS) measure was recently developed to evaluate symptom outcomes in clinical trials of ulcerative colitis (UC).
AIMS & METHODS: To examine the structure, reliability and validity of the
UC-PRO/SS. An observational study was conducted in adults with UC and
included three clinic visits: Day 1 (Visit 1), Day 7 (Visit 2), and Day 28 (Visit
3). Subjects completed the UC-PRO/SS on a daily basis using an electronic
device. Descriptive statistics, factor analysis, and Rasch analysis were conducted
to determine final structure. Test-retest reliability was assessed among stable

subjects, defined as those with no change on patient-rated global rating of


change in UC severity from Visit 2 to Visit 3, using paired t-test and intraclass
correlation coefficients (ICCs). Cronbachs coefficient alpha was used to assess
internal consistency. Construct validity was examined based on correlations with
the Inflammatory Bowel Disease Questionnaire (IBDQ), Partial Mayo Score,
and other ancillary measures. Known-groups validity was evaluated by comparing UC-PRO/SS domain scores by groups defined by the Partial Mayo Score,
Patient Global Rating of Disease Severity, and Clinician Global Rating of
Disease Severity using ANCOVA models adjusted for age and gender.
RESULTS: Of the 200 participants, 117 (59%) were female; mean (SD) age was
46 (14.6) years. The 14-item UC-PRO/SS includes three domains: Bowel
Movement (BM) Signs and Symptoms, Abdominal Symptoms, and Systemic
Symptoms. Alpha coefficients ranged from 0.66 to 0.80. No significant differences were observed in UC-PRO/SS domain scores between visits for stable
subjects, with ICC values of 0.71-0.81. The BM Signs and Symptoms scale was
strongly correlated to the Partial Mayo Score (0.79) and moderately to strongly
correlated with the IBDQ (0.51 to 0.73). Moderate correlations (0.45-0.65) were
observed between Abdominal Symptoms and Partial Mayo Score, IBDQ, and
BPI Worst Pain. Similar correlations were observed for Systemic Symptoms.
Findings indicate that UC-PRO/SS domain scores were significantly different
(p50.0001) by known groups.
CONCLUSION: Findings from this study support the UC-PRO/SS as a reliable
and valid measure for the evaluation of signs and symptoms in UC clinical trials.
Future studies conducted within the context of a clinical trial will examine relationships with clinical measures to assess treatment response.
Disclosure of Interest: P. Higgins Financial support for research from: Amgen,
Genentech, Consultancy for: Amgen and Genentech consortium-related work,
G. Harding Consultancy for: Amgen and Genentech consortium-related work,
D. Patrick Consultancy for: Amgen and Genentech consortium-related work, D.
Revicki Consultancy for: Amgen and Genentech consortium-related work, W.H. Chen Consultancy for: Amgen and Genentech consortium-related work, G.
Globe Shareholder of: Amgen shareholder, Other: Amgen employee, H.
Viswanathan Shareholder of: Amgen shareholder, Other: Amgen employee, K.
Fitzgerald Other: Genentech employee, S. Trease Other: Genentech employee, D.
Borie Shareholder of: Amgen shareholder, Other: Amgen employee, B. Ortmeier
Shareholder of: Amgen shareholder, Other: Amgen employee, N. Leidy
Consultancy for: Amgen and Genentech consortium-related work.
P1433 PSYCHOMETRIC EVALUATION OF THE COPING, DAILY LIFE
IMPACT, AND EMOTIONAL IMPACT MODULES OF THE
ULCERATIVE COLITIS PATIENT-REPORTED OUTCOMES (UCPRO) MEASURE
P.D. Higgins1,*, G. Harding2, D.L. Patrick3, D. Revicki2, W.-H. Chen2,
G. Globe4, H.N. Viswanathan4, K. Fitzgerald5, S. Trease5, D. Borie4,
B.G. Ortmeier4, N.K. Leidy2
1
University of Michigan Health System School of Public Health, Ann Arbor, MI,
2
Evidera, Bethesda, MD, 3University of Washington, Seattle, WA, 4Amgen Inc.,
Thousand Oaks, CA, 5Genentech Inc., South San Francisco, CA, United States
INTRODUCTION: The Ulcerative Colitis Patient-Reported Outcomes (UCPRO) measure includes five modules that assess the signs, symptoms, and
impact of UC. Modules 1 and 2 comprise the UC-PRO Signs and Symptoms
measures, while Modules 3-5 assess Coping, Daily Life Impact, and Emotional
Impact.
AIMS & METHODS: To examine the structure, reliability and validity of UCPRO Modules 3-5. An observational study was conducted in adults with UC and
included three clinic visits: Day 1 (Visit 1), Day 7 (Visit 2), and Day 28 (Visit 3).
Subjects completed Module 3 (Coping) on a daily basis using an electronic
device, while Modules 4 and 5 (Daily Life Impact and Emotional Impact) were
completed at clinical visits. Descriptive statistics, factor analysis, and Rasch
analysis were conducted to determine final structure. Test-retest reliability was
assessed among stable subjects, defined as those with no change on patientrated global rating of change in UC severity, using paired t-test and intraclass
correlation coefficients (ICCs). Internal consistency reliability was assessed using
Cronbachs coefficient alpha and the Kruder-Richardson Formula-20 (KR-20).
Construct validity was examined based on correlations with the Inflammatory
Bowel Disease Questionnaire, Partial Mayo Score, and other ancillary measures.
Known-groups validity was evaluated by comparing module scores by groups
defined by the Partial Mayo Score, Patient Global Rating of Disease Severity,
and the Clinician Global Rating of Disease Severity using ANCOVA models
adjusted for age and gender.
RESULTS: Of the 200 participants, 117 (59%) were female; mean (SD) age was
46 (14.6) years. The final UC-PRO Modules 3-5 include Coping (7 items), Daily
Life Impact (9 items), and Emotional Impact (8 items). Cronbachs alphas were
0.94 and 0.91 for Daily Life Impact and Emotional Impact, respectively; the KR20 coefficient was 0.71 for Coping. No significant differences were observed in
Daily Life Impact and Emotional Impact between visits for stable subjects, with
ICC values of 0.93 and 0.85, respectively. There was a significant difference in
scores observed for Coping (p value 0.001), but the ICC value was 0.84, providing support of test-retest reliability. All three modules were moderately to
strongly correlated to ancillary measures. Module scores were significantly different (p50.0001) by known-groups.
CONCLUSION: Findings from this study support the reliability and validity of
UC-PRO Modules 3-5 to assess the impact of UC on coping strategies, daily life
impact, and emotional impact.
Disclosure of Interest: P. Higgins Financial support for research from: Amgen,
Genentech, Consultancy for: Amgen and Genentech consortium-related work,
G. Harding Consultancy for: Amgen and Genentech consortium-related work,
D. Patrick Consultancy for: Amgen and Genentech consortium-related work, D.
Revicki Consultancy for: Amgen and Genentech consortium-related work, W.-

United European Gastroenterology Journal 2(1S)


H. Chen Consultancy for: Amgen and Genentech consortium-related work, G.
Globe Shareholder of: Amgen shareholder, Other: Amgen employee, H.
Viswanathan Shareholder of: Amgen shareholder, Other: Amgen employee, K.
Fitzgerald Other: Genentech employee, S. Trease Other: Genentech employee, D.
Borie Shareholder of: Amgen shareholder, Other: Amgen employee, B. Ortmeier
Shareholder of: Amgen shareholder, Other: Amgen employee, N. Leidy
Consultancy for: Amgen and Genentech consortium-related work.
P1434 COMPARISON OF BREATH AND URINE VOLATILE ORGANIC
MARKERS IN INFLAMMATORY BOWEL DISEASE (IBD)
J. Covington1, E. Daulton2, A. Pauza3, E. Westenbrink1, N. OConnell4,
C. Bailey4, M. McFarland4, A. Dhaliwal4, C. Nwokolo4, K. Bardhan5,
R. Arasaradnam4,*
1
Engineering, 2UNIVERSITY OF WARWICK, Coventry, 3Owlstone, Cambridge,
4
Gastroenterology, CSRI, Coventry, 5Gastroenterology, Rotherham NHS Trust,
Rotherham, United Kingdom
Contact E-mail Address: r.arasaradnam@warwick.ac.uk
INTRODUCTION: Early diagnosis of inflammatory bowel disease (IBD)
remains a challenge. Latterly the role of volatile organic compounds (VOCs)
have come to the fore showing distinct patterns in those with Crohns disease
as well as Ulcerative colitis compared with controls. VOC detection reflects the
altered gut fermentome which is perturbed in IBD. Moreover its sampling is noninvasive with various compounds being identified from faecal, breath and urine.
We and other have previously reported that urine can be used to diagnose IBD
and the same can be achieved with breath and stool.
AIMS & METHODS: Aim: The aim of our study was to compare urine and
breath VOC sampling using FAIMS (Field asymmetric ion mobility spectroscopy) in patients with IBD.
Methods: 133 subjects were recruited 86 patients with established IBD (formed
from both Crohns and Ulcerative Colitis patients) and 46 volunteers for controls.
Urine samples were collected and sampled using the FAIMS system. Urine was
heated to 40oC and headspace analysed for VOC patterns using an Owlstone
Lonestar FAIMS instrument, fitted with an ATLAS sampling system. For breath
analysis, a subset of the subjects (11 controls and 20 with established IBD) were
tested. End expiratory breath was captured using a Warwick device and captured
in a 3L tedlar bag prior to analysis. Linear discriminatory analysis (LDA) was
employed in all cases to determine differences between the two sample modalities,
with a leave on out, combined with a K-nearest neighbour reclassification
algorithm to calculate sensitivity and specificity.
RESULTS: VOC signature patterns were clearly separable in IBD patients compared with controls using both urine and breath. We achieved a sensitivity of
86% and specificity of 76% with the FAIMS, However, the analysis of the breath
samples achieved a sensitivity of 95% and a specificity of 90%.
CONCLUSION: In this pilot study, we have applied FAIMS technology to the
analysis of patients with IBD. Here breath samples tested by FAIMS appear to
show superior results than urine samples analysed by the same method. Further
statistical work is currently being undertaken to distinguish between Crohns
disease and Ulcerative Colitis for both urine and breath samples, whilst a
larger patient group is being recruited for further breath sample analysis.
REFERENCES
Arasaradnam RP, Covington JA, Harmston C, et al. Next generation diagnostic
modalities in gastroenterology - gas phase volatile compound biomarker detection. Aliment Pharmacol Ther 2014; 39: 780-789.
Disclosure of Interest: None declared
P1435 CAN CT ENTEROGRAPHY PREDICT LACK OF MEDICAL
RESPONSE REQUIRING COLECTOMY IN SEVERE ULCERATIVE
COLITIS? A PILOT STUDY
R.C. Gonzalez Sueyro1,*, M.J. Etchevers1, M.J. S. Sobrero1, P.R. Daffra1,
E. Varela1, M.J. Arguero1, D.C. Madrid Blanco1, A. Seehaus2, J.A. De Paula1
1
Gatroenterologa, 2Diagnostico por Imagenes, Hospital Italiano de Buenos Aires,
Ciudad Autonoma de Buenos Aires, Argentina
Contact E-mail Address: ramiro.gonzalez@hospitalitaliano.org.ar
INTRODUCTION: Magnetic resonance imaging (MRI) and Multiple Slice
Computed Tomography (CT) have improved the diagnosis and monitoring of
patients with inflammatory bowel disease (IBD), particularly in Crohns disease
(CD). In ulcerative colitis (UC) the usefulness of CT enterography (CTE) has
been limited to rule out CD during the diagnostic process. No studies to date
have evaluated the prognostic value of CTE findings in patients with severe
active UC.
AIMS & METHODS: Our main objetive was to evaluate CTE findings associated with poor response to treatment in patients with severe relapse of UC
requiring colectomy. We prospectively included adults hospitalized with a
severe relapse of UC according to TrueloveWitts criteria in the gastroenterology
unit of a university hospital from April 2010 to October 2013. CTE findings,
response to treatment and the need of colectomy were evaluated, as well as
endoscopic, biochemical and clinical findings. Variables were compared in
order to determine factors associated with poor outcome and colectomy using
the SPSS 17.0 statistical system.
RESULTS: Seventeen patients hospitalized with severe UC were included, 9 were
women, with a median age of 38.4 years (19-81). The mean time since UC
diagnosis was 3.9 years (0-19). Of the 17 patients included, 5 had progression
of the affected colon extension at the time of the flare. All patients underwent
CTE in a mean time of 3.4 days from the hospitalization. Regarding the response
to steroid treatment, 10 patients were refractory, 6 dependent and 1 responder.
Eight patients received rescue treatment with Infliximab without primary
response. When we compared CTE findings of patients requiring colectomy

A523
(n 11) versus those who did not (n 6), free fluid in the abdominal cavity
was observed in 64% vs. 0% (p 0.043): haustra loss: 100% vs. 50%
(p 0.029): megacolon (transverse colon diameter greater than 5 cm) 27 % vs.
0 % (NS): extensive involvement: 72% vs. 50% (NS), wall thickening (45mm):
100% vs. 66% (NS): and ulcers and/or pseudopolyps: 100% vs 66% (NS). None
of the patients had clinical or laboratory evidence of complications related to the
CTE.
CONCLUSION: In this pilot study, it seems that in patients with severe relapse
of UC, CTE is useful to determine the risk of colectomy while allows us to rule
out extra-intestinal complications. Although in IBD MRI is usually preferred due
to its lack of radiation, in this particular setting of severe UC, CTE is a reasonable option, widely available and fast to implement in the emergency. Prospective
studies with large number of patients are required to assess independent factors
that would allow us to choose treatment and predict response.
Disclosure of Interest: None declared
P1436 PROSPECTIVE COMPARISON OF MAGNETIC RESONANCE
IMAGING, RECTAL AND TRANSPERINEAL ULTRASOUND AND
THE SURGICAL FINDINGS OF COMPLICATED PERIANAL
CROHNS DISEASE: A NEW KID ON THE BLOCK
R. Bor1,*, K. Farkas1, A. Balint1, A. Milassin1, F. Nagy1, Z. Szepes1,
00
T. Wittmann1, M. Szu cs2, T. Molnar1, G. Baradnay3, S. Abraham3
1
First Department of Medicine, 2Department of Medical Physics and Informatics,
3
Department of Surgery, University of Szeged, Szeged, Hungary
Contact E-mail Address: bor.reni86@gmail.com
INTRODUCTION: Magnetic resonance imaging (MRI) and rectal ultrasound
(RUS) are the two accepted imaging modalities for the evaluation of perianal
fistulas and abscesses. Transperineal ultrasound (TPUS) is a new technique,
witch easy to learn and can be performed at any time.
AIMS & METHODS: To prospectively compare the diagnostic accuracy of
MRI, RUS and TPUS with the surgical findings of CD patients with perianal
fistulas and abscesses. All patients underwent MRI, RUS and PUS within a few
days before perianal surgery. Fistulas were classified as simple (43.8%) or complex (52.2%). Perianal Disease Activity Index (PDAI) was estimated in every
patient.
RESULTS: Twenty-three patients with active perianal CD (12 women, 11 men,
mean age: 36.7 years; current therapy: antibiotics in 69.6%, azathioprine in
56.5%, biologicals in 73.9%; frequency of previous surgery 26.1%; proportion
of smokers 39.1%) were included in this prospective study. The mean PDAI was
8.43 (4-15). The validity of MRI, RUS and PUS in the diagnosis of perianal
fistulas were 82.6%, 82.6% and 100%, respectively. PUS was significantly more
sensitive in the diagnosis of the perianal abscesses than MRI and RUS (100%,
58.8% and 92.8%).
CONCLUSION: PUS is a very accurate and easy to perform diagnostic method
with an outstanding sensitivity compared to MRI and RUS in the evaluation of
complicated perianal CD. Due to its simplicity and low cost, PUS is recommended be the first diagnostic modality in case of complicated CD.
Disclosure of Interest: None declared
P1437 NONINVASIVE URINARY METABONOMIC DIAGNOSIS OF
INFLAMMATORY BOWEL DISEASE USING GAS
CHROMATOGRAPHY/MASS SPECTROMETRY
L.C. Phua1, R.K. Wong2,*, Y.M. Tan1, X.H. Li3, E.C. Chan1, C.H. WilderSmith4
1
Pharmacology, National University of Singapore, 2Medicine (Gastroenterology &
Hepatology), National University Health System, 3Medicine, National University
of Singapore, Singapore, Singapore, 4Brain-Gut Research Group, Bern,
Switzerland
Contact E-mail Address: leecheng.phua@gmail.com
INTRODUCTION: Accurate diagnosis of inflammatory bowel disease (IBD)
and classification of its clinical subtypes, namely Crohns disease (CD) and
ulcerative colitis (UC), are of increasing importance in its management and
prognosis. However, diagnosis of IBD based on conventional radiological, endoscopic, and histopathological techniques is often inconclusive and invasive.
Urinary metabonomics represents an emerging systems biology approach for
the identification of noninvasive metabolic biomarkers of IBD. While previous
studies have focused on the use of NMR spectroscopy for urinary metabotyping
of IBD patients, complementary analytical tools that may broaden the metabolic
coverage for biomarker discovery have been underexplored.
AIMS & METHODS: In this study, the role of gas chromatography/mass spectrometry (GC/MS)-guided urinary metabonomics in the noninvasive characterisation of IBD was investigated for the first time. Marker metabolites
characterizing specific subtypes of IBD were further elucidated. Urine samples
from 9 IBD patients (5 UC and 4 CD patients) with active disease (CDAI4 150
or Truelove & Witt Activity 4mild activity, without biological immune-modifiers) and 10 matched healthy controls were metabotyped using gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). The acquired data were
subjected to multivariate partial least squares discriminant analysis (PLSDA).
The PLSDA model was validated using response permutation testing and subjected to receiver operating characteristic (ROC) analysis.
RESULTS: IBD patients were clearly distinguished from healthy controls based
on their urinary metabonomic profiles [validated PLSDA, R2X 0.264,
R2Y 0.669, Q2 (cumulative) 0.519]. The robustness of the PLSDA model
was demonstrated by an area of 0.978 under the ROC curve and a sensitivity
of 100% and specificity of 90% in detecting IBD. Marker metabolites that were
dysregulated similarly in UC and CD (e.g. elevated xylose), as well as unique
metabolites that characterized each subtype (e.g. increased fucose and decreased

A524
nicotinic acid, picolinic acid and valine in UC; reduced hippuric acid in CD) were
further revealed (p50.05).
CONCLUSION: While this diagnostic technique requires further evaluation, our
work established surprisingly robust proof-of-principle for the ability of a noninvasive GC/TOFMS-based urinary metabonomic approach to identify patients
with IBD and uncovered valuable marker metabolites that may aid in the diagnostic distinction between CD and UC.
Disclosure of Interest: None declared
P1438 RISK FACTORS FOR INTRAEPITHELIAL NEOPLASIA IN
ULCERATIVE COLITIS - A CROSS-SECTIONAL STUDY
P. Freire1,*, P. Figueiredo1,2, R. Cardoso1, M.M. Donato2, M. Ferreira1,
S. Mendes 1, M.R. Silva3, A. Cipriano3, A.M. Ferreira 1, H. Vasconcelos 4,
F. Portela1, C. Sofia1,2
1
Department of Gastroenterology, Centro Hospitalar e Universitario de Coimbra,
2
Center of Gastroenterology, Faculty of Medicine, University of Coimbra,
3
Department of Pathology, Centro Hospitalar e Universitario de Coimbra,
Coimbra, 4Department of Gastroenterology, Centro Hospitalar Leiria-Pombal,
Leiria, Portugal
Contact E-mail Address: pauloavfreire@gmail.com
INTRODUCTION: Ulcerative colitis (UC) is associated with an increased risk of
colorectal cancer (CRC). Identification of risk factors for CRC is important to
enhance surveillance. Risk factors identified so far resulted mainly from retrospective studies carried out in referral centers and involving high-risk patients.
AIMS & METHODS: Aim: To identify risk factors for intraepithelial neoplasia
(IN) in patients with longstanding UC and without primary sclerosing cholangitis (PSC) and/or history of IN.
Methods: 150 patients with longstanding (8 years) distal/extensive UC and
without PSC and/or history of IN, were prospectively screened by colonoscopy
with chromoendoscopy-guided endomicroscopy (n 73) or convencional colonoscopy with random biopsies (n 77). In the chromoendoscopy group aberrant
crypt foci (ACF) were sought at the lower rectum.
RESULTS: IN was detected in 10 patients (6.7%). Patients with IN have a
significantly higher number of ACF than patients without IN (4.833.13 vs
2.172.78, p 0.029). ACF prevalence was 100% in patients with IN and
56.7% in patients without IN (p 0.056). Although not reaching statistical significance, there was a trend for association between the risk of IN with older ages
(57.9013.52 vs 49.5114.26 years, p 0.070) and longer disease duration
(22.4010.26 vs 16.377.73 years, p 0.059). There is also a trend towards
lower prevalence of treatment with oral mesalazine in patients with IN (70%
vs 90%, p 0.054). Age at diagnosis, extent of disease, presence of pseudopolyps, smoking status, family history of CRC and body mass index revealed
no significant association with the risk of IN.
CONCLUSION: In longstanding UC patients without PSC and/or history of IN,
the following are risk factors for IN: prevalence/number of ACF, older age,
longer disease duration and lack of medication with oral mesalazine.
Disclosure of Interest: None declared
P1439 RISK FACTORS FOR ABERRANT CRYPT FOCI IN ULCERATIVE
COLITIS
P. Freire1,*, P. Figueiredo1,2, R. Cardoso1, M.M. Donato2, M. Ferreira1,
S. Mendes1, M.R. Silva3, A. Cipriano3, A.M. Ferreira 1, H. Vasconcelos 4,
F. Portela1, C. Sofia1,2
1
Department of Gastroenterology, Centro Hospitalar e Universitario de Coimbra,
2
Center of Gastroenterology, Faculty of Medicine, University of Coimbra,
3
Department of Pathology, Centro Hospitalar e Universitario de Coimbra,
Coimbra, 4Department of Gastroenterology, Centro Hospitalar Leiria-Pombal,
Leiria, Portugal
Contact E-mail Address: pauloavfreire@gmail.com
INTRODUCTION: Aberrant crypt foci (ACF) were identified as biomarkers of
sporadic colorectal cancer (CRC) and, more recently, of dysplasia/CCR associated with ulcerative colitis (UC). Therefore, it is important to identify risk
factors for ACF, which were previously only explored outside the scope of
inflammatory bowel disease.
AIMS & METHODS: Aim: To identify risk factors for ACF in UC.
Methods: Seventy six patients with longstanding (8 years) distal/extensive UC
and without primary sclerosing cholangitis (PSC) and/or history of intraepithelial neoplasia (IN) were prospectively included in the study. ACF were sought at
the lower rectum after chromoendoscopy with methylene blue. Demographic and
clinical data were obtained with a standardized questionnaire filled out by
reviewing the medical charts and a patient interview at the time of enrolment.
Associations of various factors with the prevalence and the number of ACF were
sought by univariate and multivariate analysis.
RESULTS: ACF were detected in 46 patients (60.5%) with a per patient average
number of 2.42.8. ACF prevalence was significantly higher in patients with a
family history of CRC (100% vs 56.5%, p 0.038) and it was also found a trend
for a positive association with body mass index (BMI) (p 0.055). The number
of ACF was significantly higher in patients aged 440 years (2.83.0 vs 1.42.0;
p 0.032), family history of CRC (4.13.6 vs 2.22.7; p 0.044) and higher
BMI (0, 1.92.6, 2.63.1, 3.72.5 for BMI 518.5, 18.5-24.9, 25-29.9 and 30
respectively, p 0.028). In multivariate analysis only the association with BMI
remained statistically significant (p 0.030).
CONCLUSION: In patients with longstanding UC and without PSC and/or
history of IN, having family history of CRC or high BMI are risk factors for
ACF.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1440 ANTI-TNF
THERAPY
AND
DISEASE
PHENOTYPE:
DETERMINANTS OF RISK OF RADIATION EXPOSURE IN
CROHNS DISEASE
R. Coelho1,*, L. Guimaraes2, S. Lopes1, F. Magro1, G. Macedo1
Gastrenterology Department, 2Radiology Department, Centro Hospitalar Sao
Joao, Oporto, Portugal
Contact E-mail Address: rosacoelhoabrantes@hotmail.com
1

INTRODUCTION: Patients with Crohns Disease (CD) require repetitive imaging of the gastrointestinal tract for diagnosis, assessment of activity and
response to therapy. Epidemiological data suggest that a protracted exposure
of a dose of 50100 millisieverts (mSv) is associated with increased risk of cancer.
AIMS & METHODS: Calculate the cumulative dose of radiation (CDR) in
patients diagnosed with CD and its correlation with different variables. Cohort
of 630 patients diagnosed with CD between January 1990 and December 2013
treated at an Inflammatory Bowel Disease outpatient clinic. The total dose of
effective radiation was estimated for each patient collecting the number and type
of radiographic imaging studies since the onset of the symptoms. The CDR was
determined for each patient according to the value set in the reference table in
units of mSv.
RESULTS: 630 patients were included (49.8% male) with CD phenotype according to the Montreal classification: B1 n 263, B2 n 54, B3 n 313. The CDR
mean value was 41.45 mSv (0 - 642.49). There was a correlation between the
number of abdominal computed tomography exams performed and the CDR.
However, the increased duration of the disease was not associated with a higher
CDR. Eighty-six patients (13.7 %) were exposed to a CDR4 50 mSv. There was
a relationship between higher CDR and CD phenotype: B1: 27.54 mSv; B2: 34.47
mSv; B3: 40.66 mSv. A CDR 4 50 mSv was related to the penetrating phenotype
(40.66 vs 27.54, p 5 0.001), anti-TNF therapy (52.38 vs 33.04, p 0.003), surgical treatment (49.86 vs 33.87, p 0.005) and continuous or intermittent course of
the disease vs chronic illness with minimum activity after diagnosis (45.56 vs 29.9,
p 0.004). Azathioprine therapy was not associated with greater CDR.
CONCLUSION: Anti-TNF therapy, surgical treatment, penetrating phenotype
and continuous or intermittent course of the disease were factors associated with
greater amount of CDR.
Disclosure of Interest: None declared
P1441 CALPROTECTIN PREDICTS RELAPSE OF IBD EVEN IN THE
PRESENCE OF A NORMAL COLONOSCOPY
R. DeBerry1,*, A. Rahman2, P. Dubois2, G. Chung-Faye2, B. Hayee2
1
IBD Service, Kings College Hospital NHSFT, 2IBD Service, Kings College
Hospital NHS Foundation Trust, London, United Kingdom
Contact E-mail Address: b.hayee@nhs.net
INTRODUCTION: Faecal calprotectin (FCALP) is a sensitive and reliable
marker of mucosal inflammation and mucosal healing in IBD. It has always
been compared against endoscopic appearance as the presumed gold standard
for assessment of disease activity. Several strands of evidence using magnifying1
or image-enhanced endoscopy as well as confocal laser endomicroscopy2 highlight abnormalities in colonic mucosa reported as normal by standard white
light colonoscopy (WLC). This may be compounded by the difficulties in bowel
preparation in IBD3 and the non-widespread use of high definition technology
(although the latter has not been specifically studied in relation to IBD). We
wished to determine whether an elevated FCALP could predict relapse even in
the presence of an ostensibly normal WLC.
AIMS & METHODS: As part of a larger study correlating FCALP to histologic
assessment of disease activity, retrospective data was collected for consecutive
patients with IBD on stable therapy undergoing colonoscopy for disease assessment. FCALP (Buhlmann ELISA) was collected as close as possible (prior) to the
colonoscopy. When the colonoscopic appearances were reported as normal
(Mayo endoscopic subscore 0 for ulcerative colitis, UC, and ulceration score
equating to SES-CD 0 for Crohns disease, CD), patients were followed to
determine if they relapsed, with time to relapse (or last recorded follow-up)
taken from the date of colonoscopy. For the purposes of this study, relapse
was defined generally as continuous or worsening intestinal symptoms requiring
an escalation in therapy. Switching between 5ASA classes was not included in
this definition unless the specifically stated to be in response to uncontrolled
symptoms.
RESULTS: 46 patients with UC and 37 with CD were identified with the above
criteria. Median time between FCALP measurement and colonoscopy was 0.70
(max 2.89) and 0.90 (max 1.5) months respectively. Normal FCALP was detected
in 16 patients with UC and 12 with CD.
Median calprotectin in the high group was 377 (229-794) in UC and 192 (118247) in CD. At 12 months, relapse-free survival proportions were 86% with UC
and normal FCALP compared to 34% in those with high FCALP (p50.01 in
Kaplan-Meier analysis). In CD, these proportions were 50% and 12% respectively (p 0.02).
CONCLUSION: Elevated levels of FCALP predict relapse even in the presence
of a macroscopically normal colonoscopy. This finding is in general agreement
with studies of state-of-the-art endoscopic techniques that detect mucosal
abnormalities predictive of relapse, when WLC is reported as normal.
FCALP may provide a cheaper and acceptable alternative to routine monitoring
endoscopy in IBD.
REFERENCES
1. Matsuura M, et al. Abstract ECCO 2014.
2. Kiesslich R, et al. Gut 2012; 61: 1146-1153.
3. Froehlich F, et al. Gastrointest Endosc 2005; 61: 378-384.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1442 THERAPEUTIC DRUG MONITORING OF INFLIXIMAB IN
INFLAMMATORY BOWEL DISEASE
S.W. Chuah1,*, M. Parkes2
Gastroenterology, Singapore General Hospital, Singapore, Singapore,
2
Gastroenterology, Addenbrookes Hospital, Cambridge, United Kingdom
Contact E-mail Address: swchuah18@gmail.com
1

INTRODUCTION: Tumour necrosis factor (TNF)antagonists are effective


treatments for inflammatory bowel disease (IBD), but secondary loss of response
(LOR) occurs in 10-15% patients/year. Therapeutic drug monitoring (TDM) has
emerged to facilitate decision-making around secondary LOR. In Addenbrookes
Hospital 107 and 41 IBD patients are on infliximab and adalimumab
respectively.
AIMS & METHODS: Assess serum infliximab and antibodies to infliximab
(ATI) in IBD patients and determine usefulness of TDM in clinical decisionmaking. Prospective cohort study of IBD patients on infliximab between Aug
2013-Jan 2014. Demographic and clinical data collected. Disease activity assessed
using Harvey-Bradshaw index (HBI) for Crohns disease (CD) and Simple
Clinical Colitis Activity Index (SCCAI) for Ulcerative colitis (UC). C-reactive
protein and faecal calprotectin were measured. Bloods assayed for trough level of
infliximab (TLI)/-ATI using LISA-TRACKER Premium ELISA kits
(Theradiag). ATI only if intermediate or subtherapeutic TLI and positive evidence of inflammatory activity. TLI interpretations:Therapeutic level42mg/mL,
Intermediate level 1.02.0mg/mL and Subtherapeutic level5 1.0mg/mL. ATI analytical range: 10200ng/mL.
RESULTS: 107 patients (55males,52females) recruited. Mean age 35.9 years
(range,18-74 years). Mean disease duration 9.6 years (range,7months-39 years).
Mean disease duration before starting infliximab 6.8 years (range,1month-39
years). Diagnoses of CD, UC and IBD-Unspecified were 104, 2 and 1 respectively. Majority 70 (66%) were on 8-weekly regime. Mean duration of infliximab
3.3 years. For TLI results,73 (68.2%),12 (11.2%) and 22 (20.6%) were in the
therapeutic, intermediate and subtherapeutic range respectively. For subtherapeutic TLI group,14 (63%) had undetectable ATI,3 (14%) had ATI of 42ng/
mL,31ng/mL and 50ng/mL; and 5 (23%) did not have ATI done as they had no
evidence of inflammatory activity. For intermediate TLI group,8 (67%) had
undetectable ATI,1 (8%) had ATI of 160ng/mL and 3 (25%) did not have
ATI done as they had no evidence of inflammatory activity. For therapeutic
TLI group,24 (33%) had evidence of inflammatory activity.39 (36%) were not
on immunomodulators (IM). Among 68 patients who were on IM,62 (91%) were
on thiopurines and 6 (9%) on methotrexate. In thiopurines group,34 (55%) had
thiopurine metabolites (6-TGN) done, of which 25 (74%) were within therapeutic
range. Among 68 patients who were on IM,51 (75%) achieved therapeutic TLI
and 2 (3%) had detectable ATI versus among 39 patients who were not on IM,24
(61%) achieved therapeutic TLI and 2 (5%) had detectable ATI (p 0.143).
There was no significant correlation between 6-TGN and TLI levels (p 0.324).
CONCLUSION: 73 (68.2%) achieved therapeutic TLI. With TDM,58 (54.2%)
patients may benefit from interventions:a) Potential infliximab discontinuation
(Subtherapeutic TLI remission)8 (7.5%),b) Potential dose intensification to
recapture response (Subtherapeutic TLI with no ATI but clinical/biochemical
activity)22 (20.6%) and (Subtherapeutic TLI with low ATI)3 (2.8%),c)
Potential switch to other anti-TNF agent (Subtherapeutic TLI with high ATI)1
(0.9%) and d) Potential switch to non-anti TNF agent (Therapeutic TLI
activity) 24 (22.4%). 26/58 (44.8%) patients needed ATI for decision making.
To save cost, initial test should be TLI with addition of ATI if needed.
Concomitant infliximab and IM seemed to be associated with higher rate of
therapeutic TLI. However, there was no significant correlation between 6TGN
and TLI levels.
Disclosure of Interest: None declared
P1443 THIOPURINES AND ANTI-TNFS IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE AND A POSITIVE HISTORY
OF NEOPLASIA
S. Onali1,*, C. Petruzziello1, G. Condino1, M. Ascolani1, E. Calabrese1, E. Lolli1,
A. Ruffa1, F. Pallone1, L. Biancone1
1
Sistems medicine, University of Rome, tor vergata, Rome, Italy
Contact E-mail Address: Sara. Onali@uniroma2.it
INTRODUCTION: The possible role of immunomodulators (IMM) in the development and/or outcome of neoplasia in Inflammatory Bowel Disease IBD) is still
debated. Whether IBD patients with a previous diagnosis of neoplasia may be
treated with IMM, including anti-TNFs is undefined.
AIMS & METHODS: In a retrospective cohort study, the outcome of IBD
patients treated with IMM and/or anti-TNFs after a diagnosis of neoplasia
was evaluated. Clinical characteristics of all IBD patients under regular follow
up at our tertiary IBD center from 2000 to 2013, with a proven diagnosis of
neoplasia were reviewed. Among this subgroup of IBD patients with a history of
neoplasia, only patients treated with IMM and/or anti-TNFs after the diagnosis
of neoplasia were included. Parameters considered: 1. IBD type (Crohns
Disease, CD vs Ulcerative Colitis, UC); 2. Gender; 3. Age at diagnosis of IBD;
4. Age at diagnosis of neoplasia (yr); 5. IMM (Azathioprine, AZA;6mercapopurine,6MP) or anti-TNF (Infliximab, IFX, Adalimumab, AD); 6.
IBD duration at time of diagnosis of neoplasia; 7. Time interval between diagnosis of neoplasia and IMM use; 8. Follow up duration after the diagnosis of
neoplasia; 9. Characteristics of neoplasia. Data were expressed as median (range)
RESULTS: In the 13 yrs follow up, a history of neoplasia was observed in 82
IBD pts. Among these 82 IBD pts, 15 (18.2%) were treated with IMM for IBD
after the diagnosis of neoplasia. This group included 12 CD and 3 UC pts.
(8M,5F; age at diagnosis of neoplasia 41, range 21-69; age at diagnosis of IBD
27, range 12-66, IBD duration at diagnosis of neoplasia 10, range 1-38). IMM

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after the diagnosis of cancer included thiopurines in 12 (AZA n 8; 6MP n 4),
anti-TNFs in 3 (ADA n .2; IFX n 1). Among the 15 IBD pts treated with
IMM after the diagnosis of neoplasia, neoplasia included: thyroid (n 4), skin
(NMSC n 2; 1 basal cell carcinoma, 1 spinal cell carcinoma); breast (n 2),
colon (n 2), prostatic cancer (n 2) lymphoma (HL n 1), seminoma (n 1),
carcinoid of the appendix (n 1). Time interval between the diagnosis of neoplasia and IMM use: 6 yrs (range 1-26). After a 10 yrs follow up from the
diagnosis of neoplasia (range 3-30), none of the 15 IBD pts treated with IMM
after the diagnosis of neoplasia showed recurrence or new onset of neoplasia. No
cancer-related deaths were observed, as only 1/15 pts. had a cirrhosis-related
death..
CONCLUSION: In a retrospective study, the use of thiopurines and anti-TNFs
did not appear to worsen the outcome of IBD pts with a positive history of
neoplasia. Larger prospective longitudinal studies are needed to further address
this relevant issue in IBD
Disclosure of Interest: None declared
P1444 PROSTAGLANDIN E-MAJOR URINARY METABOLITE AS A
RELIABLE SURROGATE MARKER FOR MUCOSAL
INFLAMMATION IN ULCERATIVE COLITIS
S. Arihiro1,*, Y. Arai1, T. Matsuura2, R. Sawada1, D. Ide 1, J. Mitobe1,
M. Mitsunaga1, M. Saruta1, M. Matsuoka1, T. Kato3, M. Fujiwara4,
I. Okayasu5, S. Ito6, M. Matsuura7, H. Tajiri1
1
Department of Internal Medicine, Division of Gastroenterology and Hepatology,
The Jikei University School of Medicine, 2Department of Laboratory Medicine,
3
Department of Endoscopy, The Jikei University School of Medicine, 4Department
of Clinical Pathology, Japanese Red Cross Medical Center, 5Department of
Pathology, Kitasato University School of Medicine, 6Department of Scientific
Information, Fujirebio, 7Division of Cancer Genomics, Cancer Institute of JFCR,
and Bioinformatics Group, Genome Center of JFCR, Japanese Foundation for
Cancer Research, Tokyo, Japan
Contact E-mail Address: sarihiro@gmail.com
INTRODUCTION: A simple, non-invasive biomarker of ulcerative colitis (UC)
activity is required. Because prostaglandin-E2 (PGE2) production is associated
with colonic inflammation, we evaluated whether prostaglandin E-major urinary
metabolite (PGE-MUM) can be used as a biomarker of UC activity by comparing the PGE-MUM levels of volunteers with those of UC patients. PGE is known
to be involved in the development of colon cancer as well as inflammation of the
large intestine.
AIMS & METHODS: Urine samples were obtained from 408 non-smoking (172
male and 236 female) volunteers who visited the Health Check Department of the
Japanese Red Cross Medical Center for general health checkups and from 79 UC
(53 male and 26 female) patients at Jikei University Hospital. UC activity was
evaluated using the simple clinical colitis activity index (SCCAI), Mayo endoscopic scoring system, and Matts grading system (histological activity scoring).
PGE-MUM levels were measured by using a radioimmunoassay kit.
RESULTS: PGE-MUM levels were associated with UC activity (P 5 0.01). The
PGE-MUM levels in the active phase were significantly higher in UC patients
than in healthy volunteers. The main advantage of PGE-MUM appears to be the
differentiation of colonoscopic or histologic remission from active disease in UC
patients. In remission, PGE-MUM levels of UC patients were close to those of
healthy volunteers.
CONCLUSION: Because PGE-MUM can be estimated using a simple, quick,
and non-invasive method and is associated with UC activity, it appears to be a
useful biomarker of UC activity. PGE-MUM levels are low in remission in UC
patients owing to successful treatment. PGE production in the colon is a risk
factor for colon cancer along with cyclooxygenase-2. By keeping PGE-MUM
levels low in the long term, it is possible to reduce UC recurrence and the
incidence of colorectal cancer.
Disclosure of Interest: None declared
P1445 POOR RECOGNITION AND MANAGEMENT OF IRON
DEFICIENCY ANAEMIA IN INFLAMMATORY BOWEL DISEASE: A
MISSED OPPORTUNITY
S. Subramaniam1,*, K. Besherdas1
1
Department of Gastroenterology, Barnet & Chase Farm Hospitals NHS Trust,
London, United Kingdom
Contact E-mail Address: sharmila.subramaniam@nhs.net
INTRODUCTION: Iron deficiency anaemia (IDA) is a common complication of
inflammatory bowel disease (IBD) that has an impact on the patients quality of
life. IDA is caused by inadequate dietary intake, malabsorption of iron and iron
loss through intestinal bleeding. Current guidelines recommend that all patients
with IBD should be assessed for IDA and that iron supplementation be given as
indicated.1
AIMS & METHODS: The aim of this study was to ascertain the prevalence of
IDA in our IBD cohort, to look at whether iron replacement therapy (and in
what form) was given and to assess treatment response.
A single centre, retrospective analysis of IBD patients from a large district general NHS trust in North London was performed. The database of patients was
collated by the IBD Clinical Nurse Specialist. Electronic patient records (blood
results and outpatient clinic letters) were used to collect data on patient demographics, diagnosis, screening parameters for IDA (Hb, Ferritin/transferrin
saturation, CRP) and iron replacement therapy. The WHO definitions of anaemia were used (Hb513g/dL in men and Hb512g/dL in non pregnant women).
Iron deficiency was diagnosed if ferritin 530 ug/L in quiescent IBD or 5100ug/
L in active IBD (CRP elevated) or transferrin saturation 516%.

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United European Gastroenterology Journal 2(1S)

RESULTS: 333 IBD patients were identified in the database. 3 patients were
excluded because of insufficient data as their care was transferred. 293/330
(88.8%) were checked for IDA using the screening parameters. 146/293
(49.8%) of this group were found to be anaemic. 101/146 (69.2%) had evidence
of iron deficiency. 61/101 (60.4%) were treated using oral and/or intravenous
(IV) iron preparations or blood transfusions. Most patients (50/61) received oral
iron while 10 patients had IV iron (4 had failed oral therapy) and 6 had a
transfusion. The recurrence rate of IDA was 21/50 with oral iron, 4/10 with IV
iron and 4/6 with transfusions. We also noted that there were 39/184 patients
(21.2%) with iron deficiency in the absence of anaemia. Only 3 of these patients
were treated for iron deficiency.
CONCLUSION: The prevalence of IDA in our IBD group was close to 50%.
Current practice in our trust does not comply with guidelines as only 60.4% of
IDA patients were treated. Iron replacement therapy was mostly administered in
the oral form. Recurrence of IDA was similar (about 40%) with both oral and IV
iron therapy. There is little guidance on management of iron deficiency in the
absence of anaemia and supplementation was not widespread in this group.
Barriers to appropriate recognition of IDA including lack of routine monitoring
and knowledge on iron data interpretation will need to be addressed to improve
practice.
REFERENCES
1. Gasche C, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis 2007; 13:
1545-1553.
Disclosure of Interest: None declared
P1446 A NOVEL SIMPLE SCORE FOR THE DIAGNOSIS OF CROHNS
DISEASE
S. Reinisch1,2,*, K. Schweiger3, E. Pablik4, B. Collet-Fenetrier5, L. PeyrinBiroulet5, J. Panes6, W. Reinisch1,2
1
Internal Medicine III, MEDICAL UNIVERSITY OF VIENNA, Vienna, Austria,
2
Internal Medicine, McMaster University, Hamilton, Canada, 3Internal Medicine
IV, Wilhelminenspital, 4Institute of Medical Statistics, MEDICAL UNIVERSITY
OF VIENNA, Vienna, Austria, 5Gastroenterology, University and Hospital,
Nancy, France, 6Gastroenterology Service, Hospital Clinic Barcelona, Barcelona,
Spain
Contact E-mail Address: sieglinde.angelberger@meduniwien.ac.at
INTRODUCTION: Rapid and accurate diagnosis of Crohns disease (CD) is
essential for early intervention, however, a gold standard is not available.
Lennard-Jones et al. defined widely adopted macroscopic and histological criteria for CD diagnosis, but these await validation.
AIMS & METHODS: To develop an alternative diagnostic model for CD based
on the criteria by Lennard-Jones.
Included were patients from 3 tertiary centres (Nancy, Barcelona and Vienna)
with long-standing CD whose records from up to 6 months after initial diagnosis
were reviewed. Cases were then re-classified according to Lennard-Jones criteria
(LJC). CD was rated as established (granuloma one minor criterion or 3
minor criteria, which include macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates or discontinuous inflammation on histology),
probable (2 minor criteria without granulomas) or non CD. Sensitivity,
specificity and balanced accuracy were calculated for the overall sample and
for each center separately including patients with ulcerative colitis (UC) as controls. The prognostic value of the 6 variables was modelled by logistic regression.
Variables which proved highly significant (p50.0001) in the first model were
included in the final model. One hundred 10-fold cross-validations were conducted. ROC-curves were calculated and the value with the best Youden-Index
was taken as the optimal cut-off for the diagnosis of CD.
RESULTS: Overall, 328 patients with CD and 170 patients with UC were
assessed. At time of diagnosis nearly half of all patients were diagnosed as
non CD (see Table 1).
Table 1 Diagnosis of CD according to LJC:
Established
CD, n (%)

Sensi/
Speci*

Probable
CD, n (%)

Sensi/
Speci**

Non
CD, n (%)

Barcelona 49/101 (48%) 0.49/1.00 18/101 (18%) 0.66/0.98 34/101 (34%)


Nancy
19/94 (20%) 0.20/1.00 21/94 (22%) 0.43/0.90 54/94 (58%)
Vienna
44/133 (33%) 0.33/0.99 15/133 (11%) 0.44/0.97 74/133 (56%)

Logistic regression of all 6 variables showed high significance by the 4 factors,


granuloma, fibrosis, transmural inflammation, and macroscopic discontinuity
with parameter estimates of 4.6, 4.4, 2.3 and 2.3, respectively. A cut-off score
value of 2.28 was associated with highest balanced accuracy (0.82), a sensitivity
of 0.8 and a specificity of 0.85 and reflecting a diagnosis of probable CD. A
cut-off value of 4.4 for established CD would be associated with a specificity
of 1, but a sensitivity of 0.45.
CONCLUSION: In nearly half of patients managed as long-standing CD at 3
referral centres the LJC would not provide the diagnosis of CD from initial
examinations. We elaborated an alternative simple score for the diagnosis of
CD resulting in higher sensitivity and specificity by subjecting the criteria by
Lennard-Jones to logistic regression modelling.
Disclosure of Interest: None declared

P1447 CHEMERIN, VISFATIN AND VASPIN SERUM LEVELS IN


RELATION TO FAT MASS AND BONE MINERAL DENSITY IN IBD
S.P. terzoudis1,*, N. Malliaraki1, J. Damilakis1, J. Neratzoulakis1,
C. Georgousaki1, V. Tzimourtos1, E. Kouroumalis1, I. Koutroubakis1
1
Gastrenterology, University Hospital of Heraklion Crete, Heraklion, Greece
Contact E-mail Address: sotiris.p.terzoudis@gmail.com
INTRODUCTION: It has been suggested that the bone and fat interface is
implicated in the pathogenesis of osteoporosis. Several studies have shown a
strong correlation between fat mass (FM) and bone mineral density (BMD) in
patients with IBD, but data including the action of adipokines on this association
are limited. The aim of this study was to investigate the role of the adipokines
chemerin, visfatin and vaspin in patients with ulcerative colitis (UC) and Crohn
Disease (CD) in relation to FM and BMD
AIMS & METHODS: 115 patients with IBD (67 CD, 48 UC) and 98 matched
healthy controls (HC) were enrolled in this study. All patients underwent bone
densitometry by dual energy x-ray absorptiometry at the femoral neck and
lumbar spine, and evaluation of body mass composition with GE-Lunar
Prodigy along with host software Encore. Chemerin, visfatin and vaspin serum
levels were measured in IBD patients and HC using commercially available
enzyme linked immunosorbent assays (ELISA)
RESULTS: Osteopenia was observed in 75 patients with IBD (65.2%, 59 CD and
26 UC) and osteoporosis in 23 patients (20%,19 CD,4 UC). Osteoporotic
patients had a significant lower total fat mass (19501.38085.2gr) than osteopenic patients (23089.29939.9 gr) and the patients with normal BMD
(2841010692 gr)(p 0.01). Mean (standard deviation) serum chemerin levels
were 14.16.6ng/ml in CD patients, 13.53.3ng/ml in UC patients and
7.82.7ng/ml in HC (P50.0001). No differences between males and females or
between UC and CD were observed. Subgroup analysis of correlation of chemerin levels with clinical characteristics showed significant association only with
indices of osteoporosis. Chemerin serum levels were found significantly correlated with T score both at the femoral neck and lumbar spine (r 0.25 p 0.007
and r 0.19, p 0.03 respectively). There was no significant correlation of chemerin levels with BMI, CRP and fat distribution. No significant correlations
between visfatin or vaspin and any of the examined parameters (including disease
type or characteristics, FM and BMD) were observed.
CONCLUSION: Fat mass seems to play an important role in the development of
osteoporosis in IBD patients. Serum chemerin levels are significantly increased in
patients with IBD compared to HC and significantly correlated with the development of osteoporosis.
Disclosure of Interest: None declared
P1448 MAGNIFYING COLONOSCOPY OF THE RECTUM
IMPORTANT IN PATIENTS WITH QUIESCENT ULCERATIVE
COLITIS: RESULTS OF 15-YEAR FOLLOW-UP

IS

T. Ando1,*, K. Ishiguro1, O. Maeda1, O. Watanabe1, Y. Hirayama1, K. Maeda1,


K. Morise1, M. Matsushita1, T. Yamamura1, K. Furukawa1, K. Funasaka1,
M. Nakamura1, R. Miyahara1, H. Goto1
1
Department of Gastroenterology and Hepatology, Nagoya University Graduate
School of Medicine, Nagoya City, Japan
Contact E-mail Address: takafumiando-gi@umin.ac.jp
INTRODUCTION: Histologic healing has been shown to be associated with
favorable outcomes in patients with ulcerative colitis (UC). Although mucosal
healing (MH) is reported to be an important goal, MH is not always an accurate
indicator of histologic healing because microscopic evidence of inflammation is
common even in patients with clinically and colonoscopically quiescent colitis.
AIMS & METHODS: We prospectively investigated the usefulness of a highresolution video-magnifying colonoscope with chromoscopy for UC patients
diagnosed with MH by routine colonoscopy to predict exacerbations over a
long period (15 years). Magnifying colonoscopy was performed in 25 UC patients
in remission who had been found to have MH by routine colonoscopy. Pit
patterns in the rectal mucosa were classified into three magnifying-colonoscopy
(MCS) grades on the basis of size, shape, and arrangement. Mucosal macrophage
inflammatory protein (MIP)-1a activity in biopsy specimens of rectal mucosa was
measured and the specimens were microscopically graded according to the system
of Riley. The patients were followed until relapse or for 15 years. Multivariate
survival analysis was performed to determine independent predictors of clinical
relapse.
RESULTS: Of the 25 patients, 4 were MCS grade 1, 10 were grade 2, and 11 were
grade 3. A positive correlation was identified among MCS grade, histological
grade and mucosal MIP-1a activity. Follow-up for 15 years after the start of the
study was possible in all patients. During the study 8 patients (grade 1: 0%, grade
2: 0%, grade 3: 73%), 20 patients (grade 1: 50%, grade 2: 80%, grade 3: 91%), 21
patients (grade 1: 50%, grade 2: 90%, grade 3: 91%), and 22 patients (grade 1:
75%, grade 2: 90%, grade 3: 91%) relapsed within 1, 5, 10, and 15 years, respectively. After magnifying colonoscopy, patients with MCS grade 1 relapsed later
than 2 years and those with MCS grade 3 relapsed within 2 years. Multivariate
proportional hazards model analysis showed that MCS grade was a significant
predictor of relapse. Kaplan-Meier estimates of relapse during the 15-year
follow-up increased with increasing MCS grade (P 0.01).
CONCLUSION: MCS grading is associated with the degree of histological
inflammation and mucosal MIP-1a activity in quiescent UC patients, and may
predict the probability of subsequent disease relapse in UC patients in remission
over a long period.
Disclosure of Interest: None declared

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United European Gastroenterology Journal 2(1S)


P1449 PREGNANCY DOES NOT AFFECT FECAL CALPROTECTIN
CONCENTRATIONS IN HEALTHY PREGNANT WOMEN
T. Molnar1,*, A. Berenyi1, A. Altorjay2, A. Csonka2, M. Krizsan3, A. Balint1,
00
E. Pallagi-Kunstar1, K. Farkas1, M. Szu cs4, F. Nagy1, Z. Szepes1, R. Bor1,
A. Milassin1, T. Wittmann1
1
First Department of Medicine, 2Department of Obstetrics and Gynecology, 3Kaali
Institute, 4Department of Medical Physics and Informatics, UNIVERSITY OF
SZEGED, Szeged, Hungary
Contact E-mail Address: molnar.tamas@med.u-szeged.hu
INTRODUCTION: Fecal calprotectin (CP) is a promising activity marker in the
differentiation of inflammatory bowel diseases (IBD) vs. functional gastrointestinal diseases. Non-invasive activity markers are extremely important in conditions, like pregnancy, when endoscopy is not recommended to be performed. No
data is available on the alteration of fecal CP concentration during pregnancy.
AIMS & METHODS: The aim of this study was to determine fecal CP concentrations in healthy non-pregnant and pregnant women and in patients with IBD.
Healthy women planning pregnancy (waiting for in vitro fertilisation (IVF) treatment), pregnant women and patients with active and inactive IBD were prospectively enrolled in the study. Demographic and clinical parameters, clinical disease
activity scores in case of patients with IBD were recorded. Blood and stool
samples were obtained from every patient to determine C-reactive protein
(CRP) and fecal CP levels. Fecal CP concentration was quantified by use of
enzyme-linked immunosorbent assay.
RESULTS: One hundred and three subjects were enrolled in the study (19
women planning pregnancy, 21 healthy pregnant females, 40 patients with
active and 23 patients with inactive IBD). Mean fecal CP and CRP levels were
32.4 g/g and 6.5 mg/l in pregnant women. Fecal CP concentration was significantly higher in both active and inactive IBD compared to pregnant women
(p50.001, p 0.001) and also to those waiting for IVF (p50.001, p 0.001).
No significant difference was detected in CRP levels between the groups. No
difference could be detected in the fecal CP concentrations between pregnant
and non-pregnant healthy women.
CONCLUSION: Since fecal CP levels did not change during pregnancy, it seems
to be useful noninvasive diagnostic tool in pregnancy and maybe beneficial in the
future for monitoring disease activity in pregnant patients suffering from IBD.
Further studies are necessary to confirm these results.
Disclosure of Interest: None declared
P1450 HEALTH
CARE
RESOURCE
UTILIZATION
AMONG
MODERATE TO SEVERE ULCERATIVE COLITIS PATIENTS
TREATED WITH CONVENTIONAL THERAPIES IN EUROPE: THE
UC CARES (ULCERATIVE COLITIS CONDITION, ATTITUDE,
RESOURCES AND EDUCATIONAL STUDY)
G. Van Assche1, L. Peyrin-Biroulet2, T. Fan3,*, Q. Ding4, N. Lara5, M. Lynam5,
S. Rojas-Farreras5
1
University Hospitals Leuven, Leuven, Belgium, 2Nancy University Hospital,
Vandoeuvre-le`s-Nancy, France, 3Merck & Co., Inc, Whitehouse Station, 4Temple
University, Philadelphia, United States, 5IMS Health, Barcelona, Spain
INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory disorder of
the gastrointestinal tract and can interfere with patients ability to have full
personal and professional lives. Thiopurine immunomodulators are recommended for moderate to severe UC patients. Little data exists on health care
resource utilization among UC patients treated with conventional therapies.
AIMS & METHODS: This study is to describe the health care resource utilization among moderate to severe UC patients who were biologics na ve and treated
with conventional therapies (5-ASA, steroids and/or thiopurines).
Biologic na ve patients with moderate to severe UC (Mayo score 6), 18 years
who received conventional therapies during the previous year were recruited in
Belgium, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden,
Switzerland, Turkey, and the United Kingdom. Patients who underwent colectomy or ileo-anal J-pouch reconstruction were excluded. Medical charts for the 12
months prior to enrollment were reviewed to collect clinical data. Health resource
utilization included the tests (imaging, diagnostics, and laboratory) and health
care professional visits such as ambulatory hospitalization, emergency room
visits and inpatient hospitalization. Descriptive analyses of the health resource
utilization during the 12 months prior to enrollment were conducted in this posthoc analysis.
RESULTS: A total of 250 patients were included in the analysis. Patients mean
(SD) age was 46.6 years (16.3) and 59% were male. The median duration of UC
was 6.9 years (IQR 2.3-14.4). Extent of UC included 21.6% proctitis, 28.4% leftsided, and 49.6% extensive colitis. At the enrollment date, the percentages of
patients receiving thiopurines, aminosalicylates, corticosteroids and other types
of immunosuppressants were 63.2%, 75.2%, 23.6% and 3.6%, respectively.
During the 12 months prior to the enrollment date, only 19 (7.6%) patients had
an abdominal X-Ray. In terms of diagnostic tests the most frequently reported
tests were colonoscopy (18.4% of patients), flexible sigmoidoscopy (9.2%), and
abdominal ultrasound (6.0%). Laboratory tests were performed on half the
patients with 51.2% reporting at least one blood chemistry test and 52% at
least one hematology test. Most imaging and diagnostic tests were performed
once on each patient. The abdominal ultrasound and colorectal biopsy which
were performed a mean (SD) of 2.27 (1.92) and 2.40 (1.15) times on each patient.
Only 2.4% of patients included in the study had at least one ambulatory hospitalization, 5.6% reported at least one emergency room visit, and 4.4% at least
one inpatient hospitalization. The median number of inpatient hospitalization
days was 7 days (IQR 4-9).
CONCLUSION: Overall, during 12 months prior to the enrollment date, less
than 20% of the patients had imaging or diagnostic tests and half of the patients

had laboratory tests. Only 2-5% of the patients had at least one health resource
utilization including ambulatory hospitalization, emergency room visit and inpatient hospitalization.
Disclosure of Interest: G. Van Assche Consultancy for: Merck & Co., Inc, L.
Peyrin-Biroulet Consultancy for: Merck & Co., Inc, T. Fan Other: Employee of
Merck & Co., Inc, Q. Ding: None declared, N. Lara Consultancy for: Merck &
Co., Inc, M. Lynam Consultancy for: Merck & Co., Inc, S. Rojas-Farreras
Consultancy for: Merck & Co., Inc.
P1451 PHOTODYNAMIC DIAGNOSIS OF COLITIS-ASSOCIATED
CANCER/DYSPLASIA BY VISUALIZATION FOLLOWING ORAL 5AMINOLEVULINIC ACID SENSITIZATION IN PATIENTS WITH
ULCERATIVE COLITIS
T. Iwasaki1,*, T. Kato2, N. Komoike1, R. Sawada1, D. Ide1, M. Mitsunaga1,
M. Saruta1, S. Arihiro1, M. Matsuoka1, H. Tajiri1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
2
Division of Gastroenterology and Hepatology, Department of Endoscopy, The
Jikei University School of Medicine, Tokyo, Japan
Contact E-mail Address: t.iwasaki1110@gmail.com
INTRODUCTION: Colitis-associated cancer or dysplasia (CC/D) is a very
important complication that is encountered during clinical management of
patients with long-standing ulcerative colitis (UC). However, it is very difficult
to detect CC/D with conventional colonoscopy (CE) and image-enhanced endoscopy (IEE). The use of many endoscopic procedures such as chromoendoscopy
and target biopsy has been suggested for more efficient detection of CC/D
lesions, but the reliability of endoscopic detection methods remains uncertain.
Recently, photodynamic diagnosis (PDD) has been utilized clinically to detect
the extent of the neoplasms, especially in neurosurgical and urologic procedures.
The 5-aminolevulinic acid (5-ALA) is converted intracellularly into the sensitizer
protoporphyrin IX (PpIX), which accumulates selectively in neoplastic tissue,
allowing the detection of its signal. As there are very few reports regarding this
use of 5-ALA for UC surveillance, its effectiveness is unclear and controversial.
AIMS & METHODS: This pilot study aimed to evaluate the efficacy of PDD for
endoscopic detection of dysplasia in patients with UC by visualization, using
autofluorescent endoscopy (AFE), following orally administered 5-ALA sensitization. Eleven patients with a 410-year history of pancolitis were enrolled at the
Jikei University Hospital from October 2010 to September 2012. Prior to this
study, we confirmed that the 5-ALA metabolite PpIX was detected in vitro as
strong fluorescence signals, using AFE (CF-FH260AZI, Olympus Medical
Systems, Tokyo, Japan). The 5-ALA (20 mg/kg BW; SBI-Pharma, Tokyo,
Japan) was administered orally, and conventional colon lavage was undertaken.
Endoscopic examination was performed 5 h after oral 5-ALA administration.
Each segment of the large intestine was first examined by CE including chromoendoscopy and then reexamined by AFE.
RESULTS: No adverse side effects of 5-ALA were observed. On examination
with CE, 81 lesions were suspected and biopsied, and 18 of these were pathologically diagnosed as CC/D. During subsequent AFE, 22 lesions with strong
fluorescence signals of a characteristic shape were detected and biopsied, and
14 lesions were diagnosed as CC/D on pathological examination. Positive
(PPV) and negative predictive values (NPV) of CE were 22% and 71%, respectively. On the other hand, those of AFE were 68% and 91%, respectively.
Among the LGD lesions, CE detected 13 of 81, and AFE detected 10 of 22
suspected lesions. The PPV and NPV of CE were 16% and 71%, and those of
AFE were 45% and 92%, respectively. Although the number of HGD/cancer
lesions was limited, the accuracy of CE was 13.6% and that of AFE was 78.4%.
CONCLUSION: AFE after 5-ALA sensitization offers the possibility of detecting CC/D lesions by their characteristic shape and color enhancement. Although
the number of patients enrolled in this study was small, our experience indicates
that AFE is a promising method for detecting CC/D lesions during UC
surveillance.
Disclosure of Interest: None declared
P1452 MARKERS OF SUBCLINICAL ATHEROSCLEROSIS
POPULATION OF PATIENTS WITH ULCERATIVE COLITIS

IN

T. ternushchak1,*, I. Chopey1, O. ternushchak2, K. Chopey1, V. Ploskina1


1
Chair of Therapy and Family Medicine, 2Chair of Surgical Diseases, Uzhhorod
National University, Uzhhorod, Ukraine
Contact E-mail Address: tanya.ttm@gmail.com
INTRODUCTION: Patients with ulcerative colitis (UC) have an excess risk of
cardiovascular (CVD) morbidity due to accelerated atherosclerosis. Markers
identifying individuals with subclinical atherosclerosis as measured by carotid
intima-medial thickness (IMT) and ankle-brachial index (ABI) may allow for
attenuation of CVD risk [1]. The aim of the study was to find the possible
correlations between inflammation and subclinical atherosclerosis; also, another
purpose was the one to establish possible correlations between ulcerative colitis
disease activity index (UCDAI), inflammation and atherosclerosis.
AIMS & METHODS: The study included 108 patients with UC (female: male
52:56, mean age 38.3  12.8 years, mean disease duration 10.97  1.04 years).
The control group consisted of 112 healthy controls (female: male 54:58 mean age
35.4  11.6). In order to detect subclinical atherosclerosis, we measured carotid
IMT and ABI. The results were correlated with markers of lipid spectrum (total
cholesterol, HDL, VLDL, triglycerides, and calculated LDL (using the
Friedewald equation), hs CRP, homocysteine, IL-6 and fibrinogen. Clinical disease activity was evaluated by UCDAI score. Lifestyle and other important
factors were examined per protocol and by questionnaire.
RESULTS: A significant difference of carotid IMT (0.843  0.11 mm vs 0.625 
0.09 mm, p  0.01) and ABI (0.97  0.12 vs 1.1  0.16, p  0.04) were found

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United European Gastroenterology Journal 2(1S)

between the UC patients and sex-age adjusted healthy controls. A significant


correlation between carotid IMT, ABI and disease duration, age, UCDAI, use
of corticosteroids were found. Conventional lipids, systolic blood pressure, fibrinogen and smoking were not significantly correlated to carotid IMT and ABI.
However, the correlation between carotid IMT and hsCRP was different regarding the cardiovascular risk: there was a significant positive correlation in patients
with hsCRP 4 3mg/l (r 0.58; CI 95% 0.513 0.644) and a inverse correlation
in patients with values between 1 and 3mg/l (r 0.27; CI 95% 0.2050.321;
p 0.14), correlated with IL 6 (r 0.36; CI 95% 0.108 0.559), statistically
significant (p 0.03) and with homocysteine (r 0.19; CI 95% 0.103 0.287 p 5
0.05). A stepwise logistic regression analysis was conducted with ABI as the
dependent variable and lipid spectrum, hs CRP, homocysteine, IL-6 and treatment with statins as independent variables. Following adjustment for age and
gender, only the hs CRP and IL-6 remained significantly associated with ABI.
CONCLUSION: Carotid IMT and ABI measurements could be used as a clinical
predictor of risk of accelerated atherosclerosis in UC patients. The association of
arterial stiffening with circulating levels of hsCRP and IL-6 implicates chronic
inflammation as important mediator of this process.
REFERENCES
1. Fowkes FGR, Murray GD, Butcher CL, et al. Ankle brachial index collaboration, ankle brachial index combined with Framingham risk score to predict
cardiovascular events and mortality: a meta-analysis. JAMA 2008; 300: 197208.
Disclosure of Interest: None declared
P1454 DIAGNOSIS OF IRON DEFICIENCY IN INFLAMMATORY
BOWEL DISEASE BY TRANSFERRIN RECEPTOR-FERRITIN INDEX
V. Abitbol1,*, D. Borderie2, V. Polin1, F. Maksimovic1, A. Esch1, M. Dhooge1,
T. Tabouret1, J. Dreanic1, G. Perkins1, S. Chaussade1
1
Gastroenterology, 2Biochemistry, Hopital Cochin AP-AP, Paris, France
INTRODUCTION: Iron deficiency (ID) is common in patients with inflammatory bowel disease (IBD) but can be difficult to diagnose in the presence of
inflammation. Serum ferritin level 5 30 ng/mL is a diagnostic criterion of ID.
Guidelines in IBD [1] consider ferritin level between 30-100 ng/mL associated
with inflammation as criteria for ID diagnostic. The sTransferrin receptor-ferritin index (TfR-F) has a high sensitivity for ID diagnosis in chronic diseases [2].
The aim of the study was to assess the added value of TfR-F index to diagnosis of
ID in a prospective cohort of IBD patients.
AIMS & METHODS: All consecutive IBD patients seen in our hospital from
February 2013 to March 2014 were asked to participate in the study. Exclusion
criteria were iron supplementation in the 3 previous months or lack of patient
consent. IBD activity was assessed on symptoms and markers of inflammation
(CRP, endoscopy, calprotectin). All patients had serum dosages of hemoglobin,
hsCRP (N52.5 mg/L), ferritin (F), transferrin saturation, vitamin B9 and B12,
LDH, haptoglobin. Soluble transferrin receptor (sTfR) was measured by Roche
Tina-quant. TfR-F index was calculated as the ratio sTfR / log10 F. ID was
defined by F 5 30 ng/mL or TfR-F index 4 2 in the presence of inflammation;
TfR-F index 5 1 excluded ID.
RESULTS: 150 patients aged 38 (16-78) years, 69 males, 105 Crohns disease
(CD), 43 ulcerative colitis (UC) and 2 indeterminate colitis were included. 68
patients (45.3%) had active disease. 42 patients (28%) had anemia (WHO criteria), including 28 CD and 14 UC. 9 patients (6%) had vitamin B12 deficiency
and 9 (6%) vitamin B9 deficiency. No one had hemolysis. Mean F level was 80
(9-359) ng/mL and sTfR, 3.7 (1.5-12.8) mg/L. 36 patients (24%) had F 5 30 ng/
mL, 69 (46%) F between 30-100 ng/mL and 45 (30%) F 4 100 ng/mL. 30
patients (20%) had F between 30-100 ng/mL and CRP 4 2.5 mg/L: 1 had
vitamin B12 deficiency excluding TfR-F analysis, 12/29 patients (41.4%) had
TfR-F 4 2 and 1 patient (3.5%) TfR-F51. Three patients (6.6%) with F 4
100 ng/mL had TfR-F 4 2. Overall, ID was diagnosed in 48/150 patients (32%),
in which 24% on the basis of F 5 30 ng/mL and 8% with TfR-F index 4 2 in the
presence of inflammation.
CONCLUSION: This prospective study in IBD shows that TfR-F index in addition to serum ferritin 5 30 ng/mL criterion, increases by 8 % diagnosis rates of
ID. Only 41.4% of the patients with ferritin between 30-100 ng/mL and inflammation have ID, suggesting that guidelines [1] overestimate ID in IBD. TfR-F
index seems useful to the diagnosis of ID in IBD and prevents from overtreating
by iron supplementation.
REFERENCES
[1] Gasche C, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis 2007; 13:
15451553.
[2] Weiss G, et al. Anemia of Chronic Disease. N Engl J Med 2005; 352: 10111023.
Disclosure of Interest: None declared
P1456 SIALIC-ACID-BINDING
IG-LIKE
LECTINS,
PERIPHERAL MARKERS FOR MUCOSAL DAMAGE OF
INFLAMMATORY BOWEL DISEASE

POTENTIAL

Y. I. Kawamura1,*, C. Maeyashiki2, T. Hagiwara1, T. Otsubo1, J. Akiyama2,


T. Dohi1
1
National Center for Global Health and Medicine, Chiba, 2National Center for
Global Health and Medicine, Tokyo, Japan
INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohns disease (CD), are characterized by relapsing/remitting nature
of the inflammatory process. While some cases with IBD are controllable by means
of medical treatment, we encounter many cases with recurrent deterioration of
disease which necessitates intensive treatment like high dose of steroid therapy,
immunosuppressant or even surgery. In damaged intestinal mucosa of IBD, the

mucus layer, which covers intestinal epithelial cell surface with heavily glycosylated
mucin, is deteriorated and abnormally glycosylated. Recently, we reported that
colonic immune cells express sialic acid-binding Ig-like lectins, siglecs, which recognize cell surface glycans preferentially expressed in normal colonic epithelium. We
have speculated that the interaction of siglecs with these glycans might be involved
in immune tolerance in the mucosal tissue. However, differential expression of
siglecs and its regulation in the peripheral immune cells, as well as the function
of siglecs in these cells, has been largely unknown.
AIMS & METHODS: The aim of this study was to investigate whether the
siglecs expression of peripheral blood mononuclear cells (PBMCs) may reflect
the condition of damaged/unhealed mucosa with abnormal glycosylation, and
moreover, predict exacerbation of the disease. IBD patients and disease control
(intestinal tuberculosis, Behcet disease (BD), and rheumatoid arthritis (RA)), and
healthy volunteers were analyzed. PBMCs were isolated and the expression pattern of siglec-7/-9 was analyzed by flowcytometry.
RESULTS: Flow cytometric analysis revealed that CD33 macrophage/dendritic
cells of healthy PBMCs expressed siglec-9 but not Siglec-7, while CD33 cells
isolated from IBD blood frequently expressed Siglec-7. The frequency of siglec7siglec-9 cells in CD33PBMCs of IBD patients was significantly higher than
that of normal control, however; there was no difference between UC and CD.
High frequency of siglec-7siglec-9 CD33 cells was not observed in intestinal
tuberculosis, BD, nor RA blood, even at active stage. In IBD cases, the incidence
of siglec-7siglec-9 cells in CD33PBMCs correlated with abdominal pain and
ESR but not CRP, ALB, Hb, the number of WBC, neutrophils, and platelets,
suggesting that inflammation is not essentially parallel to the expression of siglec7. In fact, some UC patients in clinical remission with high frequency of siglec7siglec-9 cells, resulted in aggravated disease several months later.
CONCLUSION: The frequency of siglec-7siglec-9 cells in CD33PBMCs of IBD
patients, especially at active stage, was significantly higher than those of normal
control and patients with non-IBD inflammatory disease, such as intestinal tuberculosis, BD, nor RA. These results suggest that the emergence of siglec-7siglec-9 cells
in the peripheral CD33PBMCs reflects presence of the mucosal damage in an IBDspecific manner, which may be clinically cryptic without apparent sign of inflammation. Thus, it may predict exacerbation or relapse in IBD patients.
REFERENCES
J Immunol 2012; 188: 4690-700.
Disclosure of Interest: None declared
P1457 SAFETY AND EFFICACY OF LOW DOSE AZATHIOPRINE AND
ALLOPURINOL CO-THERAPY: A LARGE SINGLE CENTRE
EXPERIENCE
P. Stamoulos1,*, A. Abdul-Rehman1, C. Bull1, M. Cowan1, G. Mackenzie1,
J. Stenner1, S. Coulthard2, A. Ansari1
1
Gastroenterology, East Surrey Hospital, Redhill, 2Institute of Cellular Medicine,
Newcastle University Medical School, Newcastle, United Kingdom
Contact E-mail Address: Azhar. Ansari@sash.nhs.uk
INTRODUCTION: The effectiveness of full dose azathioprine (FDA) for inflammatory bowel disease (IBD) has been questioned in recent scientific literature. A
popular strategy to improve its outcomes recommends the use of low dose
azathioprine with allopurinol co-therapy (LDAA) for patients profiled as
hypermethylators (30% of non-responders).
AIMS & METHODS: Aims: The aim of this study was to determine the safety
and efficacy of LDAA without using thiopurine metabolite (TM) profiling.
Methods: Records of IBD patients treated with LDAA were retrospectively analysed. Patients who had poor response and/or side-effects to FDA were offered
LDAA by all consultants whilst a single IBD physician also offered LDAA to
thiopurine-na ve patients. Azathioprine dose was reduced to 25% of the thiopurine
methyl transferase (TPMT) adjusted dose (0.5mg/kg for wild type and 0.25mg/kg
for heterozygotes) followed by conventional haematological monitoring. Nonadherence was assessed by TM measurements. Full response (FR) was defined as
steroid free remission (Harvey Bradshaw index 3, Truelove-Witts normal) for
greater than 3 months after a 3 month induction period for LDAA.
RESULTS: Of 300 LDAA patients, adequate data was available for 295 cases.
Group 1 (G1) were treated 1st line (n,105) and Group 2 (G2) were switched from
FDA to LDAA (n,190). Overall, for both groups, there were 207 (70%) full
responders (FR), 20 partial responders (PR) and 68 non-responders (NR). Full
response rate was 78% in G1 and 66% in G2. The commonest indication for
switching to LDAA was non-response to FDA (n,118).
Clinical Response (n)
Indications for LDAA
AZA Na ve
(LDAA without FDA exposure)
Switched from FDA to LDAA
Reason for switch to LDAA
and outcomes
Poor response
GI intolerance
Hepatotoxicity
Myelotoxicity
Flu-like symptoms
Other
Total

FR

PR

NR

TOTAL

Percentage FR

82
125

7
13

16
52

105
190

78%
66%

81
16
7
13
3
5
207

10
0
1
2
0
0
20

27
11
3
1
1
9
68

118
27
11
16
4
14
295

69%
60%
64%
81%
75%
36%
70%

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United European Gastroenterology Journal 2(1S)


Analysis of haematological indices revealed significant changes (p50.05) in erythrocyte sedimentation rate, white cell count and platelet count after therapy
induction.
Myelotoxicity occurred in 5 patients (all NR, WCC 42 and 53.5) and 12
patients had asymptomatic hepatotoxicity (ALT range: 100-700) which resolved
by increasing allopurinol to 200 mg in 9 patients (all FR).
Time on treatment: 208 patients took LDAA for more than twelve months with a
median length of therapy of 24 months.
CONCLUSION: Appropriately dosed LDAA therapy delivers a therapeutically
effective dose of azathioprine without the need for dose escalation. It appears to
be more effective, better tolerated and safer (less haematological disturbance)
than FDA. These results will serve to allay the fear of toxicity of LDAA and
question the need for thiopurine metabolite level profiling prior to using this
apparently superior therapeutic approach.
Disclosure of Interest: None declared
P1458 ENDOSCOPIC BALLON DILATATION IN CROHNS DISEASE:
REAL IMPACT ON CLINICAL EVOLUTION OF THE DISEASE
S. Lopes1, P. Andrade1,*, E. Rodrigues-Pinto1, F. Silva1, F. Magro1, G. Macedo1
1
Gastroenterology, Centro Hospitalar Sao Joao, Porto, Portugal
Contact E-mail Address: anapatriciarandrade@gmail.com
INTRODUCTION: Endoscopic recurrence after surgery for Crohns disease
(CD) is high; 50% of patients require additional surgery. Endoscopic balloon
dilation (EBD) is an alternative to surgery, but data on safety and efficacy, as
well as factors associated with the need for dilatation are limited.
AIMS & METHODS: The aim of this study was to determine the efficacy and
safety of EBD in patients with CD with anastomotic strictures and to evaluate
the factors associated with the need for dilatation.
Cross-sectional study of patients with CD who underwent ileocolectomy (stenosis/abscess) proposed for re-evaluation and endoscopic dilation between
March/2010 and February/2014. Success of EBD was defined as passage of the
scope into the ileum after dilatation.
RESULTS: Endoscopic evaluation of 100 patients (52% female) with a mean age
of 44  13 years; median follow-up was 12 months. Thirty-eight percent of
patients had anastomotic stricture, of which 34 were dilated (success rate 89.5%). There were no complications. Thirty-two patients had Rutgeerts
score2. Twenty patients required a second dilatation, which was performed in
median 11 months after the first procedure. The success of dilation avoided the
need for surgery after dilatation (3.2% vs 50%, p 0.014, OR 0.094 [95% CI
0020-0447]). Patients with perianal disease, occlusive symptoms and active smokers required dilatation earlier after the first surgery (p 0.042, p 0.003 and
p 0.019, respectively). Patients under treatment with immunomodulators had
less dilatations (23.4% vs 52.8%, p 0.003) and underwent dilatation later (7161
 3158 vs 4030  648, p50.001).
CONCLUSION: EBD is a safe and effective procedure and avoids the need for
surgery in most patients. Perianal disease, active smoking, occlusive symptoms
and no therapy with immunomodulators are associated with the need for early
dilatation.
Disclosure of Interest: None declared
P1459 INFLIXIMAB TROUGH LEVELS AND ANTIBODIES: ACADEMIC
INTEREST OR USEFULNESS IN CLINICAL PRACTICE?
P. Sousa1,*, S. Fernandes1, C.M. Moura1, C. Baldaia1, P. Moura dos Santos1,
A.R. Goncalves1, A. Valente1, L. Correia1, F. Serejo1, J. Velosa1
1
Gastrenterologia, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria,
Lisboa, Portugal
Contact E-mail Address: patlizbms@gmail.com
INTRODUCTION: Infliximab (IFX) has demonstrated effectiveness in inducing
and maintaining remission in Crohns Disease (CD) and Ulcerative Colitis (UC).
However, not all patients respond to the therapy and some lose response over
time. Low trough levels and high antibodies titers have been associated with loss
of response.
AIMS & METHODS: To evaluate the usefulness of trough levels and antibodies
against IFX in the clinical management of patients with CD and UC we analyzed
this group of patients followed in our IBD department. IFX trough levels and
antibodies were performed in patients with clinical activity despite optimal therapy. Tests were performed using ELISA (Theranostic, Lisa-Tracker).
RESULTS: A total of 109 patients were treated with IFX. 45 patients were
included (27 females; mean age 44 13.2 years). 39 had CD and 6 UC.
Average time of IFX therapy was 48 months. 27 (60%) patients were under
combined therapy with azathioprine and 10 had a previous abdominal surgery.
Low IFX levels (0.01-1.5 mg/mL) were detected in 15 (33.3%) patients. 11
(24.4%) patients had detectable antibodies against IFX (5-240 UA).
Of the 11 patients with antibodies against IFX: 72.7% were on combined therapy
with azathioprine, 7 (64%) had antinuclear antibodies (ANA) and 5 (45%) had
anti-dsDNA. All patients presenting with anti-dsDNA (n 5) had simultaneously antibodies against IFX.
Endoscopic evaluation around the laboratory date was performed in 17 patients
and, despite normal IFX level and absence of antibodies, 5 patients didnt show
endoscopic remission.
This data led to stopping IFX in 7 (15.5%) patients, dose adjustment in 12
(26.7%) and introduction of methotrexate in 2 (4.4%). Of the 7 who stopped
IFX, 6 were started on Adalimumab and one on methotrexate monotheraphy.
CONCLUSION: In our study, infliximab trough levels and antibodies provided
important information, leading to optimization of therapy in 47% of patients. It
may demonstrate a useful tool in the management of IBD patients, especially in
those with clinical or endoscopic activity despite optimized therapy. Our data

suggests a link between IFX antibody formation and other antibodies especially
anti-dsDNA.
Disclosure of Interest: None declared
P1460 WEIGHT-BASED MAINTENANCE DOSING OF GOLIMUMAB IN
PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS
P. Rutgeerts1,*, W. Reinisch2, B. Feagan3, W. Sandborn4, D. Tarabar5,
Z. Habzda6, H. Weng7, R. Yao7, H. Zhang8, O. Adedokun9, C. Marano8,
R. Strauss8
1
University Hospital Gasthuisberg, Leuven, Belgium, 2McMaster University,
Hamilton, 3University of Western Ontario, London, Canada, 4University of
California San Diego, La Jolla, United States, 5Military Medical Academy,
Belgrade, Serbia, 6Wojskowy Szpital Kliniczny z Poliklinika, Krakow, Poland,
7
Merck & Co., Inc., Whitehouse Station, 8Janssen R&D, LLC., 9Janssen R&D,
LLC, Spring House, United States
Contact E-mail Address: paul.rutgeerts@uz.kuleuven.ac.be
INTRODUCTION: Given that body weight is the most significant covariate
affecting golimumab (GLM) pharmacokinetics, a weight-based approach to
dosing was evaluated.
AIMS & METHODS: A posthoc analysis evaluated efficacy in the PURSUIT
Maintenance study by body weight (580kg v 80kg; 90 and 100kg cutoffs were
also evaluated). Outcomes included clinical response (30% and 3 points
decrease from induction baseline Mayo score, with either a rectal bleeding subscore of 0/ 1 or a decrease of 1), clinical remission (Mayo score 2 points; no
subscore 41), and mucosal healing (endoscopy subscore 0/1). The analysis
included patients (pts) with moderately to severely active ulcerative colitis
(UC) who were in clinical response to GLM induction therapy and were randomized (1:1:1) to receive placebo (PBO) or subcutaneous GLM 50mg or 100mg
every 4 wks through wk 52. P values were not adjusted for multiplicity.
RESULTS: 456 pts had clinical response to GLM induction, were randomized,
and included in efficacy analyses (8 pts excluded owing to site misconduct); 29%
discontinued before wk 52. In the 580kg group, the percentage of pts who
maintained clinical response through wk 54, remission at both wk 30 and 54,
and mucosal healing at both wk 30 and 54 was generally greater for GLM than
PBO; the 2 GLM dose groups had similar magnitudes of response (table). In the
80kg group, all outcomes were better for the 100mg dose than the 50mg dose,
which had outcomes similar to the PBO group. Similar patterns of efficacy were
observed using a 90kg cutoff. A 100kg cutoff was also evaluated, but very few pts
had weight 4100kg. Given the smaller number of pts 90kg or  100kg, the
results should be interpreted with caution. An 80kg cutoff resulted in a greater
percentage of patients achieving GLM concentrations favorable for efficacy in
UC.
Table. Efficacy Outcomes by Treatment Type and Body Weight.
Body Weight 580kg

Outcome, n (%)

PBO
n 105

Body Weight 80kg

GLM 50mg GLM 100mg PBO


n 108
n 100
n 49

Clinical response 31 (29.5) 53 (49.1)b


through wk 54
Clinical remission 15 (14.3) 28 (25.9)c
at wk 30 and
54
Mucosal healing at 27 (25.7) 47 (43.5)b
wk 30 and 54

GLM 50mg GLM 100mg


n 43
n 51

49 (49.0)a

17 (34.7) 18 (41.9)d

29 (29.0)a

9 (18.4)

41 (41.0)a

14 (28.6) 16 (37.2)d

7 (16.3)d

26 (51.0)c
13 (25.5)d

23 (45.1)d

CONCLUSION: In patients with UC with body weight 80kg, achievement of


optimal efficacy outcomes, including sustained remission, with GLM treatment
was more likely with a 100mg maintenance dose than a 50mg dose. Overall, the
safety profile for GLM in UC was similar to previous reports for GLM in other
indications; no new adverse events were identified. (Financial support for this
study was provided by Janssen Research & Development, LLC., Spring House,
PA, USA.)
Disclosure of Interest: P. Rutgeerts Financial support for research from: Merck
Sharp & Dohme Corp, Consultancy for: Merck Sharp & Dohme Corp, W.
Reinisch Lecture fee(s) from: Abbott Laboratories, AbbVie, Aesca, Amgen,
AM Pharma, Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen
IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor,
Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech,
Grunenthal, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC,
Consultancy for: Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma,
Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, BristolMyers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Danone Austria,
Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Grunenthal,
Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC, B.
Feagan Financial support for research from: Abbott/AbbVie, Amgen, Astra
Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen,
Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, UCB
Pharma, Lecture fee(s) from: Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-

A530

United European Gastroenterology Journal 2(1S)

Chilcott, UCB Pharma, Consultancy for: Abbott/AbbVie, Actogenix, Albireo


Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Axcan, Baxter
Healthcare Corp., Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso
Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech,
GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma,
Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd.,
Lexicon, Lilly, Merck, Millennium, Nektar, Novonordisk, Prometheus
Therapeutics and Diagnostics, Pfizer, Receptos, Salix Pharma, Serono, Shire,
Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, Tillotts, UCB
Pharma, Vertex Pharma, Warner-Chilcott, Wyeth, Zealand, Zyngenia, W.
Sandborn Financial support for research from: Janssen, Consultancy for:
Janssen, D. Tarabar: None declared, Z. Habzda: None declared, H. Weng
Other: Merck Employee, R. Yao Other: Merck Employee, H. Zhang Other:
Janssen Employee, O. Adedokun Other: Janssen Employee, C. Marano Other:
Janssen Employee, R. Strauss Other: Janssen Employee.
P1461 AZATHIOPRINE
CROHNS DISEASE

FOR

THE

TREATMENT

OF

PERIANAL

R. Meharich1,*, M. Tahiri1, S. Oussama1, A. Bellabah1, F. Haddad1, W. Hliwa1,


W. Badre1
1
Gastroenterology, Ibn Rochd University Hospital, Casablanca, Morocco
INTRODUCTION: Crohns disease may be complicated by perianal disease,
which can lead to faecal incontinence, abscess formation and stricturing. The
management of perianal lesions is complex, with surgery often performed in
conjunction with medical therapy. Thiopurines have been employed in the management of perianal Crohns disease, although evidence of their efficacy is rare.
AIMS & METHODS: The aim of this study was to evaluate whether azathioprine healed perianal Crohns disease.
Thirty-five patients (20 males and 15 females, mean age: 31 years) with active
perianal Crohns disease were treated with azathioprine for more than 6 months.
The evolution of perianal lesions during azathioprine therapy was analyzed retrospectively. Patients who had a clear anatomic improvement (fistula closure, fissure healing, and stricture dilatation) were considered responders regarding their
perianal disease.
RESULTS: There were 28 patients (80%) with an anal fistula, 13 patients
(37.1%) with anal ulcerations, and five patients (14.3%) with an anal stricture.
In 43% of patients, the anal manifestations preceded any evidence of intestinal
disease.
Twelve patients (34.2%) required surgical drainage and three patients (8.5%)
required anal dilatation.
Response to azathioprine was noted in 28 of the 35 patients (80%), with complete
healing in 16 patients (45.7%). Subsequently, five patients (14.3%) relapsed to
some degree on azathioprine.
CONCLUSION: Azathioprine is an effective and useful drug in the treatment of
perianal Crohns disease.
Disclosure of Interest: None declared
P1462 LONG TERM EFFICACY OF GRANULOCYTE-MONOCYTEAPHERESIS IN ULCERATIVE COLITIS. THE ITALIAN REGISTRY
OF THERAPEUTIC APHERESIS
R. Sacco1,*, A. Romano1, V. Mismas1, M. Bertini1, M. Bertoni1, G. Federici1,
G. Parisi1, A. Scaramuzzino1, S. Metrangolo1, E. Tumino1, G. Bresci1, P. Vernia2
on behalf of Italian Registry of Therapeutic Apheresis
1
Gastroenterology, Pisa University Hospital, Pisa, 2Gastroenterology, Sapienza
Rome University, Roma, Italy
Contact E-mail Address: r.sacco@ao-pisa.toscana.it
INTRODUCTION: Granulocyte-monocyte-apheresis (GMA) is effective in the
treatment of ulcerative colitis (UC). However, all published studies evaluated a
low number of patients, with an overall limited follow-up. This observational
study investigates the long-term efficacy of GMA in a large number of patients
included in the Italian Registry of Therapeutic Apheresis.
AIMS & METHODS: Data of patients with mild/moderate UC treated with a
standard protocol of GMA (5 sessions in 5 weeks) were evaluated. All patients
had failed to respond to mesalamine or sulphasalazine, and were under steroid
treatment. Clinical evaluations were performed at 3, 12 and 24 months since the
end of GMA session. The following parameters were assessed: incidence of clinical remission (CAI [Colits Active Index] 54); CAI; erythrocyte sedimentation
rate (ESR); c-reactive protein (CRP); white cells blood count (WBC).
Endoscopical evaluations were performed at a 3-month follow-up: the incidence
of endoscopical remission (EAI [endoscopical activity index] 0/1) was assessed.
RESULTS: Data for 347 patients (214 males, age 46.3 years; CAI 7.47) were
available; 288 patients were either steroid-resistant or steroid-dependent. The
proportion of patients with remission of disease was 66% at 3 months, 77% at
12 months and 78% at 24 months. At 24 months, all other efficacy parameters
had improved from baseline: CAI (7.47 vs 3.47), ESR (35.87 vs 24.1 mm/h), CRP
(4.31 vs 2.75 mg/dl) and WBC (8.61 vs 7.19) (p50.001 for all comparisons).
Endoscopic data were available for 107 patients. The incidence of mucosal healing was 47% and all patients with mucosal healing presented a clinical remission
over the entire follow-up period. No major adverse events were reported during
GMA sessions.
CONCLUSION: Data collected on a large sample of steroid-resistant or steroidrefractory patients included in the Italian Registry of Therapeutic Apheresis
show that GMA is a safe and effective procedure over a long-term follow-up.
Mucosal healing appears strongly associated with clinical remission.
Disclosure of Interest: None declared

P1463 IDENTIFICATION
ANTIBODIES

OF

NEUTRALIZING

ANTI-INFLIXIMAB

R. Weisshof1,*, B. Ungar2, A. Blatt1, A. Dahan1, S. Ben-Horin2, Y. Chowers3 on


behalf of the ABIRISK consortium
1
Gastroenterology department, Rambam Health Care Campus, Haifa,
2
Gastroenterology department, Sheba Medical Center Tel Hashomer & Sackler
School of Medicine, Tel-Aviv University, Ramat Gan, 3Gastroenterology department, Rambam Health Care Campus & Bruce Rappaport School of Medicine,
Technion Israel Institute of Technology, Haifa, Israel
Contact E-mail Address: r_weisshof@rambam.health.gov.il
INTRODUCTION: About 60% of Infliximab (IFX)-treated inflammatory
bowel disease patients (IBD) develop anti-drug antibodies (ADA) with a sizable
population suffering from loss of response (LOR). However, these antibodies
were shown to be heterogeneous, some of which have no therapeutic consequences. Defining their neutralizing potential has marked therapeutic
significance.
AIMS & METHODS: The aim of the study is to assess the neutralizing capability of infliximab ADA.
A biological assay in which TNF- induced IL-8 secretion from HT-29 cells
followed by application of IFX and control pooled IBD sera, or ADA-containing
sera was developed. Thereafter, IL8 amplification ratio was determined for each
serum relative to controls. In parallel, an immune test was developed in which the
IFX concentration in a standard solution was determined before and after its
incubation with ADA positive sera compared to control.
RESULTS: Forty seven infliximab ADA positive patients (43% female, 68%
Crohns disease) were tested. Of those, sera of 41 patients (87%) contained
biologically active antibodies that inhibited IFX activity in both the cellular
and immune models. No difference in the ability to detect the ADA neutralizing
effect was noted between assays. Using the immune assay, the average IFX
reduction ratio of 31 serums from patients with clinical LOR was 4.7  3.1
compared to 2.1  1.5 in patients without LOR (p 0.0003). Notably, the
ADA concentration measured by anti-lambda ELISA of both groups was similar
(13.9 and 11.6 mg/ml respectively p 0.38). Using a cutoff value of 2.5, the test
had sensitivity and specificity of 77% and 72% respectively and positive and
negative predictive values of 82% and 65% respectively. Antibody extraction
lead to loss of the neutralizing effect in the bioassay pointing to its immune
specificity. When early sera from IFX-treated patients with no detected ADA
and no IFX (double negatives) obtained from patients without, or with subsequent LOR were compared, the IFX reduction ratios were 0.64 and 1.27 respectively (p 0.01). Sera from patients with transient antibodies who maintained
clinical remission had no inhibitory effect as well (ratio of 0.55; p 0.004 compared to the LOR group).
CONCLUSION: Two assays for detection of neutralizing ADA were developed
and compared. No advantage was found for the more complex bioassay. A
predictive potential of the test was identified, allowing to identify patients
prone to develop immunogenic LOR. These findings may assist in optimizing
infliximab therapy in IBD patients.
Disclosure of Interest: R. Weisshof: None declared, B. Ungar: None declared, A.
Blatt: None declared, A. Dahan: None declared, S. Ben-Horin Consultancy for:
Abbott, Janssen, Takeda, Schering-Plough, Y. Chowers Lecture fee(s) from:
Abbvie, Janssen, Takeda, Consultancy for: Abbvie, Janssen, Takeda,
Pharmacosmos.
P1464 5-AMINOSALICYLIC ACID IS EFFECTIVE AS REMISSION
INDUCTION THERAPY IN PATIENTS WITH MODERATE TO
SEVERE INTESTINAL BEHCETS DISEASE
R. Koh1,*, R. Kunisaki1, H. Kinoshita1, H. Kimura1, S. Maeda2
IBD center, Yokohama City University Medical Center, 2Gastroenterology,
Yokohama Citu University Hospital, Yokohama, Japan
Contact E-mail Address: ryonhoko@yokohama-cu.ac.jp
1

INTRODUCTION: Behcets disease (BD), the so-called silk road disease is a


chronic relapsing-remitting autoimmune disorder with multiple organ system
involvement characterized clinically by oral and genital aphthae, cutaneous
lesions, ophthalmological, neurological, or gastrointestinal manifestations. Up
to 16% of patients with BD have gastrointestinal (GI) involvement, discrete
ulcerations are most often seen in the terminal ileum, caecum, and ascending
colon, responsible for intestinal complications like severe bleeding and perforation. Various drugs including 5-aminosalicylic acid (5-ASA) preparations, systemic corticosteroids, and immunosuppressive agents have been applied
anecdotally to treat intestinal BD. However, the clinical evidence regarding the
management of intestinal BD is very limited.
AIMS & METHODS: We were interested to evaluate the efficacy and safety of 5ASA as a remission induction therapy in patients with intestinal BD, in a retrospective cohort study. Data were obtained using a retrospective chart review of
54 consecutive patients with intestinal BD who were visiting a single centre in
Japan between 2004 and 2013. The patients were clinically and endoscopically
evaluated before treatment, then assessed after 12 weeks for a clinical response to
5-ASA, defined as a significant improvement of intestinal symptoms, and a
reduction in C-reactive protein (CRP) level, as well as the disease activity
index for intestinal BD (DAIBD). Clinical remission was defined as complete
disappearance of GI symptoms, including abdominal discomfort, GI bleeding
and diarrhoea, followed by normalization of serum CRP level. Clinical response
was defined as a significant improvement in GI symptoms accompanied by a
lower CRP level. To determine factors predictive of clinical response to 5-ASA
therapy, we used the chi squared test for nominal variables and the t-test for
continuous variables. We also assessed adverse events during 5-ASA therapy.

A531

United European Gastroenterology Journal 2(1S)


RESULTS: A total of 13 patients were treated for active intestinal BD with oral 5ASA as remission induction therapy. Their average age was 26 years at the diagnosis of BD and 34 years at the initiation of 5-ASA therapy. The response rate was
77.0% (remission 30.8%, response 46.2%). Young age, high disease activity at the
initiation of 5-ASA therapy, and short disease duration up to the initiation of 5ASA were predictors for good clinical response to 5-ASA (P50.05). There was no
severe adverse event warranting cessation of 5-ASA therapy.
CONCLUSION: In this study, 5-ASA as remission induction therapy was effective and safe in patients with moderate to severe intestinal BD. Further, use of 5ASA as first-line medication in this clinical setting is potentially interesting as it
spares the patients from exposure to stronger drugs with safety concerns.
Disclosure of Interest: None declared
P1465 PARTHENOLIDE AMELIORATES EXPERIMENTAL COLITIS
ASSOCIATED COLON CANCER BY INHIBITION OF NF-KB
SIGNALING
S.W. Kim1,*, S.-L. Kim1, S.T. Lee1, G.S. Seo2, S.H. Lee3, S.H. Kim1, S.O. Lee1
1
Internal Medicine, Chonbuk National University Hospital, Jeonju, 2Internal
Medicine, 3Pharmacy, Wonkwang University, Iksan, Korea, Republic Of
Contact E-mail Address: clickm@jbnu.ac.kr
INTRODUCTION: Parthenolide (PT), a NF-kB inhibitor, has recently been
demonstrated as a promising anticancer agent that promotes apoptosis of
cancer cells. We previously showed that PT suppresses tumor growth in a xenograft model of colorectal cancer cells by regulation of Bcl-2 family.
Unfortunately, little is known about its role in the process of tumor development
in colitis associated colon cancer (CAC).
AIMS & METHODS: Therefore, this study was designed to investigate the
effects of PT on an experimental murine CAC model. Experimental CAC was
induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). Mice were
divided into 3 groups: AOMDSS, AOMDSS2mg/kg PT and
AOMDSS4mg/kg PT.
RESULTS: We demonstrated that administration of PT significantly reduced the
severity of AOM/DSS-induced CAC as assessed by histological analysis, and
resulted in downregulation of phospho-NF-B p65 expression by the blockade of
phosphorylation and subsequent degradation of IB-a. Administration of PT ameliorated the carcinogenesis through the downregulation of antiapoptotic protein
Bcl-2 and Bcl-xL mediated by inhibition of NF-kB activation. Moreover, apoptosis
and caspase-3 expression also increased markedly in PT administration group.
CONCLUSION: These findings demonstrate that PT downregulates NF-kB
resulting in initiation of apoptosis and eventual suppression of CAC development, suggesting that PT exerts beneficial effects in experimental CAC and could
therefore be a potential chemopreventive and therapeutic agent of CAC.
Disclosure of Interest: None declared
P1466 CCR9 INHIBITOR VERCIRNON CLINICAL TRIALS IN CROHNS
DISEASE
S. Keshav1,*, T.J. Schall2, P. Bekker2
Gastroenterology, John Radcliffe Hospital, Oxford Univ, Oxford, United
Kingdom, 2Chemocentryx, Inc., Mountain View, United States
Contact E-mail Address: satish.keshav@ndm.ox.ac.uk
1

INTRODUCTION: Vercirnon (previously called CCX282-B or Traficet-EN) is an


oral, specific C-C chemokine receptor 9 inhibitor that has been studied in Crohns
disease (CD). A Phase 2b clinical trial, PROTECT-1, showed evidence of activity
of vercirnon in patients with moderate to severe Crohns disease. A subsequent
Phase 3 trial, SHIELD-1, failed to confirm efficacy. The data from the two trials
were examined to determine the potential source for the contrasting outcomes.
AIMS & METHODS: Both trials were randomized, double-blind, placebo controlled. SHIELD-1 recruited 608 and PROTECT-1 436 subjects world-wide; the
latter excluded the USA. In SHIELD-1, subjects had CDAI 220-450, and endoscopically confirmed disease, or an elevated CRP and fecal calprotectin. Subjects
received placebo, 500 mg QD or BID vercirnon for 12 weeks. In PROTECT-1,
entry criteria were CDAI 250-450 and CRP 7.5mg/L. Subjects received placebo
or CCX282-B 500 mg QD, 250 mg QD or BID for 12 weeks. Key endpoints:
CDAI 100-point response, CDAI remission, and CDAI 70-point response.
RESULTS: Areas of differences between the two trials are summarized in the
table.
Table to abstract P1466

Prior TNF inhibitor use


CDAI median (range)
CRP (mg/L) median
(range)
Drop-out rate
Gastrointestinal
adverse events
Abdominal pain
Diarrhea
Vomiting

PROTECT-1
(N 436)

SHIELD-1 (N 608)

26%
330 (249-471)
22 (3-200)

69%
317 (123-450)
14 (0.2-157)

16%
Placebo: 40%, 500
mg QD: 41%
Placebo: 13%, 500
mg QD: 12%
Placebo: 8%, 500
mg QD: 7%
Placebo: 4%, 500
mg QD: 3%

25%
Placebo: 30%, 500 mg QD:
37%, 500 mg BID: 48%
Placebo: 7%, 500 mg QD:
9%, 500 mg BID: 11%
Placebo: 1%, 500 mg QD:
4%, 500 mg BID: 5%
Placebo: 2%, 500 mg QD:
6%, 500 mg BID: 9%

The most significant difference was the higher incidence of prior TNF inhibitor
use in SHIELD-1 (69%) compared to PROTECT-1 (26%). Also, PROTECT-1
enrolled patients with more severe disease at baseline (CRP and CDAI higher).
Lastly, more GI adverse events were found in SHIELD-1, in particular at the
highest dose, 500 mg BID, which was not tested in PROTECT-1.
In the 244 patients from SHIELD-1 who would have met entry criteria for
PROTECT-1, i.e., CDAI 250-450 and CRP 7.5 mg/L, the CDAI 100-point
response at Week 12 was 31%, 45%, and 28% in the placebo, 500 mg QD, and
BID groups, respectively. CDAI remission was 13%, 21%, and 9%, respectively,
and CDAI 70-point response was 38%, 56% (p 0.02 vs. placebo), and 39%,
respectively. These results suggest activity at the 500 mg QD dose, shown efficacious in PROTECT-1. The higher 500 mg BID dose was associated with a higher
incidence of GI AEs (see table), which may increase the CDAI.
CONCLUSION: PROTECT-1 and SHIELD-1 enrolled patient populations that
differed mostly in terms of prior TNFI use, disease activity at baseline, and GI
AEs. These differences, may at least partly account for the divergent outcomes.
Disclosure of Interest: S. Keshav Financial support for research from:
ChemoCentryx, Inc., Consultancy for: ChemoCentryx, Inc., Shareholder of:
ChemoCentryx, Inc., T. Schall Shareholder of: ChemoCentryx, Inc.,
Directorship (s) for: ChemoCentryx, Inc., P. Bekker Shareholder of:
ChemoCentryx, Inc.
P1467 DISSOLUTION
OF
COMMERCIALLY
AVAILABLE
AMINOSALICYLIC ACID (5-ASA) FORMULATIONS AT VARIOUS
PH LEVELS

5-

S. tenjarla1,*
1
Pharmaceutical Sciences, Shire, Wayne, PA, United States
INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory condition
that can affect any part of the colon and is characterized by relapsingremitting
gastrointestinal (GI) and systemic symptoms. Treatment with 5-ASA, a topical,
locally acting compound that reduces inflammation of the colonic mucosa, is
recommended as first-line therapy in patients (pts) with active mild-to-moderate
UC. Minimum systemic absorption in the upper GI tract is desired in order to
maximize the amount of drug available for local action in the colon. Thus, many
5-ASA formulations employ a pH-dependent release mechanism, designed to
dissolve in the more basic environment of the distal small intestine. The pH
levels in the GI tract of pts with UC may be lower and more variable than
that of unaffected individuals. This in vitro study compared the release of mesalazine from multimatrix mesalazine (Mezavant XL; Shire Development LLC,
USA) and 5 other commercially available 5-ASA formulations.
AIMS & METHODS: The release of 5-ASA from 12 tablets each of multimatrix
mesalazine 1.2 g, Mesalazin-Kohlpharma 500 mg (Kohlpharma, Germany),
Mesalazin-Eurim 500 mg (Eurimpharm, Germany), Claversal 500 mg (Faes
Farma, Spain), Mesalazine EC 500 mg (Actavis, Netherlands), and Mesalazine
EC 500 PCH 500 mg (Pharmachemie, Netherlands) was monitored separately at
3 different pH conditions using United States Pharmacopeia dissolution apparatus II, with a paddle speed of 100 rpm. Tablets of each formulation were individually exposed to dissolution medium at pH 1 for 2 h, pH 6.4 for an additional
1 h, and pH 7.2 monitored until complete drug release. After the first 2 h, samples
were collected every hour and analyzed by UV spectroscopy at 330 nm. The
dissolution percentage was calculated as a mean of 12 units for each formulation.
RESULTS: At pH 1 and pH 6.4, 51% 5-ASA release was observed for each of
the 5-ASA formulations. Dissolution profiles for each of the formulations at pH
7.2 (after exposure to pH 1 for 2 h and pH 6.4 for 1 h) are shown in the Table. At
pH 7.2, 5-ASA was completely released from all generic 5-ASA formulations in
about 2 h. Release of 5-ASA from multimatrix mesalazine occurred in a sustained manner over 7 h.
MesalazinMultimatrix
Mesalazine
MesalazinKohlpharma
Eurim
Claversal Mesalazine EC 500 PCH mesalazine
500 mg
Time at
1.2 g
500 mg
EC 500 mg 500 mg
pH 7.2, h (% dissolution) 500 mg
0
1

51
36

51
26

51
51

51
102

51
103

51
8

2
3
4
5
6
7
8

102
102
102
102
102
102
102

100
101
101
101
101
101
101

101
101
101
101
101
101
101

101
101
101
101
101
101
101

103
103
103
103
102
102
102

26
43
63
84
98
102
102

CONCLUSION: Results of this in vitro study indicate little to no drug release at


more acidic pH conditions for all products. At pH 7.2, differences in the respective dissolution profiles suggest that multimatrix mesalazine would result in
roughly 5 more hours of sustained release of the drug compared with any of
the other examined commercially available 5-ASA formulations.
Disclosure of Interest: S. Tenjarla Shareholder of: Shire, Other: Employee of
Shire.

A532

United European Gastroenterology Journal 2(1S)

P1468 PROSPECTIVE, LONGITUDINAL OBSERVATIONAL STUDY IN


THERAPEUTIC MANAGEMENT OF MILD TO MODERATE
ULCERATIVE COLITIS (OPTIMUM): FOLLOW-UP AT ONE YEAR
1,*

IBD Centres

G. BONNAUD , S. NAHON , G. TUCAT , P. NIEZ


1
Clinique des Ce`dres, Cornebarrieu, 2Le Raincy Hospital, Montfermeil, 3CREGG,
Paris, 4Ferring Pharmaceuticals, Gentilly, France
Contact E-mail Address: philippe.niez@ferring.com
INTRODUCTION: OPTIMUM study was set up in France in 2011. Its objective
was to describe the progression and methods of therapeutic management of mild
to moderate ulcerative colitis (UC), to assess remission rate, duration of remissions and prognostic factors for relapse in patients with a flare-up.
AIMS & METHODS: From June 2011 to June 2012, 812 patients over 18 years
of age with a mild to moderate flare-up of UC (51% women, average age of 45 
15 years) were included in the observational study by 130 gastroenterologists
(64% office based). A three-years monitoring is planned. The time period selected
for a visit to one year is 365  100 days after the inclusion visit.
RESULTS: In July 2013, the one-year visit data (time period of 369  42 days)
was available for 504 patients (62%); 419 (83%) were in remission during the first
year. According to the UCCS score (Ulcerative Colitis Clinical Score), at oneyear visit, 397 (79%) patients were in remission, 67 (13%) had mild activity and
33 (7%) had moderate activity. Remission was achieved after a median period of
59 days (95% CI [5377 days]) after the inclusion consultation. At the end of the
visit, treatment with 5-ASA alone was prescribed in 479 patients (59%), treatment combining 5-ASA and another UC treatment in 175 patients (22%) and
another UC-treatment not including 5-ASA in 99 patients (12%). The UC treatment at the period of remission was the one prescribed at the end of the inclusion
visit in 366 patients (87%). After adjusting for the UCCS score and the level of
injury at visit, the patients treated solely with 5-ASA at the end of the inclusion
visit were in remission faster than the patients treated without 5-ASA (p 0.013);
but the difference with patients treated with 5-ASA in combination with another
treatment was not statistically significant (p 0.062). At one year, the remission
rate was 82.5% (95% IC [78.0%86.6%]) in the group treated with 5-ASA alone
prescribed at the end of the inclusion visit vs 71.4% (95% IC [64.0%78.4%]) in
the group treated with 5-ASA in combination with another treatment. At the
one-year visit, a UC treatment was in on going in 426 patients (84%).
Compliance was good in 92 of 394 patients (23%). In total, at least one adverse
event was reported in 15 patients (3%). Colorectal cancer or dysplasia was diagnosed in three patients (0.6%).
CONCLUSION: During treatment, the period of remission of mild to moderate
UC flare-up is about two months. After one year of monitoring, about 80% of
patients are in remission. The continuation of the OPTIMUM observational
study will help refine these results and, in particular, analyse possible relapses
over three years of monitoring.
Disclosure of Interest: G. BONNAUD Consultancy for: Honorarium, S.
NAHON Consultancy for: Honorarium (Coordinator of the study), G.
TUCAT Consultancy for: Honorarium, P. NIEZ Directorship (s) for: Medical
Director Ferring France.
P1469 DISCORDANCE BETWEEN PATIENTS AND PHYSICIANS IN
LONG-TERM USE OF STEROIDS: RESULTS FROM A PATIENTAND PHYSICIAN-REPORTED SURVEY
S. Ghosh1,*, J. Petkau1, R. Thakkar2, J. Chao2, M. Skup2, S. Wang2,
R. Panaccione1, S. Schreiber3
1
University of Calgary, Calgary, Canada, 2AbbVie Inc., North Chicago, United
States, 3Christian-Albrechts University, Kiel, Germany
Contact E-mail Address: song.wang2@abbvie.com
INTRODUCTION: POLARIS, a cross-sectional study employing paper-based
questionnaires, assessed treatment patterns from the patients with Crohns disease (CD) and their health care providers (HCPs). We assessed the concordance
in patients and their HCPs responses regarding the use of steroids, immunosuppressants, and biologics.
AIMS & METHODS: Surveys were administered at inflammatory bowel disease
(IBD) centres and community practices in Canada and Germany. Patients 18
years old with a confirmed diagnosis of CD, disease duration 1 year and 2
visits with a participating HCP (consulting gastroenterologist, nurse practitioner,
or physicians nurse) were eligible. Patients and their HCPs provided information
on steroid use (oral steroids excluding budesonide), steroid monotherapy use,
long-term (3 months) use of steroids, long-term use of steroid monotherapy,
immunosuppressant use, and biologics use. Data were summarised overall, and
by IBD centres and community practices using descriptive statistics. Agreement
between patients and HCPs responses to survey questions was tested using
kappa statistics.
RESULTS: Surveys from 809 patients and 798 HCPs were available for this
analysis. Overall, a greater percentage of patients vs. HCPs reported use of
any steroid (25.9% vs. 20.8%, kappa 0.735), steroid monotherapy (4.4% vs.
3.7%, kappa 0.514), long-term steroids (67.7% vs. 63.8%, kappa 0.598), and
long-term steroid monotherapy (11.6% vs. 7.2%, kappa 0.433). It should be
noted that the agreements between patients and HCPs were much lower in community practices than in IBD centres in all measures: use of any steroid
(kappa 0.609 vs. 0.781), steroid monotherapy (0.425 vs. 0.575), long-term steroid use (0.263 vs. 0.663), and long-term steroid monotherapy (0.250 vs. 0.520).
Overall, responses from patients and their HCPs were similar regarding use of
immunosuppressants (52.4% vs. 51.1%, kappa 0.784) and biologics (49.5% vs.
47.0%, kappa 0.909) with lower agreements observed in community practices
than in IBD centres (use of immunosuppressants: kappa 0.715 vs 0.807; use of
biologics: kappa 0.861 vs. 0.928).
Medication Use for CD in Past 12 Months.

Any steroid used


Steroid monotherapy
Long-term (3 months)
steroid use
Long-term (3 months)
steroid monotherapy
Immunosuppressant use
Biologics use

Community Practices

HCPs

PTs

HCPs

PTs

550
547
116

22.4
2.7
61.2

546
539
141

27.3
3.5
64.5

249
247
36

17.3
5.7
72.2

229
207
48

22.7
6.8
77.1

116

6.0

141

8.5

36

11.1

48

20.8

557
558

57.1
51.4

551
558

56.1
52.9

251
251

37.9
37.1

232
240

43.5
41.7

CONCLUSION: Results of this cross-sectional survey revealed a discordance


between patients and their HCPs regarding the long-term use of steroids. The
discordance was more severe in community practices than in IBD centres. These
findings suggest a need to improve the care management, e.g., more coordinated
follow-up visits by patients, or enhanced communication between patients and
their HCPs.
Disclosure of Interest: S. Ghosh: None declared, J. Petkau: None declared, R.
Thakkar Shareholder of: AbbVie, Other: Employee: AbbVie, J. Chao
Shareholder of: AbbVie, Other: Employee: AbbVie, M. Skup Shareholder of:
AbbVie, Other: Employee: AbbVie, S. Wang Shareholder of: AbbVie, Other:
Employee: AbbVie, R. Panaccione Financial support for research from:
AbbVie, Bristol-Myers Squibb, Elan, Centocor, Ferring, Jansen, Millenium,
Proctor & Gamble, Schering-Plough, Lecture fee(s) from: AbbVie,
AstraZeneca, Centocor, Elan, Jansen, Prometheus, Schering-Plough, Shire,
Warner Chilcott, Consultancy for: AbbVie, Amgen, Aptalis, AstraZeneca,
Baxter, Bristol-Myers Squibb, Centocor, Eisai, Elan, Ferring, Glaxo-Smith
Kline, Jansen, Merck, Pfizer, Schering-Plough, Shire, UCB, Warner Chilcott,
Other: Advisory board: AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, BristolMyers Squibb, Centocor, Eisai, Elan, Ferring, Glaxo-Smith Kline, Jansen,
Merck, Pfizer, Schering-Plough, Shire, UCB, Warner Chilcott, S. Schreiber
Other: Educational Grants for CME: AbbVie.
P1470 DIFFERENT METHODOLOGIES FOR DETERMINING MAYO
SCORE IN CLINICAL STUDIES CAN INFLUENCE DISEASE
ACTIVITY ASSESSMENTS IN ULCERATIVE COLITIS
S. Ghosh1,*, W. Sandborn2, J. Panes3, G. DHaens4,5, N. Reilly6, A. Lazar7,
B. Huang6, A.M. Robinson6, R. Thakkar6
1
Univ. of Calgary, Calgary, Canada, 2Div. Gastroenterology, Univ. of California,
San Diego, La Jolla, United States, 3IDIBAPS, CIBERehd, Hospital Clinic Univ.
of Barcelona, Barcelona, Spain, 4Imelda GI Clinical Research Center, Bonheiden,
Belgium, 5Academic Med. Center, Amsterdam, Netherlands, 6AbbVie Inc, North
Chicago, United States, 7AbbVie Deutschland GmbH & Co, KG, Ludwigshafen,
Germany
Contact E-mail Address: anne.robinson@AbbVie.com
INTRODUCTION: There is no standard method to determine stool frequency
(SFS) and rectal bleeding (RBS) subscores of the Mayo score in ulcerative colitis
(UC) clinical trials. In adalimumab (ADA) clinical trials, SFS and RBS were
calculated using the worst value from 3 days of patient diary entries (ie, worstrank methodology).1,2 Other clinical trials in UC have calculated RBS and SFS
using the average of each subscore from the past 3 days of patient diary entries.3,4
Recently, data from a placebo-controlled study of ADA in Japanese patients
suggested that the Mayo subscore calculation method used can influence the
effect size of remission rates by several percentage points.5 The impact of the
use of different Mayo score determination methods on Mayo scores in ULTRA
22 has not been described.
AIMS & METHODS: In this exploratory analysis, we evaluated the impact of
worst vs average score methodology for SFS and RBS by recalculating Mayo
scores in ULTRA 2 using the average scoring methodology for patients from
sites with readily-available daily diary data. In ULTRA 2, adults with UC and a
Mayo score of 612 with endoscopy score 2 were randomised to ADA (160 mg/
80 mg at wks 0/2 followed by 40 mg every other wk to Wk 52) or placebo (PBO).2
Daily diary data of 16 patients who completed the Wk 52 study visit on their
originally randomised treatment (PBO: n 7; ADA: n 9) were evaluated.
Means for full Mayo scores (FMS) at baseline and Wk 52 were recalculated
using the average of daily SFS and RBS from the 3 prior days and compared
to FMS obtained using the worst-rank methodology. For the average calculations, SFS and RBS were rounded to the nearest integer.
RESULTS: Average scoring methodology led to greater reduction in mean FMS
from baseline to Wk 52 than worst-rank methodology in ADA-treated patients
compared to PBO-treated patients (Table). The absolute difference in change in
FMS from baseline to Wk 52 between ADA and PBO was 0.59 points greater
using average scoring methodology than worst-rank methodology.

A533

United European Gastroenterology Journal 2(1S)

ADA (n 9)
FMS

Absolute difference
between overall  of
ADA and PBO

PBO (n 7)


FMS

Methodology Baseline Wk 52
Baseline Wk 52
Worst
9.11
2.89 6.22a 9.57
4.29 5.28a
Average
9.00
2.33 6.67a 9.00
3.86 5.14a
Overall 
0.45b
0.14b 0.59

, difference between scores. aDifference between baseline and Wk 52.


b
Difference between  of worst-rank and average scores.
CONCLUSION: These preliminary results suggest that differences between
Mayo scores calculated using worst-rank vs average scoring methodology for
SFS and RBS may have a disproportionate effect between active treatment
and PBO arms. These results should be confirmed in larger and more diverse
data sets.
REFERENCES
1 Reinisch W, et al. Inflamm Bowel Dis 2013; 19: 1700-1709.
2 Sandborn WJ, et al. Gastroenterology 2012; 142: 257-265.
3 Feagan BG, et al. N Engl J Med 2013; 369: 699-710.
4 Sandborn WJ, et al. Gastroenterology 2014; 146: 85-95.
5 Suzuki Y, et al. J Gastroenterol 2014; 49: 283-294.
Disclosure of Interest: S. Ghosh Financial support for research from: Research
support from AbbVie, Lecture fee(s) from: Consulting and/or lecture fees from
AbbVie, Shire, Pfizer, Bristol-Myers Squibb, Janssen, and Merck & Co,
Consultancy for: Consulting and/or lecture fees from AbbVie, Shire, Pfizer,
Bristol-Myers Squibb, Janssen and Merck & Co, Other: Served on an advisory
committee or review panel for AbbVie and Merck & Co, W. Sandborn Financial
support for research from: AbbVie, Bristol-Myers Squibb, Genentech,
GlaxoSmithKline, Janssen, Millennium, Novartis, Pfizer, Procter and Gamble
Pharmaceuticals, Shire Pharmaceuticals, and UCB Pharma, Lecture fee(s) from:
AbbVie, Bristol-Myers Squibb, and Janssen, Consultancy for: AbbVie,
ActoGeniX NV, AGI Therapeutics, Inc., Alba Therapeutics Corporation,
Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas,
Athersys, Inc., Atlantic Healthcare Limited, Aptalis, BioBalance Corporation,
Boehringer-Ingelheim
Inc,
Bristol-Myers
Squibb,
Celgene,
Celek
Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx,
CoMentis,
Cosmo
Technologies,
Coronado
Biosciences,
Cytokine
Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research Inc, Elan
Pharmaceuticals, EnGene, Inc., Eli Lilly, Enteromedics, Exagen Diagnostics,
Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc., Funxional
Therapeutics Limited, Genzyme Corporation, Genentech, Gilead Sciences,
Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood
Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc., Lexicon
Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research
Laboratories, MerckSerono, Merck & Co., Millennium, Nisshin Kyorin
Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer
Pharmaceuticals, Orexigen Therapeutics, Inc., PDL Biopharma, Pfizer, Procter
and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis
Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix
Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, Sigmoid Pharma
Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L. A. Pharma
(UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma
AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics
Limited (VBL), Warner Chilcott UK Limited, J. Panes Financial support for
research from: AbbVie and MSD, Lecture fee(s) from: AbbVie, MSD, Shire
Pharmaceuticals and UCB, Consultancy for: AbbVie, Actelion, Boehringer
Ingelheim, Bristol-Myers Squibb, Ferring, Genentech, Janssen, MSD,
Novartis, Nutrition Science Partners, Pfizer, Shire Pharmaceuticals, and
Tigenics, G. DHaens Financial support for research from: Abbott
Laboratories, Janssen Biologics, Given Imaging, MSD, DrFalk Pharma,
Photopill, Lecture fee(s) from: Consulting and/or lecture fees from AbbVie,
ActoGeniX, AM Pharma, Boehringer Ingelheim GmbH, Centocor,
ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, Engene, Dr Falf
Pharma, Ferring, Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline,
Jansen Biologics, Merck Sharp and Dohme Corp, Millennium Pharmaceuticals
Inc. (now Takeda), Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer,
Receptos, Salix, Setpoint, Shire Pharmaceuticals, Schering-Plough, Tillotts
Pharma, UCB Pharma, Versant and Vifor Pharma. Speaking Honoraria from
Abbott Laboratories, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire,
Consultancy for: Consulting and/or lecture fees from AbbVie, ActoGeniX, AM
Pharma, Boehringer Ingelheim GmbH, Centocor, ChemoCentryx, Cosmo
Technologies, Elan Pharmaceuticals, Engene, Dr Falf Pharma, Ferring,
Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline, Jansen Biologics,
Merck Sharp and Dohme Corp, Millennium Pharmaceuticals Inc. (now Takeda),
Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer, Receptos, Salix,
Setpoint, Shire Pharmaceuticals, Schering-Plough, Tillotts Pharma, UCB
Pharma, Versant and Vifor Pharma, N. Reilly Other: AbbVie employee, may
own AbbVie stock and/or options, A. Lazar Other: AbbVie employee, may own
AbbVie stock and/or options, B. Huang Other: AbbVie employee, may own
AbbVie stock and/or options, A. Robinson Other: AbbVie employee, may own
AbbVie stock and/or options, R. Thakkar Other: AbbVie employee, may own
AbbVie stock and/or options.

P1471 VACCINATION GUIDELINES: ARE WE MISSING THE TARGET


WHEN INJECTING OUR PATIENTS?
S. Vinnamala1,*, R. Iriarte1, S. Gausden1, M. McFarlane1, J. Pinnell1,
S. Kathawala1, S. Ford1, L. Knight1, J. Eaden1
1
Gastroenterology, University Hospitals Coventry and Warwickshire NHS trust,
Coventry, United Kingdom
Contact E-mail Address: drvsudheer97@yahoo.com
INTRODUCTION: Early and increasing use of Immunomodulators (IM) and
biological agents in IBD can lead to an increase in the risk of opportunistic
infections (OI). The RR of OI is 2.9 with one IM and increases to Odds ratio
of 14.5 with 2 concomitant IMs. Age (450 years) is an independent risk factor
for OI. Vaccinations are recommended by the European Crohns and Colitis
Organisation (ECCO) to minimise OI in immunocompromised IBD patients
after initial screening.
The current recommendation is to screen for Varicella Zoster Virus (VZV), latent
or active Tuberculosis (TB) and Hepatitis-B and to administer annual inactivated
Influenza vaccine, Pneumococcal (0 & 5 year) and Hepatitis-B (if seronegative)
vaccinations. Swine Flu vaccination was also recommended following the outbreak in 2009.
AIMS & METHODS: Retrospective data was collected on the serology status
for Hepatitis-B, Hepatitis-C, Varicella zoster and T-spot/ IGRA of our patients
receiving biologics from pathology results reporting system. Chest X-rays were
picked up from PACS, BCG vaccination status and history of Chicken pox was
obtained from the clinic letters.
Information about vaccination status was obtained by contacting the general
practioners, directly from patients visiting for their infliximab infusions and
IBD MDT minutes.
RESULTS: Retrospective data from our 144 patients (70 (48%) female and 74
(52%) male) showed a total of 479 patient years of biologics exposure (infliximab-319 and adalimumab-160) in our cohort of Crohns 112 (78%) and
Ulcerative colitis 32 (22%) patients. Combination therapy (Biologics and IM)
was noted in 48 (33%) (45 azathioprine and 3 methotrexate) and biologic monotherapy in 98 (67%) patients.
TB screening with IGRA was done in 144 (100%) and CXR in 53 (37%). Hep B,
Hep C and VZV serology/history of chicken pox was noted in 26 (18%), 19
(13%) and 12 (8%) respectively.
Yearly flu vaccination was given to 16% of the patients and pneumococcal
vaccine was administered in less than 11% of patients.
CONCLUSION: Relevant serological screening and appropriate vaccination
history pre-IM therapy was available in a minority of patients only. This may
represent either non/poor-adherence to ECCO guidelines or poor documentation. Information leaflets on the ECCO-recommended vaccines directed at GPs
and patients may improve compliance. Adoption of IBD registry will enable
clinicians and IBD nurses to empower patients with relevant personalised information delivered at diagnosis and during the course of their treatment. This may
increase the appropriate screening and vaccination of these patients at highest
risk of developing opportunistic infections.
REFERENCES
1) Toruner M et al. Risk factors for opportunistic infections in patients with IBD.
Gastroenterology 2008; 134: 929936.
Disclosure of Interest: None declared
P1472 TIME TO SYMPTOM RESOLUTION IN PATIENTS WITH
ULCERATIVE COLITIS ON MULTIMATRIX MESALAZINE
TREATMENT: A POOLED ANALYSIS
S.D. Silva Sanchez1,*, H. Wan2
1
Shire, Brussels, Belgium, 2Shire, Wayne, PA, United States
Contact E-mail Address: sdasilva@shire.com
INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel
disease characterized by relapsing-remitting symptoms of abdominal pain,
stool urgency, and rectal bleeding. While endoscopic remission is the ultimate
treatment goal for patients with UC, alleviation of clinical symptoms (mainly
rectal bleeding and stool frequency) is a signal that physicians can use to assess
remission status. Improvements in UC symptom scores have also been shown to
correlate with improvements in patients quality of life. Mesalazine (5-aminosalicylic acid; 5-ASA) is standard first-line therapy for treatment of mild-to-moderate UC. This study examined pooled data from several clinical trials of
multimatrix mesalazine, a once-daily (QD) formulation of 5-ASA, in patients
with UC to assess time to symptom resolution in acute treatment, and for
those achieving clinical remission, the proportion of patients remaining in remission after 12 months of maintenance treatment.
AIMS & METHODS: Data from three phase 3 (NCT00503243; NCT00548574;
NCT00151944) and two phase 4 (NCT00446849; NCT01124149) trials were
pooled for this analysis. During acute treatment, patients were randomized to
receive either placebo or multimatrix mesalazine 2.4 g/day QD or twice-daily
(BID), or 4.8 g/day QD or BID for a period of 8 weeks. All patients achieving
symptom resolution (scores of 0 for both stool frequency and rectal bleeding on a
modified UC Disease Activity Index on each of the last available 3 days immediately prior to a study visit) by the end of the acute phase were eligible for 12
months of continued treatment with multimatrix mesalazine 2.4 g/day in a maintenance phase. In 1 study (NCT01124149), those in partial remission (including
combined scores 1 on stool frequency and rectal bleeding) at the end of the
acute phase were also allowed to enroll in the maintenance phase; however, those
patients were excluded from the pooled maintenance phase analysis.
RESULTS: In the acute phase, median (95% confidence interval) time to resolution for placebo and multimatrix mesalazine 2.4 g/day, 4.8 g/day, and 2.4 4.8 g/
day, respectively, for stool frequency symptoms was: 52 days (45, not estimable

A534
[NE]); 33 days (23, 46); 38 days (35, 43); and 38 days (34, 41). For rectal bleeding,
median time to resolution was: 35 days (20, NE); 14 days (12, 18); 16 days (14,
17); and 15 days (14, 17). For stool frequency and rectal bleeding combined,
median time to resolution was: NE (56, NE); 41 days (30, 48); 45 days (42,
50); and 45 days (41, 48). Of those who achieved symptom resolution at the
end of acute phase, the following percentages of patients maintained scores of
0 after 12 months of maintenance treatment: 68.2% (462/677) for stool frequency; 68.3% (721/1055) for rectal bleeding; and 67.4% (438/650) for combined
symptoms.
CONCLUSION: Overall, acute phase treatment with multimatrix mesalazine
(either dose) led to symptom resolution in a shorter time compared with placebo
(38 vs 52 days for stool frequency; 15 vs 35 days for rectal bleeding). In addition,
more than 6 in 10 patients were able to maintain symptom resolution after 12
months of maintenance treatment with multimatrix mesalazine.
Disclosure of Interest: S. Da Silva Sanchez Shareholder of: Shire, Other:
Employee of Shire, H. Wan Shareholder of: Shire, Other: Employee of Shire.
P1473 PROTEOGLYCAN IS EFFECTIVE AND SAFE IN PATIENTS
WITH ULCERATIVE COLITIS
T. Ando1,*, K. Ishiguro1, O. Maeda1, O. Watanabe1, Y. Hirayama1, K. Maeda1,
K. Morise1, M. Matsushita1, T. Yamamura1, K. Furukawa1, K. Funasaka1,
M. Nakamura1, R. Miyahara1, H. Goto1
1
Department of Gastroenterology and Hepatology, Nagoya University Graduate
School of Medicine, Nagoya City, Japan
Contact E-mail Address: takafumiando-gi@umin.ac.jp
INTRODUCTION: Proteoglycan (PG) is a component of extracellular matrix
materials that exist in connective tissues, such as skin, bone, cartilage and vascular wall. PG has been reported to potently suppress the inflammatory
responses induced by heat-killed Escherichia coli in mouse macrophages.
AIMS & METHODS: We aimed to evaluate the efficacy and safety of oral PG
intake in the treatment of ulcerative colitis (UC). In a placebo-controlled, doubleblind study, 40 patients with UC were randomized into either a PG group or a
placebo group for 8 weeks. PG was extracted from salmon nasal cartilage. All
patients were treated with conventional medications prior to entry. Colonoscopy
was done before and at the end of 8 weeks of treatment. Efficacy of treatment
was assessed from clinical symptoms using the clinical activity index (CAI),
which covers stool consistency, rectal bleeding, abdominal pain and global
assessment, with a maximum score of 20. Endoscopic findings were assessed
using the endoscopic index (EI), which is derived from a 12-point scale from
observations at the most severe area of disease involvement within the area 5
15 cm from the anal verge.
RESULTS: EI scores significantly decreased (P 5 0.05) in patients in the PG
group, but showed no significant change in patients in the placebo group. CAI
score significantly (P 5 0.05) improved among patients with mild UC (CAI score
5 6 at enrollment). No side effects were noted in any patient in either the PG or
placebo group.
CONCLUSION: PG was safe and useful in these patients with UC as an additional therapy to conventional therapies, particularly in those at the mild stage.
Disclosure of Interest: None declared
P1474 THE IMPACT OF MUCOSAL HEALING ON SUBSEQUENT
CLINICAL COURSE IN THE MANAGEMENT OF ULCERATIVE
COLITIS: A PROSPECTIVE OBSERVATIONAL STUDY
T. Yamamoto1,*, M. Shiraki1, K. Matsumoto1
1
Inflammatory Bowel Disease Centre, YOKKAICHI HAZU MEDICAL
CENTRE, Yokkaichi, Japan
INTRODUCTION: In clinical trials of ulcerative colitis (UC), mucosal healing
(MH) has been achieved with medical treatment such as 5-aminosalicylates (5ASAs), corticosteroids, immunosuppressive drugs, and biologic agents. However,
clinical implications of MH remain unclear.
AIMS & METHODS: This study was to prospectively evaluate the impact of
MH on the subsequent clinical course in the management of UC. We included
112 UC patients who achieved clinical remission (normal stool frequency and no
rectal bleeding) with medical treatment (5-ASAs, corticosteroids, leukocytapheresis, immunosuppressants, and/or biologics), and who underwent endoscopic
examination when the clinical remission was confirmed. MH was defined as a
Mayo endoscopic subscore of either 0 (no lesions) or 1 (mild activity). All
patients were followed up for 4 1 year.
RESULTS: Of the 112 patients, 62 (55%) achieved MH and 50 (45%) did not.
During the 1-year follow-up, 74 patients (66%) maintained clinical remission,
while 38 patients (34%) relapsed. Overall, the clinical remission rate was significantly higher in patients who achieved MH (52/62, 84%) than in those who did
not (22/50, 44%) (p 0.00001). In a subgroup analysis of patients who received
5-ASA for remission maintenance therapy, the clinical remission rate was significantly higher in patients with MH (25/32, 78%) than in those without MH
(13/32, 41%) (p 0.002). Similarly, among patients who received immunosuppressive drugs and/or biologic agents during maintenance therapy, the clinical
remission rate was significantly higher in patients with MH (27/30, 90%) than in
those without MH (9/18, 50%) (p 0.002).
CONCLUSION: Patients who achieve clinical remission with MH have a
reduced risk of future clinical relapse as compared with those without MH in
the management of UC.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1475 SHORT AND MEDIUM TERM EFFICACY OF ADALIMUMAB IN
ULCERATIVE COLITIS A MULTICENTRE, PROSPECTIVE
OBSERVATIONAL STUDY
T. Molnar1,*, A. Balint1, M. Szucs2, Z. Szepes1, F. Nagy1, K. Farkas1, R. Bor1,
L. Lakner3, K. Palatka4, P. Miheller5, A. Csontos5, G. Hegede6, I. Racz7,
A. Vincze8, P.L. Lakatos9, P. Golovics9, Z. Gabor10, M. Juhasz5, F. Zsigmond11,
T. Wittmann1
1
First Department of Medicine, 2Department of Medical Physics and Informatics,
UNIVERSITY OF SZEGED, Szeged, 3Teaching Hospital Markusovszky,
Szombathely, 42nd Department of Medicine, University of Debrecen, Debrecen,
5
2nd Department of Medicine, Semmelweis University, 61st Department of
Medicine, Sandor Peterfy Hospital, Budapest, 71st Department of Medicine, Petz
Aladar Hospital, Gyor, 81st Department of Medicine, University of Pecs, Pecs, 91st
Department of Medicine, Semmelweis University, Budapest, 10Department of
Gastroenterology, Semmelweis Health Center, Miskolc, 11Department of Internal
Medicine, National Medical Center, Budapest, Hungary
Contact E-mail Address: molnar.tamas@med.u-szeged.hu
INTRODUCTION: Adalimumab is a relatively new therapeutic option in ulcerative colitis (UC). After the ULTRA trials only a few data have been published
from the real clinical practice.
AIMS & METHODS: The aim of this study was to prospectively follow the
disease course in adalimumab-treated UC patients in Hungary. Primary endpoints were the remission and response rates at week 12 and 30; while secondary
endpoints were the changes of C-reactive protein (CRP) levels and the clinical
symptoms during the therapy.79 patients who was treated with adalimumab at 10
tertiary Hungarian IBD centres were prospectively enrolled from May 2013
[male/female: 43/36; mean age: 41.7 years (in range: 19-68 years)]. 65.8% of
the patients previously received infliximab therapy. Switch to adalimumab in
these patients was due to loss of response or intolerance. Clinical data, partial
Mayo (pMayo) score and CRP levels were collected at the beginning of adalimumab therapy, at week 12 and at week 30. Colonoscopy was performed before
drug administration. Endoscopic Mayo subscore was used to assess the mucosal
activity. Clinical remission was defined as 2 points in pMayo score; response to
adalimumab was specified as decreasing 3 or more points.
RESULTS: Adalimumab induction was administered at doses of 160 mg and 80
mg at week 0 and week 2. The mean value of Mayo score at the beginning of
adalimumab therapy was 9.7 points. The mean values of pMayo subscores and
CRP were 3.5 points, 6.6 mg/l at week 12, and 3.2 points, 7.8 mg/l at week 30,
respectively. CRP levels and pMayo subscores decreased significantly at week 12
(p50.001, p50.001), and at week 30 remained significant also (p 0.027,
p50.001). Remission, response and non-response rates were 28.8 %, 43.9%,
and 27.3% at week 12, and remission, response, loss of response rates were
50%, 40.9% and 9.1% at week 30. No significant difference was detected
between patients previously treated with biologicals or naive to them. In addition, we did not find significant association between previous infliximab use and
frequency of adalimumab side effects. Adalimumab therapy needed to be discontinued in 12 subjects.
CONCLUSION: Our results suggest that adalimumab is an effective drug for the
induction of remission and for the maintenance therapy of UC.
Disclosure of Interest: None declared
P1476 SENSITIVITY ANALYSES OF DISEASE CONTROL AMONG
MODERATE TO SEVERE ULCERATIVE COLITIS PATIENTS
TREATED WITH CONVENTIONAL THERAPIES IN EUROPE: THE
UC CARES (ULCERATIVE COLITIS CONDITION, ATTITUDE,
RESOURCE AND EDUCATIONAL STUDY)
G. Van Assche1, L. Peyrin-Biroulet2, T. Fan3,*, M. Lynam4, S. Rojas-Farreras4,
Q. Ding5
1
University Hospitals Leuven, Leuven, Belgium, 2Nancy University Hospital,
Vandoeuvre-le`s-Nancy, France, 3Merck & Co., Inc, Whitehouse Station, United
States, 4IMS Health, Barcelona, Spain, 5Temple University, Philadelphia, United
States
INTRODUCTION: A large proportion of moderate to severe ulcerative colitis
(UC) patients rely on conventional therapies (5-ASA, steroids and/or thiopurines) to maintain remission. However, use of UC therapies among biologic na ve
patients varies considerably in clinical practice, and it is unknown whether disease is well controlled.
AIMS & METHODS: This analysis is to comprehensively describe rates of disease control in moderate to severe UC patients who were biologics na ve and
treated with conventional therapies.
Biologics-na ve patients with moderate to severe active UC (Mayo score 6),
aged 18 years who received conventional therapies during the 12 months prior
to enrollment were recruited from 11 European countries. Patients who underwent colectomy procedure or ileo-anal J-pouch reconstruction were excluded.
Medical charts for the 12 months prior to enrollment were reviewed to collect
clinical data. The primary endpoint was disease control, defined as maintaining
remission status, measured by full or partial Mayo scores, and patients had to
have no corticosteroid use the 2 months prior to enrollment.
Sensitivity analyses were conducted according to the criteria whether the patients
had thiopurines for at least 4 months in 12 months prior to enrollment and the
timeline (within 2 weeks vs. 2 weeks before; winthin 1 month vs. 1 month before)
when endoscopy was taken for the patients.
RESULTS: A total of 250 patients were included in the final analysis. Patients
mean age was 46.6 (SD 16.3) and 59% were male. The median duration of UC
was 6.9 years (IQR 2.3-14.4). Extent of UC included 21.6% proctitis, 28.4% leftsided, and 49.6% extensive colitis. At the enrollment date, the percentages of
patients receiving thiopurines, aminosalicylates, corticosteroids and other types

United European Gastroenterology Journal 2(1S)


of immunosuppressants were 63.2%, 75.2%, 23.6% and 3.6%, respectively.
According to the study definition, 87.2% of patients did not achieve disease
control. Specifically, 87.3% of patients (55 out of 63) with endoscopy score
within the 2 weeks prior to enrollment and 87.2% of patients (163 out of 187)
with endoscopy score more than 2 weeks prior to enrollment had uncontrolled
disease (p 0.98). In addition, 86 out of 98 patients (87.8%) with endoscopy
score within 1 month prior to enrollment and 132 out of 152 patients (86.8%)
with endoscopy score more than 1 month were not in disease control (p 0.83).
Patients who had thiopurines for at least 4 months in 12 months prior to enrollment had numerically higher percentage of uncontrolled UC (89.1% vs. 85.9%,
p 0.46)
CONCLUSION: The majority of biologics na ve UC patients (87%) were not
under control. Sensitivity analyses show that patients who had thiopurines for at
least 4 months in 12 months prior to enrollment had numerically higher percentage of uncontrolled UC, but not significant difference. Disease control did not
vary much according to the time of endoscopy measurement, noting that patients
who had more than one endoscopy may be counted in each applicable group.
Disclosure of Interest: G. Van Assche Consultancy for: Merck & Co., Inc, L.
Peyrin-Biroulet Consultancy for: Merck & Co., Inc, T. Fan Other: Employee of
Merck & Co., Inc, M. Lynam Consultancy for: Merck & Co., Inc, S. RojasFarreras Consultancy for: Merck & Co., Inc, Q. Ding: None declared
P1477 ESOPHAGEAL ULCER FEATURES OF BEHCETS DISEASE
WITH GASTROINTESTINAL LESIONS?
T. Omori1,*, S. Nakamura1, B. Iizuka1, T. Kuriyama1, A. Ito1, M. Yonezawa1,
K. Shiratori1
1
IBD Centre, Tokyo Womens Medical University Hospital, Tokyo, Japan
Contact E-mail Address: tohmori@ige.twmu.ac.jp
INTRODUCTION: The Japanese diagnostic criteria for Behcets disease (BD)
define it as a systemic inflammatory disorder characterized by 4 hallmark symptoms (recurrent oral aphthosis, skin symptoms, ocular symptoms, and vulvar
ulceration), which can coexist with other accessory/variant symptoms (such as
arthritis) that develop metachronously. BD is categorized as complete, incomplete, or suspected according to the extent of this symptom tetrad, while BD with
ileocecal ulcer, vascular, and/or nervous system involvement is categorized under
special types. That is, if ileocecal ulcer, vascular, or neurological symptoms are
present in patients with BD, the disease is classified as gastrointestinal BD,
vascular BD, or CNS-BD, respectively. Gastrointestinal lesions associated with
Behcets disease typically develop in the ileocecal ulcer, but atypical gastrointestinal lesions also often occur. This article presents our patients who had BD with
esophageal ulcers, which is an atypical gastrointestinal lesion, and outlines the
clinical and endoscopic features of their esophageal involvement.
AIMS & METHODS: At our hospital, 33 patients were diagnosed as having BD
with gastrointestinal lesions and drug-induced mucosal injury was ruled out (sex
ratio 17:16; 3 patients with complete BD, 25 patients with incomplete BD, and
5 patients with suspected BD; special types 14 with gastrointestinal BD, 3 with
vascular BD, and 1 with CNS-BD (some patients duplicated)). Among these 33
patients, those who had esophageal lesions were retrospectively reviewed to
assess their disease types and endoscopic features.
RESULTS: Among the 33 patients, esophageal lesions were found in 4 patients
(12.1%). Their sex ratio was 1:1 and their mean age was 35.7522.42 years. They
had incomplete BD, although all 4 patients had oral aphthosis (skin symptoms in
2, ocular symptoms in 2, vulvar ulceration in 0, arthritis in 3, and vascular lesions
in 1 patient). They all complained of chest pain. Ileocecal ulcers were found in 3
of the 4 patients. Their esophageal ulcers were located in the mid-esophagus at a
mean of 334.27 cm from the incisors. These ulcers were generally round and
punched-out in all 4 patients, although fused bead-like lesions were also
observed. Three patients had multiple esophageal lesions, and one had a single
lesion. Three of the 4 patients suffered relapse of esophageal ulcers that was
clearly associated with exacerbation of BD. All 4 patients were treated with
corticosteroids, and adalimumab was also administered to one patient to control
other symptoms. With corticosteroid therapy, chest pain did not relapse, and
upper gastrointestinal endoscopy confirmed healing of the esophageal lesions
after 44 weeks of treatment.
CONCLUSION: Esophageal ulcers were mostly located at the mid-esophagus in
BD. Their ulcers were generally round and punched-out, and also tended to be
fused. The ulcers relapsed repeatedly as occurs with ileocecal lesions, which may
be a characteristic of BD.
Disclosure of Interest: None declared
P1478 IS MUCOSAL HEALING ACHIEVED AFTER ADALIMUMAB
TREATMENT IN ULCERATIVE COLITIS?
T. Ilias1,*, O. Fratila1, C. Craciun2
1
University of Oradea, Oradea, 2 Electron Microscopy Center, Babes Bolyai
University, Cluj Napoca, Romania
Contact E-mail Address: tiberia_ilias@yahoo.com
INTRODUCTION: Because Crohns disease (CD) is described as corresponding
to a Th1-proinflammatory, TNF--mediated response and ulcerative colitis (UC)
is considered to be mediated by a Th2 immune response is adalimumab just as
suitable in UC as in CD?
AIMS & METHODS: To evaluate mucosal healing in UC by examining the
intracellular changes of colonic mucosa, before and after adalimumab treatment.
We studied sixteen patients (14 women, 21-65 years) previously diagnosed with
UC of moderate-severe form (Disease Activity Index-UCDAI46, Endoscopic
Index-EI44). All patients were treated with adalimumab (Humira) subcutaneous, at standard doses as it follows: 160 mg at week 0.80 mg at week 2 and
afterwards 40 mg at a 2 week interval. We performed a colonoscopy before and 6

A535
months after the first administration of adalimumab. During colonoscopy we
collected biopsies that were later processed specifically, stained with uranyl acetate and lead citrate and examined with a JEM-1010 transmission electron
microscope.
RESULTS: Before treatment we noticed severe alterations of the epitheliumdepletion of microvilli, shattering of epithelial junctions, cytoplasmic vacuolization, dilatation of the endoplasmic reticulum, pycnotic nuclei, destruction of
mitochondria and Golgi complexes which conducted to drastic reduction of
cell metabolism. Rarefaction of the goblet cells, together with abnormal mucus
formation and secretion was observed. The corresponding chorion showed
degeneration of collagen fibres and smooth muscle cells, obstructed capillaries,
neutrophilic and mononuclear infiltration. After adalimumab therapy, we
noticed improvement in morphology and function of epithelial organelles, rich
mucus secretion and recovery of the chorionic components. The clinical response
observed in all our patients was supported by a descent in UCDAI. Endoscopic
severity diminished as well- with 14 out of 16 cases entering remission (EI4).
CONCLUSION: Our study clearly demonstrated signs of epithelial barrier
recovery at the end of treatment which is one of the main goals of UC treatment.
Also the ultrastructural features that we described, might help to a deeper understanding of UC pathogenicity and mechanism of action of the anti-TNF-alpha
therapies.
Disclosure of Interest: None declared
P1479 CYCLOSPORIN A IN ACUTE STEROID-REFRACTORY OR
DEPENDENT ULCERATIVE COLITIS: A PROSPECTIVE STUDY
ON LONG TERM OUTCOME
U. Nieminen1,*, U. Turunen1, P. Arkkila1, T. Sipponen1, C.-G. Af Bjorkesten2,
M.A. Farkkila1,3
1
Department of Gastroenterology, Helsinki University Central Hospital, Helsinki,
2
Department of Gastroenterology, Helsinki University Central Hospital, Jorvi
Hospital, Espoo, 3Institute of Clinical Medicine, Helsinki University, Helsinki,
Finland
Contact E-mail Address: urpo.nieminen@hus.fi
INTRODUCTION: In severe corticosteroid refractory ulcerative colitis (UC)
cyclosporine A (CsA) or infliximab (IFX) are advantageous to avoid colectomy,
and their effectiveness is comparable (Laherie et al. Lancet 2012).
AIMS & METHODS: The aim of this prospective study (IBD-HOT) was to
evaluate the use, efficacy, and safety of CsA in treatment of acute flare of UC.
All consecutive patients with moderate to severe CU refractory, intolerant to or
dependent on corticosteroids and treated with CsA between Jan-2007 and Dec2009 were enrolled. Inclusion criteria were active ulcerative colitis with a total
Mayo score of 6 to 12 and moderate-to-severe active disease at colonoscopy.
Patients outcome and adverse effects were followed-up for three years or until
colectomy as the major endpoint. Clinical and laboratory data were collected at
the beginning of CsA therapy and at routine scheduled visits. Patients survival
w/o colectomy was analysed by Kaplan-Meier survival analysis.
RESULTS: 61 patients (28 female) fulfilled the inclusion criteria. Mean age was
35 years (MED 33, Range 18-64). CsA induction therapy was given intravenously
to 40 patients for seven days (MED 7, Range 4-8), and mean dose was 2.15 mg/
kg (MED 2.0, Range 1.8-3.6). Oral induction was given to 21 patients with mean
dose of 3.8 mg/kg (MED 3.8, Range 2.4-5.5). Eight patients had used thiopurins
before CsA longer than two weeks, but only three of them longer than 2 months.
Other patients started thiopurins during CsA induction (46 pts) or soon thereafter (7 pts). The mean MAYO scores declined significantly during the beginning
of the follow-up period and stayed low thereafter. The clinical response to CsA
during the one-week induction period was scored as good in 18 (29.5%), moderate in 26 (42.6%), only partial in 15 (24.6%) and poor in 2 (3.3%) patients.
Colectomy-free survival at 3 years was 72.1 % (95% CI 60.9 83.4). Number of
colectomies during the 3-year follow-up period was 17 (27.9 %) due to continuously active colitis (14 pts) or colonic mucosal dysplasia (3 pts). All colectomised
patients had disease duration under 5 years, and short disease duration was the
only independent risk factor for colectomy in multivariate regression analysis
including gender, hemoglobin, albumin, C-reactive protein and disease duration.
Disease duration had marginally significant predictive value for colectomy
(p 0.049; Odds Ratio 0.74, 95% CI 0.54 - 1.00).
In addition to colectomies, two patients were re-treated with CsA during the
follow-up, and twelve with infliximab due to active disease. Seven (58.3 %) of
IFX treated patients needed colectomy subsequently. Thus outcome after CsA
rescue therapy without colectomy or need for CsA re-treatment or infliximab was
62.3 % (95% CI 50.1 74.5).
Adverse events were registered in seven patients: Cytomegalo viral infection (3),
Pneumocystis jirovecii infection (1), Clostridium difficile colitis (1), transaminase
elevation (1), venous thrombosis (1).
CONCLUSION: CsA treatment was successful in 72% of patient who avoided
colectomy, and we see CsA as good option in moderate-to-severe acute corticosteroid refractory or corticosteroid resistant thiopurin na ve UC. Short disease
duration was independent risk factor for colectomy. Risk of infection under high
immunosuppression must be remembered.
Disclosure of Interest: None declared

A536

United European Gastroenterology Journal 2(1S)

P1480 ACCEPTANCE OF INFLAMMATORY BOWEL


TREATMENT RECOMMENDATIONS BASED ON
APPROPRIATENESS RATINGS: DO PRACTICING
GASTROENTEROLOGISTS AGREE WITH EXPERTS?
1,*

DISEASE

Disclosure of Interest: None declared


P1482 SUSTAINED USE OF THIOPURINES REDUCES THE RISK OF
PERIANAL SURGERY IN CROHNS DISEASE

2,3

V. Pittet , M.H. Maillard , S. Lauvergeon , M. Timmer , P. Michetti ,


F. Froehlich2,4, B. Burnand1, J.-P. Vader1, C. Mottet5
1
Healthcare evaluation unit, INSTITUTE OF SOCIAL AND PREVENTIVE
MEDICINE, 2Division of Gastroenterology & Hepatology, Lausanne University
Hospital, 3Crohn and Colitis Center, Clinique La Source-Beaulieu, LAUSANNE,
4
Division of Gastroenterology & Hepatology, University Hospital Basel, Basel,
5
Division of Gastroenterology, Hopital Neuchatelois, Neuchatel, Switzerland
Contact E-mail Address: Valerie. Pittet@chuv.ch
INTRODUCTION: Appropriateness criteria for the treatment of Crohns disease (CD) and ulcerative colitis (UC) have been developed by experts panels.
Little is known about the acceptance of such recommendations by care providers.
We aimed to explore how treatment decisions of practicing gastroenterologists
differ from experts using a vignette case study and a focus group.
AIMS & METHODS: Seventeen clinical vignettes were drawn from clinical
indications evaluated by the expert panel. A vignette case questionnaire asking
for treatment options in 9-10 clinical situations was submitted to 26 practicing
gastroenterologists. For each vignette case, practitioners answers were compared
to panel decisions by calculating the proportions of treatments judged by the
panels as being appropriate, uncertain and inappropriate. Qualitative analysis
was made based on focus group discussion to explore acceptance and divergence
reasons.
RESULTS: 239 clinical vignettes were completed, 98 for CD and 141 for UC.
Proposed treatments were more frequently considered inappropriate as compared to results from panels for CD (45%) than for UC (27%). Among UC
clinical vignettes, the main divergences with the panel were linked to 5-ASA
failure assessment and to situations where stopping treatment was the main
decision. For CD, the care provider propositions diverged with the panel in
mild-to-moderate active disease, where practitioners were more aggressive than
the panels recommendations and in stenotic complications management.
CONCLUSION: In about one third of vignettes cases, IBD treatment propositions by practicing gastroenterologists were considered inappropriate as compared to expert recommendations. Practicing gastroenterologists may not
always know current evidence and guidelines, but are often aware of the difficulties of applying recommendations in real IBD patients.
Disclosure of Interest: None declared
P1481 TEN YEARS PROSPECTIVE STUDY OF INFLIXIMAB
TREATMENT IN ULCERATIVE COLITIS PERFORMING AN
ALGORITHM OF DISCONTINUATION
V. Hansen1,1,*, K.-M. Johnsen1, G. Rasmus1, J. Florholmen1
1
gastroenterology, University Hospital Troms, Troms, Norway
Contact E-mail Address: jon.florholmen@unn.no
INTRODUCTION: Anti-tumor necrosis factor (TNF) has the last decade
become an important part of the treatment of severe ulcerative colitis (UC),
but there is no international consensus of discontinuation of the therapy.
AIMS & METHODS: To study the long term time of remission performing a
prospective study using an algorithm of discontinuation of the anti-TNF drug
infliximab (IFX) in UC
UC patients with moderate to severe disease activity admitted at the University
Hospital of North Norway in the period 2002-2011 were enrolled. Patients in the
need of IFX were enrolled in a prospective study performing the following algorithm: intensive induction therapy (week 0, 2, 6, later each 4 week) until remission
according the UCD activity index score (UCDAI) (score 0-2), discontinuation of
treatment with subsequent re-induction of IFX treatment if relapse.
RESULTS: Of the 132 patients enrolled in the study 116 patients were evaluated
according to the protocol. The mean total observation time was 43 (6-117)
months and the patients were in remission 70% of the total observation time.
Of the 3 first inductions therapies 96/116 (83 %), 37/61 (61 %) and 10/19 (53 %)
were treated to remission, respectively. The mean time of remission was 20, 19
and 12 moths in the 3 first induction therapies, respectively, and predictors of
long term remission was sex (woman) and non-smoking. The number of patients
in remission that never relapsed was 58/96 (60 %), and sex (woman) was a
predictor for never relapse. Eighteen patients (18 %) were withdrawn due to
need of colectomi, 10 (8 %) patients were withdrawn due to severe allergic
reactions.
CONCLUSION: An intensified IFX induction regime of treatment to remission
in patients with UC followed by a discontinuation of treatment showed high
efficacy even in the re-treatments, and a high overall time being in remission.
There was no tendency of increased allergic reaction to IFX during repeated
induction therapies.

V. Chhaya1,*, S. Saxena2, E. Cecil2, V. Subramanian3, V. Curcin4, A. Majeed2,


R. Pollok1
1
Gastroenterology, St Georges Hospital, 2Primary Care and Public Health,
Imperial College, London, 3Gastroenterology, St James University Hospital, Leeds,
4
Computer Science, Imperial College, London, United Kingdom
Contact E-mail Address: richard.pollok@nhs.net
INTRODUCTION: The thiopurine (TP) analogues, azathioprine and mercaptopurine are widely used in the management of Crohns disease (CD). Recent
studies suggest they reduce the risk of intestinal resection, but their impact on
perianal surgery is unknown.
AIMS & METHODS: Our aim was to determine if TPs reduced the risk of
perianal surgery in CD.
We conducted a population based study using electronic primary care records in
the UK using a validated research database, the Clinical Practice Research
Datalink (CPRD) which represents an 8% sample of the UK population. We
identified incident cases of CD between 1995 and 2009 by selecting patients
registered with a practice for at least 12 months prior to diagnosis. We excluded
patients who had perianal surgery before or at the time of diagnosis. We grouped
patients according to treatment duration and compared rates of first perianal
surgery using Kaplan-Meier survival analysis. We used a multivariable Cox proportional hazards model to adjust for confounders and compare outcomes
according to duration of treatment. We used separate models for each duration
of use: 12 months vs 512 months, 18 months vs 518months and 24 months
vs 524 months. We also evaluated early TP use, within 12 months of diagnosis.
RESULTS: Overall, 5235 patients met our inclusion criteria, of whom 124 had
perianal surgery during 15 years of follow up. 56.3% were female and the median
age at diagnosis was 38.5 years (IQR: 24.8 57.1). TP use for 12 months
duration did not impact on the 5 year cumulative probability of perianal surgery
when compared with TP use for 512 months. However, the unadjusted 5 year
cumulative probability of perianal surgery for those using TPs for 18 months
was 2.9% (95% CI: 2.0 4.3%) compared to 5.8% (95% CI: 4.0 8.2%) for
those using TPs for less than 518 months (log-rank test for trend p 0.02). After
adjustment, sustained TP use for 18 months had a 40% reduction in risk of
perianal surgery (HR 0.60, 95% CI: 0.39 0.95, p 0.03) which improved to
49% (HR 0.51, 95% CI: 0.32 0.99, p 0.004) at 2 years. Early TP use did not
offer any additional benefit.
CONCLUSION: Sustained TP use in patients with CD halves the risk of perianal
surgery at 2 years, although a long duration of treatment is required. We suggest
sustained use of TPs for greater than 18 months duration in patients with perianal CD and propose further study to evaluate rates of perianal surgery in CD
which at present is unknown.
Disclosure of Interest: None declared
P1483 IN
IBD
OUTPATIENTS
KNOWLEDGE
OF
CALPROTECTIN AND INFLIXIMAB TROUGH LEVELS
SIGNIFICANTLY ALTERS CLINICAL DECISION MAKING

FECAL

V. Huang1,*, C. Prosser1, C. Shalapay1, N. Dhami1, D. Fedorak1, H. Wang2,


K. Kroeker1, R. Fedorak1
1
Medicine, 2Surgery, University of Alberta, Edmonton, Canada
INTRODUCTION: Infliximab is an effective, but costly, therapy for inflammatory bowel disease (IBD). Loss of response to infliximab will occur in over 50%
of patients within 3 ys, resulting in infliximab dose intensification. One third of
patients with symptoms do not have actual disease recurrence.
AIMS & METHODS: Aim: The aim of this study was to determine if objective
measures of inflammation using fecal calprotectin (FCP), and infliximab trough
levels (ITL) would lead to different management decisions of patients on infliximab than those made when only clinical assessment was available.
Methods: IBD patients receiving maintenance infliximab at the University of
Alberta IBD infusion center were consented to provide stool and blood samples
for measurement of FCP and ITL prior to their infusion. FCP and ITL levels
were determined by immunodiagnostic ELISA. At the time of the infusion clinical HBI and Mayo scores were recorded. An IBD panel made a clinical decision based on the clinical assessment recorded. The decision options were no
action or an action (scope, increase dose or switch drug, decrease dose). The
panel then incorporated FCP to the clinical decision to determine clinical
FCP decision; and ITL to the clinical FCP decision to determine the
clinical FCP ITL decision. The clinical decision was compared to the
clinical FCP decision or clinical FCP ITL decision, and actions
analyzed for concordance.

Table to abstract P1483


Table 1 Contingency Table Showing Impact of Adding FCP and ITL to Expert Panel Clinical Decisions
Expert Panel Decision (Clinical plus FCP)

N 36
Expert Panel Clinical Decision

No change
Investigate (scope)
Dose escalation
Dose de-escalation

N
N
N
N

29
6
1
0

No change
N 19

Investigate (Scope)
N 16

Dose escalation
N1

Dose de-escalation
N0

19/36 (52.8%)
0
0
0

10/36 (27.8%)
6/36 (16.7%)
0
0

0
0
1/36 (2.8%)
0

0
0
0
0

A537

United European Gastroenterology Journal 2(1S)


RESULTS: A total of 36 patients were included (25 CD and 11 UC). As shown in
Table 1, the addition of FCP to expert panel clinical decisions led to a change in
decisions 10/36 (27.8%) of the cases all of which were from no change to
investigate (scope). The addition of ITL to the expert panel clinical plus FCP
decision led to a change in decisions 10/36 (27.8%) of the cases 6/36 (16.7%)
were from no change to infliximab dose de-escalation.
CONCLUSION: The addition of an infliximab trough level or a fecal calprotectin level, incorporated via a fixed algorithm or an expert IBD panel, frequently
led to different management decisions compared to clinical assessment alone. The
incorporation of fecal calprotectin and infliximab trough levels into daily care
requires careful assessment of their effect on outcomes.
Disclosure of Interest: None declared
P1484 CHARACTERIZATION OF MUCOSAL HEALING WITH
ADALIMUMAB TREATMENT IN PATIENTS WITH MODERATELY
TO SEVERELY ACTIVE CROHNS DISEASE FROM EXTEND
W. Reinisch1,*, J.-F. Colombel2, G. DHaens3, W.J. Sandborn4, P. Rutgeerts5,
J. Petersson6, S. Eichner6, Q. Zhou6, A. Iezzi7, R.B. Thakkar6
1
McMaster University, Hamilton, Canada, 2Icahn School of Medicine, New York,
United States, 3Academic Medical Center, Amsterdam, Netherlands, 4UCSD, La
Jolla, United States, 5U of Leuven, Leuven, Belgium, 6AbbVie Inc, North Chicago,
United States, 7AbbVie Inc, Rungis, France
INTRODUCTION: Patients (Pts) continuously treated with adalimumab (ADA)
in the EXTEND trial were more likely to achieve and maintain mucosal healing
(MH) than pts receiving induction ADA only/placebo (PBO) treatment.1 MH of
the individual ileocolonic segments with ADA maintenance therapy is evaluated
in pts from EXTEND.
AIMS & METHODS: In EXTEND, pts with Crohns disease (CD), CDAI 220450, and documented mucosal ulceration at study screening, received open-label
(OL) ADA (160/80 mg) at wks 0/2. Pts were randomized at wk 4 to double-blind
maintenance ADA (40 mg every other wk) or PBO to wk 52. Pts with flare/nonresponse could move to OL ADA at or after wk 8. Change from baseline (BL) in
the CDEIS variables surface involved and ulcerated surface were assessed in each
of the five ileocolonic segments at wks 12 and 52 only in pts who had measurements at all three time points. The presence of deep and superficial ulcers was
assessed at wks 12 and 52 in pts who had deep and superficial ulcers at BL. All
scores were based on central reading data. Pts were analyzed according to randomized treatment group. For pts who moved to OL ADA after wk 12, the
CDEIS variable score at time of moving to OL ADA was used as the wk 52
data point. Pts who moved to OL ADA before wk 12 are not included in this
analysis.
RESULTS: Improvement in surface involved was observed in all segments at wk
12 in induction ADA/PBO pts and at wks 12 and 52 in ADA randomized pts
(Table). Statistically significant greater mean change from BL in surface involved
was observed in the rectum, sigmoid/left colon, and transverse colon at wk 52 in
ADA randomized pts compared to induction ADA/PBO pts (Table). Similar
results were observed for CDEIS ulcerated surface. Of the pts with deep or
superficial ulcers at BL, more ADA randomized pts were without deep (13/20,
65.0%) and superficial ulcers (11/24, 45.8%) relative to induction ADA/PBO pts
at wk 52 (no deep 5/20, 25.0%; no superficial ulcers 2/20, 10.0%).
Table. Mean BL values of CDEIS surface involved by segment and randomized
treatment group and mean change from BL at wks 12 and 52.
Induction ADA/PBO

Rectum
Sigmoid/left colon
Transverse colon
Right colon
Ileum

ADA maintenance

week week BL
BL mean, cm 12, cm 52, cm mean, cm

week week
12, cm 52, cm

5.0
5.5
4.0
4.8
5.2

-3.8*
-3.4
-4.6**
-3.1
-2.4

(N 14)
(N 14)
(N 10)
(N 9)
(N 8)

-2.3
-3.0
-0.5
-2.7
-1.1

-0.5
1.4
0.5
-2.7
-0.1

3.9
3.6
4.9
3.7
4.0

(N 12)
(N 15)
(N 12)
(N 7)
(N 13)

-3.6**
-3.2***
-3.7**
-2.6
-2.2

CONCLUSION: ADA maintenance therapy was beneficial in healing deep and


superficial ulcers in pts with moderately to severely active CD. Although continuous ADA treatment improved the mucosal surface of all ileocolonic segments, the greatest improvement was in the rectum, left colon, and transverse
colon.
REFERENCES
1. Rutgeerts, et al. Gastroenterol 2012; 142: 1102-1111.
Disclosure of Interest: W. Reinisch Consultancy for: AbbVie, Aesca, Amgen,
Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix,
Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Ferring, Genentech,
Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid
Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, Austria and 4SC.,
J.-F. Colombel Consultancy for: for AbbVie, Bristol Meyers Squibb, Ferring,
Genentech, Giuliani SPA, Given Imaging, Merck & Co., Millenium
Pharmaceuticals Inc., Pfizer Inc. Prometheus Laboratories, Sanofi, Schering
Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma (previously
named Celltech Therapeutics, Ltd)., G. DHaens Financial support for research
from: Abbott Laboratories, Janssen Biologics, Given Imaging, MSD, DrFalk
Pharma, Photopill, Lecture fee(s) from: Abbott Laboratories, Tillotts,

Tramedico, Ferring, MSD, UCB, Norgine, Shire, Consultancy for: AbbVie,


ActoGeniX, AM Pharma, Boehringer Ingelheim GmbH, Centocor,
ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, Engene, Dr Falf
Pharma, Ferring, Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline,
Jansen Biologics, Merck Sharp and Dohme Corp, Millennium Pharmaceuticals
Inc. (now Takeda), Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer,
Receptos, Salix, Setpoint, Shire Pharmaceuticals, Schering-Plough, Tillotts
Pharma, UCB Pharma, Versant and Vifor Pharma, W. Sandborn Financial
support for research from: AbbVie, Bristol-Myers Squibb, Genentech,
GlaxoSmithKline, Janssen, Millennium, Novartis, Pfizer, Procter and Gamble
Pharmaceuticals, Shire Pharmaceuticals, and UCB Pharma., Lecture fee(s) from:
AbbVie, Bristol-Myers Squibb, and Janssen, Consultancy for: AbbVie,
ActoGeniX NV, AGI Therapeutics, Inc., Alba Therapeutics Corporation,
Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas,
Athersys, Inc., Atlantic Healthcare Limited, Aptalis, BioBalance Corporation,
Boehringer-Ingelheim
Inc,
Bristol-Myers
Squibb,
Celgene,
Celek
Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx,
CoMentis,
Cosmo
Technologies,
Coronado
Biosciences,
Cytokine
Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research Inc, Elan
Pharmaceuticals, EnGene, Inc., Eli Lilly, Enteromedics, Exagen Diagnostics,
Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc., Funxional
Therapeutics Limited, Genzyme Corporation, Genentech, Gilead Sciences,
Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood
Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc., Lexicon
Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research
Laboratories, MerckSerono, Merck & Co., Millennium, Nisshin Kyorin
Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer
Pharmaceuticals, Orexigen Therapeutics, Inc., PDL Biopharma, Pfizer, Procter
and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis
Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix
Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, Sigmoid Pharma
Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L. A. Pharma
(UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma
AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics
Limited (VBL), Warner Chilcott UK Limited, P. Rutgeerts Financial support
for research from: AbbVie, Centocor, Merck and UCB Pharma, Lecture fee(s)
from: AbbVie, Centocor, Merck and UCB Pharma, Consultancy for: AbbVie,
Bristol-Myers Squibb, Centocor, Merck, Millennium Pharmaceuticals Inc. (now
Takeda) and UCB Pharma, J. Petersson Shareholder of: AbbVie, Other:
Employee: AbbVie, S. Eichner Shareholder of: AbbVie, Other: Employee:
AbbVie, Q. Zhou Shareholder of: AbbVie, Other: Employee: AbbVie, A. Iezzi
Shareholder of: AbbVie, Other: Employee: AbbVie, R. Thakkar Shareholder of:
AbbVie, Other: Employee: AbbVie.
P1485 DURABILITY OF CLINICAL REMISSION WITH VEDOLIZUMAB
IN CROHNS DISEASE
W. Sandborn1, S. Danese2,*, B. Abhyankar3, W. Reinisch4, J. Xu5, K. Lasch6,
C. Milch5
1
Division of Gastroenterology, University of California San Diego, La Jolla, United
States, 2IBD Center, Istituto Clinico Humanitas, Milan, Italy, 3Takeda Global
Research & Development Centre (Europe) Ltd, London, United Kingdom,
4
Department Internal Medicine III, Medical University of Vienna, Vienna, Austria,
5
Takeda Pharmaceuticals International Co., Cambridge, 6Takeda Pharmaceuticals
International, Inc., Deerfield, United States
Contact E-mail Address: wsandborn@ucsd.edu
INTRODUCTION: Efficacy and safety of vedolizumab (VDZ) in patients with
Crohns disease (CD) were demonstrated in the GEMINI 2 study.1 However, the
proportion of patients with durable clinical remission (secondary end point;
Crohns Disease Activity Index [CDAI] score 150 points at 11 of 13 [80%]
visits from wks 6-52) was not significantly different between the VDZ and placebo (PBO) groups. To account for factors that may have led to this result (eg,
previous VDZ induction therapy in maintenance PBO patients coupled with the
long half-life of VDZ), we defined alternative post hoc end points to further
evaluate the effects of VDZ on durable clinical remission.
AIMS & METHODS: In GEMINI 2, patients with CD were randomly assigned
to receive blinded VDZ 300 mg or PBO or open-label VDZ 300 mg at wks 0 and
2 of the induction phase (wks 0-6). Wk 6 VDZ responders were rerandomized to
receive VDZ 300 mg every 8 wks (Q8W; n 154) or every 4 wks (Q4W; n 154)
or PBO (n 153) during the maintenance phase (wks 6-52). In post hoc analyses,
durable clinical remission end points were defined as a CDAI score of 150
points at 60% (8/13) of maintenance phase visits, at wks 6 and 52, and at 10
of 12 visits from wks 10 to 52.
RESULTS: Mean baseline (wk 0) CD duration was 8.4 y in the VDZ Q8W
group, 7.7 y in the VDZ Q4W group, and 9.6 y in the PBO group. Mean baseline
CDAI score (Q8W, 325.5; Q4W, 317.0; PBO, 325.2) and previous failure of
tumor necrosis factor (TNF) antagonists (Q8W, 55%; Q4W, 50%; PBO,
51%), immunosuppressants but not TNF antagonists (Q8W, 32%; Q4W, 35%;
PBO, 32%), and corticosteroids only (Q8W, 13%; Q4W, 14%; PBO, 16%) were
similar among the groups. Percentages of patients with durable clinical remission
based on 60% (8/13) of visits and at both wks 6 and 52 were significantly higher
with Q8W and Q4W than with PBO (Table). Percentages of patients with durable
remission based on 480% (10/12) of visits from wks 10 to 52 were significantly
higher for Q4W and numerically higher for Q8W than for PBO (Table).

A538

United European Gastroenterology Journal 2(1S)

Table to abstract P1485


VDZ

Durable remission based on


60% (8/13) of visitsa
P value
Remission at wks 6 and 52b
P value
Durable remission based on 10
of 12 visits from wks 10-52
P value

Q8W n 154

Q4W n 154

PBO n 153

49 (31.8)

42 (27.3)

30 (19.6)

0.003
30 (57.7)
0.040
37 (24.0)

0.022
26 (60.5)
0.020
33 (21.4)

22 (39.3)
24 (15.7)

0.060

0.044

CONCLUSION: The definition of durable clinical remission has not been standardized. These post hoc analyses of patients with CD, including those with
previous TNF antagonist failure, showed that VDZ (vs PBO) led to durable
clinical remission through wk 52 as defined by multiple clinically relevant alternative end points.
REFERENCES
1. Sandborn WJ, et al. N Engl J Med 2013; 369: 711-721.
Disclosure of Interest: W. Sandborn Consultancy for: Abbott Laboratories,
ActoGeniX, AGI Therapeutics, Alba Therapeutics, Albireo, Alfa Wassermann,
Amgen, AM-Pharma, Anaphore, Astellas Pharma, Athersys, Atlantic
Healthcare, Axcan Pharma, Bio Balance, Boehringer Ingelheim, Bristol-Myers
Squibb, Celek Pharmaceuticals, Celgene, Cellerix, Cerimon Pharmaceuticals,
ChemoCentryx, CoMentis, Coronado Biosciences, Cosmo Technologies,
Cytokine PharmaSciences, Eagle Pharmaceuticals, Eisai Medical Research,
Elan Pharmaceuticals, Eli Lilly, enGene, EnteroMedics, Exagen Diagnostics,
Ferring Pharmaceuticals, Flexion Therapeutics, Funxional Therapeutics,
Genentech, Genzyme, Gilead Sciences, Given Imaging, GlaxoSmithKline,
Human Genome Sciences, Ironwood Pharmaceuticals, Janssen, KaloBios
Pharmaceuticals, Lexicon Pharmaceuticals, Lycera, Meda Pharmaceuticals,
Merck Research Laboratories, Merck Serono, Nisshin Kyorin Pharmaceutical,
Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen
Therapeutics, PDL BioPharma, Pfizer, Procter & Gamble, Prometheus
Laboratories,
ProtAb,
PurGenesis
Technologies,
Relypsa,
Salient
Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering-Plough, Shire,
Sigmoid Pharma, Sirtris Pharmaceuticals, S. L. A. Pharma (UK), Takeda
Pharmaceuticals, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma,
TxCell, UCB, Vascular Biogenics, Viamet Pharmaceuticals, Warner Chilcott,
and Wyeth., S. Danese Consultancy for: Abbott Laboratories, AstraZeneca,
Ferring Pharmaceuticals, Merck Sharp & Dohme, Novo Nordisk, Pfizer,
Takeda Pharmaceuticals International, UCB, Vifor Pharma, B. Abhyankar
Other: Employee of Takeda Global Research & Development Centre (Europe)
Ltd, W. Reinisch Consultancy for: Abbott Laboratories, Abbvie, Aesca, Amgen,
Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix,
Chemocentryx, Celgene, Centocor, Danone Austria, Elan, Ferring, Galapagos,
Genentech, Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma,
Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, Austria and 4SC, J.
Xu Other: Employee of Takeda Pharmaceuticals International Co., K. Lasch
Other: Employee of Takeda Pharmaceuticals International, Inc., C. Milch
Other: Employee of Takeda Pharmaceuticals International Co.
P1486 RELATIONSHIP BETWEEN CLINICAL OUTCOMES
DISEASE DURATION, EXTENT, AND SEVERITY IN PATIENTS
WITH ULCERATIVE COLITIS WHO RECEIVED 6 WEEKS OF
TREATMENT WITH GOLIMUMAB

AND

W. Sandborn1, B. Feagan2,*, J.-F. Colombel3, W. Reinisch4, P. Gibson5,


P. Rutgeerts6, H. Weng7, R. Yao7, C. Marano8, H. Zhang8, R. Strauss8
1
University of California San Diego, La Jolla, United States, 2University of
Western Ontario, London, Canada, 3Centre Hospitalier Universitaire, Lille,
France, 4McMaster University, Hamilton, Canada, 5Alfred Hospital, Melbourne,
Australia, 6University Hospital Gasthuisberg, Leuven, Belgium, 7Merck & Co.,
Inc., Whitehouse Station, 8Janssen R&D, LLC., Spring House, United States

INTRODUCTION: To determine the relationship between baseline disease characteristics and efficacy of golimumab (GLM) treatment in patients with moderately to severely active ulcerative colitis (UC).
AIMS & METHODS: The PURSUIT induction study included patients with
Mayo scores of 612 inclusive, including endoscopic subscore 2. Patients were
randomized to receive at wk 0/2 either placebo (PBO)/PBO; GLM 200mg/100mg;
or GLM 400mg/200mg. At wk 6, clinical response (30% and 3 points
decrease from baseline Mayo score, with a decrease in the rectal bleeding subscore of 1 or a rectal bleeding subscore of 0 or 1) was analyzed by disease
duration (5 y, 45 to 15 y, or 415 y), extent (limited v extensive), and severity
(Mayo 59 v 9) at baseline. Missing data were considered nonresponse. P
values were not adjusted for multiplicity.
RESULTS: 761 patients were randomized and included in efficacy analyses (13
patients were excluded owing to site misconduct). 98% of patients completed to
wk 6. Overall, a greater percentage of patients had clinical response in both GLM
dose groups than the PBO group (200/100mg: 51%, 400/200mg: 55%, PBO:
30%). This pattern was similar for patients in each category of disease duration,
disease extent, and Mayo score (table). Excluding the longest disease duration
group that had the smallest number of patients, odds ratios for differences
between the GLM and PBO groups varied from 2.03.5; all differences from
PBO were statistically significant.
CONCLUSION: Clinical response to 2 doses of GLM treatment (200/100mg or
400/200mg at wks 0/2) was consistently achieved in approximately 50% of
patients at wk 6 regardless of UC disease duration, extent, or severity at baseline.
Overall, safety was comparable among treatment groups through wk 6.
Financial support for this study was provided by Janssen Research &
Development, LLC., Spring House, PA, USA.
Disclosure of Interest: W. Sandborn Financial support for research from: Janssen,
Consultancy for: Janssen, B. Feagan Financial support for research from:
Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb (BMS), Janssen
Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer,
Receptos, Santarus, Sanofi, Tillotts, UCB Pharma, Lecture fee(s) from:
Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott, UCB Pharma,
Consultancy for: Abbott/AbbVie, Actogenix, Albireo Pharma, Amgen, Astra
Zeneca, Avaxia Biologics Inc., Axcan, Baxter Healthcare Corp., BoehringerIngelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen,
EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given
Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/
Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Merck, Millennium,
Nektar, Novonordisk, Prometheus Therapeutics and Diagnostics, Pfizer,
Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma
Inc., Takeda, Teva Pharma, Tillotts, UCB Pharma, Vertex Pharma, WarnerChilcott, Wyeth, Zealand, Zyngenia, J.-F. Colombel Lecture fee(s) from:
AbbVie, ABScience, Amgen, Bristol Meyers Squibb, Celltrion, Danone,
Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen, Immune
Pharmaceuticals, Merck & Co., Millennium Pharmaceuticals Inc., Nutrition
Science Partners Ltd., Pfizer Inc. Prometheus Laboratories, Protagonist,
Receptos, Sanofi, Schering Plough Corporation, Second Genome, Takeda,
Teva Pharmaceuticals, UCB Pharma, Vertex, Dr. August Wolff GmbH & Co,
Consultancy for: AbbVie, ABScience, Amgen, Bristol Meyers Squibb, Celltrion,
Danone, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen, Immune
Pharmaceuticals, Merck & Co., Millennium Pharmaceuticals Inc., Nutrition
Science Partners Ltd., Pfizer Inc. Prometheus Laboratories, Protagonist,
Receptos, Sanofi, Schering Plough Corporation, Second Genome, Takeda,
Teva Pharmaceuticals, UCB Pharma, Vertex, Dr. August Wolff GmbH & Co,
W. Reinisch Lecture fee(s) from: Abbott Laboratories, AbbVie, Aesca, Amgen,
AM Pharma, Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC,
Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Danone
Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech,
Grunenthal, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC,
Consultancy for: Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma,
Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, BristolMyers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Danone Austria,
Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Grunenthal,
Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC, P.
Gibson Financial support for research from: Falk Pharma Gmb, Norgine,

Table to abstract P1468


Table Percentage of Patients With Clinical Response at Wk 6 by Disease Characteristics at Baseline

All patients
UC duration, y

Extent of disease
Mayo score

5
45 to 15
415
Limited
Extensive
59
9

PBO N,
(% response)

200/100mg N,
(% response)

OR vs PBO
(95% CI)

251 (30)
143 (32)
84 (29)
24 (25)
143 (33)
107 (27)
141 (31)
110 (29)

253 (51)
143 (52)
91 (53)
19 (32)
148 (49)
105 (53)
117 (54)
136 (49)

2.4
2.3
2.8
1.4
2.0
3.1
2.6
2.3

(1.66,
(1.44,
(1.49,
(0.36,
(1.24,
(1.73,
(1.55,
(1.35,

3.45)a
3.76)a
5.23)a
5.28)
3.20)a
5.45)a
4.28)a
3.91)a

400/200mg N,
(% response)

OR vs PBO
(95% CI)

257 (55)
139 (51)
93 (58)
25 (64)
146 (58)
111 (51)
129 (57)
128 (53)

2.8
2.2
3.5
5.3
2.8
2.8
2.9
2.8

(1.94,
(1.36,
(1.85,
(1.55,
(1.71,
(1.61,
(1.75,
(1.61,

4.03)a
3.57)a
6.48)a
18.30)a
4.47)a
5.00)a
4.73)a
4.73)a

A539

United European Gastroenterology Journal 2(1S)


Orphan Australia, Fresenius Kabi, Shire, and Abbott, Lecture fee(s) from:
Abbott, Merck, Janssen, and Fresenius Kabi, Consultancy for: Ferring
Pharmaceuticals, Abbott, Janssen, Schering-Plough, and Merck, P. Rutgeerts
Financial support for research from: Merck Sharp & Dohme Corp,
Consultancy for: Merck Sharp & Dohme Corp, H. Weng Other: Merck
Employee, R. Yao Other: Merck Employee, C. Marano Other: Janssen
Employee, H. Zhang Other: Janssen Employee, R. Strauss Other: Janssen
Employee.
P1487 ADHERENCE
DETAILS MATTER

TO

ULCERATIVE

COLITIS

TREATMENT:

W. Kruis1,*, H. Luhrs2, B. Keck3, H. Schmidt4, S. Ceplis-Kastner5, B. Reimers5


on behalf of MUKOSA Study Group
1
Evangelische Krankenhaus Kalk, Koln, 2Gemeinschaftspraxis Dres. Dillmann,
Metz, Luhrs, Melcher, Aschaffenburg, 3Praxis Dr. Blaker and Dr. Keck,
Hamburg, 4Praxis Dr. Schmidt, Berlin, 5Ferring Arzneimittel GmbH, Kiel,
Germany
Contact E-mail Address: kruis@evkk.de
INTRODUCTION: The adherence of patients to their therapy is essential for the
success of treatment. Many determinants of adherence, especially in the longterm treatment of ulcerative colitis (UC), are, however, still inadequately understood. There is some evidence that frequency of administration and dosage form
affect acceptance and compliance with mesalazine therapy.
AIMS & METHODS: The aim of this prospective, non-interventional study was
to identify factors that influence adherence to mesalazine therapy in patients with
UC.
In 113 specialized private gastroenterology practices, patients with UC who
received mesalazine for acute treatment or maintenance of remission, rated
their own compliance at time 0 (A), after 4-8 months (B) and after 12 months
(C) on a visual analogue scale, where 0 signified I have taken all medication
correctly and 10 I have taken no medication. At the outset, patients were
asked about their preference regarding the oral dosage form (tablets/granules/no
preference). It was recorded whether the doctors prescription matched the
patients wishes. The results were shown as median values.
RESULTS: 520 patients (47% female) were enrolled and observed prospectively
for up to 12 months. 76% of the patients preferred granules, 14% tablets, and
10% had no preference. Almost all patients received their preferred dosage form.
Among patients who preferred and received granules, compliance improved
during the observation period (0.50 (A), 0.30 (B) and 0.25 (C)). Patients who
preferred and received tablets rated their compliance at all times worse than those
taking granules. However, their compliance also improved during the study (1.80;
0.70; 1.0). The group with no preference initially rated compliance as high, but
this worsened with time (0.45; 0.70; 0.78). No evidence of other influencing
factors such as age, sex, duration of disease or UC severity was found.
CONCLUSION: Documentation by the patient and consideration of the preferred dosage form of mesalazine increase adherence. Indifference of the patient
is associated with poorer compliance. The dosage form of mesalazine should be
discussed with the patient at the start of treatment.
Disclosure of Interest: W. Kruis Financial support for research from: Dr. Falk
Pharma GmbH, Ferring Arzneimittel GmbH, Tigenix, Lecture fee(s) from: Falk
Foundation, Ferring Arzneimittel GmbH, Abbvie, Novartis, Consultancy for:
Dr. Falk Pharma GmbH, Ferring Arzneimittel GmbH, Genetic Analytics, H.
Luhrs Financial support for research from: Ferring Arzneimittel GmbH, B. Keck
Financial support for research from: Ferring Arzneimittel GmbH, H. Schmidt
Financial support for research from: Ferring Arzneimittel GmbH, S. CeplisKastner: employee of Ferring Arzneimittel GmbH, B. Reimers: employee of
Ferring Arzneimittel GmbH
P1488 SAFETY
AND
EFFECTIVENESS
OF
SEQUENTIAL
INTRAVENOUS ADMINISTRATIONS IN A SINGLE SESSION OF
IRON CARBOXYMALTOSE AND INFLIXIMAB IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE AND IRON DEFICIENCY
X. Cortes1,*, J. Rodr guez1, M. Moreno1, J. Borras2, A. Garayoa1, J.R. Moles1,
J. Clofent1, J. Primo1
1
Intern Medicine Department, Gastroenterology Section, 2Pharmacy Department,
Hospital of Sagunto, Valencia, Spain
Contact E-mail Address: xacori@gmail.com
INTRODUCTION: The objective of this study was to evaluate the safety and
effectiveness of combined intravenous (IV) administration in a single session of
ferric carboxymaltose [Ferinject] and infliximab [Remicade] in patients with
inflammatory bowel disease (IBD) treated with infliximab for the combined
management of underlying disease and iron deficiency anemia (IDA) or iron
deficiency (ID), in contrast to the usual pattern of two or more hospital visits
to administer both treatments.
AIMS & METHODS: Prospective observational study which included 22 consecutive patients with IBD of  6 months evolution (mean age 40.5  10.7 years;
50% women). 16 patients had Crohns Disease and 6 Ulcerative Colitis, all
treated with infliximab and diagnosed with ID or IDA according to WHO criteria. After completion of IV administration of 5 mg/kg infliximab, 50 ml of
saline were injected using the same venous access, followed by the Ferinject
infusion (accordance with Ganzoni formula). 63.4% of patients received
Ferinject infusions of 500 mg and 36.6 % received 1000 mg iron. Laboratory
analyses of the ferric profile and inflammatory activity index (modified Truelove
I. or Harvey-Brasdshaw I.) pre-infusion and at 2 months were performed.
Presence of adverse events was evaluated at 7 and 60 days after the sequential
infusions. Ferinject effectiveness was measured after a mean of 69.0  41.3 days
after infusions.

RESULTS: At the end of the evaluation period no adverse events associated with
sequential IV infusion of ferric carboxymaltose or infliximab were recorded.
After this period, the mean hemoglobin levels increased from 11.5  2.5 to
12.5  1.9 g/dL (p 0.143). Increases in mean levels of serum iron (41.1 
19.5 to 69.6  33.8 mg/dL, p 0.002), ferritin (73.4  122.8 to 304.9  390.7
ng/mL, p 0.001) and mean transferrin saturation (12.3  4.3 to 21.5  11.4%,
p 0.004) were statistically significant.
CONCLUSION: Sequential IV administration of infliximab following IV ferric
carboxymaltose [Ferinject] in a single session was well tolerated and effective.
Contrary to the usual practice of infusing infliximab and IV iron on separate
days, this sequential regimen can offer a good cost- benefit ratio and could
improve treatment adherence and patients quality of life.
Disclosure of Interest: None declared
P1489 INTEREST
OF
COMBINATION
THERAPY
WITH
IMMUNOSUPPRESSIVE TREATMENT IN IBD PATIENTS IN LOSS
OF RESPONSE TO INFLIXIMAB AND EXHIBITING VERY HIGH
ANTI-INFLIXIMAB ANTIBODY (ATI) LEVELS
X. Roblin1,*, E. Deltedesco1, L. Peyrin Biroulet2, S. Paul3
1
CHU Saint Etienne, saint etienne, 2CHU Nancy, Nancy, 3CHU Saint Etiennne,
Saint Etiennne, France
INTRODUCTION: For IBD patients treated with IFX as monotherapy and
exhibiting undetectable IFX levels combined with high anti-IFX levels (ATI),
the recommended course is to switch to another anti TNF. A single case study
has however reported a potential benefit of the addition of immunosuppressants
(IS). In this study we studied the clinical and pharmacological impact of adding
an IS in patients treated with IFX and exhibiting undetectable trough levels of
IFX concurrent with high ATI levels.
AIMS & METHODS: Within a prospective cohort of patients with IBD, all
patients receiving IFX as monotherapy at the dose of 5mg/kg were identified.
Inclusion was restricted to patients exhibiting undetectable IFX levels and high
levels of ATI (4 200 ng/ml) measured using ELISA LISA-TRACKER
(Theradiag) technique and detected at least twice. In cases of declining clinical
response an IS was added to the prescription of IFX at the same dose, for a
minimum period of 6 months.
RESULTS: 15 patients (13 with Crohns disease (CD)), sex ratio 1, mean
age 36 years) were included. All patients had IFX levels 5 0.1mg/ml and
ATI 4 200ng/ml. Loss of clinical response was moderate in 10 and minimal in
5, all with faecal calprotectin 4 450 mg/g of stools or with an endoscopic Mayo
score 2. The addition of IS (thiopurines in 13 cases) was proposed.
Pharmacological data revealed a median IFX level which increased from 0.015
mg/ml [0.01-0.02] to 0.9 mg/ml [0.01-2.2] after 6 months of combination therapy.
Median ATI levels decreased from 320 ng/ml [200-600] to 60 ng/ml [20-500]. At 6
months, 8 patients out of 15 exhibited IFX levels greater than 1.5 mg/ml. assoiciated with ATI below 20ng/mL Clinically, 7 of the 13 patients with CD and in
relapse on inclusion were in clinical remission at 6 months with normal faecal
calprotectin values and in all cases a favourable pharmacological outcome (IFX
4 1.5mg/ml with ATI 5 20 ng/ml). The pharmacological profile of the 7 other
patients remained unchanged.
CONCLUSION: The addition of IS in patients relapsing during IFX treatment
and having high ATI levels lead to remission, in 54% of cases as evidenced by
clinical, pharmacological and biomarker data. This clinical response is slow: 6
months for a pharmacological effect, 4 months for an effect on the biomarkers
and 5 months for a favourable clinical outcome to be observed.
REFERENCES
1. Afif W, Loftus EV Jr, Faubion WA, et al. Am J Gastroenterol 2010; 105: 11331139.
Disclosure of Interest: None declared
P1490 INDIRECT
COMPARISON
OF
ADALIMUMAB
AND
VEDOLIZUMAB IN INFLAMMATORY BOWEL DISEASE IN THE
UNITED KINGDOM: COST PER RESPONDER/REMITTER
ANALYSIS
Y. Liu1, W. Reichmann2, S. Wang3,*, D. Macaulay2, M. Skup3, J. Chao3,
Y. Bao3
1
University of MissouriKansas City, Kansas City, 2Analysis Group, Inc., Boston,
3
AbbVie Inc., North Chicago, United States
INTRODUCTION: Adalimumab (ADA) and vedolizumab (VDZ) have been
shown to induce and maintain clinical remission in patients with moderate to
severe inflammatory bowel disease (IBD). The objective was to calculate cost per
responder and remitter associated with ADA and VDZ from the perspective of
the National Health Service in the United Kingdom (UK).
AIMS & METHODS: RCTs comparing ADA (CHARM and ULTRA 2) or
VDZ (GEMINI 1 and 2) to placebo in ulcerative colitis (UC) or Crohns disease
(CD) at 1 year were included. Relative response and remission of each biologic
therapy was estimated using a network meta-analysis (NMA) in UC and CD
separately. The number needed to treat (NNT) was estimated for each biologic
based on the results of the NMA. In CD, the annual cost of ADA (10,564)
assumed all patients were on therapy for 1 year. In UC, the annual cost of ADA
(6,722) assumed patients not in response at week 8 discontinued therapy, as per
the European Medicines Agency product information. Because VDZ is not yet
approved in the UK, annual cost was assumed to be equal to the indicationspecific cost of treating with ADA or the 2013 average annual cost of anti-TNF
therapies in the UK (17,915). The cost of VDZ was assumed to be the same for
both VDZ 300mg every 8 weeks (Q8) and every 4 weeks (Q4) dosing regimens.
The 1-year costs per responder and remitter were estimated in UC and CD by
multiplying the NNT by the annual cost. Blended costs per responder and

A540

United European Gastroenterology Journal 2(1S)

remitter in IBD were estimated by weighting the UC and CD results by their


respective market size.
RESULTS: When VDZs annual cost was assumed to equal ADAs, the 1-year
treatment costs per responder in patients with IBD were numerically lower for
ADA (60,370) than VDZ Q8 (146,255) and VDZ Q4 (128,462). 1-year treatment costs per remitter were also numerically lower for ADA (60,996) than
VDZ Q8 (118,814) and VDZ Q4 (137,521). When VDZs annual cost was
assumed to be 17,915 in IBD, the cost per responder of ADA compared to
both VDZ dosing regimens was significantly different (Table).
Cost per responder
Mean (95%
Treatment Credible Interval)

Cost per remitter


Mean (95%
Credible Interval)

ADA

60,996 (38,865, 106,716)

VDZ Q8
VDZ Q4
VDZ Q8
VDZ Q4

60,370 (41,174,
98,167)
146,255 (58,751,
491,114)
128,462 (58,980,
346,582)
252,800 (104,360,
836,914)

118,814 (58,724,
271,587)
137,521 (60,944,
369,964)
208,382 (102,409,
465,272)

223,428 (104,808,
593,699)

239,344 (108,709,
635,055)

Cost assumption
for VDZ

VDZ treatment costs equal


ADAs

VDZ treatment costs equal


the average of all anti-TNF
therapies

CONCLUSION: Costs per responder and remitter in IBD in the UK were


numerically lower for ADA-treated patients compared to VDZ-treated patients,
indicating that ADA may have better economic value than VDZ in patients with
IBD.
REFERENCES
1 Colombel JF, et al. Gastroenterology 2007; 132: 52-65.
2 Feagan BG, et al. N Engl J Med 2013; 369: 699-710.
3 Sandborn WJ, et al. Gastroenterology 2012; 142: 257-265.
4 Sandborn WJ, et al. N Engl J Med 2013; 369: 711-721.
Disclosure of Interest: Y. Liu Other: Employee: University of Missouri-Kansas
City, W. Reichmann Other: Employee: Analysis Group, Inc, under contract with
AbbVie, S. Wang Shareholder of: AbbVie, Other: Employee: AbbVie, D.
Macaulay Other: Employee: Analysis Group, Inc, under contract with AbbVie,
M. Skup Shareholder of: AbbVie, Other: Employee: AbbVie, J. Chao
Shareholder of: AbbVie, Other: Employee: AbbVie, Y. Bao Shareholder of:
AbbVie, Other: Employee: AbbVie.
P1491 WHAT IS OUR SUCCESS ON COMPLEX PERIANAL FISTULA
HEALING IN THE CLINIC?: FROM ANTIBIOTIC TO COMBINED
ANTI-TNF BASED TREATMENT, ENDING WITH OR WITHOUT
ILEOSTOMY
Y. Erzin1,*, A. Ercaliskan1, I. Hatemi1, D. Eyice1, B. Baca1, N. Demir1,
A.F. Celik1
1
Gastroenterology, Istanbul University Cerrahpasa Medical Faculty, Istanbul,
Turkey
INTRODUCTION: Our aim was to determine overall treatment (Tx) success and
factors influencing the medical Tx (MedTx) response in complex perianal fistulas
(Cpfis).
AIMS & METHODS: Patients charts between 1999-13 retrospectively were
reviewed. There were 51/705 (7%) CD patients with Cpfis. All patients were
treated with different combinations of antibiotics, azathioprine (AZA) and
anti-TNFs but our aim was to put them on triple MedTx if there was no drug
intolerance. In case of an abscess, drainage and seton was applied remaining
between 3 to 6 mo. in case of no recurrence. Tx success was stratified as complete
discharge cessation or additional closure of external orifice, and ultimately radiological disappearance by MRI. In case of MedTx failure a diverting stoma was
applied. Age, sex, disease duration, location, behaviour, rectal involvement, age
at fistula onset, fistula duration, number of fistula, smoking, number of setons,
duration of each MedTx, time with seton, total durations of drugs, and type of
surgery was noted. Each patients fistula status at the last visit was determined
and re-opening and re-closing events and closure time after seton removal were
noted.
RESULTS: There were 51 Cpfis pts., 20 (39%) being female with a mean age of
35.6611.66 yrs. The mean fistula follow-up time was 41.6831.31 mo., 19/51
(37%) patients had one fistula the remaining multiple. 34 patients (66%) were
complicated by abscesses and loose seton was applied to 30/34 (88%), four of
P1491

Age of the fistula in months


Sex (Female/male)
Rectal involvement(absent/present)
Treatment duration(follow up in month)
Number of fistula (1/2/3/4)
Perianal absecess during follow up (no/yes)
Total anti-TNF duration in month
Total AZA duration in month
Total antiobiotic duration in month

them with permanent setons for repeating abscesses. During whole follow up 50
abscesses (12 of them while having a seton) were observed. Fistula closure after
seton removal was achieved between 1-21 (median 8) mo. Ileostomy was performed in 14 (28%) patients and fistula closure was achieved in only 4/14 (30%)
between 2-9 mo. At the last visit 27/51 (53%) were in remission, and only 7/51
(14%) achieved radiological. The follow up Tx time was significantly longer in
response-positive group (50.33 vs. 31.95 mo., p 0.031), and total anti-TNF Tx
time significantly correlated with Tx success (r -0.339, p 0.021). An age-sex
adjusted Cox regression analysis disclosed total anti-TNF Tx time as the only
independent predictor of Tx response (p 0.001).
CONCLUSION: Anti-TNFs necessary for even small success of complex fistula
closure. Clinical response rate within the mean 41 mo. of follow up was 53% with
its own re-opening risk. Only 14% had radiological tract closure reaching our
ultimate aim. Long term antibiotic use either solo or combined did not show any
effect on perianal fistula closure.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
OTHER LOWER GI DISORDERS III POSTER EXHIBITION HALL
XL_____________________
P1492 RISK OF MICROSCOPIC COLITIS DURING USE OF PPIS,
NSAIDS, BETA-BLOCKERS AND OTHER DRUGS
G.M. Masclee1,2,*, P.M. Coloma2, E.J. Kuipers1, M.C. Sturkenboom2
1
Gastroenterology and Hepatology, 2Medical Informatics, Erasmus University
Medical Center, Rotterdam, Netherlands
Contact E-mail Address: g.masclee@erasmusmc.nl
INTRODUCTION: Microscopic colitis (MC) is a disease characterized by
chronic watery diarrhea, normal radiological and endoscopic appearance but
microscopic inflammation. MC includes two distinct entities: lymphocytic (LC)
and collagenous colitis (CC). In recent years, several drugs were reported to
increase the risk of MC. However, these studies lacked a clear exposure definition
or did not address dose- and duration-relationships. Aim of this study was to
estimate the risk of MC during use of several drugs, such as NSAIDs, PPIs, betablockers and SSRIs.
AIMS & METHODS: Case-control study nested within a population based
cohort using a primary care database from the Netherlands (1999- 2013). MC
cases were identified using free text search with manual validation to ensure
histological confirmation. Cases were persons aged18 years with incident MC
diagnosis. Controls (community-based and patients with negative colonoscopy
results), being MC and colorectal cancer-free, were matched to cases on age, sex
and primary care practice. Drug use was determined within 1 and 2 years prior to
date of earliest symptoms leading to MC diagnosis (matching date). Odds ratios
(OR) with 95% CI were calculated by conditional logistic regression, while
adjusting for confounders (ORa), including auto-immune diseases, type 2 diabetes mellitus, polyarthritis, colonoscopy and concomitant drug exposure.
RESULTS: From the source population of 1,458,410 subjects we identified 218
incident MC cases (92 CC, 70 LC, 56 unspecified) that were matched to 15,045
community controls. Current use ( 3 months) of proton pump inhibitors (PPIs),
NSAIDs, selective serotonin re-uptake inhibitors (SSRIs), low-dose aspirin
(LDA), ACE-inhibitors (ACEI) and beta-blockers (BBL) significantly increased
the risk of MC compared to never use, with adjusted ORs ranging from 2.6
(95%CI:1.5-4.4) for BBL to 7.2 (95%CI:4.4-11.9) for PPIs when evaluating 1
year prior to date of earliest symptoms. At 2 years prior to the matching date,
accounting for diagnostic delay, only current use of NSAIDs, PPIs, LDA and
ACEI showed increased risk of MC. Statins did not increase the risk of MC.
Increasing doses did not show higher risks for MC. When estimating the risk of
MC compared to colonoscopy-test negative controls, only current use of PPIs
and beta-blockers significantly increased the risk of MC (ORa 4.3 and 6.8,
respectively).
CONCLUSION: The risk of microscopic colitis increases from 3 up to 7-fold
with current use of drugs, including NSAIDS, PPIs, low-dose aspirin, ACEinhibitors and beta-blockers when compared to community-based controls.
When compared to colonoscopy negative controls, however, only PPIs and
beta-blockers increased the risk of MC, suggesting that use of NSAIDs, lowdose aspirin, ACE-inhibitors increases the likelihood of receiving a colonoscopy
or worsen underlying colonic diseases or diarrhea rather than increases the risk of
MC.
Disclosure of Interest: None declared

Response
positive(n)

Response
positive(%)

Response
negative(n)

Response
negative(%)

36.4 30.5
12 /15
12/15
27
12/10/4/1
12/15
24
20
27

44.5%/ 55.5%
44.5%/ 55.5%
50.3 36.3
44%/37%/15%/4%
45%/55%
31.5 19
35.1 26.1
11.1 10.3

32.5 20.1
8 /16
11/13
24
7/9/8/0
5/19
22
22
24

33%/ 66%
46%/54%
31.9 21.2
29%/38%/33%/0
21%/79%
19.4 10.8
21.6 11.5
14.3 10.4

NS
NS
NS
0.031
NS
0.074
0.011
0.040
NS

A541

United European Gastroenterology Journal 2(1S)


P1493 ADMINISTRATION OF IRT-5, MIXTURE OF FIVE PROBIOTICS
AMELIORATES COLITIS AND PROTECTS COLITIS ASSOCIATED
CANCER IN MICE MODELS
J.W. Kim1,*, B.J. Lee1, J.W. Choe1, M.K. Joo1, H.J. Kim1, B. Keum1, J.S. Koo1,
J.-J. Park1, Y.T. Jeen1, J.S. Kim1, Y.-T. Bak1
1
Korea University College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: neucjw@naver.com
INTRODUCTION: The aim of this study is to define the effect of IRT-5, new
probiotics combination on the mice colitis and colitis associated cancers using
mice colitis and colitis associated cancer (CAG) models.
AIMS & METHODS: IRT-5 was composed of five probiotics (L.acidophilus, L.
casei, L.reuteri, B.bifidum and S. thermophilus). We used two mice colitis models
(DSS and IL-10-/-piroxicam). After 2.5% DSS induction for 5 days, normal
chow or IRT-5 (5x108 cfu/day) was administrated for 7 days and B6 mice
were sacrificed at day 12. 8- to 10-week-old IL-10-/- mice were fed pellet-chow
containing piroxicam for 2 weeks. Then normal chow or IRT-5 mixed chow was
administered for 2 weeks after piroxicam induction. Four-weeks old Apc min/
mice were given 2% DSS for 7 days and normal chow or IRT-5 was administrated for 6 weeks after the initiation of DSS. IL-10-/- mice were fed normal
chow or IRT-5 mixed chow was administered for 6 weeks after piroxicam induction. Macroscopic tumors were measured and histologic analyses were done.
Real-time PCRfor inflammatory cytokines and immunohistochemistry (IHC)
for CD 163 and F4/80 were performed.
RESULTS: IRT-5 reduced the colonic inflammations in both DSS-colitis and
colitis in IL-10 -/- mice. Mean tumor incidence (9.552.51 vs 4.723.09,
p50.05), tumor size (3.871.69 vs 2.631.01 p5 0.05) and the tumor portion
in 43mm were significantly decreased in IRT-5 treated Apc min/ mice compared with control mice. Histologic grade was more severe in control IL-10 -/mice compared with IRT-5 treated IL-10 -/- mice (invasive caricinoma, 70% vs
40%). The activities of CD 163, and F4/80 were decreased in the tumor of IRT-5
treated Apc min/ in IHC analyses.
CONCLUSION: IRT-5, combination of probiotics ameliorated mice colitis and
inhibits CAC in Apc min/-DSS model and IL-10 -/- mice by the modulation of
macrophage activation.
Disclosure of Interest: None declared
P1494 CLINICOPATHOLOGICAL FEATURES OF ACUTE GRAFTVERSUS-HOST DISEASE IN LOWER GASTROINTESTINAL TRACT
K. Nomura1,*, T. Iizuka1, D. Kaji2, H. Yamamoto2, Y. Kuribayashi1,
R. Kimura1, A. Yamada1, T. Furuhata1, S. Yamashita1, D. Kikuchi1,
A. Matsui1, T. Mitani1, O. Ogawa1, S. Hoteya1, Y. Ota3, S. Taniguchi2,
M. Kaise1
1
Gastroenterology, 2Hematorogy, Toranomon Hospital, 3Pathology, Research
Hospital, The Institute of Medical Science, Tokyo, Japan
Contact E-mail Address: med20365nomura@yahoo.co.jp
INTRODUCTION: Acute graft-versus-host disease (GVHD), which typically
occurs within 100 days of transplantation, is an important factor influencing
prognosis in transplant resipients. In this study, we retrospectively investigated
the diagnostic accuracy of acute GVHD that developed in the lower gastrointestinal tract.
AIMS & METHODS: Of the 660 patients who underwent allogeneic hematopoietic stem cell transplantation at our hospital between January 2008 and June
2013, 335 developed acute GVHD-like symptoms such as watery diarrhea.
Subsequently, 107 of these patients underwent lower gastrointestinal endoscopy
within 100 days of transplantation, as well as biopsy for histological diagnosis.
The frequency of each endoscopic findings and their probability of indicating
GVHD were assessed in these 107 patients.
RESULTS: Endoscopic observation up to the terminal ileum was possible in 86
(80.4%) patients, and 98 patients were diagnosed as having GVHD based on
histological findings, accounting for 29.3% of the 335 patients initially suspected
of having GVHD and 91.6% of the 107 patients who underwent endoscopic
examination. Of 12 patients infected with cytomegalovirus, 10 also showed the
coexistence of GVHD. After excluding these 10 patients, GVHD was observed in
the terminal ileum of 59 patients, with endoscopic findings of redness in 27,
villous atrophy in 25, edema in 20, erosion in 19, ulcer in 4, and mucosal exfoliation in 5. GVHD was also observed in the colon of 88 patients, with endoscopic
findings of reduction or loss of vascular visibility or orange peel appearance of
the mucosa in 76 patients, edema in 68, redness in 42, erosion in 34, ulcer in 10,
and mucosal exfoliation in 6. The diagnostic accuracy of each finding as an
indicator of GVHD was 100% for villous atrophy, ulcer, and mucosal exfoliation, 97.7% for redness, and 96.3% for erosion in the terminal ilium. In the
colon, the accuracy was 100% for orange peel appearance of the mucosa
and mucosal exfoliation, 97.1% for erosion, and 96.2% for reduction or loss
of vascular visibility. Six patients had GVHD only in the terminal ilium, and 5
had GVHD only in the right colon. The remaining 86 (87.8%) patients were
diagnosed with GVHD in the left colon based on the biopsy results.
CONCLUSION: The characteristic endoscopic findings of GVHD were villous
atrophy, turtleback-like appearance of the mucosa, and mucosal exfoliation.
Approximately 90% of patients who underwent biopsy of the left colon were
accurately diagnosed with GVHD, indicating that biopsy should be performed of
the left colon regardless of poor bowel preparation.
Disclosure of Interest: None declared

P1495 EFFECTS OF POLY (I:C), A LIGAND


RECEPTOR 3, IN COLON BARRIER FUNCTION

FOR

TOLL-LIKE

V. Moyano-Porcile1, J.A. Bravo1, M. Julio-Pieper1,*


1
Grupo de NeuroGastroBioqumica, Laboratorio de Qumica Biologica. Instituto de
Qumica, Facultad de Ciencias, Pontificia Universidad Catolica de Valparaso,
Valparaso, Chile
Contact E-mail Address: marcela.julio@ucv.cl
INTRODUCTION: The gastrointestinal (GI) tract and especially the gut wall act
as a barrier to prevent translocation of harmful biological and chemical entities
from the lumen. Accordingly, intestinal and colonic barrier functions depend on
an adequate response to pathogens by immune but also epithelial cells. Toll-like
receptor 3 (TLR-3) recognizes pathogen-associated molecular patterns, particularly double-stranded RNA. TLR-3 activation is noxious to nasal epithelial cells
and perturbs blood brain barrier. Although it has been shown that systemic
activation of TLR-3 induces intestinal damage, there is little information regarding the mechanisms for TLR-3 actions on epithelial cells in the GI tract. In
addition, the effects of direct TLR-3 activation on gut barrier function are
unknown.
AIMS & METHODS: We aimed to evaluate the effects of TLR-3 activation on
rat colon permeability ex vivo as well as in vivo. For the ex vivo approach, we used
the everted gut sac technique. The synthetic ligand for TLR-3, Poly (I:C), was
applied at the mucosal side of the colon at doses of 0, 0.5, 5, 50 and 200 ug/mL,
and the transit of fluorescent probes (TRITC-dextran 4.4 kD, TD4.4 and FITCdextran 40 kD, FD40) from the mucosal to the serosal side was measured for up
to 3 hours. At the end of this protocol RNA was extracted from the mucosa in
order to quantify the mRNA expression of tight junction proteins ZO-1 and
Occludin. The effects of Poly (I:C) on colon mucosal morphology and ZO-1
immunostaining were evaluated in another set of tissues. For the in vivo experiments, either saline or 100 ug of Poly (I:C) were applied along 7 cm into the
colorectal cavity of adult male rats. Six hours later the colon was removed and
subjected to the everted gut sac permeability test as described before.
RESULTS: Tissues exposed to 200 ug/mL Poly (I:C) ex vivo displayed a
decreased thinning of mucosal layer after 2 hours and a decrease in the transit
of FD40 (but not of TD4.4) from the mucosal to the serosal side after 3 hours, in
comparison to controls. No changes were found in mRNA levels of ZO-1 and
Occludin or in the immunostaining for ZO-1 in the mucosa. Colons removed
from rats that received Poly (I:C) intrarrectally also showed decreased permeability to FD40 in the everted gut sac assay at 3 hours post-extraction.
CONCLUSION: Our results suggest that an acute exposure to the TLR-3 ligand
Poly (I:C) reduces colon permeability to a 40 kD molecule, both ex vivo and
in vivo. This effect is accompanied by a reduction in mucosal thinning ex vivo but
not by a modification in the expression of ZO-1 or Occludin. Although the
mechanism and significance of this potentially protective effect need further
investigation, to our knowledge this is the first report showing a direct effect
of a TLR-3 ligand in colon barrier function. FUNDED BY: Conicyt 79112017,
Fondecyt 1130213.
Disclosure of Interest: None declared
P1496 GUT REGION-SPECIFIC ALTERATIONS IN THE COMPOSITION
OF THE INTESTINAL MICROBIOTA IN STREPTOZOTOCININDUCED DIABETIC RATS
N. Bodi1,*, R. Wirth2, G. Maroti3, P. Talapka1, E. Fekete1, K.L. Kovacs2
1
Department of Physiology, Anatomy and Neuroscience, 2Department of
Biotechnology, University of Szeged, 3Institute of Biochemistry, Biological
Research Center, Hungarian Academy of Sciences, Szeged, Hungary
Contact E-mail Address: bodiniki85@gmail.com
INTRODUCTION: Among the potential environmental triggers that are implicated in the development of the diabetes-related myenteric neuropathy, the intestinal microbiome is considered as primary candidate.
AIMS & METHODS: Therefore, the aim of this study was to map the alterations
of the composition of microbiota along the gut in diabetic rats. Luminal samples
of streptozotocin-induced diabetic and insulin-treated diabetic rats were compared with healthy controls. Segments of duodenum, ileum and colon were dissected and microbiomes of the luminal contents were analyzed by next generation
DNA sequencing from phylum to genus level.
RESULTS: No significant differences in the bacterial composition were observed
in luminal contents derived from the duodenum of different experimental groups.
However, distinct patterns of microbiomes were recognized in the ileum and
colon, depending on the history of the luminal samples. Ileal samples from
diabetics exhibited particularly striking alterations while the richness and diversity obscured some of these in the colon. Proteobacteria displayed most pronounced shifts, while the dominating phyla (Firmicutes and Bacteroidetes)
apparently were modified to smaller degree. Characteristic rearrangements and
diversity in the microbiome were detected after insulin replacement, although the
normal gut flora was not restored.
CONCLUSION: Diabetes and also insulin treatment affect the composition of
the intestinal microbiota on a different but strictly gut region-specific way. The
luminal samples from the ileum appear more suitable for diagnostic purposes
than the colon/faeces. Proteobacteria should be in the center of diagnosis and
potential therapy.
Disclosure of Interest: None declared

A542

United European Gastroenterology Journal 2(1S)

P1497 THE LEAKY GUT IN PATIENTS WITH CRONIC KIDNEY


DISEASE
S. Lemesch1,*, W. Ribitsch1, G. Schilcher1, B. Leber2, A. Horvath1, L. Pasterk3,
G. Marsche3, W. Spindelboeck1, M.T. Tawdrous1, G. Zettel2, H. HafnerGiessauf1, A.R. Rosenkranz1, V. Stadlbauer1
1
Internal Medicine, 2Transplantation Surgery, 3Pharmacology, Medical University
Graz, Graz, Austria
Contact E-mail Address: sandra.lemesch@medunigraz.at
INTRODUCTION: Bacterial infections and sepsis are common complications
leading to high morbidity and mortality in patients with chronic kidney disease
(CKD). A defective gastrointestinal barrier may contribute to increased translocation of bacterial products.
The aim of this study was to investigate gut permeability, oxidative stress and
phagocytic capacity of neutrophils in CKD patients.
AIMS & METHODS: Diamine oxidase (DAO),a marker of gut permeability,
was measured by ELISA (DAO, Immundiagnostic, Germany). The LPS surrogate markers lipopolysaccheride binding protein (LBP) and soluble (s)CD14 were
measured by ELISA (Human LBP, Human sCD14, Hycult biotech,
Netherlands). Advanced Oxidation Protein Products (AOPP) were determined
by HPLC. Neutrophil function was determined by co-incubating whole blood
with FITC labelled E. coli (Phagotest, Glycotope, Germany) and analysed by
flow cytometry.
RESULTS: Predialysis (PDL, n 73), hemodialysis/hemodiafiltration (HD,
n 32), peritoneal dialysis (PD, n 28) patients as well as peritoneal dialysis
patients with peritonitis (PDP, n 14) were studied and compared to healthy
controls (Ctrl, n 33). DAO levels were significantly higher patient groups
(except PDP patients) compared to Ctrl (see Tab.1). LBP and sCD14 were significantly higher in patient groups compared to Ctrl (see Tab.1). Among the
patient groups LBP and sCD14 were highest in the PDP group. AOPP were
significantly increased in patient groups (see Tab.1). Neutrophil phagocytosis
was significantly reduced in the HD group (see Tab.1).
Tab. 1 Results are shown as median (interquartile range). Significance is shown
as a p50.001, b p50.01, c p50.05 compared to ctrl. A p50.001, B p50.01, C
p50.05 compared to patient groups (DAO: compared to PDL; LBP: compared
to PDP; sCD14: compared to PDP; AOPP: compared to HD; phagocytosis:
compared to HD).
parameters
DAO
LBP
sCD14
AOPP
phagocytosis

[ng/ml]
[mg/ml]
[mg/ml]
[mmol/l]
[%]

ctrl

PDL

HD

PD

PDP

21.0 (13.1)
16.7 (9.9)
1.5 (0.8)
31.1 (12.9)
96.0 (57.4)

33.8 (16.9)a
34.1 (21.1)a, A
2.7 (2.1)a, A
53.2 (40.9)a, A
110.8 (60.5)A

31.9 (23.0)a
28.3 (26.3)a, A
3.3 (1.6) a, A
90.5 (50.3)a
75.7 (40.2)a

25.6 (.10.3)c, B
28.35 (17.7)a, A
2.8 (0.7)a
67.9 (30.3)a, C
98.8 (74.5)C

27.5 (20.9)
59.9 (48.2)a
6.3 (5.1)a
70.2 (38.4)a
96.8 (79.8)

CONCLUSION: These results reveal an increased gut permeability in CKD


patients. It can therefore be hypothesized that translocation of bacterial products
may be increased, leading to an increase in the LPS surrogate markers LBP and
sCD14. Additionally, protein oxidation as measured by AOPP is increased in
patient serum. Our findings are akin with previous studies showing that CKD
patients are exposed to circulating endotoxemia and systemic inflammation on
the basis of a leaky gut, altered intestinal microbiota and ultrafiltration- induced
splanchnic ischemia. A pathophysiological role of the type of renal replacement
therapy is underlined by the fact that neutrophil phagocytosis is impaired in patients
undergoing hemodialysis/hemodiafiltration but not in PDL and PD-patients.
Disclosure of Interest: None declared
P1498 INCREASED LEVELS OF PROINFLAMMATORY SERUM
CYTOKINES AND LOWER MUCOSAL EXPRESSION OF TLR4 IN
IBS PATIENTS
S.M. P. Bennet1,*, H. Tornblom1, F. Rusu2, S. Isaksson1, B.L. Neve3,
M. Simren1, L. Ohman1
1
Dept. of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at
University of Gothenburg, Gothenburg, Sweden, 22nd Medical Department,
University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania,
3
Dept. of Life Science, Danone Research, Palaiseau, France
INTRODUCTION: Alterations in immune function by means of increased activity and potential low-grade inflammation have been suggested as being important
in irritable bowel syndrome (IBS). We therefore studied the serum cytokine
profile as well as expression of mucosal host mRNA targets of relevance to
inflammation and bacterial recognition in IBS patients.
AIMS & METHODS: MesoScale Discovery (MSD) multiplex immunoassay
analysis was used for the measurement of serum cytokines, IL-12p70, IL-13,
IL-2, IL-4, IL-6, IL-17A, IL-5, IFN-g, IL-1,IL-8, IL-10 and TNF in 154 IBS
patients (female 105, median age 29 years (24-40)), (Rome III; IBS-C 16, IBSD 38, IBS-M 98) and 45 healthy controls (female 30, median age 27 years
(23-41)). Mucosal expression of FOXP3, TLR4, TLR6, TLR9, NOX1, IL-8, IL10 and TNF was determined by qRT-PCR in sigmoid colon biopsies from 114
IBS patients (female 72, median age 32 years (27-39)), (Rome III; IBS-C 14,
IBS-D 26, IBS-M 73) and healthy controls (female 25, median age 27 years
(23-35)). The qRT-PCR results were normalized to the mean expression level of
housekeeping (HK) genes 18s, POLR2A and RPLP0, or HPRT, and expressed as
2^-target-HK. Data is shown as median, range 25-75 percentile.
RESULTS: IBS patients had higher serum levels of TNF compared to healthy
controls (Table 1) with higher levels in IBS-D compared to IBS-M (2.7 pg/mL

(2.2-3) vs. 2.1 pg/mL (1.7-2.5); p 0.02) and healthy controls (2.7 pg/mL (2.2-3)
vs. 2.2 pg/mL (1.5-2.5); p 50.001), respectively. Also levels of IL-6 and IL-8
tended to be higher in serum of IBS patients (Table 1), without differences
between IBS subgroups. In contrast, serum levels of IFN-g were lower in IBS
patients compared to healthy controls (Table 1). Remaining serum cytokines
were similarly expressed in IBS and healthy controls. In colon biopsies, the
expression of NOX1 and FOXP3 tended to be lower in IBS than in healthy
controls (0.02 (0.02-0.03) vs. (0.03 (0.02-0.03) arbitrary units; p 0.06) and
(2.5e-4 (1.8e-4-3.5e-4) vs. 3.1e-4 (2.9e-4-3.7e-4); p 0.1) respectively. The expression of TLR4 was lower in IBS patients than healthy controls (2.1e-3 (1.6e-32.5e-3) vs. 2.4e-3 (2.0e-3-2.8e-3); p 0.02), with IBS-M having lower expression
of TLR4 compared to healthy controls (1.9e-3(1.6e-3-2.4e-3) vs. 2.4e-3(2.0e-3-2.8e2
); p 0.003). The mucosal expression of TNF, IL-8, IL-10, TLR6 and TLR9
was similar in IBS patients and healthy controls.
Table 1. Levels of serum cytokines in IBS patients and healthy controls.
Target (pg/mL)

IBS (n 151)

Healthy (n 48)

TNF
IFNg
IL-6
IL-8

2.3 (1.8-2.8)
8.0 (5.1-11.7)
0.4 (0.3-0.7)
11.4 (7.6-14.5)

2.2 (1.6-2.5)
11.2 (6.2-16.2)
0.4 (0.2-0.6)
9.5 (6.5-13.2)

p 0.03
p 0.01
p 0.1
p 0.1

CONCLUSION: This study supports the notion that a subset of IBS patients has
a low-grade inflammation with higher serum levels of pro-inflammatory cytokines. Also, lower mucosal expression of TLR4 and NOX1 RNA suggest
impaired recognition and subsequent clearance of bacteria in intestinal tissue.
Disclosure of Interest: None declared
P1499 THE BURDEN OF CLOSTRIDIUM DIFFICILE INFECTION
BETWEEN 2010 AND 2013: TRENDS AND OUTCOMES FROM AN
ACADEMIC CENTER IN EAST EUROPE
B.D. Lovasz1,*, Z. Kurti1, M. Mandel1, Z. Csima1, P.A. Golovics1, B. Szilagyi1,
A. Mohas1, B.D. Csako1, K.B. Gecse1, M. Szathmari1, P.L. Lakatos1
1
1st Department of Medicine, Semmelweis University, Budapest, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: Clostridium difficile infection (CDI) is one of the most
important healthcare associated infections (HAI). Increasing incidence of CDI
were reported.
AIMS & METHODS: Our aim was to analyze incidence and possible risk factors
in inpatients treated with CDI between 1 January 2010 and 1 May 2013 at 1st
Department of Medicine, Semmelweis University, Budapest, Hungary. A total of
11751 inpatients were treated in our clinic in the follow-up period. 247 inpatients
were diagnosed with a CDI infection. For the risk analysis a 1:3 matching was
used. Data of 732 matched for age, gender, inpatient care period and unit were
compared to the CDI population. Inpatient records were collected and comprehensively reviewed.
RESULTS: The incidence of CDI infection was 21.0/1000 admissions (2.1% of all
cause-hospitalizations and 4.45% of total inpatient days). The incidence of severe
CDI was 126/1000 admission (12.55% 31/247 cases), Distribution of CDI cases
was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions)
and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine
(14.2 and 16.9/1000 admissions) units. Recurrence of CDI infection was 11.34%/12
week after discharge. Duration of hospital stay was longer (17.66 (SD:10.78) vs.
12.4 (SD: 7.71) days) in patients with CDI infection. CDI accounted for 6.3% of
all-inpatient deaths, 30 day mortality rate was 21.86% (54/247 cases). Risk factors
for CDI infection were: antibiotic therapy (including 3rd generational cephalosporins or fluoroquinolons, OR:4.559, p50.001), use of proton pump inhibitors
(OR:2.082, p50.001), previous hospitalization within 12 months (OR:3.167,
p50.001), previous CDI infection (OR:15.32, p50.001), while presence of diabetes mellitus was identified as a protective factor against CDI (OR:0.484,
p50.001). Treatment but not outcome of relapsing cases was significantly different
with more frequent use of vancomycine alone or in combination (p50.001) and
longer (p50.02) antibiotic therapy.
CONCLUSION: Incidence of CDI was high and CDI accounted for a significant
burden with longer hospital stay and adverse outcomes. Antibiotic therapy,
proton pump inhibitor therapy and previous hospitalization/CDI infection
were identified as risk factors for CDI
Disclosure of Interest: None declared
P1500 UTILITY OF AN INTERFERON GAMMA RELEASE ASSAY, TBFERON GOLD (TBG), IN DIAGNOSING ILEOCOLONIC
TUBERCULOSIS
C. Panackel1,*, P. Ramaswami1, H. Joshy1, R. Thomas1, B. Sebastian1,
S. Mathai1
1
Department of Gastroenterology and Hepatology, Medical trust Hospital, Kochi,
kerala, India, Kochi, India
Contact E-mail Address: charlespanackel@hotmail.com
INTRODUCTION: Both Ileocolonic tuberculosis and Crohns disease are
common in developing world. In spite of all present day gadgetries at times it
is difficult to differentiate Ileocolonic tuberculosis from Crohns disease.
AIMS & METHODS: Aim - The aim of our study was to assess the utility of an
Interferon Gamma Release Assay, Quantiferon TB Gold in tube test (TBG), in
diagnosing Ileocolonic tuberculosis.

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United European Gastroenterology Journal 2(1S)


Methods: We prospectively included 18 patients with Ileocolonic tuberculosis
(ITB) and 30 patients with IBS (as per ROME III Criteria) who had a normal
chest X-ray and Ileocolonoscopy and biopsy as controls. Demographic, clinical,
laboratory, chest x-ray, endoscopic and histological features were noted in all the
patients. All patients were evaluated with a TBG test. Diagnosis of ITB was
made combining established clinical, endoscopic and histologic criteria.
Patients were followed up and a repeat colonoscopy was performed at 3
months to look for response and at the end of 6 months of therapy to ensure
mucosal healing. The diagnosis was revised if no healing was noted at 3 months.
RESULTS: Results: Eight of the 18 patients (44%) were male, and the mean age
was 42.9 years (Range 16-81 years). All 30 control subjects had a negative TBG
test. Seventeen out of the 18 ITB patients (94.4%) had a positive TBG test. The
sensitivity was 94.4%, Specificity was 100%. Positive predictive value was 100%
and a negative predictive value of 96.7%.

Male/Female
Mean Age in years (Range)
TBG Positive
Abdominal pain
Diarrhoea
Hb
Platelet
CRP
Alb

IBS (n 30)

TB (n 18)

18/12
41.9 (16-80)
0
30
8 (26.7%)
12.4  1.55
2.85  0.75
9
3.66  0.29

8/10
44 (18-81)
17 (94.4%)
17 (94.4%)
9 (50%)
10.97  1.83
2.67  0.89
57
2.7  0.7

comorbidities (trauma, imobility, diabetes, dementia, COPD, IBD) and type of


department (surgical/internal) were obtained. Community onset of CDI and
recurrent CDI were also recorded. Hospital mortality and risk of recurrence
were analyzed in univariate analysis.
RESULTS: Our group consists of 174 patients, 84 men, 90 women, average age
74 years. 27 patients had a recurrent disease (up to 4 recurrences). 51 patients
died during hospital stay (hospital mortality 29%). Majority of patients stayed in
internal medicine department (100/174, 57%). 39 patients (22%) had onset of
disease in the community. In univariate analysis only patients with age 70 years
(121/174) had significantly higher mortality than those with age under 70 (53/
174) (OR 2.599, 95%CI 1.158-5.836, p 0.021). Other variables were not significant. No risk factor for recurrent CDI was statistically significant.
CONCLUSION: Patients with CDI had overal hospital mortality 29%. 22% of
patients had onset of their disease in the community. Age over 70 was the only
significant risk factor of mortality in our group of patients. We believe that novel
treatment strategies should be considered preferably in elderly patients.
Disclosure of Interest: None declared
P1503 NECESSITY
OF
COLONOSCOPY
AFTER
TOMOGRAPHY- DIAGNOSED ACUTE RIGHT-SIDED
DIVERTICULITIS

0.016
0.38
0.09
0.5

CONCLUSION: The TBG Test is both specific and sensitive for diagnosing
ilieocolonic Tuberculosis, and can be can be added to the armamentarium for
diagnosing Ileocolonic tuberculosis.
REFERENCES
1. Kim BJ, Choi YS, Jang BI, et al. Prospective evaluation of the clinical utility of
interferon-c assay in the differential diagnosis of intestinal tuberculosis and
Crohns disease. Inflamm Bowel Dis 2011: 17; 1308-1313.
2. Kobashi Y, Mouri K, Yagi S, et al. Clinical utility of a T cell-based assay in the
diagnosis of extrapulmonary tuberculosis. Respirology 2009; 14: 276281.
Disclosure of Interest: None declared
P1501 ASYMPTOMATIC CARRIAGE OF CLOSTRIDIUM DIFFICILE IN
A JAPANESE LONG-TERM CARE FACILITY FOR THE ELDERLY:
PREVALENCE AND RISK FACTORS
I. Yoshikawa1,*, S. Kumei1, T. Watanabe1, K. Kume1, M. Harada1
Third Department of Internal Medicine, University of Occupational and
Environmental Health, Japan, School of Medicine, KItakyushu-city, Japan
Contact E-mail Address: ichiro@med.uoeh-u.ac.jp
1

INTRODUCTION: Clostridium difficile (CD) is the most frequent cause of nosocomial infectious diarrhea in developed countries. Recent studies suggest asymptomatic carrier may be a major source of CD in healthcare settings. The aim of
this study was to identify the prevalence and risk factors for asymptomatic CD
carriage in a long-term care facility for the elderly.
AIMS & METHODS: Fecal samples were collected from 171 asymptomatic
patients (68.4% woman) with a median age of 83 (range 43 to 101 years).
Data on demographic or clinical information, including age, sex, body mass
index, major diagnosis leading to admission, duration of facility stay, medication
use of antibiotics, proton pump inhibitors (PPI), H2 blockers, or probiotics, and
concurrent diabetes mellitus were studied.
RESULTS: CD was isolated from 61 (35.7%) of 171 asymptomatic patients. 26
(42.6%) of the 61 isolates were toxin A-, B, 18 (29.5%) were toxin A, B, and
17 (27.9%) were toxin A-, B-. Demographic or clinical data were analyzed
between CD carriers and CD noncarriers. Multivariate analysis showed only
PPI use was significant risk factor for CD carriage (odds ratio 2.193, 95% confidence interval 1.026-4.687, p 0.043).
CONCLUSION: This study showed asymptomatic CD carriage was common in
a Japanese long-term care facility for the elderly and was significant association
with PPI use. The findings add to the understanding of CD carriage and have
implication for prevention.
Disclosure of Interest: None declared
P1502 AGE IS THE MAIN RISK FACTOR OF MORTALITY AMONG
PATIENTS WITH CLOSTRIDIUM DIFFICILE INFECTION
P. Vitek1,2,*, O. Zela2, I. Mikoviny Kajzrlikova2, J. Kuchar2, J. Chalupa2
Department of Clinical Studies, University of Ostrava, Faculty of Medicine,
Ostrava, 2Internal medicine department, BESKYDY GASTROCENTRE,
HOSPITAL FRYDEK-MISTEK, Frydek-Mistek, Czech Republic
Contact E-mail Address: vitek-petr@seznam.cz
1

INTRODUCTION: Clostridium difficile infection (CDI) has become important


cause of hospital morbidity and mortality during last decade. Recurrent CDI is
difficult to treat and novel therapies (i.e. fecal transplantation) are evaluated in
this group of patients. In our retrospective study we have decided to analyze
group of patients with CDI from last three years in our hospital.
AIMS & METHODS: All patients with CDI from all hospital departments
diagnosed during period from 1/2011 to 12/2013 were included in the study.
Information about sex, age, previous antibiotic treatment, PPI therapy, various

COMPUTED

R. Hashimoto1,*, A. Chonan1
Gastroenterology, Sendai Kosei Hospital, Sendai, Japan
Contact E-mail Address: rinhahsimoto@gmail.com
1

INTRODUCTION: Several recent studies have reported that screening colonoscopy is not necessary after computed tomography (CT)-diagnosed uncomplicated diverticulitis in Western countries where most diverticulitis are left-sided. In
Japan, as in other Asian countries, more than half of the diverticulitis cases are
right-sided. No study has reported on the need for screening colonoscopy after
diagnosing diverticulitis in Asian patients.
AIMS & METHODS: The aim of this study was to determine if screening
colonoscopy is required in patients with CT-diagnosed diverticulitis. A retrospective cohort study was carried out in a tertiary hospital using hospital registry
codes for diverticulitis. All patients diagnosed with acute diverticulitis between
April 2008 and January 2014, confirmed by CT, were included.
RESULTS: A radiological diagnosis of acute diverticulitis was made in 173
patients. Six patients (1 right-sided and 5 left-sided) underwent emergency resection at hospital admission, whereas 167 were treated conservatively. Among the
conservatively treated patients, 146 (93 right-sided and 53 left-sided) underwent
colonoscopy during follow up. The mean age of right-sided diverticulitis patients
was significantly lower than that of left-sided diverticulitis patients (46.9  14.1
years vs. 60.7  15.5 years, p 5 0.01). There was no colorectal cancer in both
groups. There were 8 patients with advanced adenoma (6/93 [6.5%] and 2/53
[3.8%], p 0.49) and 35 with non-malignant colonic polyp (19/93 [20.4%] and
16/53 [30.2%], p 0.32).
CONCLUSION: This study showed that the prevalence of colorectal cancer/
advanced adenoma/non-malignant colonic polyp in patients with diverticulitis,
regardless of the involved side, may be similar to that of asymptomatic averagerisk individuals which has been previously reported. In the absence of other
indications, routine colonoscopy after CT-diagnosed diverticulitis, even if it
was right-sided, may be unnecessary.
Disclosure of Interest: None declared
P1504 DIGESTIVE
TUBERCULOSIS
IN
THE
REGION
CASABLANCA. EPIDEMIOLOGICAL, DIAGNOSTIC AND
THERAPEUTIC ASPECTS

OF

S. Oussama1,*, M. Tahiri1, R. Meharich1, F. Haddad1, W. Hliwa1, A. Bellabah1,


W. Badre1
1
gastroenterology, university hospital Ibn Rochd, Casablanca, Morocco
INTRODUCTION: Tuberculosis remains a public health problem in Morocco
despite the introduction of the vaccination program. Digestive tuberculosis is a
common site of extrapulmonary locations.
It can affect any segment of the gastrointestinal tract; however, peritoneal and
intestinal locations remain the most frequent. Symptoms are highly variable and
non specific, not necessarily referring to the diagnosis of tuberculosis. Diagnosis
confirmation is based on microbiological or histological examinations. The treatment is essentially medical.
AIMS & METHODS: This is a retrospective study including 32 patients with
tuberculosis over a period of 72 months in the departement of Gastroenterologie
in the university hospital of Casablanca:Ibn Rochd. The data have been selected
from medical records.
The diagnosis of gastrointestinal tuberculosis was selected on histological or
bacteriological evidence.
RESULTS: The average age of patients was 39 years, the sex ratio: 1.8 with a
male predominance. Tuberculosis contagion was found in 27% of patients.
Clinically all patients had pain and abdominal distention, fever in 36% of
cases, a pleural effusion syndrome in 27% and diarrhea in 34% of cases.
Abdominal ultrasonography and computed tomography have objectivied peritoneal effusion in all patients, thickening of digestive handles with lymphadenopathy in 30% of cases.
The ascites puncture revealed liquid rich in proteins in all cases with an average
of 57 g/l proteins (40-94 g / l) with lymphocytic predominance.
Search of Mycobacterium tuberculosis was positive in one patient in a rectal
biopsy.
At the end of this report 13 cases of peritoneal tuberculosis were isolated and the
others were associated with intestinal disease in 10 patients, pleuro-peritoneal
localization in 9 patients and one case of hepato-splenic tuberculosis.

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United European Gastroenterology Journal 2(1S)

Patients with tuberculosis received an antituberculous treatment for 6 months;


the outcome was favorable in 82% of cases.
CONCLUSION: Digestive Tuberculosis is a common location of extra pulmonary locations (4th rank) with a predominance of peritoneal involvement, the
gastrointestinal tract and solid organs.
Diagnosis is suggested by clinical, biological and radiologic arguments. The
diagnosis confirmation is histological or bacteriological.
REFERENCES
J Afr dHepato Gastro-Enterologie 2011; 5: 188-192.
La tuberculose digestive dans la region de Marrakech. Aspects epidemiologiques,
diagnostiques et therapeutiques.
Disclosure of Interest: None declared
P1505 THE COST OF ANTIBIOTICS-ASSOCIATED DIARRHOEA IN
HOSPITALIZED PATIENTS
S. Vermeersch1,*, A. Tanghe1, M. Elseviers2, L. Annemans3,4
hict NV, Brugge, 2Centre For Research And Innovation In Care, Faculty of
Medicine and Health Sciences, University of Antwerp, Antwerp, 3Faculty of
Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, 4Department of
Public Health, Ghent University, Gent, Belgium
Contact E-mail Address: sebastian.vermeersch@hict.be
1

INTRODUCTION: Antibiotic-associated diarrhoea (AAD) is a common


adverse event of antibiotic (AB) treatment. Symptoms range from mild and
self-limiting to severe diarrhoea, particularly in the case of a Clostridium difficile
infection (CDI). The cost be it from a societal, healthcare payer or hospital
perspective for a hospitalized patient experiencing AAD (including non-CDI) is
not well established. A better insight in the cost of AAD in hospitalized patients
is essential for robust health-economic evaluations of interventions aiming to
prevent AAD.
AIMS & METHODS: A cost model was developed for determining the cost of
AAD from a societal, healthcare payer and hospital perspective using two complementary approaches: (a) a top-down approach comparing the total (invoice)
cost for hospitalization of AAD and non-AAD patients and (b) a bottom-up
approach establishing the additional cost for a hospitalized patient with AAD as
compared to a hospitalized patient without AAD based on additional resources
used in AAD patients.
Data for the top-down and bottom-up models were obtained as part of a study
investigating the prevalence of AAD in 743 patients on antibiotics therapy
admitted to internal medicine wards in 4 Belgian hospitals. As part of the
study protocol, hospital invoices for all included patients (both AAD and nonAAD) were collected and additional resource use specifically attributable to the
occurrence of AAD was registered. Resource use registrations included medical
acts, lab tests, drugs, number of days in isolation and extra nursing time for the
treatment of diarrhoea. Additionally, length of stay differences were calculated
from the invoice registrations comparing AAD to non-AAD patients.
For the bottom-up analysis, the cost of hospitalization was calculated by assigning unit costs to the registered additional resource use applicable for the Belgian
context based on local health-economic evaluation guidelines. A literature review
was performed to determine the cost per day of isolation for the hospital perspective. Length of stay and total invoice cost differences between AAD and nonAAD patients were corrected for confounders using logistic regression analysis,
including age, number of AB treatments, type of ward and known risk factors for
development of diarrhoea after exclusion of outlier results.
RESULTS: Using the top-down analysis approach, from a healthcare payer
perspective, a hospitalization where AAD occurs is 811 EUR more expensive
than a hospitalization where no AAD occurs (4,101 EUR AAD; 3,290 EUR nonAAD). Using a bottom-up analysis approach, this cost difference amounts to
1,253 EUR from a healthcare payer perspective; 2,133 EUR from a societal
perspective and 274 EUR from a hospital perspective.
CONCLUSION: The results from this study using two complementary cost
calculation approaches - one based on total invoice data, one based on additional
resource use registrations for AAD clearly demonstrate the significant impact
of the occurrence of AAD on hospitalization cost.
Disclosure of Interest: S. Vermeersch Financial support for research from: Biocodex,
Consultancy for: Biocodex, A. Tanghe Financial support for research from:
Biocodex, Consultancy for: Biocodex, M. Elseviers Financial support for research
from: Biocodex, L. Annemans Financial support for research from: Biocodex.
P1506 VALIDATION OF A NEW IN VITRO COLONIC FERMENTATION
MODEL WITH IMMOBILIZED ELDER MICROBIOTA FOR
CLOSTRIDIUM DIFFICILE INFECTION AND ANTIBIOTIC
TREATMENT TESTING
1,*

S. Fehlbaum , C. Chassard , S. Poeker , C. Fourmestraux , M. Derrien ,


C. Lacroix1
1
Institute for Food Nutrition and Health, ETH Zurich, Zurich, Switzerland,
2
Danone Vitapole, 91767 Palaiseau Cedex, France
Contact E-mail Address: sophie.fehlbaum@hest.ethz.ch
INTRODUCTION: C. difficile infection (CDI) is a frequent hospital acquired
infection in the elderly often associated with broad-spectrum antibiotics treatments. Currently, vancomycin and metronidazole are the standard therapies for
CDI but increasing antibiotic resistances and high recurrence rates emphasizes
the need for alternative treatments. In vitro intestinal fermentation and cell
models are useful platforms for studying separately the interactions between
complex microbiota and cell responses.
AIMS & METHODS: The objective of this study is to validate novel intestinal
in vitro fermentation models of the elderly gut microbiota for the investigation of
CDI and antibiotic treatment.

The PolyFermS models were designed to allow parallel testing under highly
controlled conditions of treatments applied in test reactors simulating the conditions of the proximal or distal colon reactor. The test reactors were continuously inoculated with the same intestinal microbiota composition produced in a
first stage immobilized cell reactor operated under conditions of the proximal
colon. CDI was induced in test reactors by spiking C. difficile vegetative cells of
ribotype 001 or by addition of spores of ribotypes 001 and 012. The elderly
models with CDI were validated through antibiotic treatments with the application of daily 150 mg/l ceftriaxone or twice daily 330 mg/l metronidazole. The
main bacterial groups (qPCR), metabolite production (HPLC), gut microbiota
profiles (pyrosequencing) and cytotoxin titre (Vero cell assay) were determined.
RESULTS: The elderly PolyFermS models showed very high stability for all
tested bacterial groups and metabolites over the fermentation period (two
models run for 70 and 80 days). V5-V6 sequencing showed that the diversity
of the fecal inoculum was maintained in the inoculum reactor while the ratios
among the bacterial groups differed. Upon inoculation C. difficile colonized in
the distal (pH 6.8) but not in the proximal intestinal reactors (pH 5.7), reaching
high and stable copy numbers of up to log 8 per ml fermentation effluent and
increasing toxin titre over time. Metronidazole administration during ten days
strongly impaired growth of butyrate producing bacteria and decreased the C.
difficile numbers to below the detection limit of qPCR. Two days after cessation
of metronidazole treatment C. difficile started to re-colonize the reactors.
CONCLUSION: The new PolyFermS model of the elderly gut microbiota and
CDI is especially suitable for assessing the potential and mechanisms of new
antimicrobials and alternative strategies (e.g. probiotics) to prevent and/or
treat CDI.
Disclosure of Interest: None declared
P1507 AEROMONAS
SPECIES:
AN
OPPORTUNISTIC
ENTEROPATHOGEN IN PATIENTS WITH INFLAMMATORY
BOWEL DISEASES? A SINGLE CENTER COHORT STUDY
T. Lobaton1,*, I. Hoffman1, S. Vermeire1, M. Ferrante1, J. Verhaegen2, G.
Van Assche1
1
GASTROENTEROLOGY, 2MICROBIOLOGY, LEUVEN UNIVERSITY
HOSPITAL, Leuven, Belgium
Contact E-mail Address: tlobaton@bellvitgehospital.cat
INTRODUCTION: Exacerbation of inflammatory bowel disease (IBD) has been
classically linked to pathogens such as Clostridium difficile (C.diff) and cytomegalovirus. We recently observed 4 cases with a positive Aeromonas stool culture
at the time of a severe IBD flare or diagnosis. Its role as an enteropathogen is
debated.
AIMS & METHODS: Aim: To explore the significance of positive Aeromonas
stool cultures in IBD patients and controls.Methods: Observational prospective
study. All patients with positive Aeromonas stool cultures between 1-1-2011 (start
of massaspectrometry detection) to 30-10-2013 were indentified in the microbiology database at a referral hospital. Demographics, clinical, biological and endoscopic data were extracted from medical records. Ethics approval was obtained.
RESULTS: 77 patients (11 IBD) were identified. Baseline characteristics are
summarized in Table 1. Symptoms were diarrhea in 87%, abdominal pain in
51%, fever in 35% and vomiting in 26%. Median (IQR) C-reactive protein
was 28 (9-98) mg/L. In 48% of the cases, Aeromonas caused a very mild selflimited gastrointestinal infection (GII) and no antibiotics (ATB) were given.
Among the 40 cases needing ATB, 20 had a mild-moderate GII; 4 a severe GII
with complications; 4 a co-infection by Campylobacter and 2 de novo Crohns
disease (CD). Hospitalization was needed in 31 cases and in other 21 Aeromonas
was detected during the hospitalization for other reasons. A.caviae and A.veronii
were isolated in 32 and 27 cases respectively. A.veronii was more frequent in IBD
patients (50 vs. 32%) and was isolated in 7/18 and 3/4 of the moderate and severe
GII whereas A.caviae was found in 12/20 of mild self-limited GII. Among the
IBD patients, Aeromonas triggered a moderate-severe flare in 2 cases of silent
ulcerative colitis (UC) on 5-ASA, and appeared in the context of de novo CD in 2
more cases. In contrast, Aeromonas appeared in 3 CD patients (1 on infliximab
(IFX) and azathioprine (AZA) and the other 2 with an ileostoma without treatment) with already active disease;in 3 IBD patients in remission (1 UC on 5-ASA,
1 CD with ileostoma on IFX and 1 CD on AZA) it presented as a mild GII and
in 1 asymptomatic CD patient it appeared in a control culture after C.diff infection. IBD cases were treated more often with ATB (82 vs. 37%, P 0.005) and
had more complications (45 vs. 12%,P 0.025).
Table 1. Baseline characteristics.
Table to abstract P1507
N 77
Median (IQR) age (years)
Female (%)
IBD: CD/UC/IBDU (%)
Previous chronic diarrhea/
Reflux esophafgitis/GI surgery (%)
Active oncologic disease (%)
Solid organ Transplant (%)
Previous hospitalization within
previous 3m (%)
Previous ATB within previous
3m (%)

65 (27-78)
35 (46)
7/3/1 (64/27/9)
14/8/8 (18/10/10)

22 (29)
7 (9)
35 (46)
19 (25)

A545

United European Gastroenterology Journal 2(1S)


CONCLUSION: Aeromonas infection presented as a milder infection in nonIBD patients. A.veronii was more prevalent in IBD and was associated with
worse clinical outcomes. Prospective case controlled data in larger cohorts are
needed to establish the true significance of Aeromonas as an opportunistic enteropathogen in IBD.
Disclosure of Interest: T. Lobaton: None declared, I. Hoffman Lecture fee(s)
from: Nutricia, Mead Johnson, Takeda, Consultancy for: Mead Johnson, S.
Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie,
Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor,
Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring,
Shire, Pfizer, M. Ferrante Financial support for research from: Janssen Biologics,
Lecture fee(s) from: Merck, Tillotts, Ferring, Abbvie, Consultancy for: Abbvie,
Merck, Janssen Biologics, J. Verhaegen Lecture fee(s) from: Bayer, G. Van
Assche: None declared

Multivariate analysis showed that male gender (HR 1.78, 95%CI 1.25-2.55),
multiple lesions (HR 2.01, 95%CI 1.46-2.77), large lesion (HR 1.88, 95%CI
1.31-2.69), right/both sided-lesion (HR 1.38, 95%CI 1.01-1.90), and lesions of
high grade dysplasia or cancer (HR 1.49, 95%CI 1.04-2.14) were statistically
significant factors for metachronous lesions, and male gender (HR 2.11,
95%CI 1.18-3.75), multiple lesions (HR 1.70, 95%CI 1.02-2.82), large lesion
(HR 2.26, 95%CI 1.28-3.98), and lesions of high grade dysplasia or cancer
(HR 1.75, 95%CI 0.99-3.08) were statistically significant factors for metachronous advanced lesions.
CONCLUSION: Male gender and patients with multiple lesions, large lesions
more than 10 mm, lesions with advanced pathology at initial resections were
confirmed as the major predictors of metachronous advanced lesions during
colonoscopic surveillance.
Disclosure of Interest: None declared

P1508 COLORECTAL CANCER IN PATIENTS WITH INFLAMMATORY


BOWEL DISEASE IN UPPSALA COUNTY, SWEDEN 1970-2010

P1510 METABOLIC FACTORS WHICH ASSOCIATE WITH PATIENTS


HAVING METACHRONOUS COLORECTAL NEOPLASMS DURING
SURVEILLANCE AFTER INITIAL COLONOSCOPIC RESECTIONS

P.M. Hellstrom1,*, K. Bjorner1, P. Sangfelt1


Medical Sciences, Uppsala University, UPPSALA, Sweden
Contact E-mail Address: per.hellstrom@medsci.uu.se
1

INTRODUCTION: Inflammatory bowel disease (IBD), ulcerative colitis as well


as Crohns disease, is associated with an increased risk of colorectal cancer
(CRC). The level of lifetime risk of malignant development does however
differ between studies and conditions in different countries over time.
AIMS & METHODS: The aim of our study was to review historic cases of IBDrelated CRC in the Uppsala region, Sweden, and analyse the clinical characteristics of the cases in question.
From the patient diagnosis registry of Uppsala University Hospital, all patients
with a diagnosis of IBD were scrutinized over a period spanning 40 years from
1970 to 2010. The outcome of CRC cases were retrieved and reviewed for clinical
information in association with development of malignant disease.
RESULTS: Over the period of 40 years, 49 cases of CRC were found. Out of
these, 37 were males and 12 females. The median age for diagnosis of CRC was
46 years, as compared to 72 years for CRC in non IBD-patients (p50.001). The
standardized incidence ration (SIR) calculated from 38 patients in the Uppsala
region was for the whole CRC group 0.97 (95% confidence interval (CI) 0.921.03). For males, SIR was 1.23 (CI 1.18-1.27) and for females SIR was 0.65 (CI
0.59-0.71). There was no preponderance for CRC in smokers or patients with
high BMI. The overall 5-year survival was 43.3% with no significant difference
between men and women (p 0.54). Of note, the younger cases with CRC diagnosis before 30 years of age had a 14.3% 5-year survival, whereas those diagnosed between 30-60 years had a 49.2% 5-year survival, p50.013). The 5-year
survival of those diagnosed after 60 years was 44.9% (p 0.20).
Mortality from CRC was numerically higher for those diagnosed between 19701990 with a 31.7% 5-year survival rate, whereas cases between 1991-2010 had a
47.9% 5-year survival rate (p 0.25).
CONCLUSION: Patients with IBD are prone to develop CRC at a much
younger age than the population in general. Albeit, the overall lifetime risk for
CRC in IBD is similar to that of the general population. However, men seem to
be at a higher risk, almost twice that of women for developing CRC in IBD.
There was a considerably higher 5-year mortality among those diagnosed at an
early age before 30 years of age.
Disclosure of Interest: None declared
P1509 THE PREDICTORS FOR METACHRONOUS ADVANCED
NEOPLASMS AFTER INITIAL COLONOSCOPIC RESECTIONS OF
SPORADIC ADENOMA AND CARCINOMA
S. Kimura1,*, M. Tanaka2
1
Gastroenterology, Aomori Rousai Hospital, Hachinohe, 2Pathology and
Laboratory Medicine, Hirosaki Municipal Hospital, Hirosaki, Japan
Contact E-mail Address: georgiabroad@aomorih.rofuku.go.jp
INTRODUCTION: We aimed to investigate the major predictors for developing
metachronous colorectal advanced neoplasms during colonoscopic surveillance
after initial resections of sporadic adenoma and carcinoma.
AIMS & METHODS: The study included 403 patients (mean age 66.29.9yr,
M:F 1.55:1) with initial endoscopic resections of colorectal adenomas and/or
intramucosal carcinomas with repeated follow up colonoscopies (an average time
of surveillance: 73.9 months). During surveillance colorectal lesions less than
5mm in diameter were not resected. The patients were divided into two groups
according to the following risk factors at initial resections; age of patients (less or
more than 65 yr), gender (male or female), number of colorectal lesions (single or
multiple), size (less or more than 10mm), location (left or right/both), histology
(adenoma with low grade dysplasia or high grade dysplasia / cancer). The statistical comparisons were made by Logrank test between 2 groups as for the
cumurative incidences of patients with metachronous lesions, and those with
metachronous advanced lesions (larger than 10mm, adenoma with high grade
dysplasia or cancer). The hazard ratio (HR) values of risk factors for metachronous lesions and those for metachronous advanced lesions according to Cox
proportional hazard models were also investigated.
RESULTS: The cumurative incidences of patients with metachronous lesions
were significantly higher in male patients (p50.001), those with multiple lesions
(p50.0001), those with large lesions more than 10mm (p50.001), those with
right/both sided-lesions (p50.05), and those with lesions of high grade dysplasia
or cancer (p50.005). The cumurative incidences of patients with metachronous
advanced lesions were significantly higher in male patients (p50.01), those with
multiple lesions (p50.01), those with large lesions more than 10mm (p50.0001),
and those with lesions of high grade dysplasia or cancer (p50.0001).

S. Kimura1,*, M. Tanaka2
1
gastroenterology, Aomori Rousai Hospital, Hachinohe, 2Pathology and
Laboratory Medicine, Hirosaki Municipal Hospital, Hirosaki, Japan
Contact E-mail Address: georgiabroad@aomorih.rofuku.go.jp
INTRODUCTION: Recently visceral obesity, insulin resistance, and metabolic
syndrome are considered to be important risk factors for developing colorectal
neoplasms. After initial resections of colorectal adenoma and carcinoma many
metachronous neoplasms requiring endoscopic or surgical resections were
detected during surveillance. In this study we aimed to determine the risk factors
for occurrence of metachronous colorectal tumors using health examination data
of patients undergoing colonoscopic surveillance.
AIMS & METHODS: The study included 348 patients with initial endoscopic
resections of colorectal adenomas and/or intramucosal cancers with follow-up
repeated colonoscopies after at least one year interval (a median follow-up period
63.2 months). They were classified into 156 patients with subsequent resections of
metachronous colorectal lesions (group A), and 192 patients with no metachronous lesions during surveillance (group B). 306 subjects with normal colorectum
were also studied as a control group (group C). Health examination data in
group A, B, and C were statistically compared to determine the risk factors for
developing metachronous neoplasms during surveillance.
RESULTS: Mean age and gender ratio were 66.1 yr, 113:43 (group A), 67.5 yr,
100:92 (group B), 66.4 yr, 181:125 (group C), respectively. No difference of age
between 3 groups, but male to female ratio was higher in group A than group B
and C (p50.01). Body mass index (kg/m2) were 24.5 (group A), 23.7 (group B),
and 23.5 (group C), demonstrating higher BMI in group A than group B and C
(p50.05). The percentages of drinking and smoking were 31.4%, 23.7% (group
A), 18.8%, 15.6% (group B), and 22.2%, 14.7% (group C), disclosing higher
percentages of drinking in group A than group B and C (p50.05). Mean blood
pressures (mmHg) were 139.4/80.4 (group A), 136.9/79.2 (group B), and 135.1/
79.1 (group C), respectively. Systolic pressure in group A was significantly higher
than that in group C (p50.05) but no difference from group B. Serum total
cholesterol and triglyceride (mg/dl) were 203.7, 128.1 (group A), 201.0, 122.0
(group B), 200.8, 103.3 (group C), respectively. Serum triglycerides showed
higher serum levels of group A and B than group C (p50.005), although no
significant difference of serum cholesterol. Liver function test disclosed higher
serum level of GTP in group A (59.7IU/L) than that in group B (41.6IU/L) and
C (34.4IU/L) (p5 0.005), although no significant difference of AST and ALT
levels. The prevalence of fatty liver evaluated by ultrasound were 38.3% (group
A), 26.2% (group B), and 24.1% (group C), respectively. Fatty liver was significantly frequent in group A than group B and C (p50.05). Fasting blood sugars
(mg/dl) were 109.2 (group A), 105.6 (group B), 103.0 (group C), disclosing higher
level in group A than group C (p50.01) but no difference from group B.
CONCLUSION: Health examination data disclosed that male gender, obesity,
high percentage of drinking, high serum level of GTP, and high prevalence of
fatty liver were considered to be the risk factors for developing metachronous
colorectal tumors during surveillance after initial colonoscopic resections.
Disclosure of Interest: None declared
P1511 CONTRASTING COLON/RECTAL CANCER RATIOS IN TWO
CHINESE CITIES WITH DIFFERENT BACKGROUND
COLORECTAL CANCER INCIDENCES
W.-K. Leung1,*, L. Gu2, D. Long2, W.-Q. Chen2
1
Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong,
2
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical
University, Chongqing, China
Contact E-mail Address: waikleung@hku.hk
INTRODUCTION: The incidences of colorectal cancer (CRC) are rising rapidly
in Chinese, particularly in Hong Kong (HK) where it has emerged as the most
common cancer. In contrast, some cities in West China like Chongqing (CQ) are
still having a relatively low CRC incidence.
AIMS & METHODS: We studied the epidemiology of colon and rectal cancers
in these two Chinese cities (HK and CQ) with different background CRC incidences to gain further insight into the changing CRC epidemiology in Chinese.
Data on CRC incidences were retrieved from the HK Cancer Registry and from
two large regional hospitals in CQ (West China). We included all patients newly
diagnosed to have CRC in a 10-year period (2003-2012). The baseline demographic of CRC patients and the Colon/Rectal cancer ratios (CR ratio) of the
two cities were compared.

A546
RESULTS: There was no significant change in CRC incidence over the study
period in both cities. The mean age at diagnosis of CRC was significantly
younger in the lower prevalent area (CQ) than in the higher prevalent area
(HK) (61 vs 71 years; P 50.001). Although the proportion of young (540
years) CRC patients was significantly higher in CQ than in HK (6.7% vs
2.1%, P 50.001), there was a significantly higher proportion of older (70
years) CRC patients in HK (53.1% vs 36.3%; P 50.001). CRC was more
common in men in both cities (M:F ratio, 1:3). There was also a remarkable
difference in the distribution of colon and rectal cancer between the two cities.
Colon cancer was more prevalent in the higher prevalent area (HK) with an
overall CR ratio of 1.34, whereas rectal cancer is the predominant cancer in
CQ (CR ratio 0.63; P 50.0001). In all age groups, colon cancer is more prevalent
than rectal cancer in the high prevalent area (HK) with the CR ratios 1. In HK,
the CR ratio was significantly higher in female than in male (1.79 vs 1.34; P
50.0001) and progressively increased with ages with the highest CR ratio in
the 80 years group (women: 2.18; men: 1.74). In contrast, rectal cancer is
more prevalent than colon cancer in lower prevalent area (CQ) in all age
groups (CR ratio 51). Similar patterns of rising CR ratios with age and sex
were not obvious in the lower prevalent region.
CONCLUSION: When comparing two Chinese regions with different background CRC incidences, there are significantly higher proportions of rectal
cancer and young patients with CRC in the lower prevalent region. The increase
in CRC in higher prevalent region is attributed to the older population and the
marked increase in colon rather than rectal cancer. These findings have important ramifications on the pathogenesis, screening and treatment of CRC in
Chinese. The CR ratio may serve as a surrogate marker for monitoring the
rapidly changing epidemiology of CRC in developing regions.
Disclosure of Interest: None declared
P1512 LOWER RISK OF ADVANCED ADENOMA (AA) AND
COLORECTAL CANCER (CRC) AMONG PATIENTS WITH A
PREVIOUS NEGATIVE RESULT FROM A FECAL
IMMUNOCHEMICAL TEST (FIT) FOR CRC. PRELIMINARY DATA
ON SECOND ROUND SCREENING
X. Bessa1,*, L. Carot2, C. Hernandez3, C. Alvarez1, J.M. Auge4, J. Grau4,
A. Buron3, F. Macia3, A. Castells5, M. Andreu1
1
Gastroenterology Department, 2Hospital del Mar. Barcelona, Barcelona, Spain,
3
Epidemiology and Evaluation Unit, Hospital del Mar. Barcelona, 4Preventive
Medicine and Epidemiology Unit, 5Gastroenterology Department, Hospital Clinic,
Barcelona, Spain
INTRODUCTION: Screening for colorectal cancer by FIT is based on consecutive rounds to detect precursor lesions or CRC in early stages. Data on consecutive rounds of FIT screening are limited and based mostly on small population
studies.
AIMS & METHODS: We assessed the preliminary data regarding positivity
predictive values (PPVs) for advanced adenoma (AA) and CRC among patients
with a previous negative result from a FIT.
Methods: Data were collected from 2 rounds of FIT screening in populationbased CRC screening program (50 to 70 years old). The PPV for AA and CRC
were compared among the first-round participants and second-round participants with a previous negative FIT result.
RESULTS: The rate of positive results from FIT was significantly superior in the
first vs. second round screening (6.2% vs. 4.1%, p5 0.0001). Data comparing all
participants in the first and preliminary results on second round participants who
tested FIT positive and were eligible for colonoscopy were compared (4.195 vs.
1.890 colonoscopy studies performed, respectively). A significant decrease in the
PPV was observed for AA and CRC between the first and second round (33.3%
to 23.5%; p50.0001 and 6.29% to 3.1%; p50.0001), respectively. There were no
significant differences in stages (III vs. IIIIV) of CRC detected in the first and
second round (p50.408). Although not achieving statistical significance, proximal AA were more frequent in the first round (9.0% vs. 7.6%, p50.083). A
significantly increase in proximal location of detected CRC were observed on
second round (20.1% vs. 34.5%, p5 0.031)
CONCLUSION: In our population-based CRC screening program the rate of
positive results from FIT decrease after a first round, and PPVs of FIT for AA
and CRC are significantly lower among second-round participants who tested
negative in the first round. Although no differences are observed in CRC stage,
more proximal CRC are detected on second round screening for CRC. These
results could have a significant impact on the provision cost for population-based
CRC screening programs.
Disclosure of Interest: None declared
P1513 THE DIAGNOSTIC RELEVANCE OF FAECAL LACTOFERRIN
TEST IN COLORECTAL CANCER SCREENING
Y. Kazuyoshi1,*, K. Sato1, Y. Yabe1, C. Hongo1, K. Ito1, M. Shindo1,
M. Kojima1, Y. Asanuma1
1
Health Administration, Japanese Sendai Red Cross Hospital, Sendai, Japan
INTRODUCTION: Faecal haemoglobin (Hb) and transferrin (Tf) tests are often
used in colorectal cancer screening. However, these tests are inadequate when the
amount of blood in the test sample is very low. Lactoferrin (LF) is a glycoprotein
secreted by most mucosal cells and predominantly by neutrophils as a component
of inflammatory response.
AIMS & METHODS: Between June 2011 and June 2012, faecal Lf along with
the conventional faecal Hb and Tf tests were undertaken in 2,012 consecutive
subjects who underwent screening for colorectal cancer at our hospital.
Nescauto Hemo Plus, Nescauto Transferrin Plus, and Nescauto
Lactoferrin Plus test reagents were used to assay faecal Hb, Tf and Lf,

United European Gastroenterology Journal 2(1S)


respectively by using the NS-PlusC15 instrument (all from Alfresa Pharma).
Any subject with at least one positive test result underwent colonoscopy as an
additional screening test.
RESULTS: There were 477 subjects (23.7%) with two or three positive test
results. The positive rates were 6.6% for faecal Hb, 5.7% for Tf, and 17.2%
for Lf, reflecting markedly better sensitivity for faecal Lf assay. Further, among
the 183 subjects who underwent colonoscopy, 107 had colorectal cancer, ulcerative colitis, or other colonic lesions like diverticula or haemorrhoids. Of the 107
subjects with lesions, 79 were positive in the faecal Lf test; in 64 of these, only Lf
test was positive. In contrast, in the conventional faecal Hb and Tf tests, only 43
of the 107 subjects were positive. Additionally, 3 subjects had colorectal cancer,
and only one of these was positive for faecal Hb or Tf test, while all 3 were
positive in the faecal Lf test.
CONCLUSION: In this comparative study, the positive rate for faecal Lf was
about 3 times higher than for either faecal Hb or Tf. This led to more precise cutoff value for faecal Tf test. Therefore, in the screening for colorectal cancer and
other colonic lesions that cannot be detected by using the occult blood test, faecal
Lf should yield better screening outcome, and serve as a clinically relevant biomarker in this clinical setting.
Disclosure of Interest: None declared
P1514 LOW PREVALENCE OF SERRATED POLYPOSIS SYNDROME IN
SCREENING POPULATIONS A SYSTEMATIC REVIEW
Y.J. Van Herwaarden1,*, M.H. P. Verstegen1, W. Kievit2, P. Dura1,
F.M. Nagengast1, I.D. Nagtegaal3, T.M. Bisseling1
1
Department of Gastroenterology and Hepatology, 2Department for Health
Evidence, 3Department of Pathology, Radboud university medical centre,
Nijmegen, Netherlands
Contact E-mail Address: Yasmijn.vanHerwaarden@Radboudumc.nl
INTRODUCTION: Population screening programs offer unique opportunities
to study prevalence of less common polyposis syndromes in relatively unbiased
populations. For serrated polyposis syndrome (SPS) the most cited prevalence is
1 patient in every 3000 persons (Lockett et al. 2001), but this number has been
subject of debate. The change of WHO criteria for diagnosis of SPS in 2010
might also affect the prevalence. An up-to-date estimate of the prevalence of
SPS is necessary to predict the number of cases in screening programs.
AIMS & METHODS: A systematic literature search was conducted in the electronic databases Cochrane Library, PubMed, EMBASE and Web of Science up
to February 2014 using a search strategy including the terms serrated, hyperplastic, metaplastic, polyp, polyposis and syndrome. Studies reporting the prevalence
of SPS defined by the WHO criteria in screening populations were selected. Two
reviewers independently calculated prevalence numbers and appraised risk of
bias1.
RESULTS: Prevalence of SPS in screening populations was reported in six studies (Table 1) and varied between 0 0.66%. The highest prevalence (0.34% and
0.66%) was seen in studies (2-3) based on screening programmes preselecting
patients with a positive stool test. Colonoscopy based screening programmes
(4-6) have the lowest risk of bias reporting prevalences ranging from 0 to
0.09%. The most cited study (1) reporting a prevalence of 0.03%, has a high
risk of bias because it is based on data from a sigmoidoscopy based screening
trial. Only patients with high risk adenomas or  20 distal hyperplastic polyps
were referred for colonoscopy. Therefore it is likely that patients presenting with
proximal serrated polyps were missed.

1
2
3
4
5

Lockett et al, 2001


Biswas et al, 2013
Moreira et al, 2013
Orlowska et al, 2009
Kahi et al, 2012

Screening
method

SPS
Prevalence,
WHO patients/
criteria participants (95% CI)

Risk of bias

Sigmoidoscopy
gFOBT
FIT
Colonoscopy
Colonoscopy

2000
2010
2010
2000
2010

12/40674
5/755
8/2355
28/50148
3/3170

0.03%
0.66%
0.34%
0.06%
0.09%

High
High
High
Intermediate
Intermediate

2010

0/1426

0% (NA)

6 Hazewinkel et al, 2014 Colonoscopy

(0.01-0.05)
(0.08-1.24)
(0.10-0.57)
(0.04-0.08)
(0 0.20)

Low

Table 1. Overview of included studies. CI Confidence Interval,


gFOBT guaiac Fecal Occult Blood Testing, FIT Faecal Immunochemical
Testing, NA Not Applicable.
CONCLUSION: Due to the low number of high quality studies, true prevalence
of SPS is unclear but is likely to be below 0.09%. Prevalence in preselected
screening populations after positive stool testing are higher with reported
range between 0.34 and 0.66%.
REFERENCES
1 Loney PL, et al. Critical appraisal of the health research literature: Prevalence
or incidence of a health problem. Chron Dis Can 1998; 19: 170-176.
Disclosure of Interest: Y. Van Herwaarden: None declared, M. Verstegen: None
declared, W. Kievit: None declared, P. Dura Financial support for research from:
Mosaic grant, Netherlands Organisation for Scientific Research, F. Nagengast
Other: scientific adviser for Sensus; part of COSUN, I. Nagtegaal: None
declared, T. Bisseling: None declared

A547

United European Gastroenterology Journal 2(1S)


P1515 EFFECT OF VISCERAL OBESITY
METASTASIS IN COLON CANCER

ON

LYMPH

NODE

Y.W. Ahn1,*, E.Y. Doo1, H.L. Lee1, K.N. Lee1, D.W. Jun1, O.Y. Lee1,
D.S. Han1, B.C. Yoon1, H.S. Choi1, J.S. Hahm1
1
Department of Internal Medicine, Hanyang University College of Medicine,
Seoul, Korea, Seoul, Korea, Republic Of
Contact E-mail Address: 01714u@naver.cm
INTRODUCTION: An association between obesity and unfavorable outcomes
for various types of malignancy has been established. However, the relationship
between fat distribution and lymph node metastasis has not been well studied.
AIMS & METHODS: The aim of our study is to determine the impact of visceral
obesity on lymph node metastasis and overall survival in colon cancer. This study
reviewed medical records for consecutive patients who underwent radical resection for colon cancer between 2003 and 2008. Metastatic lymph node ratio
(MLR) was defined as the number of involved nodes by tumor divided to the
total number of resected lymph nodes. Visceral obesity was determined by measuring abdominal fat volume distribution via CT scan and then calculating the
percentage of visceral fat (VF%) to total fat area.
RESULTS: 278 patients were divided into two groups: VFs (VF%  29, n 81)
and VFv (VF% 4 29, n 197). The baseline characteristics showed some differences between two groups with respect to body mass index, total cholesterol and
the proportion of MLR. In the multivariate analysis, MLR significantly
decreased with the higher VF% (OR 0.406, 95% CI 0.2060.801,
P 0.009). In addition, MLR was significantly associated with HbA1c, differentiation, lymphovascular invasion and perineural invasion. There was significant difference in overall survival between patients with VF%  29 and those
with VF% 4 29 (P 0.009).
CONCLUSION: Visceral obesity was associated with a lower ratio of metastatic
lymph nodes and higher overall survival.
Disclosure of Interest: None declared
P1516 MEK5/ERK5 SIGNALLING ACTIVATES NF-KB AND PROMOTES
A MORE AGGRESSIVE PHENOTYPE IN HUMAN COLON CANCER
CELLS
A.E. S. Simoes1, D.M. Pereira1, S.E. Gomes1, M. Caridade1, T. Carvalho2,
R.E. Castro1,3,*, C.J. Steer4, S.N. Thibodeau5, P.M. Borralho1,3, C.M.
P. Rodrigues1,3
1
iMed. ULisboa, Faculdade de Farmacia, Universidade de Lisboa, 2IMM,
Faculdade de Medicina, Universidade de Lisboa, 3Dep. Bioqumica e Biologia
Humana, Faculdade de Farmacia, Universidade de Lisboa, Lisbon, Portugal,
4
University of Minnesota, MN, 5Mayo Clinic, Rochester, Minneapolis, United
States
Contact E-mail Address: asimoes@ff.ul.pt
INTRODUCTION: ERK5 and its direct activator, MEK5, are overexpressed in
prostate and breast cancer, correlating with overall poorer disease prognosis, and
leading to increased proliferation, metastasis and chemoresistance. In addition,
we have previously demonstrated that ERK5 silencing increases colon cancer
(CC) cell apoptosis and 5-FU-sensitivity, highlighting the relevance of ERK5
signalling in CC.
AIMS & METHODS: In the present study, we evaluated the expression of
MEK5, ERK5, NF-kB and IkB in 284 human CC samples, including normal
colonic mucosa, tubulovillous adenomas, and adenocarcinomas with proficient
or deficient DNA mismatch repair system (pMMR and dMMR, respectively). In
addition, to further evaluate ERK5 signalling in CC, we produced a stable cell
line model with differential ERK5 activation via lentiviral transduction and cell
sorting of SW620 colon carcinoma cells, to overexpress constitutively active
MEK5 (MEK5-CA), dominant-negative (MEK5-DN), or empty vector control.
Next, we evaluated the impact of MEK5/ERK5 signalling in cell cycle progression, by flow cytometry following PI staining, and cell migration, by wound
healing and Boyden assay. NF-kB activation was estimated by the ratio of
NF-kB and IkB expression levels, NF-kB nuclear translocation, and also by
luciferase reporter assay. Finally, we performed cecum orthotopic xenografts in
NOD. SCID mice and evaluated tumor cell metastization.
RESULTS: Our results show that ERK5 and MEK5 are overexpressed in human
adenomas (p50.01) and pMMR and dMMR adenocarcinomas (p50.05).
Similarly, NF-kB is overexpressed in adenomas, pMMR and dMMR adenocarcinomas, and significantly overactivated in pMMR and dMMR adenocarcinomas (p50.05). According to TNM staging, more aggressive tumors displayed
higher ERK5 overexpression and NF-kB activation (p50.05), suggesting that
ERK5 might be relevant in CC progression and to the acquisition of more
invasive and metastatic potential. Interestingly, we observed a significant correlation between ERK5 expression and NF-kB activation, in human adenocarcinoma samples (p50.05). We also showed that in vitro, ERK5 overactivation
(MEK5-CA) significantly accelerates cell cycle progression (p50.01) and
increases cell migration (p50.001), as compared to inactive ERK5 (MEK5DN) and empty control cell lines. In parallel, MEK5-CA cells displayed
increased NF-kB nuclear translocation and transcriptional activity (p50.05),
together with increased expression of mesenchymal marker Vimentin (p50.05).
Finally, we observed that 6-weeks post tumor cell injection into the cecum wall of
NOD. SCID mice, MEK5-CA-injected mice presented increased incidence of
lymph node metastasis (2/4), compared to MEK-DN mice (0/5).
CONCLUSION: Our results suggest that ERK5/NF-kB signalling pathway is
important for tumor onset, progression and metastization, possibly representing
a novel therapeutic target in CC treatment.
(PTDC/SAU-ORG/119842/2010 and SFRH/BD/79356/2011, and SPG)
Disclosure of Interest: None declared

P1517 SYSTEMATIC, ROBUST, REVERSIBLE DNA METHYLATION


PRECEDE SPORADIC, RANDOM MUTATIONS IN COLORECTAL
ADENOMA-DYSPLASIA-CANCER DEVELOPMENT
B. Molnar1,2,*, B. Peterfia1,2, A. Kalmar1,2, B. Wichmann1,2, A. V. Patai2,
Z. Tulassay1,2
1
Molecular Medicine Research Unit, Hungarian Academy of Sciences, 22nd
Department of Internal Medicine, SEMMELWEIS UNIVERSITY, Budapest,
Hungary
Contact E-mail Address: molnar.bela1@med.semmelweis-univ.hu
INTRODUCTION: Colorectal adenoma-dysplasia-cancer (AD-CRC) development is characterised by sequential, random and sporadic (545% frequency)
mutations of certain genes. Recent epigenetic investigations showed that methylation of selected genes occurs in high frequency (495%) in early stages of cancer
already. New generation sequencing and array technologies now allow the systematic investigation and comparison of genetic or epigenetic alterations in ADCRC.
AIMS & METHODS: We aimed to evalate the role of epigenetic and genetic
alterations in the AD-CRC development using new generation sequencing and
DNA methylation arrays. DNA was isolated from fresh frozen biopsy specimens
(20 normals; 33 adenomas; 17 CRCs). First, a multiplex PCR panel was designed
to amplify mutation hot spots of 12 selected genes (APC, BRAF, CTNNB1,
EGFR, FBXW7, KRAS, MSH6, NRAS, PIK3CA, SMAD2, SMAD4, TP53).
Amplicons of eight samples were sequenced together at once by a GS Junior
instrument (Roche) using ligated, barcoded adaptors for library preparation.
Further methylation analysis of 94 genes was performed on Human Colon
Cancer EpiTect Methyl II Signature PCR Array (Qiagen) from the same DNA
specimen. After RNA isolation whole genome expression analysis was performed
with HGU133plus2 microarrays (Affymetrix) from 49 normal, 49 adenoma and
49 CRC specimens and on HT-29 cells with and without 5-aza-deoxycytidin
treatment. Immunohistochemistry confirmation of expression changes on protein
level was performed using tissue microarrays.
RESULTS: Mutations were found in 76% of adenomas and 78% of the cancer
cases. The average number of mutations found in mutated samples was 1; 1,8; 1,9
and 2,3 in low grade adenomas, high grade adenomas, carcinomas and serrated
adenomas, respectively. The only mutation found in normal samples was a germ
line APC mutation. The APC suppressor gene was mutated in adenomas more
frequently than in carcinomas (36% vs. 24%). The most frequently mutated
genes were APC, TP53 and KRAS with 36%, 18% and 26% frequencies in
adenomas and 24%, 47% and 45% frequencies in carcinomas. Interestingly,
no sample was found bearing APC and TP53 mutations together. DNA methylation was found in 100 % of the investigated colorectal adenoma and cancer
specimens. Eight genes were found to be methylated in all of the cases. This
gen set included SFRP1, MAL, SLIT2, SST, VIM; another set of genes
(DKK1, SLI3, TMEFF2) was found to be hypermethylated in adenomas and
cancers in 475% of the cases. In adenomas 56 genes, in dysplasias 40 in cancer
37 genes were methylated (450% of the cases). The effect of methylation could
be confirmed by decreased mRNA and protein expression. Demethylation treatment successfully restored the expression profile of the top methylated genes.
CONCLUSION: Methylation occurred in early premalignant stages in parallel
followed by somatic random mutations in increasing number through the ADCRC development. Demethylation treatment could reverse the systematic, robust
methylation alterations. Epigenetic alterations precede the somatic mutations of
the AD-CRC and show higher significance in CRC development than genetic.
Disclosure of Interest: None declared
P1518 AN ABNORMAL BODY MASS INDEX IS ASSOCIATED WITH AN
INCREASED RISK OF RECTOSIGMOID CANCER RISK: INTEREST A
SHORT RECTO-SIGMOIDOSCOPY FOR EARLY DETECTION
C. Eveno1,*, Y. Parc 2, A. Laurent 3, C. Tresallet4, J.C. Vaillant 4, M. Ducreux5,
J.F. Emile 6 on behalf of COINCIDE group
1
lariboisiere hospital, 2saint antoine, 3mondor, 4Pitie, 5IGR, 6ambroise pare, paris,
France
INTRODUCTION: Obesity is a well-known risk factor for colorectal cancer
(CRC) and is associated with underweight with a poor prognosis. The French
CRC screening is based on cancer register which allow diagnosing one cancer for
2000 performed colonoscopy. We studied the influence of body mass index
(BMI), which is evolving during past decades, on the location of CRC and its
relevance to adapt the screening.
AIMS & METHODS: From January 2008 to December 2010, all patients consecutively operated for CRC in 20 Parisian centres were collected in a prospective
database (COINCIDE project). Data analysis was done through its proprietary
algorithm clustering supervised non-parametric (Q-Finder).
RESULTS: Of the 1908 patients, CRC primary localization was sigmoid or rectal
in 1095 patients. Six subgroups of patients with an excess risk of developing
rectosigmoid cancer were linked to abnormal BMI. For example, 142 patients
from 42 to 69 years, with a BMI from 24 to 33 (overweight and obese) had a surrisk of 1.8. Another subgroup of 123 patients from 53 to 63 years, with a BMI
from 14 to 22.4 (underweight) had a 1.9 times higher risk.
CONCLUSION: COINCIDE database is representative, on a very recent period,
of the Parisian population of CCR. Abnormal BMI (overweight and underweight) is associated with an excess risk of rectosigmoid CRC. We discuss an
intensification of CRC screening for this population by achieving a sigmoidoscopy at the age of 45 years. The validation of the cost and effectiveness of such a
practice should be performed prospectively.
Disclosure of Interest: None declared

A548
P1519 MEK5-ERK5
SIGNALLING
INHIBITION
DECREASES
PROLIFERATION AND INCREASES 5-FLUOROURACIL-INDUCED
APOPTOSIS IN COLON CANCER CELLS
D.M. Pereira1,*, A.E. S. Simoes1, S.E. Gomes1, R.E. Castro1,2, P.M. Borralho1,2,
C.M. P. Rodrigues1,2
1
Instituto de Investigacao do Medicamento (iMed. ULisboa), 2Departamento de
Bioqumica e Biologia Humana, Faculdade de Farmacia, Universidade de Lisboa,
Lisboa, Portugal
Contact E-mail Address: dampereira@ff.ul.pt
INTRODUCTION: Aberrant MEK5-ERK5 signalling has been reported in several types of human cancer, being established as a critical player in cancer development, and as a key survival signal for chemoresistance in response to several
antitumor agents. In colon cancer (CC), MEK5 overactivation was correlated
with disease stage progression. Moreover, recent data from our group demonstrated that MEK5 and ERK5 expression is increased in human colon adenomas
and adenocarcinomas. Importantly, we have also demonstrated that ERK5 silencing enhances CC cell sensitivity to 5-fluorouracil (5-FU), the most widely used
chemotherapeutic for CC treatment.
AIMS & METHODS: In the present study, we aimed to investigate the role of
MEK5-ERK5 signalling in CC cell proliferation and sensitivity to 5-FU exposure. For this purpose, HCT116 and SW620 cell lines expressing a constitutively
active (CA) or a dominant negative (DN) form of MEK5 were produced by
lentiviral transduction, followed by sorting of stably transduced cells.
RESULTS: Our results demonstrate that CA-MEK5 increased cell proliferation
(p 5 0.05) and KRAS expression (p 5 0.01), in both HCT116 and SW620 cells.
In turn, in the HCT116 model, DN-MEK5 increased the expression of p53 (p 5
0.05) and its transcriptional targets p21 and Puma (p 5 0.01), as well as cell
death following 5-FU exposure (p 5 0.05). This was further associated with
increased caspase-3/7 activation and apoptosis (p 5 0.05). Conversely, CAMEK5 reduced 5-FU-induced cytotoxicity and apoptosis (p 5 0.05).
Furthermore, 5-FU exposure markedly decreased the levels of endogenous
MEK5 and ERK5 expression and activation (p 5 0.05). Finally, our results
show that MEK5-ERK5 activation may modulate cell proliferation and sensitivity to 5-FU through downregulation of the expression of the tumour suppressor
miRNAS, miRNA-143, -145, and -34a (p 5 0.05).
CONCLUSION: Overall, our results indicate that MEK5/ERK5 pathway overactivation may contribute to CC aggressiveness and chemoresistance, suggesting
ERK5-targeted inhibition, via siRNA, miRNA or small-molecule inhibitors, may
provide a promising therapeutic approach for CC treatment.
Supported by Sociedade Portuguesa de Gastroentrologia and Fundacao para a
Ciencia e Tecnologia (PTDC/SAU-ORG/119842/2010, SFRH/BD/96517/2013,
SFRH/BD/88619/2012 and SFRH/BD/79356/2011). The authors thank Dr.
Robert Doebele for the kind gift of pWPI-MEK5AA and pWPI-MEK5DD
constructs.
Disclosure of Interest: None declared
P1520 PTP1B EXPRESSION AND PHOSPHATASE ACTIVITY ARE
INCREASED IN PRIMARY COLORECTAL CANCER WHICH
LEADS TO A MORE INVASIVE PHENOTYPE
E. Hoekstra1,*, M. Bruno1, J.van Der Woude1, M. Peppelenbosch1, G. Fuhler1
Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands
Contact E-mail Address: e.hoekstra@erasmusmc.nl
1

INTRODUCTION: Cell signaling is dependent on the balance between phosphorylation of proteins by kinases and dephosphorylation by phosphatases. This
balance if often disrupted in colorectal cancer (CRC), leading to increased cell
proliferation and invasion. For many years research has focused on the role of
kinases as potential oncogenes in cancer, while phosphatases were commonly
assumed to be tumor suppressive. However, this dogma is currently changing
as phosphatases have also been shown to positively affect cancer growth. One of
these phosphatases is protein tyrosine phosphatase 1B (PTP1B).
AIMS & METHODS: The aim of this study was to investigate the expression
and phosphatase activity of PTP1B in CRC, and elucidate its effects on cellular
functions and signaling. PTP1B expression was analysed by immunohistochemistry on microsections from biopsies of dysplasia (n 6), adenocarcinoma (n 9)
and control (inactive ulcerative colitis, n 5), as well as by western blotting of
paired freshly frozen CRC and normal adjacent tissue (n 10). Phosphatase
activity was also assessed in these latter samples by immunoprecipitating
PTP1B under saturating conditions, followed by a phosphatase activity assay
using PNPP as substrate. To investigate the effects of PTP1B on proliferation,
adhesion, migration, and elucidate its downstream targets, we manipulated the
PTP1B expression in vitro by lentiviral transduction of HCT116 and Caco-2 cells
with 2 different shRNAs against PTP1B.
RESULTS: PTP1B expression in intestinal epithelial cells (IECs) is low in normal
colon (14% positive; mean intensity 0.20.1) and increases from dysplasia to
carcinoma (100% positive IECs; with mean intensity rising from 1.40.3 to
1.80.3 respectively). These results were confirmed by western blot analysis.
The intrinsic enzymatic activity of the PTP1B protein is significantly increased
in cancer compared to adjacent normal tissue (mean OD 1.0 in CRC compared to
0.2 in normal tissue) (p 0.001). Knocking down PTP1B in CRC cells reduced
the phosphorylation of the mitogenic kinase ERK by approximately 50%, and
decreased mRNA levels of downstream targets involved in proliferation; i.e. cMYC and CyclinD1. Furthermore, adhesion, migration, and proliferation were
significantly reduced in PTP1B knockdown cells.
CONCLUSION: Not only is the expression of PTP1B is increased in colorectal
cancer as compared to normal tissue, but strikingly, the intrinsic enzymatic
activity of the protein is also enhanced, suggesting a role for PTP1B phosphatase
activity in CRC progression. Knocking down PTP1B in CRC cell lines results in

United European Gastroenterology Journal 2(1S)


a less invasive phenotype with lower adhesion, migration and proliferation capabilities, by interfering in the RAS-RAF-ERK pathway. Together these results
suggest that inhibition of PTP1B activity is a promising new target in the treatment of colorectal cancer and the prevention of metastasis.
Disclosure of Interest: None declared
P1521 REVERSIBLE DNA METHYLATION OF SFRP1 IN STROMAL
MYOFIBROBLASTS IS A FINAL STEP IN EPITHELIAL CELL
GROWTH BLOCKADE IN COLORECTAL CANCER DEVELOPMENT
G. Valcz1, A. V. Patai2, A. Kalmar1,2, B. Peterfia1, F. Istvan2,*, B. Molnar1,2,
Z. Tulassay1,2
1
Molecular Medicine Research Unit, Hungarian Academy of Sciences, 22nd
Department of Internal Medicine, Semmelweis University, Budapest, Hungary
Contact E-mail Address: valczg@yahoo.com
INTRODUCTION: Loss of stroma-mediated inhibitory mechanisms can contribute to uncontrolled proliferation and growth of tumor cells. Expression changes
of stromal secreted frizzled-related protein 1 (SFRP1) Wnt pathway inhibitor
were not evaluated in colorectal carcinoma (CRC) development yet.
AIMS & METHODS: Our aims were to evaluate SFRP1 expression changes in
CRC development by mRNA analysis and immunohistochemistry (IHC). We
also aimed to analyse SFRP1 promoter DNA methylation levels in order to
identify epigenetic alterations from laser microdissected epithelial and stromal
components as well as from isolated myofibroblasts. We aimed to examine the
effect of recombinant SFRP1 protein administration and demethylation treatment to CRC cell lines harboring different mutations. For SFRP1 gene expression examination biopsy samples from CRC (moderately differentiated tumors
from sigmoid colon and rectum; n 49) areas and paired histologically normal
colonic mucosa (n 49) were analyzed by HGU133Plus2.0 microarrays
(Affymetrix) and were validated with real-time PCR. SFRP1 IHC was detected
on normal biopsy samples (n 20), surgically removed CRC (n 35) and colonic
tissues containing normal adjacent tumor (NAT), adenoma and CRC areas on
the same slide (n 14). We microdissected at least 104 cells from epithelial and
stromal components, furthermore, approx. 103 -smooth muscle actin immunopositive myofibroblasts from similar stromal areas of consecutive slides. SFRP1
promoter DNA methylation was evaluated by bisulfite sequencing. Effect of
recombinant SFRP1 protein treatment to cell proliferation and apoptosis were
examined on SW480 (APC mutant) and HCT116 (APC wild type, -catenin
mutant) cell lines. SFRP1 gene expression analysis was performed on HT-29
(p53 mutant) cells with or without 5-aza-2-deoxycitidine demethylation
treatment.
RESULTS: SFRP1 showed decreased expression in mRNA and no expression
on protein level in parallel in adenoma and CRC epithelium. We identified smooth muscle actin positive myofibroblasts as the main source of stromal
SFRP1 protein in NAT areas and adenomas, but this protein expression disappeared along the transition into the malignant stage. DNA hypermethylation of
the SFRP1 promoter was detected in microdissected epithelium in adenoma and
CRC and in CRC only in myofibroblasts. Recombinant SFRP1 treatment
induced apoptosis and inhibition of proliferation in SW480 and less in
HCT116 cells. Demethylation treatment could increase SFRP1 expression significantly in HT-29 CRC cell line.
CONCLUSION: Decreased expression of SFRP1 in CRC development is related
to DNA hypermethylation. Epithelial methylation of SFRP1 could be observed
in NAT, adenoma and cancer, but myofibroblast SFRP1 methylation could be
detected in cancer stage only. The restored expression of SFRP1 in colorectal
cancer cell lines leads to decrease in proliferation and apoptosis induction. 5-azadeoxycytidin is a potential demethylation agent for SFRP1 with consecutive
increase in gene expression.
Disclosure of Interest: None declared
P1522 THE S100B-P53 PROTEIN-PROTEIN INTERACTION: A NOVEL
ROLE FOR ENTERIC GLIA IN COLON CANCER
G. Esposito1, E. Capoccia1, S. Tiberi1, A. DAlessandro2, M. Pesce2, L. Steardo1,
I. Palumbo2, R. Cuomo2, G. Sarnelli2,2,*
1
Human Physiology and Pharmacology, "La Sapienza" Univeristy, Rome, 2Clinical
Medicine and Surgery, University of Naples "Federico II", Naples, Italy
Contact E-mail Address: sarnelli@unina.it
INTRODUCTION: The connection between intestinal inflammation and tumorigenesis is well-established. We previously showed that upregulation of the enteroglial-derived S100B protein amplifies intestinal inflammation via its interaction
with the Receptor for Advanced Glycation Endproducts (RAGE). Recently,
S100B-p53 protein-protein interaction has been described to be involved in the
melanoma. Our aim is to investigate the role of S100B and its interactions with
the tumor suppressor p53 in human sporadic colon cancer.
AIMS & METHODS: The expression of S100B, RAGE, p53 was evaluated in
cancer and control colonic tissues (n 8 and 6 subjects, respectively); secretion of
VEGF and Filamin was also assessed to estimate cancer cell invasion and angiogenesis, respectively. In order to investigate the direct involvement of the enteroglial protein in tumorigenesis, control colonic tissues were challenged with
increasing concentration of S100B (0.05, 0.5 and 5mM, for 48 h) and expression
of RAGE, p53, VEGF and Filamin were analysed. Similarly, the effect of
Pentamidine (0.05, 0.5 and 5mM, for 48 h), that was previously demonstrated
to disrupts the S100B-p53 protein-protein interaction, on p53 expression was
assessed on control colon tissues.
RESULTS: In colon cancer the expression of p53 was significantly reduced
(182 vs. 0.8 0.1 mm2, p50.001), while S100B, RAGE, VEGF and Filamin
A were all significantly higher than in control tissues (282 vs. 60.8 mm2, 183
vs. 21 mm2, 71 vs. 1.80.9 ng/ml and 72 vs. 2.51ng/ml, all p50.001).

United European Gastroenterology Journal 2(1S)


In vitro challenge with 5mM of S100B induced a tenfold decrease of p53 (150.4
vs. 2.20.6 mm2, p50.01) and a significant increase of RAGE VEGF and
Filamin (123 vs. 1.30.2 mm2, 1.90.3 vs. 51 and 1.30.2 vs. 82 ng/ml,
respectively, all p50.01 vs. control); data with S100B 0.05 and 0.5 mM are not
shown. Most interestingly, pentamidine treatment yields to a concentrationdependent (0.05-5mM) and significant increase of p53 (80.3, 103 and 183
vs. 30.3 mm2, p50.05, 50.01 and 50.001, respectively).
CONCLUSION: We showed that the S100B protein is significantly increased in
human sporadic colon cancer. We also showed that exogenous S100B is able to
significantly reduce the expression of p53 protein, together with a consistent
increase of RAGE, VEGF and Filamin A and that these effects were completely
abolished by pentamidine, that is known to disrupts the S100B-p53 proteinprotein interaction. Our data for the first time indicate that the enteric glia is
likely involved in the tumorigenesis of colon cancer; at the same time we indicate
in the disruption of S100B-p53 protein-protein interaction a new potential target
of intervention for colon cancer.
Disclosure of Interest: None declared
P1523 ENTERIC GLIAL CELLS ACTIVATE COLON CANCER STEM
CELLS TO PROMOTE TUMORIGENESIS
S. Vale`s1, M. Biraud1, S. Marionneau-Lambot2, T. Oullier2, M. Neunlist1,*, L.
Van Landeghem1
1
UMR Inserm 913, IMAD, Nantes University, 2Canceropole Grand Ouest, Nantes,
France
Contact E-mail Address: laurianne.van-landeghem@univ-nantes.fr
INTRODUCTION: Similar to the cellular hierarchy that drives normal/healthy
intestinal crypts, only a limited number of colon cancer cells possess the ability to
self-renew and to give rise to all the different cancer cell types of the tumor1, 2.
These cells, called cancer stem cells (CSCs), are thought to be responsible for
colorectal cancer (CRC) initiation, propagation and recurrence. Current views in
the field suggest that similar to normal intestinal stem cells, CSCs are regulated
by their niche composed of resident or recruited cells that have been hijacked/
altered by the tumor in order to exploit them as nurturing cells delivering paracrine signals crucial to CSC maintenance and tumor growth. Among CSC neighboring cells are enteric glial cells (EGCs) that are potent regulators of intestinal
epithelial barrier functions3, but whose impact on CSCs has not yet been studied.
We hypothesized that EGCs modulate CSC functions and associated
tumorigenesis.
AIMS & METHODS: In vitro. CSCs have been FACS-isolated from HT29 CRC
cell line based on CD44 and CD133 expression (CD133High/CD44High), and
cultured in 3D Matrigel in presence of EGCs seeded on Transwell filters. Two
types of EGCs were used: a non-transformed EGC line purified from rat embryo
(EGC-JUG) and primary cultures of human EGCs (EGC-HOG). Impact of
EGCs was assessed on numbers and size of tumorspheres grown from CSCs,
and compared to non-transformed human fibroblast CCD-18Co cells as well as
known glial-derived soluble factors. In vivo. CSCs were injected alone vs. concomitantly with EGCs subcutaneously in immunodeficient mice.
RESULTS: Our data demonstrate that in vitro EGC-JUG massively increased
numbers and size of tumorspheres grown from CSCs. These results were recapitulated by EGC-HOG. In contrast, CCD-18Co fibroblasts induced an increase in
tumorspheres size but not in numbers. In vivo, concomitant injection of CSCs
and EGCs increased tumor load as compared with CSCs injected alone.
Furthermore, our in vitro preliminary data indicate that EGC-conditioned
medium (CM) did not impact CSCs, suggesting that at basal state, EGCs do
not release pro-tumorigenic factors. However, CM of EGCs that have been preincubated with CRC cells exhibited similar impact on CSCs than direct co-culture with EGCs, indicating that tumor cells activate EGCs to acquire pro-tumorigenic abilities. Among all known EGC-derived soluble factors tested, only
prostaglandin E2 (PGE2) reproduced EGC effects on CSC-derived tumorsphere
growth in vitro. Furthermore, RT-qPCR data show that CRC cells induced
increased expression of mPGES-1, the terminal synthase responsible for generating PGE2, in EGCs. Finally, CM of EGCs that have been first pre-incubated
with CRC cell-CM and then treated with a specific inhibitor of mPGES-1
(CAY10526), did not impact CSCs, indicating that CAY10526 abolished protumorigenic properties induced by CRC cells in EGCs.
CONCLUSION: Altogether these results strongly suggest that CRC cells activate EGCs to acquire pro-tumorigenic abilities, and that tumor-activated EGCs
stimulate CSC clonogenicity and tumorigenicity via PGE2-dependent pathways.
REFERENCES
1. OBrien CA, et al. Nature 2007; 445: 106-110.
2. Ricci-Vitiani L, et al. Nature 2007; 445: 111-115.
3. Neunlist M, et al. Nat Rev Gastroenterol Hepatol 2013; 10: 90-100.
Disclosure of Interest: None declared
P1524 ESTABLISHMENT OF AN ENDOSCOPY-BASED MURINE
ORTHOTOPIC TUMOR IMPLANTATION MODEL TO STUDY
COLORECTAL CANCER
D. Bettenworth1, M.M. Mucke1, K. Schwegmann2, A. Faust2, C. Poremba3,
M. Schafers2, D. Domagk1, L. Philipp1,2,*
1
Department of Medicine B, 2European Institute for Molecular Imaging, University
of Muenster, Muenster, 3Institute of Pathology Munich-North, Munich, Germany
Contact E-mail Address: lenz.philipp@ukmuenster.de
INTRODUCTION: Despite recent advances in diagnostics and therapy of colorectal cancer (CRC) the prognosis is still limited, especially in patients with
advanced stages of the disease. New diagnostic and therapeutic approaches are
therefore highly desirable. Aim of this study was to establish an orthotopic tumor

A549
model for CRC by endoscopy-guided implantation of tumor cells in the colon of
immunodeficient mice.
AIMS & METHODS: The implantation of CRC tumor cells (Caco-2 and HT29)
was primarily performed either subcutaneously or orthotopic by submucosal
injection during murine colonoscopy (coloview miniendoscopic system) in CD1
nude mice (n 6) as well as in NOD/SCID mice (n 10). For monitoring of
tumor development, matrixmetalloproteinases (MMP) expression of tumors
was assessed 24h after i.v.-injection of a Cy5.5-labeled MMP-selective tracer
(Cy5.5-AF443) by Fluorescence Reflectance Imaging (FRI) and Fluorescence
Endoscopy. Finally, tumors were histologically evaluated.
RESULTS: Subcutaneaously implanted HT-29 cells resulted in a marked tumor
growth 14 days after implantation. In contrast, orthotopic implantation in the
colon of CD1 mice lead to decelerated tumor development after 17 weeks. In the
NOD/SCID mice, distinct tumor growth could already be detected beginning at
day 14 after submucosal cell injection. Subsequently, rapid tumors growth with
occupation of the entire colonic circumference could be observed. Notably, post
mortem analysis revealed suspect liver lesions, which were confirmed to be metastasis by histological evaluation. Pathology revealed CRC limited to the submucosa, explaining the low signal detected by fluorescence endoscopy.
As opposed to HT-29 cells, successful implantation of Caco-2-cells could not be
achieved, neither by s.c. nor by orthotopic implantation.
FRI revealed only a discreet tracer uptake in s.c. implanted tumors with a targetto-background ratio of 1.55  0.49. Confirmatively, western blot analysis and
IHC proved no significant MMP-2/-9 expression in s.c. implanted tumors. In
contrast, MMP-tracer uptake was markedly enhanced in orthotopic implanted
tumors.
CONCLUSION: Orthotopic, endoscopy-guided implantation of HT-29 colorectal carcinoma cells was successful in immunodeficient NOD/SCID mice.
Therefore, this model appears to be promising for examination of tumor biology
and preclinical evaluation of novel diagnostic and therapeutic approaches in the
future.
Disclosure of Interest: None declared
P1525 MISMATCH REPAIR GENES INHIBITION ENHANCE CD80
EXPRESSION IN COLORECTAL CANCER CELL LINE AND
SPORADIC DEFECTS ARE ASSOCIATED TO HICD80 LAMINA
PROPRIA MONUCLEAR CELLS INFILTRATION AND BETTER
SURVIVAL
M. Scarpa1,*, C. Ruffolo2, F. Canal3, M. Scarpa1, S. Basato4, F. Erroi4,
A. Fiorot2, A. Pozza2, I. Castagliuolo5, A. Dei Tos3, N. Bassi6, C. Castoro1
1
Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova,
2
General Surgery Unit (IV), 3Pathology Unit, Ospedale Ca Foncello, Treviso,
4
General Surgery Unit, 5University of Padova, Padova, 6General Surgery Unit
(IV), Veneto Institute of Oncology (IOV-IRCCS), Treviso, Italy
Contact E-mail Address: marcoscarpa73@yahoo.it
INTRODUCTION: Genomic defects in DNA mismatch repair (MMR) genes
(MSH2, MLH1, PSM2 or MSH6) characterize the hereditary non polyposis
colon cancer (HNPCC). Moreover, most colorectal cancers (CRC) have MMR
defect caused by DNA methylation. Several studies demonstrated that patients
with MMR-deficient colon cancers have a more favourable stage-adjusted prognosis. Since the immune environment has been demonstrated to influence CRC
prognosis, we aimed to investigate whether MMR genes modulate the immune
response in CRC.
AIMS & METHODS: A group of 108 consecutive patients operated on for CRC
was retrospectively analysed. The presence of Bethesda criteria for HNPCC
diagnosis was assessed. Inflammatory infiltration was quantified by standard
histology. Immunohistochemistry for costimulatory molecule CD80, innate
immunity (TLR4 and MyD88), tumor infiltrating lymphocytes (CD4, CD8)
and MMR genes was performed. Patients were stratified in three groups: no
MMR genes defect, MMR genes defects alone and MMR genes defects and at
least one positive Bethesda criteria. HT29 (CRC cell line) cells were cultured and
transfected with specific siRNAs (siMSH2, siMLH1, siMSH6 and siPSM2) and
the rate of CD80 positive cells was quantified by flow cytometry in presence
and in absence of oxidative stress condition. Non parametric statistics and survival analysis were used.
RESULTS: Patients with at least one MMR gene defect had more frequently a
high CD8 lymphocytes infiltration (p 0.01) and more frequently a high CD8/
CD4 ratio (p 0.01). Patients with MMR defects alone had a better survival than
patients with no defects (HR 0.40 (95% CI 0.06-1.03), p 0.051). LPMC infiltration, frequency of highCD8 lymphocytes infiltration and frequency of
highCD8/CD4 ratio were significantly higher in patients who had a MMR
genes defect alone compared to those who had no MMR genes defect and to
those with MMR genes defect and positive Bethesda criteria (p 0.014, p 0.01
and p 0.05). A significantly greater frequency of patients with high CD80
expression was observed in patients who had a MMR genes defect alone compared to patients who had no MMR gene defect and to those with MMR genes
defect and positive Bethesda criteria (p 0.048). In standard condition, RNA
silencing of MSH2, MLH1 and MSH6 significantly increased CD80 cells rate
(p 0.007, p 0.023 and p 0.015). In oxidative condition, RNA silencing of
MSH2 and MSH6 further increased CD80 cells rate (p 0.031 and p 0.015).
CONCLUSION: Patients with MMR defects and no Bethesda criteria have a
better survival. In this group, the antigen presenting cells and CD8 tumor
infiltrating lylmphocyte cross talk was enhanced as shown by higher LPMC
infiltration and higher frequency of hiCD80 and hiCD8 patients. In vitro
silencing of MMR genes expression significantly increase CD80 expression in
CRC cells. All together these data support the view that a more effective
immune activation in CRC may be responsible of a better prognosis in patients
with MMR defects.
Disclosure of Interest: None declared

A550

United European Gastroenterology Journal 2(1S)

P1526 HIGH NITRIC OXIDE PRODUCTION, SECONDARY TO HIGH


INDUCIBLE- NITRIC OXIDE SYNTHASE EXPRESSION, IS
ESSENTIAL IN REGULATING TUMOUR INITIATING PROPERTIES
OF COLON CANCER STEM CELLS
M.A. Puglisi1,2,*, V. tesori1, L. Ricci-Vitiani3, M. Cappellari3, C. Cenciarelli4,
M. Martini5, E. Giorda6, R. Carsetti6, G. Gasbarrini2, G.B. Pani7,
A. Gasbarrini1
1
Internal Medicine and Gastroenterology, GEMELLI HOSPITAL, ROME,
2
Medical Research Foundation ONLUS, Bologna, 3Hematology, Oncology and
Molecular Medicine, Istituto Superiore di Sanita`, 4Translational Pharmacology,
National Research Council, 5Anatomic Pathology, GEMELLI HOSPITAL,
6
Cytofluorimetry Laboratory, Bambino Gesu` Pediatric Hospital, 7General
Pathology, GEMELLI HOSPITAL, ROME, Italy
Contact E-mail Address: ausiliapuglisi@yahoo.it
INTRODUCTION: Several studies have indicated that continuous exposure to
high concentrations of Nitric Oxide (NO), produced by inducibile-NO synthase
(iNOS), promote neoplastic transformation in many human cancers and especially in colon cancer (CC). Recently, it has also been suggested that high NO
synthesis is a distinctive feature of cancer stem cells (CSC), a tumor subpopulation with self-renewal capacity, that may be identified by the expression of the
CD133 surface marker.
AIMS & METHODS: Aims of this study were to explore the contribution of NO
in the definition of colon CSC features and evaluate potential strategies to treat
CC by modulating NO production. By immunohistochemistry analysis we evaluated iNOS and CD133 expression in 30 samples of human CC. Using the DAF2DA detection system, we assayed the production of intracellular NO in 5 colon
CSC lines obtained from human CC tissues. By FACS sorter, we purified the
NOhigh and NOlow fractions from all colon CSC lines. We compared the tumorigenic potential of both cell fractions by in vitro and in vivo assays. To tested the
potential antitumor effects of iNOS modulation, we treated colon CSCs with the
selective iNOS inhibitor 1400W or we stably transfected these cells with two
distinct iNOS-directed short-harpin RNA (shRNAs).
RESULTS: NOhigh CSCs display an overespression of stem cell markers and
higher expression levels of iNOS than NOlow cells. Interestingly, immunohistochemistry analysis confirmed that, regardless of tumor differentiation grade and
TNM stage, there was a significant association between iNOS overexpression
and higher expression level of the stem cell marker CD133, in human CC.
Moreover, we demonstrated, by in vitro and in vivo assays, that NOhigh cells
displayed higher tumorigenic abilities than NOlow fractions. The blockade of
endogenous NO availability using a specific iNOS inhibitor and genetic knockdown of iNOS resulted in a significant reduction of colon CSC growth and
tumorigenic capacity: a lower capacity to give rise to colonies in soft agar, a
dramatic decrease of invasivness and in vivo tumor growth (xenotransplantations
in nude mice). These data confirmed an integral role for endogenous NO and
iNOS activity in the biology of colon CSCs. Interestingly, analysis of the genes
altered by iNOS-directed shRNA showed that the knockdown of iNOS expression was associated with a significant down regulation of a wide range of signaling pathways in colon CSCs, especially genes involved in stemness and tumor
progression (such as CD133, BMI, b-Catenin and NF-kB pathway).
CONCLUSION: These findings have demonstrated for the first time that endogenous NO plays an important role in defining the stemness properties of colon
CSCs through cross-regulation of several cellular signaling pathways. This discovery could shed light on the mechanisms by which NO induces the growth and
invasiveness of CC gathering new insights on the link between inflammation and
colon tumorigenesis.
Disclosure of Interest: None declared
P1527 PROGRESSION OF AZOXYMETHANE-INDUCED
CARCINOGENESIS IS AFFECTED BY CD80 SIGNALING
MODULATION

COLON

M. Scarpa1, M. Scarpa1,*, I. Castagliuolo2, S. Morgan3, A. Kotsafti1,


A. Porzionato2, P. Brun2, I. Angriman2, C. Castoro1
1
Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS),
2
University of Padova, Padova, Italy, 3Sheffield Teaching Hospitals, Sheffield,
United Kingdom
Contact E-mail Address: marcoscarpa73@yahoo.it
INTRODUCTION: In patients with ulcerative colitis, the inconsistency between
cumulative risk of colon cancer and cumulative rate of dysplasia suggested the
presence of an immune surveillance mechanism. In non inflammatory colorectal
cancer, T cell populations were demonstrated to play a significant role in the
patients prognosis although it is not clear the trigger of this immune response and
its efficiency. Costimulatory interactions are decisive in sensitization of T cells by
antigen presenting cells and important for the elicitation of the immune
responses. In previous studies, we observed a significant overexpression of
CD80 costimulatory molecule in the colonic mucosa of patients with UC with
dysplasia and its down-regulation at more advanced stages of carcinogenesis
[1,2].
AIMS & METHODS: The aim of this study was to explore the effect of CD80
signaling modulation in a murine model of sporadic carcinogenesis of the colon.
Male C57/Bl6 mice (12 weeks old) were injected i.p. with AOM (10 mg/Kg) once
a week for 6 weeks. Neutralizing antibodies against CD80 or its inhibitory
receptor CTLA4 were administered in order to inhibit or enhance CD80 signaling, respectively. Mice were randomized into three groups and treated i.p. with
specific abs or isotype control twice, 3 and 4 months after the first AOM injection. Mice were euthanized 6 months after the first AOM injection. Colons were
removed, flushed with PBS, fixed as Swiss rolls in formalin and paraffin
embedded for histology. Hematoxylin and eosin colonic sections were examined

for high grade dysplasia (HGD), low grade dysplasia (LGD), adenoma and
inflammation. Non parametric statistics was used.
RESULTS: Invasive carcinoma was absent in all the three groups while adenoma
was more frequent in mice injected with anti-CD80 compared to control and
anti-CTLA4 treated mice (p 0.10). HGD frequency was significantly augmented in mice treated with anti-CD80 antibody compared to the other two groups
(p 0.02). Moreover, HGD extension resulted increased in mice administered
with anti-CD80 antibody and minimal in anti-CTLA4 treated mice (p 0.034).
LGD foci number and extension were significantly reduced in mice injected with
anti-CTLA4 (p 0.005). The inflammatory score resulted lower in mice treated
with anti-CD80 but it was similar in control mice and those who received antiCTLA4.
CONCLUSION: CD80 signaling inhibition caused a significant increase in HGD
frequency and extension while its enhancement triggered a complete elimination
of HGD and a dramatic reduction of LGD extension. These data suggest that
CD80 signaling may control the immune surveillance mechanism in sporadic
colon carcinogenesis.
REFERENCES
1: Scarpa M et al. Eur J Cancer 2013; 49: 254-263.
2: Scarpa M et al. Eur J Cancer 2011; 47: 611-619.
Disclosure of Interest: None declared
P1528 SUPPRESSION OF INTESTINAL TUMOR-INITIATING CELLS
BY INHIBITION OF DNA METHYLATION
Y. Saito1,*, K. Sakai1, K. Toshimitsu1, T. Muramatsu1, M. Kimura1, T. Sato2,
H. Suzuki2, T. Kanai2, H. Saito1
1
Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy,
2
Division of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
Contact E-mail Address: yoshimasa.saito@gmail.com
INTRODUCTION: Cancer stem cells with self-renewal and multipotent capacity
play critical roles in refractory cancers with high metastatic and invasive potential. Although DNA methylation inhibitors such as 5-aza-2-deoxycytidine (5Aza-CdR) are emerged as promising drugs in the treatment of malignant disorders, little is known about the effect of DNA methylation inhibition on cancer
stem cells. Recently, the new 3-D culture system for stem cells called organoid
culture has been developed (Sato T. et al. Nature; 459: 262-5, 2009).
AIMS & METHODS: To investigate the effect of DNA methylation inhibition
on colon cancer stem cells, treatment with 5-Aza-CdR and knockdown of Dnmt1
were performed in organoids derived from intestinal tumors of ApcMin/ (Min)
mice, which is an animal model of colon cancer. Min mice were treated with 5Aza-CdR (1 g/body weight, n 12) or PBS (n 11) by subcutaneous injection
weekly from 6 weeks of age. At 21 weeks of age, mice were dissected and number
of intestinal polyps was counted. Stem cells were isolated from intestinal tumors
of Min mice and maintained by organoid culture. Treatment with 5-Aza-CdR
and lentivirus-mediated knockdown of Dnmt1 were performed in organoids
derived from intestinal tumors. Expression profiles of genes including
microRNAs after treatment with 5-Aza-CdR and Dnmt1-knockdown were
analyzed.
RESULTS: Treatment of Min mice with 5-Aza-CdR significantly reduced the
average number of intestinal adenomas from 66 to 44 (male) and from 65 to 47
(female). The average number of large adenomas ( 3 mm) in Min mice treated
with 5-Aza-CdR was significantly decreased from 24 to11, whereas there was no
significant difference in the average number of small adenomas (5 3 mm). We
successfully established organoids containing stem cells from intestinal adenomas
of Min mice by 3-D culture with serum-free medium including epidermal growth
factor (EGF) and Noggin. Treatment with 5-Aza-CdR and Dnmt1-knockdown
significantly reduced the cell proliferation activity of tumor organoids.
Microarray analyses of tumor organoids after treatment with 5-Aza-CdR and
knockdown of Dnmt1 revealed that interferon-related genes including interferon
regulatory factor 7 (IRF7) were activated by inhibition of DNA methylation.
CONCLUSION: These findings indicate that inhibition of DNA methylation
prominently suppresses the growth of intestinal tumor-initiating cells through
activation of interferon-related genes. Treatment of colon cancers with DNA
methylation inhibitors such as 5-Aza-CdR may be a novel therapeutic strategy
targeting cancer stem cells.
REFERENCES
Sato T, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a
mesenchymal niche. Nature 2009; 459: 262-265.
Disclosure of Interest: None declared
P1529 CHARACTERISTIC AND VERIFIED MICRORNA EXPRESSION
PATTERNS IN COLORECTAL ADENOMA-CARCINOMA
SEQUENCE
Z.B. Nagy1,*, B. Wichmann2, A. Kalmar1, B. Bartak1, N.L.1, B. Peterfia2,
I. Furi1, Z. Tulassay2, B. Molnar2
1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular
Medicine Research Group, Hungarian Academy of Science, Budapest, Hungary
Contact E-mail Address: nagyzsofiab@gmail.com
INTRODUCTION: miRNA expression alterations can be observed in colorectal
cancer (CRC), however dysregulation of miRNA might be present in various
stages of precancerous lesions, such as adenoma. High-throughput screening
platforms became available recently: whole genome miRNA expression microarrays and RT-qPCR panels with hundreds of miRNA specific oligos.
AIMS & METHODS: Our primary aim was to identify the microRNA expression alterations between normal colonic tissue (N), tubular adenoma
(AD5SUB4T5/SUB4), tubulovillous adenoma (AD5SUB4TV5/SUB4)
and colorectal cancer (CRC) samples. Another purpose was to determine the

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United European Gastroenterology Journal 2(1S)


level of miRNA by different methods and in several types of samples such as
fresh frozen, FFPET.
Sixty fresh frozen biopsy samples (n 20 N, n 11 AD5SUB4T5/SUB4,
n 9 AD5SUB4TV5/SUB4, n 20 CRC) were collected; and, total RNA
were isolated. A miRNA microarray experiment was performed. Then, a series of
pools of RNA from the same groups of samples was made to validate the data of
microarray by RT-qPCR. Then, RT-qPCR data of FFPET tissues (N n 3,
AD5SUB4TV5/SUB4 n 3, CRC n 3) were compared to the microarray
and PCR results from fresh-frozen samples. miRNA-mRNA interactions were
predicted based on four algorithm and validated by biopsy mRNA microarray
data. miRNA-126 was selected to be visualized by in situ hybridization.
RESULTS: Out of the 1733, the detectable number of miRNAs, which could be
detected in each group was only a small percentage (N n 442, AD n 460,
CRC n 441). 12 miRNA were upregulated (miR-31 logFC 3, p50.001) and
11 miRNA were downregulated only (e.g. miR-10b, logFC -1.7 p50,001) in
neoplastic lesions (ADCRC) compared to N samples. 11 miRNA showed
altered expression between AD5SUB4T5/SUB4 and AD5SUB4TV 5/
SUB4 (e.g. miR-183 LogFC 1.5 p50.007). Expression levels of 9 miRNA
were found to be changed between AD5SUB4T,TV5/SUB4 and CRC
groups based on microarray data (e.g. miR-196a logFC -1.8 p50.001).
MiRNA expression data could be confirmed by RT-PCR in both FFPE and
fresh frozen samples. miRNA-126 array expression results could be confirmed
by in situ hybridization. MAP3K1 were identified as the targets of miR-196a in
the MAPK signaling pathway.
CONCLUSION: A small number (n 23) miRNA showed characteristic alteration during neoplastic development, but their impact is remarkable and systematic as a key control element of the upstream mRNA pathways. The identified
miRNA expression changes are reproducible through adenoma-dysplasia-carcinoma sequence and in the FFPE tissues as well.
Disclosure of Interest: None declared
P1530 TEXTURE ANALYSIS AS IMAGING BIOMARKER OF TUMORAL
RESPONSE TO NEOADJUVANT CHEMORADIOTHERAPY IN
RECTAL CANCER PATIENTS STUDIED WITH 3T MR
M. Rengo1,*, C.N. De Cecco1, M. Ciolina1, D. Bellini1, D. Caruso1, D. Caruso1,
A. Laghi1
1
Department of Radiological Sciences, Oncology and Pathology, SAPIENZA
University of Rome, rome, Italy
Contact E-mail Address: marco.rengo@uniroma1.it
INTRODUCTION: To determine whether texture features of rectal cancer on
T2-weighted MR images can predict tumoral response in patients treated with
neoadjuvant chemoradiotherapy (CRT)
AIMS & METHODS: We prospectively enrolled 15 consecutive patients (6
females, 63.213.4 years) with rectal cancer, who underwent pre- and post-treatment 3T MRI. Treatment protocol consisted of neoadjuvant chemoradiotherapy
(CRT) with oxaliplatin and 5-Fluorouracile. Texture analysis using a filtrationhistogram technique was performed using a commercial research software algorithm (TexRAD Ltd, Somerset, England, UK) on unenhanced axial T2-weigthed
images by manually delineating a region-of-interest (ROI) around the tumor
outline for the largest cross-sectional area. The technique selectively filters and
extracts textures at different anatomic scales followed by quantification of the
histogram using kurtosis, entropy, skewness and mean value of positive pixels
(MPP). After chemoradiotherapy, all patients underwent complete surgical resection and the surgical specimen served as the gold standard.
RESULTS: Six patients showed pathological complete response (pCR) and 4
patients, partial response (PR). Five patients were classified as non-responders
(NR). Baseline medium texture-scale quantified as kurtosis was significantly
lower in the pCR sub-group in comparison with PRNR (p .01). Post-treatment kurtosis without filtration was significantly higher in pCR in comparison
with PRNR (p .045). The change in kurtosis between post-treatment and pretreatment images was significantly lower in the PRNR sub-group compared to
pCR (p .038). At baseline, the area under the ROC curves (AUC), to discriminate between pCR and PRNR, was significantly higher for kurtosis (0.907,
p50.001) compared to all others parameters. The optimal cut-off value for baseline kurtosis was 0.19. Using this value, the sensitivity and specificity for pCR
prediction were 100% and 77.8%.
CONCLUSION: Texture parameters derived from T2w images of rectal cancer
have the potential to act as imaging biomarkers of tumoral response to neoadjuvant chemoradiotherapy.
REFERENCES
Group MS. Diagnostic accuracy of preoperative magnetic resonance imaging in
predicting curative resection of rectal cancer: prospective observational study.
BMJ 2006; 333: 779.
Bipat S, Glas AS, Slors FJ, et al. Rectal cancer: local staging and assessment of
lymph node involvement with endoluminal US, CT, and MR imaginga metaanalysis. Radiology 2004; 232: 773-783.
Patel UB, Taylor F, Blomqvist L, et al. Magnetic resonance imaging-detected
tumor response for locally advanced rectal cancer predicts survival outcomes:
MERCURY experience. J Clin Oncol 2011; 29: 3753-3760.
Sebag-Montefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy
versus selective postoperative chemoradiotherapy in patients with rectal cancer
(MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet
2009; 373: 811-820.
Peeters KC, Marijnen CA, Nagtegaal ID, et al. The TME trial after a median
follow-up of 6 years: increased local control but no survival benefit in irradiated
patients with resectable rectal carcinoma. Ann Surg 2007; 246: 693-701.
Disclosure of Interest: None declared

P1531 THE IMMUNOCHROMATOGRAPHIC FECAL TUMOR M2


PYRUVATE KINASE TEST DETECTS COLORECTAL CANCER
WITH HIGHER SENSITIVITY THAN FECAL OCCULT BLOOD TEST
M. Jeong1,*, J.K. Kim2, D.Y. Cheung1, J. I. Kim1, Y.C. Kim1, J.H. Kim1
Internal Medicine, the Catholic University of Korea College of Medicine, Seoul,
2
Internal Medicine, the Catholic University of Korea College of Medicine, Seou,
Korea, Republic Of
Contact E-mail Address: ditto9981@naver.com
1

INTRODUCTION: The M2 pyruvate kinase (M2-PK) is known a specific


enzyme produced in undifferentiated and proliferating tissues. This study aims
to evaluate the usefulness of the immunochromatographic M2 pyruvate kinase
(iM2-PK) for screening of colorectal cancer (CRC) and premalignant lesions.
AIMS & METHODS: Healthy volunteers and patients with colorectal neoplasms were enrolled in six academic hospitals in capital province of Korea.
The value of iM2-PK was compared with immunochromatographic fecal
occult blood test (iFOBT) and fecal tumor M2-PK enzme-linked immunosorbent
assay (ELISA).
RESULTS: A total of 323 subjects were enrolled. The sensitivity of iM2-PK for
CRC was 92.8%, and was superior to that of iFOBT, 47.5% (p50.0001). For
adenomatous lesions, the sensitivity of iM2-PK was 69.4% and was also superior
to 12.1% of iFOBT (p50.001). In comparison with M2-PK ELISA, iM2-PK
proved significantly better sensitivity for CRC, 97.5% and 80.0% (p 0.0289).
The sensitivity of iM2-PK was higher in advanced stage of CRC compared to
cancers confined to mucosa and submucosa (p50.05), however, lymph node
metastasis had no influence on the sensitivity of iM2-PK.
CONCLUSION: The iM2-PK proved higher sensitivity for CRC and adenomatous lesions than iFOBT. With rapidity and convenience, CRC screening using
iM2-PK is promising.
REFERENCES
1 Jung KW, Won YJ, Kong HJ, et al. Cancer statistics in Korea: incidence,
mortality, survival and prevalence in 2010. Cancer Res Treat 2013; 45: 1-14.
2 Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin
2011; 61: 69-90.
3 Zhu MM, Xu XT, Nie F, et al. Comparison of immunochemical and guaiacbased fecal occult blood test in screening and surveillance for advanced colorectal
neoplasms: a meta-analysis. J Dig Dis 2010; 11: 148-160.
4 Christofk HR, Vander Heiden MG, Wu N, et al. Pyruvate kinase M2 is a
phosphotyrosine-binding protein. Nature 2008; 452: 181-186.
5 Christofk HR, Vander Heiden MG, Harris MH, et al. The M2 splice isoform of
pyruvate kinase is important for cancer metabolism and tumour growth. Nature
2008; 452: 230-233.
Disclosure of Interest: None declared
P1532 EFFECT
OF
ANTIPLATELET
AND
ANTICOAGULANT
TREATMENTS ON THE DIAGNOSTIC ACCURACY OF FECAL
IMMUNOCHEMICAL TEST IN COLORECTAL CANCER
DETECTION IN SYMPTOMATIC PATIENTS
J. Cubiella1,1, P. VEGA1,*, M.T. ALVES1, M. SALVE1, DIAZ-ONDINA M.2,
P. MACIA2, I. BLANCO2, L. BUJANDA3, E. SANCHEZ1, J. FERNANDEZSEARA1
1
GASTROENTEROLOGY, 2CLINICAL ANALYSIS, COMPLEXO
HOSPITALARIO UNIVERSITARIO DE OURENSE, OURENSE,
3
GASTROENTEROLOGY, Hospital de Donostia, San Sebastian, Spain
Contact E-mail Address: joaquin.cubiella.fernandez@sergas.es
INTRODUCTION: There are discrepancies regarding the effect of antiplatelet
and/or anticoagulant therapies in the diagnostic accuracy of fecal immunochemical test (FIT) for colorectal cancer (CRC) detection.
AIMS & METHODS: The aim of this analysis is to assess the influence of
anticoagulant and/or antiplatelet treatments in FIT diagnostic accuracy for
CRC detection in symptomatic patients. COLONPREDICT study is a prospective blind study of diagnostic tests that has evaluated FIT diagnostic accuracy for
CRC detection in symptomatic individuals undergoing a colonoscopy. In the
1567 patients included chronic treatment with acetylsalicylic acid (ASA), clopidogrel and/or acenocumarol was collected. The overall diagnostic accuracy was
compared with ROC curves, area under the curve (AUC) and homogeneity test
areas and the sensitivity and specificity (at a 100 ng/ml cutoff) was compared
using the chi-square test.
RESULTS: 426 (27%) patients were receiving antiplatelet and/or anticoagulant
treatments. 215 CCR were detected no difference in prevalence between the two
groups (treatment 12%, control 14.3%; p 0.2). FIT diagnostic accuracy for
CRC was statistically lower in the treatment group (treatment AUC 0.81, control AUC 0.88; p 0.04). With a 100ng/ml cutoff, 175 (41.1%) patients in the
treatment group and 434 (38%) in the control group had a positive result
(p 0.2). At this cutoff, treatment with antiplatelet and/or anticoagulant treatments produced a non significant reduction of FIT sensitivity (90.2%, 91.5%,
p 0.7) and specificity (65.6%, 71%; p 0.05) for CRC detection. Comparisons
of the diagnostic accuracy according to the treatment received are shown in the
accompanying table.

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United European Gastroenterology Journal 2(1S)

Table to abstract P1532


Treatment

AUC p

ASA

0.78
0.87
0.79
0.86
0.80
0.86

Yes (16.2%)
No (83.8%)
Clopidogrel
Yes (3.8%)
No (96.2%)
Acenocumarol Yes (7.9%)
No (92.1%)

Sensitivity P

0.04 84.6%
92.1%
0.2 90%
91.2%
0.3 94.1%
91%

Specificity p

0.2 64%
70.6%
0.9 70%
69.4%
0.6 62.6%
70%

0.05

the BCL2L1 protein was significantly up-regulated in LST-adenoma compared


to Ip-adenoma (p 0.0089).
CONCLUSION: Our findings suggest that LSTs have an unusual profile of gene
expression compared to other tumors. BCL2L1 might be an important gene for
the organization of LST.
Disclosure of Interest: None declared

0.9
0.1

CONCLUSION: Treatment with acetylsalicylic acid reduces FIT diagnostic


accuracy for CRC detection in symptomatic patients.
Disclosure of Interest: None declared
P1533 THE GROWTH PATHWAY AND THE PATHOLOGICAL
FEATURES OF DEPRESSED-TYPE COLORECTAL CARCINOMAS
S.-E. Kudo1,*, Y. Kouyama1, H. Miyachi1, K. Ichimasa1, S. Matsudaira1,
H. Oikawa1, Y. Mori1, M. Misawa1, T. Kudo1, T. Hisayuki1, K. Kodama1,
T. Hayashi1, K. Wakamura1, A. Katagiri1, M. Kaga1, E. Hidaka1, F. Ishida1,
S. Hamatani1
1
Showa University Northern Yokohama Hospital, Tsuzuki-ku, Yokohama-shi,
Japan
Contact E-mail Address: kudo-hisho@med.showa-u.ac.jp
INTRODUCTION: Advanced colorectal cancers were conventionally considered
to develop from sessile-type polyps. And it has been maintained as the mainstream of development of cancers in colorectum.
But recently advances in endoscopic diagnosis and colonoscopy technology have
revealed the existence of many depressed-type cancers, which have a growth
pathway different from adenoma-carcinoma sequence.
AIMS & METHODS: The aim is to clarify the pathological features of
depressed-type colorectal carcinomas compared with flat- and sessile-type. A
total of 20160 colorectal neoplasms excluding advanced carcinomas were resected
endoscopically or surgically in our Center from April 2001 to September 2013. Of
these, 847 lesions were T1 carcinomas. According to the morphological/development classification, 194 lesions (22.9%) were depressed-type, 281 lesions (33.2%)
were flat-type and 372 lesions (43.9%) were sessile-type. We analyzed the pathological features of these lesions.
RESULTS: The rate of submucosal invasion in all the lesions was 45.9% in
depressed-type, 2.7% in flat-type and 2.8% in sessile-type. Within under 5mm
in diameter, that was 8.8%, 0.02% and 0.02% respectively. In T1 carcinomas, the
rate of vessel permeation was 65.0% in depressed-type, 32.4% in flat-type and
37.6% in sessile-type, that of tumor budding was 37.6%, 15.7% and 17.7%, and
that of poorly differentiated adenocarcinoma was 9.8%, 3.9% and 4.6% respectively. The rates of these pathological factors were significantly higher in the
depressed-type lesions. On the other hand, the rate of adenomatous component
was 6.2%, 51.2% and 55.4%, respectively. This was significantly lower in
depressed-type lesions, suggesting that they emerge directly from the normal
epithelium without going through the adenoma stage.
CONCLUSION: Depressed-type early colorectal carcinomas tend to invade submucosal layer and grow downward even when they are small in size and show the
worth pathological characteristics than the other types. Therefore, more careful
endoscopic diagnosis - whether the lesion is depressed type or not - would be
needed.
Disclosure of Interest: None declared
P1534 GENE EXPRESSION PROFILING OF LATERAL SPREADING
COLORECTAL TUMORS
S. Minemura1,*, T. Tanaka1, M. Arai1, K. Okimoto1, D. Maruoka1,
T. Matsumura1, T. Katsuno1, O. Yokosuka1
1
Department of Gastroenterology and Nephrology, Graduate School of Medicine,
Chiba University, chiba, Japan
Contact E-mail Address: koshoramunemi@yahoo.co.jp
INTRODUCTION: Laterally spreading tumors (LSTs) are generally defined as
lesions 410 mm in diameter, characterized by lateral expansion along the luminal wall with a low vertical axis. In contrast to other forms of tumor, LSTs are
generally considered to have a superficial growth pattern and the potential for
malignancy.
AIMS & METHODS: We focused on this morphological character of LSTs, and
analyzed the gene expression profile of LSTs. The expression of 168 genes in 41
colorectal tumor samples (17 LST-adenoma, 12 LST-carcinoma, 12 Ip (pedunculated type of the Paris classification)-adenoma, all of which were 10 mm or
more in diameter) was analyzed by PCR array. Based on the results, we investigated the expression levels of genes up-regulated in LST-adenoma, compared to
Ip-adenoma, by hierarchical and K-means clustering. Next, using an additional
61 samples (39 LST-adenoma, 22 Ip-adenoma), we confirmed the results of the
array analysis and determined the localization of the gene product by immunohistochemical staining.
RESULTS: The expression of 129 genes differed in colorectal tumors from
normal mucosa by PCR array analysis. As a result of K-means clustering, the
expression levels of 5 genes, AKT1, BCL2L1, ERBB2, MTA2 and TNFRSF25,
were found to be significantly up-regulated (p50.01) in LST-adenoma, compared to Ip-adenoma. Analysis by immunohistochemical analysis showed that

P1535 EVALUATION OF FECAL TUMOR M2-PYRUVATE KINASE (M2PK) AS A SCREENING TOOL FOR ORGANIC BOWEL DISEASES
PRELIMINARY RESULTS
S. Siminkovitch1,* on behalf of Tankova L., Gerova V., Vladimirov B., Penchev
P., Nakov V., Valerieva Y.
1
Gastroenterology, University Hospital Tzarica Ioanna, Sofia, Bulgaria
Contact E-mail Address: sylvie.mitova@abv.bg
INTRODUCTION: Evaluation of the potential role of fecal M2 pyruvate kinase
(L2-PJ) test as a screening tool for colorectal cancer (CRC), inflammatory bowel
disease (IBD) and colonic polyps and to compare the rapid chromatographic
qualitative and ELISA quantitative test for M2-PK determination.
AIMS & METHODS: Fecal samples of 40 patients (19 male, 21 female) at mean
age 5617 were collected in our centre for the period March November 2013.
Ten patients had CRC, 11 patients IBD (3 had Crohns disease, 7 ulcerative
colitis), 8 had colon adenomas (4pts 41 cm), 11 had normal colonoscopy findings. We also subdivided patients according to disease burden subgroup A
comprised of CRC, IBD and adenomas 4 1cm and subgroup B - of small
polyps and controls. Rapid M2-PK immunochromatographic test, M2-PK
ELISA test and immunological fecal occult blood test (FOBT) were performed
in all samples.
RESULTS: In the CRC group Rapid M2-PK test results were positive in 100%,
in IBD group 72.7%, in adenomas group 50% positive (all 41cm), controls 18.2%. The M2-PK ELISA test results were positive in 100%, 63.6%, 37.5% and
18.2% respectively. The FOBT resulted positive in 90% of CRC, 72.7% of IBD,
12.5% in polyps group and 0% of controls. In the subgroup analysis the Rapid
test was positive in 88% of patients in subgroup A, and negative in 86.7% of
subgroup B (p50.001), while the FOBT was positive in 72% of subgroup A and
negative in 100% of subgroup B. When comparing the immunochromatographic
qualitative test with M2-PK ELISA test we found statistically significant correlation 91.7% of patients with positive Rapid test had positive ELISA test
(p50.001). The estimated sensitivity and specificity of Rapid M2-PK for patients
in subgroup A is 91% with a positive predictive value of 92%. The sensitivity and
specificity of M2-PK ELISA in the same subgroup is 90% and 81% respectively
with a positive predictive value of 90%.
CONCLUSION: Fecal rapid M2-PK test is an easily performed and reliable tool
for screening of bowel pathology. The Rapid test correlates with the quantitative
ELISA for the determination of M2-PK
REFERENCES
1. Alexander F, Palazzo1 and Kohila M. Alternative splicing rewires cellular
metabolism to turn on the Warburg effect. Biomedical 2012; 23: 25-30.
2. Chung-Faye G, Hayee B, Maestranzi S, et al. Fecal M2-pyruvate kinase (M2PK): a novel marker of intestinal inflammation. Inflamm Bowel Dis.
3. Cellular control mechanisms that regulate pyruvate kinase M2 activity.
4. Hardt PD. Tumor M2-pyruvate.
Disclosure of Interest: S. Siminkovitch Other: M2-PK immunohrmatographikc
tests were contributed from Naturpharma, _Biotech AG, Giessen, Germany
representative in Bulgaria.
P1536 RELATIONSHIP BETWEEN THE EXPRESSION OF ONCORELATED MIRNAS AND ENDOSCOPIC APPEARANCE IN
COLORECTAL TUMORS
Y. Nakagawa1,*, Y. Akao2, A. Kamatani1, N. Ohmiya1, T. Shibata1, T. Tahara1,
I. Hirata1
1
Gastroenterology, Fujita health University School of Medicine, Toyoake, 2Drug
Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
Contact E-mail Address: yo-hi@fujita-hu.ac.jp
INTRODUCTION: Accumulating data indicate that some microRNAs
(miRNAs or miRs) function as tumor suppressors or oncogenes in cancer development. The certain miRNAs (miR-143, -145, -34a, -7) were differently expressed
in the samples between the tumor and the paired non-tumorous samples in the
same patient in colorectal tumors, which was reported by us and others. On the
other hand, recent studies indicated that exophytic tumors and flat elevated
tumors were different for the expression profile of genome. In the current
study, we demonstrated the difference in the miRNA expression profile between
exophytic tumors and flat elevated tumors in colorectal tumors.
AIMS & METHODS: We examined the expression of these miRNAs in 131
sporadic exophytic adenomas or early cancers, and 52 sporadic flat elevated
adenomas or early cancers to clarify the relationship between the expression of
the miRNAs and the endoscopic morphological appearance in the colorectal
tumors.
RESULTS: The expression levels of miRs-143, -145, and 34a were significantly
reduced in exophytic tumors compared with those in flat elevated tumors. The
expression levels of miR-7 and were significantly up-regulated in flat elevated
adenomas compared with those in exophytic adenomas.
CONCLUSION: These findings indicated that the expression of onco-related
miRNA associated with the morphological appearance of colorectal tumors.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1537 IMMUNOHISTOCHEMICAL ANALYSIS USING D2-40 AND EVG
ENHANCE THE DETECTABILITY OF LYMPHOVASCULAR
INVASION IN RECTAL NETS LESS THAN 10MM IN DIAMETER
Y. Kitagawa1,*, T. Suzuki2, T. Hara2, D. Ikebe3, M. Itami3, T. Yamaguchi1
1
Gastroenterology, 2Endoscopy Division, 3Pathology Division, Chiba Cancer
Center, Chiba, Japan
INTRODUCTION: Rectal neuroendocrine tumors less than 10mm in diameter
(RNETs510mm), confined to submucosal layer (SM), are usually treated by
endoscopic resection (ER), and ER is reported to successfully achieve clear resection margin [1]. Previous studies have demonstrated that RNETs510mm had
relatively low incidence of lymphovascular invasion [2]. Nonetheless, we often
detect lymphovascular invasion by immunohistochemical analysis using D2-40
and EVG in addition to HE stain.
AIMS & METHODS: This study aimed to demonstrate enhancement of detection rate of lymphovascular invasion in RNETs510mm using D2-40 and EVG
stain. We retrospectively reviewed consecutive RNETs510mm patients treated
by EMR or ESD between November 2005 and March 2014 at Chiba Cancer
Center Hospital. Specific data extracted from the medical records included
patient sex, age, tumor site, tumor size, depression in the lesion, margin status,
depth of SM invasion, mitotic rate, and lymphovascular invasion. According to
World Health Organization 2010 classification, tumors were divided into the two
groups: G1 (52/10 high-power fields [HPF]) or G2 (2=10HPF). In addition to
conventional HE stain, lymphatic invasion was identified by D2-40 and venous
invasion by EVG stain.
RESULTS: Thirty three patients were recruited in the study (18 male, 15 female;
median age 59 years). Characters of the tumor were as below: 3 located in upper
rectum, 30 in lower; median size 5 mm (range 1-10); no surface depression in all.
On histopathological examination, resection margin was free in 23 patients,
indeterminate in 7 and positive in 3. The median depth of SM invasion was
1500m (range 800-7000) and all tumors were classified as G1. Regarding lymphatic and venous invasion, they were 0% (0/33) and 3.0% (1/33) by HE stain,
respectively. While by D2-40 and EVG stain, lymphatic and venous invasion
were detected in 6.1% (2/33) and 36.4% (12/33), respectively. Finally, the rate
of lymphovascular invasion detected by D2-40 and EVG stain was increased to
36.4% (12/33) as compared to 3.0% (1/33) by HE stain. Assessing the rate of
lymphovascular invasion according to tumor size, lymphatic and venous invasion
were 7.1% (1/14) and 42.9% (6/14) in the size of 45mm, and 5.3% (1/19) and
31.6% (6/19) in the size of 55mm, respectively, showing no significant difference.
Similarly assessing the rate according to SM invasion, lymphatic and venous
invasion were 11.1% (2/18) and 33.3% (6/18) in the depth of SM invasion
41500m, and 0% (0/15) and 40% (6/15) in 51500m, respectively, showing
no difference.
CONCLUSION: Compared to HE stain, D2-40 and EVG stain is proved to
significantly increase detection rate of lymphovascular invasion in
RNETs510mm. Therefore, application of D2-40 and EVG stain is considered
to be indispensable to RNETs510mm after ER.
REFERENCES
[1]Park HW, Byeon JS, Park YS, et al. Endoscopic submucosal dissection for
treatment of rectal carcinoid tumors. Gastrointest Endosc 2010; 72: 143149.
[2]Fahy BN, Tang LH, Klimstra D, et al. Carcinoidoftherectumriskstratification (CaRRs): a strategy for preoperative outcome assessment. Ann Surg
Oncol 2007; 14: 1735-1743.
Disclosure of Interest: None declared
P1538 INDIVIDUALIZED
CHEMOTHERAPY
FOR
ADVANCED
COLORECTAL CANCER (CRC) BASED ON COLLAGEN GEL
DROPLET-EMBEDDED DRUG SENSITIVITY TEST (CD-DST) IN
CLINICAL SETTING
T. Ochiai1,*, K. Nishimura1, T. Watanabe1, A. Nakatani1, K. Yoshino1, T. Sato1,
K. Kishine1, H. Murakami1, M. Myoujin1, I. Nagaoka2
1
Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical
Treatment Corporation, 2Host Defense and Biochemical Research, Juntendo
University School of Medicine, Tokyo, Japan
Contact E-mail Address: takumi-o@ma.kitanet.ne.jp
INTRODUCTION: The leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI)
regimens with or without molecularly-targeted drugs are widely used as first-line
chemotherapy in the treatment of advanced colorectal cancer (CRC). Whether
FOLFOX or FOLFIRI is administered first is not significant, however, it is
essential that full administration of the targeted dosages of all 3 drugs, 5-FU,
l-OHP, and SN-38 is achieved. However, this is not always possible and secondline chemotherapy must be abandoned in certain cases due to disease progression, adverse effects or high medical cost in clinical setting. Where possible, the
most effective regimen should be selected as the first line of treatment.
AIMS & METHODS: The aim of this study was to determine whether first-line
chemotherapy mat be individualized using the collagen gel droplet-embedded
drug sensitivity test (CD-DST).
Specimens of primary tumors were obtained between March 2008 and November
2013 from 87 CRC patients who had received no preoperative chemotherapy.
Informed consent to measure drug sensitivity was obtained from all patients. The
CD-DST allows evaluation of drug sensitivity using isolated, 3-dimensionally
cultured tumor cells in a small collagen gel droplet. The CD-DST was performed
and the growth inhibition rate (IR) obtained under incubation conditions (5-FU
with l-OHP at 6.0 and 3.0 g/ml, or 5-FU with SN-38 at 6.0 and 0.2 g/ml,
respectively, for 24 h). The cumulative distributions of the IR under each condition were evaluated based on evidence that the clinical response rates to
FOLFOX and FOLFIRI were almost the same; approximately 50%,

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respectively. The histogram of individual discrepancy of antitumor effects
between FOLFOX and FOLFIRI was also evaluated. Histogram was analyzed
with DAgostino-Pearson omunibus normality test.
RESULTS: Individualization of first line treatment was possible in all patients.
FOLFOX and FOLFIRI were recommended as first line chemotherapy in 37 and
44 patients, respectively, and equal efficacy in 6 cases. The histogram of the
individual discrepancy showed normal distribution (p 0.00679). The standard
deviation (SD) was 15.82.
CONCLUSION: This method has the potential to facilitate the establishment of
individualized first line chemotherapy for CRC patients. Improvement in the
further prognosis is expected by selection of more effective regimen for advanced
CRC patients whose discrepancy of anti-tumor effects between two regimens is
greater than one SD in clinical setting.
REFERENCES
Ochiai T, et al. Individualized chemotherapy for colorectal cancer based on
collagen gel droplet-embedded drug sensitivity test. Oncol Lett 2012; 4: 621-624.
Disclosure of Interest: None declared
P1539 PREDICTIVE VALUE OF VEGFR AND EGFR PATHWAYS FOR
ADJUVANT TREATMENT WITH FLUOROURACIL, LEUCOVORIN
/- IRINOTECAN IN PATIENTS WITH LOCAL ADVANCED
COLORECTAL CANCER: TRANSLATIONAL RESULTS OF THE
FOGT-4 STUDY
T. Thomaidis1,*, A. Maderer1, A. Formentini2, S. Bauer1, M. Schwarz1,
W. Neumann1, M. Trautmann1, K.-H. Link3, A. Schad4, P. Galle1,
M. Kornmann2, M. Moehler1
1
I. Medical Clinic, Johannes-Gutenberg University, Mainz, 2Department of
Surgery, University Clinic, Ulm, 3Center of Surgery, Asklepios Clinic, Wiesbaden,
4
Institute of Pathology, Johannes Gutenberg University, Mainz, Germany
INTRODUCTION: The introduction of molecular biomarkers as predictive factors for palliative chemotherapy improved the clinical outcome and led to efficient treatment personalization in metastatic colorectal cancer (CRC). However,
such a predictive value has not yet been established in patients with locally
advanced CRC receiving adjuvant chemotherapy. Since EGFR- and VEGFRsignalling cascades are fundamental for the development of cancer, we assessed
correlations of VEGF-C, VEGF-D, VEGFR-3, Hif-1 alpha, PTEN, amphiregulin (AREG) and epiregulin (EREG) expression levels with the clinical outcome in
a randomized phase III study of patients with stage II/III CRC receiving adjuvant treatment.
AIMS & METHODS: The patients data examined in this study were from the
collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial.
Tumor tissues from 269 patients were stained via immunohistochemistry for
VEGF-C, VEGF-D, VEGFR-3, Hif-1 alpha, PTEN, AREG and EREG expression. The results were evaluated by two independent, blinded investigators.
Survival analyses were calculated for all patients receiving 5-FU/FA vs. 5-FU/
FA/irinotecan in relation to expression of all makers above.
RESULTS: Patients with negative AREG and EREG expression had a significant longer disease free survival (DFS) in comparison to AREG/EREG positive
ones (p5 0.05). The benefit on DFS in AREG-/EREG- patients compared to
AREG/EREG patients was even stronger under 5-FU/FA/irinotecan
(p 0.002). Patients expressing PTEN on their tumor tissues lived longer receiving adjuvant treatment including irinotecan than PTEN- ones (p5 0.05). No
correlation between clinical outcome and markers related with the VEGFRpathway was found. Patients with negative VEGF-D expression had a trend
for a loobger DFS when treated with 5-FU/FA (p 0.106). Patients with lack
of Hif-1 alpha expression remained longer disease free than Hif-1 alpha
(p 0.007) and profited more treated with the triple adjuvant regime
(p 0.026). Finally, patients who were AREG-/EREG-/PTEN showed a
trend for better overall survival (OS) under 5-FU/FA/irinotecan than without
irinotecan (p 0.071).
CONCLUSION: Patients with AREG/EREG negative, PTEN positive and Hif1 alpha negative CRC tumors might profit in terms of DFS from a treatment
containing fluoropyrimidines and irinotecan. Our results suggest a predictive
value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA
/- irinotecan in stage II/III colorectal cancer.
Disclosure of Interest: None declared
P1540 A PRO-ACTIVE MODEL TO IDENTIFY PATIENTS AT HIGH
RISK FOR FAMILIAL CANCER SYNDROMES RESULTS OF A
HIGH YIELD OUTREACH PROGRAM
T. Adar1,*, L. Tribich1, S. Lieberman2, E. Levy-Lahad2, E. Goldin1
1
Digestive Diseases Institute, 2Genetic Institute, Shaare Zedek Medical Center,
Jerusalem, Israel
Contact E-mail Address: adartom@szmc.org.il
INTRODUCTION: Identifying patients with familial colorectal cancer syndromes is of great importance, for both patients and their family members.
Some centers have utilized a reflex testing system, in which every colorectal
cancer (CRC) patient is screened for Lynch syndrome (LS). However, the associated cost of such programs hampers their widespread implementation. One
possible alternative is to refer only high risk patient for genetic evaluation. We
present the results of a proactive outreach program, set to identify patients at risk
for familiar colorectal cancer.
AIMS & METHODS: Aim: To evaluate the yield of a proactive outreach program designed to identify patients at high risk for familial colorectal cancer,
using discharge letters following surgery for colorectal cancer.
Methods: Charts of patients hospitalized in our tertiary center during 2011-2013
with the diagnosis of CRC were identified. For each case, the discharge letter

A554
from the hospitalization during which they underwent surgery was identified.
Un-operated patients were excluded. Then, patients were alphabetically contacted by phone to complete follow up and personal details to ascertain their
Bethesda criteria status. We then compared the data from the discharge letters to
the follow-up, mainly the recommendation to complete genetic counseling for
either LS or polyposis syndromes.
RESULTS: The program included 96 patients (M:F ratio of 1:1), with a mean
age of 67.79. The mean age at diagnosis was 66.29y (31-93y). Mean time to follow
up was 545 days after surgery, during which 13 patients had died, one patient was
admitted to hospice and 4 were lost to follow up.
After revising the clinical and pathological data of the 96 patients, 26 (27%) have
had an indication to complete genetic counseling. Two patients had an indication
to complete evaluation for polyposis syndromes, while the other 24 qualified for
testing for LS according to the modified Bethesda criteria (16 were under the age
of 50y at diagnosis, 4 patients had synchronous or metachronous tumors of the
colon, 1 patient had a metachronous Lynch associated tumor, 1 patient was
known to have LS, 1 had a suggestive family history and in 1 patients evaluation
was recommended according to tumors biopsy). From the entire study groups, 2
patient were already after genetic counseling (1 with known LS), and only two
patients with indication were referred to genetic counseling (ages 31 and 43y at
diagnosis). This means that out of the patients with indication to complete
genetic evaluation who have not received previous counseling, approximately
90% of cases did not receive the recommendation.
CONCLUSION: The rate of identification of high risk patients for familial CRC
in surgical departments is sub-optimal, even when the indication is obvious at the
time of discharge after surgery for CRC. We present a high yield out-reach
program which can be easily implemented in any center, and offers a potential
for identifying missed cases of LS.
Furthermore, identification of high risk patients and adequate referral for genetic
counseling following surgery for CRC should be considered a quality control
measurement for surgical departments.
Disclosure of Interest: T. Adar Financial support for research from: Synageva,
Lecture fee(s) from: Shire, Consultancy for: Janssen, Other: Boston Scientific,
Immune Pharma, L. Tribich: None declared, S. Lieberman: None declared, E.
Levy-Lahad: None declared, E. Goldin Consultancy for: Immune Pharma,
Bioline Rx Ltd.
P1541 COLONIC STENTING AS BRIDGE TO SURGERY VERSUS
EMERGENCY SURGERY IN OBSTRUCTIVE COLORECTAL
CANCER
T. Stigaard1,* on behalf of Dr Kristina Safir-Hansen, dr Trine Stigaard, dr Jakob
Lykke, dr Per Jess.
1
Endoscopy unit, The gastrounit, Herlev Hospital, Denmark, Herlev, Denmark
Contact E-mail Address: Trine@stigaardlarsen.dk
INTRODUCTION: About 7-29 % of the colorectal cancers presents with acute
obstruction. Acute obstruction is an emergency situation with risk for necrosis,
perforation due to colonic distention, bacterial translocation and intracorporal
electrolytic fluid imbalance. The situation calls for decompression, traditionally
emergency surgery (ES) is performed. ES is associated with a high mortality in
15-34 % of patients and morbidity in 32-64 %, compared to 55% for elective
surgery.
AIMS & METHODS: Comparing patients with malignant obstruction treated
with self-expanding metal stent (SEMS) versus primary surgery. Endpoints: 30
days mortality, technical and clinical success. Tumor placement and cancer
related death.
Method: Retrospective register study done in the period of 1.1.2008-1.9.2013. 364
patients from the surgical department Kge-Roskilde. 99 treated with SEMS and
256 had surgery.
RESULTS: 130 patients, median age 72 years, 66 women and 64 men. ASA 1:
19.5 %, ASA 2: 79.7% and ASA 3: 0.8 %. Median follow-up 22 months (5-56).
There is a significant difference between patient groups and tumor placement.
Most patients with palliative stent and patients with bridge to surgery without
later surgery, had tumor placed in the sigmoid colon 41.5 %, and the recto
sigmoid colon 17 %. Technical and clinical success is respectively 94.6 % and
93.8 %. 6.9 % had complications after SEMS, no significant difference between
patient groups. No significant difference in 30 days complications between SEMS
versus primary surgery. Overall survival SEMS versus primary surgery shows no
significant difference. 15.4 % died before 30 days. No significant difference
between patient groups. The number of dead is larger among patients with
primary operation, patients with SEMS 9.6 % versus 31.4 % patients with primary operation. Cancer related mortality sjows no significant difference, p 0.6.
Regarding adjuvant chemotherapy and cancer related mortality no significant
difference found between the patient groups.
CONCLUSION: Colonic stenting followed by elective surgery shows no significant difference compared to primary surgery regarding 30 days mortality and
complications, but a trend towards higher mortality in the group who went
through primary surgery.
REFERENCES
www.cancer.dk krftens bekmpelse, krft i tal.
Ho K-S, Quah H-M, Lim J-F, et al. Endoscopic stenting and elctive surgery
versus emergency surgery for lef-sided malignant colonic obstruction: a prospective randomizes trial. Int J Colorectal Dis 2012; 27: 355-362.
Cennamo V, Luigiano C, Cocclini F, et al. Meta-analysis of randomized trials
comparing endoscopic stenting and surgical decompression for colorectal cancer
obstruction. Int J Colorectal Dis 2012.
Zhang Y, et al. Self-expanding metallics stenta s a bridge to surgery versus
emergency surgery for obstructive colorectal cancer: a meta nalysis. Sur Endosc
2012; 26: 110-119.

United European Gastroenterology Journal 2(1S)


Sabbagh C, Browet F, Diouf M, et al. Is stenting as a bridge til surgery an
oncologically safe strategy for the management of acute, left-sided, malignant
colonic obstruction? Ann Surg 2013; 00: 1-9.
Kim HJ, Choi G, Park JS et al. Higer rete of perineural invasion in stent-laparoscopic approach in comparison to emergent open resection for obstructiong leftsided colon cancer. Int J Colorectal Dis 2012.
Disclosure of Interest: None declared
P1542 CRC SCREENING USING FEACAL IMMUNOCHEMICAL TEST
(FIT) IN IBARAKI PREFECTURE, JAPAN -AN ADVANTAGE OF A
TWO-DAY SAMPLING METHODY. Saito1,2,*, H. Suzuki3, I. Hyodo2,3, I. Yamaguchi4
1
Department of Gastroenterology, Ibarakiken Medical Center, 2Sub-committee for
Colorectal Cancer, Ibaraki Prefectural Council for Controlling and Preventing Life
Style-related Disease, Mito, 3Department of Gastroenterology, University of
Tsukuba, Tsukuba, 4Ibaraki Health Service Association, Mito, Japan
INTRODUCTION: A two-day method was shown to have higher sensitivity
than a one-day method in 1988, therefore a two-day sampling method through
immunological fecal occult blood test (FIT) has been widely accepted by colorectal cancer screening program according to Japanese Colorectal Cancer (CRC)
screening guidelines.
AIMS & METHODS: The purpose of this study is to evaluate the positive
predictive values and Dukes classification of identified colorectal cancer between
the first day positive and the first day negative group. For Regional Screening
Program from 2007 to 2012, FIT participants, who were over 40 years old, were
screened with 2 samples of stool measured by the OC-SENSOR (Eiken, Japan)
with a cut-off value of 100ng/mL (20g Hb/g stool). The number of participants
was 750,839. The participant gender was 41.3% male and 58.7% female. The FIT
positive participants were classified into the first day positive group () (-)
() and negative group (-).
RESULTS: The positive FIT participants was 53,847 in number, and the total
FIT positive rate was 7.17%. The number of the first day positive and negative
participants were 33.172 (61.6%) and 20.675 (38.4%) respectively. Work-up
examination rates were 72.8% and 74.3% respectively. The number of two-day
positive participants was 10.163 (18.8%). CRCs were identified in 1,330 cases.
One thousand and forty-one (1,041) cases were from the first day positive group
and 289 cases were from the first day negative group. The positive predictive
values between the first day positive and negative group were 3.138% and
1.398% respectively. The positive predictive value of FIT-positivity in both
days was 6.839%. Identified CRCs were classified according to Dukes classification. Those were 632 (Dukes A intra-mucosal carcinoma), 387 (Dukes A invasive
carcinoma), 128 (Dukes B), 153 (Dukes C), 23 (Dukes D) and 7 (unknown).
Seventy-eight % of total identified CRCs were from the first day positive
group; 459/632 (Dukes A intra-mucosal carcinoma), 72.6%; 310 /387 (Dukes
A invasive carcinoma), 80.1%; 116/128 (Dukes B), 90.6%; 130/153 (Dukes C),
85.0%; and 20/ 23 (Dukes D), 87.0%.
CONCLUSION: If one-day sampling of FIT were adopted in the screening
program, 27.4% (173/632) of Dukes A intra-mucosal carcinoma and 19.9%
(77/387) of Dukes A invasive one would be missed. The highest positive predictive value was shown in the FIT both days-positive group.
Disclosure of Interest: None declared
P1543 ENDOSCOPIC TREATMENT IN RECTAL NEUROENDOCRINE
TUMOR- NET REGISTRY MULTICENTER STUDY
Y.K. Cho1,*, S.H. Kim1, S.J. Park2, B.R. Keum3, J.-H. Kim4, S.K. Lee4,
B.K. Park5, J.H. Park6, T.J. Jeon7, H.J. Kim8, J.H. Cho9, H.S. Choi10,
Y.E. Joo11, J.T. Jung12, Y.J. Lim13, J.H. Lee14, B. I. Jang15, Y.K. Cheon16,
J.K. Sung17, Y.J. Kim18, B.W. Bang19, B.C. Kim20, J.H. Hwang21, S.C. Park22,
T.H. Lee23 on behalf of NET Registry group
1
INTERNAL MEDICINE, Eulji Medical Center, Seoul, 2INTERNAL
MEDICINE, Kosin University College of Medicine, Pusan, 3INTERNAL
MEDICINE, Korea University College of Medicine, 4INTERNAL MEDICINE,
Yonsei University College of Medicine, Seoul, 5INTERNAL MEDICINE,
National Health Insurance Corporation Ilsan Hospital, Goyang, 6INTERNAL
MEDICINE, Inje University College of Medicine, Pusan, 7INTERNAL
MEDICINE, Inje University College of Medicine, Seoul, 8INTERNAL
MEDICINE, Kyeongsang National University School of Medicine, Jinju,
9
INTERNAL MEDICINE, Kwandong University College of Medicine,
Gangneung, 10INTERNAL MEDICINE, Hanyang, Seoul, 11INTERNAL
MEDICINE, Chonnam national University Medical School, Hwasun,
12
INTERNAL MEDICINE, Catholic University of Daegu School of Medicine,
Daegu, 13INTERNAL MEDICINE, Dongguk University College of Medicine,
Goyang, 14INTERNAL MEDICINE, Dong-A University School of Medicine,
Pusan, 15INTERNAL MEDICINE, Yeungnam University College of Medicine,
Daegu, 16INTERNAL MEDICINE, Konkuk University School of Medicine,
Seoul, 17INTERNAL MEDICINE, Chungnam National University School of
Medicine, Daejeon, 18INTERNAL MEDICINE, Gachon University College of
Medicine, 19INTERNAL MEDICINE, Inha University School of Medicine,
Incheon, 20INTERNAL MEDICINE, National Cancer Center, Seoul,
21
INTERNAL MEDICINE, Seoul National University College of Medicine,
Seongnam, 22INTERNAL MEDICINE, Kangwon National University School of
Medicine, Gangneung, 23INTERNAL MEDICINE, Soonchunhyang University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: cyk@eujlj.ac.kr
INTRODUCTION: Rectal neuroendocrine tumor (NET) incidence is low. So
previous studies of Endoscopic treatment in rectal NET have been small
sample size studies.

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United European Gastroenterology Journal 2(1S)


AIMS & METHODS: The aim of this study was to investigate effectiveness of
endoscopic treatment in rectal NET below 2cm. From Jan. 2003 to Dec. 2012.
1366 patients diagnosed Rectal NET in 24center was enrolled. Inclusion criteria
were endoscopic treatment, under 2cm size, over 18 age. Exclusion criteria
included no treatment, treatment, operation, chemotherapy, octreotide therapy,
imcomplete data. After exclusion, 411 patients was enrolled. We analyzed the
clinicopathologic data and factors affecting incomplete resection. We used Kisqure, t-test statistically.
RESULTS: In total 411 patients, Age was 49.6411.33, Male were 238 (57.9%),
All symptom were 59 (14.4%), Carcinoid symptom were 13 (3.2%), Family
history of NET were 4 (1%), Multiple lesion were 15 (3.6%), Elevated /Flat/
Depressed lesions were 407 (99)/2 (0.5%)/2 (0.5%), Lesion size was 0.58 
0.32cm, In histology, Well differentiated neuroendocrine tumor/Well differentiated neuroendocrine carcinoma wred 403 (98.1%)/8 (1.9%), Mucosa/
Submucosa/Proper muscle invasion were 117 (28.5%)/288 (70.1%)/6 (1.5%),
Lymphovascular invasion were 4 (1%), EMR/ESD were 300 (73%)/111 (27%),
Complete/Incomplete resection were 344 (83.7%)/67 (16.3%), Additional treatment after incomplete resection were 5 (1.5%), Recurrence were 8 (1.9%). The
lymphovascular invasion, ESD, Recurrence were significant factor in Incomplete
resection.
CONCLUSION: We suggest endoscopic treatment was effective in rectal neuroendocrine tumor below 2cm size. But further study including complication
result will be needed.
Disclosure of Interest: None declared
P1544 INCREASED ZONULIN SERUM LEVELS AND CORRELATION
WITH SYMPTOMS IN NON-CELIAC GLUTEN SENSITIVITY AND
IRRITABLE BOWEL SYNDROME WITH DIARRHEA
M.R. Barbaro1,*, C. Cremon1, G. Caio1, L. Bellacosa1, R. De Giorgio1,
U. Volta1, V. Stanghellini1, G. Barbara1
1
Department of Medical and Surgical Sciences, University of Bologna, Bologna,
Italy
Contact E-mail Address: maria.barbaro2@unibo.it
INTRODUCTION: Increased intestinal permeability plays a role in the pathophysiology and symptom generation in celiac disease (CD), non-celiac gluten
sensitivity (NCGS) and irritable bowel syndrome (IBS). The pre-haptoglobin 2,
also known as zonulin, is an endogenous modulator of epithelial tight junctions
(TJs) and intestinal permeability. Zonulin is the human homolog of the zonula
occludens toxin secreted by Vibrio cholerae. Intestinal bacterial infections and
gluten evoke zonulin release in the intestinal milieu and in the bloodstream.
Zonulin serum levels, their correlation with symptoms and diagnostic value as
a disease biomarker in NCGS and IBS remain undetermined.
AIMS & METHODS: In the present study, we aim at characterizing zonulin
serum levels in patients with NCGS (n 11) and IBS-D (n 9) compared with
CD (n 7; positive control) and healthy controls (n 7; HC, negative control).
NCGS patients were diagnosed based on the presence of gastrointestinal symptoms referable to the ingestion of gluten and in the absence of serological and
histological criteria for celiac disease. IBS patients were diagnosed according to
Rome III criteria. Celiac disease patients were identified on the basis of symptoms, antibodies and confirmation with duodenal biopsy. ELISA assay was used
to evaluate zonulin serum levels; total protein amount was evaluated spectrophotometrically using Nanodrop (Thermo Scientific) and used to normalize data.
Clinical data were recorded for each patient including: anti-transglutaminase
(TTG) antibodies, anti-deamidated gliadin peptide (DPG) antibodies, IgE,
abdominal symptoms and bowel habit.
RESULTS: Zonulin serum levels were significantly different among the four
groups (p50.001). CD patients showed significantly higher serum zonulin
levels compared to HC (0.044  0.003 vs 0.01 0.002, p50.001) and to IBS-D
patients (0.018  0.003, p50.05). NCGS zonulin serum levels were significantly
higher than HC (0.01 0.002 vs 0.036  0.007, p50.05). Compared to all other
subgroups, zonulin values in NCGS patients showed a broader range of distribution. Compared to IBS-D, NCGS zonulin values were higher although did not
reach statistical significance (p 0.06). Zonulin levels were positively correlated
with the titer of anti-DPG antibodies (r:0.6; p50.05,) and anti-TTG antibodies
(r:0.6; p50.05). In NCGS patients zonulin levels were positively correlated to
total serum IgE levels (r:0.6; p50.05).
CONCLUSION: Our results suggest that zonulin could play a role in the pathophysiology of NCGS and IBS-D. Further studies are needed to assess its role as a
biomarker with diagnostic potential in conditions characterized by increased
intestinal permeability.
Disclosure of Interest: None declared
P1545 SACCHAROMYCES
BOULARDII
SUPPLEMENTATION
REDUCES THE SEVERITY OF HERPES SIMPLEX VIRUS TYPE 1INDUCED GASTROINTESTINAL DYSFUNCTION
P. Brun1,*, E. Grandis1, T. Filippetto2, G. Schirato1, V. Russo1, L. Spagnol1,
M. Pasqualin1, V. Caputi2, A. Porzionato1, M.C. Giron2, I. Castagliuolo1
1
Molecular Medicine, 2Pharmacological sciences, University of Padova, Padova,
Italy
Contact E-mail Address: ignazio.castagliuolo@unipd.it
INTRODUCTION: The development of effective treatments for Irritable bowel
syndrome (IBS), a functional gastrointestinal (GI) disorder, have been hampered
by the lack of animal models. We have established a model of anomalous GI
contractility secondary to persistent infection of Herpes simplex virus type 1
(HSV-1) in enteric nervous system (ENS) (Gastroenterology 2010;138:1790).
AIMS & METHODS: Since previous studies have suggested that S. boulardii
may improve quality of life in IBS patients we assessed its effects on HSV-1-

induced GI neuromuscular dysfunctions. Male C57/Bl6 mice were inoculated


intranasally with HSV-1 and 4 weeks (W) later intragastrically (IG). Mice were
allocated to receive IG either S. boulardii or vehicle. In an experimental group,
the treatment started 1W before IG viral inoculum and lasted until the sacrifice
(1W after viral inoculum). The second experimental group were treated from 6W
to 10W after IG viral inoculum. At the time of sacrifice (1 or 10W after viral IG
inoculum) we determined a) GI motility, fecal pellet expulsion and water content,
and distal colonic transit; b) ENS integrity by immunohistochemistry and WB; c)
changes in isometric muscle tension following electric field stimulation of ileal
segments; d) inflammation by IL-1, TNF and MCP-1 ELISA in LMMP.
RESULTS: After 1 W, HSV -1 infection of ENS caused delayed GI transit time,
impaired cholinergic neuromuscular transmission, altered expression and distribution of the neurofilaments peripherin and III-tubulin, and increased expression of MCP-1. Even if supplementation with S. boulardii reduced the production
of inflammatory cytokines and the deregulated expression of neurofilaments, the
treatment failed to influence HSV-1-induced GI neuromuscular dysfunction.
However, 10 W after HSV-1 IG administration, S. boulardii supplementation
almost completely corrected the severity of GI neuromuscular anomalies, restoring GI transit time, cholinergic neuromuscular contractility, faecal water content
and colonic expulsion time to levels comparable to those obtained from control
mice. Furthermore, S. boulardii completely abolished ENS structural alterations
and the mild inflammation in ileal LMMP.
CONCLUSION: Dietary S. boulardii ameliorates GI neuromuscular dysfunction
and ENS anomalies secondary to chronic but not acute HSV-1 infection, underlying its beneficial effects for the treatment of enteric dysmotility disorders associated to mild inflammatory conditions.
REFERENCES
Disclosure of Interest: P. Brun: None declared, E. Grandis: None declared, T.
Filippetto: None declared, G. Schirato: None declared, V. Russo: None declared,
L. Spagnol: None declared, M. Pasqualin: None declared, V. Caputi: None
declared, A. Porzionato: None declared, M. Giron: None declared, I.
Castagliuolo Financial support for research from: Research partially supported
by Biocodex spA (France)
P1546 IMMUNE ACTIVATION IS ASSOCIATED WITH SYMPTOM
FLARE IN DIARRHOEA PREDOMINANT IRRITABLE BOWEL
SYNDROME
M. Moretta1, J.M. Andrews1,2, P.A. Bampton3, P.A. Hughes1,2,*
Medicine, University of Adelaide, 2Dept. of Gastroenterology and Hepatology,
Royal Adelaide Hospital, 3Department of Gastroenterology, Flinders Medical
Centre, Adelaide, Australia
Contact E-mail Address: patrick.hughes@adelaide.edu.au
1

INTRODUCTION: IBS has historically been described as a functional neurological motility disorder resulting from alterations in the brain-gut axis, but the
underlying mechanisms remain unclear. There is increasing evidence that the
immune system is also altered in IBS patients, consistent with a chronic low
grade immune activation (Hughes et al. Am. J. Gastro. 2013). However the
nature of the immune response remains controversial with conflicting findings
as to whether it comprises a predominantly typical or atypical allergic or autoimmune type response. Much of this controversy stems from grouping of all IBS
patient subtypes and the use of cross-sectional data.
AIMS & METHODS: We aimed to investigate immune activation in IBS
patients longitudinally, comparing immune responses in patient flare vs. when
symptom free. 5 IBS-D patients were enrolled in the study and blood samples
were taken quarterly (baseline) over a 1 year period and again whenever the
patient self-reported symptom flare (flare). Questionnaires related to symptom
severity (IBSS) were completed at each blood sample. PBMC were isolated from
whole blood via density centrifugation and 1*106/ml cells were cultured in culture
media only (unstimulated) overnight, in the presence of PMA/ionomycin for 4
hours or LPS overnight. Cell culture supernatants were collected and analysed
for cytokine concentrations using multiplex bead based assay (eBioscience).
Baseline cytokine concentrations and IBSS scores were averaged and compared
against cytokine concentrations and IBSS scores from patients in flare using
paired student t-test.
RESULTS: IBSS scores were significantly increased during self-reported symptom flare compared to baseline. PMA/ionomycin stimulation increased concentrations of IFN-gamma, IL-2, IL-13, IL-21, GMCSF and TNF-alpha and
decreased concentrations of IL-4, IL-5, IL-9, IL-10, IL-22, IL-23 and IL-27
relative to concentrations in unstimulated supernatants. LPS stimulation
increased concentrations of GMCSF, IFN-gamma, IL-10, IL-13, IL-17, IL-18,
IL-21, IL-22, IL-23, IL-27 and TNF-alpha, and decreased concentrations of IL-4
relative to unstimulated supernatants. Cytokine concentrations varied considerably between patients but remained stable at baseline within patient samples. The
concentration of unstimulated cytokines did not differ between baseline and
flare. The concentration of PMA/ionomycin stimulated IFN-gamma, IL-2, IL4, IL-5, IL-18 and IL-23 were significantly increased during flare relative to
baseline. The concentration of LPS stimulated GMCSF and IL-10 were significantly increased during patient flare vs baseline.
CONCLUSION: Our preliminary findings indicate both innate and adaptive
arms of the immune response are altered in IBS-D patients in symptom flare
vs baseline. Future investigations with more patients, including IBS-C and IBS-A
subtypes, will indicate whether these alterations are IBS-D specific. These studies
will potentially identify biomarkers for IBS patients in symptom flare and also
novel treatments targeting specific aspects of the immune response.
Supported by NHMRC Australia.
Disclosure of Interest: None declared

A556
P1547 LOW SERUM LEVELS OF SHORT-CHAIN FATTY ACIDS AFTER
LACTULOSE INGESTION MAY INDICATE IMPAIRED MICROBIAL
FERMENTATION IN PATIENTS WITH IRRITABLE BOWEL
SYNDROME
R. Undseth1,*, G. Jakobsdottir2, M. Nyman2, A. Berstad3, J. Valeur3
1
Department of Radiology, Lovisenberg Diakonale Hospital, Oslo, Norway,
2
Applied Nutrition and Food Chemistry, Department of Food Technology,
Enigneering and Nutrition, LTH, Lund University, Lund, Sweden, 3Unger-Vetlesen
Institute, Lovisenberg Diakonale Hospital, Oslo, Norway
Contact E-mail Address: jorgen.valeur@med.uib.no
INTRODUCTION: Poorly absorbable, but fermentable carbohydrates may provoke symptoms in patients with irritable bowel syndrome (IBS). This indicates
that fermentation plays a role in symptom generation.
AIMS & METHODS: We aimed to measure microbial fermentation products
before and after ingestion of an unabsorbable carbohydrate (lactulose) in IBS
patients compared to healthy subjects.
Patients with IBS according to Rome III criteria (n 22) and healthy controls
(n 20) ingested a 10 gram lactulose solution. Short chain fatty acids (SCFA)
were measured in serum in fasted state and 90 minutes after lactulose intake,
using hollow fiber supported liquid membrane extraction coupled with gas chromatography (1). Symptoms following lactulose ingestion were also assessed.
RESULTS: Lactulose induced more symptoms in patients with IBS than in
healthy controls (p 0.0004). Fasting serum levels of SCFA were not different
in patients and controls (p 0.1). Levels of SCFA in serum obtained after 90
minutes were significantly lower in patients with IBS compared to healthy controls, both for total SCFA (p 0.0002), acetic acid (p 0.0049), propionic acid
(p 0.0204) and butyric acid (p 0.0111).
CONCLUSION: Patients with IBS had lower serum levels of SCFA in response
to lactulose ingestion than healthy controls. The results suggest a failure of
colonic salvage of carbohydrates in IBS that may be involved in abdominal
symptom development.
REFERENCES
1. Zhao G, Liu JF, Nyman M, et al. Determination of short-chain fatty acids in
serum by hollow fiber supported liquid membrane extraction coupled with gas
chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 846: 202208.
Disclosure of Interest: None declared
P1548 DEVELOPMENTAL LEVEL OF DEFENSE MECHANISMS AND
TENDENCY OF CORPORAL DISCOURSE IN IRRITABLE BOWEL
SYNDROME A COMPARATIVE PILOT STUDY
L. Avnat1, S. Levy2, R. Reicher-Atir1, S. Aizic3, I. Fahn3, Y. Niv3, R. Dickman3,*
The Academic College of Tel Aviv Yaffo, Tel Aviv-Yaffo, Israel, 2Biostatistics,
The Academic College of Tel Aviv Yaffo, Tel Aviv-Yaffo, 3Gastroenterology, Rabin
Medical Center, Petach Tikva, Israel
Contact E-mail Address: dickmanr1@gmail.com
1

INTRODUCTION: Corporal discourse is the pronounced utilization of somatic


modalities as a mean of communication and emotional expression. The maturity
level of defense mechanisms allows the quantification and understanding of
developmental level of psychological defenses used by an individual. In irritable
bowel syndrome (IBS), both, the developmental level of defense mechanisms and
the tendency of corporal discourse have not been extensively assessed.
AIMS & METHODS: To evaluate the developmental level of defense mechanisms and the tendency of corporal discourse among IBS patients compared to
healthy volunteers and medical staff members.
We performed a survey assessing for the maturity level of defense mechanisms
and the tendency of corporal discourse in 40 adult patients with IBS, 40 adult
healthy volunteers and 39 local medical staff members. All participants completed the Defense Style Questionnaire (DSQ-40) and the Corporal Discourse
questionnaire. Responses were statistically analyzed by group using one way
ANOVA and the Pearson correlation coefficient.
RESULTS: IBS patients tended to use a lower order of defense mechanisms
compared to medical staff, but not to healthy volunteers (F (2.116) 3.27,
p 0.04). Compared to the other groups, IBS patients tended to use more extensively a corporal discourse (F (2.116) 28.36, p5 0.01). In IBS patients, correlations were found between maturity level of defense mechanisms and tendency of
corporal discourse (mature factor r -0.41, p5 0.01; neurotic factor r -0.35,
p 0.03) and between tendency to use somatization as a defense mechanism and
tendency to use corporal discourse (r -0.38, p 0.01). Finally, a correlation
between situational anxiety/depression and the tendency of corporal discourse
was found in both IBS patients and medical staff, (IBS: r 0.65, p5 0.01;
r 0.59, p5 0.01 respectively. Medical staff: r 0.42, p5 0.01; r 0.41, p5
0.01 respectively).
CONCLUSION: A lower developmental level of defense mechanisms and a
higher tendency of corporal discourse are more pronounced in IBS patients.
Furthermore, medical staff members and IBS patients share a relation between
situational anxiety/depression and the tendency of corporal discourse.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1549 INFLUENCE OF A LOW-FODMAP DIET ON SYMPTOMS AND
GUT MICROBIOTA IN PATIENTS WITH IRRITABLE BOWEL
SYNDROME
J. Valeur1,*, T. Knudsen2, T. Mellin-Olsen2, A. Rseth1
Unger-Vetlesen Institute, 2Department of Clinical Nutrition, Lovisenberg
Diakonale Hospital, Oslo, Norway
Contact E-mail Address: jorgen.valeur@med.uib.no
1

INTRODUCTION: Reducing intake of fermentable oligo-, di- and monosaccharides and polyols (FODMAP) may improve functional bowel symptoms.
We aimed to investigate the effect of such a dietary change on intestinal and
extra-intestinal symptoms and gut microbiota in patients with irritable bowel
syndrome (IBS).
AIMS & METHODS: IBS patients admitted to Lovisenberg Diakonale Hospital
were investigated consecutively from April 2013 to January 2014. Symptoms
were assessed by using validated questionnaires to measure both intestinal
(IBS-SSS) and extra-intestinal symptoms (HADS, FIS) before and after 4
weeks on a low-FODMAP diet. Fecal gut bacteria DNA analysis was performed
by using the GA-mapTM Dysbiosis Test (Genetic Analysis AS, Oslo, Norway).
This 16S rRNA DNA test utilizes DNA probes to recognize gut bacteria (1)
found to best correlate with dysbiosis in patients with IBD and IBS. Dysbiosis
index is an index calculated by an algorithm based on bacterial abundance and
profile in a fecal sample, measured on a scale from 1 to 10, where values above 2
are considered abnormal. Change in dysbiosis index between week 0 and 4 were
investigated.
RESULTS: Forty-eight patients (4 M, 44 F) completed the study. At baseline, 23
and 25 patients had a dysbiosis index classified as normal and abnormal,
respectively. These two groups were significantly different regarding intestinal
symptom severity (mean IBS-SSS scores 263 versus 304, respectively; p 0.04),
but similar regarding extra-intestinal symptom severity. A correlation between
dysbiosis index and IBS-SSS was demonstrated (r 0.29, p 0.04), including the
subscale measuring pain (r 0.30; p 0.04). Following dietary intervention,
symptomatic improvement was demonstrated as a reduction in IBS-SSS (from
285 to 157; P 5 0.0001), HADS (from 14 to 9; P 5 0.0001) and FIS (from 72 to
38; P 5 0.0001). The dysbiosis index changed in 31 (65%) patients while it
remained unchanged in 17 (35%) patients. There was no correlation between
change in dysbiosis index and change in symptoms following diet.
CONCLUSION: A low-FODMAP diet seems to improve not only intestinal, but
also extra-intestinal symptoms in patients with IBS. The GA-mapTM Dysbiosis
Test showed that patients with higher dysbiosis indices had more severe intestinal
symptoms at baseline. The test thus provides information on alterations in bacterial abundance and profiles that may prove valuable for individual patients.
However, we did not demonstrate any associations between change in dysbiosis
indices and symptoms following dietary intervention.
REFERENCES
1. Veb HC, et al. Temporal development of the infant gut microbiota in immunoglobulin E-sensitized and non-sensitized children determined by the GA-map
infant array. Clin Vaccine Immunol 2011; 18: 1326-1335.
Disclosure of Interest: None declared
P1550 TREATMENT SATISFACTION AFTER RETREATMENT AND
LONG-TERM THERAPY WITH LINACLOTIDE
C. D az1,*, M. Falques1, M. Moya1, D. Vilardell1, J. Fortea1, S.J. Shiff2,
J.M. Johnston3
1
Almirall SA, Barcelona, Spain, 2Forest Laboratories, Jersey City, NJ, 3Ironwood
Pharmaceuticals, Cambridge, MA, United States
INTRODUCTION: The chronic nature of irritable bowel syndrome (IBS)
requires pharmacological treatments to achieve long-term sustained symptom
control. As IBS symptoms fluctuate over time, it is important that symptom
control with pharmacological treatment can be re-established if treatment is reintroduced after a period of discontinuation. Linaclotide (LIN) is a first-in-class,
minimally absorbed, guanylate cyclase-C agonist for the treatment of adults with
IBS with constipation (IBS-C). One of the pivotal Phase 3 LIN trials (Trial 31)
included a 4-week post-treatment randomised withdrawal period (RWP); upon
completion of the trial, including the RWP, patients were allowed to continue
treatment in an open-label, long-term study (LTS).
AIMS & METHODS: This post-hoc analysis examined the impact on treatment
satisfaction of reintroducing LIN after 4 weeks off treatment in patients who
were randomised to LIN 290g once daily in the initial 12-week treatment period
in Trial 31. Of these, 158 were subsequently re-randomised to LIN (LIN-LIN)
and 154 were re-randomised to PBO (LIN-PBO) in the 4-week RWP. Eligible
patients could then receive LIN for a further 78 weeks in the LTS. Patientreported treatment satisfaction was used as an efficacy measure in the LTS,
measured at study visits during Weeks 2, 4, 8, 12, 14 and 16 during Trial 31
and at Weeks 2, 6, 14, 26, 39, 52, 65 and 78 during the LTS. Patients were asked
to rate how satisfied they were with the ability of the study medication to relieve
their IBS symptoms on a 1-5 point scale (1 not at all satisfied, 2 a little
satisfied, 3 moderately satisfied, 4 quite satisfied, 5 very satisfied). Data
were analysed using a last observation carried forward approach.
RESULTS: At the end of the 12-week treatment period in Trial 31, treatment
satisfaction was similar for LIN patients who were re-randomised to PBO and
patients who remained on LIN (mean [standard deviation, SD] treatment satisfaction at Week 12: 3.42 [1.34] vs 3.37 [1.34]). During the 4-week RWP, patients
re-randomised from LIN to PBO (LIN-PBO) showed a statistically significant
(P50.05) mean reduction in treatment satisfaction compared to patients who
remained on LIN (LIN-LIN) and at the end of the RWP the mean (SD) treatment satisfaction for patients in the LIN-PBO group was 3.18 [1.34] vs 3.47 [1.37]
for patients in the LIN-LIN group. Following reintroduction of LIN during the

A557

United European Gastroenterology Journal 2(1S)


LTS, mean (SD) treatment satisfaction increased to previous levels in the LINPBO treatment group within 2 weeks of starting LIN (LIN-PBO, 3.69 [1.17] vs
LIN-LIN, 3.70 [1.05]) and this effect was sustained to the end of the 78-week
follow-up period (LIN-PBO, 3.93 [1.32] vs LIN-LIN, 3.81 [1.21]). LIN treatment
satisfaction increased throughout the long-term study. Similar to the Phase 3
trials, the most common AE observed during the LTS among LIN-treated
patients was diarrhoea.
CONCLUSION: Patients with IBS-C who discontinued LIN therapy for a 4week period experienced a significant reduction in treatment satisfaction; however, subsequent reintroduction of these patients to LIN therapy resulted in a
similar, relatively high level of treatment satisfaction to patients who remained on
LIN during long-term therapy.
Disclosure of Interest: C. D az Other: Employee Almirall SA, M. Falques Other:
Employee Almirall SA, M. Moya Other: Employee Almirall SA, D. Vilardell
Other: Employee Almirall SA, J. Fortea Other: Employee Almirall SA, S. Shiff
Shareholder of: Forest Laboratories, Other: Employee Forest Laboratories, J.
Johnston Shareholder of: Ironwood Pharmaceuticals, Other: Employee
Ironwood Pharmaceuticals.
P1551 BASELINE CHARACTERISTICS AS A PREDICTOR OF
RESPONSE TO LINACLOTIDE IN PATIENTS WITH IRRITABLE
BOWEL SYNDROME WITH CONSTIPATION: A POOLED ANALYSIS
OF 2 PHASE 3 TRIALS
C. D az1,*, M. Falques1, M. Moya1, D. Vilardell1, J. Fortea1, J.M. Johnston2
1
Almirall SA, Barcelona, Spain, 2Ironwood Pharmaceuticals, Cambridge, MA,
United States
INTRODUCTION: In 2 Phase 3 trials in irritable bowel syndrome with constipation (IBS-C), linaclotide (LIN) treatment was superior to placebo (PBO) based
on European Medicines Agency co-primary endpoints (rate of abdominal pain/
discomfort responders [Trial 31: 54.8% vs 41.8%; Trial 302: 54.1% vs 38.5%;
P50.001] and IBS degree-of-relief responders [Trial 31: 37.0% vs 18.5%; Trial
302: 39.4% vs. 16.6%; P50.0001]). Improvements after 1 month of LIN therapy
were highly likely to be maintained at 3 months.1 A potential association between
baseline patient characteristics and likelihood of therapeutic response to LIN is
unclear.
AIMS & METHODS: This pooled analysis evaluated potential predictive value
of baseline characteristics in 2 pivotal Phase 3 IBS-C trials by comparing demographics (age, sex, body mass index [BMI]) and baseline symptoms (Complete
Spontaneous Bowel Movements [CSBM] rate, Bristol Stool Form Scale [BSFS],
straining, abdominal pain, discomfort, and bloating) for LIN non-responders vs
responders, defined as (1) 12-week abdominal pain/discomfort responders
(30% reduction in abdominal pain and/or discomfort score [11-point scales],
with neither worsening from baseline, for 6/12 weeks) and (2) 12-week IBS
degree-of-relief responders (symptoms considerably or completely relieved
for 6/12 weeks).
RESULTS: The pooled analysis included 1602 patients (LIN, n 805; PBO,
n 797). Baseline characteristics were similar for responders and non-responders
in the LIN group and the PBO group (Table). Abdominal discomfort scores and
BMI were also similar for responders and non-responders (not shown).
CONCLUSION: Baseline demographics and disease characteristics did not predict treatment response to LIN or PBO in patients with IBS-C in the Phase 3
pivotal trials.
REFERENCES
1. Chey WD, et al. Poster P980 presented at UEG Week, 12-16 October 2013,
Berlin, Germany.
Disclosure of Interest: C. D az Other: Employee Almirall SA, M. Falques Other:
Employee Almirall SA, M. Moya Other: Employee Almirall SA, D. Vilardell
Other: Employee Almirall SA, J. Fortea Other: Employee Almirall SA, J.
Johnston Shareholder of: Ironwood Pharmaceuticals, Other: Employee
Ironwood Pharmaceuticals.
P1552 PINAVERIUM BROMIDE PLUS SIMETHICONE IMPROVES
BLOATING IN IBS PATIENTS INDEPENDENTLY OF BMI WHILE
DAY/NIGHT VARIABILITY IN DISTENSION IS RELATED TO
WEIGHT
G. Mateos1,* on behalf of Mexican IBS Working group, J.C. Soto-Perez2,
J. Chiu-Ugalde3, A. Vargas4, J.C. Lopez-Alvarenga5, M. Schmulson6
1
Departamento de Ciruga General y Gastroenterologa, Hospital Angeles del
Pedregal, 2Departamento de Endoscopia, Hospital de Alta Especialidad PEMEX
Sur, Mexico City, 3Medical Research Department, Takeda Mexico, Naucalpan,

Medical Research Department, Takeda Mexico, 5Direccion de Investigacion,


Hospital General de Mexico, Eduardo Liceaga, 6Laboratorio de Hgado, Pancreas
y Motilidad, Departamento de Medicina Experimental, Facultad de Medicina,
UNAM, Mexico City, Mexico
Contact E-mail Address: jazmin.chiu@takeda.com
INTRODUCTION: In IBS, bloating seems related to visceral hypersensitivity,
while visible abdominal distension to related to hyposensitivity due to delayed
intestinal transit.1 We have previously shown that pinaverium bromide 100 mg
simethicone 300 mg (PBS), bid, improves bloating but not distension in IBS.2
However, the relationship of BMI over these responses is unknown. Therefore, in
this post hoc analysis, we explored the effect PBS on bloating/distension according to BMI.
AIMS & METHODS: In this post hoc analysis, we explored the effect PBS on
bloating/distension according to BMI.
IBS-Rome III patients were randomly allocated to PBS (n 127) or placebo
(n 128) during 12-weeks in a double-blind placebo-controlled trial. A 10-cm
VAS was used to evaluate the severity of bloating. Abdominal girth was measured twice a day (morning and night) during 7 consecutive days in weeks 1, 6
and 12. Abdominal volume (V) was calculated as: V (girth cm)3/[6 p2] and
day/night differences were determined. Partial etha^2 was calculated by
ANCOVA for abdominal volume differences due to treatment and body
weight adjusted by the initial volume differences and sex.
RESULTS: Patients were (meanSD) 35.98.9 years old, women: 83.2% and
BMI: 26.55.3 (Normal: 43%, Overweight: 36%, Obesity: 21%). IBS-subtypes
were classified as IBS-C: 44%, IBS-D: 23%, IBS-M: 31% and IBS-U: 2%. At 12
weeks, bloating severity decreased by 18% in the overweight patients and 22% in
the obese with respect to normal-weight subjects (p 0.32); PBS had a 37%
effect size vs. placebo (p50.006). Also, a higher variability in the day/night
change of abdominal volume was found in the overweight (39%) and obese
(42%) patients compared to the normal ones (p50.03); the effect size of PBS
was 13% vs. placebo (p50.39).
CONCLUSION: While PBS improved bloating in IBS patients independently
of BMI, variability in abdominal volume was higher in overweight and obese
patients compared to those with normal-weight with a low treatment effect.
REFERENCES
1 Agrawal A, et al. Gastroenterology 2008; 134: 1882-1889.
2 Schmulson M, et al. Gastroenterology 2011; 140 (Suppl. 1): M1327.
This study was funded by Takeda Mexico.
Disclosure of Interest: G. Mateos Consultancy for: Takeda Mexico, J. C. SotoPerez Consultancy for: Takeda Mexico, J. Chiu-Ugalde Other: Employee Takeda
Mexico, A. Vargas Other: Employee Takeda Mexico, J. Lopez-Alvarenga
Consultancy for: Takeda Mexico, M. Schmulson Consultancy for: Takeda
Mexico, Procter & Gamble, Novartis, Schering-Plough, Alfa-Wasserman,
Janssen and Nestle Ltd.
P1553 BLOATING IN IRRITABLE BOWEL SYNDROME
CONSTIPATION: BASELINE SEVERITY AND RESPONSE TO
TREATMENT IN 2 PHASE 3 TRIALS OF LINACLOTIDE

WITH

B. Lacy1, B. Lavins2, S.J. Shiff3, J. MacDougall2, R. Blakesley3, X.D. Jia3,


M. Currie2, C. Kurtz2, J.M. Johnston2,*
1
Dartmouth-Hitchcock Medical Center, Lebanon, NH, 2Ironwood
Pharmaceuticals, Cambridge, MA, 3Forest Research Institute, Jersey City, NJ,
United States
INTRODUCTION: Irritable bowel syndrome with constipation (IBS-C) is
defined by the presence of abdominal pain or discomfort in association with
symptoms of constipation; another common symptom of IBS-C is bloating,
but its severity and association with bowel movements (BMs) are not well
defined. Linaclotide (LIN) is a guanylate cyclase C agonist approved in the
United States and European Union for the treatment of IBS-C.
AIMS & METHODS: The aim of this post-hoc analysis was to: (1) characterise
the severity of bloating in IBS-C patients; (2) describe the effect of LIN on
bloating; and (3) assess the relationship between bloating and complete spontaneous BMs (CSBMs). Data from 2 LIN phase 3 IBS-C trials (Trials 302 and 31)
were pooled for this analysis. Both trials randomised patients to oral once-daily
LIN 290 g or placebo (PBO) after a 2-week pretreatment period. Trial 302 had
a 26-week treatment period; Trial 31 had a 12-week treatment period. Patients
rated their bloating on a 0-10 point scale (0 none; 10 very severe) daily during
the pretreatment and treatment periods. Patients also reported spontaneous BM
(SBM) and CSBM frequency, stool consistency, straining, and other abdominal
symptoms (pain, discomfort, fullness, cramping). Effect of CSBMs on bloating

Table to abstract P1553


Table Pooled responder rates in Phase 3 trials stratified by baseline characteristics
Abdominal pain/discomfort

IBS degree of relief

Abdominal pain/discomfort

IBS degree of relief

LIN R

LIN NR

LIN R

LIN NR

PBO R

PBO NR

PBO R

PBO NR

44.50 (12.05)
408 (92.9)
0.19 (0.44)
2.34 (1.01)
3.60 (0.79)
5.63 (1.67)
6.73 (1.83)

43.36 (13.91)
327 (89.3)
0.19 (0.42)
2.31 (1.08)
3.53 (0.80)
5.65 (1.72)
6.62 (1.81)

45.03 (12.08)
287 (93.2)
0.20 (0.44)
2.41 (0.99)
3.53 (0.76)
5.66 (1.70)
6.63 (1.82)

43.33 (13.41)
448 (90.1)
0.19 (0.43)
2.27 (1.07)
3.59 (0.82)
5.63 (1.69)
6.71 (1.82)

43.61 (13.75)
288 (90.0)
0.25 (0.49)
2.32 (1.00)
3.49 (0.79)
5.27 (1.68)
6.22 (1.79)

43.96 (12.71)
420 (88.1)
0.21 (0.47)
2.38 (1.00)
3.48 (0.80)
5.79 (1.71)
6.67 (1.87)

42.34 (13.45)
125 (89.9)
0.31 (0.51)
2.25 (0.89)
3.42 (0.81)
5.42 (1.70)
6.26 (1.80)

44.13 (13.05)
583 (88.6)
0.21 (0.47)
2.38 (1.02)
3.50 (0.79)
5.61 (1.72)
6.54 (1.86)

Characteristic
*

Age, years
Female, n (%)
CSBM* (no. per week)
BSFS* (1-7)
Straining* (0-5)
Abdominal pain* (0-10)
Abdominal bloating* (0-10)

A558
was assessed by stratifying the patients change in daily bloating score by number
of days since the patient had a CSBM.
RESULTS: The pooled intent-to-treat (ITT) population consisted of 1602
patients; 98% had baseline bloating scores 3. During pretreatment, 50% of
patients had an average bloating score 6.5; only 6% of patients reported 1 day
with no bloating (score of 0). LIN significantly reduced bloating within the first
week of treatment compared with PBO and provided sustained benefit across 26
weeks of treatment. Mean percentage reduction in bloating from baseline for
LIN vs PBO was 16% vs 7% at Week 1, 39% vs 24% at Week 12 and 44% vs
24% at Week 26. During the treatment period, the number of days since a patient
had a CSBM was strongly associated with a patients bloating score (i.e. a greater
reduction in bloating was associated with more recently having had a CSBM), in
both LIN and PBO patients. When controlling for days since last CSBM, the
percent decrease in bloating for the LIN group was consistently greater than the
PBO group (with non-overlapping 95% confidence intervals). For patients with 0
days since last CSBM, mean percentage improvement in bloating from baseline
was 42% vs 33% in the LIN vs PBO treatment groups; this decreased to 35% vs
28% for patients with 2 days since last CSBM and to 21% vs 13% for patients
with 4 days since last CSBM.
CONCLUSION: Bloating is a significant issue in IBS-C patients, as evidenced by
high baseline scores. LIN provides sustained reduction in bloating over PBO
starting at Week 1 of treatment. Having a CSBM was associated with reduced
bloating for LIN and PBO patients, with greater decreases in bloating on LIN vs
PBO regardless of time since last CSBM.
Study sponsored by Forest Laboratories, Inc., and Ironwood Pharmaceuticals, Inc.
Disclosure of Interest: B. Lacy Consultancy for: Ironwood/Forest, Prometheus,
Salix, Takeda, B. Lavins Shareholder of: Ironwood Pharmaceuticals, Other:
Employee of Ironwood Pharmaceuticals, S. Shiff Shareholder of: Forest
Laboratories, Inc, Other: Employee of Forest Laboratories, Inc, J.
MacDougall Consultancy for: paid consultant of Ironwood Pharmaceuticals,
R. Blakesley Shareholder of: Forest Laboratories, Inc, Other: Employee of
Forest Laboratories, Inc, X. Jia Shareholder of: Forest Laboratories, Inc,
Other: Employee of Forest Laboratories, Inc, M. Currie Shareholder of:
Ironwood Pharmaceuticals, Other: Employees of Ironwood Pharmaceuticals,
C. Kurtz Shareholder of: Ironwood Pharmaceuticals, Other: Employees of
Ironwood Pharmaceuticals, J. Johnston Shareholder of: Ironwood
Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals.
P1554 EFFECT OF NICKEL FREE DIET IN IBS PATIENTS WITH
NICKEL SENSITIZATION
L. Laterza1,*, A. Rizzi1, E. Gaetani2, E. Nucera1, V. Valenza1, D. Schiavino2,
A. Gasbarrini1
1
CATHOLIC UNIVERSITY OF ROME, Rome, Italy, 2Internal Medicine and
Gastroenterology, CATHOLIC UNIVERSITY OF ROME, Rome, Italy
INTRODUCTION: Irritable bowel syndrome (IBS) is characterized by chronic
abdominal pain or discomfort accompanied by abnormal bowel movements,
such as diarrhoea or constipation.
In sensitized subjects, the ingested nickel may induce gastrointestinal symptoms
similar to IBS, in addition to typical systemic cutaneous lesions.
This clinical picture is known as Systemic Nickel Allergy Syndrome (SNAS).
Although there is no general agreement, a low nickel diet could improve the
systemic manifestations. The prevalence of nickel allergy and the effect of
nickel-free diet on IBS symptoms are not known.
AIMS & METHODS: To evaluate the prevalence of nickel allergy among IBS
patients and to evaluate the effect of nickel-free diet on gastrointestinal symptoms in patients with IBS and nickel-sensitized patients. We selected 35 consecutive patients affected by IBS defined by Rome III criteria and tested them with
nickel patch tests. Patients positive for nickel allergy and meeting criteria for
suspected SNAS (history for abdominal symptoms and nickel patch-test) underwent intestinal permeability test. Gastrointestinal symptoms (bloating, abdominal pain, flatulence, cramps, constipation, diarrhoea, epigastric pain, nausea,
vomiting) were evaluated using visual analogue scale (VASIBS: 010) before
and after diet. Gut permeability was evaluated by measuring 24-hour urine excretion of orally administered 51Cr-EDTA and expressed as percentage of urinary
excretion of the orally administered dose of 51Cr-EDTA (%, cut off 5 3%/24h).
Then, all patients started a three months low nickel diet. Subjects with increased
intestinal permeability at baseline repeated nuclear exam after the diet.
RESULTS: Thirteen patients (M/F: 3/10; age: 399) met inclusion criteria. The
most frequent profile was diarrhoea predominant IBS (IBS-D, 10/13) compared
to mixed (IBS-M, 2/13) and constipation (IBS-C, 1/13). Lactose intolerance was
found in 9 patients. 6 subjects showed also sensitization to other haptens (palladium, cobalt, kathon). Mean urinary output of 51Cr-EDTA was 5.88%/24h
(1.44). There was a variable and inconstant behaviour of the change of intestinal permeability after treatment. Conversely, low nickel diet induced a significant and constant improvement of gastrointestinal symptoms (i.e. a reduction of
VASIBS) in all patients.
CONCLUSION: There is a high prevalence of suspected SNAS and intestinal
permeability impairment in patients with IBS. Low nickel diet has significant
beneficial effects on gastrointestinal symptoms in subjects with IBS and positive
nickel patch test. The effect of such diet on gastrointestinal permeability requires
further investigation.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1555 HOW DO IBS PATIENTS TREAT THEIR SYMPTOMS UNDER
REAL LIFE CONDITIONS? RESULTS FROM A SURVEY AMONG
THE MEMBERS OF A GERMAN IBS PATIENT ORGANIZATION
(DEUTSCHE REIZDARMSELBSTHILFE E. V.)
M. Plomer1,*, T. Weiser1, H. Weigmann1, T. Muck1, M. Eberlin1, U. Kohler2
1
Medical Affairs Germany, 2Corporate Medical Affairs, Boehringer Ingelheim
Pharma GmbH & Co. KG, Ingelheim, Germany
Contact E-mail Address: manuel.plomer@boehringer-ingelheim.com
INTRODUCTION: Irritable bowel syndrome (IBS) is a chronic, relapsing and
often life-long gastrointestinal disorder1. Although not being life-threating,
patients suffering from IBS report a significant impact on quality of life by
their various symptoms which consist of abdominal discomfort (stomach
cramps and bloating) and disordered defaecation (constipation, diarrhea, or
both)1,2. Besides dietary and lifestyle advices, guidelines recommend pharmacological treatment, adjusted to individual symptoms and patient preferrences2.
Little data is yet available about patient preferences and treatment habits.
AIMS & METHODS: To investigate the prevalence and severity of the main IBS
complaints, as well as the preferred treatment options among the members of a
German IBS patient organization (Deutsche Reizdarmselbsthilfe e. V.).
In 2013, non-personalized questionnaires were sent to all the members of the
Deutsche Reizdarmselbsthilfe e. V., and returned questionnaires were analyzed
by the patient organization.
RESULTS: 717 questionnaires were returned. 62% of respondents were female;
on average, IBS patients were 54 years old and over 73% suffered from IBS
symptoms for at least 10 years. 87% reported abdominal cramping and pain at
least several times per month (categories: up to once every three months/once per
month/several times per month/once per week/every day or several times per
week), followed by 84% reporting flatulence with the same frequency. There
were fewer patients reporting diarrhea, gastric cramps and constipation (several
times per month or more often: 69%, 62% and 61%, respectively).
When asked "Do abdominal pain and spasms affect your quality of life permanently and massively? (categories: very strong/strong/moderate/weak/not at all)",
93% of patients answered with "moderate", "strong", or" very strong".
Open questions were asked concerning the preferred therapeutics. Abdominal
cramping and pain, as well as gastric cramps were most often treated with the
antispasmodic hyoscine butylbromide (N 318 and 172, respectively), flatulence
with simethicone (N 320). The preferred treatment for diarrhea was loperamide
(N 205), and constipation was treated most often with bisacodyl (N 138).
68% of hyoscine butylbromide users report good or very good efficacy
against their abdominal cramps, 86% at least moderate efficacy (categories:
very good/ good/ moderate/ not sufficient/ very bad).
CONCLUSION: Abdominal cramping and pain was reported most often and
had a high and sustainable influence on quality of life among IBS patients. The
preferred treatment options for all symptoms consisted of classical OTC drugs.
Hyoscine butylbromide was the most often named and best rated treatment
option for the most frequent symptom abdominal cramping and pain.
REFERENCES
1 National Institute for Health and Care Excellence. Irritable bowel syndrome in
adults: diagnosis and management of irritable bowel syndrome in primary care.
CG61. London: National Institute for Health and Care Excellence, 2008.
2 Layer P et al. Z Gastroenterol 2011; 49: 237.
Disclosure of Interest: M. Plomer Other: Employee of Boehringer Ingelheim
Pharma GmbH&Co KG, Ingelheim, Germany, T. Weiser Other: Employee of
Boehringer Ingelheim Pharma GmbH&Co KG, Ingelheim, Germany, H.
Weigmann Other: Employee of Boehringer Ingelheim Pharma GmbH&Co
KG, Ingelheim, Germany, T. Muck Other: Employee of Boehringer Ingelheim
Pharma GmbH&Co KG, Ingelheim, Germany, M. Eberlin Other: Employee of
Boehringer Ingelheim Pharma GmbH&Co KG, Ingelheim, Germany, U. Kohler
Other: Employee of Boehringer Ingelheim Pharma GmbH&Co KG, Ingelheim,
Germany.
P1556 SAMPLE SIZE CALCULATION IN CONFIRMATORY TRIALS IN
IRRITABLE BOWEL SYNDROME WITH CONSTIPATION:
EXPERIENCE WITH LINACLOTIDE
M. Falques1,*, C. D az1, M. Moya1, D. Vilardell1, J. Fortea1, J.M. Johnston2
Almirall SA, Barcelona, Spain, 2Ironwood Pharmaceuticals, Cambridge, MA,
United States

INTRODUCTION: Calculation of sample size (SS) with sufficient power to


detect expected meaningful significant differences vs placebo is necessary for
the success of confirmatory pivotal trials in irritable bowel syndrome with constipation (IBS-C). Phase 2b trial data on linaclotide in IBS-C were used as a
benchmark to simulate different approaches for SS calculation in Phase 3 linaclotide trials to identify the best option for obtaining sufficiently powered results,
and to assess the corresponding power to reject the null hypothesis that no
difference in effect exists between active treatment and placebo.
AIMS & METHODS: Protocol design, patient population and endpoint assessments of a pilot Phase 2b (Trial 202) and two Phase 3 pivotal trials (Trial 302;
Trial 31) of linaclotide in IBS-C were compared. Two statistical assumptions for
the Phase 3 SS calculation for European Medicines Agency (EMA) co-primary
endpoints were compared: 1) replication of Phase 2b 290 mg/day results and 2)
minimally important clinical differences (MICD).
RESULTS: No relevant differences in protocol design or patient population were
identified in the Phase 2b/3 trials. For endpoint assessments, only the range of the
pain/discomfort scale differed (Phase 2b: range 1-5; Phase 3: range 0-10). For
both clinical endpoints, Phase 2b data showed a non-statistically significant
higher placebo effect and a non-statistically significant higher improvement
over placebo compared with Phase 3 data (Table). The SS for the Phase 3

A559

United European Gastroenterology Journal 2(1S)


Table to abstract P1556
Table Responder rates in Phase 2b/3 studies of linaclotide
Endpoint

Study

12-week abdominal pain or discomfort responder rate


Patient with 30% improvement from baseline in either
abdominal pain or abdominal
discomfort (with neither getting
worse) for 50% of the treatment period
12-week IBS degree-of-relief
responder rate
Patients who are considerably
relieved or completely relieved
(score 2/5) for 50% of the
treatment period

Phase 2b (Trial 202)


N169
Phase 3 (Trial 302)
N804
Phase 3 (Trial 31)
N800
Phase 2b (Trial 202)
N169
Phase 3 (Trial 302)
N804
Phase 3 (Trial 31)
N800

trials was estimated to have 95% power to detect a MICD of 15% in both coprimary endpoints. Based on replication of Phase 2b results for SS calculation
assumptions, an SS of 134 patients per treatment arm in Phase 3 trials would
have been sufficient to achieve 95% power to detect the expected efficacy (i.e.
comparable efficacy to Phase 2b). However, this SS would have only 46% and
67% overall power to detect the actual observed results of Trial 31 and Trial 302,
respectively, and even less overall power (13% and 47%, respectively) when the
MICD is reduced to 10%.
CONCLUSION: In the linaclotide IBS-C clinical programme, Phase 2b results
were not a good predictor of Phase 3 outcome, even without major differences in
study design. Caution should be exercised when calculating SS for Phase 3 pivotal trials in IBS-C to ensure sufficient power to detect clinically relevant differences vs placebo.
Disclosure of Interest: M. Falques Other: Employee Almirall SA, C. D az Other:
Employee Almirall SA, M. Moya Other: Employee Almirall SA, D. Vilardell
Other: Employee Almirall SA, J. Fortea Other: Employee Almirall SA, J.
Johnston Shareholder of: Ironwood Pharmaceuticals, Other: Employee
Ironwood Pharmaceuticals.
P1557 STATISTICAL APPROACHES TO MISSING DATA IN TRIALS OF
IRRITABLE BOWEL SYNDROME WITH CONSTIPATION:
EXPERIENCE WITH LINACLOTIDE
M. Falques1,*, C. D az1, M. Moya1, D. Vilardell1, J. Fortea1, J.M. Johnston2
1
Almirall SA, Barcelona, Spain, 2Ironwood Pharmaceuticals, Cambridge, MA,
United States
INTRODUCTION: Missing data may affect validity and interpretation of clinical trials and different statistical approaches for handling missing data may lead
to different conclusions. As patterns of missing data are often unknown until
unblinding, pre-planning the most appropriate method can be difficult but may
be guided by experience from similar trials in the same therapeutic area.
Information on handling missing data in trials in irritable bowel syndrome
with constipation (IBS-C) is limited.
AIMS & METHODS: This post-hoc analysis compared imputation methods for
missing data in 2 pivotal Phase 3 clinical trials of linaclotide in IBS-C. Both were
randomised, double-blind, placebo-controlled, multicentre trials of linaclotide
290g once-daily for 12 (Trial 31) or 26 weeks (Trial 302). Pre-specified
European Medicines Agency (EMA)-recommended co-primary endpoints were
(1) 12-week abdominal pain/discomfort responder rate (patients with 30%
reduction in abdominal pain and/or discomfort [11-point scales], with neither
worsening from baseline, for 6/12 weeks) and (2) 12-week IBS degree-ofrelief responder rate (patients with symptoms considerably/completely relieved
for 6/12 weeks). These endpoints were analysed using observed cases (OC), last
observation carried forward (LOCF), baseline observation carried forward
(BOCF), drop-out as non-responder and multiple imputation analysis.
RESULTS: In Trial 302, the different imputation methods for missing data
yielded results consistent with the initial OC approach for both co-primary endpoints (Table). Results were similar for Trial 31, with statistically significant
treatment differences for all imputation methods for both endpoints

Linaclotide 290
g/day (%)

Placebo
(%)

Delta

68

45

23 (P50.001)

54.11

38.46

15.65 (P50.0001)

54.81

41.77

13.04 (P0.0002)

47

21

26 (P50.0001)

39.40

16.63

22.77 (P50.0001)

37.04

18.48

18.56 (P50.0001)

(P50.0001 for all except for 12-week abdominal pain/discomfort responder:


OC, P 0.0002 and drop-out as non-responder, P 0.0056).
CONCLUSION: All five imputation methods for handling missing data yielded
non-biased results in both linaclotide Phase 3 IBS-C trials, supporting the robustness of linaclotide treatment effects on EMA endpoints. The approach that could
be considered to be the most conservative, if any, was drop-out as non-responder because using this method, the treatment effect estimates for both co-primary endpoints were numerically lower than those obtained by other methods.
Disclosure of Interest: M. Falques Other: Employee Almirall SA, C. D az Other:
Employee Almirall SA, M. Moya Other: Employee Almirall SA, D. Vilardell
Other: Employee Almirall SA, J. Fortea Other: Employee Almirall SA, J.
Johnston Shareholder of: Ironwood Pharmaceuticals, Other: Employee
Ironwood Pharmaceuticals.
P1558 REGION-SPECIFIC EFFECTS OF THE HERBAL MEDICINE STW
5 (IBEROGAST) AND ITS INDIVIDUAL EXTRACTS ON HUMAN
INTESTINAL MOTILITY
S. Allam1,*, D. Krueger1, O. Kelber2, I.E. Demir3, G. Ceyhan3, F. Zeller4,
M. Schemann1
1
Human Biology, TUM, Freising, 2steigerwald, Darmstadt, 3Surgery, TUM,
Munich, 4Surgery, Freising, Germany
Contact E-mail Address: shadyallam@yahoo.com
INTRODUCTION: The multiherbal drug STW5 (Iberogast a hydroethanolic
extract ofangelica, peppermint, liquorice, greater celandine, caraway, lemon
balm, chamomile, bittercandy tuft and milk thistle) is approved in Germany to
treat functional dyspepsia and IBS. Recently, we reported region-specific effects
in guinea pig and human stomach. Additionallywe demonstrated prosecretory
effects on human intestinal epithelium and proposed thatthese effects may be
involved in its clinical efficacy.
AIMS & METHODS: Now we investigated the effects ofSTW5 and its individual extracts on smooth muscle from different regions of human gut, alsoto
address its mode of action. Methods: We recorded changes in muscle strip activity due to STW5 in 575 circular (CM) orlongitudinal muscle (LM) strips of small
or large human intestine from 114 patientsundergoing abdominal surgery.
Measured parameters were muscle tone (MT) and phasiccontractions (Motility
index, MI).
RESULTS: STW5 induced significantly and dose dependently MT inhibition
(64-5120mg/ml). Relaxation was significantly higher in large vs. small intestine
and in CM vs. LM. STW5. At aconcentration of 5120mg/ml (which is still subtherapeutic) duodenum and jejunum (DJ) CMshowed comparable spasmolytic
effect compared to ileum CM (-5.52.2 vs. -6.81.1mNrespectively n 6,
p 0.6). However, they showed region-specific responses to MI reduction
(MI; -147.568.4mN/min, n 6, p 0.004 vs. -20.654.2mN/min, n 6,
p 0.6). MT relaxationof large intestinal CM was significantly higher than in
small intestine by 224.2% (n 12, p 0.01). In large intestinal CM STW5 changed the pattern of contractions into clusters with ahuge transient increase in MI
(MI; 292.4150.4 mN/min; n 11, p50.05) followed byinhibition of phasic
contractility. Apart from milk thistle and bitter candy tuft, all extractscontributed to inhibitory actions of STW5 on MT and MI of small intestine. G.

Table to abstract P1557


Table Imputation methods for Trial 302
12-week abdominal pain/discomfort
responder, n (%)

12-week IBS degree-of-relief


responder, n (%)

Analysis

Placebo
(N403)

Linaclotide
(N401)

; OR
(95% CI)

OC
LOCF
BOCF
Drop-out as non-responder
Multiple imputation approach

155
172
132
134
177

217
246
191
186
246

15.6;
18.7;
14.8;
13.1;
17.5;

(38.5)
(42.7)
(32.8)
(33.3)
(43.8)

(54.1)
(61.3)
(47.6)
(46.4)
(61.3)

1.89
2.15
1.88
1.75
2.05

(1.43;2.51)*
(1.62;2.85)*
(1.41;2.51)*
(1.31;2.33)*
(1.53;2.74)*

Placebo
(N403)

Linaclotide
(N401)

; OR
(95% CI)

67
74
68
65
70

158
174
158
139
167

22.8;
25.0;
22.5;
18.6;
24.3;

(16.6)
(18.4)
(16.9)
(16.1)
(17.4)

(39.4)
(43.4)
(39.4)
(34.7)
(41.7)

3.26
3.39
3.20
2.75
3.40

(2.34;4.53)*
(2.46;4.67)*
(2.30;4.44)*
(1.97;3.84)*
(2.42;4.76)*

A560
celandineincreased MI in DJ vs. reduction of ileum contractility (MI;
74.729.0mN/min, n 9, p 0.001vs. -76.620.7mN/min, n 7, p 0.001
respectively). In large intestine, additionally caraway had no influence on MT.
Peppermint, liquorice and angelica mimicked STW5 effect on MI. G. celandine
increased MT without affecting MI. STW5 effects on MT and MI were reduced
by blockade of TRPA1 channels (HC030031, by 50.4 and 74.0%, respectively),
SOCs blocker (SK&F96365, by 35.2% and 69.5%), and TRPC3 antagonist
(Pyr3, by 39.3% and 100.0%)(all 10mM).
CONCLUSION: Our experiments identified region and layer specific effects of
STW5 in human intestinal smooth muscle. The inhibitory effects were mediated by
a closure of SOCs belonging to the TRPC3/TRPA1 family, resulting in decreased
intracellular calcium levels. With the exception of milk thistle and iberis amara all
extracts contributed to the effects of STW5. Peppermint, angelica and liquorice
mimicked its inhibitory action on muscle activity. Due to the region and target
specific effects of STW5 and its components we propose a potential to treat motility
disorders of small and large intestine.
Disclosure of Interest: S. Allam: None declared, D. Krueger: None declared, O.
Kelber Other: Employee, I. E. Demir: None declared, G. Ceyhan: None declared,
F. Zeller: None declared, M. Schemann: None declared
P1559 REDUCED QUALITY OF LIFE (QOL) IN SUBJECTS WITH
IRRITABLE BOWEL SYNDROME (IBS) HOW COULD IT BE
IMPROVED?
V.L. Michalsen1,2,*, P.O. Vandvik2,3, P.G. Farup1,2
Faculty of Medicine, Norwegian University of Science and Technology,
Trondheim, 2Dept. of Medicine, Innlandet Hospital Trust, Gjvik, 3Faculty of
Medicine, University of Oslo, Oslo, Norway
Contact E-mail Address: pfarup@gmail.com
1

INTRODUCTION: Reduced Quality of Life (QoL) is common and often the


main problem for subjects with Irritable Bowel Syndrome (IBS), and treatment
should focus more on this problem to improve and individualize the treatment of
these patients.
AIMS & METHODS: This study aimed at finding predictors of reduced physical
and mental QoL in patients with IBS. Consecutive subjects with IBS (Rome II
criteria) in general practice were included in this cross-sectional study.
Information about gender, age (years), smoking habits (daily: yes/no), alcohol
(more or less than twice a week), education (more or less than 10 years), duration
of IBS (years), and severity of IBS-symptoms (a product of severity and frequency, score 0-12) were noted. Short Form 12 (SF12) was used for the measurement of physical QoL (SF-12 PCS, reference value 50) and mental QoL (SF-12
MCS, reference value 50). Somatic comorbidity was measured as the number of
organic diseases and unspecified organic symptoms with Subjective Health
Complaints 17 (SHC-17, reference value 6.2). Mental health complaints (anxiety,
depression and somatization) was measured with Hopkin Symptom Checklist 10
(SCL-10, score 1-4, reference value 5 1.85), hypochondria with Whiteley index
(WI, score 14-70, ref. value 5 40), and personality with Eysenck Personality
Questionnaire (EPQ) short form 10 with focus on neuroticism (score 0-10).
The study conforms to the principles of the Declaration of Helsinki and was
approved by the Norwegian Regional Committees for Medical and Health
Research Ethics. Results are given as mean (SD) or median (range), and multivariable analyses as partial correlation (pc) and p-values (p).
RESULTS: Out of 208 consecutive subjects with IBS, 149 were included in the
study. Demographics; age: 52 years (SD 15.3); women: 105 (70%); daily smokers:
49 (36%); alcohol  twice a week: 23 (17%); duration of IBS: 10 years (1-55); and
IBS symptom score: 2 (0-12). Somatic comorbidity: number of organic diseases: 2
(0-9); and SHC-17: 12 (0-42). Psychiatric comorbidity: SCL-10: 1.7 (1.0-3.8); WI:
25 (14-60); and EPQ: 4 (0-10). QoL: SF-12 PCS: 38.4 (11.9); and SF-12 MCS:
45.0 (11.3). Independent predictors (multivariable analyses) of high SF-12 PCS
were number of organic diseases (pc - 0.168; p 0.046) and SHC-17 (subjective
health complaints, pc - 0.304; p 5 0.001). Independent predictors of high SF12 MCS were SCL-10 (anxiety, depression and somatization, pc - 0. 421,
p50.001) and EPQ (neuroticism, pc - 0.174, p 0.050). Neither duration nor
severity of IBS symptoms was independent predictors of QoL.
CONCLUSION: Somatic comorbidity and subjective health complaints were
significant predictors of physical QoL, and anxiety/depression, somatization
and neuroticism were significant predictors of mental QoL. Neither duration
nor severity of IBS symptoms was associated with QoL. The study indicates
that treatment of patients with IBS and reduced QoL should focus more on
comorbidity than on IBS symptoms.
Disclosure of Interest: V. Michalsen: None declared, P. Vandvik: None declared,
P. Farup Consultancy for: Shire and Almirall.
P1560 FECAL CALPROTECTIN IN PREDICTING RECURRENCE AFTER
ATTACK OF COLONIC DIVERTICULITIS
A. Tursi1, W. Elisei2, M. Picchio3, L. Di Cesare4, P.G. Lecca4, G. Brandimarte4,*
Gastroenterology Service, ASL BAT, Andria, 2ASL Roma H, Division of
Gastroenterology, Albano Laziale (Roma), 3Division of Surgery, "P. Colombo"
Hospital, ASL Roma H, Velletri (Roma), 4Division of Internal Medicine and
Gastroenterology, "Cristo Re" Hospital, Rome, Italy
Contact E-mail Address: antotursi@tiscali.it
1

INTRODUCTION: Colonic diverticulitis shows a high recurrence rate, but the


role of fecal markers in predicting recurrence is unknown.
AIMS & METHODS: The aim of this study was to investigate the role of fecal
calprotectin (FC) in predicting recurrence of diverticulitis.
A prospective cohort study was performed on 54 patients suffering from Acute
Uncomplicated Diverticulitis (AUD) and treated with antibiotics to obtain remission.

United European Gastroenterology Journal 2(1S)


After remission, patients underwent to clinical follow-up every 2 months. During
the follow-up, C-reactive protein (CRP) and FC was analysed at each medical
control visit starting 2 weeks after the end of the antibiotic therapy. Recurrence
of diverticulitis was defined as return to our observation due to left lower quadrant pain with or without other symptoms (e.g. fever), associated with leucocytosis and/or increased CRP, and confirmed by means of Computerized
Tomography (CT).
RESULTS: The mean follow-up was 20 months (range 12-24 months). Fortyeight patients were available for the final evaluation, and 6 patients were lost to
follow-up.
During the follow-up, increased FC was detected in 17 (35.4%) patients.
Diverticulitis recurred in 8 (16.7%) patients: 7 (87.5%) patients showed increased
FC during the follow-up, and only 1 (12.5%) patient with recurrent diverticulitis
didnt show increased FC.
FC sensitivity, specificity, positive predictive value and negative predictive value
were 87.5%, 75.0%, 41.2%, and 96.8%, respectively.
Only higher FC values (460 g/g) correlated with CRP levels (rho 0.351, 95%
CI 0.163 to 0.5267; p 0.001). Finally, extension of diverticulosis showed correlation with FC expression (rho 0.632, 95% CI 0.515 to 0.791; p 0.000).
CONCLUSION: Increased FC was found to be predictive of diverticulitis
recurrence.
Disclosure of Interest: None declared
P1561 DEVELOPMENT AND VALIDATION OF AN ENDOSCOPIC
CLASSIFICATION OF DIVERTICULAR DISEASE OF THE COLON:
THE DICA CLASSIFICATION
A. Tursi1, G. Brandimarte2,*, F. Di Mario3, A. Andreoli4, M.L. Annunziata5,
M. Astegiano6, M.A. Bianco7, L. Buri8, G. Cammarota9, E. Capezzuto10,
F. Chilovi11, M. Cianci12, R. Conigliaro13, G. Del Favero14, L. Di Cesare2, M. Di
Fonzo2, W. Elisei15, R. Faggiani16, F. Farroni17, G. Forti18, B. Germana`19,
G. Giorgetti20, M. Giovannone21, P.G. Lecca2, S. Loperfido22, R. Marmo23,
G. Occhigrossi24, A. Penna25, A.F. Rossi26, A. Spadaccini27, C. Zampaletta16,
M. Zilli28, A. Zullo29, M. Picchio30
1
Gastroenterology Service, ASL BAT, Andria, 2UO di Medicina Interna, Servizio
di Endoscopia Digestiva, "Cristo Re" Hospital, Rome, 3Gastroenterology Division,
University of Parma, Parma, 4Hepatology Division, "San Camillo" Hospital,
5
Division of Gastroenterology, "Campus BioMedico" Hospital, Rome, 6Division of
Gastroenterology, "Molinette" Hospital, Torino, 7Gastroenterology Division, "T.
Maresca" Hospital, Torre del Greco (NA), 8Division of Gastropenterology and
Degistive Endoscopy, "Cattinara" Hospital, Trieste, 9Digestive Endoscopy Unit,
Catholic University, Rome, 10Division of Gastroenterology and Surgical
Endoscopy, "G. B. Grassi" Hospital, Ostia - Rome, 11Division of Gastroenterology,
Physiopathology and Digestive Endoscopy, Bolzano Hospital, Bolzano, 12Digestive
Endosocpy Unit, "Pierangeli" Home of Care, Pescara, 13Digestive Endoscopy Unit,
"SAntAgostino Estense" Hospital, Baggiovara (MO), 14Division of
Gastroenterology, ULSS 18, Rovigo, 15Gastroenterology Division, ASL Roma H,
Albano Laziale (Roma), 16Division of Gastroenterology, "Belcolle" Hospital,
Viterbo, 17Division of Gastroenterology, ASL3 Umbria, Foligno (PG), 18Digestive
Endoscopy Unit, "Santa Maria Goretti" Hospital, Latina, 19Division of
Gastroenterology, San Martino Hospital, Belluno, 20Digestive Endoscopy &
Nutrition Unit, "S. Eugenio" Hospital, Rome, 21Gastroenterology Division, S.
Camillo de Lellis Hospital, Rieti, 22Gastroenterology Service, AUSL Treviso,
Treviso, 23Division of Gastroenterology, Curto Hospital, Polla (SA), 24Division
of Gastroenterology and Digestive Endoscopy, "S. Pertini" Hospital, Rome,
25
Gastroenterology Division, "S. Paolo" Hospital, Bari, 26Division of
Gastroenterology and Interventional Endoscopy, Niguarda-Ca` Granda Hospital,
MIlano, 27Division of Gastroenterology and Digestive Endoscopy, "Padre Pio"
Hospital, Vasto (CH), 28Division of Gastroenterology, Santa Maria della
Misericordia Hospital, Udine, 29Division of Gastroenterology and Digestive
Endoscopy, Nuovo Regina Margherita Hospital, Rome, 30Division of Surgery,
"P. Colombo" Hospital, ASL Roma H, Velletri (Roma), Italy
INTRODUCTION: A validated endoscopic score on Diverticular disease (DD)
of the colon is lacking at present.
AIMS & METHODS: We developed a simple endoscopic score of DD, the
Diverticular Inflammation and Complication Assessment (DICA) score. The
DICA score for DD resulted in the sum of the scores for extension of diverticulosis (left and right colon), number of diverticula per district (up to 15 and 415
diverticula), presence and type of inflammation (edema, hyperemia, erosions),
and presence and type of complications (rigidity, pus, stenosis, bleeding): DICA 1
(up to 3 points); DICA 2 (score from 4 to 7 points); DICA 3 (over 7 points).
Videos of 70 consecutive patient at first diagnosis of DD were visualized during
plenary session and classified by endoscopists that did not know the DICA
classification.
Validation was carried out by estimating the correlation between DICA score
and symptoms, Erythro-Sedimentation Rate (ESR) and C-Reactive Protein
(CRP) expression. Finally, 50 videos of DD patients not involved in the development of DICA were reassessed in order to investigate the predictive role of
DICA on the outcome of the disease.
RESULTS: A total of 960 ratings were performed. Overall agreement in using DICA
was 0.847 (95% CI 0.812 to 0.893). It was 0.878 (95% CI 0.832 to 0.895) for DICA 1,
0.765 (95% CI 0.735 to 0.786) for DICA 2, and 0.891 (95% CI 0.845 to 0.7923) for
DICA 3. Intra-observer agreement kappa was 0.91 (95% CI 0.886 to 0.947).
A significant correlation was found between DICA score and both ESR
(p 0.0001) and CRP values (p 0.0001), as well as between median pain
score and DICA score (p 0.0001).
With respect to the 50 patients reassessed, recurrence or occurrence of disease
complications were recorded in 10 pts (34.5%) classified as DICA 1 and 19 pts
(65.5%) as DICA 2 (p 0.036).

A561

United European Gastroenterology Journal 2(1S)


CONCLUSION: Diverticular Inflammation and Complication Assessment
(DICA) score is a simple, reproducible, validated, and easy-to-use endoscopic
scoring system for diverticular disease of the colon.
Disclosure of Interest: None declared
P1562 POSSIBLE ASSOCIATIONS BETWEEN COLONIC DIVERTICULA
AND BOWEL HABITS: A MULTICENTER STUDY IN JAPAN
E. Uchida1,*, S. Uchiyama2, E. Yamada3, E. Sakai2, H. Ohkubo 2, T. Higurashi 2,
H. Endo2, M. Inamori 2, A. Nakajima 2
1
Chigasaki Municipal Hospital, 2Yokohama City University, 3Saiseikai Yokohama
South Hospital, Kanagawa, Japan
INTRODUCTION: The association of diverticula on bowel habits are unclear.
We therefore analyzed the association between diverticula and bowel habits in
over 1000 Japanese individuals.
AIMS & METHODS: Japanese subjects who underwent total colonoscopies at
seven centers in Japan from June to September 2013 were analyzed. Bowel habits
were evaluated using the Gastrointestinal Symptom Rating Scale, and stool form
was assessed using the Bristol Scale. Diverticula were diagnosed by colonoscopy
with a transparent soft-short hood.
RESULTS: The study evaluated 1066 subjects, 648 males and 418 females (ratio,
1.55:1), of mean age 63.9  13.0 years. After adjusting for age and gender, the
presence of constipation was associated with a significantly reduced likelihood of
diverticula (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.520.93,
p 0.0152). When assessed according to the location of diverticula, the presence
of constipation was associated with a significantly decreased likelihood of leftsided (OR 0.39, 95% CI 0.160.93, p 0.0338), but not right-sided (OR 1.10,
95% CI 0.48-2.53, p 0.8230), diverticula. Furthermore, stool form was unrelated with the presence or absence of diverticula.
CONCLUSION: The wide-spread hypothesis that hard, small caliber stools
could lead to colonic diverticula was not supported. Rather, we found that the
absence of diverticula was associated with constipation, suggesting the need to
reassess the etiology of colonic diverticula.
Disclosure of Interest: None declared

Disclosure of Interest: None declared


P1564 ARE ANTIPLATELET AGENTS OR HEMODIALYSIS RISK
FACTORS FOR COLONIC DIVERTICULAR RE-BLEEDING?
K. Sato1,*, N. Toda1, T. Yamada1, M. Yamagami1, K. Kojima1, T. Ohki1,
T. Arizumi1, M. Seki1, K. Tagawa1
1
Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan
Contact E-mail Address: s-koki@mitsuihosp.or.jp
INTRODUCTION: Colonic diverticular bleeding is frequently encountered, but
there have been few reports of its recurrence. In general, antiplatelet and hemodialysis are reported to be risk factors of gastrointestinal bleeding of various
situations.
AIMS & METHODS: The aim of this study was to identify risk factors for
diverticular rebreeding, especially whether antiplatelet and hemodialysis contributed or not.131 hospitalized patients, who were diagnosed with diverticular
bleeding on the basis of colonoscopy findings between April 2002 and May
2013, were analyzed. The cumulative bleeding recurrence rate and potential
risk factors for rebleeding, such as patient attributes (Age, sex, underlying conditions, and medication), treatment methods, were retrospectively investigated.
RESULTS: The 131 patients diagnosed with colonic diverticular bleeding
included 96 men (73 %) and 35 women (27 %). The mean age was 62.5  3.5
years, and the location of the diverticulum was the right colon in 31 cases, left
colon in 21 cases, and both sides in 79 cases. 57 patients used antiplatelets and 9
underwent hemodialysis for end-stage renal failure. The method of hemostasis
for first bleeding was clipping in 31 patients (23 %), local injection in 23 (17 %),
surgery in 2, and conservative treatment in 91 (69 %). Rebleeding was noted in 51
patients (38 %), with the mean period before recurrence being 54  30 months
(mean follow up periods: 43.538.5 months). By multivariate analysis, conservative treatment (hazard ratio, 2.57; p 0.02) is the only significant risk factor of
rebleeding. But antiplatelet (hazard ratio, 1.51; p 0.27) or hemodialysis (hazard
ratio, 1.05; p 0.94) were not significant.
CONCLUSION: In this study, antiplatelet or hemodyalysis were proven to be
not significant risk factors for colonic diverticular rebleeding. Conservative treatment was identified as only independent risk factor.
Disclosure of Interest: None declared

P1563 ARE CT SCAN BASED SCORING SYSTEMS OF ANY USE IN THE


PRACTICAL MANAGEMENT OF ACUTE DIVERTICULAR DISEASE?
K. Macconaill1,*, J. Downing1, D. Pai2, G. Kaur1
Surgery, 2Radiology, SCUNTHORPE GENERAL HOSPITAL, Scunthorpe,
United Kingdom
Contact E-mail Address: gkaur@email.com

INTRODUCTION: A large number of emergency patients are admitted with


complaints of pain in the left lower quadrant, fever, and soiling and labeled
acute diverticulitis. Contrast enhanced CT scans are the most important imaging modality for acute diverticular disease in todays clinical practice. A CT scan
can demonstrate an associated abscess and assist with direct percutaneous drainage. In the case of diverticular bleeding, CT angio may demonstrate a contrast
blush. Hinchey described a traditional classification for acute diverticulitis in
1978; since then, several CT based modifications have been presented to display a
more contemporary overview of the disease; these translate into management
strategies for the patient. However, not all patients admitted with left iliac
fossa pain undergo a CT scan; far fewer have CT scoring.
AIMS & METHODS: We aimed to look at patients diagnosed with acute
diverticulitis in our Hospital, with specific reference to CT scans, classification,
management and outcomes.
Methods: Data was retrospectively collected for all patients admitted with a
diagnosis of acute diverticulitis, during the period November 2013 to
February 2014. Data collected included CT scans, surgery/ radiological drainage,
outcomes etc. All CT scans were then reviewed by a single GI radiologist and
scored using a modified Hinchey scoring system.
RESULTS: 271 patients were identified with a diagnosis of acutediverticulitis; of
these, only 144 had had a CT scan. Of these, only 29 had a CT diagnosis of
diverticulitis, with no scoring used. On review by the GI radiologist, this number
further dwindled to 21. Of these, 18 had a modified Hinchey score assigned- 8
patients were IA, 5 were IB, 2 were II and 3 were III. 5 of these underwent
Hartmans procedure/ sigmoid colectomy. One patient was successfully managed
with CT guided drainage, while 1 underwent attempted drainage. There was no
mortality. Of the 24 patients with an original CT diagnosis of diverticulitis who
did not undergo surgery/ drainage, 15 were followed up with a colonoscopy later.
CONCLUSION: Since the introduction of the CT in the 1980s, this imaging
modality has established itself as the primary diagnostic tool in the assessment
of diverticular disease, leading on to the use of new treatment strategies, such as
CT-guided percutaneous drainage of abscesses. A good CT scan based classification system of acute diverticular disease helps guide clinical decision making and
management; unfortunately, we found this lacked a translation into daily clinical
practice. Many patients with diverticulosis were therefore unnecessarily treated
as acute diverticulitis; fortunately, pelvic abscesses, purulent and fecal peritonitis
were accurately diagnosed clinically and managed appropriately. We emphasise
the importance of performing a CT scan at acute presentation of diverticular
disease to diagnose/ rule out/ manage complicated disease; this baseline scan is
also crucial if the patient deteriorates during conservative treatment.

P1565 THE PRESENCE OF DIVERTICULOSIS


ASSOCIATED WITH POLYP DETECTION RATE

IS

NEGATIVELY

R. Gingold-Belfer1,*, A. Geller1, A. Vilkin1, Y. Kelner1, D. Comanester2, Y. Niv1,


Z. Levi1
1
Gastroenterology Department, Rabin Medical Center, Petah Tikva, 2Statistics
department, Clalit Research Institute, Tel Aviv, Israel
Contact E-mail Address: rachelgingoldbelfer@gmail.com
INTRODUCTION: The association between diverticulosis and colorectal cancer
(CRC) is controversial, since some of the data indicated a positive association,
whereas some studies could not confirm this. Addressing this issue is very important since finding an association between diverticulosis and CRC may have
implications for CRC prevention.
AIMS & METHODS: Therefore, we aimed to examine the association between
the presence of diverticulosis and polyp detection rate (PDR).
Methods: We included 13,554 subjects aged 50 years and above (mean
65.410.3y) who underwent their first colonoscopy with acceptable preparation
at our endoscopy unit between the years 2003-2010. Multivariable logistic regression analysis including the patients age and gender, the examination hour, the
quality of preparation and the presence of diverticulosis, were carried out to
assess the association between diverticulosis and the presence of the polyps
that were detected.
RESULTS: Polyp was detected in 4,667 (34.4%) subjects and increased from
26.2% at age 50-54y to 38.3% at age 84y. Diverticulosis was reported in
2,229 (16.4%), and increased from 6.9% at age 50-54 to 32.8% at age 84y.
Both diverticulosis and PDR were increased significantly with age (p50.001 for
both). Among 11,325 subjects without diverticulosis, 4,048 (35.7%) had polyps,
as compared to 2,029 subjects with diverticulosis, out of them only 619 (27.8%)
had polyps (p50.001). Using multivariable logistic regression analysis the presence of diverticulosis was negatively associated with PDR, (OR: 0.60 95% confidence interval 0.53-0.66, p50.001). An older age, male gender and the
preparation quality were all significantly associated with PDR.
CONCLUSION: Although both diverticulosis and PDR were increased with age,
the presence of diverticulosis was negatively associated with PDR. Whether this
finding reflects a true phenomenon or could the presence of diverticulosis interferes with detecting polyps, should be further investigated.
REFERENCES
1. Rondagh EJ, Sanduleanu S, le Clercq CM, et al. Diverticulosis and colorectal
polyps at younger age: a possible link? Eur J Gastroenterol Hepatol 2011; 23:
1050-1055.
2. Kieff BJ, Eckert GJ and Imperiale TF. Is diverticulosis associated with colorectal neoplasia? A cross-sectional colonoscopic study. Am J Gastroenterol 2004;
99: 2007-2011.
Disclosure of Interest: None declared

A562

United European Gastroenterology Journal 2(1S)

P1566 ASSOCIATION BETWEEN THE LOCATION OF DIVERTICULAR


DISEASE AND IRRITABLE BOWEL SYNDROME: A MULTICENTER
STUDY IN JAPAN
S. Uchiyama1,*, E. Yamada1, A. Fuyuki1, S. Umezawa1, T. Higurashi1, E. Sakai1,
H. Ohkubo1, H. Endo1, H. Takahashi1, A. Nakajima1
1
Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan
INTRODUCTION: No previous reports have shown an association between
location of diverticular disease (DD) and irritable bowel syndrome (IBS).
AIMS & METHODS: We included 1009 consecutive patients undergoing total
colonoscopy in 7 centers in Japan from June 2013 to September 2013. IBS was
diagnosed using Rome III criteria and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid
colon, descending colon, and rectum. Right-sided colon was defined as cecum,
ascending colon, and transverse colon. We divided the patients into IBS and nonIBS groups and compared characteristics.
RESULTS: Patient characteristics included: mean age, 64.2  12.9 years and
male: female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects.
Left-sided and bilateral DD was identified in 6.6% and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis
showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI), 1.47.1;
P 0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.35.2; P 0.0070) were
independent risk factors for IBS. Right-sided DD was not a risk factor for IBS.
CONCLUSION: Our data showed that the presence of left-sided and bilateral
DD, but not right-sided disease, were associated with a higher risk of IBS,
indicating that differences in pathological factors caused by the location of the
DD is important in the development of IBS. Clarifying the specific changes
associated with left-sided DD could lead to elucidation of the pathogenesis of
IBS.
Disclosure of Interest: None declared
P1567 NSAIDS, HYPERURICEMIA, AND CARDIOVASCULAR DISEASE
WERE INDEPENDENT RISK FACTORS FOR DIVERTICULAR
BLEEDING: ANALYSIS BY MATCHED CASE CONTROL STUDY
1,*

Y. Sugihara , S.-E. Kudo , H. Miyachi , M. Misawa , A. Yamauchi , Y. Mori ,


T. Kudo1, N. Ogata1, T. Hisayuki1, K. Kodama1, J. Ukegawa1, K. Wakamura1,
T. Hayashi1, F. Ishida1, H. Inoue1, S. Okoshi1
1
Digestive disease center, Showa University Northern Yokohama Hospital,
Yokohama, Japan
Contact E-mail Address: y.sugi117@gmail.com
INTRODUCTION: Colonic diverticulum is one of the common diseases especially in elderly patients. However diverticular bleeding occasionally causes massive bleeding that requires urgent colonoscopy (CS) and treatment.
AIMS & METHODS: The aim of this study is to clarify the significant risk
factors for the diverticular hemorrhage in the colorectum.
Between January 2009 and December 2012, 26602 patients had a CS in our
institution. One hundred twenty three patients had an urgent CS with the symptom of acute lower gastrointestinal hemorrhage. Seventy-two (72) patients of
them received diagnosis with colonic diverticular hemorrhage. Age and sex
matched 149 controls were selected from non-bleeding diverticulum patients
who underwent CS by other reasons during the same period. The information
checked were included the presence of cerebrovascular disease, ischemic heart
disease, hypertension, hyperlipidemia, diabetes mellitus, chronic renal disease,
osteoporosis, hyperuricemia. The information also contained medication including NSAIDs, antithrombotic agents. The relationship between these factors and
diverticular bleeding were compared between cases and controls.
RESULTS: Among the 123 patients, 72 patients were diagnosed as colonic
hemorrhage caused by colon diverticular. Age range of patients was from 33
years to 93 years old (average7012.8). Sex ratio of men versus women of
patients was 51:21. In the result of the univariate analysis, the factors of cerebrovascular disease, hypertension, hyperuricemia, chronic renal disease and
usage of antithrombotic agents, and NSAIDs were significant to increase of
ORs. Using these factors, we performed multivariate conditional logistic regression with stepwise variable selection. Finally, present usage of NSAIDs
(OR 14.70, 95% CI: 3.890-55.800, P50.0001), cerebrovascular disease
(OR 8.66, 95% CI: 2.330-32.100, p 0.00126), and hyperuricemia
(OR 15.5, 95% CI: 1.740-138.000, p 0.014) remained statistically significant.
CONCLUSION: This study indicated the present usage of NSAIDs, cerebrovascular disease, and hyperuricemia were significant risk factors for colonic diverticular hemorrhage. The knowledge obtained by this study may give some insight
in the diagnostic process for the patients with acute lower gastrointestinal
bleeding.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


NERVE GUT AND MOTILITY
XL_____________________

III

POSTER

EXHIBITION

9:0014:00
HALL

P1568 ENDOFLIP: A NEW DIAGNOSTIC MODALITY FOR MEASURING


ANAL CANAL FUNCTION
L. Kumar1,1,*, F. Zaman1, A. Emmanuel1
1
GI Physiology Unit, UCLH, London, United Kingdom
INTRODUCTION: Anorectal manometry is a commonly used technique to
assess patients with fecal incontinence, but is known to have low reproducibility
and poor validation in assessment of anal sphincter function. We report a pilot
study on a novel technique using Functional Lumen Imaging Probe (FLIP) to

improve assessment. Although FLIP has been used in upper GI studies its use in
anorectal region is limited to three published studies, all of which used a 12 cm
probe (as in upper GI studies). We used a purpose built shorter catheter to
demonstrate bio-mechanical properties of the anus.
AIMS & METHODS: Aims: Primary objective was to demonstrate reproducibility of measurement taken by EndoFLIP. Secondary objective was to demonstarte its utility in assessment of anal canal. Methods: 19 healthy volunteers were
recruited (9 females), mean age 34 (20-75). Catheters were purpose built, incorporating a rectal and anal canal balloon (three different sizes 2, 3 and 4cm long).
Appropriate sized catheter corresponding to the length of subjects anal canal
(based on manometry) was used. Participants underwent standard water-perfused anal manometry followed by FLIP on the same day. To test repeatability
the FLIP was repeated after 30 minutes on the same day. The parameters
checked for repeatability included CSA during rest, squeeze, endurance squeeze
and cough in addition to the intra balloon pressure during these phases. Anal
canal was divided into three parts- distal, mid and proximal based on anatomy
and preliminary data analysis. There were different inflation volumes used,
according to the balloon size, determined by analysing the pre-study test results.
RESULTS: 3 cross sectional area (CSA) readings were obtained with 2cm balloon, 5 with 3cm and 10 with 4cm balloon. Study established the test-retest and
intra-observer repeatability for CSA using Bland-Altman plot and Intra-class
correlation coefficient (ICC). Pearson correlation coefficient (PCC) was used to
establish a correlation between CSA and pressure.
Bland Altmans plots showed measurement points for all parameters to be within
2 SD of line of equality. ICC calculated individually for each part of anal canal
showed high levels of repeatability for CSA measurements (Table 1). Pressure
readings were also repeatable (Table 1). Pearson correlation coefficient esablished a negative correlation between CSA and pressure during resting phase,
at all the balloon volumes apart from the highest.

Measured phase

ICC for
proximal
anal canal

ICC for
proximal
anal canal

ICC for
proximal
anal canal

ICC for
pressure
readings

Resting
Squeeze
Cough
Endurance squeeze

.960
.978
.970
.965

.960
.960
.970
.960

.928
.919
.943
.937

.806
.776
.867
.868

Table 1
CONCLUSION: By allowing determination of serial CSAs during distension
EndoFLIP allows detailed and segmental description of geometric and mechanical properties of the anal canal. The CSA and intra balloon pressure were
repeatable and lower CSA was associated with higher pressure across all balloon
volumes apart from the highest. Most likely cause for this was excessive distension of anal canal at higher balloon volumes. Validity and repeatability of
EndoFLIP have been demonstrated by this study and future work will assess
its utility in patients with faecal incontinence.
Disclosure of Interest: None declared
P1569 PERCUTANEOUS
TIBIAL
NERVE
STIMULATION
INEFFECTIVE FOR PATIENTS WITH CONSTIPATION

IS

L. Kumar1,*, A. Alam1, V. Aikins1, A. Raeburn1, A. Emmanuel1


1
GI Physiology Unit, UCLH, London, United Kingdom
Contact E-mail Address: l.kumar@ucl.ac.uk
INTRODUCTION: The efficacy of percutaneous tibial nerve stimulation
(PTNS) in faecal incontinence has been well proven. However its value in managing constipation has not been studied. Current literature search (Pubmed &
Embase) brings up only one study assessing its effect in managing constipation.
Chronic constipation can be aetiopathogenically classified into slow transit
(STC), rectal evacuation difficulty (RED) or a combination (BOTH). We studied
the effects of PTNS in these patient subgroups.
AIMS & METHODS: Aims: We aimed to evaluate the effectiveness of PTNS in
patients with range of constipation aetiologies by measuring change in wexner
score, atransit study and anorectal physiology. Methods: 34 patients (30 women,
median age 50 years, range 20-79) with constipation previously failing maximal
laxative and biofeedback therapy participated in the study. All patients underwent baseline transit study and anorectal physiology to identify constipation
subtype. All patients had 12 sessions of 30 minutes of PTNS. Responder rate
(judged by Wexner constipation score fall to 15 or by 5points) was the primary outcome. Transit study and anorectal physiology were evaluated posttreatment.
RESULTS: There were 11 STC, 14 RED and 9 BOTH patients. Response was
seen in 5 patients (2/11 STC, 2/14 RED and 1/9 BOTH). Comparing pre- vs postPTNS, change in mean wexner scores was not significant (p 0.10). There was no
change in colonic transit time in the whole population (p 0.56) or those with
STC (p 0.47). Balloon expulsion did not significantly improve in the whole
group (p 0.73) or those with RED (p 0.69).
CONCLUSION: The data available from single study done so far, evaluating
PTNS response in constipation, demonstrated a response rate of 33% based on
reduction of improvement in constipation score of  5 points. However, this was
not replicated in our study which had a response rate of only 15% based on the
same criteria. Common finding in both the studies was a lack of improvement in
transit time. Percutaneous tibial nerve stimulation is not of benefit in patients
with constipation, whatever aetiopathogenic mechanism is responsible for their
symptoms.
Disclosure of Interest: None declared

A563

United European Gastroenterology Journal 2(1S)


P1570 RECTAL HYPOSENSITIVITY TO BALLOON DISTENSION IS
INFLUENCED BY RATE OF INFLATION
L. Kumar1,*, J. Gosling1, A. Raeburn1, A. Emmanuel1
1
GI Physiology Unit, UCLH, London, United Kingdom
INTRODUCTION: Impaired rectal sensation to mechanical distension, rectal
hyposensitivity (RH), has been suggested to be causally linked to constipation
in a quarter of patients. Although the exact mechanism of rectal distension
sensitivity remains uncertain it is postulated to relate to populations of slowand fast- adapting mechanoreceptor populations in the rectal wall. In clinical
practice the measurement is elicited by manual inflation of a balloon, rather than
the more predictable (but cumbersome) use of barostat-driven inflation.
Interventions such as behavioural retraining, neuromodulation and rectal surgery
have suggested that normalising distension volume thresholds, is a desirable
biomarker of treatment outcome. In an attempt to standardise protocols, we
conducted a study to investigate the influence of rate of ramp rectal distension
on volume thresholds.
AIMS & METHODS: Aims - To investigate the influence of rate of ramp rectal
distension on rectal volume thresholds. Methods: We studied 49 patients (42
female, mean age 40 [21-74]) and 23 asymptomatic controls (18 female, mean
age 36 [22-60]). Patients underwent transit studies and MR proctography, and
accordingly stratified in to slow transit, ST (n 18, 15 female, mean age 38 [2160]) and puborectalis dyssynergia, PD (n 21, 16 female, mean age 41 [23-74]):
10 patients had combined abnormalities and were excluded from further analysis.
The participants underwent anorectal physiology test in the following sequence:
rectal distension manometry RAIR expulsion rectal distension. Rectal
distension was done by hand at rate of 1ml/sec and 5ml/sec in random order.
Patients were asked to report first sensory awareness, urge to defaecate and
maximal tolerable thresholds.
RESULTS: Results are shown in the table. There was no order effect, and no
difference in thresholds between constipation subtypes. At 1ml/sec distension 5/
18 and 6/21 ST and PD patients, respectively, were determined to have rectal
hyposensitivity; this fell to 1/18 and 1/21 at 5ml/sec. Amongst controls 4 had
elevated volumes at 1ml/sec and none at 5ml/sec.

FS in
FS in
FS in
DDV
DDV
DDV
MTV
MTV
MTV

healthy controls (n 23)


slow transit (n 18)
puborectalis dyssynergia (n 21)
in healthy controls (n 23)
in slow transit (n 18)
in puborectalis dyssynergia (n 21)
in healthy controls (n 23)
in slow transit (n 18)
in puborectalis dyssynergia (n 21)

1ml/sec

5ml/sec

p value

115
142
131
165
202
189
304
349
333

49 23
71 33
78 34
91 37
129 49
128 51
202 93
221 101
223 105

0.01
0.04
0.07
0.08
0.03
0.05
0.03
0.03
0.05

 61
64
74
79
87
90
111
150
145

CONCLUSION: We have shown a significant difference in thresholds between


slow and rapid distension rates. Slower rate of distension was associated with
higher thresholds across all the three sensory volumes. Rectal hyposensitivity is
identified less often at more rapid distension rate. Distension rates play a crucial
part in diagnosing RH and standardised of protocol is required in future studies.
Disclosure of Interest: None declared
P1571 DIMINISHED
THE
UPPER-GUT
MOTILITY
AND
ENTEROHORMONES LEVEL IN THE CELIAC DISEASE PATIENTS
M. Zwolinska-Wcislo1,*, M. Przybylska- Felus 2, A. Furgala 3, J. KaszubaZwoinska3, P. Thor 3, T. Mach 2
1
Institute of Clinical Dietetics Dept. of Gastroenterology and Hepatology, 2Dept. of
Gastroenterology and Hepatology, 3Dept. of Patophysiology, Jagiellonian
University Collegium Medicum, Krakow, Poland
Contact E-mail Address: mzwcislo@su.krakow.pl
INTRODUCTION: The chronic inflammation in gastrointestinal tract in celiac
disease (CD) patients may cause alterations of the upper-gut motility. The aim of
study was to investigate the influence of CD on the upper-gut motility and release
of enterohormones.
AIMS & METHODS: We studied 25 CD patients (8 males, 17 females, aged
42.415.8 years). CD was diagnosed by serological (serum level of anti-endomysial antibodies) and histological evaluation of duodenal mucosa. The gastric
myoelectric activities (EGG), performed by 4-channels electrogastrography,
were measured in fasted and fed subjects. The ghrelin and pancreatic polypeptide
(PP) plasma level were measured. The results obtained were compared with a
healthy, asymptomatic control group (9 males and 21 females, aged 42.1  9.2
years).
RESULTS: Fasting CD patients showed decreased parameters of % of normogastria (54.824.5 vs. 8612.3, p 0.02) and SWC (61.117 vs. 6718, p 0.01)
with increased dominant power (log DP) (13.31 vs. 11.11.1, p 0.0001) compared to control group. In fed CD patients: % of normogastria, log DP, dominant frequency (DF), slow wave coupling (SWC) did not improve on the
contrary for the control group in which log DP, DF, SWC and percent of
normogastria increased (p50.05). Fasting ghrelin plasma level was lower in
CD in comparison to control group 156.886.7 pg/ml vs 260.287.6 pg/ml
(p50.05) but PP level was higher 265.2123.1 pg/ml vs 211.4114.6 pg/ml
(p50.05) consequently.

CONCLUSION: CD causes subsequent disturbances of gastric myoelectric


activity and fasting enterohormones levels. CD patients demonstrated diminished
response to food. Observed diminished responsiveness suggests dysfunction of
autonomic nervous system as common pathophysiological mechanisms.
Disclosure of Interest: None declared
P1572 INVESTIGATION OF DYSPHAGIA AND REFLUX SYMPTOMS
AFTER ANTIREFLUX SURGERY BY HIGH RESOLUTION
MANOMETRY: IMPACT OF MULTIPLE WATER SWALLOWS AND
A SOLID TEST MEAL ON DIAGNOSIS, MANAGEMENT AND
CLINICAL OUTCOME
M. Fox1,*, Y.T. Wang2, A. Saqib3, M. Kasi4, L.F. Tai5, E. Yazaki2, J. Jafari5,
R. Sweis6, E. Tucker5, K. Knowles5, J. Wright5, K. Hamlett7, D. Sifrim2
1
Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich,
Switzerland, 2Division of Gastroenterology and Hepatology, Barts and London,
London, 3Division of Gastroenterology and Hepatology, Nottingham University
Hospital, 4Division of Gastroenterology and Hepatology, NUH, Nottingham,
5
Division of Gastroenterology and Hepatology, NIHR, Notts, 6Division of
Gastroenterology and Hepatology, St Thomas, London, 7NIHR, Notts, United
Kingdom
Contact E-mail Address: dr.mark.fox@gmail.com
INTRODUCTION: Management of patients with persistent dysphagia and / or
recurrent reflux after anti-reflux surgery is challenging 1,2. This prospective, casecontrol study tested the hypothesis that, compared to standard high resolution
manometry (HRM) with single water swallows (SWS), adding multiple water
swallows (MWS) and solid swallows increase diagnostic yield and clinical
impact of physiological investigation after fundoplication surgery.
AIMS & METHODS: 57 symptomatic and 12 asymptomatic control patients
underwent HRM with SWS, MWS and a solid test meal. Diagnostic yield of
standard and full HRM studies with 24hr pH-impedance monitoring was compared. Clinical outcome of pneumatic dilatation for outlet obstruction on HRM
studies was assessed on an analogue scale from inadequate 540%, satisfactory
40-60%, good 60-80% to excellent 480% improvement. A satisfactory
response was defined by a clear improvement in symptoms from baseline to a
level where no further treatment was necessary.
RESULTS: Baseline EGJ pressure was similar in all groups. Abnormal EGJ
morphology (double high pressure band) was more common in symptomatic
than control patients (13/57 vs. 0/12; p 0.004). Overall diagnostic yield of HRM
was 11 (19%), 11 (19%) and 33/57 (58%) with SWS, MWS and solids respectively (p50.001), being greatest for solids in patients with dysphagia (19/27
(70%)), see table. Outlet obstruction was present in 4 (7%), 11 (19%) and 15/
57 (26%) patients with SWS, MWS and solids respectively (p50.009). Note that
4 patients that presented with reflux had outlet obstruction on HRM and negative pH-impedance studies. No asymptomatic control had clinically relevant
dysfunction on solid swallows. Dilatation was performed in 12/15 patients with
symptomatic outlet obstruction during the test meal. Symptom response was
satisfactory, good or excellent in 7/12 (58%) with no serious complications.
Table: Diagnosis based on SWS and solid test meal (*p50.05, ** p50.01)

Main Symptom
Dysphagia n 27

SWS
Meal
Reflux n 30
SWS
Meal
14 (46%)**
0 (0%)
4 (13%)
Asymptomatic n 12 SWS
Meal

Overall
HRM

Outlet
Peristaltic
Functional
Obstruction Dysfunction Reflux (no cause)

8 (30%)
4 (15%)
19 (70%)** 11 (41%)*
3 (10%)

4 (15%)
8 (29%)

3 (10%)
10 (33%)*
1 (8%)
0 (0%)

17 (57%)
9 (30%)*
1 (8%)
0 (0%)

10 (33%)
0 (0%)
0 (0%)

2 (7%) 17 (63%)
6 (22%)**

0 (0%) n/a

CONCLUSION: The addition of MWS and a solid test meal increases the diagnostic yield of HRM studies in patients with symptoms post-fundoplication and
identifies additional patients with clinically relevant, symptomatic esophageal
dysfunction. This includes patients with outlet obstruction post-fundoplication
that benefit from endoscopic dilatation.
REFERENCES
1. Pessaux P, et al. Arch Surg 2005; 140: 946-951.
2. Broeders JA, et al. Ann Surg 2009; 250: 698-706.
Disclosure of Interest: None declared
P1573 THE ASSOCIATION OF SOMATIZATION WITH IRRITABLE
BOWEL SYNDROME (IBS) AND UNINVESTIGATED DYSPEPSIA
IN THE U. S. GENERAL POPULATION
O. Palsson1,*, M.van Tilburg1, W.E. Whitehead1
Department of Medicine, Division of Gastroenterology and Hepatology,
University of North Carolina, Chapel Hill, United States
Contact E-mail Address: opalsson@med.unc.edu
1

INTRODUCTION: Multiple studies have reported elevated somatization, i.e.,


excess frequency of general non-gastrointestinal physical symptoms, in clinical
samples of IBS and functional dyspepsia (FD) patients. Much less is known
about whether somatization is associated with these disorders in the general
community.
AIMS & METHODS: Data from a nationwide U. S. internet survey of 1,665
adults were used to assess somatization in FD and IBS in the general population.
The survey included the validated Recent Physical Symptoms Inventory (RPSQ)

A564
developed by our team to measure somatization in IBS (MacLean et al. J
Psychosom Res. 2012;73 (5):351-5), the SF-12 quality of life scale, the Rome
III Diagnostic Questionnaire with new validated response formats
(Gastroenterology 2013;144 (5) Suppl.1:S-916) planned for Rome IV, and demographic and health history questions. Responders providing inconsistent survey
answers on 3 repeated quality-check questions were excluded from analysis,
leaving 1277 response sets. Somatization scores were calculated as the number
of different non-GI symptoms (out of the 26 on the RPSQ) experienced more
than once in the past month.
RESULTS: The analysis sample was 648 females and 629 males; 701 white, 218
black, 240 hispanic and 118 other or undeclared race/ethnicity. Mean age was
46.4 years (range 18-94). A total of 91 individuals (7.1%) met Rome III IBS
criteria (after subjects with organic bowel diagnoses were excluded), 146 (11.4%)
met FD criteria, and 57 (4.5%) met both criteria. Mean somatization score was
twice as high (p50.0001) in subjects with IBS (Mean /- SD: 14.1 /- 6.4) and
FD (13.1 /- 6.7) compared to those qualifying for neither diagnosis (6.5 /5.7). These subgroup differences were significant even when all individuals
reporting physician diagnosis of any upper or lower GI disorders were removed
from the analysis, and were found within every race/ethnicity, gender and age
group. Whole sample analysis showed that somatization scores were significantly
correlated with frequency of each of the key gastrointestinal symptoms defining
FD and IBS, including pain anywhere in the abdomen (r 0.50), uncomfortable
fullness after meals (r 0.49), pain/burning in the middle of the abdomen
(r 0.41), and frequency of hard (r 0.38) and loose (r 0.38) stools; all correlations p50.01. All 26 non-GI symptoms of the RPSQ were significantly more
prevalent in IBS and FD than in other subjects, even after controlling for multiple comparisons. The most common non-GI symptoms were the same in IBS and
FD: Sleep difficulties (IBS 86%,FD 74%), muscle aches (82%,78%), back
pain (81%,75%), headaches (79%,76%), and muscle stiffness (66%,60%).
Excess somatization (score above 95th percentile in the comparison subjects
meeting neither disorder criteria) was seen in 42.9% of IBS and 30.8% of FD
cases. For both IBS and FD, somatization was negatively correlated (p50.01)
with the physical (r -0.51, -0.42) and mental (r -0.35, -0.32) composite SF-12
quality-of-life scales.
CONCLUSION: Increased somatization (excess number of general non-GI
symptoms) is robustly associated with both FD and IBS not only in clinic samples but also in the general population, and is seen across all gender, race and age
groups. Somatization tendency is associated with higher frequency of functional
GI symptoms and impairment in quality of life. [Supported by funding from the
Rome Foundation]
Disclosure of Interest: None declared
P1574 DOES
PERCEIVED
STIGMA
AFFECT
HEALTHCARE
CONSULTING AND QUALITY OF LIFE IN FECAL INCONTINENCE?
O. Palsson1,*, S. Heymen1, W.E. Whitehead1
Department of Medicine, Division of Gastroenterology and Hepatology,
University of North Carolina, Chapel Hill, United States
Contact E-mail Address: opalsson@med.unc.edu
1

INTRODUCTION: Fecal incontinence (FI) is a sensitive social topic, but it is


unknown to what degree the perceived stigma of the condition impairs the quality of life (QoL) of FI sufferers or contributes to the common avoidance of
healthcare-seeking for the problem.
AIMS & METHODS: We aimed to quantify the associations of perceived FI
stigma with QoL impairment and the tendency to consult doctors about FI. A
validated Perceived Stigma Scale (PSS) developed to measure gastrointestinal
illness stigma and previously used (Taft et al Qual Life Res 2011;20:1391
1399) in irritable bowel syndrome and inflammatory bowel disease was adapted
for FI (FI-PSS). Subjects indicate for each of 10 questions how often on a 5-point
frequency scale from 0 Never to 4 Always they perceive potential or
actual FI-associated stigma (like concerns that they would be treated differently
or their opportunities limited if people knew about their FI) from six categories
of people in their life; family members, friends, significant others, healthcare
workers, coworkers and boss/supervisor. A nationwide U. S. internet survey
that included the FI-PSS, Fecal Incontinence Quality of Life (FI-QOL), Fecal
Incontinence Severity Index (FISI) and demographic questionnaires was completed by 234 adults with FI (defined as accidental loss of liquid or solid stool at
least once a month in the past 6 months). Subjects who responded inconsistently
(n 48) on either of two repeated quality-check questions were excluded from
analysis, leaving 186 response sets for analysis.
RESULTS: The 186 FI subjects were 52.2% female. Race/ethnicity was 82.8%
white, 9.1% hispanic, and 8.1% black. Subject ages ranged from 20-91; 39.2%
under age 40, 38.2% ages 40-65, and 22.6% age 65. Nearly all subjects (93.5%)
reported some perceived FI-related social stigma on the FI-PSS; least stigma was
perceived from healthcare providers (mean score 15.6) and most from co-workers
and employers (mean score 21.5 for both). Respondents who had consulted
doctors about their FI (55.4% of the sample) had substantially greater FI severity
(FISI mean /- SD: 39.5 /- 15.7 vs. 18.0 /- 10.2) and higher perceived FI-PSS
stigma scores (118.3 /- 51.9 vs. 91.1 /- 51.5) than non-consulters, and were
also younger, more educated and more affluent (p50.0001 for all comparisons).
However, when these variables were combined in a binary logistic regression
equation, FI severity was the only significant predictor of consulting doctors
for FI, explaining 53% of the variance (Nagelkerke R2 0.53). FI-QOL scores
(higher score better QoL) were negatively correlated with FI severity (Pearson
r -0.73), stigma scores (r -0.51), younger age (r -0.37), education (r -0.28)
and household income (r -0.36). When these were all combined in a linear
regression equation, FI severity was the only significant contributor to the
56% total variance in QoL scores explained (adjusted R2 0.56).
CONCLUSION: Perceived stigma is pervasive among FI sufferers. It is robustly
associated with symptom severity, but it does not seem to be associated with

United European Gastroenterology Journal 2(1S)


avoidance of healthcare consultation for FI nor to have an independent effect on
quality of life. [Supported by a research grant from Salix Pharmaceuticals]
Disclosure of Interest: O. Palsson Financial support for research from: Salix
Pharmaceuticals, S. Heymen Financial support for research from: Salix
Pharmaceuticals, W. Whitehead Financial support for research from: Salix
Pharmaceuticals.
P1575 NEUROTRANSMITTER CONCENTRATION IN PREGENUAL
ACC IN STOOL CONSISTENCY PATIENT SUBGROUPS WITH IBS
O. Bednarska1,*, S. Tapper2,3, P. Lundberg2,3, A. Tisell2,3, M. Lowen1,
M. Engstrom2,3, S. Walter1,3
1
Institution for Clinical and Experimental medicine (IKE), Gastroenterology,
2
Department of Radiation Physics, and Department of Medical and Health
Sciences, 3Center for Medical Image Science and Visualization (CMIV),
Linkoping University, Linkoping, Sweden
Contact E-mail Address: susanna.walter@liu.se
INTRODUCTION: The Anterior Cingulate Cortex (ACC) is a key region of the
central autonomic brain network. Irritable Bowel Syndrome (IBS) is characterized abdominal pain and bowel habit disturbances. Autonomic dysregulation has
been reported in IBS as well as altered ACC activation in pregenual ACC during
visceral stimulation 1 2. Glutamate is the major excitatory and Gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain.
AIMS & METHODS: We aimed to measure neurotransmitter concentration in
the pregenual ACC, in stool consistency subgroups with IBS by using quantitative neurotransmitter Magnetic Resonance Spectroscopy (qMRS)
Seven patients with IBS-mixed (6 women) and five patients with IBS -diarrhea (4
women) according to Rome 3 were included. Mean age was 34.2 years (SD 5.3)
with no significant difference between subgroups. Patients completed symptom
severity score (IBS-SSS). Quantitative MRS was measured in a 3T MRI scanner.
A water-suppressed MEGA-PRESS sequence (TR 2.0 s, TE 68 ms) was used with
the editing pulses placed at 1.90 ppm (ON-dynamics) and at 7.46 ppm (OFFdynamics) with a voxel (3x3x3 cm3) placed in the pACC. Each MEGA-PRESS
measurement resulted in a sequence of 40 OFF- and ON-dynamics, where each
was computed by 8 phase cycles. Directly after each water-suppressed MEGAPRESS measurement, a shorter 2-dynamic unsuppressed water MEGA-PRESS
measurement was performed within the same voxel, which was used to obtain the
concentrations in physically well-defined units of [mM]. The GABA concentrations were computed by averaging the difference spectra obtained by subtracting
each OFF-dynamic from subsequent ON-dynamic and using LCModel (Version
6.3) for the final quantification. The Glutamate concentrations were obtained by
only averaging the OFF-dynamics, which were not affected by the editing pulses.
Additionally, all dynamics were phase and frequency corrected prior to the averaging. For group comparison unpaired T-tests were used.
RESULTS: Patients had moderate to severe symptoms with IBS-SSS of 367 (SD
79.7). There was no significant difference between IBS subgroups in terms of IBSSSS. Mean pACC GABA concentration was 1.66 (SD 0.17) mM in IBS-M and
1.65 (SD 0.27) mM in IBS-D. There was no significant difference between groups
(p 0.9). Mean pACC Glutamate concentration was 4.54 (0.35) mM in IBS-M
and 5.13 (SD 0.64) mM in IBS-D. There was no significant difference between
groups, although a trend with p 0.06 was observed.
CONCLUSION: Further qMRS data have to be collected in IBS patients as well
as healthy controls to evaluate if IBS subgroups demonstrate alterations in
pACC glutamate and GABA concentrations.
REFERENCES
1. Tillisch K, Mayer EA and Labus JS. Quantitative meta-analysis identifies
brain regions activated during rectal distension in irritable bowel syndrome.
Gastroenterology 2011; 140: 91-100.
2. Larsson MB, Tillisch K, Craig AD, et al. Brain responses to visceral stimuli
reflect visceral sensitivity thresholds in patients with irritable bowel syndrome.
Gastroenterology 2012; 142: 463-472 e3.
Disclosure of Interest: None declared
P1576 GLP-1 INHIBITS PRE- AND POSTPRANDIAL ANTRODUODENO-JEJUNAL MOTILITY IN HEALTHY SUBJECTS AND
PATIENTS WITH IRRITABLE BOWEL SYNDROME
P.M. Hellstrom1,*, M. Degerblad2, M.A. Halim1, D.-L. Webb1 on behalf of IBS,
Motility
1
Medical Sciences, Uppsala University, UPPSALA, 2Endocrinology, diabetologi
and metabolism, Karolinska Institutet, Stockholm, Sweden
Contact E-mail Address: Per. Hellstrom@medsci.uu.se
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) is secreted from gut endocrine L-cells in response to nutrient ingestion. GLP-1 acts as an incretin to lower
blood glucose via stimulation of pancreatic islet beta cells. GLP-1 also exerts
actions independent of insulin, including inhibition of gastrointestinal (GI) motility, inhibition of gastric emptying and acid secretion. IBS is characterized by
abdominal pain or discomfort, associated with altered bowel habits and motor
function in the GI tract. The positive actions of the GLP-1 in preclinical motility
research and clinical IBS studies, highlights potential use of GLP-1 for treatment
of IBS. Since recent studies indicate IBS symptoms to be prominent postprandially, we found it reasonable to investigate if GLP-1 would have an effect on
upper GI motility in the pre- and postprandial period.
AIMS & METHODS: To investigate if GLP-1 can reduce GI motility after a
meal.
The motility pattern of the proximal small intestine was monitored using a multichannel polyvinylchloride recording tube with its distal recording site at the angle
of Treitz. Pressure transducers were connected via a PC Polygraph HR

United European Gastroenterology Journal 2(1S)


(Synectics) to a PC. The software program Polygram Lower GI 6.40 (Synectics)
was used with sampling frequency 4 Hz.
The over-all frequency of contractions, their amplitude and duration were computed during the respective 4-h infusion periods with saline and GLP-1 and
transferred to a motility index.
Studies in vitro were done with muscle strips mounted between two platinum ring
electrodes in 5 mL organ bath chambers containing Krebs solution, continuously
bubbled with 5% CO2 and 95% O2 and and pH 7.4. Data acquisition was
performed using Powerlab hardware and LabChart 7 software
(ADInstruments). Tissues were equilibrated to a 2 g tension. After equilibration,
muscle strips were studied with GLP-1 alone and in combination with the nitric
oxide synthase inhibitor, LNMMA.
RESULTS: After food-intake, GI motility index increased in healthy volunteers
and IBS patients. In volunteers, GLP-1 0.7 pmol/kg min-1 suppressed motility
index in antrum, duodenum and jejunum from 6.2 0.4 to 4.8 0.7, from 5.6
0.6 to 4.9 0.6 and from 5.8 0.1 to 5.6 0.4 Ln( (mmHgsmin-1)), respectively. In IBS patients, GLP-1 2.5 pmol/kg min-1 decreased motility index in
antrum from 6.2 0.1 to 6.0 0.2 Ln( (mmHgsmin-1)) whereas, in duodenum
and jejunum inconsistent motility responses were found. Studies on gastrointestinal smooth muscle strips confirmed our results in by inducing an inhibitory
action of GLP-1 on spontaneous motility.
CONCLUSION: Inhibitory motility responses to GLP-1 in healthy volunteers
are similar to that in earlier animal studies. In IBS, an inhibitory effect of GLP-1
seems to require higher dosage of the peptide. Studies in vitro confirm our studies
by relaxing intestinal smooth muscle strips. The relaxatory effect of GLP-1 on
motility together with its inhibitory action on gastric emptying and small intestinal motor activity opens the possibility of using GLP-1 as a plausible treatment
of IBS.
Disclosure of Interest: None declared
P1577 COMBAT-TRAINING STRESS MEDIATES METABOTYPIC
CHANGES ASSOCIATED WITH GASTROINTESTINAL SYMPTOMS
AND ALTERED INTESTINAL PERMEABILITY
L.C. Phua1, R.K. Wong2,*, Y.M. Tan1, T. Gopalakrishnan1, M.E. Kan3, J. Lu3,
A. Keshavarzian4, E.C. Chan1, C.H. Wilder-Smith5
1
Pharmacology, National University of Singapore, 2Medicine (Gastroenterology &
Hepatology), National University Health System, 3Defence Science Organisation,
Singapore, Singapore, 4Medicine, Rush University Medical Center, Chicago,
United States, 5Brain-Gut Research Group, Bern, Switzerland
Contact E-mail Address: leecheng.phua@gmail.com
INTRODUCTION: Physical and psychological stress have been shown to precipitate gastrointestinal (GI) symptoms and impair intestinal barrier function.
The neuroendocrine and immune axes, as well as probably modulation of the
microbiome, are involved mechanisms, but the molecular basis of stress-induced
GI manifestations remains elusive. Global urinary metabolic profiling represents
a novel approach for interrogating the multiparametric metabolic fluxes that
occur in response to pathophysiologic stimuli such as stress.
AIMS & METHODS: Here, we characterized the stress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat-training and correlated the metabotype with changes in GI physiology, particularly the
development of GI symptoms and alteration in intestinal permeability. In a
prospective, longitudinal study, urinary metabotyping was conducted on 38
male soldiers (ages 19-23) during combat training and the subsequent rest
period using gas chromatography-mass spectrometry. Stress was measured
using the perceived stress scale-10 item (PSS-10) questionnaire, while incidence
and severity of GI symptoms were assessed using the irritable bowel syndrome
symptom severity score (IBS-SSS). Whole gut intestinal permeability was evaluated by quantifying the 24h urinary excretion of sucralose as a percentage of the
orally administered 1g dose.
RESULTS: PSS-10 stress and IBS-SSS scores were higher during the combattraining period than at rest. The urinary metabotype was clearly distinct from the
rest period [partial least squares discriminant analysis (PLSDA) R2X 0.386,
R2Y 0.712, Q2 (cumulative) 0.563], confirming the presence of a unique
stress-induced metabotype. Based on PLSDA, differential metabolites related
to combat stress were uncovered (e.g. elevated pyroglutamate and fructose;
reduced gut microbial metabolites such as hippurate and m-hydroxyphenylacetate) [p50.05]. The extent of pyroglutamate upregulation exhibited a positive
correlation with the increase in IBS-SSS in soldiers during combat-training
[r 0.504, p50.05]. Additionally, the rise in fructose levels during combat-training was positively correlated with an increase in intestinal permeability [r 0.630,
p50.005].
CONCLUSION: Protracted and mixed psychological and physical combat-training stress yielded unique metabolic changes that corresponded with the incidence
and severity of GI symptoms and alteration in intestinal permeability. Taken
together, our data provided new insights into the molecular changes underlying
stress-induced GI perturbations which could be exploited for future biomarker
research or therapeutic strategies.
Disclosure of Interest: None declared

A565
P1578 DYSMOTILITY IN PARKINSONS DISEASE CORRELATES TO
GUT SYMPTOMS: FINDINGS OF A WIRELESS MOTILITY
CAPSULE STUDY
S.K. Butt1,*, R. Leung1, A. Batla2, K. Bhatia2, A. Raeburn1, N. Zarate-Lopez1,
A. Emmanuel1
1
Gastroenterology, UCLH, 2Movement Disorder Unit, National Hospital for
Neurology & Neurosurgery, London, United Kingdom
Contact E-mail Address: s.butt@ucl.ac.uk
INTRODUCTION: Parkinsons disease (PD) is a neuro-degenerative disorder
with frequent involvement of the gut. Symptoms arise throughout the gastrointestinal tract through dysmotility secondary to autonomic and enteric nervous
system involvement, as well from skeletal muscle involvement in the oropharynx
and anorectum. It has been speculated that gut involvement may precede motor
symptoms. The Wireless Motility Capsule (WMC) yields data on transit and
motility throughout the gut.
AIMS & METHODS: We report the first use of WMC to systematically assess
motility in PD patients with and without gut symptoms, compared to controls. 15
patients with established PD completed the study: eight (2 f, mean age 70 [47-85])
had GI symptoms and seven (2 f, mean age 61 [49-77]) did not based on history
and baseline scores on the Gastroparesis Cardinal Symptom Index (GCSI) and
Wexner constipation score. Data comparison with seven controls (3f, mean age
52 [39-63]). Medications affecting GI motility /pH were discontinued for the
study and the WMC was ingested following a standardized nutrient bar meal.
Data on gastric emptying time (GET), small bowel transit time (SBTT), colonic
transit time (CTT) and whole gut transit time (WGTT) were calculated.
RESULTS: PD patients with gut symptoms showed significantly slower transit in
the stomach (GET 5.2 vs 2.7h, p 0.0003), colon (CTT 57.8 vs 27.4h, p 0.02)
and overall gut (WGTT 67.2 vs 34.7h, p 0.02) compared to asymptomatic
patients. Small Bowel transit (mean SBTT 4.17h) did not significantly differ.
GET, SBTT, CTT and WGTT did not differ between asymptomatic PD and
controls. There was a significant correlation between the Wexner constipation
score and CTT in all patients (p50.01), but no correlation between GCSI and
gastric emptying (p40.05).
CONCLUSION: This study demonstrates that symptomatic PD patients have
markedly delayed transit times throughout the whole gut compared to asymptomatic PD patients and controls. The correlation between scores and transit times
suggest that WMC is a less useful indicator of gastric emptying than small bowel
and colonic transit.
Disclosure of Interest: None declared
P1579 NOVEL METHOD FOR MEASUREMENT GASTRIC EMPTYING
USING 3D MICRO-CT IN LIVE SMALL ANIMAL
Y.S. Kim1,*, N.-H. Kim2, S.H. Park2, J.M. Park2, E.-S. Choi3, H.S. Ryu4,
S.C. Choi4
1
Gastroenterology, Wonwkang Digestive Disease Research Institute, Wonkwang
University Sanbon Hospital, Gunpo-si, 2Radiology, Institute for Metabolic Disease,
3
Wonwkang Digestive Disease Research Institute, 4Gastroenterology, Wonwkang
Digestive Disease Research Institute, Wonkwang University, Iksan, Korea,
Republic Of
Contact E-mail Address: wms89@hanmail.net
INTRODUCTION: Delayed gastric emptying (GE) is one of the important
pathogenic mechanisms of functional dyspepsia. Traditionally, oral gavage of
phenol red/methylcellulose mixture has been used to measure the change of
GE in small animals like rat or mice. However this method has a disadvantage
to sacrifice animals at each measurement. 3D micro-CT has been used in the
study for bone and soft tissues with the small animal, however it has not been
applicated to the functional gastrointestinal study until now.
AIMS & METHODS: We aimed to establish a novel method for measurement of
gastric volume and GE without sacrifice of rat using 3D micro-CT (Polaris-G90,
NanoFocusRay, Jeonbuk, Korea). Sprague-Dawley rat (210310g) were used.
Rats were divided into Control (vehicle, n 5), Delayed GE (atropine, n 6),
and Enhanced GE (bethanechol, n 5) groups. After overnight fasting, distilled
water, atropine (7.5mg/kg), and bethanechol (1mg/kg) was given by I. P. route in
each group, respectively. After 20 minutes of IP, 3ml of radiopaque semisolid
food was fed into stomach by gastric gavage under isoflurane anesthesia.
Immediately after gastric gavage, baseline CT (fed volume) was performed,
and after 1h freely moving time, 2nd CT (residual volume) was performed.
Conventional CT image was converted to 3D image and the volume of radiopaque intragastric food was measured from baseline and 2nd CT. GE was calculated as [(fed volume-residual volume)/residual volumex100].
RESULTS: Fed food volume was 3.0  0,02 ml, 2.99  0.05 ml, and 2.4  0.7 ml
and residual volume was 1.33  0.22 ml, 2.59  0.35 ml, and 0.740.24 ml in
Control, Delayed GE, and Enhanced GE groups, respectively. Fed volume at
baseline CT of bethanechol treated rat was lower than 3ml because gastric contraction was very active and food was emptied immediately after gavage. The 1h
GE rate, which was calculated using fed volume and residual volume on CT, was
55.9  7.09 %, 13.5  11.9 %, and 68.7  6.64 % in Control, Delayed GE, and
Enhanced GE group, respectively. (P50.05 compared to vehicle).
CONCLUSION: Gastric food volume was measured by 3D micro-CT in live
small animal and GE rate was calculated using CT volume. This novel method
can measure GE serially in a same animal. It seems that this method will be useful
in the functional study for FD with decreasing the sacrifice of animal.
Disclosure of Interest: None declared

A566
P1580 THE MOTILITY RESPONSE OF ESOPHAGUS TO PER-ORAL
ENDOSCOPIC MYOTOMY IN PATIENTS WITH ACHALASIA:
HIGH-RESOLUTION MANOMETRY APPROACH WITH CHICAGO
CLASSIFICATION
Y. Ren1,*, F. Cheng1, Z. Deng1, X. Tang1, J. Wu1, F. Zhi1, W. Gong1, B. Jiang1
1
Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou,
China
Contact E-mail Address: renytpumc@hotmail.com
INTRODUCTION: Although per-oral endoscopic myotomy (POEM) is widely
studied for achalasia, the motility response has been mainly focused on lower
esophageal sphincter (LES). This study investigated the esophageal motility
response including upper esophageal sphincter (UES), esophageal body (EB)
and LES in subtypes of achalasia.
AIMS & METHODS: Achalasia patients who received POEM were included for
analysis. Eckardt score was used to assess symptom improvement. High-resolution manometry was applied for studying motility change. HRM parameters
analyzed were (i) LES: resting pressure (restP), 4-second integrated relaxation
pressure (4s-IRP), intrabolus pressure (IBP); (ii) EB: contraction amplitude (CA);
contraction duration (CD), distal contraction integral (DCI); distal delay (DL);
esophageal length; (iii) UES: resting pressure (restP), relaxation pressure (relaxP);
relaxation duration (RD).
RESULTS: There were 11 type I achalasia and 21 type II achalasia patients
included. (i) LES tone was reduced significantly in both subtypes. (ii) Motility
parameters of EB (length, CA, CD and DCI) were all lowered in type II achalasia, but were not in type I achalasia. (iii) UES relaxP was reduced in type II
achalasia (13.906.76 vs. 5.226.80 cm, p50.001); change of UES parameters in
type I achalasia was insignificant. (iv) Eckardt score decreased more in type II
achalasia without statistical significance [6.00 (3-10) vs. 5.00 (3-9), p 0.056]. (v)
Proximal segment of esophagus without myotomy changed with distal segment
with myotomy in both subtypes.
CONCLUSION: Type I and type II achalasia had different motility response
patterns to POEM, which could lead to different clinical outcome. Distal myotomy of POEM would have a feedback l inhibition on proximal esophageal
motility such as body contraction and relaxation of upper esophageal sphincter.
REFERENCES
1. Bredenoord AJ, Fox M, Kahrilas PJ, et al. Chicago classification criteria of
esophageal motility disorders defined in high resolution esophageal pressure
topography. Neurogastroenterol Motil 2012; 24: 57-65.
2. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy
(POEM) for esophageal achalasia. Endoscopy 2010; 42: 265-271.
3. Wauters L, Van Oudenhove L, Selleslagh M, et al. Balloon dilation of the
esophagogastric junction affects lower and upper esophageal sphincter function
in achalasia. Neurogastroenterol Motil 2014; 26: 69-76.
4. Pandolfino JE, Kwiatek MA, Nealis T, et al. Achalasia: a new clinically
relevant classification by high-resolution manometry. Gastroenterology 2008;
135: 1526-1533.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS III POSTER
EXHIBITION HALL XL_____________________
P1581 THE IMMUNE RESPONSE IN THE LUNGS AND PHENOTYPE
OF ALVEOLAR MACROPHAGES IN ASTHMA,
GASTROESOPHAGEAL REFLUX DISEASE AND THEIR
COMBINATION
I.Y. Malyshev1,*, S. V. Lyamina2, G.L. Yurenev3, I. V. Maev3
1
Pathophysiology, 2Pathophysiology, Propaedeutics of Internal Diseases and
Gastroenterology, 3 Propaedeutics of Internal Diseases and Gastroenterology,
Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: iymalyshev1@gmail.com
INTRODUCTION: The portion of patients with a combination of bronchial
asthma (BA) and gastroesophageal reflux disease (GERD) grows steadily. We
must understand particular features of this combined pathology to treat lung
symptoms of these diseases. Our hypothesis: immune response abnormalities in
the lungs during bronchial asthma (BA), GERD and in their combination is
determined by faulty reprogramming of alveolar macrophages.
AIMS & METHODS: To verify the hypothesis and compare changes in immune
response in the lungs with changes in phenotype of alveolar macrophages in
patients with BA, GERD and their combination.
Methods: We measured the concentration of pro-inflammatory M1 cytokines:
IL-1, IL-8, IL-12, IFN-, TNF- and TNF-; anti-inflammatory M2 cytokines:
IL-4, IL-5 h IL-10 and bivalent cytokines: IL-2 h IL-6 in bronchoalveolar lavage
fluid (BALF) and in the alveolar macrophages culture medium. Changes in
immune response in the lungs and changes in phenotype (reprogramming) of
macrophages were evaluated using M1 cytokines to M2 cytokines ratio (M1/
M2 index) in BALF and culture medium, respectively.
RESULTS: Patients with GERD had M1/M2 index of 4.2 in BALF; patients
with combined pathology 0.6; patients with BA 0.9. So in GERD immune
response in the lungs shifts to proinflammatory, in BA and combined pathology
to anti-inflammatory. Pro-inflammatory shift in GERD is due to increased
concentration of M1 cytokines and decreased concentration of M2 cytokines
in BALF, anti-inflammatory shift in BA is due to decreased concentration of
M1 cytokines IL and decreased concentration of M2 cytokines, anti-inflammatory shift in combined pathology is due to decreased M1 cytokines and increased
M2 cytokines. Along with specificity of cytokine pattern all three diseases have
similar features: increased concentration of TNF-, IL-6 and IL-2 in BALF.

United European Gastroenterology Journal 2(1S)


Phenotype of cultivated macrophages isolated from BALF in GERD and BA
shifts to M1, in combined pathology shifts to M2. CD markers of phenotype
confirmed these shifts. Pro-inflammatory shift of macrophage phenotype in
GERD is due to the increased production of M1 cytokines and decreased production of M2 cytokine; pro-inflammatory shift in BA is due to decreased production of M1 cytokines and decreased production of M2 cytokine; antiinflammatory shift in combined pathology is due to decreased production of
M1 cytokines and and increased production of M2 cytokines. Along with specific
changes in production of cytokines by macrophages in GERD, BA and their
combined pathology, similar features were observed: increased production of M1
cytokines IL-8 and TNF-, L2 cytokine IL-10 and cytokine IL-6.
CONCLUSION: analysis of cytokine spectrum from BALF and those produced
by macrophages proved our hypothesis, that immune response abnormalities in
the lungs during BA, GERD and in their combination is determined by faulty
reprogramming of alveolar macrophages. This allows us to initiate new clinical
direction abnormalities in reprogramming of immune cells in the pathogenesis
of lung diseases. Our results also indicate that the therapy of inflammatory
component in the lungs should be conducted with consideration about specificity
of the cytokine response abnormality.
Disclosure of Interest: None declared
P1582 ACTIVATION OF CB2 RECEPTORS HAS GASTROPROTECTIVE
EFFECT ON EXPERIMENTALLY INDUCED GASTRIC ULCERS IN
MICE
M. Salaga1,*, H. Zatorski1, M. Sobczak1, A. Piechota-Polanczyk1, M. Storr2,
J. Fichna1
1
Deartment of Biochemistry, Medical University of Lodz, Lodz, Poland,
2
Department of Medicine, University of Munich, Munich, Germany
Contact E-mail Address: salaga.maciej@gmail.com
INTRODUCTION: Cannabinoid (CB) receptors type 2, which belong to the
endogenous CB system, are distributed in the central nervous system and in
the periphery. Recent studies indicated that CB2 receptors are expressed profusely in the non-neuronal systems, including immunocytes and the gastrointestinal
(GI) tract. It has therefore been suggested that cannabinoids may be involved in
alleviating GI inflammation and the CB2 receptor agonists may represent potential therapeutics in GI inflammatory states, where immune system is activated.
The aim of the study was to investigate the effect of the activation of CB2
receptors by a novel and highly selective CB2 agonist, MJ2010, on the development of gastric lesions in two murine models of gastric ulcer.
AIMS & METHODS: We used two well-established mouse models of gastric
ulcer, induced by oral administration of acidified ethanol (60% EtOH in 0.3 M
HCl) and a non-steroid anti-inflammatory drug (NSAID) diclofenac (30 mg/kg).
Clinical parameters for gastroprotection were assessed based on the inhibition of
gastric lesion area. To establish the mechanism of gastroprotective action, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity, as well as glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and H2O2
levels were assessed in gastric tissues.
RESULTS: CB2 agonist MJ2010 produced a dose-dependent gastroprotective
effect in NSAID-induced gastric lesions, as evidenced by significantly lower
macroscopic damage score. Moreover, we observed that the administration of
MJ2010 (5 mg/kg p.o.), stimulated the oxidative stress protection mechanisms in
the tissue, as demonstrated by an increased GSH level. We also found that our
compound reduced the superoxide dismutase (SOD) activity, which was followed
by lower levels of H2O2 in the tissue.
CONCLUSION: Activation of CB2 receptors by MJ2010 reduced gastric lesion
through enhancing cell response to oxidative stress. Our data suggest that CB2
receptors are a new potential target in the treatment of gastric ulcers.
Disclosure of Interest: None declared
P1583 GASTROPANEL HELPS TO PREDICT ATROPHIC
GASTRITIS IN PATIENTS WITH AUTOIMMUNE THYROID
DISEASE

BODY

R. De Bastiani1,*, A. Tursi2, I. Grattagliano3, M. De Polo4, E. Baldi4,


M. Zamparella3, G. Sanna5, E. Pirrotta6, F. Bernard6, P. Bacchin6,
L. Boscariolo6, M. Bortot6, G. Polizzi6, L. Maurizio6, F. Di Mario7
1
GIGA-CP ASSOCIATION, Feltre (BL), 2GIGA-CP (Italian Group for Primary
Care Gastroenterology), Andria (BT), 3GIGA-CP (Italian Group for Primary
Care Gastroenterology), Bari, 4GIGA-CP (Italian Group for Primary Care
Gastroenterology), Venezia, 5GIGA-CP (Italian Group for Primary Care
Gastroenterology), Cagliari, 6SNAMID (National Society for General
Practitioners Educational), Rome, 7University of Parma, Parma, Italy
Contact E-mail Address: rudeba@libero.it
INTRODUCTION: The prevalence of autoimmune thyroiditis in the general
population is high (5-15%) and it is often associated in the same subject with
other autoimmune disorders. One of them is the autoimmune atrophic gastritis,
which occurs in 20-30% of asymptomatic patients carrying an autoimmune thyroiditis and likely affects 2-8% of the general population. This is a precancerous
lesion of the stomach greatly affecting the absorption of vitamins, oligonutrients
and some oral given drugs. Diagnosis is currently made by the serum detection of
antibodies against parietal cells (APCA) and histology. Gastropanel, a combination of PG-I (pepsinogen-I), PG-II (pepsinogen-II), sG-17 (gastrin-17) and
Helicobacter pylori antibodies, has been proposed as a simple non-invasive serological test to select patients with a high risk of harboring atrophic gastritis, who
deserve endoscopic examination. This study assessed, non-invasively, the presence of chronic atrophic gastritis in patients carrying autoimmune thyroiditis,
as managed in the primary care setting.

A567

United European Gastroenterology Journal 2(1S)


AIMS & METHODS: Patients (n 160) with autoimmune thyroiditis were
extracted from the database of n 16 Italian primary care physicians. After
exclusion of thyroid cancer, drug-induced hypothyroidism, inability to suspend
PPI and contraindications to perform endoscopy, n 145 of them
(females 130, median age 52 yrs) were further studied for gastric alterations.
After overnight fasting, venous blood was taken for APCA and Gastropanel. PG
I/II 53 was considered suggestive of moderate to severe body gastric atrophy
and an indication to perform an upper gastrointestinal endoscopy.
RESULTS: APCA was positive in n 22 (15.2%) and PG I/II 53 in n 20
(13.8%) patients with autoimmune thyroiditis. Fifteen patients (75%) with PG
I/II53 were also APCA positive. Gastric atrophy was present in 24/145 (16.6%)
patients: 11/22 (50%) APCA positive, 13/20 (65%) PG I/II53 and in 10/15
(67%) with both APCA positivity and PG I/II 53. Patients (n 24) with atrophy
at histology were 11/24 (46%) APCA positive, 13 (54%) PG I/II 53, 10 (42%)
positive and 10 (42%) negative for both markers. By multiple "multiple" logistic regression, APCA alone showed a positive predictive value for atrophic gastritis of 50%, PG I/II 53 alone had a positive predictive value of 67%, whereas
the PG I/II 43 had a negative predictive value of 86%. The presence of both
APCA positivity and PG I/II 53 increased to 69% the positive predictive value
for chronic atrophic gastritis.
CONCLUSION: Although based on a low number of patients, our results indicate that PG I/II 53 has a higher predictive value than APCA for gastric atrophy. The simultaneous presence of both APCA and PG I/II 53 increases the
predictive value for gastric atrophy in patients with autoimmune thyroiditis.
Gastropanel together with APCA positivity may represent a promising noninvasive tool to select patients needing endoscopy and histology.
REFERENCES
Lahener E. et al. Occurrence and risk factors for autoimmune thyroid disease in
patients with atrophic body gastritits. Am J Med 2008; 121: 136-141.
Disclosure of Interest: None declared
P1584 EXPLORATION OF THE POTENTIAL OF
ASSOCIATED AUTOANTIBODIES AS BIOMARKERS FOR
GASTRIC CANCER DETECTION

TUMOUR-

Z. Kalnina1,*, I. Meistere1, P. Zayakin1, K. Silina1, A. Pismennaja1, M. Leja2,


A. Line1
1
Cancer Biomarker group, Latvian Biomedical Research and Study center,
2
Faculty of Medicine, University of Latvia, Riga, Latvia
Contact E-mail Address: zane@biomed.lu.lv
INTRODUCTION: Gastric cancer (GC) represents the third leading cause of
cancer-related deaths worldwide in both sexes, which is mainly due to the belated
diagnosis. Currently there are no reliable non-invasive biomarkers in clinics that
could be used for prompt and early GC diagnosis. Research by many research
groups including ours has demonstrated that circulating IgG class autoantibodies
that are generated against tumour-associated antigens, due to their specificity,
stability in serum and production even in early stages of cancer development may
serve as promising non-invasive biomarkers for early detection of certain
malignancies.
AIMS & METHODS: In a previous study1, we applied T7 phage display-based
SEREX (PhD-SEREX) approach and phage-displayed antigen microarray
(PDAM) technology to identify GC-associated antigens and analyse Ag-specific
autoantibody responses in patients with GC, which resulted in the identification
of 45 autoantibody biomarker panel having promising diagnostic value
(AUC 79). The aim of the current study was to assess the GC-associated antigen repertoire in the proportion of patients that tested negative with the assay,
and to evaluate its potential to increase the diagnostic performance of the serological test. We applied PhD-SEREX to identify GC antigen repertoire in 28
patients, and exploited PDAM for serum autoantibody reactivity profiling
against the identified antigens in 67 GC patients (from these, 56 tested negative
previously) and 54 healthy controls (HC). After microarray data processing and
normalisation, each antigen was ranked basing on the detected serum signal
intensity and frequency of reactivity in the two groups. For each of the tested
serum, a score was calculated by summing up the intensities of sero-positive
antigens.
RESULTS: By using serum samples from 28 GC patients, 183 different serumreactive clones were identified. Clone sequence analyses revealed different antigen repertoire in comparison to that identified in our previous study1. According
to the serum autoantibody profiling results, positive rank was assigned to 50
antigens, autoantibody responses against which were detected predominantly
in GC patients. Autoantibody reactivity to individual antigens ranged from 17% of the GC patients. Mean serum score in GC group was 3.19 and 0.6 in HC
group. From the top ranked antigens, autoantibody responses against 29 were
found only within the group of GC patients that tested negative previously, and
thus might represent valuable biomarker candidates. From these, majority represented novel serologically active tumour-associated antigens.
CONCLUSION: The results of this study demonstrate that there might exist
different sets of induced autoantibody responses possibly reflecting immunologically distinct processes induced during tumour development in stomach or,
alternatively, immune responses to molecularly different types of GC. The addition of the newly identified biomarker candidates to the previously established
serological GC test set may substantially increase its diagnostic performance and
thus awaits for further testing and validation within larger serum sample sets.
REFERENCES
1. Zayakin P, et al. Tumor-associated autoantibody signature for the early detection of gastric cancer. Int J Cancer 2013; 132: 137-147.
Disclosure of Interest: None declared

P1585 NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING:


HOW TO PREDICT THE PRESENCE OF LESIONS WARRANTING
ENDOSCOPIC TREATMENT?
P. Boal Carvalho1,*, J. Magalhaes1, F. Dias de Castro1, B. Rosa1, J. Cotter1,2
1
Gastrenterology, Centro Hospitalar do Alto Ave, 2Life and Health Sciences
Research Institute (ICVS), School of Health Sciences, University of Minho,
Guimaraes, Portugal
Contact E-mail Address: Pedro.n.carvalho@gmail.com
INTRODUCTION: Non-variceal upper gastrointestinal bleeding (NVUGIB)
constitutes one of the most frequent emergency presentations in the gastroenterology field. Esophagogastroduodenoscopy (EGD) plays a predominant role in its
approach and management.
AIMS & METHODS: Our objective was to identify variables at hospital admission with predictive value for the presence of high risk hemorrhagic lesions in
EGD.
We included consecutive patients undergoing emergency EGD for upper gastrointestinal bleeding presenting with hematemesis or melena during a one-year
period. Patients with either esophageal or gastric varices as well as portal hypertensive gastropathy were excluded.
Lesions with active hemorrhage, ulcers with a visible vessel and ulcers with
adhering clot were defined as high risk hemorrhagic lesions, warranting endoscopic therapy.
Statistical analysis was performed using SPSS 21.0, and a p-value 50.05 was
considered statistically significant.
RESULTS: Ninety-two patients were included, 54.3% (n 50) were male, mean
age 69 years (23-93 years). Ulcers (53%) and Mallory-Weiss lesions (12%) were
the most frequently observed hemorrhagic lesions; no potentially bleeding lesion
was found in 14% of the procedures.
Lesions with high hemorrhagic risk criteria were observed during EGD in 32.6%
(n 30) of the patients. In multivariate analysis, hematemesis (p 0.026), systolic
hypotension (p 0.022), leukocytosis (p 0.004) and EGD performed in the first
12 hours after the bleeding event (p 0.002) were significantly associated with the
presence of high risk hemorrhagic lesions.
CONCLUSION: One third of the patients undergoing EGD for non-variceal
gastrointestinal bleeding were shown to have a high risk hemorragic lesion.
Patients undergoing EGD during the first 12 hours of the hemorrhage, presenting
with hematemesis, systolic hypotension or leukocytosis were more frequently
diagnosed with high risk hemorrhagic lesions.
Disclosure of Interest: None declared
P1586 THE IMPACT OF MANDATORY INCLUSION OF GLASGOW
BLATCHFORD BLEEDING SCORE IN THE INPATIENT REFERRAL
PATHWAY TO A TERTIARY ENDOSCOPY UNIT
R. I. I. Rusu1,*, G. Chakrabarty1, C. Groves1, R. Pollok1
Gastroenterology Department, St Georges Hospital, London, United Kingdom

INTRODUCTION: The Glasgow Blatchford Bleeding Score (GBS) is a validated pre-endoscopy scoring system, which stratifies patients presenting with
acute upper gastrointestinal (GI) haemorrhage according to the likelihood of
the need for intervention. Previous research indicates that patients with a low
GBS score (0 or 1) are safe to have endoscopy as outpatients. An initial review in
our own institution indicated 10% of inpatient endoscopies were in this low risk
group. We therefore aimed to assess the impact of the introduction of GBS as
standard part of the referral pathway on inpatient endoscopic activity. We also
aimed to establish whether patients with a score of 2 could also avoid inpatient
endoscopy.
AIMS & METHODS: We undertook a retrospective study of all inpatient referrals over a 6 month period. The GBS scores were completed by the referrer or
calculated based on information recorded in patients notes and electronic patient
record. A review of the endoscopic findings and use of proton pump inhibitors
(PPI) prior to endoscopy was performed and compared with previous findings.
RESULTS: During the study period (comparative first study data included in
parenthesises) there were 140 (97) referrals, 137 (97) patients mean GBS 8.92 /3.79 (6.2 /- 4.2). Mean difference between the two studies was 2.72 (CI 1.68,
3.75), p 5 0.0001. GBS was completed for 48 referrals - 34% (1010%) and
calculated in 92 66% (8790%). Overall GBS was 0 or 1 in 2 patients 1.5%
(1818.5%), 2 in 5 patients- 3.5% and 2 or more in 138 patients 98.5% (79
81.5%). Of those with GBS 0 or 1, only 1 patient (18) had inpatient endoscopy.
Endoscopic findings in the five patients scoring 2 were: normal-2, oesophagitis-2,
Barretts-1 and oesophageal ulcer-1. None had stigmata of recent haemorrhage
or required end therapy. Amongst the whole group 21 patients 15.2% (12
15.2%) required endotherapy. 102 patients 72.8% (6971.1%) were prescribed
PPI prior to endoscopy. Of these, 48 patients 47% (4362.3%) had oral PPI, 51
50% (2231.8%) had IV PPI and 3 3% (35.9%) PPI infusion.
CONCLUSION: Completion of the GBS proformas improved substantially
from 10 to 34%. There was also a concurrent significant reduction in the
number of inpatient referrals for endoscopy with a low risk score of 0 or 1
from 10% to 1.5 %. It appears the introduction of the GBS score has led to a
wider appreciation of the importance of risk stratification amongst referrers in
triaging inpatient endoscopy. Our findings also support recent research suggesting low risk stratification may safely be extended to include patients with a score
of two.
Disclosure of Interest: None declared

A568

United European Gastroenterology Journal 2(1S)

P1587 IMPORTANCE OF ANGIOTENSIN-(1-7), A VASOACTIVE


METABOLITE OF ANGIOTENSIN I IN THE MECHANISM OF
GASTRIC ADAPTATION TO REPEATED ASPIRIN INSULT. A KEY
IN UNDERSTANDING OF GASTRIC ADAPTATION TO ASPIRIN?
R. Pajdo1,*, Z. Sliwowski1, M. Pawlik1, S. Kwiecien1, B. Bujak-Gizycka2,
S.J. Konturek1, W.W. Pawlik1, T. Brzozowski1
1
Department of Physiology, 2Department of Pharmacology, Jagiellonian
University Medical College, Cracow, Poland
INTRODUCTION: The rodent and human gastric mucosa of the stomach can
adapt to damaging action of aspirin (ASA) but the contribution of renin-angiotensin system (RAS) and vasoactive metabolites of angiotensin I, e.g. angiotensin-(1-7) (Ang-(1-7) in phenomenon of gastric adaptation to ASA has been little
studied.
AIMS & METHODS: Using advance LC-ESI-MS method we determined
whether 1) Ang-(1-7) is detectable in gastric tissue and whether 2) the treatment
with Ang II, the blockade of specific Ang-(1-7)/Mas receptor, exogenous Ang-(17) or AVE 0991, the agonist of Mas receptor, could influence the gastric damage
induced by single and repetitive ASA treatment. Gastric adaptation was induced
by daily repeated exposure of acidified ASA (100 mg/kg-d) given p.o. for 5 days
to rats treated daily i.g. with or without: 1) Ang II (100 g/kg), 2) A-779 (50 g/
kg), 3) Ang-(1-7) (20 g/kg), and 4) AVE 0991 (50 g/kg i.p.). The area of gastric
lesions was determined by planimetry, the gastric blood flow (GBF) was assessed
by H2-gas clearance technique, the mucosal malondialdehyde (MDA) content as
an index of lipid peroxidation, the plasma levels of IL-10, IL-1 and TNF-
(ELISA) were assessed. The expression of mRNAs for ACE, HIF-1, IL-10,
IL-1 and TNF-, cNOS and iNOS was analyzed by RT-PCR.
RESULTS: We found that the rat stomach mounted in organ bath ex vivo is a
source of Ang-(1-7) which is abundant metabolite product of Ang I conversion in
the gastric mucosa. The single treatment with ASA produced gastric lesions and
decreased GBF while raising both the mucosal MDA contents and the plasma
IL-1 and TNF- levels but significantly decreased the plasma IL-10 levels. The
lesion area was reduced by 75% at 5 repeated exposures to ASA followed by a
significant increase in the GBF and the significant decrease in the MDA content
and the plasma IL-1 and TNF-. Treatment with Ang-(1-7) (50 g/kg i.g.)
significantly reduced ASA-induced gastric lesions and the mucosal MDA content
and raised GBF and these effects were reversed by concurrent treatment with A779 (p50.02) or Ang II (10 g/kg i.g.). In ASA-adapted rats the reduction in the
lesion area and an increase in GBF were further improved by concomitant treatment with Ang-(1-7) or AVE 0991. Expression of mRNA for ACE was normal in
intact mucosa but mRNAs for IL-1, TNF-, HIF-1 and iNOS which were
negligible in intact gastric mucosa, were strongly upregulated in single ASAtreated mucosa and these effects were significantly attenuated in rats treated 5
times with ASA with or without treatment with AVE 0991.
CONCLUSION: We conclude that 1) Ang-(1-7) produced in excessive amounts
by the gastric mucosa of the stomach is involved in the mechanism of gastric
mucosal defense and mucosal resistance to subsequent repetitive ASA treatment,
2) blockade of specific Ang-(1-7) Mas receptor impairs the ASA adaptation
suggesting that Ang-(1-7) plays an important role in the mechanism of gastric
adaptation to repetitive ASA insult, and 3) Ang-(1-7) mediates ASA-induced
adaptation via its antiinflammatory, vasodilatatory and hyperemic properties
resulting in suppression of proinflammatory cytokines, lipid peroxidation and
attenuating effect on oxidative stress.
Disclosure of Interest: None declared
P1588 A
NEW
SIMPLE
SCORING
SYSTEM
FOR
GASTROINTESTINAL BLEEDING COLOGNE-WATCH RISK
PREDICTION (C-WATCH)

composite endpoint, while 36% of patients in the high risk group ( 2 points)
experienced a complication.
CONCLUSION: In emergency settings, our easy to use scoring system is able to
separate high-risk patients who need hospitalization or immediate upper endoscopy from low-risk cases that are suitable candidates for outpatient management or in whom endoscopy can be postponed. A prospective validation of the
C-WATCH risk score in different patient populations outside a university hospital setting seems warranted.
Disclosure of Interest: None declared
P1589 HEALTHCARE COSTS AND QUALITY OF LIFE ASSOCIATED
WITH ACUTE UPPER GASTROINTESTINAL BLEEDING IN THE UK
H. Campbell1, E. Stokes1, D. Bargo1, R. Logan2, M. Murphy3, V. Jairath4,* on
behalf of TRIGGER Investigators
1
Nuffield Department of Population Health, Oxford, 2University of Nottingham,
Nottingham, 3NHS Blood and Transplant, 4Nuffield Department of Medicine,
University of Oxford, Oxford, United Kingdom
INTRODUCTION: Acute upper gastrointestinal bleeding (AUGIB) accounts
for over 70,000 hospital admissions in the UK annually. Its incidence is likely
to rise due to an ageing population and increasing burden of liver disease. Data
on the healthcare costs and health related quality of life (HRQoL) associated
with this condition are sparse.
AIMS & METHODS: The TRIGGER trial is a cluster randomised feasibility
trial evaluating restrictive versus liberal red cell transfusion for patients with
AUGIB. The study collected data on resource use, costs and outcomes during
hospitalisation and up to day 28 to explore the feasibility of gathering inputs
required for a cost-effectiveness analysis. Resource use data were collected during
the inpatient episode on the use of laboratory tests, medications, blood components, endoscopy and endoscopic therapy, clinical events including ischaemic/
thromboembolic events and length of hospital stay (LOS) by ward type. Data
were also collected on primary and secondary care resource use, as well as informal care/days off work, post-discharge to day 28. Resource use for each patient
was multiplied by national unit costs to generate an estimate of the costs of
AUGIB to 28 days. HRQoL was measured on a scale anchored at 0 (death)
and 1 (full health), using the EuroQol EQ-5D-3L questionnaire at day 28.
RESULTS: 936 patients were enrolled into TRIGGER between August 2012 and
March 2013 in 6 UK hospitals. Preliminary analyses show that the mean (standard error (SE)) cost of the inpatient episode was 2436 (87) per patient. LOS
was a key cost driver; mean LOS was 5.3 days with an associated cost of 1432.
Additional cost drivers included: (1) endoscopy, with mean of 0.8 endoscopies
per patient at a cost of 627; (2) red cell transfusion, with a mean of 1.6 units
transfused per patient at a cost of 198. Mean (SE) costs from hospital discharge
to 28 days were 386 (25) per patient. The main cost driver post discharge was
readmission to hospital; 11% of patients were readmitted within 28 days for a
mean of 4.8 days. The mean cost associated with readmission across all patients
was 145. HRQoL was on average (SE) 0.68 (0.01) at 28 days.
CONCLUSION: The mean (SE) cost up to 28 days for patients presenting with
AUGIB is 2822 (90). At 28 days, the mean HRQoL in patients who have
experienced an AUGIB is well below the average population level of 0.86. This
is the first study to provide detailed estimates of the costs and HRQoL associated
with AUGIB in the UK. These data can be used by healthcare providers and
researchers to inform the design of subsequent cost-effectiveness analyses of
interventions for AUGIB.
Disclosure of Interest: None declared

UPPER
P1590 SIMULTANEOUS
COMBINED
BALLOON-OCCLUDED
RETROGRADE TRANSVENOUS OBLITERATION AND PARTIAL
SPLENIC EMBOLIZATION FOR GASTRIC FUNDAL VARICES

V. Hoffmann1,*, M. Hellmich2, A. Bowe1, A. Pelc1, M. Demir1, S. Schulte1,


U. Toex1, D. Nierhoff1, H.-M. Steffen1
1
Gastroenterology and Hepatology, University Hospital of Cologne, 2Institute for
Medical Statistics, Informatics and Epidemiology, Universitiy of Cologne, Cologne,
Germany
Contact E-mail Address: Vera. Hoffmqnn_@uk-koeln.de

N. Waguri1,*, S. Ikarashi1, A. Osaki1, M. Ogawa1, M. Sato1, T. Aiba1,


O. Yoneyama1, K. Furukawa1, K. Igarashi1
1
Department of Gastroenterology and Hepatology, Niigata City General Hospital,
Niigata, Japan
Contact E-mail Address: wagurinobuo@gmail.com

INTRODUCTION: Acute upper gastrointestinal bleeding (UGIB) is the leading


indication for emergency endoscopy. Scoring systems have been developed for
immediate risk stratification. However most of these scores include endoscopic findings and are based on data from patients with non-variceal bleeding. The aim of our
study was to design a pre-endoscopic scoring system for acute UGIB - including
variceal bleeding in order to differentiate between high-risk patients in need of early
endoscopy from low-risk patients with justifiable outpatient management.
AIMS & METHODS: The scoring system was developed using a training set
consisting of 586 patients with acute UGIB. These patients were recruited from
the emergency department as well as all inpatient services at the University
Hospital of Cologne within a two year period (01/2007 12/2008). A cohort of
322 patients, who presented to our endoscopy unit with acute UGIB in 2009
served as validation set. Clinical, laboratory and endoscopic parameters as well
as further data on medical history and medication were retrospectively collected
from the electronic clinical documentation system. A multivariate logistic regression was fitted to the data to obtain a predictive risk score using recurrent
bleeding, need for intervention (angiography, surgery) or death within 30 days
as composite endpoint.
RESULTS: Only CRP, white blood cells, ALT, thrombocytes, creatinine, and
hemoglobin could be identified as significant predictors for the composite endpoint. Based on the odds ratios of these variables an easy to use point scoring
scheme (C-WATCH) was derived predicting the risk of complications from 3%
to 86% with an AUC of 0.723 in the training set and 0.704 in the validation set.
None of the low risk patients (0-1 points) needed any intervention included in our

INTRODUCTION: Balloon-occluded retrograde transvenous obliteration (BRTO) has been widely adopted for the management of gastric fundal varices
(GV). We previously reported the efficacy and safety of simultaneous combined
B-RTO and partial splenic embolization (PSE) based on the hypothesis that
concomitant PSE can diminish the increase in portal venous pressure following
B-RTO for GV (JVIR 2012). With more cases and long-term observation, we reevaluated the efficacy of simultaneous combined B-RTO and PSE.
AIMS & METHODS: We performed B-RTO in 36 consecutive patients with GV
between 2005 and 2013 at a single institute. Of these, 8 and 4 patients with ruptured
GV were treated emergently and electively, respectively. The remaining 24 patients
with unruptured GV were treated prophylactically. Twenty-three patients received
simultaneous combined B-RTO and PSE (Group 1) and 13 received B-RTO
monotherapy (Group 2). Outcomes were retrospectively assessed.
RESULTS: No significant differences were observed in the baseline characteristics
between the two groups except for significantly larger spleen volumes in Group 1.
B-RTO was performed successfully in 33 of 36 patients (91.7%). Gastrorenal
shunts were well-embolized, and GV resolved in all patients successfully treated
by B-RTO. The procedure time was not significantly different between Groups 1
and 2 (p 0.2623). In Group 1, the volume of sclerosing agent required for B-RTO
was significantly smaller (p 0.0118) and exacerbation of esophageal varices was
significantly less frequent (p 0.0013) than in Group 2.
CONCLUSION: This study indicated that concomitant PSE may improve the
success of B-RTO.
Disclosure of Interest: None declared

A569

United European Gastroenterology Journal 2(1S)


P1591 NO CORRELATION OF ALARM SYMPTOMS AND CLINICALLY
SIGNIFICANT FINDINGS IN UPPER ENDOSCOPY IN
AMBULATORY SETTING: CONTINUATION OF THE PROSPECTIVE
STUDY
L. Jonaitis1,*, G. Kiudelis1, S. Sriuoginys1, L. Mockute1, L. Kupcinskas2
1
Gastroenterology, 2Institute of Digestive diseases, Lithuanian University of Health
Sciences, Kaunas, Lithuania
Contact E-mail Address: laimasj@takas.lt
INTRODUCTION: In our former report (1) we represented the interim results
on the correlation of alarm symptoms and clinically significant findings found on
EGDS in 502 ambulatory patients. The results raised the doubts if the presence of
alarm symptoms yields in much more clinically significant findings. Therefore we
continued the study and the amount of patients was doubled.
AIMS & METHODS: Aim. To evaluate the correlation of alarm symptoms and
clinically significant findings found on Esophagogastroduodenoscopy (EGDS) in
the routine clinical practice in ambulatory setting.
Methods. A prospective study performed in 5 hospitals in Lithuania: Hospital of
Lithuanian University of Health Sciences (tertiary level), and 4 secondary level
hospitals. The data of ambulatory patients referred to upper endoscopy were
collected and analyzed. Alarm symptoms that were evaluated as an indication
to perform EGDS were: dysphagia, odynophagia, anemia, signs of upper GI
bleeding (suspicion of melena), weight loss, recurrent vomiting, fever. The following endoscopic findings were considered as a clinically significant: erosive
esophagitis, gastric ulcer, duodenal ulcer, gastric or duodenal polyps, malignant
tumors.
RESULTS: Data from 1010 patients (mean age- 56.416.3) were analyzed: 379
(37.5%) males and 631 (62.5%) females. Mean age of males 53.815.9, of
females 58.0 16.3 years, p50.01. Alarm symptoms were found in 137
(13.6%) patients: in 75 (11.9%) females and in 62 (16.4%) males, p50.05.
Mean age of patients with alarm symptoms- 57.618.6, without alarm symptoms- 56.215.9, p40.05. Clinically significant findings found in 381 (37.7%)
patients. Malignant tumor found only in 7 (0.7%) patients. Mean age of patients
with clinically significant findings was 56.315.4, without clinically significant
findings- 56.516.8, p40.05. Among patients with alarm symptoms, clinically
significant findings were found in 48 (35.0%) patients, among patients without
alarm symptoms in 333 (38.1%), p40.05. Duodenal or gastric ulcer was found
in 4 (26.7%) out of the 15 patients with melena, and in 66 (6.6%) out of 995
patients without melena, p50.05. We did not find any differences in clinically
significant findings if the patients were referred to upper endoscopy by gastroeneterologist or not gastroenterologist.
CONCLUSION: The presence of alarm symptoms in our cohort was not associated with the clinically significant findings. Only the presence of signs of upper
gastrointestinal bleeding was associated with more frequent detection of peptic
ulcer. There is no correlation between the age and alarm symptoms and clinically
significant findings in our cohort. The prevalence of esophageal, gastric and
duodenal malignancies is extremely low (0.7%) in our studied setting.
Therefore it is not feasible to determine the role of alarm symptoms in predicting
the malignant diseases.
REFERENCES
1. Jonaitis L, et al. Alarm symptoms are not associated with the clinically significant findings in upper endoscopy in ambulatory setting. United Eur
Gastroenterol J 2013; 1: A557.
Disclosure of Interest: None declared
P1592 UPPER GASTROINTESTINAL MUCOSAL INJURY AND
SYMPTOMS IN ELDERLY PATIENTS TAKING LOW-DOSE ASPIRIN
Y. Shimada1,*, A. Nagahara1, I. Tanaka1, Y. Nakagawa1, K. Izumi1,
K. Matsumoto1, H. Ueyama1, H. Sasaki1, K. Matsumoto1, D. Asaoka1,
M. Hojo1, S. Watanabe1
1
Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Contact E-mail Address: yshimada@juntendo.ac.jp
INTRODUCTION: It is well known low-dose aspirin (LDA) not only increases
the risk of gastrointestinal (GI) mucosal injury but also worsens the quality of life
(QOL) because of the symptoms like dyspepsia. Today, many elderly patients are
taking LDA to prevent atherosclerosis diseases. Moreover, the number of LDA
users is expected to increase in the future.
AIMS & METHODS: To reveal the clinical features of LDA related upper
gastrointestinal mucosal injury (u-GI) especially in elderly patients, we investigated the prevalence, severity and symptom of esophageal mucosal injury (EI),
gastric mucosal injury (GI) and duodenal mucosal injury (DI) individually
between elderly patients (sixty-five years of age or over) LDA users (Users)
and non-users (Non-users). Data was extracted from the records of subjects
who underwent upper gastrointestinal endoscopy at our department between
April 2008 and December 2013. Among 3162 elderly patients answering
Frequency of Scale for Severity of GERD (FSSG) and SF8-QOL (SF8) were
analyzed after excluding proton pump inhibitor or histamine type 2 receptor
antagonist users. Prevalence was compared between Users and Non-users.
Among patients who were diagnosed to have mucosal injuries, symptoms and
QOL were compared between Users and Non-users. FSSG items were classified
into total score (TS), reflux score (RS) and dyspepsia score (DS). SF8 has physical component summary (PCS) and mental component summary (MCS).
RESULTS: The study included 281 Users (199 men, 82 women; mean age, 72.7
years), and 2881 Non-users (1617 men, 1264 women; mean age, 71.7 years),
respectively. Prevalence of EI in Users: Non-users was 10.0% (n 28): 9.6%
(n 276) (p 0.83), GI was 35.9% (n 101): 27.5% (n 792) (p 0.003) and
DI was 3.2% (n 9): 3.4% (n 99) (p 0.84). Regarding symptoms and QOL,
TS, RS and DS of EI were Users: Non-users 5.8  6.6: 6.4  6.3 (p 0.61), 3.3

 4.3: 3.7  3.9 (p 0.57) and 2.5  3.1: 2.7  2.9 (p 0.72), GI were 5.0  5.8:
6.0  6.3 (p 0.13), 2.6  3.2: 3.1  3.7 (p 0.15) and 2.4  3.1: 2.9  3.1
(p 0.17), DI were 2.6  2.1: 4.8  4.5 (p 0.13), 0.7  1.1: 2.6  2.8 (p 0.04)
and 1.9  1.8: 2.6  2.8 (p 0.69). PCS and MCS of EI were Users: Non-users
were 44.5  9.1: 48.9  5.8 (p 0.0004) and 50.6  5.9: 50.0  6.3 (p 0.65), GI
were 47.4  7.1: 47.8  6.4 (p 0.60) and 50.5  5.4: 49.5  6.6 (p 0.14), DI
were 48.8  6.7: 49.0  6.6 (p 0.93) and 45.3  6.6: 50.3  6.3 (p 0.02).
CONCLUSION: Prevalence of gastric mucosal injury in elderly LDA users was
significantly higher than Non-users, although the prevalence of esophageal and
duodenal mucosal injury was about the same. LDA users diagnosed with duodenal mucosal injury had significantly less symptom score on RS. LDA users
diagnosed with esophageal mucosal injury had significantly less PCS score and
LDA users diagnosed with duodenal mucosal injury had significantly less MCS
score. These results give us the important clinical information that symptom
based management was not appropriate in elderly LDA users in terms of
upper gastrointestinal mucosal injuries.
Disclosure of Interest: None declared
P1593 ESOPHAGEAL MUSCULAR RING: CLINICAL REVIEW OF 10
CASES
H.S. Hwang1,*, J.S. Oh1, H.H. Kim1, H.N. Choi1, J.S. Park1, S.H. Kim1,
S.M. Kang1, J.G. Kwon1, E.Y. Kim1, J.T. Jung1
1
Department of Internal Medicine, Catholic University of Daegu School of
Medicine, Daegu, Korea, Republic Of
INTRODUCTION: The lower esophageal muscular ring remains a poorly
defined entity. Distinguishing the muscular ring from achalasia and other
causes of focal esophageal stenosis is important because of the differences in
treatment and outcome.
AIMS & METHODS: The aim of this study is to analyze clinical characteristics
of lower esophageal muscular ring. Medical records of 10 cases of lower esophageal muscular ring diagnosed at Daegu Catholic University Hospital from 2002
to 2013 were reviewed and analyzed retrospectively.
RESULTS: 10 patients comprised of 5 men and 5 women, with mean age of 57.4
years (range 43-72 years). The nine patients (90%) had symptoms consisting of
chronic, intermittent dysphagia for both liquids and solids. Upper gastrointestinal endoscopic examinations revealed a focal smooth concentric narrowing of
esophagus located a few centimeters above the squamocolumnar junctions.
Endoscopic ultrasound examination showed a focal thickening of inner circular
muscle at the luminal narrowing and mean thickness of muscle ring was 5.2  1.4
mm. Nine patients underwent esophageal manometry and mean lower esophageal sphincter (LES) pressure was 35.2  18.4 mmHg. Five cases showed complete LES relaxation and 8 cases showed well propagated esophageal body
peristalsis. Mean amplitude of distal esophageal body contraction was 105.9 
43.9 mmHg. Barium esophagogram showed concentric narrowing of distal esophagus or patent esophageal lumen. Mean maximal diameter of luminal narrowing was 6.1 mm (range 2.6 -12 mm). Six cases were treated with calcium channel
blocker and 4 cases had significant symptomatic improvement.
CONCLUSION: We have presented a series of 10 cases of patients with lower
esophageal muscular rings. Considering a possibility of a muscular ring in the
distal esophagus, well propagated esophageal body peristalsis, complete LES
relaxation and variable luminal opening at barium esophagogram may help
differential diagnosis of focal esophageal stenosis.
Disclosure of Interest: None declared
P1594 THE
EFFECT
OF
K027,
A
NOVEL
ACETYLCHOLINESTERASE REACTIVATOR, ON GASTRIC
MYOELECTRIC ACTIVITY ASSESSED BY
ELECTROGASTROGRAPHY IN EXPERIMENTAL PIGS

OXIME

J. Bures1,*, J. Kvetina1, J. Zdarova Karasova2, I. Tacheci1, M. Pavlik3,


M. Kunes4, K. Musilek2, S. Rejchrt1, T. Douda1, K. Kuca4, M. Kopacova1
1
2nd Department of Internal Medicine - Gastroenterology, Charles University
Faculty of Medicine and University Teaching Hospital, 2Department of
Toxicology, 3Centre of Advanced Studies, University of Defence, Faculty of
Military Health Service, 4Biomedical Research Centre, University Teaching
Hospital, Hradec Kralove, Czech Republic
Contact E-mail Address: bures@lfhk.cuni.cz
INTRODUCTION: Reactivators of acetylcholinesterase (AChE) are essential in
the treatment of organophosphate intoxication. Wider clinical use of several
AChE modulators is limited because of the significant side effects, including
serious gastrointestinal toxicity. Our research team has synthesised our own
priority compound K027, 1-(4-carbamoylpyridinium)-3-(4-hydroxyiminomethylpyridinium)-propane dibromide. This novel oxime AChE reactivator was already
tested in-vitro and on small laboratory animals with excellent results. K027 might
thus be a candidate for human therapeutic use in the event of industrial poisoning
or catastrophic situations. The small adult pig can be used in experiments as an
omnivorous representative due to its relatively very similar gastrointestinal functions in comparison to man.
AIMS & METHODS: The aim of this study was to evaluate the effect of K027
on porcine electrogastrography (EGG). Six mature female pigs (3 months old,
mean weight 23.22.1 kg) were included in the study. All EGG recordings were
performed under general anaesthesia in the morning after 24 hours of fasting (by
means of the MMS EGG System, Enschede, the Netherlands). After 10-minute
baseline EGG, K027 (1500 mg i.m.) was administered. The EGG trial recording
lasted 150 min. Running spectral analysis was used for initial evaluation of the
EGG. The gastric myoelectric activity was estimated by EGG power analysis
(areas of amplitudes) and by power ratio assessment (ratio of the areas of amplitudes after and before K027 administration).

A570
RESULTS: After i.m. administration, K027 did not cause any significant
changes in EGG dominant frequency. EGG power results displayed nonnormal distribution. The power increased from the baseline mean values
648326 (V^2) to 48817756 (at 5 min.) and 1273024404 (at 10 min.),
p 0.032, p 0.151. Afterwards, the power values decreased gradually to those
comparable with baseline ones (536301 V^2 at 150 min.). The EGG power
ratio reached the highest values at 5 min. (11.320.3) and 10 min. (31.262.7),
decreased significantly at 20 min. (3.02.9; p50.001) and stayed at low values
until 150 min. (1.00.9).
CONCLUSION: K027, a novel AChE reactivator, caused only a transient
increase in the EGG power with quick subsequent equalisation comparable
with initial basal myoelectric values.
Acknowledgement: The study was supported by research grant IGA NT/14270-3
from the Ministry of Health.
Disclosure of Interest: None declared
P1595 EFFECTS OF NESFATIN-1 ON GASTRIC DISTENSION
SENSITIVE NEURONAL DISCHARGE AND GASTRIC MOTILITY
IN THE ARCUATE NUCLEUS OF RATS
L. Xu1,*, F. Guo1, S. Gao1, X. Sun1, Y. Gong2
1
Pathophysiology, Medical College of Qingdao University, 2Department of
Pharmacy, Qingdao University of Science and Technology, Qingdao, China
Contact E-mail Address: xu.luo@163.com
INTRODUCTION: Nesfatin-1, derived from the precursor NEFA/ nucleobinding-2 (NUCB2), is a newly identified 82-amino-acid anorexigenic neuropeptide
which was initially discovered in the neurons of the hypothalamus. Several studies have showed that central administration of nesfatin-1 could suppress food
intake and body weight gain, underscoring the potential importance of this peptide in the controlling of feeding behavior. Although the novel satiety peptide
nesfatin-1 has been revealed to regulate the motor function, the underlying
mechanisms have yet to be elucidated.
AIMS & METHODS: The study aims to explore effects of nesfatin-1 in arcuate
nucleus (Arc) on gastric distension sensitive neurons (GD) and gastric motility,
and the potential regulation mechanisms by lateral hypothalamic area (LHA).
Single unit discharges in Arc were recorded extracellularly and gastric motility in
conscious rats was monitored when administration of nesfatin-1 to Arc or electrical stimulation of LHA. Retrograde tracing and fluo-immunohistochemistry
staining were used to determine NUCB2/nesfatin-1 neuronal projections.
RESULTS: Nesfatin-1 could inhibit most of GD-excitatory neurons (GD-E), but
excite GD-inhibitory neurons (GD-I) in Arc. The reduced firing by nesfatin-1 on
GD-E neurons could be partly absorbed by SHU9119 (P50.05), an antagonist of
melanocortin 3/4 receptor. The gastric motility was significantly reduced by
administration of nesfatin-1 into Arc (P50.05). Electrical stimulation of LHA
could excite most of GD neurons in Arc (P50.05) and promote gastric motility
(P50.05). However, pretreatment of anti-NUCB2/nesfatin-1 antibody in Arc
could further increase the firing rates of GD-E neurons induced by electrical
stimulating LHA (P50.05). NUCB2/nesfatin-1/fluorogold-double labeled neurons were observed in the LHA.
CONCLUSION: The results suggested that the effects of nesfatin-1 on GD-E
neurons may be related with melanocortin signal pathway. Nesfatin-1 in the
LHA perhaps was involved in the regulation of Arc on gastric activity.
REFERENCES
This work was supported by the National Natural Science Foundation of China
(Nos.31071014, 81100260, 81270460 and 81300281); Qingdao Municipal Science
and Technology Commission (13-1-4-170-jch and 11-2-3-3-(2)-nsh).
Disclosure of Interest: None declared
P1596 IMPEDANCE PLANIMETRY (ENDOFLIP) MEASUREMENTS
AT THE ESOPHAGO-GASTRIC JUNCTION DISTINGUISH
NEUROMUSCULAR DISEASE FROM FIBROTIC LESIONS IN
DYSPHAGIA PATIENTS
J. Lenglinger1,*, E. Rieder1, S.F. Schoppmann1
1
Surgery, MEDICAL UNIVERSITY OF VIENNA, Wien, Austria
Contact E-mail Address: johannes.lenglinger@meduniwien.ac.at
INTRODUCTION: Impaired opening of the esophago-gastric-junction (EGJ) is
a frequent cause of dysphagia and may be due to neuromuscular disease or
fibrosis. Aim of this study was to test whether impedance planimetry parameters
can be used to distinguish these etiologies.
AIMS & METHODS: Based on endoscopy, histopathology, HR-manometry
and videofluoroscopy dysphagia was ascribed to be of neuromuscular (NM) or
fibrotic (F) origin. A catheter fitted with a 25 mm balloon (EndoFLIP EF-320)
was inserted into the stomach transnasally and retracted until it was centered
across the esophagogastric junction. The EndoFLIP catheter acts as a functional imaging probe (FLIP) converting voltage measurements inside the balloon
to estimations of balloon diameters at 5 mm intervals over 8 cm length.
Intraballoon pressure is monitored by a solid state pressure transducer, facilitating the calculation of compliance data. EGJ distensibility measurements over 30
seconds were performed with balloon filling volumes of 20, 30, 40, and 50 ml
volumes, respectively. Estimations of diameter and the distensibility index (DI,
cross sectional area in mm2 divided by intraballoon pressure in mm Hg) were
used as parameters. Study hypothesis was that DI is inversely correlated with
balloon filling volume in patients with fibrotic lesions whereas it remains constant in subjects with neuromuscular disease affecting the esophago-gastric junction. The quotient of DI at 50 ml and at 30 ml volumes (DI 50 ml/DI 30 ml) was
used to account for the change of distensibility with balloon filling volume.
RESULTS: The NM group comprised 20 subjects (4 females). Diagnoses were
achalasia in 7, hypertensive lower esophageal sphincter (LES) in 4, and impaired

United European Gastroenterology Journal 2(1S)


LES relaxation upon swallowing in 9 patients. In the F group of patients (1
female) 4 had eosinophilic esophagitis, 5 a Schatzki-ring, and 6 a peptic stenosis.

Age (yrs)
EGJ diameter 30 ml (mm)
EGJ diameter 50 ml (mm)
DI 30 ml (mm2/mm Hg)
DI 50 ml (mm2/mm Hg)
Distensibility Index Quotient
(DI 50 ml/DI 30 ml)

NM n 20

F n 15

p-value

42.1  19.4
6.2 (5.0 - 7.9)
11.6 (8.7 - 12.7)
1.4 (0.9 - 2.4)
2.1 (1.5 - 2.7)

52.9  17.8
7.2 (6.5 - 10.0)
9.3 (8.7 - 10.7)
2.3 (1.7 - 3.0)
1.3 (0.9 - 1.6)

n.s.
0.007
n.s.
n.s.
n.s.

1.4 (1.0 - 2.0)

0.6 (0.5 - 0.9)

0.001

CONCLUSION: In patients with neuromuscular disorders DI remained constant or increased with filling volume, whereas a decrease was encountered in
patients with fibrosis. In this study we have shown that a new parameter, the
distensibility index quotient (DI 50 ml/DI 30 ml), can be used to distinguish
neuromuscular disease from fibrotic lesions at the EGJ. This might have implications for the choice of treatment.
Disclosure of Interest: None declared
P1597 CLINICAL
OUTCOME
OF
PATIENTS
UNDERGOING
ESOPHAGEAL HIGH-RESOLUTION MANOMETRY (HRM) IS
ASSOCIATED WITH MANOMETRIC FINDINGS
J. Keller1,*, V. Andresen1, P. Layer1
1
Internal Medicine, Israelitisches Krankenhaus, Hamburg, Germany
Contact E-mail Address: j.keller@ik-h.de
INTRODUCTION: Esophageal manometry is the reference method for diagnosis of achalasia and other esophageal motility disorders. It is also frequently
recommended for patients with refractory reflux disease, particularly for those
scheduled for fundoplication. The association between manometric findings
obtained by HRM and clinical outcome parameters is unknown.
AIMS & METHODS: It was our aim to investigate clinical outcome in patients
undergoing HRM with special respect to patients with impaired relaxation of the
lower esophageal sphincter (IR-LES). Between September 2011 and June 2013
250 patients undergoing HRM were enrolled into a prospective study assessing
demographics, manometric findings, pH-data, reflux symptoms (GerdQ) and
dysphagia (HODQ, 5 items). Quality of life (QoL, SF-36) was also evaluated
at the time of the investigations and 4-6 months later. The kind of treatment was
assessed and patients rated overall treatment satisfaction. Data of all subjects
with IR-LES and of an identical number of subjects with normal LES relaxation
(NR-LES) were analysed.
RESULTS:

Achalasia
EGJ-OO
NR-LES
p-value

LES basal pH54,


tone, mmHg %
GerdQ

HODQ

Invasive SF-36
SF-36 pre TX
post

323 7
312
131
50.0001

122
31
21
50.0001

796
903
963
0.026

43.5
3.41.6
9.71.4
0.017

111
91
111
50.0001

70%
14%
22%
0.002

1006
973
1063
NS

Age and BMI were similar for subjects with IR-LES (n 55) and NR-LES
(n 55). NR-LES patients were more frequently male (53% vs. 26% p50.05).
15 patients with IR-LES were diagnosed with achalasia, 40 had signs of EGJ
outlet obstruction (EGJ-OO). Only 7 subjects with NR-LES had completely
normal manometric findings. Patients with achalasia had similar GERD symptoms compared with NR-LES patients but more severe dysphagia and the lowest
QoL (table). They received more invasive treatment (endoscopic or surgical) and
had a more profound increase in QoL, although QoL improved significantly in
all patient groups (p50.05 pre vs. post).
CONCLUSION: HRM has a high diagnostic yield and manometric findings are
associated with choice of treatment modalities and posttherapeutic alterations of
QoL. Patients identified as having achalasia according to HRM receive more
invasive treatment and have the highest increase in QoL.
Disclosure of Interest: J. Keller Financial support for research from: Given
Imaging, Lecture fee(s) from: Standard Instruments, Given Imaging,
Consultancy for: Given Imaging, V. Andresen: None declared, P. Layer: None
declared
P1598 EFFECTS OF PNEUMATIC DILATION ON LES AND UES
PARAMETERS AND THEIR CORRELATION WITH SYMPTOMS
IMPROVEMENT IN PROSPECTIVELY EVALUATED PATIENTS
WITH ESOPHAGEAL ACHALASIA
M. Pesce1,*, R. Cuomo1, P. Andreozzi1, F.P. Zito1, A. DAlessandro1,
A. Santonicola1, N. Gennarelli1, G. De Carlo1, G. Sarnelli1
1
Clinical Medicina and Surgery, UNIVERSITY OF NAPLES " FEDERICO II",
Naples, Italy
Contact E-mail Address: mapesc@hotmail.com
INTRODUCTION: An impairment in lower esophageal sphincter (LES) function is recognized as the hallmark feature of idiopathic achalasia; however, it has

A571

United European Gastroenterology Journal 2(1S)


become apparent that malfunctioning in upper esophageal sphincter (UES) may
also occur in achalasia, but not in other esophageal motor disorders. In a recent
study, pneumatic dilation has been retrospectively linked to an improvement in
UES function.
AIMS & METHODS: Aim of this study was to prospectively evaluate the impact
of pneumatic dilation on HRMI parameters. 27 (14 Males; age 41  12 ys) newly
diagnosed achalasia patients were enrolled. All patients underwent to pneumatic
dilatation with a 30 mm diameter balloon, inflated for 120 seconds at 12 psi. In
all patients a standardized questionnaire assessing the frequency and the intensity
of achalasia-related symptoms (dysphagia for solids and liquid graded from
0:absent to 9: at each meal and precluding daily activities) was administered
before and 6 months after pneumatic dilation. At the same time points, a
HRMI study was performed in all patients. Manometric parameters studied
were (i) LES basal pressure (LESbasalP) and 4-second integrated relaxation
pressure (IRP4); (ii) UES resting pressure (restP) (iv) UES basal pressure
(UESbasalP) and (v) incomplete esophageal clearance. All data are given as
mean  SD.
RESULTS: According to the Chicago Classification, 20 out of 27 were classified
as having type-2 achalsia, 2 patients had type-3 achalasia and 5 patients were
diagnosed as type 1. Six months after treatment, patients showed a sustained
symptomatic improvement in terms of dysphagia for both solids and liquids
(11.4 vs 6.72.2 and 0.61.1 vs 5.33.2 respectively; all p50.001). After the
pneumatic dilation, a significant reduction in LES basal pressure and IRP4 was
observed (2812 vs 4612 mmHg and 179 vs 3511 mmHg respectively; all p
50.001). Similarly, UES resting pressure resulted significantly decreased as compared to pretreatment values (85 vs 168 mmHg; p 0.002); whilst no differences were observed in UES basal pressure or incomplete esophageal clearance
(9032 vs 7842 mmHg and 7529 vs 7429%, respectively; all p NS). A
positive correlation between the severity of dysphagia and LES pressure, IRP4
and UES resting pressure was observed (r2 0.305, r2 0.592 and r2 0.419,
respectively, all p50.001), while UES basal pressure or incomplete esophageal
clearance were not significantly correlated.
CONCLUSION: Here we demonstrated that pneumatic dilation of LES induced
a sustained reduction of UES resting pressure, showing a positive correlation
with patients symptomatic improvement. Although LES pressure remains the
main target of pneumatic dilatation; the positive effect of this technique on UES
appears to contribute to the symptomatic improvement of these patients, supporting the idea that pneumatic dilatation has an undervalued effect on UES
function.
Disclosure of Interest: None declared
P1599 TRAINING IN PER ORAL ENDOSCOPIC MYOTOMY USING
PRECLINICAL ANIMAL MODEL: ANALYZING THE LEARNING
CURVE
R. Dolezel1,*, J. Martinek2, H. Svecova2, O. Ryska3, S. Juhas4, J. Juhasova4,
P. Stirand2, J. Spicak2, M. Ryska1
1
Department of Surgery, Military University Hospital, 2Department of
Hepatogastroenterology, IKEM, Prague, 3Department of Surgery, Horovice
Hospital, Horovice, 4Institute of Animal Physiology and Genetics, Academy of
Sciences, Libechov, Czech Republic
Contact E-mail Address: dolezrad@uvn.cz
INTRODUCTION: POEM is a complex and demanding endoscopic procedure
with a potential of serious complications. Therefore it requires a set of endoscopic skills. Training requirements and a learning curve for POEM are to be still
defined. Increasing experience with POEM leads to an urgent need of defining
adequate training program for new trainees to assure the appropiate clinical
safety.
AIMS & METHODS: We report results of our training program for experienced
endoscopists using a preclinical porcine model. Prospective cohort study from a
single center involved 39 patients (24 men, 15 women) undergoing POEM. All
procedures were performed by one experienced endoscopist after training on 10
pigs. The first clinical procedure was supervised by an expert in the field. All
patients had a diagnosis of esophageal achalasia. We divided patients into 3
consecutive groups (3x n 13). We set the length of procedure (LOP) divided
by length of myotomy (LOM) as an appropriate outcome (LOP/LOM) of skills
progression in time. Analysis of a learning curve was based on LOP/LOM and
frequency of complications (e.g. inadvertent mucosotomies).
RESULTS: POEM was successfully completed in all ten pigs. As for complications we reported 5 bleedings, 2 esophageal perforations and 2 inadvertent mucosotomies in animal model. Autopsies revealed safe closures of porcine esophagus
(6.11.1 clips), LOP/LOM was 5.11.8 minutes/cm. All POEM procedures in 39
patients (aged 45.6  13.6 years; BMI 25.2  4.5 kg/m2) were performed without
any serious intraoperative complications. Mean length of hospitalization was 2.5
.0.7 days. The mean LOP was 83.6  22.6 minutes and the mean myotomy
length was 12.5  2.6 cm. The mean LOP/LOM (7.1  2.7 minutes/cm) decreased
with increasing experience (P-value50.001): first group (10.1  1.9 minutes/cm);
second (5.9  1.5 minutes/cm); and third (5.3  1.6 minutes/cm).
An inadvertent mucosotomy was reported in 3 patients (7.7%), all of them
occurred in the first group of patients and were successfully treated endoscopically with clips. The frequency of carbon dioxide extravasation (capnoperitoneum requiring a puncture (41%) and subcutaneous emphysema (23%)) were
not influenced by experience (P-value 1).
Plateau phase of learning curve (based on LOP/LOM) began with the 12th
patient and has fully stabilized since the 14th patient (24th procedure including
animal training).
CONCLUSION: A significant learning curve of POEM after preclinical animal
training was recorded in decreasing LOP, faster myotomy itself and decreasing
number of inadvertent mucosotomies. Carbon dioxide extravasation was not
influenced by learning. Our results suggest that primary POEM training of

experienced endoscopist on at least ten pigs might shorten the achievement of


plateau phase to approximately 14 clinical procedures.
Supported by a grant form IGA NT-13634-4.
Disclosure of Interest: None declared
P1600 HYDRAULIC DILATION IN IDIOPATHIC ACHALASIA USING
THE ESOFLIP DILATION BALLOON: A FEASIBILITY STUDY
W. Kappelle1,*, A. Bogte1, P. Siersema1
Gastroenterology and hepatology, UMC Utrecht, Utrecht, Netherlands
Contact E-mail Address: w.f.w.kappelle@umcutrecht.nl
1

INTRODUCTION: Pneumatic dilation is a commonly used treatment in achalasia. Fluoroscopy enables positioning of the balloon at the oesophagogastric
junction (OGJ) but has the disadvantage of radiation exposure. An important
element of dilation is oesophageal distensibility, defined as compliance of the wall
at a certain point, which can be used to assess the effect of dilation and possibly
the risk of perforation. It is currently not possible to measure distensibility during
dilation. A new hydraulic dilation balloon, the EsoFLIP, is able to visualise the
shape of the balloon in vivo, thereby obviating the need for fluoroscopy, and
measures distensibility during dilation.
AIMS & METHODS: The aim of this study was to evaluate technical feasibility
and safety of the 30mm EsoFLIP hydraulic dilation balloon in patients with
achalasia. Consecutive patients with newly diagnosed achalasia were dilated on
two separate days using the EsoFLIP balloon under endoscopic visualisation.
Patients were contacted one week, one month and three months after dilation.
Technical success (placement at the OGJ and successful dilation while measuring
diameter, pressure and distensibility), clinical success and major complications
were evaluated.
RESULTS: Ten patients (4 male [40%], median age 50 years, range 27-62) were
included between August 2013 and February 2014. Patients were subjectively
symptomatic for a median of 9 months (range 3-24) prior to dilation.
Technical success was achieved in all cases. Gradual inflation showed that the
balloon had a tendency to migrate during inflation but in vivo imaging enabled
precise placement at the OGJ. On day one, the median minimal diameter (mm) of
the OGJ before and after dilation were 9.5 (range 7.2-12.9) and 16.3 (range 13.421.4), respectively. On day two, these diameters were 13.9 (range 8-15.2) and 16.7
(range 14.2-18.6), respectively. Median difference in diameter before the first and
after the second dilation was 7.2 (range 3.2-9.2). Median pressures (mmHg) used
during the first and second dilation were 551 (range 310-1130) and 603 (range
390-815), respectively. Median oesophageal distensibility (mm2/mmHg) on the
first day before and after dilation were 1.0 (range 0.2-2.2) and 8.2 (range 0.820.1), respectively, while on the second day this was 1.7 (range 1-4.3) and 5.9
(range 3.3-29.3). Median difference in distensibility before the first and after the
second dilation was 5.7 (range 2.1-28.3). No major complications were seen.
Three patients (30%) reported recurrent dysphagia and laparoscopic Heller
myotomy was performed in two (66.7%).
CONCLUSION: Dilation with the 30mm EsoFLIP balloon in achalasia is feasible and safe. In vivo imaging of the balloon shape facilitates placement of the
balloon while oesophageal distensibility and diameter measurements allow for a
patient-specific dilation regimen, which may improve effectiveness and safety of
the procedure.
Disclosure of Interest: W. Kappelle Financial support for research from: Crospon
Ltd., A. Bogte: None declared, P. Siersema: None declared
P1601 PATTERNS OF PERISTALSIS RECOVERY AFTER PERORAL
ENDOSCOPIC MYOTOMY IN ACHALASIA PATIENTS
Z. Vackova1,*, J. Krajciova1, H. Svecova1, L. Fremundova2, P. Loudova3,
R. Dolezel4, J. Spicak1, J. Martinek1
1
Department of Hepatogastroenterology, Institute for Clinical and Experimental
Medicine, Prague, 2Department of Internal Medicine, University Hospital in
Pilsen, Pilsen, 3Endoscopic Centre, Kolin Hospital, Kolin, 4Department of Surgery,
Military University Hospital, Prague, Czech Republic
Contact E-mail Address: vackova.zuz@gmail.com
INTRODUCTION: A detailed analysis of whether impaired esophageal peristalsis in achalasia patients can recover after peroral endoscopic myotomy (POEM)
has not been performed. We tested the hypothesis that the normalization of
esophagogastric junction outflow obstruction after POEM is associated with a
partial recovery of esophageal peristalsis.
AIMS & METHODS: We performed an analysis of prospectively collected high
resolution manometry (HRM) data of patients undergoing POEM at a single
institution (IKEM). 27 patients (8 women, 19 men) underwent HRM before and
3 months after POEM. Twenty-six patients were diagnosed with achalasia (type
I- 2 patients, type II- 22 patients, type III-2 patients) and one patient had
Jackhammer esophagus. Detailed HRM analysis according to the Chicago classification was performed. The main outcome measurements were: changes in
integrated relaxation pressure (IRP) and changes in esophageal peristalsis pattern
related to the symptomatic response after POEM.
RESULTS: Before POEM, peristaltic fragments were present in 3 patients only
(2 with type III achalasia and 1 with Jackhammer esophagus). After POEM, 15
patients (55%) were classified according to the Chicago classification as either
frequent failed peristalsis (n 6) or weak peristalsis with large breaks (n 9).
Nine patients (33%) persisted in having absent peristalsis and three patients
(11%) were still meeting the criteria of achalasia (type II). In 17 patients out
of 22 with type II achalasia (77%), the panesophageal pressurization completely
disappeared or has been reduced to compartmentalized pressurization after
POEM. The mean IRP decreased from 24.7 ( 11) mmHg before to 12.0 (5)
mmHg after POEM. All patients with IRP normalization (IRP515 mmHg) had
an excellent symptomatic response. Among 4 patients with post-POEM IRP415

A572
mmHg, three had only partial symptomatic improvement (Eckhard score 2, 3
and 5), which corresponded with persistence of panesophageal pressurization.
CONCLUSION: More than half of achalasia patients with IRP normalization
after POEM have signs of partial recovery of esophageal peristalsis. Successful
POEM is associated with a disappearance of panesophageal pressurization in
type II achalasia. Patients with abnormal IRP after POEM have partial symptomatic improvement without signs of peristaltic recovery.
Supported by a grant form IGA NT-13634-4.
Disclosure of Interest: None declared
P1602 CORRELATION BETWEEN GERD AND BMI: ITS TIME TO
THINK ABOUT HYPOSENSITIVITY IN OBESITY
A. DAlessandro1,*, I. Arnone1, C. Buonfantino1, R. Civiletti1, M. Pesce1,
F.P. Zito1, G.D. De Palma1, V. Passananti1, R. Cuomo1, G. Sarnelli1
1
Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
Contact E-mail Address: alessa.dalessandro@gmail.com
INTRODUCTION: The positive correlation between GERD symptoms and
weight gain is well defined. However, we previously demonstrated that severe
upper-GI symptoms may negatively affect body weight by limiting food intake.
The aim of our study is to evaluate the correlation between BMI and GERD
features and symptoms severity in a large cohort of GERD patients.
AIMS & METHODS: 201 (119 F, mean age: 46.215.6 ys, BMI: 25.96) outpatients referring for GERD symptoms (heartburn, regurgitation, chest pain,
epigastric pain, dysphagia, odynophagia, respiratory symptoms) were enrolled.
All patients underwent careful history taking, physical examination and upperGI endoscopy. Upper-GI symptoms were scored according to standardized questionnaire, assessing the type and the severity of symptoms and their impact on
quality of life (PAGY-SYM/QoL). A pH-impedance monitoring was performed
in 198 patients, with 89 and 109 of them being off and on-therapy (68 F, mean
age: 45.213.7 ys; BMI 25.35.3 and 67 F, mean age 47.414.7 ys; BMI
26.25.9, respectively). BMI was recorded and patients were divided, according
to internationally accepted criteria, in normal- and overweight. Patients with
history of diabetes mellitus were excluded.
RESULTS: Among all the investigated parameters, acid exposition and number
of proximal refluxes were significantly higher in over- than in normal-weight
patients (34.4 vs 1.82.6 %pH54 and 40.622.5 vs 31.922.2; all p50.05).
This finding was confirmed in both off- and on-therapy patients subgroups
(4.55.5 vs 2.31.9 and 1.82.9 vs 0.60.9 %pH54, all p50.05); while the
number of proximal refluxes resulted significantly higher only in off-therapy
subgroup (39.720 vs 28.616.7; p50.05). The analysis of symptoms severity
yields no significant differences in terms of cumulative symptoms score between
over- and normal-weight patients (12.79.9 vs 13.910). However, a significant
correlation between GERD-symptoms score and BMI values was overall
observed (r2 0.03, CI:-0.3 to -0; p50.01), with a significant correlation being
present in the subgroup of off-therapy (r2 0.01, CI:-0.4 to 0; p50.05), but not
in those on therapy (r2 0.01, CI: -0.3 to 0.1; p n.s.). The reduced symptoms
severity in overweight patients did not reflect a significantly different quality of
life.
CONCLUSION: In this study we observed that despite a higher esophageal acid
exposition and increased number of proximal refluxes, overweight GERDpatients had less severe symptoms and this did not significantly affect their
quality of life. Although the underlying mechanisms are unknown, if confirmed
by mechanistic studies, our results suggest that the reduced sensitivity in overweight GERD, by limiting patients complaining, may explain the increased risk
of GERD-complications frequently observed in this subset of patients.
Disclosure of Interest: None declared
P1603 SYNDROMIC ACHALASIA IN ALGERIA: ABOUT A NOVEL
SERIES
A. tebaibia1,*, M.A. Boudjella 1, M. Lahcene1, F. Benmediouni1, N. Oumnia1
1
Internal medicine department, Kouba Hospital, Algiers, Algeria
Contact E-mail Address: tebaibia@hotmail.com
INTRODUCTION: non-syndromic or isolated achalasia represents the most
commonly found form in adults. It is most often observed in sporadic cases.
In rare cases, achalasia can occur in genetic syndromes or be associated with
isolated abnormalities.
AIMS & METHODS: To identify the conditions associated with achalasia and
study the clinical profile in these syndromes.
This is a prospective study of 86 consecutive patients (M: 41, F: 45, mean age
18.23 / - 10.4 (3 months - 42 years) enrolled over a period of 21 years (Jan1992 Oct 2013). There were 52 children (60%) and 34 adults (40%). All patients
underwent a standardized symptoms questionnaire, a complete clinical check
up, an ophthalmologic check up with a Schirmer test, an adrenal hormone balance, an esophageal barium swallow, upper endoscopy and an esophageal
manometry.
RESULTS: Down syndrome (mental retardation, particular facies.) was
observed in 6 isolated cases from 6 families. Allgrove syndrome was noticed in
80 cases. It was familial (siblings) in 35 cases (16 families). Consanguineous
parents were found in 71% of cases. All patients had alacrima at birth, they
all developed achalasia later (100%). Whereas, adrenal insufficiency was found
in 43 cases (54%) and autonomic dysautonomia/ neurological abnormalities
(thenar and hypothenar muscle atrophy, reduced force of abduction and adduction of fingers, mental retardation, optic atrophy, ataxia, . . .) in 19 cases (24%).
It was a 3A syndrome (achalasia, alacrima, Addison) in 46 cases and a 4A
syndrome in eight cases. The syndrome was incomplete or called syndrome 2A
(alacrima, achalasia) in the other cases. In familial 3A (08 families), 17 cases of

United European Gastroenterology Journal 2(1S)


probable Allgrove syndrome who had at least alacrima were identified, they died
probably after an acute adrenal insufficiency.
CONCLUSION: Allgrove and Down syndrome are the two most common conditions associated with achalasia. They are more frequent in children than in
adults. Every achalasia or alacrima of children should lead to look for the
others components of the syndrome.
Disclosure of Interest: None declared
P1604 THE TRINITY OF GASTRIC EMPTYING SCINTIGRAPHY, 13C
ACETATE GASTRIC EMPTYING BREATH TESTING, AND REAL
TIME GASTRIC ULTRASONOGRAPHY INDICATES HIGH
PREVALENCE OF GASTRIC MOTOR DYSFUNCTION IN
FUNCTIONAL DYSPEPSIA
D. Nastou1,*, M.F. Jaboli1, C. Clayman1, O. Epstein1
Institute for Minimally Invasive Gastroenterology, Royal Free London NHS
Foundation Trust, London, United Kingdom
Contact E-mail Address: desnastos@yahoo.gr
1

INTRODUCTION: Gastric motor physiology can be assessed by gastric emptying scintigraphy (GES), 13C breath testing (GEBT) and real time gastric ultrasound (GUS). The aim of this study was to evaluate how commonly these tests
are abnormal in patients with functional dyspepsia (FD).
AIMS & METHODS: Twenty-seven patients fulfilling the Rome III criteria for
FD were enrolled in the study. All patients had a normal upper GI endoscopy
and underwent standard GES using 131I-technetium labeled mashed potato. On a
separate day, these patients underwent a combined liquid GEBT (four hour
breath test protocol using 170ml chocolate Ensure liquid substrate 50mg
13
C-acetate) and GUS (calculating antral area at the time of ingestion and 15
minutes after ingestion of the GEBT liquid test meal).
RESULTS: Eight of the 27 patients had one abnormal test, six had two and in
five, all three tests were abnormal. In fifteen of the 27 patients with a normal
GES (56%), eight had normal GEBT and GUS studies. Of the remaining seven
patients, four had a normal GEBT and an abnormal GUS, two had normal GUS
with an abnormal GEBT, and in one, both the GEBT and GUS were abnormal.
GES was delayed in ten of the 27 patients (37%). In four of these, both GEBT
and GUS were abnormal, three had delayed gastric emptying on GEBT with a
normal GUS, two had delayed gastric emptying on GUS with normal GEBT,
and in one patient, both GUS and GEBT were normal. GES was abnormally
rapid in two patients (7%). In one patient, both GEBT and GUS indicated rapid
gastric emptying and in the other, GUS revealed rapid gastric emptying with a
normal GEBT. Assuming GES as the gold standard for diagnosing abnormal
gastric emptying, GUS has a sensitivity and specificity for detecting a motor
disorder of 66% and GEBT has a sensitivity of 66% and a specificity of 80%.
CONCLUSION: In this group of FD patients, 70% had at least one abnormal
test of gastric motor function. Whilst GES is regarded as the gold standard test,
in seven patients with normal GES, the GEBT, GUS, or both, were abnormal.
This discrepancy might reflect the day-to-day variability of gastric motor function testing or that each investigation measures a different component of gastric
motor physiology. We conclude that in FD, adding GEBT and GUS to GES
substantially increases the positive diagnostic yield and the heterogeneous patterns might indicate a variety of FD subtypes.
Disclosure of Interest: None declared
P1605 SCREENING OF GASTRITIS IN A POPULATION OF DYSPEPTIC
PATIENTS: ROLE OF STOMACH SPECIFIC PLASMA BIOMARKERS
A. Antico1, M.P. Panozzo1, M. Franceschi2, F. Tomba2, A. Ferronato2,
S. Bencivenni2, D. Sella2, E. Vanzetto3, F. Di Mario4, G. Baldassarre2,*
1
Laboratory Service, 2Endoscopic Unit - Department of surgery, 3Health Service,
ULSS4 - Alto Vicentino, Santorso (VI), 4Department of Clinical and
Experimental Medicine, University of Parma, Parma, Italy
INTRODUCTION: A no invasive screening procedure able to identify subjects
at high or low risk for gastritis should allow to limit unnecessary endoscopy and
histology. The role of specific stomach plasma biomarkers in diagnosis and
screening for chronic atrophic gastritis (CAG) is emerging as useful tool in
provide informations about gastric mucosa function.
AIMS & METHODS: To evaluate the utility of a serological stomach panel as
screening method for identifying patients with high or low risk for gastritis with
respect to those with normal gastric function or gastro esophageal reflux disease.
652 dyspeptic patients (M 223, F 429, mean age 42.415.3 years,
range 18-87 years) without any alarm symptom (dysphagia, anemia, weight
loss and vomiting) were selected from General Practitioners for fasting blood
collection and stomach markers assays (Biohit Plc, Finland).
For each of them a standard questionnaire was requested including upper gastrointestinal symptoms, thyroiditis history and PPI therapy. For the study 429
patients were examinated; 223 patients were excluded because of PPI therapy.
Patients affected by CAG were submitted to EGDS and histology and to parietal
cell antibodies (PCA) assay (IFA method).
RESULTS: The table reports four groups of patients subdivided according to the
stomach marker results.

A573

United European Gastroenterology Journal 2(1S)

Patients (n )
Age (years)
Thyroiditis (%)
PG1 (ug/L)
PG2 (ug/L)
PG1/PG2
G17 (pmol/L)
Hp Abs (EIU)

P1607 SAFETY AND EFFICACY OF PNEUMATIC BALLOON DILATION


AFTER HELLERS MYOTOMY

Normal (N)

Gastroesophageal
reflux Disease
(GERD)

H. pylori
Gastritis
(HPG)

CA Gastritis
(CAG)

132
40.822.2
6.1
79.426.8
5.82.4
14.54.3
5.413.2
5.85.9

163
39.611.1
11.7
84.837.7
6.22.9
14.54.6
0.60.3
4.95.1

114
42.412.4
12.3
130.411.7
14.18.2
10.03.9
12.615.2
83.931.8

20
58.015.8
50
15.211.5
7.33.6
2.52.5
47.442.9
29.832.8

GERD patients showed significantly lower G17 values with respect to the other
groups (p50.0001). HPG subjects had higher Hp Abs and PG2 values
(p50.0001). 3.3% were identified as CAG and presented significant lower PG1
and PG1/PG2 values and higher G17 levels (p50.0001). CAG subjects were
older than the other patients. 65% of CAG patients showed PCA positivity.
CONCLUSION: A no invasive serological stomach panel allows to distinguish
Normal and GERD from HPG and CAG groups in a general population of
dyspeptic patients; particularly, patients showing CAG serological findings are
also characterized by histological alterations and PCA positivity. Considering
these findings, it is necessary to identify as early as possible patients at risk of
developing precancerous gastric lesions.
Disclosure of Interest: None declared
P1606 THE IMPACT OF PERCEIVED JOB STRESS, ANXIETY,
DEPRESSION, COPING AND SOCIAL SUPPORT ON FUNCTIONAL
GASTROINTESTINAL DISORDERS: A CROSS-SECTIONAL STUDY
OF FIREFIGHTERS
H.S. Ryu1,*, Y.S. Kim2, H. Sung2, J. Jahng2, J.T. Oh3, G.S. Seo1, S.-Y. Lee4,
S.C. Choi1
1
Division of Gastroenterology, Department of Internal Medicine, Wonkwang
University Hospital, Digestive Disease Research Institute, Iksan, 2Division of
Gastroenterology, Department of Internal Medicine, Wonkwang University Sanbon
Hospital, Digestive Disease Research Institute, Gunpo-si, 3Department of Surgery,
Wonkwang University Hospital, 4Department of Psychiatry, Wonkwang University
Hospital, Digestive Disease Research Institute, Iksan, Korea, Republic Of
Contact E-mail Address: hanseung43@naver.com
INTRODUCTION: Psychological factors play a role in the development of functional gastrointestinal disorders (FGIDs). The work of firefighters is characterized by its danger, urgency, unique work environment, and by its considerable
high level of job stress.
AIMS & METHODS: The purpose of this study was to determine the effect of
job stress and other psychosocial factors on FGIDs in this high risk population.
Within a cross-sectional survey, 1140 firefighters completed validated questionnaires regarding FGIDs including gastroesophageal reflux disease (GERD),
functional dyspepsia (FD), irritable bowel syndrome (IBS) and functional constipation (FC) by at least once a week of typical reflux symptoms and Rome III
criteria. Self-reported questionnaires for perceived job stress (KOSS-26), anxiety
(GAD-7), depression (PHQ-9), coping styles (WCC), social support and quality
of life (WHOQOL-BREF) was also completed. Odds ratio with 95% confidence
intervals were estimated using unconditional logistic regression in adjusted
models.
RESULTS: A total of 425 (37.3%) subjects reported to be bothered by at least
one FGIDs and the proportions of GERD, FD, IBS, FC was 362 (31.8%), 132
(11.6%), 101 (8.9%) and 124 (10.8%), respectively. Perceived job stress significantly associated with GERD (OR 6.4, 95% CI: 2.2-18.3, p5.001) and FD
(OR 8.2, 95% CI: 1.1-38.0, p .007), modestly associated with IBS (OR 4.2,
95% CI: 0.8-20.8, p .070), but not in FC (OR 1.2, 95% CI: 0.4-4.1, p .697).
Subjects reporting anxiety had a 4.1, 3.7, 3.1-fold (95% CI: 2.7-3.8, 2.5-5.4, 2.04.8) increased risk of GERD, FD and IBS, respectively (p5.001), and with
depression had a 5.4, 4.3, 4.3-fold (95% CI: 4.1-7.1, 2.8-6.5, 2.7-6.9) increased
risk compared to subjects without depression (p5.001). We observed a weak
inverse association between measures of emotional support and GERD
(OR 0.3, 95% CI: 0.1-0.8, p .020); esteem, informative support and FD
(OR 0.2, 0.2; 95% CI: 0.4-1.0, 0.0-0.8; p .032, .024). Among the subdomain
of job stress, physical environment, job demand and lack of reward were related
to the occurrence of FGIDs. Impaired quality of life was found in all FGIDs. The
overlap syndrome was observed in 134 (11.8%) and highly associated with perceived job stress (OR 10.6, 95% CI: 2.3-49.3, p .002) compared to non-overlap FGIDs (OR 5.3, 95% CI: 1.6-17.3, p .005). We also observed a weak
inverse association between informative support and overlap syndrome
(OR 0.1, 95% CI: 0.0-0.9, p .043). Among the subdomain of job stress, all
domains were related to the overlap syndrome.
CONCLUSION: Perceived job stress is strongly associated with FGIDs in firefighters. Anxiety and depression was related to FGIDs and weak inverse association between social support while no consistent association regarding coping
styles was found. The psychosocial factors such as high level of job stress and
lack of social support could affect the development of FGIDs. Recognition and
management of these psychosocial factors may aid in the management of FGIDs.
Disclosure of Interest: None declared

J. Mikaeli1, M. Amani1, N. Fazlollahi1,*, R. Sotoudehmanesh1, M. Khatibian1,


R. Malekzadeh1
1
Tehran University of Medical Sciences, Iran, Digestive Disease Research Institute,
Tehran, Iran, Islamic Republic Of
INTRODUCTION: Although Hellers myotomy is one of the most effective
treatments for achalasia, symptoms of disease relapse after that in some patients.
AIMS & METHODS: Aim: To evaluate the safety and efficacy of pneumatic
balloon dilation (PBD) in cases of symptoms relapse after Hellers myotomy
(HM).
Method: 36 patients with achalasia in whom symptoms had relapsed after HM
referred to our center from 1993 to 2013. Nine patients who had comorbid
diseases or epiphrenic diverticula were treated by botulinum toxin injection
and excluded from the study. 27 patients were treated with PBD and followed
up prospectively. A good initial response was defined as a decrease in symptom
score to 4 or less and a reduction greater than 80% from the baseline in the height
and volume of barium in timed barium esophagogram at 1.5 months after the
first PBD (with 3 cm rigiflex balloon). Achalasia symptom score (ASS) was
assessed every six months in all patients and when symptoms relapsed
(ASS44), PBD was repeated.
RESULTS: The Mean age of the patients was 47.4813.91 years (range: 21-73).
Good initial response was seen in seventeen patients and five others revealed
good response after second PBD with 3.5 cm rigiflex balloon. The mean ASS
of patients dropped from 6.88 before treatment to 3.18 at the end of the study
(p 0.003). The mean duration of follow up was 11.815.97 years. At the end of
the study sustained good response was reported by twenty two patients (81%).
No major complications like perforation or gross bleeding were seen after PBD
sessions.
CONCLUSION: We conclude that PBD is effective and safe treatment option of
achalasia patients in whom symptoms relapse after Hellers myotomy.
Disclosure of Interest: None declared
P1608 DISTINCT
ETIOPATHOGENESIS
IN
SUBGROUPS
FUNCTIONAL DYSPEPSIA ACCORDING TO ROME III CRITERIA

OF

J.-M. Liou1,*, Y.-J. Fang2, C.-C. Chen 1, M.-J. Chen1, J.-T. Lin1, M.-S. Wu1 on
behalf of Taiwan GI and Helicobacter Consortium
1
Internal Medicine, NATIONAL TAIWAN UNIVERSITY HOSPITAL, Taipei,
2
Internal Medicine, Yun-Lin Branch, NATIONAL TAIWAN UNIVERSITY
HOSPITAL, Yun-Lin, Taiwan, Province of China
Contact E-mail Address: dtmed046@pchome.com.tw; dtmed046@yahoo.com.tw
INTRODUCTION: Whether there are distinct pathogenesis in subgroups of
functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), remain controversial.
AIMS & METHODS: Aims: We aimed to identify the risk factors of FD and its
subgroups in Chinese.
Methods: Patients with dyspepsia and health subjects who underwent gastric
cancer screening were enrolled in this multicenter study from 2010 to 2012. All
patients were evaluated by questionnaire, esophagoduodenoscopy, histological
examination, and Helicobacter pylori tests. Subgroups of FD were classified
according to Rome III criteria. Psychiatric stress was assessed by short form
Brief Symptom Rating Scale.
RESULTS: Of the 2378 patients with dyspepsia, 818 and 512 fulfilled the diagnostic criteria of uninvestigated dyspepsia and FD, respectively. Of them, 310
(60.6%) and 368 (71.9%) subjects fulfilled the diagnosis of EPS and PDS, respectively, whereas 176 (34.4%) had overlap syndromes. As compared to 1033
healthy controls, we found that PDS and EPS shared some common risk factors,
including females (Odd ratio [OR] 1.91, 95% confidence interval [CI] 1.362.68),
younger age (OR 0.96, 95%CI 0.940.97), nonsteroidal anti-inflammatory drugs
(OR: 6.70, 95%CI 4.1710.77), and anxiety (OR 3.30, 95%CI 2.354.63). In
contrast, Helicobacter pylori (OR 1.83, 95%CI 1.21-2.79), unmarried status (OR
4.06, 95%CI 2.45-6.72), sleep disturbance (OR 2.57, 95%CI 1.61-4.1), and
depression (OR 2.12, 95%CI 1.22-3.69) were independently associated with
PDS, but not with EPS. Betel nut chewing (OR 5.32, 95% CI 1.42-20) and
psychological inferiority (OR 0.38, 95% CI 0.19-1.78) were independently associated with EPS, but not with PDS.
CONCLUSION: Different risk factors exist for subgroups of FD based on Rome
III criteria, supporting the distinct etiopathogenesis of the subdivisions that
might necessitate different therapeutic strategies.
Disclosure of Interest: None declared
P1609 SUPRAGASTRIC
BELCHING:
PREVALENCE
AND
ASSOCIATION WITH GASTRO-OESOPHAGEAL REFLUX DISEASE
AND OESOPHAGEAL HYPOMOTILITY
N. Koukias1,*, J. Jafari1, E. Yazaki1, P. Woodland1, D. Sifrim1
1
Barts and the London School of Medicine and Dentistry, Queen Mary, University
of London, London, United Kingdom
Contact E-mail Address: nkoukias@gmail.com
INTRODUCTION: Supragastring belching (SGB) is a phenomenon during
which air is sucked into the oesophagus and then rapidly expelled through the
mouth without reaching the stomach. Patients often complain of excessive belching with a severe impact on quality of life. SGB is considered to be a behavioral
disorder, and in some cases a response to an unpleasant sensation originating
from the oesophagus or the abdomen. Furthermore, SGB has been shown in
itself to induce gastro-oesophageal reflux.

A574
AIMS & METHODS: We aimed to investigate the prevalence of pathological
SGB and its association with gastro-oesophageal reflux and motility disorders.
We established normal values for SGB by analyzing 24h pH-impedance in 20
healthy asymptomatic volunteers. We interrogated the database of the Upper GI
Physiology Unit of the Royal London Hospital (total number of patients referred
for assessment of GORD, dysphagia, chest pain) between 2010-2013 n 2950).
We identified all patients with diagnosis of SGB in their final report and reviewed
predominant symptoms, 24h pH-impedance and high resolution oesophageal
manometry (HRM).
RESULTS: Asymptomatic controls had between 0 and 15 SGB episodes per 24h.
The 95th percentile was 12 episodes. 100/2950 patients showed excessive SGB (54
females), mean age 48 (range 12 84 years). The median number of SGB in this
group was 69/24h (range 17-510). The 25th percentile was 37 and the 75th 125
SGB episodes. 15 patients had undergone prior Nissen fundoplication.
86 of the patients complained of excessive belching, with 50 feeling that belching
was their predominant symptom. 95 patients complained of typical reflux symptoms (heartburn and/or regurgitation). 65 patients complained of dysphagia, 51
had excessive bloating, 16 chest pain and 15 epigastric pain. On 24h pH-impedance, 41 patients had pathological oesophageal acid exposure. In these patients,
27% of oesophageal acid exposure was due to reflux occurring immediately after
a SGB. On HRM, 44/100 patients had oesophageal hypomotility (frequent failed
peristalsis and weak peristalsis with defects). 31 of these patients referred
dysphagia.
CONCLUSION: Increased SGB was identified in 100/2950 patients investigated
at the GI physiology Unit over a 4 years period. Increased belching is rarely a
symptom in isolation and almost always coexists with other oesophageal symptoms, most commonly dysphagia (65%) and heartburn/regurgitation (95%).
Whether SGB is a disordered response to other oesophageal symptoms or their
cause is still unclear. Behavioral therapy and baclofen have shown promising
results in patients with predominant belching. The role of SGB reduction in
patients with SGB-associated reflux symptoms or dysphagia is under current
investigation.
Disclosure of Interest: None declared
P1610 THE FUNCTIONAL DYSPEPSIA TREATMENT TRIAL (FDTT):
ANTIDEPRESSANT EFFECT ON GASTRIC ACCOMMODATION
Y.A. Saito1,*, G.R. Locke1, E.P. Bouras2, C.W. Howden3, B.E. Lacy4,
J.K. DiBaise5, C.M. Prather6, B.P. Abraham7, H.B. El-Serag7, P. Moayyedi8,
L.A. Szarka1, D.L. Burton1, M. Camilleri1, F.A. Hamilton9, L.M. Herrick1,
K.E. Tilkes1, N.J. Talley1,10
1
Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN,
2
Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL,
3
Gastroenterology and Hepatology, Northwestern University, Chicago, IL,
4
Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center,
Lebanon, NH, 5Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ,
6
Gastroenterology and Hepatology, Saint Louis University, Saint Louis, MO,
7
Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX,
United States, 8Gastroenterology and Hepatology, McMaster University Centre,
Hamilton, ON, Canada, 9Digestive Diseases and Nutrition, NIDDK, Bethesda,
United States, 10University of Newcastle, Callaghan, NSW, Australia
Contact E-mail Address: saito.yuri@mayo.edu
INTRODUCTION: A large, multicenter trial of antidepressants in individuals
with functional dyspepsia (FD) was conducted and the primary outcome of
adequate relief was presented at DDW 2013. In addition to symptom data,
physiologic data was collected including gastric accommodation. The effect of
antidepressants on gastric accommodation in FD patients is not known.
AIMS & METHODS: Aims: To determine whether antidepressant use affects
gastric accommodation in individuals with FD. Methods: This NIH-funded study
(DK065713) is a prospective, randomized, double-blind, placebo-controlled 12week treatment trial conducted at 8 sites in North America that recruited 292
subjects with FD to 3 arms: 50 mg amitriptyline (AMI), 10 mg escitalopram
(ESC), placebo (PLA). Gastric accommodation data was collected at baseline
in 162 participants at three sites (MCR, MCJ, MCS). Gastric volume was measured using single photon emission computed tomography (SPECT) gastric imaging after administration of intravenous 99 mTc pertechnetate. The
ANALYZETM program was used for volume rendering, three-dimensional
reconstruction, and estimation of volumes. The Kruskal-Wallis test was used
to assess treatment differences.
RESULTS: Data was analyzed from 59 individuals with post-treatment gastric
accommodation data, 46 (78%) female, median age 43 (IQR: 35-52). 46 (78%)
were dysmotility-type FD; 13 (22%) were ulcer-like FD. At baseline, 3 (5%) had
impaired gastric accommodation, defined by a change in gastric volume 5428
mls). Post-meal gastric volume changes at baseline were similar among treatment
arms (51723 ml PLA (n 18), 54221 ml AMI (n 21), 59123 ml ESC
(n 20). At followup after 12 weeks of treatment, no differences in fasting
volumes or fed volumes between treatment arms (p 0.71 and p 0.09).
Changes in gastric volume from fasting to fed were modestly different between
arms (56522 ml PLA [n 18], 49427 ml AMI [n 21], 50816ml ESC
[n 20], p 0.08).
CONCLUSION: Data from this small sample suggests that both tricyclic and
SSRI antidepressants may decrease gastric accommodation in individuals with
FD. Additional studies are warranted to evaluate whether this finding is real and
correlates with FD symptoms.
Research support: National Institutes of Health (DK065713) and Forest
Pharmaceuticals (medication)
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1611 SYMPTOMS DONT REFLECT MUCOSAL HEALING IN
PATIENT WITH REFLUX ESOPHAGITIS DURING MAINTENANCE
THERAPY
A. Nagahara1,*, D. Asaoka1, M. Hojo1, H. Sasaki1, Y. Shimada1, H. Ueyama1,
K. Matsumoto1, S. Watanabe1
1
Gastroenterology, JUNTENDO UNIVERSITY SCHOOL OF MEDICINE,
Tokyo, Japan
Contact E-mail Address: nagahara@juntendo.ac.jp
INTRODUCTION: During the maintenance therapy for reflux esophagitis (RE),
patients take PPIs regardless presence of symptoms. Many studies are carried out
about endoscopic finding or symptom relief in maintenance therapy, however
there has been few studies investigating correlation among endoscopic healing,
symptom and dosing schedule.
AIMS & METHODS: The aim of this study is to reveal correlation among
endoscopic healing, symptom and dosing schedule during maintenance therapy.
Among patients with RE who enrolled randomized prospective study for 24
weeks PPI maintenance therapy (continuous arm (Omeprazole 20mg od) or
on-demand arm (Omeprazole 20mg on-demand)), we extracted patients data
who undertook EGD at 24 week. Patients were divided to healing group and
non-healing group by LA classification at 24week EGD. Symptom relief was
defined as percentage of patients who achieved no or minimal symptom at
24week visit by Global Overall Symptom questionnaires. Difference of symptom
relief and endoscopic findings was analyzed between continuous group and ondemand group.
RESULTS: Seventy patients (M/F:48/22, mean60.9 (range 29-89)yr) were
extracted. Patients with LA classification Grade A:B:C:D were 35:29:5:1 before
initial therapy and healing group/ non-healing group were 49/21 (Grade A:14,
B:5, C:2, D:0) at 24week, respectively. Regarding patients characteristics between
healing and non-healing group, age, gender, BMI, presence of hiatal hernia,
drinking and smoking had no significant difference but prevalence of recurrent
RE was significantly higher in non-healing group (p50.01). Although there was
no significant difference in symptom relief between healing (70.8%) and nonhealing group (80.0%) at 24 week, number of non-healing patient was significantly higher in on-demand group (44.4%) than in continuous group (14.7%)
(p50.01).
CONCLUSION: Symptoms were well controlled regardless endoscopic mucosal
healing and on-demand therapy was insufficient to maintain mucosal healing
during maintenance therapy. These results suggest that PPI should be taken
continuously regardless presence of symptoms in patients with reflux esophagitis
to prevent recurrence especially recurrent reflux esophagitis.
Disclosure of Interest: A. Nagahara Lecture fee(s) from: AstraZeneca, D.
Asaoka: None declared, M. Hojo: None declared, H. Sasaki: None declared,
Y. Shimada: None declared, H. Ueyama: None declared, K. Matsumoto:
None declared, S. Watanabe: None declared
P1612 IMPROVED CONTROL OF GASTROESOPHAGEAL REFLUX ON
FODMAP-RESTRICTED DIET
C.H. Kristianslund1,2,*, J.G. Hatlebakk3, T. Hausken3, M.H. Morken2,
G.E. Kahrs2
1
Clinical Insitute 1 (K1), University of Bergen, 2Department of Clinical Nutrition,
3
Section of Gastroenterology, Department of Medicine, Haukeland University
Hospital, Bergen, Norway
Contact E-mail Address: camilla@kristianslund.com
INTRODUCTION: Diet is recommended as first-line treatment for gastroesophageal reflux disease (GERD), but its role is debated. Refractory disease is often
due to residual reflux and proximal extent of reflux.
AIMS & METHODS: Colonic fermentation may affect gastroesophageal motility in GERD and we therefore aimed to evaluate the effect of a diet with less
fermentable carbohydrates, the FODMAP-restricted diet, on gastroesophageal
reflux. 12 patients with symptoms of GERD and/or reflux esophagitis (6M/6F,
age 36.812.3y) underwent 24h multichannel intraluminal impedance and pH
(MII-pH) before and after diet intervention lasting 7.32.2 weeks. 8 patients
were on stable medication with a proton pump inhibitor (PPI) during the intervention. The patients were instructed in the diet and followed by a dietitian.
Symptoms (GerdQ and ReQuest) and health related quality of life (SF36) were
recorded before and after the diet intervention. Results (median [IQR] or
meanSD) were compared with Wilcoxon signed rank test or paired t-test
(p50.05).
RESULTS: Intake of FODMAPs was significantly reduced from 197 to 22 g/
day (p50.0001). The total number of reflux episodes decreased on FODMAPrestricted diet compared to a normal diet (115135 vs. 152164, p 0.0305), and
particularly the number of proximal refluxes (2224 vs. 4237, p 0.0076).
Fewer symptom episodes were recorded during the MII-pH on FODMAPrestricted diet compared to a normal diet (12 [16] vs. 24 [46], p 0.0278). For
GerdQ there was a decrease in total score on FODMAP-restricted diet compared
to a normal diet (83 vs. 92, p 0.0679). Less frequent heartburn and regurgitation (32 vs. 51, p 0.0028), less impact of GERD (12 vs. 22,
p 0.0311) and more nausea and epigastric pain (51 vs. 32, p 0.0039) was
reported. However the patients did not experience any differences by nausea
(from 0.0 [2.1] to 0.0 [0.0], p 0.3125) and epigastric pain (from 1.8 [4.6] to 0.4
[4.1], p 0.5703) while engaged in daily life activities as recorded on ReQuest.
CONCLUSION: FODMAP-restricted diet improved symptoms of GERD and
reduced total and proximal gastroesophageal reflux. This may be effective both
as a first-line treatment and in patients refractory to PPI treatment.
Disclosure of Interest: None declared

A575

United European Gastroenterology Journal 2(1S)


P1613 DURABILITY OF EFFECT AND LACK OF REBOUND
SYMPTOMS FOLLOWING A 14-DAY REGIMEN OF
ESOMEPRAZOLE 20 MG TREATMENT IN SUBJECTS WITH
FREQUENT HEARTBURN
D.A. Peura1, A.L. Moigne2, C. Pollack2,*, P. Nagy2,3
1
University of Virginia, School of Medicine, Charlottesville, 2Pfizer Consumer
Healthcare, Madison, United States, 3Astra Zeneca, Molndal, Sweden
INTRODUCTION: Durability of effect and lack of rebound symptoms following a 14-day regimen of esomeprazole 20 mg were evaluated in 2 identical randomized, double-blind, placebo-controlled studies (study one: NCT01370525;
study two: NCT01370538) in subjects with frequent heartburn (HB) who are
likely to self-treat with over-the-counter (OTC) medications.
AIMS & METHODS: Adults without a confirmed diagnosis of gastro-oesophageal reflux disease who were experiencing HB 2 days per week in the past 4
weeks were eligible for study inclusion. Following HB medication washout and a
7-day placebo run-in period, subjects continuing to meet inclusion criteria were
randomly assigned to double-blind treatment with esomeprazole 20 mg (administered as esomeprazole magnesium trihydrate 22.3 mg) once daily or placebo
for 14 days. All subjects entered a 1-week single-blind placebo follow-up period
after the 14-day treatment period. Episodes of HB were documented by daily
patient diary via interactive voice response system during the placebo run-in
period, treatment period, and placebo follow-up. The primary efficacy outcome
was the percentage of HB-free 24-hour days (defined as days when the subject
had no HB episodes) during 14 days of treatment. Primary and secondary outcomes from the treatment period have been reported separately elsewhere. The
current report presents data collected during the placebo follow-up period.
RESULTS: In study one, 331 subjects were treated in the double-blind treatment
phase and 321 entered the placebo follow-up period; study two included 326 and
303 subjects, respectively. The percentage of HB-free 24-hour days achieved
during the treatment period for esomeprazole 20 mg was greater than with placebo and remained consistent in the placebo follow-up period (Table). The percentage of HB-free 24-hour days in the placebo follow-up for study one was 43%
for those who had been treated with esomeprazole 20 mg compared to 35% for
placebo. Similarly, in study two, the percentages of HB-free 24-hour days were
43% and 39% in the esomeprazole 20 mg and placebo groups, respectively.
Table: Percentage of 24-Hour Heartburn-Free Days During the 3 Study Phases.
Study One

7-day single-blind placebo runin period, mean (%)


14-day double-blind treatment
period, mean (%)
7-day
single-blind
placebo
follow-up period, mean (%)

Study Two

ESO-20mg

Placebo

ESO-20mg

Placebo

18

19

22

21

43

29

47

31

43

35

43

39

CONCLUSION: In frequent HB sufferers who are likely to self-treat with OTC


medications, the rate of HB control during the 14-day double-blind treatment
period with esomeprazole 20 mg was maintained for the 7-day placebo follow-up
after cessation of study medication. No evidence of rebound symptoms was
observed following 14-day treatment with esomeprazole 20 mg.
REFERENCES
The studies were sponsored by AstraZeneca, entered into an agreement with
Pfizer for the over-the-counter (OTC) rights for NEXIUM (esomeprazole magnesium). Medical writing support provided by Diane M. Sloan, PharmD, of
Peloton Advantage, LLC, funded by Pfizer.
Disclosure of Interest: D. Peura Lecture fee(s) from: Takeda, Horizon, Otsuka,
Consultancy for: Astra Zeneca, Pfizer, Takeda, Horizon, A. Le Moigne Other:
Employee of Pfizer Consumer Healthcare, C. Pollack Other: Employee of Pfizer
Consumer Healthcare, P. Nagy Other: employee of Astra Zeneca.
P1614 IMPACT OF SHORT-TERM ESOMEPRAZOLE TREATMENT ON
PERFORMANCE OF DAILY ACTIVITIES AND ANTACID USE IN
SUBJECTS WITH NONEROSIVE SYMPTOMATIC GASTROOESOPHAGEAL REFLUX DISEASE AND FREQUENT HEARTBURN
P. Katz1, A. LeMoigne2, K. Park2, C. Pollack2,*
1
Einstein Medical Center, Philadelphia, Philadelphia, 2Pfizer Consumer
Healthcare, Madison, United States
INTRODUCTION: Symptomatic gastro-eosophageal reflux disease (GORD)
can impair performance of daily activities, and self-treatment of reflux symptoms
(e.g., heartburn [HB] and acid regurgitation) with antacids is common. We evaluated subject-reported outcomes and antacid use in 2 studies of short-term
esomeprazole (ESO) in a population likely to seek self-treatment in an overthe-counter setting.
AIMS & METHODS: Study 1 (N 368) and study 2 (N 349) were similarly
designed randomized, double-blind, placebo-controlled trials conducted at 26
and 27 gastroenterology centres, respectively, in the US. Subjects with frequent
HB for 6 months without endoscopic erosive oesophagitis were randomized to
ESO 20 mg, ESO 40 mg, or placebo once daily. Antacid tablets (6/day) were
permitted as rescue for breakthrough symptoms. Week 4 data were previously
published (Katz et al. Aliment Pharmacol Ther. 2003;18[9]:875-82). The current
report includes data from a subject-reported overall treatment evaluation questionnaire and use of rescue medication in the first 2 weeks.

RESULTS: At end of week 2, significantly more subjects (all P.001) taking


ESO 20 mg and 40 mg vs placebo had relief of HB (1 mild HB episode for 7
consecutive days) and rated themselves as better than baseline. The majority of
those who improved rated it as at least "important" in performing daily activities
(ESO 20 mg, 79%86%; ESO 40 mg, 78%82%; placebo, 65%479%). Mean
antacid use in weeks 1 and 2 was lower with ESO (0.9-1.0 tablets/day) vs placebo
(1.7 tablets/day).
CONCLUSION: ESO 20 mg for 2 weeks (typical over-the-counter dose/duration) was associated with improvement deemed by subjects as important for daily
functioning and lower rates of rescue antacid use.
REFERENCES
This abstract was previously presented at 74th FIP World Congress of Pharmacy
and Pharmaceutical Sciences 2014, August 31September 4, 2014, Bangkok,
Thailand.
The studies were sponsored by AstraZeneca, which entered into an agreement
with Pfizer for the over-the-counter (OTC) rights for NEXIUM (esomeprazole
magnesium).
Medical writing support was provided by Diane M. Sloan, PharmD, of Peloton
Advantage, LLC, and was funded by Pfizer.
Disclosure of Interest: P. Katz Consultancy for: Ironwood, Pfizer Consumer
Health, Other: Honorarium Takeda, A. LeMoigne Other: Employee of Pfizer
Consumer Healthcare, K. Park Other: Employee of Pfizer Consumer Healthcare,
C. Pollack Other: Employee of Pfizer Consumer Healthcare.
P1615 CLINICAL AND IMPEDANCE-PH FEATURES PREDICT
RESPONSE TO PROTON PUMP INHIBITORS IN PATIENTS WITH
NON-CARDIAC CHEST PAIN
C. De Cassan1,*, V. Savarino2, E. Marabotto2, M. Furnari2, P. Zentilin2,
N.de Bortoli3, S. Marchi3, M. Frazzoni4, E. Savarino5
1
Division of Gastroenterology, Department of Surgery, Oncology and
Gastroenterology, University of Padua, Padua, 2Division of Gastroenterology,
Department of Internal Medicine, University of Genoa, Genoa, 3Division of
Gastroenterology, Department of Internal Medicine, University of Pisa, Pisa,
4
Digestive Pathophysiology Unit, Baggiovara Hospital, Modena, 5Division of
Gastroenterology, Department of Surgery, Oncology and Gastroenterology,
University of Padua, Padua, Italy
Contact E-mail Address: esavarino@libero.it
INTRODUCTION: Non cardiac chest-pain (NCCP) is defined as recurrent
angina-like retrosternal chest-pain diagnosed after a negative cardiac workup.
Gastroesophageal reflux disease (GERD) is by far the most common cause of
NCCP. Previous studies showed that proton pump inhibitors (PPIs) are less
effective in relieving NCCP than heartburn, but predictors of PPI response in
NCCP patients have not been yet investigated.
AIMS & METHODS: We aimed to determine whether any symptom profile or
reflux pattern at impedance-pH monitoring was associated with refractoriness to
PPI therapy. Consecutive patients with NCCP lasting more than 6 months and
with at least three episodes per week, were prospectively enrolled. Demographics,
clinical data and symptoms of functional diseases (i.e. functional dyspepsia and
irritable bowel syndrome) were collected by means of previously validated questionnaires based on Rome III criteria for functional gastrointestinal disorders.
All patients underwent upper endoscopy and, within 3 days, conventional manometry and 24-hour impedance-pH testing while off-PPI therapy. During impedance-pH tracings analysis we measured distal esophageal acid exposure time
(AET), characteristics of reflux episodes (acid/weakly acidic) and symptomreflux association using both symptom association probability (SAP if
95%) and symptom index (SI if 50%). Patients were classified as PPI-non
responders (PPI-NR), if they had a symptom relief 450% from baseline or if
they had fewer than 1 day of mild NCCP per week while receiving a double dose
of PPI treatment for at least 8 weeks.
RESULTS: One-hundred and twenty-two NCCP patients (56F/66M; mean age
47; 4% erosive esophagitis/ 96% endoscopy negative; 100 PPI-NR/22 PPIResponders) reporting NCCP during the impedance-pH monitoring were
included. At univariate analysis, PPI-R presented more frequently erosive esophagitis and hiatal hernia (p 0.057 and p 0.03, respectively). Moreover, PPIR complained of NCCP more frequently in association with either typical (heartburn and/or regurgitation) or atypical (cough and/or asthma) reflux symptoms
compared to PPI-NR (p 0.003) and reported less often symptoms of dyspepsia
(p 0.02). Finally, PPI-R had more frequently an abnormal AET (45% vs. 21%,
p 0.02), a greater mean AET (9.9 [2.9-48] vs. 1.15 [0.6-15], p50.01), an higher
mean number of total (80 [16-177] vs. 47 [10-228], p 0.0037), weakly-acidic
(34.5 [7-101] vs. 24 [2-145], p 0.031) and acidic (44 [6-91] vs. 24 [8-98],
p 0.011) reflux episodes compared to PPI-NR. No differences were found
between PPI-r and PPI-NR in terms of SI and SAP positivity for acid, weakly
acid or both kind of reflux (data not shown). At multivariate analysis, the factors
associated with the absence of response were the lack of concomitant reflux
symptoms, functional dyspepsia, normal AET and reduced number of reflux
episodes (p50.01).
CONCLUSION: Our data show that symptom profile (concomitant reflux
symptoms and functional dyspepsia) and reflux features detected at impedance-pH (AET and number of reflux episodes) are associated with response
to PPI therapy in patients with NCCP. On the other hand, reflux symptom
association analysis does not seem useful to predict PPI response.
Disclosure of Interest: None declared

A576
P1616 LAPAROSCOPIC SLEEVE GASTRECTOMY (LSG) VERSUS
LAPAROSCOPIC ADJUSTABLE GASTRIC BANDING (BGAL):
RESULTS AND EFFECTS ON GASTROESOPHAGEAL REFLUX
DISEASE (GERD) AND METABOLIC DISORDER
C. Cicerone1,*, P.L. Marini2, L. Papa3, M.G. Graziani4
1
dipartimento di medicina interna e specialita` mediche, Policlinico Umberto I,
Roma, 2Chirurgica bariatrica, 3Chirurgia bariatrica, 4Endoscopia Digestiva, San
Camillo Forlanini, Roma, Italy
Contact E-mail Address: teofillina84@yahoo.it
INTRODUCTION: Bariatric surgery is the gold-standard treatment for morbid
obesity because it has low morbidity rates and generates long term sustaned
weight loss.
AIMS & METHODS: The aim of this study was to compare short and midterm
results between LSG and BGAL. Weight loss, comorbidity improvement or
resolution, effect on reflux disease and post-operative complications were evaluated. An observational retrospective study from a database of patients undergoing LSG and BGAL between 2011 and 2012. Patients were followed at 3, 6 and
12 months.
RESULTS: A total of 52 obese patients who underwent sleeve gastrectomy (26
patients) and gastric banding (26 patients). The first group (LSG) comprised 23
female and 3 males with a median age 44 years and a median preoperative BMI
of 45.65 kg/m2. The second group comprised 24 female and 2 males with a
median age 42.8 years and a median preoperative BMI of 43.36 kg/ m2. In the
first group (LSG) the incidence of comorbidity was 42% (incidence of hypertension was 38%, of diabetes 30%); in the second group (BGAL) was 38% (incidence of hypertension was 26%, of diabetes 23%). The incidence of reflux disease
was 77% in patients undergoing sleeve gastrectomy and 46% in patients undergoing gastric banding. The excess weight loss at one year was 55% in LSG and
29% in BGAL. The complications rate was 7.6% for LSG (one bleeding treated
with conservative therapy and one gastric fistula). Diabetic remission and hypertension at six months and sustained at one year were 100% in the first group and
50% and 80% in the second group. The reflux disease improved in 30% of
patients (suspension or reduction of therapy).
CONCLUSION: LSG and BGAL are safe procedures that provide good results
in weight loss and resolution of comorbidities at 12 months. Our data confirmed
recent studies that LSG may be effective in improving/resolving diabetes in obese
patients and confirmed some studies that improved reflux disease.
Disclosure of Interest: None declared
P1617 WEIGHT LOSS PRODUCES SYMPTOMATIC IMPROVEMENT
IN PATIENTS WITH GERD: PROSPECTIVE, CONTROLLED AND
RANDOMIZED
D. Fernandes1,*, R. Gurski 1
Gastroenterology, Universidade Federal do Rio Grande do Sul, Porto Alegre,
Brazil
Contact E-mail Address: daienifernandes@ig.com.br
1

INTRODUCTION: Objective: Assess the dietary intervention effect for weight


loss, in the improvement of symptoms of gastroesophageal reflux disease in
patients with over weight and obesity. The secondary objective was to assess
the quality of life through the domain general health (SF-36).
AIMS & METHODS: Prospective, controlled and randomized with individuals
in out patient follow-up and who fulfilled the criteria of inclusion (age  18 years,
BMI  25 m2/kg, present typical symptoms: heartburn or regurgitation 1 x per
week or more, the presence of confirmed diagnosis through digestive endoscopy
and GERD treatment with Omeprazole 20 mg, voluntary acceptance to participate in the study) and exclusion (hospitalized patients, pregnant or lactating
women, subjected to surgery of the esophagus and/or stomach, inability of cognitive understanding of the guidelines, with chronic diseases such as: diabetes
mellitus and neoplasms, presence of GERD complicated with grade C or D
esophagitis, Barretts esophagus, desire to opt for surgical treatment). All
patients underwent evaluation anthropometric (weight, height, BMI) and randomized to receive guidance from individualized, low-calorie diet with out patient
follow-up monthly (n 31) for six months, or to a control group that received
general guidelines for healthy eating, but without action oriented (n 31).
Validated questionnaires were applied: QS-GERD for symptoms of GERD
and the generic quality of life questionnaire SF-36, addressing the General
State of health in both groups in two moments. The comparison between the
groups was performed by Student paired t-test. For confounders factors control
ANCOVA and was applied to evaluate the association between weight loss and
improvement of symptoms by QS-GERD, the Pearson correlation coefficient.
considered statistically significant when p value was 5 0.05.
RESULTS: The mean age was 59.1 in intervention group and 59.7 years in the
control group. Dietary intervention provided a weight loss average of 4.4 ( 5.3,
p 5 0.001) kg, representing 5% of the initial weight, an average reduction of
IMC 1.7 ( 2.9, p 5 0.023) kg/m and a decrease in symptoms of GERD 6.8 (
5.5, p 5 0.001). Individuals in the control group had worsening of their symptoms with increase of 3.3 points ( 4, p 5 0.001) and won on average 2 kg ( 4.4
p 5 0.001). The intervention group showed improvement in the General Health
State domain, 56.6 vs 64 (p 5 0.001).
CONCLUSION: The study showed that weight loss through dietary intervention
for 6 months with low-calorie diet individualised led to reduction of GERDrelated symptoms, as well as improvement in the quality of life as general
health status score.
REFERENCES
Moraes-Filho JP. Doenca Refluxo gastroesofagico fazer: Prevalencia e Gestao
no Brasil A Melhor Pratica e pesquisa Gastroenterologia Cl nica. de 2004; 18
(Suppl.): 23-26.

United European Gastroenterology Journal 2(1S)


Singh M, Lee J, Gupta N, Gaddam S, Smith BK, Wani SB, et al. A perda de peso
pode levar a resolucao dos sintomas da doenca do refluxo gastroesofagico: um
estudo prospectivo de intervencao. Obesidade 2013; 21: 284-290.
Disclosure of Interest: None declared
P1618 EFFECTS OF METOCLOPRAMIDE ON ESOPHAGEAL MOTOR
ACTIVITY AND ESOPHAGOGASTRIC JUNCTION COMPLIANCE IN
HEALTHY VOLUNTEERS
H. Mikami1,*, N. Ishimura1, K. Fukazawa2, M. Aimi1, G. Uno1, S. Ishihara1,
Y. Kinoshita1
1
Second Department of Internal Medicine, Shimane University Faculty of
Medicine, Izumo, 2Department of Gastroenterology and Hepatology, Kasai city
hospital, Kasai, Japan
INTRODUCTION: Presently, proton pump inhibitors are used as first-line treatment against gastroesophageal reflux disease (GERD). However, approximately
30% of GERD patients fail to respond. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of
GER[1], thus prokinetic agents, such as mosapride and metoclopramide, are
often used as second-line therapy for patients with GERD in clinical settings,
though their beneficial effects remain unclear. We previously showed that highdose mosapride not only augmented peristaltic contractions and mean resting
lower esophageal sphincter (LES) pressure, but also significantly reduced EGJ
compliance[2]. Although metoclopramide has been reported to increase LES
pressure, its effects on EGJ compliance have not been evaluated.
AIMS & METHODS: The aim of this study was to investigate the effects of
metoclopramide on esophageal motor activities and EGJ compliance. Nine
healthy male volunteers without abdominal symptoms were enrolled. Peristaltic
esophageal contractions and LES pressure were measured using high resolution
esophageal manometry (ManoScan360; Sierra Scientific Instruments), while EGJ
compliance was evaluated with an endoluminal functional lumen-imaging probe
(EndoFLIP; Crospon Ltd). After obtaining baseline values for esophageal motor
activities and EGJ compliance, metoclopramide (10mg) was intravenously administered, then all measurements were repeated at 15 and 30 minutes after administration in each subject.
RESULTS: We successfully analyzed EndoFLIP data in 8 subjects, with 1
excluded because of mechanical trouble. All subjects subjected to
ManoScan360measurements completed the protocol. Consistent with previous
reports, mean resting LES pressure was significantly increased after administration of metoclopramide (15minutes,26.7mmHg; 30minutes, 27.6mmHg) as compared with the baseline (13.7mmHg) (p50.05 for both). In addition,
metoclopramide significantly augmented peristaltic contractions, especially in
the distal esophageal segment (p50.05). On the other hand, distensibility index
(DI) did not change after administration of metoclopramide (5.2 vs. 5.8mm2/
mmHg), suggesting no significant difference in EGJ compliance caused by its
administration.
CONCLUSION: This is the first study to evaluate the effects of metoclopramide
on esophageal motor activity and EGJcompliance in healthy volunteers using
high resolution esophageal manometry and an EndoFLIP device. Although
metoclopramide significantly augmented esophageal motor activities, no significant effect on EGJ compliance was seen in healthy volunteers, unlike mosapride.
Our findings indicate that the effect on EGJ compliance differs between these
prokinetic agents, despite their similar pharmacological characteristics. This difference may be derived from the mechanism between the dopamine D2receptor
antagonist and serotonin 5-HT4receptor agonist, and may also explain, at least in
part, the different effects of these prokinetic agents on GERD.
REFERENCES
1 Kwiatek MA, et al. Esophagogastric junction distensibility assessed with an
endoscopic functional luminal imaging probe (EndoFLIP). Gastrointest Endosc
2010; 72: 272-278.
2 Fukazawa K, et al. Effects of mosapride on esophageal motor activity and
esophagogastric junction compliance in healthy volunteers. J Gastroenterol 2014
in press.
Disclosure of Interest: None declared
P1619 INFLUENCE OF URSODEOXYCHOLIC ACID ON PROGRESS OF
ATROPHIC GASTRITIS IN COMBINATION WITH DUODENAL
GASTRIC REFLUX
M.Y. Drzak19951,*
Medicine and Pharmacology, Prydneprovskyy Scientific Center, Dnepropetrovsk,
Ukraine
Contact E-mail Address: maxzak@ua.fm
1

INTRODUCTION: Reflux of biliary acids (BA) in gastric (G) opening favors to


epitheliolysis or destruction of protective epithelium and leads to inflaming,
atrophic and metaplastic lesions in gastric mucosa (GM). Ursodeoxicholic acid
(UDCA) has a binding effect on toxic fractions of GM which gives grounds to
apply these for patients with AG in combination with DGR. This give the
grounds to make an assumption that application of UDCA will allow neutralizing an aggressive impact of toxic fractions of BA and will promote repair of cell
structure of gastric epithelium.
AIMS & METHODS: To determine the influence of UDCA in combination with
itoprid on AG progress of DGR patients. Clinical series of 45 Mo negative
patients with AG combined with DGR carried out. Morphological diagnostics of
GM lesions have been done based on Sydney Huston recommendations and
OLGA system. Verification of DGR carried out based on endoscopic data, daily
intragastric oM-monitoring and biochemical testing of gastric aspirate. All
patients were referred to take UDCA with dosage of 10 mg per kg of body
weight during 6 months period in combination with standard drug therapy of

United European Gastroenterology Journal 2(1S)


pro-kinetic. Assessment of therapy efficiency carried out on the basis of endoscopic, pathogistological examinations data and analysis of proliferation index
(IP) (marker Ji 67). Investigation results were processed using analysis of
variance.
RESULTS: Dynamics of indicants characterized progress of AG and DGR were
assessed at average in 12 months from start of therapy. Disappearance of DGR
resulting from therapy referred to daily oM-monitoring recorded for 39 (86.7%)
of patients. And reflux load which remained for 6 (13.3%) of patients were
minor. Based on endoscopic data minimal symptoms of DGR took place in 8
(18.6%) of 43 cases. Morphological characteristics of inflammation of GM were
determined for 41 of patients (17 II stage, 24 I stage by criterions of OLGA
system). Up to the end of monitoring minimal inflammation remained only for 7
(17.1%) of patients. Regress of MT G atrophy registered for 8 (17.6%), foveolar
hyperplasia 20 (55.6%) of 36, full intestinal metaplasia (IM) 10 (40.0 %) of 25,
and partial IM 5 (14.7 %) out of 34 patients. Therapy applied promoted
decrease of IP: from 87.345.54 points to 51.233.22 points (o50.01) in hotbeds
of partial IM and from 56.324.11 points to 49.413.96 points (o50.01) at
atrophy areas.
CONCLUSION: UDCA therapy associated with DGR leads to disappearance of
reflux in 86.7% of cases, jugulation of chronic inflammation, regress of atrophy
and metaplasia of gastric epithelium. Ongoing therapy has contributed to the
reduction of proliferation index in the centers of full and partial intestinal
metaplasia.
REFERENCES
Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis.
The updated Sydney system. International Workshop on the Histopathology of
gastritis, Houston 1994. Am J Surg Pathol 1996; 20: 11611181.
Rugge M, de Boni M, Pennelli G, et al. Gastritis OLGA-staging & gastric cancer
risk: a twelve year clinico-pathological follow-up study. Minerva Gastroenterol
Dietol 2010; 56: 1317.
Turk J Gastroenterol 2013; 24: 251-259.
Disclosure of Interest: None declared
P1620 LOWER ESOPHAGEAL SPHINCTER (LES) ELECTRICAL
STIMULATION IMPROVES SLEEP QUALITY, WORK
PRODUCTIVITY, AND QUALITY OF LIFE IN PATIENTS WITH
REFRACTORY GERD
N. Bouvy1,*, N.F. Rinsma1, A. Escalona2, J.P. Ruurda3, J. Conchillo1,
A. Bredenoord4, M.van Berge Henegouwen4, P. Chiu5, M. Booth6, A. Hani7,
D. Reddy8, A. Smout4, J. Wu5, P. Siersema3
1
Maastricht University Medical Center, Maastricht, Netherlands, 2Pontificia
Universidad Catolica de Chile, Santiago, Chile, 3University Medical Center,
Utrecht, 4Academic Medical Center, Amsterdam, Netherlands, 5Chinese University
of Hong Kong, Hong Kong, Hong Kong, 6Watemata Specialist Centre, Auckland,
New Zealand, 7Pontificia Universidad Javeriana - Hospital San Ignacio, Bogota,
Colombia, 8Asian Institute of Gastroenterology, Hyderabad, India
INTRODUCTION: Sleep-Quality and Work-Productivity are commonly
affected in refractory GERD patients which in-turn negatively affects patients
quality of life.
AIMS & METHODS: AIM: Evaluate Sleep-Quality, Work-Productivity and
QoL in refractory GORD patients undergoing long-term electrical stimulation
therapy (EST) using the LOS Stimulation System (EndoStim BV, the Hague,
Netherlands).METHODS We evaluated GORD patients (n 37) partially
responsive to PPI with Off-PPI GERD HRQL20 and at least 5 point improvement on PPI, % 24 hour esophageal pH54 for 5%, hiatal hernia 3cm and
esophagitis LA Grade-C. The LOS stimulation system was implanted laparoscopically and EST was initiated at 20Hz, 220usec, 5 mAmp in 12, 30-min sessions. Patients completed the Pittsburgh Sleep Quality Index (PSQI), WorkProductivity and Activity-Impairment Questionnaire: Specific Health Problem
V2.0 (WPAI:SHP) and SF-12 QoL instrument both On-PPI and Off-PPI at
baseline, and at 6 and 12-mo on LOS-EST
RESULTS: Sleep scores [median (IQR)] at baseline On-PPI were 6.5 (5.2-9.5)
and 8 (6.2-10.5) when Off-PPI. At 6mo, sleep scores significantly improved to 5
(3.2-6; p 0.02 vs. On-PPI and p 0.02 vs. Off-PPI scores) and was sustained at
12months [5 (3.2-7) p 0.057 vs On-PPI, p 0.075 vs. Off-PPI) on LOS-EST.
Patients median %time missed from work due to GORD at baseline was 0 (06.9)% On-PPI and 3.8 (0-11.2)% Off-PPI. At 6mo, this improved to 0 (0-0)%
(n 15; p 0.04 vs. off-PPI) and was sustained at 12mo 0 (0-0)% (n 8; p 0.10
vs. off-PPI). Median percent impairment while working due to GERD at baseline
was 15 (0-45)% on-PPI and 60 (30-80)% off-PPI. At 6mo, this improved to 0 (010) (n 16; p 0.07 vs. On-PPI and p 0.002 vs. Off-PPI) and was 0 (0-10) at
12mo (n 9; p 0.21 vs. On-PPI, p 0.15 vs. Off-PPI) on LOS-EST. Median %
overall impairment due to GERD at baseline was 20 (0-55.5)% On-PPI and 63
(33.3-81.8)% Off-PPI. At 6mo, this improved to 0 (0-10)% (n 16; p 0.05 vs.
baseline On-PPI and p 0.003 vs. Off-PPI) and was sustained at 0 (0-2.5)%;
n 8; p 0.02 vs. On-PPI, p 0.06 vs. Off-PPI] at 12mo on LOS-EST.
Subjects reported a median % activity impairment due to GERD of 25 (10-50)%
On-PPI and 60 (30-80)% Off-PPI at baseline. This improved to 0 (0-20)% at
6mo, (n 27; p 0.04 vs. On-PPI, p50.001 vs. Off-PPI) and remained improved
at 5 (0-30)% at 12mo (n 18; p 0.03 vs. On-PPI, p 0.02 vs. Off-PPI) on LOSEST.
Median SF-12 physical health score was 44 on-PPI, 37 off-PPI at baseline, 52 at
6mo (p50.0001), and 50.5 at 12mo (p50.0001). Median SF-12 mental health
score was 49 on-PPI, 46 off-PPI at baseline, 52 at 6mo, and 55 at 12mo (p NS)
on LOS-EST. There was improvement in all other GORD specific outcomes.
CONCLUSION: In refractory GERD patients, LES-EST significantly improves
sleep-quality, work-productivity and overall impairment in activity resulting in
improvement in patient QoL. These results were significantly better than baseline
PPI therapy in many of the parameters evaluated.

A577
Disclosure of Interest: N. Bouvy Financial support for research from: EndoStim
B. V., N. Rinsma Financial support for research from: EndoStim B. V., A.
Escalona Financial support for research from: EndoStim B. V., J. Ruurda
Financial support for research from: EndoStim B. V., J. Conchillo Financial
support for research from: EndoStim B. V., A. Bredenoord Financial support
for research from: EndoStim B. V., M. van berge Henegouwen Financial support
for research from: EndoStim B. V., P. Chiu Financial support for research from:
EndoStim B. V., M. Booth Financial support for research from: EndoStim B. V.,
A. Hani Financial support for research from: EndoStim B. V., D. Reddy
Financial support for research from: EndoStim B. V., A. Smout Financial support for research from: EndoStim B. V., J. Wu Financial support for research
from: EndoStim B. V., P. Siersema Financial support for research from:
EndoStim B. V.
P1621 ELECTRICAL STIMULATION THERAPY (EST) OF THE LOWER
ESOPHAGEAL SPHINCTER (LES) AN EFFECTIVE THERAPY FOR
REFRACTORY GERD INTERIM RESULTS OF AN
INTERNATIONAL MULTICENTER TRIAL
P.D. Siersema1,*, A.J. Bredenoord2, J.M. Conchillo3, J.P. Ruurda1, N. Bouvy3,
M. I.van Berge Henegouwen1, P.W. Chiu4, M. Booth5, A.C. Hani6,
D.N. Reddy7, A.J. Smout2, J. Wu4, A. Escalona8
1
University Medical Center, Utrecht, 2Academic Medical Center, Amsterdam,
3
Maastricht University Medical Center, Maastricht, Netherlands, 4Chinese
University of Hong Kong, Hong Kong, Hong Kong, 5Waitemata Specialist Centre,
Auckland, New Zealand, 6Pontificia Universidad Javeriana-Hospital San Ignacio,
Bogota, Colombia, 7Asian Institute of Gastroenterology, Hyderabad, India,
8
Pontifica Universidad Catolica de Chile, Santiago, Chile
INTRODUCTION: A long-term single-center trial previously showed that LOSEST significantly improves esophageal acid exposure and symptoms in GORD
patients (Endoscopy 2013; 45:595-604).
AIMS & METHODS: We studied GORD patients partially responsive to proton
pump inhibitors (PPI) with off-PPI GORD-HRQL 20 and 5 point improvement on-PPI, LOS end-expiratory pressures of 45 mmHg, % 24 hour oesophageal pH4 for 45%, hiatal hernia 3cm and esophagitis LA Grade C. Bipolar
stitch electrodes and a pulse generator (EndoStim BV, Hague, Netherlands) were
implanted laparoscopically. EST was initiated at 20Hz, 220usec, 5mAmp in 12
30-minute sessions post-implant. Patients GERD-HRQL, daily symptom diaries, SF-12, oesophageal pH, and manometry were evaluated at regular intervals.
Stimulation sessions were optimized based on residual symptoms and oesophageal pH.
RESULTS: Thirty-seven patients (50.1yr, men 19) were implanted with the
LOS stimulator. Twenty-nine subjects completed their 6mo, and 19 their 12mo
visits. Median (IQR) GORD-HRQL improved from 33 (25-37) off-PPI and 16
(8-22) on-PPI at baseline to 5 (3-9) and 5 (0.2-16.8) at 6mo and 12mo (p50.001),
respectively. Median oesophageal acid exposure (pH54.0) improved from 9.9 (812.9)% at baseline to 5.4 (2.8-10)% and 5.2 (1.8-6.1) at 6 mo and 12mo, respectively (p50.01). Seventy-nine% of patients (15/19) at 12mo were completely off
PPI; one patient reported intermittent PPI use (550% days with PPI) and 3
patients reported regular (50% days with PPI) use. There were statistically
significant improvement in SF-12 physical health scores and trends towards
improvement in SF-12 mental health scores on LOS-EST vs. both on and offPPI baseline SF-12 scores. There was significant improvement in sleep quality as
measured by PSQI (p 0.02) and work productivity as measured by WPAI
(p 0.003) in patients treated with LOS-EST. Subgroup analysis revealed
numerically better distal esophageal pH response (normalized or 450%
improved) in women (75% vs. 57% in men; p 0.4) and comparable response
in patients with and without hiatal closure performed at the time of implant
(60% vs. 69%; p 0.7).
One procedure related serious adverse event; trocar perforation of the small
bowel during laparoscopy, successfully repaired and device prophylactically
explanted; was reported. Thirty-seven non-serious device or procedure-related
events were typical of surgical implant procedures, e.g. post-op nausea and
pocket pain. Five instances of dysphagia in 4 patients (all in patients with
hiatal closure) resolved without intervention.
CONCLUSION: Our interim results show that LOS-EST is safe and effective in
treating refractory GORD. LOS-EST results in significant improvement in oesophageal acid exposure, GORD symptoms, and PPI usage, with no device or
therapy-related serious events reported. Subgroup analysis revealed comparable
results in patient with a significant hiatal defect requiring a hiatal closure to those
without a significant hiatal defect.
Disclosure of Interest: P. Siersema Financial support for research from: EndoStim
B. V., A. Bredenoord Financial support for research from: EndoStim B. V., J.
Conchillo Financial support for research from: EndoStim B. V., J. Ruurda
Financial support for research from: EndoStim B. V., N. Bouvy Financial support for research from: EndoStim B. V., M. van Berge Henegouwen Financial
support for research from: EndoStim B. V., P. Chiu Financial support for
research from: EndoStim B. V., M. Booth Financial support for research
from: EndoStim B. V., A. Hani Financial support for research from:
EndoStim B. V., D. Reddy Financial support for research from: EndoStim B.
V., A. Smout Financial support for research from: EndoStim B. V., J. Wu
Financial support for research from: EndoStim B. V., A. Escalona Financial
support for research from: EndoStim B. V.

A578

United European Gastroenterology Journal 2(1S)

P1622 LONG-LASTING ESOPHAGEAL MUCOSAL PROTCTION WITH


ALGINATES: A POTENTIAL FOR TOPICAL MUCOSAL THERAPY
IN GASTROESOPHAGEAL REFLUX
P. Woodland1,*, C. Lee1, P. Dettmar2, D. Sifrim1
Barts and The London School of Medicine and Dentistry, Queen Mary University
of London, London, 2Technostics Ltd, Hull, United Kingdom
Contact E-mail Address: p.woodland@qmul.ac.uk
1

INTRODUCTION: Introduction.
Patients with non-erosive reflux disease (NERD) exhibit impaired esophageal
mucosal integrity in the form of dilated intercellular spaces and low transepithelial electrical resistance (TER). Such refluxate-induced changes to the mucosal
integrity may underlie increased sensitivity to perception of reflux events, even on
PPI, and could potentially be modified by application of topical solutions.
Sodium alginate solutions are used in treatment of GERD, with proposed
mechanisms of action including acid buffering, displacement of the gastric acid
pocket, and reduction of GER events. We have recently described that in vitro
topical application of a sodium alginate solution is able to protect mucosal
biopsies against impairment of esophageal mucosal integrity when exposed to
acidic solutions shortly after application. The potential durability of this protection is unclear.
We aimed to assess the protective effect and physical location of a topically
applied sodium alginate solution 1 hour after application.
AIMS & METHODS: Methods.
3 mucosal biopsies were taken from the distal oesophagus (3 cm above the z-line)
in 15 patients attending the Royal London Hospital for gastroscopy examination. All biopsies were transferred immediately to Krebs buffer pH 7.4. Biopsies
were then each placed in a specially adapted Ussing chamber and bathed in
Krebs pH 7.4 (neutral) solution for 20 minutes to equilibrate. The luminal surfaces of 2 biopsies were coated with 200 ml of either a sodium alginate solution
(Gaviscon Advance, Reckitt Benckiser, Hull, UK) or a viscous control solution
(of same viscosity, but without alginate). The biopsies were mechanically washed
with 5 ml Krebs, then returned to the chambers then bathed in neutral solution
for a further 1 hour. The luminal aspect of the biopsy was then exposed for 30
min to an acidic solution pH 2 1 mg/ml pepsin 1 mM taurodeoxycholate.
Percentage changes in TER from baseline at the end of exposure were recorded.
For the 3rd biopsy sodium alginate solution containing fluorescein-labeled alginate was used, and after 1 hour bathing in neutral solution the biopsy was fixed
for immunohistological examination of the location of the alginate.
RESULTS: Results.
Our previous experiments have demonstrated that exposure of unprotected biopsies to the acidic solution results in a -14.42.9% change in TER from baseline.
I hour after protection with alginate solution the same exposure caused a -8.3 
2.2% change in TER compared to -25.1  4.5% change after protection with the
viscous control (p50.01).
Labeled alginate could be seen coating the luminal surface in all cases.
CONCLUSION: Conclusion.
In vitro, alginate solutions can adhere to the esophageal mucosa for up to 1 hour
and exert a topical protectant effect against acid, pepsin and bile acids. This
suggests that durable topical protectants can be further explored and developed
as first-line / add-on therapies for GERD, including refractory disease.
REFERENCES
Woodland P, et al. Am J Gastroenterol 2013; 108: 535-543.
Disclosure of Interest: P. Woodland: None declared, C. Lee: None declared, P.
Dettmar Consultancy for: Reckitt-Benckiser, D. Sifrim Financial support for
research from: Reckitt-Benckiser.
P1623 SRS PROCEDURE COMBINATED TO POEMS IN
TREATMENT OF ACHALASIA: A FEASEABILITY STUDY ON
ANIMAL MODEL

THE

R. Bozzi1,*, A. Roy Shapira2, E. Capezzuto3, C. DeWerra4, D. Cattaneo5 on


behalf of working group of Italian Society of Surgical Endoscopy and The
ISSE International Board
1
Dept.of Surgery, UOC Chirurgia ed Endoscopia Digestiva Azienda Ospedaliera
dei Colli, Napoli, Italy, 2Dept.of Surgery-University of Bersheeva -Israel, General
Surgery, Bersheeva, Israel, 3Dept.of Surgery, Surgical Endoscopy Ospedale Grassi,
Ostia - Roma, 4Dept.of Surgery, general surgery Federico II university -Naples,
5
Dept.of Surgery, UOC CHIRURGIA ED ENDOSCOPIA DGESTIVA "V.
MONALDI", Napoli, Italy
Contact E-mail Address: chicca.bozzi@libero.it
INTRODUCTION: Both SAGES and the American Gastroenteroloists
Association (AGA) now recommend laparoscopic myotomy combined with anterior fundoplication for the treatment of achalasia. Peroral endoscopic myotomy
(POEM TM) is a novel approach to performing esophageal myotomy through a
long submucosal tunnel and rapprents a feasible, safe, and effective treatment for
achalasia. Recently, FDA approved a method for transoral stapled anterior
funduplicatio (SRSTM). SRS TM Endoscopic Stapling System (Medigus, Tel
Aviv, Israel) is an advanced endoscope procedure to create an effective reflux
barrier, like a laparoscopic anterior funduplicatio, using two or three quintuplets
of standard 4.8mm titanium B shaped surgical staples.
AIMS & METHODS: The aim of this study was to test the feasibility of combining the two procedures, thereby achieving a completely transoral myotomy
with anterior fundoplication, functinally equivalent to the standard laparoscopic
operation for achalasia.
The feasibility experiment was performed on a swine model at a laboratory
certified according to the Israeli Animal Welfare Act. After induction of general
anesthesia. A standard gastroscope was inserted into the stomach, and an overtube was slided into the mid-esophagus. A submucosal tunnel, starting about 5

cm above the GE junction and extending to 2 cm below it, was created, and the
circular layer of esophageal muscle was incised using the POEM electrode.
Following the myotomy, the SRS stapler was inserted through the overtube,
and the fundus of the stomach was stapled over the myotomy, using three quintuplets of staples, in a semi-circle. At the end of the procedure, the animal was
sacrificied, and the stomach with the distal esophagus were dissected out carefully, and examined macroscopically.
RESULTS: Macroscopically, the resulting fundoplication covered the distal half
of the myotomized muscle, including the gastric part. No perforation was
observed. The macroscopic apearance was similar to that of a standard anterior
fundoplicatio.
CONCLUSION: CONCLUSIONS / EXPECTATIONS:
It is feasible to combine the two procedures, at least in the swine model, and add
a transoral reflux barrier to the submucosal myotomy. If the aganglionic segment
is short (53cm) it is possible to cover all the myotomized esophagus with the
fundus, which may reduce the risk of perforation. It is probably easier to to
ensure that the myotomy is on the side of the esophagus covered by the fundic
flap perform the stapling first, and start the myotomy between the two topmost
quintuplets,. Although further experiments are needed to optimize stapling location vis-a-vis the myotomy site, the combined procedure may enable the operator
to achieve a result which is similar to the standard laparoscopic operation for
achalasia, without violating the abodominal cavity, and without any incisions.
REFERENCES
Bozzi, et al. SSAT Poster selected DDW 2014.
Disclosure of Interest: None declared
P1624 IN VITRO MODELLING OF THE POST-PRANDIAL ACID
POCKET AND TESTING THE INFLUENCE OF ALGINATE ANTIREFLUX SUSPENSIONS
J. Fisher1, V. Strugala1,*, P.W. Dettmar1
technostics Ltd, technostics Ltd, Cottingham, United Kingdom
Contact E-mail Address: vicki.strugala@technostics.com
1

INTRODUCTION: The region of unbuffered acidity on top of the gastric contents after a meal, known as the acid pocket was initially reported by Fletcher
et al 1 and is well established. The acid pocket exists from 15 to 90 minutes after a
meal and has a volume of 50-70ml and length of 2cm 2,3. Post-prandial reflux is
linked to this existence of this acid pocket.
Clinical studies utilise complex and invasive techniques including pH pullthrough techniques and as a result only a few centres have the skills necessary
to carry out such studies. It has been suggested that acidic gastric juice could
partition on top of a homogenised fatty meal 1.
AIMS & METHODS: Aim: The aim was to develop a robust and fully validated
in vitro model of the post-prandial acid pocket using physiologically relevant
conditions stated in the literature. The in vitro model would then be used to
investigate the impact of alginate anti-reflux suspensions and antacids on the
acid pocket.
Methods: A standard refluxogenic meal (McDonalds double sausage and egg
McMuffin black coffee) was blended with simulated gastric acid and transferred to the model vessel (equilibrated to 37 C). An acid pocket layer was
applied to meet the established clinically measured parameters. pH was recorded
2cm into the meal/acid homogenate and within the acid pocket every 5 min. A
pull-through pH measurement was performed at 0.5cm intervals 30 minutes after
addition of a test product (n 6).
RESULTS: The acid pocket had a volume of 70ml and was 2.5cm in depth with a
mean pH of 1.08 (SD 0.04) at 1 cm into the acid pocket. On addition of a placebo
product to the acid pocket the pH marginally increased to 1.33 (0.16). The
addition of Antacid Liquid Supreme increased the acid pocket to 3.99 (1.99).
The addition of raft forming alginate antacid product Gaviscon Double Action
(GDA) neutralised the acid pocket to pH 5.89 (0.30).
CONCLUSION: A robust in vitro model of the post-prandial acid pocket has
been developed taking into account all relevant clinical literature. The model
using a pH pull-though method, allows the evaluation of alginate raft forming
products and antacids. Gaviscon Double Action formed an alginate raft which
floated on the top of the acid pocket and significantly changed the pH compared
to antacid and placebo (P50.001). Whereas the antacid sank below the acid
pocket similar to placebo.
REFERENCES
1 Fletcher, et al. Gastroenterol 2001; 121: 775-783.
2 Clarke, et al. Gut 2008; 58: 904-909.
3 Beaumont, et al. Gut 2010; 59: 441-451.
Disclosure of Interest: J. Fisher: None declared, V. Strugala: None declared, P.
Dettmar Financial support for research from: study funded by Reckitt Benckiser.
P1625 COST-UTILITY ANALYSIS OF ENDOSCOPIC SURVEILLANCE
OF PATIENTS WITH GASTRIC PREMALIGNANT CONDITIONS
SUCH AS EXTENSIVE ATROPHY OR INTESTINAL METAPLASIA
M. Areia1,2,*, M. Dinis-Ribeiro1,3, F. Rocha Goncalves1,4
CINTESIS - Center for Research in Health Technologies and Information
Systems, Faculty of Medicine, Porto University, Porto, Porto, 2Gastroenterology
Department, Portuguese Oncology Institute Coimbra, Coimbra,
3
Gastroenterology Department, 4Portuguese Oncology Institute Porto, Porto,
Portugal
Contact E-mail Address: miguel.areia75@gmail.com
1

INTRODUCTION: Progression of gastric premalignant conditions to cancer


might warrant surveillance programmes. Recent guidelines suggested an endoscopic surveillance every 3 years for these patients (1).

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United European Gastroenterology Journal 2(1S)


AIMS & METHODS: Our aim was to determine the cost-utility of endoscopic
surveillance of patients with extensive gastric premalignant conditions such as
extensive atrophy or intestinal metaplasia to the corpus. A cost-utility economic
analysis for the Portuguese population was performed from a societal perspective
using a Markov model to compare two strategies: surveillance versus no surveillance. Clinical data was collected from a systematic review of the literature, costs
from published national data and community utilities derived from a population
study by the EuroQol questionnaire in terms of Quality Adjusted Life Years
(QALY). Population started the model at the age of 50 and for a time horizon
of 25 years. The threshold was set at E 36,575, corresponding to the proposed
guideline limit of USD 50,000 (2) and an annual discount rate of 3% was used for
both cost and effectiveness. The primary outcome was the incremental cost-effectiveness ratio (ICER) of a 3-yearly endoscopic surveillance versus no surveillance
for a base case scenario and in deterministic and probabilistic sensitivity analysis.
Secondary outcomes were ICER of 5- and 10-yearly endoscopic surveillance
versus no surveillance.
RESULTS: Endoscopic surveillance every 3 years provided an ICER of E
18,336, below the adopted threshold and this strategy dominated surveillance
every 5 or 10 years. In deterministic analysis, variables that most influenced
the ICER were the proportion of males or females affected by the disease
(ICER: 17.857-18.841), proportion of patients progressing to dysplasia (13.68431.887), utilities for endoscopic treatment (12.326-42.875) and the cost of transportation (17,909-20,044), even more relevant than medical costs such as endoscopy (18,117-18,555), anaesthesia (18,223-18,449), surgery (18,302-18,370),
chemotherapy (18,330-18,342) and radiotherapy (18,317-18,355). In probabilistic
analysis the model remained cost-effective in 78% of simulations.
CONCLUSION: Endoscopic surveillance every 3 years of patients with extensive
premalignant conditions is cost-effective for the Portuguese population.
REFERENCES
(1) Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous
conditions and lesions in the stomach (MAPS): guideline from the European
Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study
Group (EHSG), European Society of Pathology (ESP), and the Sociedade
Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.
(2) Drummond MF and Jefferson TO. Guidelines for authors and peer reviewers
of economic submissions to the BMJ. The BMJ Economic Evaluation Working
Party. BMJ 1996; 313: 275-283.
Disclosure of Interest: None declared
P1626 CLINICOPATHOLOGICAL
CHARACTERISTICS
PROGNOSTIC FACTORS OF PRIMARY GASTROINTESTINAL
LYMPHOMA: A 22-YEAR EXPERIENCE FROM SOUTH CHINA

AND

M. Li1,*, S. Zhang2, Y. Jiayan 1, K. Chao1, B. Zhong2


Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen
University, Guangzhou, 2Division of Gastroenterology, The First Affiliated
Hospital, Sun Yat-sen University, Guangzhou, China
Contact E-mail Address: sophiazhong@medmail.com.cn
1

INTRODUCTION: Primary gastrointestinal lymphoma (PGIL) is rare, and few


studies have addressed it well, especially in China.
AIMS & METHODS: This study was to investigate its clinicopathological features and prognosis, and also to make comparisons between different locations of
PGIL in South China. All patients with PGIL confirmed by histopathology
between January 1991 and October 2012 in the First Affiliated Hospital, Sun
Yat-sen University were included. Clinicopathological data were collected and
prognostic factors influencing survival were analyzed.
RESULTS: The cohort included 160 males and 56 females, accounting for 0.02%
of all hospitalized patients and 1.5% of hospitalized patients with GI cancers.
Abdominal pain (75.9%) was the most frequent symptom. The percentage of
tumor in Stomach group, Intestine group, and GI group was 38.5%, 55.1%
and 6.4%, respectively. Patients in Stomach and GI group were older than
Intestine group (Mean age: 54 and 53 years vs. 43 years, p50.001).
Histologically, intermediate-grade lymphoma was the most common (53.7%),
but high-grade lymphoma almost occurred in Intestine group (82.5%). Fiveyear overall survival (OS) and event-free survival (EFS) was 56.4% and
49.3%, respectively. Univariate and multivariate analysis revealed that performance status, LDH level and histological type were independent prognostic
factors for OS and EFS. Stomach group had better OS and EFS (72.3% and
48.4%) than Intestine group (43.1% and 23.6%), respectively (p 0.003 and
p 0.021), but it lost the significance in the multivariate analysis.
CONCLUSION: PGIL is uncommon and lacks specific symptom in China.
Intermediate-grade lymphoma is the most common histological type, while
high-grade lymphoma almost occurred in the intestine. Patients with good performance status, normal LDH and non-high-grade phenotype may have better
prognosis.
Disclosure of Interest: None declared

have a prognostic value for therapeutic regimes. HER-2/neu over expression has
proved to have predictive value in breast cancer patients, responding to
Trastuzumab treatment. Some researchers also indicated the importance of this
element in GC.
AIMS & METHODS: We investigated the frequency of HER-2/neu over expression in gastric carcinoma and its correlation with clinicopathologic variables.
101 paraffin embedded tissue blocks from the pathology archives of Firoozgar
Hospital with established diagnosis of gastric carcinoma were used for the study
of HER-2/neu over expression using immunohistochemistry (IHC) staining and
using tissue microarray method (TMA).
RESULTS: Mean age of patients was 60.13  11 (32-82) years. Male to female
ratio was 2.4:1. HER2/neu over expression was positive in 13 cases (12.9%). The
frequency of HER2/neuoverexpression in tumors 5cm was significant. There
was no statistically significant correlation between HER2/neu over expression
and other pathological features such as grade, stage, lymph node involvement,
tumor location, histopathological type, as well as age and sex.
CONCLUSION: In conclusion, in our study the over expression rate of Her2/
neu was reach to 13% which is same as other studies. We confirm that TMA
could allow to determining the paten of biomarkers of GC and consequently can
be used in clinical practices. Also this study can not confirm the association
between Her2 and GC
Disclosure of Interest: None declared
P1628 FEATURES OF THE GASTRIC CANCER IN PATIENTS WITH
SYSTEMIC NOT-DIFFERENTIATED DYSPLASIA OF CONNECTIVE
TISSUE
N. Lyudmila1,*, O. Osipova1
Medical Institute, Department of the Pathological physiology and General
Pathology, Surgut State University of Khanty-Mansi Autonomous Okrug-Ugra,
Surgut, Russian Federation
Contact E-mail Address: naumovala@yandex.ru
1

INTRODUCTION: The problem of gastric carcinogenesis is closely connected


with the concept of border epithelia. The structure and operation of border
epithelia are based on the epithelial-stromal relations. The violations of the
epithelial-stromal relations in gastric cancer (GC) are marked both in the intestinal (IGC) and diffuse (DGC) types. It results in the interest in GC with systemic
non-differentiated dysplasia of connective tissue (DCT), that initially determines
other character of "substrate" for the epithelium, or other epithelial-stromal
relationship.
AIMS & METHODS: The aim is to study the peculiarities of GC in patients with
systemic non-differentiated DCT. The analysis of the clinical data and morphological study (light microscopy) of surgical specimens were done in 76 patients
with GC aged 29-79 years. Among them 41 (54%) patients with visceral signs of
DCT amounted group 1; 35 patients without signs of DCT formed group 2.
Comparative statistical analysis was performed by 2- criterion and Fisher s
exact test at p50.05.
RESULTS: Groups did not differ in structure of histotypes GC: IGC was respectively diagnosed in 51.2 and 45.7% of cases, DGC - in 26.8 and 22.9%, mixed GC
- in 22.0 and 31.4% of cases. The stigmatization of the genitourinary system
(51.2%) and the gastrointestinal tract (41.5%) prevailed in group 1 among
stigma. The nature of stigma was cysts in different organs (68.3%), but mostly
in kidneys (41.5%). Peculiarities of GC with DCT were as following: high frequency of gastritic anamnesis (80.5 and 48.6% respectively, p 50.05) and chronic
ulcers (41.5% and 17.1%, p50.05) which prevailed in group 1 in IGC (52, 4%),
but in general in DGC (42.1%); localization of the tumor in the body of
stomach (61.0%, in group 2 34.3%, p50.05), in group 2 in cardia (31.4%,
in group 1 9.8%, p50.05); greater (in 2.5 times higher than in group 2) proportion of patients aged under 40 years (14.6% in group 1 and 5.7% - in group 2);
high frequency of combined lesion of gastric mucosa (GM) and other border
epithelium mucosa of urinary tract in particular (48.8%, in group 2 8.6%, p
50.05); combined lesion of GM and colonic mucosa (atrophic colitis, adenomatous polyps and in two cases - meta-and synchronous colorectal cancer) 14.6
and 8.6% of cases in groups respectively (i.e. 1.7 times more frequently in
patients of group 1); combined lesion of GM and bronchial mucosa (obstructive
bronchitis, bronchial asthma, lung cancer) - by groups of respectively 24.4 and
14.3 % of cases (1.7 times more often in group 1). The features of epithelial
substrate or system of connective tissue can be one of the basic mechanisms
of combined lesions of the mucous membranes of various localizations.
CONCLUSION: The revealed features (stigmatization of gastrointestinal tract
and urinary system, in particular cysts in kidneys, gastritic anamnesis, chronic
ulcers) can have a marker value in patients with DCT for inclusion in group of
risk of developing GC.
Disclosure of Interest: None declared
P1629 DETECTION RATES OF GASTRIC CANCER AT THE QUEEN
ELIZABETH HOSPITAL BIRMINGHAM 2009-2013

P1627 PREVALENCE OF HER-2/NEU OVER EXPRESSION IN GASTRIC


CARCINOMA;BY USING TISSUE MICROARRAY (TMA)
M. Sohrabi1, N. Rakhshani1,*, F. Zamani1, M. Khonsari1
Gastrointestinal and Liver Disease Research Centre, Iran University, Tehran,
Iran, Islamic Republic Of
Contact E-mail Address: sohrab_r@yahoo.com
1

INTRODUCTION: Usually anatomical location and histological phenotype of


gastric cancer (GC) is considered for selection of chemotherapy regime against
GC. In other hand, genetic factors is also influence on out-come of GC and
treatment. During recent years many researchers concentrate on molecular characteristics of cancer cell and it is believed that some molecular elements could

N. Sagar1,*, N. Bhala1
1
Gastroenterology, Queen Elizabeth Hospital Birmingham, Birmingham, United
Kingdom
Contact E-mail Address: dr.nidhisagar@gmail.com
INTRODUCTION: Despite open-access endoscopy, previous series have suggested that between 8-20% of early gastric cancers (GC) are potentially missed
at prior endoscopy1,2. Although upper gastrointestinal alarm symptoms are
more frequently associated with malignancy, this may represent advanced
cancer with poorer survival rates, as patients with early GCs may be asymptomatic. The false-negative rate for the diagnosis of GC may also be a measure of
quality for endoscopy services. This is based on a reported median duration of 37

A580
months between endoscopic diagnosis of early GC and progression to advanced
GC2,3, so we assessed all oesophagogastroduodenoscopy (OGD) findings to
assess detection of GC in a large tertiary hospital in the West Midlands.
AIMS & METHODS: Patients with histologically confirmed GC were identified
from histopathology and endoscopy records. Patients who had undergone at
least one OGD before the diagnosis were studied. Detection of GC within 3
years of a negative OGD was interpreted as a false negative.
RESULTS: Between September 2009 and September 2013, 16823 OGDs were
performed. GC was diagnosed in 75 (0.45%) patients (male/female ratio 1.78;
median age 74; 85% Caucasian). Sixty-seven (89%) of the 75 patients with GC
presented with alarm symptoms. 33% (25) were done as inpatients, with 43% (at
least 32 of 50 outpatients) being referred as urgent outpatients. Five of the 75
(7%) patients had previous OGDs within three years preceding diagnosis. Only
one of these was planned because of a suspicious gastric ulcerative lesion at the
same site, with other causes being gastric polyps (2); normal (1) and gastritis (1).
There were 53 (71%) deaths in total, 47 (89%) of these patients had alarm
symptoms at diagnosis of GC.
CONCLUSION: The absolute rates of GC are low (0.1%/OGD/year) and falsenegative rates of 5% (within 3 years) for diagnosis of GC are reassuring with only
a minority of preceding OGDs in this series demonstrating suspicious lesions.
Whilst GC presents with alarm symptoms in the vast majority, the prognosis
remains very poor, so continued quality measures in endoscopy will be required
to ensure that early gastric cancers are not missed.
REFERENCES
1. Vradelis S, Maynard N, Warren BF, et al. Quality control in upper gastrointestinal endoscopy: detection rates of gastric cancer in Oxford 2005-2008.
Postgrad Med J 2011; 87: 335-339.
2. Hosokawa O, Tsuda S, Kidani E, et al. Diagnosis of gastric cancer up to three
years after negative upper gastrointestinal endoscopy. Endoscopy 1998; 30: 669674.
3. Tsukuma H, Mishima T and Oshima A. Prospective study of early gastric
cancer. Int J Cancer 1983; 31: 421-426.
Disclosure of Interest: None declared
P1630 TRENDS AND RESULTS IN TREATMENT OF GASTRIC CANCER
OVER LAST TWO DECADES AT SINGLE EAST EUROPEAN
CENTRE
P. Ignatavicius1,*, A. Mickevicius1, Z. Dambrauskas1, R. Markelis1,
A. Parseliunas1, M. Kiudelis1, Z. Endzinas1, A. Maleckas1
1
Department of Surgery, Lithuanian University of Health Sciences, Kaunas,
Lithuania
Contact E-mail Address: ignatavicius@gmail.com
INTRODUCTION: A steady decline in gastric cancer mortality rate over the last
few decades is observed in Western Europe. However it is still not clear if this
trend applies to Eastern Europe where high incidence rate of gastric cancer is
observed.
AIMS & METHODS: This was a retrospective non-randomized, single center,
cohort study. During this period 557 consecutive patients diagnosed with gastric
cancer in which radical operation was performed and who met the inclusion
criteria were included in the study. The study population was divided into two
groups according to two equal time periods: 01-01-1994 31-12-2000 (Group I
273 patients) and 01-01-2001 31-12-2007 (Group II 284 patients). Primary
(five-year survival rate) and secondary (postoperative complications, 30-day
mortality rate and length of hospital stay) endpoints were evaluated and
compared.
RESULTS: Rate of postoperative complications was similar between the groups,
except Grade III (Clavien-Dindo grading system for the classification of surgical
complications) complications, where significantly (p 0.02) less complications
were observed in Group II (26 (9.5%) vs. 11 (3.9%)). Length of hospital stay
was significantly (p 0.001) shorter (22.628.9 vs. 16.217.01 days) and 30-day
mortality was significantly (0.02) lower (15 (5.5%) vs. 4 (1.4%)) in Group II. In
both groups similar number of patients died of cancer (92.3% vs. 90.7%).
However survival analysis revealed significantly (p 0.02) better overall 5-year
survival rate in Group II (35.6%, 101 of 284) than in Group I (23.4%, 64 of 273).
There was no difference in 5-year survival rate when comparing different TNM
stages.
CONCLUSION: Despite positive changes in early postoperative mortality rate,
hospital stay and overall survival over the time, gastric cancer treatment results in
Eastern Europe remain poor. Prognosis of treatment of gastric cancer depends
mainly on the stage of the disease. Absence of screening programs and lack of
clinical symptoms in early stages of gastric cancer lead to circumstances when
most of the patients presenting with advanced stage of the disease can expect a
median survival of less than 30 months even after curative intent surgery.
Disclosure of Interest: None declared
P1631 PALLIATION OF INTRACTABLE VOMITING CAUSED BY
INOPERABLE GASTROINTESTINAL MALIGNANCY: EFFICACY
OF A VENTING GASTROSTOMY
S. Beg1,*, R. Nathwani2, M. Yalchin2, M. Mensa1, J. Deacon2, I. Sargeant2,
D.L. Morris2, S. Catnach1, A. Leahy1 on behalf of Hertfordshire and
South Bedfordshire Network Cancer Group
1
Gastroenterology, West Hertfordhire NHS trust, 2Gastroenterology, East and
North Hertfordshire NHS trust, Hertfordshire, United Kingdom
Contact E-mail Address: sabina.beg@nhs.net
INTRODUCTION: The insertion of percutaneous endoscopic gastrostomy
(PEG) tubes for decompression of gastrointestinal obstruction in patients in
whom a surgical option is not possible is well established. There is however,

United European Gastroenterology Journal 2(1S)


very little information on the safety or success of this intervention, which is
usually performed in cohort of patients with poor baseline function and prognosis. The aim of this study is to assess the efficacy of a venting gastrostomy to
relieve intractable vomiting in a palliative setting.
AIMS & METHODS: We retrospectively analysed our computer based endoscopy databases to identify all venting gastrostomies inserted over a four year
period, between January 2010 and January 2014 in three NHS hospital Trusts
within a Network Cancer Group (catchment population 1.4 million). Cases were
analysed with respects to indication, complications, success at subsequent hospital discharge and survival.
RESULTS: Within a four year period a total of seven venting gastrostomies were
inserted. The median age of this cohort was 68 years old (range 61 81 years),
with a male to female ratio of 5:2. The most common indication for insertion was
malignant obstruction (duodenal cancer n 2, metastatic mesothelioma n 1,
colorectal adenocarcinoma n 2, pseudomyxoma peritonei n 1). One patient
however, did not have evidence of active cancer, with instead multiple foci of
fibrotic small bowel strictures secondary to pelvic radiotherapy from a previously
treated gynaecological malignancy. Gastrostomy insertion was a palliative measure in five patients, whilst in two patients it was a temporising measure with
concomitant total parenteral nutrition (TPN) support, whilst definitive complex
surgery at a tertiary referral centre was considered.
The Corflo gastrostomy tube was used in all cases, with PEG size ranging from
16 fr (n 3) to 20 fr (n 4). At the time of insertion 57% had a American Society
of Anesthesiology (ASA) score of 3, whilst 43% had an ASA score of 4.
Successful placement was achieved in all patients, with no immediate complications. A single patient had several episodes of heamatemesis 22 days post insertion whilst an inpatient, a gastroscopy revealed gastritis only and confirmed
normal appearances of the gastrostomy site. The median hospital stay after
gastrostomy insertion was 12.4 days (range 1 29 days), with the longest continued hospital stay attributable to a patient awaiting transfer to a tertiary centre
for home TPN. There were no PEG related readmissions or deaths, and the
median survival after gastrostomy insertion was 37 days.
CONCLUSION: This study demonstrates the safety of venting gastrostomy
insertion for gastrointestinal obstruction due to a variety of pathologies.
Whilst patients undergoing venting gastrostomies may be expected to have a
short post procedural survival, our data shows this procedure can lead to a
successful palliation and a subsequent successful discharge home in the majority
of cases.
Disclosure of Interest: None declared
P1632 THE ROLE OF RADIOLOGICAL STUDY AND ENDOSCOPIC
ULTRASONOGRAPHY FOR PRE-OPERATIVE EVALUATION FOR
EARLY GASTRIC CARCINOMA
S. Shimaoka1,*, A. Matsuda1, T. Nioh1, S. Iifuku1, Y. Baba1, M. Toyoda1,
K. Iwaki1, N. Nishimata1, K. Tsukasa1, K. Tashiro1, T. Niihara1, Y. Nishimata1,
M. Hori1, H. Nishimata1, S. Tanaka2
1
Gastroenterology, 2Diagnostic Pathology, NANPUH HOSPITAL, Kagoshima,
Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) is a developed
EMR technique for reliable en bloc resection and is rapidly becoming standard
of treatment for early gastric carcinoma.
AIMS & METHODS: The aims of this study is to clarify the role of radiological
study and endoscopic ultrasonography for pre-operative evaluation for early
gastric carcinoma. We investigated the 287 gastric carcinoma cases that had
been treated by ESD or surgery. Endoscopic, Radiological, EUS findings that
indicated SM2 carcinoma were set beforehand respectively. The accuracy of the
diagnosis and the additional diagnostic value of radiological and EUS diagnosis
were investigated.
RESULTS: The accuracy rates of endoscopic diagnosis were high enough to
decide the indications of ESD in the lesions 30mm or less in size, differentiated
type without Ul. However in the lesions larger than 30mm, differentiated type
with Ul, the accuracy rates were lower than the lesions without Ul because of
over-diagnosis. Even in such lesions, using radiological diagnosis, the accuracy
rates rose enough to decide the indication of ESD. The accuracy rates of endoscopic diagnosis in the lesions larger than 30mm, differentiated type without Ul
were lower than the lesions equal or less than 30mm because of under-diagnosis.
The accuracy rates rose using radiological diagnosis in such lesions. In the lesions
equal or less than 20mm, undifferentiated type without Ul, the accuracy rates of
endoscopic diagnosis were high enough to decide the indications of ESD. EUS
was useful in the upper gastric lesions that compression methods could not be
used in radiological examinations.
CONCLUSION: Radiological examinations were useful in large lesions that
were under-diagnosed in endoscopy to avoid unnecessary ESD and the lesions
without Ul that were over-diagnosed in endoscopy to avoid unnecessary surgery.
Even in ESD age, it is important to use endoscopy, radiological examination,
EUS complementarily according to the lesions to get neither too much nor too
little information for deciding treatment strategy.
Disclosure of Interest: None declared

A581

United European Gastroenterology Journal 2(1S)


P1633 SERUM C-REACTIVE PROTEIN CAN BE A PREDICTIVE
MARKER FOR DELAYED BLEEDING AFTER ENDOSCOPIC
SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER
S. Yoshii1,*, S. Yamamoto2, M. Kato1, K. Nagai1, T. Fujinaga1, Y. Tsujii1,
A. Maekawa1, M. Hirao2, T. Inoue1, Y. Hayashi1, M. Nishiyama2, M. Komori2,
T. Nishida1, H. Iijima1, M. Tsujii1, H. Yoshihara2, T. Takehara1
1
Department of Gastroenterology and Hepatology, Osaka University Graduate
School of Medicine, Suita-shi, 2Department of Gastroenterology, Osaka Rosai
Hospital, Sakai-shi, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) has become a promising procedure as a therapeutic tool for early gastric cancer (EGC). However,
delayed bleeding occasionally occurs and it sometimes leads to severe hemorrhage or shock. There has been no useful indicator to predict the risk of bleeding
after ESD for EGC.
AIMS & METHODS: The aim of this study is to clarify the usefulness of the
parameters of blood examination in addition to clinico-pathological factors for
the prediction of delayed bleeding after ESD for EGC. A total of 548 subjects
with EGC who underwent gastric ESD in Osaka University Hospital and Osaka
Rosai Hospital between April 2007 and December 2013 were enrolled. Cases
having intraoperative perforation (n 16) or more than two lesions treated on
the same day (n 45) were excluded. Delayed bleeding was defined as bleeding
from post-ESD ulcer with hematemesis, melena or massive blood retention in the
stomach at an emergent endoscopy or planned follow-up endoscopy. Cases with
bleeding before planned blood examination test on a day after ESD were
excluded. We analyzed associations between delayed bleeding and the parameter
of blood examination including white blood cell count, hemoglobin level, Creactive protein (CRP) level (mg/dL), and blood urea nitrogen-to-creatinine
ratio. In addition, we also analyzed the following clinico-pathological factors;
age, sex, gross-morphology, location, size, presence of the ulceration, and the
invasion depth of the tumor, procedure time, comorbidity (hypertension, cardiac
disorder, liver cirrhosis, diabetes mellitus and dialysis) and the use of anticoagulants and/or antiplatelet drugs.
RESULTS: Of 26 (5.3%) post-ESD bleeding cases, 23 cases fulfilled the criteria
of delayed bleeding and were included in the study. Univariate analysis revealed
that presence of the ulceration in tumor, upper third location of the stomach, and
the elevations of the serum CRP levels on post-ESD 1day (CRP-DAY1), were
significantly associated with bleeding (p 0.009, p 0.04 and p 0.007, respectively). Multivariate logistic regression analysis revealed that the presence of
ulceration in tumor (OR, 4.1; 95%CI: 1.2-13.0, p 0.02) and the elevation of
the serum CRP-DAY1 (OR, 3.2; 95%CI: 1.1-9.9, p 0.04) were independent risk
factor for delayed bleeding. When classified the patients into 4 subgroups based
on CRP-DAY1, the prevalence of the post-ESD bleeding gradually increased as
CRP-DAY1 increased (p 0.03, for trend, table 1).

Q1
Q2
Q3
Q4

in 57 patients, including 13 patients were graded as C2-3, 37 as 01-2, and 7 as 03p. Moreover, 21 patients had GA, including 1 graded as C2-3, 11 as 01-2, and 9
as 03-p. The degree of atrophy associated with GA was significantly higher than
that associated with EGC (P 5 0.05).
CONCLUSION: Conclusion: The current findings showed that gastric neoplasia
was well correlated with severe atrophic gastritis. Based on the current findings,
the degree of atrophy appears to be useful for discriminating between EGC and
GA.
Disclosure of Interest: None declared
P1635 SIGNET RING CELL EXISTENCE CAN BE A NEGATIVE
PREDICTOR OF PACLITAXEL CHEMOTHERAPY EFFICACY FOR
PATIENTS WITH UNRESECTABLE GASTRIC CANCER
T. Yamada1,2,*, Y. Saida1, T. Matsuura1, S. Onoue1, K. Sugimoto2
1
Department of Gastroenterology, Iwata City Hospital, Iwata, 2First Department
of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

CRP level (mg/dL)

The rate of post-ESD bleeding

INTRODUCTION: The efficacy of chemotherapy is critical for quality of life


(QOL) and prognosis of patients with unresectable gastric cancer. Cisplatin/
fluoropyrimidine-based chemotherapy is commonly considered first line chemotherapy for gastric cancer, whereas taxian as well as CPT-11 is accepted for
second line chemotherapy. However, clinicopathological parameters or biomarkers to decide second line chemotherapy regimen for gastric cancer remain to be
elucidated.
AIMS & METHODS: We evaluated efficacy of weekly paclitaxel systemic chemotherapy (wPTX) for patients with unresectable gastric cancer using progress
free survival (PFS) retrospectively. From 2008 to 2013, 32 unresectable gastric
cancer patients were treated with wPTX as second line chemotherapy in two
hospitals, a university hospital and a general hospital.
RESULTS: The mean PFS of all patients was 21.6 weeks (2 to 108 weeks). Three
was no significant differences in sex (male; female, 9 cases; 23 cases), age (mean
69.4 years old, 16 cases are younger than 70, others are 70 or older), location of
lesion (Upper 9 cases; Middle 16 cases; Lower 7 cases), peritoneal dissemination
(18 cases), and clinical stage (IIIb 1 case, IV 31 cases). Microscopic morphology
was classified into 4 groups (tubular 13 cases; poorly differentiated 16 cases;
signet ring cell 8 cases; mucinous 2 cases). The cases consist of 2 or more types
of cancer cell were counted in all their cell type groups. The mean PFS of tubular,
poorly differenciated, signet ring cell (SRC), and mucinous were 28.1, 17.6, 8.5,
and 12.0 weeks, respectively. There was signifincant difference of PFS only
between SRC positive group (mean PFS 8.5 weeks) and negative (26.0 weeks)
group (p 0.006).
CONCLUSION: These results suggest that SRC existence can be a negative
predictor of PTX efficacy for unresectable gastric cancer. Further investigation
is needed to reveal the precise mechanism and development effective chemotherapies, including CPT-11, for SRC positive gastric cancer.
Disclosure of Interest: None declared

0.03-0.33
0.34-0.74
0.75-1.49
1.5-10.09

1.7%
5.0%
4.2%
8.3%

P1636 PRELIMINARY RESULTS OF ENDOSCOPIC SUBMUCOSAL


TUNNEL DISSECTION FOR GASTROINTESTINAL
SUBEPITHELIAL TUMORS ORIGINATED FROM MUSCULARIS
PROPRIA LAYER; A SINGLE CENTER EXPERIENCE

(2/117)
(6/121)
(5/118)
(10/120)

Table 1
CONCLUSION: A higher level of serum CRP on the next day of gastric ESD
may serve as a predictor for delayed bleeding.
Disclosure of Interest: None declared
P1634 DISCRIMINATION OF EARLY GASTRIC CANCER FROM
GASTRIC ADENOMA, BASED ON THE CHARACTERISTICS OF
GASTRIC NEOPLASIA
T. Miike1,*, Y. Miyata1, S. Yamamoto1, Y. Noda1, T. Noda1, S. Suzuki1,
S. Takeda1, K. Maemura1, K. Hashimoto1, T. Yamaji1, H. Abe1, Y. Tahara1,
K. Yorita2, H. Kataoka2, K. Shimoda1
1
Gastroenterology and Hematology, 2Oncopathology and Regenerative Biology,
university of miyazaki, 5200 kihara kiyotake, Japan
INTRODUCTION: Background and Aim: Chronic atrophic gastritis has
received increased attention, in Japan, because the observed gastric mucosa characteristics have been reported to be associated with gastric neoplasia. However,
chronic atrophic gastritis is caused by a Helicobacter pylori infection. In the
present study, we aimed to discriminate between early gastric cancer (EGC)
and gastric adenoma (GA) by analyzing the characteristics of gastric neoplasia.
AIMS & METHODS: Methods: We retrospectively examined the records of 211
patients who underwent endoscopic submucosal dissection for gastric neoplasia
at the Miyazaki University Hospital between October 2009 and March 2014. Of
these, 78 patients who had not previously undergone H. pylori eradication treatment were evaluated and assessed for the presence of pepsinogen and the degree
of gastric atrophy. If the border of the atrophy was on the lesser curvature of the
stomach, it was defined as a closed-type (C-type). These were subdivided into C0,
Cl, C2, and C3 patterns. If the border was shifted orally and did not exist on the
lesser curvature, it was defined as an open-type (0-type), subdivided into 01, 02,
O3, and 0p patterns. Therefore, gastric atrophy was graded as C0-l, C2-3, 01-2,
and 03-p, based on its severity. Statistical analyses were conducted using a chisquared test, with P 5 0.05 indicating statistical significance.
RESULTS: Results: In total, 78 patients had gastric neoplasia; of these, 64 were
graded as having the 0-type (82%), and 14 with the C-type. EGC was diagnosed

J.W. Choe1, Y. Jeoung1,*, M.K. Joo1, B.J. Lee1, J.-J. Park1, J.S. Kim1, Y.-T. Bak1
1
Korea University College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: neucjw@naver.com
INTRODUCTION: Although the majority of gastrointestinal subepithelial
tumors (SETs) are benign, some do have a malignant potential. Resection of
SETs would aid in establishing the diagnosis and may be curative. So, we aim
to present the feasibility and safety of a novel endoscopic submucosal tunnel
dissection (ESTD) method for resection of upper gastrointestinal SMTs originating from the muscularis propria (MP).
AIMS & METHODS: In 8 patients who presented with an upper gastrointestinal
SMT located in the stomach, we underwent submucosal tunnel endoscopic resection between August 2011 and February 2013. A submucosal tunnel was endoscopically created by starting approximately 4cm distant to the lesion. After
careful submucosal dissection of the tumor from the surrounding submucosal
tissue and the unaffected MP layer with making the tunnel, the SETs were
completely removed by the technique of endoscopic submucosal dissection.
Finally, the mucosal entrance of the tunnel was closed using endoclips after
the tumor was removed.
RESULTS: SETs had a mean size of 21.5mm (range 1725mm); 4 were located in
the antrum,3 in the body and 1 in the cardia. SET resection was successful in all
patients with en bloc resection 88% rate. 6 lesions affected the deep MP, so Full
thickness resection including MP layer was performed; except ectopic pancreas
partialy resected for the purpose of diagnosis. 2 lesions affected the superficial
MP for a partial MP resection. The mean procedure time was 66.1 minutes (range
4080 minutes). The endoscopic procedure was converted into laparoscopic surgery in three patients. Two patients had lost the full thickness resected samples in
the peritoneal space. One patient had sustained abdomen pain and fever after
successful procedure. The other five patients had no any complications such as
delayed hemorrhage and chronic fistula after then. No residual tumor or tumor
recurrence were detected during the follow-up period (mean: 4.5 months, range:
39 months). Pathological diagnoses of these tumors were low risk gastrointestinal stromal tumors (6/8), a schwannoma (1/8), and a etopic pancreas (1/8).
CONCLUSION: In this study, endoscopic submucosal tunnel dissection (ESTD)
was appeared to be feasible endoscopic procedure to remove tumors originating
from the muscularis propria layer in the stomach.
Disclosure of Interest: None declared

A582
P1637 COLLAGEN TYPE XI A1 IS ASSOCIATED WITH T STAGE OF
GASTRIC CANCER AND REGULATES THE MIGRATION,
INVASION AND PROLIFERATION OF HUMAN GASTRIC CANCER
HGC-27 CELLS
A. Li1,*, J. Li1, W. Zhuo2, J. Si1
Department of gastroenterology, Sir Run Run Shaw Hospital, Zhejiang
University, 2Institution of Gastroenterology, Zhejiang University, Hangzhou,
China
Contact E-mail Address: li_aq2003@aliyun.com
1

INTRODUCTION: Collagen type XI 1 (COL11A1) which plays important


roles in carcinogenesis is increasingly recognized, including ovarian cancer and
head and neck squamous cell cancer. However, the relation between COL11A1
and gastric cancer is still unclear.
AIMS & METHODS: The main purpose of this study is to investigate the
expression levels and potential roles of COL11A1 in gastric cancer.
We examined the COL11A1 mRNA expression levels in fifty-three gastric cancer
lesions and twenty normal gastric mucosa from endoscopy or surgery by qualitative real-time PCR. We also evaluated its expression level in seven gastric
cancer cell lines by qualitative real-time PCR and western blotting.
Furthermore, we established a stable cell line HGC-27 with COL11A1 gene
knock-down to study its functional role in regulating cell proliferation, migration
and invasion. To identify target candidates of COL11A1, we performed cDNA
microarray.
RESULTS: Our qualitative real-time PCR results demonstrated that COL11A1
expression was significantly increased in tumor samples (n 53) compared with
that in normal tissues (n 20) (p50.01). The up-regulation of COL11A1 was
associated with T stage (p50.01). In addition, COL11A1 was highly expressed in
the gastric cancer cell line HGC-27 as compared with other gastric cancer cells
(SGC-7901, MGC-803, BGC-823, AGS, MKN-28, MKN-45) and a normal
immortalized epithelial cells GES-1. We found that knockdown of COL11A1
significantly inhibited the migration (p50.01), invasion (p50.01) and proliferation (p50.01) of HGC-27 cells. Knockdown of COL11A1 also induced cell
apoptosis (p50.01) and impaired cell cycles (p50.01). HGC-27 cells cDNA
microarray showed that COL11A1 regulated multiple tumor metastasis-related
genes such as CXCR4, CTSK, SET, KRAS, TPBG, MGAT5 and so on.
CONCLUSION: Our findings suggest that COL11A1 is overexpressed in gastric
cancer, which may contribute to tumorigenesis and tumor aggressiveness. These
results encourage the exploration of COL11A1 as a potential therapeutic target
for gastric cancer.
Disclosure of Interest: None declared
P1638 ALBUMIN AS A MEDIATOR CONJUGATES DOXORUBICIN
WITH GOLD NANOPARTICLES TO IMPROVE DELIVERED AND
THERAPEUTIC EFFICACY OF DOXORUBICIN IN GASTRIC MKN45INDUCED TUMOR XENOGRAFTS
A.-S. Ho1,*, C.-C. Cheng2, C.-C. Chang3, H.-C. Lin1, T.-Y. Luo2, J. Chang4
Cheng Hsin General Hospital, Taipei, 2Institute of Nuclear Energy Research,
Taoyuan, 3Taipei Medical University Hospital, 4Taipei Medical University, Taipei,
Taiwan, Province of China
Contact E-mail Address: js.chang@tmu.edu.tw
1

INTRODUCTION: Doxorubicin (DOX) is a drug used in cancer treatment in


wide ranges of tumors. More effectively DOX targeting into tumor foci can
benefit a better therapeutic efficacy coupled with a lower drug dosage and minimized side effects. With the goal of improving the therapeutic utility of DOX,
several forms of drug delivery vehicles to target cancer has been developed and
characterized such as liposomes.
AIMS & METHODS: In our current work, we used gold nanoparticles (GNPs)
as our drug carrier vehicles loaded with DOX to target MNK45-derived tumors
in xenograft nude mice. To avoid the forming of GNPs aggregations and provide
the bridges on GNPs to DOX, we formulated bovine serum albumin (BSA) to
coat the surface of GNPs and then evaluate the therapeutic effects of DOXGNPs in animals.
RESULTS: The results demonstrated that our synthesized GNPs after BSA
modification with size ranged from 15 to 300nm and the average diameters is
near to 76.157.6 nm. The peak absorbance of these BSA-decorated GNPs was
measured at 534 nm wavelength of light. To determine the cytotoxicity of BSAdecorated GNPs, gastric cancer cells, MNK45, were cultured with medium containing GNPs from concentration of 10 to 100 M and no cytotoxicity was
measured. To evaluate the specificity in tumor targeting of BSA-decorated
GNPs in animals, the fluorescein isothiocyanate (FITC) molecules were also
directly tagged onto the BSA layers of GNPs for later in vivo real time detection
and imaging. The results demonstrated that our BSA-decorated GNPs were more
effectively targeting to tumors than other organs. To assess the therapeutic efficacy, DOX were covalently bound to the BSA-decorated GNPs and then was
characterized in vitro and in vivo by intravenously administration into xenograft
animals. It revealed that GNP vehicle-driven DOX uptaked by tumor cells
in vitro was higher and also impact more severe cytotoxicity to tumors. We
also observed a better therapeutic outcome in vivo therapy in the xenograft
nude mice with intravenously injection of DOX driven by BSA-decorated
GNPs by displaying the lower tumor volume after 24 days therapeutic period
time.
CONCLUSION: It suggests that BSA is a good mediator to bridge chemotherapeutic drugs such as doxorubicin to GNPs for improving tumor targeting and
therapeutic outcome with lower cytotoxicity, indicating that GNPs display as a
good and safer vehicles for delivering antitumor drugs to tumors.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1639 EPIGENETIC SILENCING OF MIR-137 IS A FREQUENT AND
EARLY EVENT IN GASTRIC CARCINOGENESIS
A. Link1,*, R. Steponaitiene2, J. Kupcinskas3, C. Langner1, F. Balaguer4,
L. Venclauskas2, H. Pauzas5, A. Tamelis5, J. Skieceviciene2, L. Kupcinskas3,
P. Malfertheiner1
1
Gastroenterology, Hepatology and Infectious Diseases, OTTO-VONGUERICKE UNIVERSITY HOSPITAL MAGDEBURG, Magdeburg, Germany,
2
Institute for Digestive Research, 3Department of Gastroenterology, Lithuanian
University of Health Sciences, Kaunas, Lithuania, 4Department of
Gastroenterology, Hospital Clinic, CIBEREHD, University of Barcelona,
Barcelona, Spain, 5Department of Surgery, Hospital of Lithuanian University of
Health Sciences, Kaunas, Lithuania
Contact E-mail Address: alinkmail@gmail.com
INTRODUCTION: microRNAs (miRNA) are functional molecules that control
gene expression and are frequently dysregulated during carcinogenesis, in particular in gastric cancer (GC). miR-137 functions as a tumor-suppressor-miRNA
through silencing various oncogenes. CpG island methylation of miR-137 is a
common event in glioblastoma and colorectal cancer (CRC). In this study, we
systematically characterize the miR-137 promoter methylation and miR-137
expression in gastric carcinogenesis and correlate these results with overall survival of gastric cancer patients.
AIMS & METHODS: Tissue specimens were prospectively collected in Kaunas,
Lithuania and in Magdeburg, Germany. Overall, 287 tissues were included to the
study. We analyzed 81 pairs of primary gastric cancer tissues (T-GC) with corresponding adjacent normal gastric mucosa (N-GC), 25 normal gastric tissues
from controls (N), 44 tissues from patients with chronic/atrophic gastritis 
intestinal metaplasia (CG) and 28 pairs of primary CRC tissues (T-CRC) with
corresponding adjacent normal colonic mucosa (N-CRC). We determined the
methylation status of miR-137 using bisulfite pyrosequencing. TaqMan RTPCR was used to analyze miR-137 expression. Survival differences were evaluated using Kaplan-Meier analyses.
RESULTS: Defined by the distribution of miR-137 methylation in normal
mucosa (mean2SD), methylation of miR-137 is rare in normal mucosa (5%,
mean methylation  SD: 7.470.89%), however, increased in CG patients
(10.680.97%). In correlation, miR-137 methylation was more frequent in
tumorous compared to non-tumorous conditions both in CRC and GC (TCRC 75% vs. N-CRC 15.8% and T-GC 46.8% vs N-GC 42.3%). Quantitative
miR-137 methylation analyses revealed higher methylation in T-CRC compared
to N-CRC (30.1217.37% vs. 11.129.07%, p 0.0009) and in similar fashion
in T-GC to N-GC (21.0813.88% to 16.9211.55%, p 0.015). miR-137 expression is inversely correlated with miR-137 CpG methylation as tumors with low
methylation level showed higher expression compared to tumors with intermediate or high miR-137 methylation (p 0.0006). In subgroup analyses, miR-137
methylation was higher in GC with intestinal type compared to diffuse one and
higher in antrum compared to cardia and corpus, while no association existed to
H. pylori infection or TNM stages. Overall survival analyses revealed an association between miR-137 methylation and worse prognosis in diffuse type gastric
cancer, but not in intestinal type.
CONCLUSION: miR-137 is frequently methylated in gastrointestinal cancers.
Increasing methylation of miR-137 from normal mucosa, chronic gastritis to
cancerous tissues suggests it is an early event in gastric carcinogenesis. The
alterations of miR-137 may play probably a more considerable role in development of intestinal type GC; but also worse prognosis of patients with miR-137
methylation in diffuse type GC supports the need of further functional analyses
in both types of GC.
Disclosure of Interest: None declared
P1640 IMMUNOFLUOROMETRIC ANALYSIS OF THE EXPRESSION
AND CLINICAL SIGNIFICANCE OF KALLIKREIN-RELATED
PEPTIDASES 5 AND 7 (KLK5 & KLK7) IN COLON CANCER
A. Malachias1,*, M. Brown2, Y. Zheng2, D. Kypraios1, S. Bassioukas1,
M. Nikaki1, D. Dimitroulopoulos1, D. Xynopoulos1, M. Talieri3
1
Gastroenterology, Saint Savvas Cancer Hospital, Athens, Greece, 2Biostatistics &
Biomathematics, Fred Hutchinson Cancer Research Center, Washington, United
States, 3Cellular Physiology, G. Papanicolaou Research Center of Oncology, Saint
Savvas Hospital, Athens, Greece
Contact E-mail Address: talieri@agsavvas-hosp.gr
INTRODUCTION: Existing, colon cancer (CC) markers lack sensitivity and
specificity. KLKs present a new class of cancer biomarkers under investigation.
KLKs are concomitantly expressed in various tissues participating in proteolytic
cascades. KLK5 and KLK7 in human tumors facilitate metastasis by directly
degrading components of the extracellular matrix in the area surrounding KLK5
or KLK7-producing cells. KLK5 activates its own pro-enzyme as well as
proKLK7. Also, KLK5 promotes tumorigenesis by activating proteinase-activated receptors (PAR2).
AIMS & METHODS: The aim of this study was to analyse the expression of
KLKs 5 & 7 in colon cancer and to find out their clinical significance. In the
present study we examined the concomitant expression of KLK5 and KLK7 in
the cytosols of 121 CC tissues as well as their paired normal mucosa. We used a
non-competitive ELISA methodology (monoclonalmonoclonal for both
KLKs).
RESULTS: It was shown that whereas KLK7 protein of CC tissue is up-regulated in comparison to normal mucosa the same does not hold for KLK5. Both
KLKs were significantly associated with overall survival in univariate analysis.
Also, in multivariate analysis, after adjusting for age, TNM and differentiation
stage, both proteins were shown to be significantly associated with overall survival (p 0.032, p 0.015 respectively).

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United European Gastroenterology Journal 2(1S)


CONCLUSION: KLK7 is up-regulated in colon cancer, whereas the KLK5 is
not in comparison to normal mucosa. Both KLKs are associated with overall
survival in univariate as well as in multivariate analysis using as parameters the
patients age, the TNM and the differentiation stage.
Disclosure of Interest: None declared
P1641 CATHEPSIN-B GENE EXPRESSION IN THE PROGRESSION
FROM ADENOMA TO COLON CANCER
D. Kypraios1,*, A. Vakrakou2, A. Malachias1, M. Nikaki1, S. Bassioukas1,
D. Xynopoulos1, M. Talieri2
1
Gastroenterology, Saint Savvas Hospital, 2Cellular Physiology, G. Papanicolaou
Research Center of Oncology, Saint Savvas Hospital, Athens, Greece
Contact E-mail Address: talieri@agsavvas-hosp.gr
INTRODUCTION: Colon cancer (CC) remains the third leading cause of worldwide cancer-related death in men and women. Currently, available prognostic
and/or predictive markers for colon cancer lack specificity and sensitivity.
Developing new biomarker for early detection, accurate diagnosis and therapeutic treatment for CC is of great importance in improving the clinical outcome of
the disease. Cathepsin B (CB), a lysosomal cysteine protease, is expressed constitutively in lysosomes, however its expression and localization change in cancer.
High levels of expression of CB at both gene and protein levels have been
observed in different types of cancer.
AIMS & METHODS: The aim of this study was to analyze the CB expression in
different stages of CC progression and to evaluate its clinical relevance. We
examined for first time, using quantitative real time PCR, the expression of
CB in 185 colonic tissue specimens from 130 patients; 50 were pairs of cancerous-normal tissues, 17 were cancerous tissues and 63 were adenomas for 5 of
which normal paired mucosa were also available.
RESULTS: We proved that CB was up regulated in the cancer specimens in
comparison to their normal paired mucosa (p50.001), as well as in the adenomas
in comparison to normal tissue (p50.001). CB expression was found to be associated with histological grade (p 0.037). Cox proportional hazard regression
model using univariate and multivariate analysis revealed that high status CB
expression is a significant factor for disease-free survival (DFS) (p 0.037 and
0.0038, respectively) and overall survival (OS)(p 0.003 and p 0.0037, respectively) of patients. Receiver-operating characteristic (ROC) analysis of our results
showed that CB has discriminatory value between CC and adenomas tissues
(area under the curve [AUC] 0.711). Kaplan-Meier survival curves demonstrated that CB expression of low status is significantly associated with longer
DFS (p 0.023) as well as OS (p 0.002).
CONCLUSION: Present results suggest that CB gene expression may represent a
useful marker of unfavorable prognosis for CC patients with discriminatory
power between CC and adenoma patients.
Disclosure of Interest: None declared
P1642 OVEREXPRESSION OF LASP1 IS ASSOCIATED
PROLIFERATION, MIGRATION AND INVASION IN GASTRIC
CANCER

WITH

H. Zhang1,2,*, Y. Zhang1,2, D. Li3, W. Sha1


Department of Gastroenterology and Hepatology, Guangdong General Hospital,
2
Guangdong Provincial Institute of Geriatrics, 3Medical Research Center of
Guangdong General Hospital, guangdong General hospital, guangzhou, China
Contact E-mail Address: zhang.han@139.com
1

INTRODUCTION: LIM and SH3 protein 1 (Lasp1) is an actin-binding protein


involved in numerous biological and pathological processes. The overexpression
of Lasp1 has been described in many types of cancers[1-4]. But the role of Lasp1 in
gastric cancer (GC) remains unclear. We sought to analyze the expression level of
Lasp1 in GC, and the role of Lasp1 in the development of GC.
AIMS & METHODS: The mRNA level and protein expression of Lasp1 in 82
cases of gastric cancer tissues and the paired normal gastric tissues were detected
by real-time RT-PCR, Western blots and immunohistochemistry (IHC) respectively. The relationship between the Lasp1 expression level and the various clinicopathological parameters were analyzed. Using gene transfection and RNA
interference (RNAi) stratage, we investigated the effects of Lasp1 overexpression
and depletion on tumor cellular behavior respectively.
RESULTS: The Lasp1 mRNA and protein expressionin cancerous tissues were
both increased significantly as compared to the normal gastric tissues (p50.05).
Though there was no significant correlation was found between Lasp1 expression
and tumor size and pathological differential degree, Lasp1mRNA level was significantly higher in patients with lymph node metastasis (N1-3) (P50.05 ) and
those with more advanced clinical stages (P50.05) respectively. Consistently,
IHC revealed that patients with lymph node metastasis (P50.05) and those
with more advanced clinical stages (P50.05) were prone to show higher Lasp1
protein level. Overexpression of Lasp1 was found in metastatic GC tissues
(p50.01), and its expression level was closely correlated with overall survival
of patients with GC (p50.01). RNA interference mediated silencing of the Lasp1
gene in BGC823 GC cells inhibited cell proliferation and migration significantly.
Furthermore, gene transfection-mediated overexpression of Lasp1 in SGC7901
GC cells resulted in aggressive phenotypes of GC cancer cells and promoted
cancer growth and metastasis.
CONCLUSION: Above results suggested that Lasp1 was overexpressed in gastric cancer tissues, and the increased expression of Lasp1 may contribute to
cancerous progression and lymph node metastasis.
REFERENCES
[1] He B, Yin B, Wang B, et al. Overexpression of LASP1 is associated with
proliferation, migration and invasion in esophageal squamous cell carcinoma.
Oncol Rep 2013; 29: 1115-1123.

[2] Zhao L, Wang H, Sun X, et al. Comparative proteomic analysis identifies


proteins associated with the development and progression of colorectal carcinoma. FEBS J 2010; 277: 4195-4204.
[3] Wang B, Feng P, Xiao Z, et al. LIM and SH3 protein 1 (Lasp1) is a novel p53
transcriptional target involved in hepatocellular carcinoma. J Hepatol 2009; 50:
528-537.
[4] Chiyomaru T, Enokida H, Kawakami K, et al. Functional role of LASP1 in
cell viability and its regulation by microRNAs in bladder cancer. Urol Oncol
2012; 30: 434-443.
Disclosure of Interest: None declared
P1644 EPIGENETIC REGULATION OF SH2-CONTAINING PROTEIN
TYROSINE PHOSPHATASE 1 (SHP1) IN GASTRIC CARCINOMA
CELL LINES
H. Kim1,*, M.K. Joo1, J.-J. Park1, H.S. Yoo1, J. Kim1, J.W. Choe1, B.J. Lee1,
J.S. Kim1, Y.-T. Bak1
1
Division of Gastroenterology, Department of Internal Medicine, Korea University
Guro Hospital, Seoul, Korea, Republic Of
INTRODUCTION: The SH2-containing protein tyrosine phosphatase 1 (SHP1)
is an important negative regulator in cytokine-mediated signal transduction and
cell cycling. Recent studies demonstrated that promoter methylation of SHP1 is
frequently observed in gastric adenocarcinoma tissues. However, the functional
effect of epigenetic silencing of SHP1 in gastric carcinogenesis has not been
reported yet.
AIMS & METHODS: We tried in this in vitro study to reveal promoter hypermethylation of SHP1 and to investigate the its carcinogenic effects in gastric
carcinoma cell lines.
RESULTS: We observed that both gene and protein expression of SHP1 were
negative in 8 of 10 gastric cancer cell lines (SNU-1, SNU-5, SNU-16, SNU-638,
SNU-719, MKN-28, MKN-45, AGS), whereas KATO-III and NCI-N87 showed
weakly positive protein expression by Western blot. Conventional methylation
specific PCR (MSP) showed methylation-specific band only in all 10 gastric
cancer lines. Bisulfite pyrosequencing revealed 96.5%, 97.3% and 94.8% of
methylation frequency in AGS, SNU-719 and MKN-28 cells, respectively,
whereas only 5.3% in peripheral blood mononuclear cells. When treating
SNU-719, MKN-28 and AGS cells with 5 M of 5-Aza-2-deoxycytidine (5Aza-dc) for 4 days, SHP1 was re-expressed in all three cell lines. SHP1 expression
is known to be correlated with Janus kinase (JAK) and signal transducers and
activators of transcription (STAT) signaling pathway. When introducing exogenous SHP1 in SNU-719 and MKN-28 cells by transient transfection, protein
expression of phospho-JAK2 (Tyr 1007/1008) and phospho-STAT3 (Tyr 705)
were substantially down-regulated, which in turn decreased the expression of
target genes of phospho-STAT3, including Cyclin D1, MMP-9, VEGF and
Survivin. Furthermore, induction of SHP1 significantly reduced cell proliferation
and inhibited cell migration and invasion in SNU-719 and MKN-28 cells.
CONCLUSION: Epigenetic silencing of SHP1 is frequently caused by promoter
hypermethylation in gastric carcinoma cell lines. Exogenous expression of SHP1
down-regulates JAK2/STAT3 pathway to modulate various target genes and
inhibit cell proliferation, migration and inhibition in gastric carcinoma cell
lines, which suppports that epigenetic silencing of SHP1 contributes various
carcinogenic and progressive effects in gastric cancer cell lines.
REFERENCES
J Cell Mol Med 2009; 13: 3668-3679.
Disclosure of Interest: None declared
P1645 THE CLINICOPATHOLOGIC
EXPRESSION IN GASTRIC CANCER

SIGNIFICANCE

OF

EZRIN

H.-M. Kwon1,*, S.S. Kim1, J.S. Kim1, J. I. Kim1, S.W. Han1


Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea,
Republic Of
1

INTRODUCTION: Ezrin belongs to the ezrin/radixin/moesin protein family,


which acts as membrane organizer and link between the plasma membrane
and the cytoskeleton. Recent studies have found that through the regulation of
adhesion molecules and signal transduction pathways, the Ezrin protein might
play an important role in the process of tumor cell invasion and metastasis. There
have been reports on the relationship of Ezrin expression to clinical outcome in
solid tumors. However, reports on Ezrin expression in H. pylori infection and
gastric cancer have been rare.
AIMS & METHODS: In this study, we investigated the relationship of Ezrin
expression to clinicopathologic parameters and prognosis in H. pylori infection
and gastric cancer. 113 gastric cancer tissues and same numbers of adjacent nontumor tissues were obtained from patients who received gastrectomy for curative
resection. Prognosis and clinicopathlogic characteristics of patients according to
the grade of Ezrin expression were assessed. Western blot was analyzed to reveal
differences of expression according to presence of H. pylori infection and duration of infection in AGS and HS3C cell line. Thirty pre-eradication gastric
mucosal tissues and the same numbers of post-eradication gastric mucosal tissues
were obtained from peptic ulcer patients with H. pylori infection and immunohistochemical staining was conducted.
RESULTS: The expression rates and Ezrin score were significantly increased in
gastric cancer tissue compared to adjacent normal tissue (81.4% vs 66.4%,
P 0.015, 4.51  3.29 vs 3.18  3.11, p 0.003, respectively). The expression
of Ezrin was also increased in cases of lymphatic invasion, progression of N and
TNM staging. As to the analysis of survival and correlation with Ezrin, Ezrin
expression score and rates were significantly correlated with survival. In western
blot analysis of AGC and HS3C cell lines, the expression of Ezrin protein
increased according to presence of infection and duration of infection. In vivo

A584

United European Gastroenterology Journal 2(1S)

study using gastric mucosal tissues, The expression rates and score of Ezrin was
not significantly elevated in pre-eradication state.
CONCLUSION: Ezrin expression may be used as a marker of not only cancer
progression and metastasis but also as a prognostic indicator in gastric cancer
and the effect of helicobacter pylori on expression of Ezrin in normal gastric
mucosa may be needed further study to conclude.
Disclosure of Interest: None declared
P1646 THE EXPRESSION OF MMPS IN GASTRIC CANCER IS NOT
ASSOCIATED WITH THE ACTIVATION OF MTOR
J. Bornschein1,2,*, T. Seidel1, C. Langner1, A. Link1, T. Wex1, D. Kuester3,
M. Vieth4, P. Malfertheiner1
1
Gastroenterology, Hepatology & Infectious Dis., Otto-von-Guericke University of
Magdeburg, Magdeburg, Germany, 2MRC Cancer Unit, University of Cambridge,
Cambridge, United Kingdom, 3Institute for Pathology, Otto-von-Guericke
University of Magdeburg, Magdeburg, 4Pathologie Klinikum Bayreuth, University
of Bayreuth, Bayreuth, Germany
INTRODUCTION: Degradation of the extracellular matrix by matrix metallo
proteinases (MMPs) enables invasive growth of gastric cancer. Regulation of
MMP expression by activation of mTOR (mammalian target of rapamycin)
and related signalling pathways has been demonstrated, although not thus far
in gastric cancer.
AIMS & METHODS: We investigated the expression of MMP2, MMP7 and
MMP9 in gastric cancer and their association to mTOR in its activated, phosphorylated form (p-mTOR). The study compromised 130 patients with gastric
cancer resections; 72% male, mean age 7412.4 years, 66.2% intestinal type.
Quantitative real-time PCR was performed for MMP2, MMP7 and MMP9 in
fresh frozen tissue in a pilot of 43 gastric cancer patients and 30 healthy controls.
Following this, immune-histochemical (IHC) staining of the MMPs as well as
mTOR and p-mTOR was undertaken in the complete study population (n 130).
A semiquantitative immune-reactivity score (IRS) was applied to assess the staining separately for the tumour centre as well as the invasion front. Groups were
compared by Mann-Whitney U and Wilcoxons signed rank test and expression
between sites and targets correlated by Spearmans rank correlation test. mTORdependent regulation of MMP expression was furthermore assessed in MKN45
gastric cancer cells by rapamycin specific inhibition of mTOR signalling.
RESULTS: RT-PCR demonstrated an up-regulated expression of all MMPs in
gastric cancer compared to both non-malignant tissue and gastric mucosa from
non-cancer controls. IHC revealed only for MMP2 a higher expression at the
invasion front compared to the tumour centre; MMP7 was more highly expressed
in the tumour centre, there was no difference for MMP9 between tumour centre
and invasion front (Table). There was a trend for higher expression of mTOR in
the tumour centre and the IRS for p-mTOR was higher at the tumour centre
when compared with the invasion front (Table). These effects were observed in
intestinal type cancers but not in diffuse ones. IRS of tumour centre and invasion
front correlated positively for all MMPs, mTOR and p-mTOR (p50.001). There
was no correlation between mTOR or p-mTOR expression with any of the
MMPs. However, MMP2 expression correlated with MMP9, and mTOR with
p-mTOR staining. By treatment of MKN45 cells with rapamycin a reduction of
p-mTOR in the Western blot was achieved; however, expression of MMPs was
not affected by this.
Tumorcenter

Invasion Front

Positive
staining

IRS
(meanSD)

Positive
staining

IRS
(meanSD)

96%
80%
60%
42%
44%

10.367.34
2.983.76
3.754.76
5.498.59
4.977.43

78%
50%
74%
43%
41%

9.668.27
2.724.59
6.757.36
4.707.77
4.236.91

Target

mTOR
p-mTOR
MMP2
MMP7
MMP9

p-value

n.s.
0.019
50.001
0.003
n.s.

CONCLUSION: Expression of MMP2, MMP7 and MMP9 in gastric cancer is


not associated with mTOR activation.
Disclosure of Interest: None declared
P1647 AUTOIMMUNE ATROPHIC GASTRITIS PRESENTS DISTINCT
METAPLASTIC AND INFLAMMATORY PHENOTYPES
COMPARED WITH CANCER-ASSOCIATED CHRONIC ATROPHIC
GASTRITIS
M. Romano1,*, S. Jeong2, C. Petersen2, E. Hoi2, A. Federico1, R. Ippolito3,
F.P. DArmiento3, J.R. Goldenring2
1
SECOND UNIVERSITY OF NAPLES, ITALY, Naples, Italy, 2Vanderbilt
University, Nashville, United States, 3Federico II University, Naples, Italy
Contact E-mail Address: marco.romano@unina2.it
INTRODUCTION: Patients with autoimmune atrophic gastritis (AAG) have an
increased risk of carcinoid tumors whereas patients with chronic atrophic gastritis (CAG) carry an elevated risk of adenocarcinoma.
AIMS & METHODS: We evaluated whether AAG and CAG have distinct
metaplastic and inflammatory phenotypes which might contribute to their different evolution. We studied 20 female patients with AAG (age 56.4  9.8 yrs)
and 6 patients with CAG (4M, 2 F, age 66.3  16.5 yrs). Diagnosis of AAG was
through histology and positivity to anti-parietal cell antibodies. We evaluated by

immunohistochemistry the gastric body expression of TFF2 as a spasmolyticpolypeptide expressing metaplasia (SPEM) marker, MUC2 as an intestinal metaplasia marker, CD68 as a macrophage marker, myeloperoxidase (MPO) as a
neutrophil marker, CD44 variant, a marker of SPEM in mice, DMBT1, a
marker of IM in humans, and Ki67 as a proliferation activity marker.
RESULTS: 1) All AAG patients showed parietal cell loss and TFF2-staining
SPEM; 2) 75% AAG patients (15/20) demonstrated MUC2-positive goblet cell
intestinal metaplasia; 3) All CAG samples showed parietal cell loss and both
TFF2-staining SPEM and MUC2-positive intestinal metaplasia; 4) CD44 variant
was expressed in SPEM in both AAG and CAG patients, with weak or absent
expression in IM in both groups. In contrast, DMBT1 labeled IM but not SPEM
in both groups, although the intensity of staining for DMBT1 in IM was uniformally weaker in the IM associated with AAG; 5) AAG patients showed significantly fewer MPO-positive neutrophils (2.9/1000 cells) as compared to CAG
patients (37.0/1000 cells) and significantly fewer CD68-positive macrophages
(10.5/1000 cells) as compared to CAG patients (28.0/1000 cells); 6) AAG patients
demonstrated significantly lower rates of proliferation as assessed by Ki67-immunostaining cells (3.8/1000 gland cells compared with 103.7/1000 gland cells in
CAG patients).
CONCLUSION: Metaplasia in AAG patients has a low proliferative rate and
low macrophage and neutrophil infiltration, suggesting that metaplasia in AAG
lacks crucial pro-adenocarcinoma influences. This may explain the lower incidence of gastric adenocarcinoma in AAG as compared to CAG.
Disclosure of Interest: None declared
P1648 GASTRIC SECRETORY CELL DENSITY PROVIDES FURTHER
EVIDENCE FOR TWO AETIOLOGIES OF GASTROESOPHAGEAL
JUNCTIONAL CANCERS
M.H. Derakhshan1,*, T. Harvey1, R.K. Ferrier2, E. V. Robertson1, C. Orange2,
M. Forshaw2, J.J. Going2, K.E. McColl1
1
Institute of Cardiovascular & Medical Sciences, 2Institute of Cancer Sciences,
University of Glasgow, Glasgow, United Kingdom
Contact E-mail Address: Kenneth. McColl@glasgow.ac.uk
INTRODUCTION: Serum pepsinogen I:II ratio, a surrogate marker of atrophic
gastritis, suggests that some adenocarcinomas at the gastroesophageal junction
(GOJ) develop on a background of atrophic gastritis, similar to non-cardia gastric cancer, while others arise on a background of healthy, non-atrophic gastric
mucosa similar to oesophageal adenocarcinoma (OAD). In this study, we compare background gastric body mucosa in patients with junctional adenocarcinomas, oesophageal adenocarcinomas and non-cardia gastric (NCG) cancers.
AIMS & METHODS: A total of 127 gastrectomy and oesophagectomy specimens for adenocarcinoma had clear topographic description allowing assignment
to oesophageal, junctional (including cardia) and gastric non-cardia locations. In
each case a block of gastric body mucosa was identified well clear of the carcinoma. Parietal and chief cells were immunostained for H/K ATPase and
pepsinogen-1, respectively. Secretory cells density was counted in 3 to 5 welloriented fields (1 mm2 each) and expressed as mean cell number per 1 mm2 area
in each patient. Reactive atypia (RA) and inflammation indicated by polymorphonuclear (PMN) and mononuclear (MN) cells were also scored. Non-parametric statistics were used to compare distributions.
RESULTS: Ten (8%) cases lacked well-orientated blocks of body mucosa. The
remaining 117 patients included 34 oesophageal, 52 GOJ and 31 non-cardia
gastric adenocarcinomas. Median (IQR) parietal cell densities were 836 (173),
602 (389) and 411 (334) per mm2 in gastric mucosa of oesophageal, GOJ and
gastric cancers, respectively (all differences P 50.001). Using a parietal cell density of 630/mm2, 85% of oesophageal adenocarcinomas had a higher and 84% of
non-cardia gastric cancers had a lower values. Applying the same cut-off, 50% of
GOJ adenocarcinomas would be classified as gastric and the remainder oesophageal in origin. Parietal cell density was normally distributed in the non-cardia
gastric cancer and oesophageal adenocarcinoma groups. In contrast, the junctional adenocarcinoma group showed a biphasic distribution with one peak corresponding to that of non-cardia gastric cancer and the other to that of
oesophageal adenocarcinoma. Chief cells show density distributions closely similar to parietal cells in all samples.
Chronic inflammatory score expressed as median (IQR) was higher in non-cardia
gastric cancer than in oesophageal adenocarcinoma [0 (IQR:1) vs. 3 (IQR:2),
p50.001], but in junctional cancer [1 (IQR:2)] it was higher than oesophageal
adenocarcinoma and lower than non-cardia gastric cancer (P 50.001 for both).
CONCLUSION: This study shows marked differences in gastric mucosal phenotype in the patients with oesophageal versus gastric non-cardia cancer, with the
former being healthy and uninflamed, but the latter atrophic and inflamed. The
background gastric mucosa of GOJ cancer supports being two distinct aetiologies, one group resembling oesophageal adenocarcinoma and other gastric noncardia cancer.
Disclosure of Interest: None declared

United European Gastroenterology Journal 2(1S)


P1649 ABERRANT AMPLIFICATION OF RECEPTOR TYROSINKINASES (RTK) INVOLVED IN CELL CYCLE SIGNALING
APPEARS TO DETERMINE PROGNOSIS OF GASTRIC CANCER
PATIENTS
P. Minarikova1,*, L. Benesova2, B. Belsanova2, T. Halkova2, L. Dusek3,
M. Zavoral1, M. Minarik1,2
1
Internal clinic, 1st Faculty of Medicine, Charles University and Central Military
Hospital, Military Faculty Hospital, 2Center for applied genomics of solid tumors,
Genomac Research Institute, Prague, 3Institute of Biostatistics and Analyses,
Masaryk University, Brno, Czech Republic
Contact E-mail Address: pminarikova@gmail.com
INTRODUCTION: Gastric cancer, which ranks among the top malignancies
worldwide, exhibits a notable variety in the course of the disease. Clinical factors,
such as tumor stage and localization, are key in patient survival. Lauren histology type is used to discriminate levels of differentiation; however, it is not directly
applicable in the anticancer treatment. With the recent rise of molecular targeted
therapies, genomic signatures comprising of somatic mutations and gene copy
number variations are essential in treatment prediction as well as in prognosis of
patient survival. A study by Deng et al. (Gut 2012) has identified molecularly
distinct subclones by evaluating aberrant deletions or amplifications of key receptor tyrosin kinases (RTKs).
AIMS & METHODS: In this work we have related survival of gastric cancer
patients to molecular classes/clusters derived from comprehensive evaluation of
gene amplification with special emphasis on cell cycle signaling. Tumor samples
(FFPE or freshly acquired) from a total of 76 patients (all caucasians/Europeans)
with clinically confirmed gastric cancer were included in this study along with
relevant clinical data including disease stage, Lauren type and tumor localization.
The panel of gene amplifications included multiple receptor tyrosin-kinases
families as well as other genes involved in cell cycle and proliferation. A hierarchical clustering using Wards method was applied to cluster patients according
to molecular profiles. Kaplan-Meyer survival analysis was then applied to test
survival of the subgroups.
RESULTS: There was a significant difference in survival for tumor localization
(210 days for cardia vs. 563 days for bodyantrum, p 0.0154). Amplifications
were frequent at 5q, 8q, 10q, 17q and 20q chromosomal locations. Several transmembrane RTKs exhibited importance when related to the patient survival,
including PDGFRB, EGFR, HER2 and RET along with of CCND1 (Cyclin
D1), and important cell cycle regulator. A subgroup of patients whose tumors
revealed amplification of at least one of the prior genes exhibited a significantly
shorter survival compared to a group with none of the amplifications detected
(904 days vs. 205 days, p 0.029).
CONCLUSION: As reported previously receptor tyrosin kinases play a dominant role in initialization of gastric cancer and its subsequent progression. By
using a panel of RTKs along with Cyclin D1 we have observed an effect of gene
amplifications on patients prognosis. An independent validation on a separat
patient cohort is now in progress. Supported by the Czech Ministry of Health
grant no. 13640.
REFERENCES
Deng N, et al., A comprehensive survey of genomic alterations in gastric cancer
reveals systematic patterns of molecular exclusivity and co-occurrence among
distinct therapeutic targets. Gut 2012; 61: 673-684.
Disclosure of Interest: None declared

A585
treatment with Angiotensin II caused the progression of EMT-like change. On
the other hand, SF-CM of pretreatment with ARB suppressed this change.
CONCLUSION: ARB can significantly reduce TGF-1 expression and EMTlike change, and suppress the tumor proliferation and stromal fibrosis. Targeting
the Angiotensin II signaling pathway may be a novel, efficient strategy for treating the tumor proliferation and tissue fibrosis.
REFERENCES
Tsukada T, Fushida S, Harada S, et al. The role of human peritoneal mesothelial
cells in the fibrosis and progression of gastric cancer. Int J Oncol 2012; 41: 476482.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
H. PYLORI III POSTER EXHIBITION HALL XL_____________________
P1651 ROLE OF CAGA-POSITIVE STRAINS OF H. PYLORI IN ACUTE
MYOCARDIAL INFARCTION WITH ST-SEGMENT ELEVATION
F. Franceschi1,*, A. Tortora1, M. Roberto2, G. Niccoli2, T. Di Rienzo1,
G. DAngelo1, F. Scaldaferri1, L.R. Lopetuso1, V. Gerardi1, L. Laterza1,
G. Zuccala1, G. Gasbarrini3, A. Gasbarrini1
1
Internal medicine Institute, 2Institute of Cardiology, CATHOLIC UNIVERSITY
OF SACRED HEART, Rome, 3Fondazione Ricerca in Medicina, Bologna, Italy
Contact E-mail Address: francesco.franceschi@rm.unicatt.it

P1650 ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER SUPPRESS THE


FIBROSIS AND PROGRESSION OF GASTRIC CANCER

INTRODUCTION: We have previously shown a significant epidemiological


association between CagA-positive strains of H. pylori and unstable angina or
non ST-elevation myocardial infarction (n-STEMI).
AIMS & METHODS: Therefore, we have designed a study aimed at assessing
the prevalence of CagA-positive strains in patients with ST-elevation myocardial
infarction (STEMI) and of recurring acute coronary syndromes (ACS) as well as
the usefulness of the assessment of serum levels of anti-CagA IgG as a predictor
of the clinical outcome in patients with STEMI.
Methods: We enrolled 181 patients (155 males, mean age 6413 years) with
STEMI and 50 controls (38 males, mean age 6310 years) without any history
of coronary artery disease and matched for sex, age and socioeconomical status.
In all patients, serum levels of IgG anti-CagA were assessed. Moreover, levels of
IgG anti-HAV were also evaluated in all patients in order to exclude the presence
of a bystander activation of the immune system. Finally, a previous history of
ACS and the rate of major adverse cardiovascular events (MACEs) were evaluated in all STEMI patients with a 2 years follow-up.
RESULTS: Prevalence of CagA-positive strains was significantly higher in
patients with STEMI compared to controls (33.1% vs 9%, p 0.026).
Moreover, anti-CagA antibody titer was significantly increased in patients with
STEMI compared to controls (62.739 vs 25.642.7, p 0.02). Interestingly,
patients with STEMI and a previous history of ACS had an higher prevalence
of CagA-positive strains (50% vs 29.3%, p 0.019) and higher antibody serum
levels (97.550.4 vs 55.225.3, p 0.001) as compared with patients without
previous history of ACS. Furthermore, MACEs rate was significantly higher in
patients infected by CagA-positive strains compared to CagA-negative
(LogPrank 0.014). Finally, there was a negative correlation between levels of
anti-HAV and anti-CagA IgG (R 0.271, p 0.11) thus excluding the presence
of an aspecific bystander activation of the immune system.
CONCLUSION: CagA-positive strains of H. pylori may be involved in the
pathogenesis of STEMI and in the recurrence of ACS. Moreover, serum assessment of IgG anti-CagA may be an useful tool for risk stratification in patients
with STEMI as they may positively predict MACEs rate.
Disclosure of Interest: None declared

S. Fushida1,*, M. Okazaki1, T. Tsukada1, J. Kinoshita1, K. Okamoto1,


K. Oyama1, I. Ninomiya1, T. Fujimura1, T. Ohta1
1
Gastroenterological Surgery, KANAZAWA UNIVAERSITY HOSPITAL,
Kanazawa, Japan

P1652 A NOVEL STRATEGY OF PPI-PRETREATMENT IMPROVE


ERADICATION RATE IN TRIPLE THERAPY

INTRODUCTION: Peritoneal dissemination is the most frequent metastatic


pattern of gastric cancer. The clinical outcome was poor prognosis because of
the presence of rich stromal fibrosis and acquired drug resistance. Our previous
study demonstrated that the epithelial-mesenchymal transition (EMT) of human
peritoneal mesothelial cells (HPMCs) drives tumor fibrosis. In recent study,
Angiotensin II type I (AT1) receptor blocker (ARB) has been attracted attention
as drug with direct anti-fibrotic activity.
AIMS & METHODS: In this study, we examined whether ARB attenuates
tumor proliferation and fibrosis, and explores the interaction between HPMCs
and gastric cancer cells through the Angiotensin II / AT1 receptor / TGF-1. The
effects of ARB in vivo were evaluated in our established fibrotic tumor model,
and the expression of fibrosis, E-cadherin and -SMA was assessed by immunohistochemical staining. The effects of Angiotensin II and ARB on the proliferation of MKN45 were assessed by MTT assay. The AT1 receptor expression of
gastric cancer cells was evaluated by western blotting. TGF-1 expressions by the
influence of Angiotensin II and ARB were evaluated by ELISA and western
blotting. In addition, the effects of serum-free conditioned media (SF-CM) of
MKN45 cells in HPMCs were examined by western blotting and immunofluorescence examination.
RESULTS: In fibrotic tumor model, the mean tumor volume of ARB treatment
group was significantly reduced compared with that of absence of ARB. ARB
treatment group was increased E-cadherin expression and decreased -SMA
expression and fibrotic area compared with absence of ARB. All gastric cancer
cell lines showed AT1 receptor expression. The cell proliferation and TGF-1
expression was significantly increased with 100nM of Angiotensin II compared
with absence of Angiotensin II, and pretreatment with 1000nM of ARB showed
significantly decreased compared with treatment of Angiotensin II. SF-CM of

K. Yanamoto1,*, A. Shimozato1, N. Okaniwa1, A. Tanabe1, H. Noda1,


Y. Tamura1, S. Izawa1, Y.K. Kondo1, A. Iida1, Y. Funaki1, S. Yamamoto2,
K. Utsumi3, M. Sasaki1, T. Joh4, K. Kasugai1
1
Aichi Medical University School of Medicine, Nagakute, 2Yuri Clinic, Chita,
3
Aichi Medical University Medical Clinic, 4Department of Gastroenterology and
Metabolism, Nagoya City University Graduate School of Medical Sciences,
Nagoya, Japan
INTRODUCTION: A proton pump inhibitor (PPI), amoxicillin (AMPC), and clarithromycin (CAM) are recommended widely used as first-line therapy for
Helicobacter pylori (H. pylori) eradication in Japan. The guideline of Japan
Helicobacter Association recommends eradication about all patients infected by H.
pylori. From 2013, national health insurance covered eradication therapy about all
patients who were infected with H. pylori. Yet, a decline in eradication rate associated
with an increase in the prevalence of CAM resistance is increasingly problematic.
AIMS & METHODS: To improve the outcome, we retrospectively analyzed the
factors which influence the failure in eradication conducted multicenter from
1997 to 2013 (n 2582).
RESULTS: By univariate analysis, young subjects (under 35 years), non-peptic
ulcer history, non-PPI therapy before eradication, and CAM-resistance were
detected as risk factors of eradication failure. Gastric mucosal atrophy, dose of
CAM, and types of PPI had no influence on outcome of triple therapy. By
multivariate analysis, young subjects (under 35 years), non-peptic ulcer history,
non-PPI therapy before eradication, and CAM-resistance were risk factor of
eradication resistance ([OR: 0.63, 95%CI: 0.481 0.944], [OR: 0.78, 95%CI:
0.641 0.948], [OR: 0.78, 95%CI: 0.0.626 0.977], and [OR: 0.16, 95%CI:
0.081 0.306], respectively).

A586

United European Gastroenterology Journal 2(1S)

CONCLUSION: Pretreatment of PPI may be a novel strategy improving eradication rate in triple therapy. Further prospective study is necessary to clarify
about this.
Disclosure of Interest: None declared

patients. While the production of prohepcidin is induced by H. pylori infection,


the iron deficiency state in the NG patients appears to be strongly associated with
the prohepcidin production.
Disclosure of Interest: None declared

P1653 HELICOBACTER PYLORI IN CHRONIC GASTRITIS: WHAT IS


THE RELATIONSHIP BETWEEN THE GASTRIC COLONIZATION
AND THE HISTOLOGICAL LESIONS?

P1655 EXPRESSION OF BH3 ONLY PROTEIN BIM IS ASSOCIATED


WITH MUCOSAL INFLAMMATION IN GASTRITIS PATIENTS

S. Martin1,*, A. Laila1, S. Mouna1, A. Mohamed1, K. Nawal1


1
EFD, CHU Ibn Sina Rabat (Maroc), rabat, Morocco
INTRODUCTION: Infection with Helicobacter Pyroli (Hp) is acquired in childhood and the prevalence increases with age. Hp is now recognized as the main
etiologic factor of chronic gastritis. Indeed, this infection is responsible for the
majority of inflammatory gastric lesions. The aim of our study was to analyze the
relationship between the density of gastric colonization by Hp and different
gastric histological lesions (inflammation activity, atrophy, intestinal metaplasia
and dysplasia).
AIMS & METHODS: From January 2010 to March 2014, were included 336
patients infected with Hp histologically proven on gastric biopsies according to
the Sydney system. Statistical analysis of data was performed by SPSS 20.0. The
association between the density of Hp and the lesions of chronic gastritis was
studied by the chi-square test of Pearson, p 5 0.05 was considered statistically
significant.
RESULTS: The mean age of patients was 44.5 years  15.34 with female predominance in 54.8%. The chronic gastritis was mild in 13.1 %, moderate in
44.9%, severe in 7.7% and follicular in 34.2%. The density of the Hp colonization was minimal () in 24.1 %, moderate () in 56% and high ( ) in 19.9
%. Gastritis was antrofundic in 80 % of cases and only antral in 20 % of cases.
There is a statistically positive association between the density of Hp and activity
of gastritis with (P 5 0.001). In patients with a minimal density of Hp, chronic
gastritis was slightly active in 43.2 % of cases. In patients with a moderate density
Hp, gastritis was moderately active in 58.5 % of cases. In patients with a high
density of Hp, gastritis was moderately to severely active in 98.8 % of cases.
Patients with moderate density of Hp had moderate atrophy gastritis in 8.5 % of
cases and patients with significant density of Hp, gastric atrophy was severe in
16.4%, but these differences were not statistically significant. Intestinal metaplasia was present in 3% of our patients, including patients with mild density HP
and intestinal metaplasia in 4.93%, and those with a moderate density HP and
intestinal metaplasia in 3.14% of cases, but these results were not statistically
significant. There were no cases of dysplasia in our series.
CONCLUSION: The activity of gastritis was significantly correlated to the density of Hp. However, the relationship between gastric atrophy, intestinal metaplasia and the density of Hp was no statistically significant in this study.
Disclosure of Interest: None declared
P1654 IRON DEFICIENCY ANEMIA DUE TO HELICOBACTER PYLORI
INFECTION IS RELATED TO HYPOCHLORHYDRIA IN THE
PATIENTS WITH GASTRIC HYPERPLASTIC POLYP, AND
RELATED TO THE SERUM PROHEPCIDIN IN THE PATIENTS
WITH NODULAR GASTRITIS
Y. Sato1,*, Y. Nishigaki1, Y. Aoyagi1
1
Gastroenterology, Niigata University Graduate School of Medical and Dental
Sciences, Niigata, Japan
Contact E-mail Address: yuichi@med.niigata-u.ac.jp
INTRODUCTION: Helicobacter pylori (H. pylori) is recognized as a causative
agent for unexplained iron deficiency anemia (IDA). However, the mechanism by
which H. pylori infection contributes to IDA remains unclear.
AIMS & METHODS: To clarify the association between H. pylori infection and
IDA, we evaluated many background factors influencing an iron deficiency state
in adult patients with various H. pylori infection-positive upper gastrointestinal
tract diseases. Study 1 H. pylori-infected 121 patients (those with nodular gastritis
(NG) (n 19), duodenal ulcer (DU) (n 30), or gastric ulcer (GU) (n 47), or
gastric hyperplastic polyp (GHP) (n 25)) were enrolled in the study. The red
blood cell count and hemoglobin, serum ferritin, serum iron, serum pepsinogen
(PG) I, PGII, serum gastrin, and anti-H. pylori antibody (Ab) levels were measured. Study 2 H. pylori-infected 105 patients (NG, n 19; DU, n 43; GU,
n 32; GHP, n 11) and non-H. pylori infected individuals (n 35) were examined for the levels of prohepcidin, ferritin, and iron in the serum. We evaluated
the relationship between the prohepcidin and ferritin or iron levels. In addition,
we measured the data before and after the H. pylori eradication.
RESULTS: In the patients with GHP and NG, hypoferritinemia was observed in
comparison to the GU and DU patients (p50.05). In the GHP patients, low
levels of PG I (26.4  5.1 ng/ml, p 5 0.01 vs DU, GU, and NG) and a decreased
PG I/ II ratio (1.6  0.2, p50.01 vs DU, GU and NG) in the serum were
observed, in addition to hypergastrinemia (469.5 78.4 pg/ml, p50.01 vs DU,
GU and NG). The levels of serum prohepcidin in the patients with H. pyloriassociated disease were higher than those in the uninfected adults (p50.01 vs
NG, GU and GHP, p50.05 vs DU). In the patients with NG, the serum prohepcidin levels were higher than those in the other H. pyloriinfected patient
groups (p50.01 vs GU, DU), and decreased after the eradication. Moreover,
there was a negative correlation (p50.01, r -0.59) between the serum levels of
prohepcidin and the serum iron levels in the NG patients.
CONCLUSION: There were differences the iron status among the patients with
different H. pylori-associated diseases. Hypochlorhydria due to H. pylori-associated gastric mucosal atrophy would affect the hypoferritinemia in the GHP

Y. Akazawa1,2,*, H. Isomoto2, K. Matsushima 2, K. Matsuda 1, Y. Kido2,


T. Kanda 2, H. Minami2, N. Yamaguchi2, K. Shiozawa 2, K. Ohnita2,
K. Nakao2, F. Takeshima2, M. Nakashima1
1
Department of tumor and diagnostic pathology, Atomic bomb disease institute,
Nagsaki University, 2gastroenterology and hepatology, NAGASAKI
UNIVERSITY HOSPITAL, Nagasaki, Japan
INTRODUCTION: H. Pylori is a major cause of gastroduodenal diseases including gastritis, peptic ulcer, and gastric adenocarcinoma. Mechanisms by which H.
pylori infection leads to persistent inflammatory responses are not completely
understood. BH3-only protein Bim is known as a pro-apoptotic protein which
participates in mitochondrial cell death (1, 2). Of note, recent study also indicated
a paradoxical role of Bim in activating inflammatory cells (3). We have recently
shown that Bim was up-regulated in H. pylori-infected mucosa (4). However, role
of Bim in human gastritis remains unclear.
AIMS & METHODS: Our aim was to examine if Bim is associated with mucosal
inflammation in gastritis patients. Patients who underwent upper gastrointestinal
endoscopy from June 2007 to May 2013 were enrolled in the study (Total
number; 36, H. pylori negative: n 14, positive: n 22). Biopsy specimens were
obtained from the gastric antrum along the lesser curvature during endoscopic
examinations, and samples were subjected to real time PCR to assess Bim mRNA
expression. Localization of Bim was examined by immunohistochemistry.
Correlation of Bim mRNA expression with the degree of gastritis was evaluated
according to the updated Sydney system.
RESULTS: Expression of Bim mRNA was significantly elevated in H. pyloriinfected
mucosa
compared
to
uninfected
controls
(p50.01).
Immunohistochemistry revealed the localization of Bim in inflammatory cells
at both lamina propria and submucosa. Double-staining confirmed co-localization of Bim and myeloperoxidase, but not with either B cell marker (CD20) or T
cell marker (CD3), indicating that Bim was predominantly expressed by neutrophils. In accordance with the updated Sydney system, levels of Bim mRNA
expression were positively correlated with degree of infiltrating neutrophils and
monocytes. In contrast, Bim negatively correlated with degree of intestinal metaplasia. Other factors, such as degree of H. pylori colonization and atrophy, did
not correlate with expression of Bim.
CONCLUSION: Bim is expressed by neutrophils and correlates with activity of
gastritis. This study implied a possible link between Bim and pathogenesis of
human gastritis. Further studies are awaited to determine the detailed role of
BH3-only proteins in H. pylori infection.
REFERENCES
1) Puthalakath H. Mol Cell 1999.
2) Akazawa, et al. J Hepatol 2009.
3) Maciej W, et al. J Clin Invest 2009.
4) Akazawa, et al. Plos One 2013.
Disclosure of Interest: None declared
P1656 HEPCIDIN WAS EXPRESSED NOT ONLY IN THE CYTOPLASM
BUT ALSO IN INTRACELLULAR CANALICULI OF GASTRIC
PARIETAL CELLS AND EXPRESSED IN LYMPHOCYTES IN THE
DEEP LAYER OF THE LAMINA PROPRIA
Y. Nishigaki1,*, Y. Sato1, M. Iwafuchi2, Y. Aoyagi1
1
Niigata University Graduate School of Medicine and Dental Sciences, 2Division of
Pathology, Niigata University School of Health Sciences, Niigata, Japan
Contact E-mail Address: yuki216@med.niigata-u.ac.jp
INTRODUCTION: Hepcidin is an antimicrobial peptide and the key hormone in
iron homeostasis. In the stomach, hepcidin is located in parietal cells and is
related to acid secretion. Moreover, serum hepcidin levels are upregulated by
Helicobactor pylori infection; therefore, hepcidin is an important factor in iron
deficiency anemia (IDA) during the course of H. pylori infection. However, the
localization of hepcidin in the parietal cell and the distribution of hepcidin in the
gastric mucosa are unclear. In addition, it is unclear whether H. pylori infection
influences gastric hepcidin expression in the gastric mucosa.
AIMS & METHODS: We evaluated hepcidin expression and its distribution in
the gastric mucosa of H. pylori-infected and non-infected patients by immunohistochemistry. We enrolled 20 patients with H. pylori infection (mean age 55.6 
7.2 years, M:F 1:1.5) and 20 patients without H. pylori infection (mean age 51.6
 9.8 years, M:F 1:1.5). All patients underwent esophagogastroduodenoscopy
(EGD). During EGD, biopsy specimens were obtained from the greater curvature of the gastric antrum and corpus. Biopsy specimens were fixed in 10%
formalin and embedded in paraffin. Immunohistochemical staining was performed using these sections using monoclonal antibodies against hepcidin
(Abnova, Taiwan). The present study was approved by the ethics committee of
our institution. Written informed consent was obtained from all patients.
RESULTS: Hepcidin was expressed not only in the cytoplasm but also in intracellular canaliculi of gastric parietal cells in the both groups. Hepcidin was not
expressed in other cell types in gastric epithelia. Hepcidin was also expressed in
lymphocytes in the deep layer of the lamina propria, and its expression in the H.
pylori-infected group was stronger than that in the non-infected group.
CONCLUSION: Our study revealed the expression of hepcidin in intracellular
canaliculi of gastric parietal cells. Schwarz et al. have reported that hepcidin was
detected in human gastric juice (Gut 2012); therefore, our findings suggest that

United European Gastroenterology Journal 2(1S)


gastric hepcidin is released into the gastric lumen with gastric acid concurrently
from parietal cells. The strong expression of hepcidin in lymphocytes in the
gastric mucosa of H. pylori-infected patients suggests its role in inflammation
and in the etiology of IDA associated with H. pylori infection.
Disclosure of Interest: None declared
P1657 14 DAYS SEQUENTIAL OR HYBRID REGIMEN FOR
HELICOBACTER PYLORI ERADICATION IN CLINICAL PRACTICE
IN SOUTHERN GREECE. A PROSPECTIVE PILOT STUDY
P.N. Kalapothakos1,*, P. Kourkoulis1, G. Koutoufaris1, E. Startigakos1,
E. Dimitroulia1, E. Georgakila1
1
Gastroenterology, Lakonia General Hospital, Sparti, Greece
Contact E-mail Address: pankalap@gmail.com
INTRODUCTION: First line empirical treatment, non bismuth quadruples
either 10-day sequential therapy with omeprazole and amoxicillin 5 days followed by omeprazole clarithromycin, metronidazole for another 5 days or concomitant the same drugs for 10 days, in previous studies, in our area (southern
Greece) achieve PP eradication 86% and 92% respectively (1,2)
AIMS & METHODS: Investigation in a prospective, randomized, pilot study
whether prolonging the treatment duration of sequential therapy and/or continuing the amoxicillin throughout the 14 days (sequential-concomitant hybrid) could
raise the PP eradication rate to 495%. METHODS: 3 years single centre
study.130 na ve H. pylori infected patients were randomly assigned to receive
either: Sequential (omeprazole 20 mg and amoxicillin1gr for 7 days followed
by omeprazole 20 mg, clarithromycin 500 mg, and metronidazole 500 mg for 7
days; n 65) or Sequential-Concomitant hybrid: (Sq-Con hybrid) (omeprazole
20 mg and amoxicillin 1 gr for 7 days followed by omeprazole 20mg, amoxicillin1
gr, clarithromycin 500 mg, and metronidazole 500 mg for 7 days; n 65). All of
them given twice daily. UBT or endoscopy was performed 4-8 weeks post treatment to assess the outcome.
RESULTS: 65% male, mean age 46.25 /- 14.7 years, 55% endoscopic lesions
(ulcer, erosions), 35% smokers. Eradication rate by intention to treat analysis
was 84%; (95% CI, 76.7% - 90.9%) for 14 days sequential, 91% (95% CI, 86.5%
- 97.3%) for sq-con hybrid therapy. Per-protocol analysis yielded 88% (95% CI,
82, 4% - 93.9%) for 14 days sequential and 93% (95% CI, 90.4% - 97.9%) for
sq-con hybrid therapy. Both regimens exhibited similar adverse events (42% vs.
46%) and treatment compliance (95 % vs. 97%).
CONCLUSION: Our pilot study, apart from the number of tablets needed per
day, is unable to support that extending the duration of sequential therapy to 14days, neither adopting the hybrid regimen, as first line empirical treatment, will
achieve better results than the obtained by either sequential 10 or concomitant in
H. pylori eradication in our area.
REFERENCES
1. Kalapothakos P, Liantiniotis G, Koulentis M, et al. Ten days sequential
treatment for Helicobacter pylori eradication in clinical practice in Greece. Gut
2012; 61 (Suppl. 3): A444.
2. Kalapothakos P, Georgakila E, Georgantas P, et al. Initial empirical treatment
for helicobacter pylori eradication in routine clinical practice. Non bismuth
sequential or concomitant regimen? A preliminary prospective comparative
study in Sparta Greece. UEGW 2013 P519.
Disclosure of Interest: None declared
P1658 DOES TAILORED THERAPY BASED ON ANTIMICROBIAL
SUSCEPTIBILITY TESTING OVERCOME THE INCREASING
FAILURE OF STANDARD EMPIRICAL THERAPY FOR
HELICOBACTER PYLORI INFECTION?
R.B. Haider1,2,*, S. Smith1, G. Holleran1, B. Hall1, C. OMorain3,
H.J. OConnor2, D. McNamara1
1
Departments of Gastroenterology & Clinical Medicine Tallaght Hospital., TAGG
(Trinity Academic Gastroenterology Group), Dublin, 2Departments of
Gastroenterology & Clinical Medicine Naas Hospital., Naas Hospital, Naas,
3
Charlemont Clinic, Dublin, Ireland
Contact E-mail Address: bhrana@hotmail.com
INTRODUCTION: First-line triple therapy for H. pylori involves the use of a
PPI with amoxicillin & clarithromycin or clarithromycin & Metronidazole in case
of penicillin-allergy for one week. However, due to increased resistance to these
commonly employed antibiotics, eradication has fallen considerably short of the
80% intention-to-treat (ITT) rates that are considered the minimal acceptable
levels as recommended in the Maastricht guidelines. Despite these worrying
trends, there are no centres routinely monitoring Irish resistance rates. Data
which could help adapt new first line therapies and improve outcome.
AIMS & METHODS: To compare the efficacy of standard empirical triple
therapy with tailored therapy based on antimicrobial susceptibility testing.
A prospective, multicentre, randomised controlled study was conducted after
ethical approval in all participating hospitals. Treatment na ve H. pylori-infected
patients (418 years old), as assessed by a positive antral CLO-test at endoscopy,
were invited to participate and informed consent was obtained. Information on
age, gender, previous antibiotic use & smoking history was recorded. A single
antral biopsy was processed for antimicrobial susceptibility testing employing
both standard culture and E-testing & genotyping for antibiotic resistance associated SNPs. Patients were randomised to receive either standard empirical therapy with Amoxicillin, Clarithromycin & PPI or tailored treatment based on their
antibiotic resistance profile which included standard triple therapy or if resistance
was detected triple therapy with Amoxicillin, Levofloxacin & PPI or Denoltab,
Tetracycline, Metronidazole & PPI based quadruple therapy. A follow up UBT
was performed after 6-8 week to assess treatment success.

A587
RESULTS: To date 247 consecutive patients had CLO tests assessed at endoscopy. Of these 52 (21%) were H. pylori positive. Infected patients tended to be
younger men with a mean age of 47 versus 53 years, p50.05 and 56% versus
46% were male. In all 47 (90%) patients have been randomised to a treatment
arm and 40 (85%) have completed the study. Of those 40, 15 (37.5%) and 25
(62.5%) received tailored and empirical therapy respectively. In the tailored arm
6 (40%) received quadruple and 4 (27%) Levofloxacin and 5 (33%) standard
triple therapy. Eradication rates were higher for tailored versus empirical therapy, 87% (13/15) and 68% (17/25). This trend did not reach statistical significance. Only 1 (3%) patient had a severe side effect with mild anaphylaxis to
amoxicillin. Overall 42% of strains were clarithromycin resistant and 7 of 8
(88%) patients who failed empirical therapy had resistant strains, p50.001. Of
the 2 (13%) who failed tailored therapy neither treatment type nor resistance
profiles were predictive.
CONCLUSION: Resistance levels to clarithromycin are high at 42%. Targeted
therapy can enhance eradication rates. Larger numbers will be required before a
new first line treatment can be recommended.
Disclosure of Interest: R. Haider: None, S. Smith: None, G. Holleran: None, B.
Hall: None, C. OMorain: None, H. OConnor: None, D. McNamara: None.
P1659 RANDOMIZED CLINICAL TRIAL: COMPARISON OF 10-DAY
CONCOMITANT THERAPY AND HYBRID THERAPY FOR
HELICOBACTER PYLORI INFECTION IN KOREA-PRELIMINARY
RESULT. (CRIS KCT0000728)
S.W. Jeon1,*, J. Heo1, J.T. Jung2, D.W. Lee3, C.H. Yang4, K.S. Park5, S.H. Lee6
on behalf of Daegu-Gyeongbuk Gastrointestinal Study Group
1
Internal Medicine, Kyungpook National University Hospital, 2Internal Medicine,
Catholic University of Daegu School of Medicine, 3Internal Medicine, Daegu
Fatima Hospital, Daegu, 4Internal Medicine, Dongguk University Gyeongju
Hospital, Gyeongju, 5Internal Medicine, Keimyung University School of Medicine,
6
Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea,
Republic Of
Contact E-mail Address: sw-jeon@hanmail.net
INTRODUCTION: In the era of increasing resistance of Helicobacter pylori
against antibiotics, non-bismuth-containing regimens have been validated for
the optimal treatment.
AIMS & METHODS: We aimed to identify the superb treatment option comparing concomitant and hybrid regimen as a first-line treatment for H. pylori
infection. A total of 359 na ve H. pylori-infected patients from six hospitals in
Korea were randomly assigned to concomitant and hybrid therapy groups. The
concomitant regimen consisted of 20 mg of esomeprazole, 1 g of amoxicillin, 500
mg of clarithromycin, and 500mg of metronidazole, twice daily for 10 days. The
hybrid regimen consisted of a 5-day dual therapy (20 mg of esomeprazole, and 1
g of amoxicillin, twice daily) followed by a 5-day quadruple therapy (20 mg of
esomeprazole, 1 g of amoxicillin, 500 mg of clarithromycin, and 500 mg of
metronidazole, twice daily).
RESULTS: Concomitant and hybrid eradication rates were 78.2% (161/206
patients, 95% CI 72.6-83.8) vs. 81.9% (163/199 patients, 95% CI 76.6-87.2) by
intention-to-treat (p 0.841) and 89.9% (151/168 patients, 95% CI 85.3-94.5) vs.
90.5% (153/169 patients, 95% CI 86.1-94.9) by per-protocol (p 0.841), respectively. The incidence of adverse events was similar between the two groups.
CONCLUSION: Concomitant and hybrid therapy were proven to be equally
efficient regimens as the first line treatment option for H. pylori infection.
Disclosure of Interest: None declared
P1660 COMPARATIVE
STUDY
OF
HELICOBACTER
PYLORI
ERADICATION RATES WITH 10-DAY NON-BISMUTH
QUADRUPLE THERAPY AND 10-DAY SEQUENTIAL THERAPY
S.Y. Kim1,*, J. Lee1, S.J. Suh1, J.J. Hyun1, S.W. Jung1, J.S. Koo1, J.J. Park1,
H.J. Chun1, S.W. Lee1
1
Internal Medicine, Korea University College of Medicine, Seoul, Korea, Republic
Of
Contact E-mail Address: seung0md@gmail.com
INTRODUCTION: Since the efficacy of the standard triple therapies for
Helicobacter pylori (H. pylori) eradication has decreased, novel antibiotic regimens have been introduced.
AIMS & METHODS: The aim of this study was to compare non-bismuth quadruple therapy with sequential therapy for the first-line H. pylori eradication.
One hundred and thirty-seven with proven H. pylori infection were randomly
assigned to one of 2 regimens: amoxicillin 1000mg with clarithromycin 500 mg,
metronidazole 500 mg, and pantoprazole 40mg twice daily for 10 days (nonbismuth quadruple therapy) or amoxicillin 1000mg with pantoprazole 40mg
twice daily for 5 days followed by clarithromycin 500mg with metronidazole
500mg, and pantoprazole 40mg twice daily for 5 days (sequential therapy).
The success of H. pylori eradication was evaluated 4-5 weeks after completing
treatment.
RESULTS: Eradication rates were 93.4% in the concomitant therapy and 85%
in the sequential therapy (per protocol), but the difference was not statistically
significant (P 0.154). Compliances were 97.2% in non-bismuth quadruple therapy and 97.1% in sequential therapy. Adverse events were generally mild in both
groups.
CONCLUSION: Non-bismuth quadruple therapy led to a non-statistically
advantage over sequential therapy, It is well tolerated and could be considered
as the first-line empirical therapy for H. pylori in Korea.
Disclosure of Interest: None declared

A588

United European Gastroenterology Journal 2(1S)

P1661 COMPARISON OF 10-DAY SEQUENTIAL THERAPY WITH


BISMUTH BASED QUADRUPLE THERAPY FOR SECOND LINE
HELICOBACTER PYLORI ERADICATION
S.H. Lee1,*, S.B. Kim1, K.H. Kim1, K.O. Kim1, B. I. Jang1, T.N. Kim1, H.J. Lee1
1
Internal Medicine, Yeungnam University, College of Medicine, Daegu, Korea,
Republic Of
Contact E-mail Address: dr9696@nate.com
INTRODUCTION: 10-day sequential therapy has been evaluated as the first line
therapy for Helicobacter pylori eradication and studies of sequential therapy as a
second line therapy has been scarce.
AIMS & METHODS: The aim of our study was to evaluate the efficacy of 10day sequential therapy as second line treatment after failure of standard triple
therapy.
Patients diagnosed as H. pylori infection by rapid urease test, giemsa staining, or
13
C-urea breath test and who failed from standard triple therapy for H. pylori
eradication from January, 2010 to June, 2013 in Yeungnam university hospital
were included. Post treatment H. pylori status was determined by rapid urease
test, giemsa staining, or 13C-urea breath test. Eradication rate, side effects were
compared.
RESULTS: A total of 123 H. pylori infected patients were included and 39
patients were treated by bismuth based quadruple therapy and 84 patients, by
10-day sequential therapy. Age and sex were not significantly different between
both groups. The per-protocol eradication rates were 82.1% (32/39) in quadruple
group and 60.7% (51/84) in sequential group. Side effects were similar in both
groups (quadruple group, 20.5% vs sequential group, 11.9%, p 0.273).
CONCLUSION: For second line H. pylori eradication after failure of standard
triple therapy, bismuth based quadruple therapy showed significantly higher H.
pylori eradication rate than 10-day sequential therapy. Further prospective studies are needed to evaluate efficacy of 10-day sequential therapy as second line H.
pylori eradication treatment.
Disclosure of Interest: None declared
P1662 2ND LINE LEVOFLOXACIN-BASED TRIPLE THERAPIES
PROVIDE SIMILAR HELICOBACTER PYLORI ERADICATION
RATES TO BISMUTH-BASED QUADRUPLE THERAPIES
S. Michopoulos1,*, E. Zampeli1, K. Argyriou1, V. Xourafas1, I. Kisouras1,
H. Kourkoutas1, B. Martinez-Gonzalaz2, D. Sgouras2, A. Mentis2
1
Gastroenterology, ALEXANDRA HOSPITAL, 2Laboratory of Medical
Microbiology, Hellenic Pasteur Institute, Athens, Greece
Contact E-mail Address: michosp@hol.gr
INTRODUCTION: The eradication rate of 1st line treatment with standard
triple therapy in Greece remains persistently under 80% since 2007 and parallels
Clarithromycin resistance of 4 20%. Quadruple bismuth containing regimens
were the standard of care as 2nd line treatments until 2010 when bismuth was
withdrawn from the market.
AIMS & METHODS: The aim of our study was to evaluate the efficacy of 2nd
line treatments over the periods before and after bismuth withdrawal.
Patients Methods: Data from patients, who received 2nd line treatment for
Helicobacter pylori, were collected retrospectively. Two periods were compared
in terms of eradication success: period A (2010) and period B (2011). During
period A patients received: {proton pump inhibitor bid metronidazole 500mg
tid amoxicillin 1gr bid bismuth subcitrate 120mg qid} for 14 days while
during period B: {proton pump inhibitor bid levofloxacin 500mg bid amoxicillin 1gr bid} for 10 days. Patients tested with urea breath test (UBT) 4-6 weeks
after completion of treatment were analyzed. Susceptibility to levofloxacin was
evaluated by E-test.
RESULTS: 159 patients (61 men), age (meanSD 51.712.3 years). Period A:
88 (34 men), and B: 71 (27 men). The 2 groups did not differ neither for age,
gender, smoking and other demographic parameters nor for endoscopic lesions.
Eradication rates according to UBT results for the 2 periods are shown in table 1.
Eradication rates according to UBT results for period B 2011 are shown in
table 2. For the years 2011-2013 the primary levofloxacin resistance rate as
evaluated continuously in samples of our population remained stable (8-9%).
Table1

52010
42011

UBT ()
13 (15%)
14 (20%)

UBT (-)
75 (85%)
57 (80%)

Chi-square
p 0.41

Table2
2011
2012
2013
2014

15
19
18
5

4
4
6
0

Fisher test
p 0.80

CONCLUSION: 1) 2nd line treatment with 10 days of levofloxacin-based treatment is equally effective to 14 days of quadruple bismuth-based treatment, with a
levofloxacin resistance of 510% for the studied period. 2) During 4 years of
levofloxacin use, the success rate did not change in this group and parallels the
stability of levofloxacin resistance rates. However, increase of resistance is probable in the future and it may affect the efficacy of levofloxacin-based treatments.

Disclosure of Interest: S. Michopoulos Financial support for research from: msd,


E. Zampeli: None declared, K. Argyriou: None declared, V. Xourafas: None
declared, I. Kisouras: None declared, H. Kourkoutas: None declared, B.
Martinez-Gonzalaz: None declared, D. Sgouras: None declared, A. Mentis:
None declared
P1663 TEN-DAYS CONCOMITANT THERAPY IS SUPERIOR TO
SEQUENTIAL THERAPY FOR HELICOBACTER PYLORI
ERADICATION
S.Y. Kim1,*, J.W. Chung1, D.K. Park1, K.A. Kwon1, Y.J. Kim1, K.O. Kim1
1
Department of Gastroenterology, Gachon University, Gil Medical Center,
Incheon, Korea, Republic Of
Contact E-mail Address: breeze1212@naver.com
INTRODUCTION: Helicobacter pylori (H. pylori) infection is the main cause of
gastritis, peptic ulcer disease, gastric MALT lymphoma, and gastric cancer. The
first-line international choice for treating H. pylori was consists of standard triple
therapy, which includes two antibiotics (clarithromycin plus amoxicillin or
metronidazole) plus proton-pump inhibitor for 7-14 days. Because the efficacy
of the standard triple therapy for H. pylori eradication has declined, new regimens such as sequential therapy (ST) and concomitant therapy (CoCTx) have
been introduced.
AIMS & METHODS: The aim of this study was to compare the efficacy of 10days sequential therapy and 10-days CoCTx (non-bismuth quadruple drugs) for
H. pylori eradication. We retrospectively reviewed the medical records of 316
patients with proven H. pylori infection. They were assigned to one of 2 regimens:
(a) ST (n 191): lansoprazole 30mg and amoxacillin 1g for 5 days followed by
lansoprazole 30mg, metronidazole 500mg, and clarithromycin 500mg for 5 days;
(b) CoCTx (n 125): lansoprazole 30mg, amoxicillin 1g, metronidazole 500mg,
and clarithromycin 500mg for 10 days. All drugs were administered twice a day.
Bacterial eradication was checked by using a 13C-urea breath test, at least 4 weeks
after treatment. Side effects and compliances were evaluated with interview and
more than 90% of drug administration.
RESULTS: The mean age and male to female ratio was 51.74 and 1.03. Baseline
characteristics (age, gender, smoking) were not different in both groups. Ten days
CoCTx group (94.4%, 118/125) showed better eradication rate than ST group
(82.2%, 157/191) (p 0.002). The difference was statistically significant. Drug
compliances were not statistically different between both groups (ST: 96.3%,
184/191; CoCTx: 92.8% 116/125) (p 0.19). Side effects were more frequently
reported in the CoCTx group (42.4%) than in the ST group (29.8%) (p 0.03).
The most common side effect was taste disturbance.
CONCLUSION: Ten-days CoCTx was superior to ST in terms of eradicating H.
pylori infection. Although the CoCTx was producing more side effects than ST,
CoCTx is thought to be a promising alternative to ST as a treatment regimen for
H. pylori eradication.
REFERENCES
Sequential therapy for Helicobacter pylori infection in Korea: systematic review
and meta-analysis. Gut Liver 2013; 7: 546-551.
Clinical outcomes of two-week sequential and concomitant therapies for
Helicobacter pylori eradication: a randomized pilot study. Helicobacter 2013;
18: 180186.
Sequential therapy of Helicobacter pylori infection. Korean J Helicobacter Upper
Gastrointest Res 2011; 11: 103-111.
Meta-analysis: sequential therapy is superior to conventional therapy for
Helicobacter pylori infection in Korea. Korean J Gastroenterol 62: 267-271.
Randomised clinical trial comparing sequential and concomitant therapies for
Helicobacter pylori eradication in routine clinical practice. Gut 2014; 63: 244-249.
Disclosure of Interest: None declared
P1664 INFLUENCE
OF
CYP2C19
GENOTYPE
AND
SERUM
PEPSINOGEN LEVEL ON FIRST-LINE ERADICATION THERAPY
WITH ESOMEPRAZOLE FOR PATIENTS WITH HELICOBACTER
PYLORI-POSITIVE GASTRITIS
Y. Saito1,2,*, H. Serizawa2, Y. Kato2, M. Nakano2, M. Nakamura3, H. Suzuki4,
H. Saito1, T. Kanai4
1
Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy,
2
Division of Gastroenterology, Kitasato Institute Hospital, 3School of
Pharmaceutical Sciences, Kitasato University, 4Division of Gastroenterology, Keio
University School of Medicine, Tokyo, Japan
Contact E-mail Address: yoshimasa.saito@gmail.com
INTRODUCTION: Esomeprazole is the proton pump inhibitor (PPI) that was
developed as the S-isomer of omeprazole. Although extensive metabolizer genotype of CYP2C19 metabolizes omeprazole rapidly, it is believed that esomeprazole is not affected by CYP2C19 genotype and is more effective for suppression
of gastric acid secretion. However, there is no evidence for clinical advantage of
esomeprazole in first-line Helicobacter pylori (H. pylori) eradication therapy.
AIMS & METHODS: In the present study, we investigated influence of
CYP2C19 genotype and serum pepsinogen level on first-line eradication therapy
with esomeprazole for patients with H. pylori-positive gastritis. Patients with
gastritis who were diagnosed as positive for H. pylori were included in this
study between January and September 2013. They were treated by first-line
eradication therapy with esomeprazole 40 mg/day, amoxicillin 1500 mg/day
and clarithromycin 400 mg/day for 7 days. Three-months after eradication, H.
pylori infection was validated by 13C-urea breath test. Correlation between H.
pylori eradication and CYP2C19 genotype and serum pepsinogen level was analyzed. This study is registered with the UMIN Clinical Trials Registry, number
UMIN000009642.

A589

United European Gastroenterology Journal 2(1S)


RESULTS: H. pylori eradication rate of first-line therapy with esomeprazole was
68.3% (54/79), which was similar to that of first-line therapy with lansoprazole
(69%; 80/116). Eradication rates of first-line therapy with esomeprazole in three
different CYP2C19 genotypes, extensive metabolizer (EM), intermediate metabolizer (IM) and poor metabolizer (PM) were 50% (11/22), 72.7% (32/44) and
84.6% (11/13), respectively. Eradication rate of EM group was significantly
lower than that of PM group (p 0.043) and IMPM group (p 0.03). Serum
pepsinogen I level and pepsinogen I/II ratio were significantly increased after
eradication of H. pylori (p 0.007), suggesting that gastric atrophy was improved
by eradication therapy.
CONCLUSION: These findings suggest that EM genotype of CYP2C19 metabolizes esomeprazole more rapidly, and therefore plasma concentration of
esomeprazole become lower, resulting in higher gastric acid secretion and
lower H. pylori eradication rate. Evaluation of CYP2C19 genotype and serum
pepsinogen level is important to develop effective personalized therapy of firstline eradication with esomeprazole for patients with H. pylori-positive gastritis.
Disclosure of Interest: None declared
P1665 MALT OR NOT MALT, THATS THE QUESTION UPPER
GASTROINTESTINAL ENDOSCOPY IN DIAGNOSIS AND
FOLLOW-UP OF GASTRIC MALT LYMPHOMA
A.R. Alves1,*, S. Giestas1, A. Casela1, D. Perdigoto1, Z. Romao1, D. Gomes1,
C. Gregorio1, R. Caetano Oliveira2, M.A. Cipriano2, M. Gomes3, L. Ribeiro3,
C. Sofia1
1
Gastroenterology Department, 2Anatomical pathology Department, 3Clinical
Hematology Department, Coimbra Hospital and University Centre, Coimbra,
Portugal
Contact E-mail Address: alvess.anarita@gmail.com
INTRODUCTION: Diagnosis of gastric mucosa-associated lymphoid tissue
(MALT) lymphoma (G-MALT) is frequently established after an upper gastrointestinal endoscopy (UGE) with biopsies, for investigation of nonspecific digestive symptoms. Described endoscopic changes of this rare neoplasia are
heterogeneous.
AIMS & METHODS: The aim of this study was to characterize endoscopic
findings of G-MALT in diagnosis and follow-up endoscopies.
We performed a retrospective study of all G-MALT cases, in a single tertiary
center, over a 14-year period (2000-2013). Data regarding patients demographics
and clinical factors and endoscopic findings were collected.
RESULTS: Sixteen patients were included, with a mean age of 60.82.7 years
and 9 (56.3%) were male. Indications for UGE were: epigastric pain in 8 (57.1%)
patients, postprandial fullness in 6 (26.1%), heartburn in 2 (8.7%), asthenia in 2
(8.7%), hematemesis in 2 (8.7%), anorexia and weight loss in 2 (8.7%) and
anaemia in 1 (4.3%). G-MALT was located in the (gastric) body in 9 (56.3%)
cases, antrum in 5 (31.3%) and both in 2 (12.4%). According to endoscopic
findings, changes were classified as: erosions of gastric folds in 3 (18.8%)
patients, gastric ulcer in 3 (18.8%), nonspecific areas of irregular mucosa in 3
(18.8%), structural modifications in gastric folds in 2 (12.5%), hypertrophic
gastric folds in 2 (12.5%), erythematous mucosa in 2 (12.5%) and exophytic
tumor in a single case (6.3%). The mean follow-up time was 5.6  0.9 years,
with no mortality. On follow-up endoscopies in non-gastrectomized patients,
gastric ulcers only maintained an area with a scar and there were no gastric
folds erosions. The remaining changes persisted similar to the first UGE, regardless disease evolution.
CONCLUSION: Endoscopic findings of G-MALT are nonspecific and, most of
the times, apparently benign. Given this, histological characterization of these
lesions is preponderant to its diagnosis and follow-up.
Disclosure of Interest: None declared
P1666 PRIMARY GASTRIC LOW-GRADE MALT LYMPHOMA:
EVALUATION OF CLINICAL AND LABORATORIAL FACTORS
FOR ACHIEVING COMPLETE REMISSION
A.G. Antunes1,*, D. Trabulo2, M. Eusebio1, S. Ribeiro2, B. Peixe1,
J. Mangualde2, A. Paula2, H. Guerreiro1
1
Gastroenterology department, Centro Hospitalar do Algarve - Hospital de Faro,
Faro, 2Gastroenterology department, Centro Hospitalar de Setubal, Setubal,
Portugal
INTRODUCTION: Gastric mucosa associated lymphoid tissue (MALT) lymphoma, is an indolent cancer, that occurs in the presence of pre-existing prolonged lymphoid proliferation in mucosal sites. In that instance, the most well
established trigger is the gastric Helicobacter pylori (Hp) infection.
AIMS & METHODS: Evaluation of clinical and laboratorial factors, and the
effect of therapy in achieving Complete Remission (CR) in 1 year of patients with
gastric MALT lymphoma. Multicentric study, in which clinical and pathological
features of patients with gastric MALT lymphoma, according Dawson criteria
for primary gastrointestinal lymphoma, were evaluated retrospectively.
RESULTS: A total of 34 cases were identified, 23 men, and 11 women, with an
average age of 59 years. The most common symptom was epigastric pain (74%),
six patients presented Gastrointestinal Bleeding and three patients had type B
symptoms. The most prevalent localization was gastric body and 18 patients had
ulcerative pattern at presentation. At diagnosis, 91% and 94% were classified has
limited disease (Lugano I-II and Ann Arbor IE-IIE respectively) and 94% had an
International Prognostic Index (IPI) 53. A total of 20 patients (59%) had histologic evidence of Hp infection. One year rate of CR was 77% (70% in the Hppositive versus 86% in the Hp-negative), with an average remission time of 8.5
months. Using Lugano Staging System, CR was achieved in 77% of patients with
limited disease versus 67% in those with advanced disease. In the Hp-positive
group, isolated antibiotic therapy led to a CR in 60% of the cases, including a

CR in a patient with advanced disease. There was achieved a CR in a patient of


the Hp-negative group treated only with isolated antibiotic therapy. The variables Limited Disease, IPI score 53, age, histologic evidence of HP, serum LDH,
Albumin and Beta2-microglobuline levels, were not associated with one year rate
of CR (P 5 0.05). At one year there was 1 death (Hp-positive patient).
CONCLUSION: The results confirm the good prognosis and the indolence of
MALT lymphoma. The variables studied couldnt predict CR in 1 year, but
enhances the idea that patients with early stage Hp-negative MALT lymphoma
and with advanced disease, might still benefit from antibiotic treatment.
Disclosure of Interest: None declared
P1667 THE GASTRIC CANCER DEVELOPMENT IN PEPTIC ULCER
PATIENTS WITH HELICOBACTER PYLORI INFECTION
J.J. Hwang1,*, D.H. Lee1, K.C. Yoon1, H.J. Lee1, Y. Jeong1, A.-R. Lee1,
Y.H. Kwon1, H. Yoon1, C.M. Shin1, Y.S. Park1, N. Kim1, S.Y. Seol2
1
Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
2
Internal Medicine, Inje University Paik Hospital, Busan, Korea, Republic Of
Contact E-mail Address: frontierassa@hanmail.net
INTRODUCTION: Helicobacter pylori (H. pylori) is a risk factor for gastric
cancer. We investigate the incidence for gastric cancer development in peptic
ulcer patients with H. pylori infection.
AIMS & METHODS: This was a retrospective study created from chart review
for patients who diagnosed by gastric cancer in peptic ulcer patient with H. pylori
infection between 2003 and 2013. They consisted of 86 gastric ulcer patients and
15 duodenal ulcer patients. Gastric and duodenal ulcer patients were excluded
from the analysis because of their limited number.
RESULTS: The prevalence rates of gastric cancer in gastric ulcer with H. pylori
infection were 3.60% (86/2387) and in duodenal ulcer with H. pylori infection
were 0.84% (15/1775). Kaplan-Meier analysis showed that the incidence of gastric cancer in duodenal ulcer patients was lower than that in gastric ulcer patients,
and the prognosis of gastric cancer in duodenal ulcer patients was poorer than
that in gastric ulcer patients (log-rank test, p 0.191). Coxs proportional hazard
model denotes the relative risk for duodenal ulcer against gastric ulcer adjusted
by pathologic differentiation as 1.71 (95% CI: 1.09-2.70, p 0.02). In univariate
and multivariate analysis, pathologic differentiation, stage and cell type were
related to gastric cancer in peptic ulcer patients with H. pylori infection (p 5
0.05).
CONCLUSION: In duodenal ulcer patients with H. pylori infection, the risk of
gastric cancer development was less and the prognosis was poorer than that of
gastric ulcer patients with H. pylori infection. The prevalence rates of gastric
cancer were 3.60% in gastric ulcer with H. pylori infection and 0.84% in duodenal ulcer with H. pylori infection. The relative risk for duodenal ulcer against
gastric ulcer adjusted by pathologic differentiation as 1.71 (95% CI: 1.09-2.70,
p 0.02).
Disclosure of Interest: None declared
P1668 THE
EFFECT
OF
H.
PYLORI
ERADICATION
METACHRONOUS GASTRIC NEOPLASMS AFTER ENDOSCOPIC
RESECTION OF GASTRIC DYSPLASIA

ON

S.H. Shin1,*, D.H. Jung1


Department of Internal Medicine, Institue of Gastroenterology, Yonsei University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: earth-peace@yuhs.ac
1

INTRODUCTION: Helicobater pylori (H. pylori) infection was closely related in


gastric atrophy, intestinal metaplasia (IM), and a progression to dysplasia or
cancer. Furthermore, some studies showed that the eradication of H. pylori
after endoscopic resection (ER) of early gastric cancer (EGC) was helpful to
prevent the development of metachronous gastric cancer.(1.2) However, there
are no sufficient data about the role of eradication of H. pylori after ER for
gastric dysplasia.
AIMS & METHODS: The aim of this study was to investigate the effect of H.
pylori eradication would affect the development of the metachronous gastric
neoplasms after ER in patients with gastric dysplasia.
We retrospectively reviewed 1850 patients who underwent endoscopic resection
of gastric dysplasia from January 2007 to February 2012 at Severance hospital.
We excluded patients with follow-up period of 5 2 years and who had not
undergone tests for active H. pylori infection at the time of endoscopy. Total
of 289 patients were enrolled in this study. Then divided them into three groups:
those without active H. pylori infection (Hp negative group, n 131), those who
successfully underwent H. pylori eradication (eradicated group, n 119), and
those who failed or did not undergo H. pylori eradication (non-eradicated
group, n 39). The rate of metachronous recurrence after ER was compared.
RESULTS: Metachronous reccurence was diagnosed in 42 patients, including 25
in the Hp negative, 8 in the eradicated, 9 in the non-eradicated group. Median
time to metachronous recurrence was 36 months (range, 6-85 months). The
incidence of metachronous recurrence was 5.13 cases per 1,000 person-years in
the Hp negative group, 1.57 cases per 1,000 person-years in the eradicated group,
and 6.07 cases per 1,000 person-years in the noneradicated group. Patients in
non-eradicated group had a higher risk of developing metachronous gastric neoplasms than eradicated group (hazard ratio [HR] 3.974, p 0.005).
CONCLUSION: The successful H. pylori eradication may reduce the development metachronous gastric neoplasms after ER in patients with gastric dysplasia.
Also regular follow-up of test for H. pylori infection is important to prevent the
metachronous recurrence in those high-risk patients.

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REFERENCES
1. Maehata Y, Nakamura S, Fujisawa K, et al. Long-term effect of Helicobacter
pylori eradication on the development of metachronous gastric cancer after
endoscopic resection of early gastric cancer. Gastrointest Endosc 2012; 75: 39-46.
2. Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of Helicobacter
pylori on incidence of metachronous gastric carcinoma after endoscopic resection
of early gastric cancer: an open-label, randomised controlled trial. Lancet 2008;
372: 392-397.
Disclosure of Interest: None declared

divided and supplied cells to both crypt base columnar cells and transit amplifying cells. These results suggested that epithelial cells in a crypt might be permanently supplied from independent different stem cells in a crypt but not single
stem cell.
CONCLUSION: Our original lentiviral transduction system to mark stem cells
might be useful to elucidate the subpopulation of intestinal stem cells in a crypt.
Live imaging of single cell in a crypt is useful for the analysis of the stem cell
division and maintenance.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
SMALL INTESTINAL III POSTER EXHIBITION HALL XL_____________________

P1671 NOTCH SIGNALING REGULATES EXPRESSION OF GELSOLIN


SUPERFAMILY GENES, GELSOLIN AND SCINDERIN, AND
PROMOTES RE-ASSEMBLY OF ACTIN CYTOSKELTON IN HUMAN
INTESTINAL EPITHELIAL CELLS

P1669 THE PH IN THE NORMAL GASTROINTESTINAL DECREASE


FROM THE TERMINAL ILEUM TO CECUM BY USING PH
CAPSULE FOR RECORDING SEQUENTIAL IMAGES AND THE PH
OF THE GASTROINTESTINAL TRACT
H. Iida1,*, M. Inamori2, K. Kanoshima1, Y. Inoh1, M. Matsuura1, T. Nonaka1,
A. Nakajima1
1
Gastroenterology Division, 2Office of Postgraduate Medical, Yokohama City
University Hospital, Yokohama city, Japan
Contact E-mail Address: hiro0905@yokohama-cu.ac.jp
INTRODUCTION: Before the introduction of capsule endoscopy and doubleballoon endoscopy, there were no effective modalities for reliable evaluation of
the small bowel. Evans D F reported the measurement of gastrointestinal pH
profiles in normal ambulant human subjects by using pH sensitive radiometry
capsule in 1988 (Evans D F et al. Gut 1988;29:1035-41). Recently, the SmartPill,
a wireless pH, temperature and pressure recording capsule, has been utilized to
measure the whole gut transit time. This modality can record gastrointestinal pH,
but could not record correct gastrointestinal location, especially ileum into
cecum. Evans reported that the pH in the normal gastrointestinal increase in
pH from the duodenum to the terminal ileum, decrease in the cecum by using
sensitive radiometry capsule. Recently we have designed a new noninvasive modality pH capsule for recording sequential images and the pH of the gastrointestinal tract (Iida H, et al. Hepatogastroenterology 2011;59:114).
AIMS & METHODS: The aim of this study was to investigate the pH changes
from the terminal ileum to cecum by using the pH capsule. Ten healthy male
volunteers swallowed the pH capsule with 50cc water. The pH capsule
transmitted the acquired images and pH to a recorder unit located outside the
body for about ten hours while the subject was fasting.
RESULTS: Ten male subjects completed this study. The intragastric pH was low,
and the pH in the small intestine ranged from 7.2 to 8.1 (mean of 7.61). The pH in
the terminal ileum (mean of 8.15) significantly decreased in the cecum (mean of
6.60).
CONCLUSION: We could noninvasively monitor sequential images and the pH
of the gastrointestinal tract, especially terminal ileum to cecum, with the pH
capsule. Thus, the pH capsule is expected to become a valuable tool for the
assessment of gastrointestinal pH abnormalities in various kind of diseases with
the accurate location and mucosal images of gastrointestinal tract.
REFERENCES
1. Iida H, Endo H, Sekino Y, et al. A new non-invasive modality for recording
sequential images and the pH of the small bowel. Hepatogastroenterology 2012;
59: 413-414.
2. Evans DF, Pye G, Bramley R, et al. Measurement of gastrointestinal pH
profiles in normal ambulant human subjects. Gut 1988; 29: 1035-1041.
Disclosure of Interest: None declared
P1670 A NOVEL GENE TRANSDUCTION SYSTEM INTO SMALL
INTESTINAL ORGANOID ENABLED THE IDENTIFICATION OF
THE STEM CELL SUBPOPULATIONS IN A CRYPT
N. Horita1,*, K. Tsuchiya2, R. Hayashi1, K. Fukushima1, S. Hibiya1,
M. Watanabe1
1
Gastroenterology and Hepatology, 2Advanced Therapeutics for Gastrointestinal
Diseases, Tokyo Medical and Dental University, Tokyo, Japan
Contact E-mail Address: nhorita.gast@tmd.ac.jp
INTRODUCTION: Recently, two kinds of stem cell population are advocated;
4 quiescent stem cell and Lgr5 crypt base columnar (CBC) cell by the progress
of stem cell research using small intestinal organoids that was generated from a
single stem cell by the 3-dimentional culture method. However, single stem cell
dynamics in a crypt remains not to be fully elucidated, because plural stem cells
exist in a crypt. We therefore hypothesized that the identification of a single stem
cell by fluorescent labeling might enable to explore the dynamics and relationship
between plural stem cells in a crypt.
AIMS & METHODS: Lentivirus encoding mCherry gene was mixed with matrigel to directly infect the small intestinal organoids. The localization of mCherry
positive cells in whole organoids was analyzed by confocal microscope and timelapse imaging microscope. The cell types of mCherry positive cells were identified
by the immunostaining with OLFM4 and Lysozyme.
RESULTS: We have established a lentiviral transduction system into the intestinal organoids to detect mCherry protein expression for a long time, 50 weeks
after transduction. Three-dimensional analysis using confocal microscope
showed both mCherry -positive and -negative cells in a crypt, which suggested
that both mCherry-positive and -negative stem cells might be long lived in the
same crypt. Moreover, we found a single mCherry positive cell in a crypt, which
was co-localized with stem cell marker: OLFM4. Furthermore, Paneth cells in a
crypt were differentiated from both mCherry-positive and -negative stem cells.
Time-lapse imaging showed that a single mCherry-positive stem cell in a crypt

R. Okamoto1,*, G. Ito1, H. Shimizu2, S. Fujii1, T. Nakata3, K. Suzuki1,


M. Watanabe1
1
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental
University, 2Department of Gastroenterology and Hepatology, Tokyo Medicai and
Dental University, 3Department of Gastroenterology and Hepatology, Tokyo
Medical and Dental University, Tokyo, Japan
Contact E-mail Address: rokamoto.gast@tmd.ac.jp
INTRODUCTION: In our previous study, we have shown that activation of
Notch signaling plays an indispensable role in differentiation and proliferation
of human intestinal epithelial cells (IECs). Dynamic change of the actin cytoskeleton is regulated by actin-binding proteins, including Gelsolin superfamily proteins, and is critically involved in fundamental cellular processes such as cell
adhesion or cell migration. However, the role of Notch signaling in regulation
of actin cytoskeleton dynamics remains completely unknown.
AIMS & METHODS: The present study was planned to identify whether Notch
signaling may also regulate the dynamic changes or reassembly of actin cytoskeleton in human IECs. To analyze the cellular effect of Notch activation, tetracycline-dependent overexpression of the Notch intracellular domain (NICD) was
induced in LS174T or DLD1 cells. Microarray analysis was performed to compare the expression of genes encoding actin-binding proteins, before and after
activation of Notch signaling in IECs. Change in gene expression was further
confirmed by quantitative PCR or immunoblot analysis. Also, the dynamic
change of actin-based cell structures was visualized by phalloidin staining.
Finally, assembly of focal adhesion, a cell structure indicating actin- and integrin-mediated cell adhesion to the extracellular matrix, was examined by double
staining of phalloidin and paxillin.
RESULTS: Microarray analysis of LS174T cells showed a significant increase in
expression of two Gelsolin superfamily genes, Gelsolin and Scinderin, upon
Notch activation. Validation of the data by quantitative PCR confirmed significant increase of Gelsolin and Scinderin mRNA expression by Notch activation,
in both LS174T and DLD-1 cells. Significant up-regulation of the Gelsolin protein expression was also clearly confirmed by immunoblot analysis. However, in
sharp contrast, expression of other Gelsolin family genes, such as Villin or
Supervillin remained completely unchanged. Consistent with the up-regulation
of Gelsolin and Scinderin expression, phalloidin staining clearly revealed promotion of actin cytoskeleton reassembly by Notch activation, resulting in significant
increase of lamellipodia and filopodia formation, but decrease of actin stress fiber
formation. Futhermore, double staining of phalloidin and paxillin showed a
significant decrease in formation of focal adhesions upon activation of Notch
signaling in DLD-1 cells, suggesting decreased cell adhesion, as well as increased
cell motility of those cells.
CONCLUSION: Activation of Notch signalling up-regulates expression of
Gelsolin superfamily genes, Gelsolin and Scinderin, in human IECs. Such an
up-regulation of actin-binding proteins may mediate the promotion of actin
reassembly by Notch activation, and subsequently regulate the behavior of
IECs, such as cell adhesion or cell migration.
Disclosure of Interest: None declared
P1672 ENTEROHEMORRAGIC ESCHERICHIA COLI TARGET PEYERS
PATCHES VIA LONG POLAR FIMBRIAE
C. Cordonnier1,*, L. Etienne-Mesmin1, A. Rougeron1, J. Thevenot1, S. BlanquetDiot2, A. Darfeuille-Michaud1, V. Livrelli1
1
M2iSH, 2EA CIDAM, Clermont-Ferrand, France
Contact E-mail Address: charlotte.cordonnier@udamail.fr
INTRODUCTION: Enterohemorrhagic Escherichia coli (EHEC) are food-borne
pathogens associated with diarrhea, hemorrhagic colitis and life-threatening
complications such as hemolytic-uremic syndrome. EHEC interact preferentially
with the Follicule-Associated Epithelium (FAE) of Peyers patches (PPs) regions
of the distal ileum in humans and translocate across the intestinal epithelium via
M cells. The Long Polar Fimbriae (LPF), encoded by two lpf operons, contribute
to epithelial cells adhesion and intestinal colonization.
AIMS & METHODS: To investigate the involvement of LPF in the ability of
EHEC strain EDL933 to target PPs, we generated the DlpfA1, DlpfA2, DlpfA1DlpfA2 isogenic mutants and trans-complemented them with lpfoperons.
In vivo interactions with murine PPs were analyzed in ileal loop assays. Mice
were infected with a mixture of two bacterial strains, and the numbers of PPsinteracting bacteria were determined using a competitive index analysis. LPF
interaction with M-like cells was investigated using the in vitro model of specialized M cells.
RESULTS: Lpf isogenic mutants (i) were not able to interact with ileal biopsies
containing PP compared to the wild type strain in competitive colonization
assays, and (ii) did translocate across M cells at levels significantly lower than
those observed for the wild type strain. Trans-complementation of the mutants

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United European Gastroenterology Journal 2(1S)


with the cloned lpf operons restored their ability to interact with PPs and M cells,
indicating that expression of lpfA1 or/and lpfA2 operons is required for interactions with PPs.
CONCLUSION: We conclude that LPF are involved in the interaction of EHEC
with murine PPs and are needed for an active translocation across M cell
monolayer.
Disclosure of Interest: None declared
P1673 LACTOBACILLUS PARACASEI SUBSPECIES PARACASEI F19
PREVENTS BOWEL SYMPTOMS IN PATIENTS AT LONG-TERM
PPI TREATMENT: A RANDOMIZED DOUBLE-BLIND PLACEBO
CONTROLLED CROSS-OVER MULTICENTER STUDY
D. Compare1,*, A. Rocco1, C. Sgamato1, P. Coccoli1, A. Martino1, S.M.
A. Campo2, I. Nazionale3, T. Larussa3, F. Luzza3, G. Nardone1
1
Clinical Medicine and Surgery, University Federico II of Naples, NAPOLI,
2
Gastroenterology Unit, Nuovo Regina Margherita Hospital, Roma, 3Health
Science, University Magna Grecia, Catanzaro, Italy
INTRODUCTION: Proton pump inhibitors (PPIs) may foster intestinal dysbiosis and related-bowel symptoms.
AIMS & METHODS: Aim of this study was to evaluate the effect of
Lactobacillus paracasei subspecies paracasei F19 (LP-F19) on bowel symptoms
onset in patients at long-term PPIs. Patients with typical gastroesophageal reflux
disease symptoms were screened. Enrolled patients received pantoprazole 40mg/d
for 6 months and were randomly assigned to: 1) LP-F19 for 6 months (LP-F19);
2) placebo for 6 months (PBO); 3) LP-F19 for the first 3 and placebo for the
following 3 months (LP-F19!PBO); 4) placebo for the first 3 and LP-F19 for
the following 3 months (PBO!LP-F19). Bowel symptoms (bloating, flatulence,
abdominal pain) and bowel habit were assessed baseline and monthly.
RESULTS: 100/312 patients were enrolled, 84 of whom completed the study. The
percentage of patients who developed at least one bowel symptom at 3-month
checkpoint was 4% in the LP-F19 group and 27% in the PBO group (p 0.04).
At 6-month checkpoint, the percentage of symptomatic patients increased up to
18% in the LP-F19 and 57% in the PBO group (p 0.01). In details, only the
percentage of patients who complained of bloating and flatulence, were significantly higher in PBO group in respect to LP-F19 group. In the LP-F19!PBO
group the percentage of patients who developed at least one bowel symptom was
20% during active treatment and increased up to 55% during placebo treatment
(p 0.05). Opposite, in the PBO!LP-F19 group, the percentage of symptomatic
patients was 48% during placebo treatment and progressively decreased to 14%
during active treatment (p 0.04). In details, in the LP-F19!PBO group, the
percentage of patients who complained of bloating, flatulence and abdominal
pain did not significantly differ in respect to baseline during active treatment.
Opposite, during placebo treatment, 40% of patients developed bloating
(p 0.003) and 35% flatulence (p 0.008). In the PBO!LP-F19 group, 14%
of patients complained of bloating (p 0.003) and 33% of flatulence (p 0.008)
during placebo treatment in respect to baseline. Opposite, during active treatment, only 5% of the patients still complained of bloating (p 0.02) and none of
flatulence (p 0.008). At multivariate analysis, LP-F19 treatment was the only
covariate independently associated with absence of symptoms (OR 0.2; 95%CI
0.09-0.46; p 0.0001). Mean stool frequency/week and stool form significantly
changed only during placebo treatment in both standard and cross-over groups.
CONCLUSION: LP-F19 supplementation prevents the onset of bowel symptoms in patients at long-term PPI treatment. In view of the growing number of
patients requiring long-term, high-dose PPIs, our results provide evidence for
new treatment strategies to reduce the burden of PPI-related intestinal diseases.
Further studies to define the best strain, dose, and timing of probiotics are
needed.
Disclosure of Interest: None declared
P1674 EVALUATION OF PROBIOTIC AND POSTBIOTIC EFFECTS OF
LACTOBACILLUS CASEI DG ON ENTEROGLIAL-DERIVED S100B
PROTEIN EXPRESSION AND NITRIC OXIDE PRODUCTION IN
HUMAN INTESTINAL BIOPSIES
F. Turco1,*, I. Palumbo1, G. Sarnelli1, R. Civiletti1, M. Di Somma1, T. Baldoni1,
P. Andreozzi1, R. Cuomo2
1
Clinical Medicine and Surgery, 2Clinical Medicine and Surgery, UNIVERSITY
OF NAPLES " FEDERICO II", Naples, Italy
Contact E-mail Address: fabio.turco81@yahoo.it
INTRODUCTION: Intestinal bacterial translocation is usually increased in
inflamed tissues. Postbiotics (probiotic-produced soluble factors) have been proposed to specifically manipulate intestinal functions1. We have previously shown
that pathogen bacteria-induced release of the enteroglial derived S100B protein
plays an active role in nitric oxide (NO)-dependent gut inflammation2.
AIMS & METHODS: We aim to study the effects, in human intestinal biopsies,
of the probiotic Lactobacillus Casei DG (LC) and of the postbiotics derived from
LC (LC-PB), on Enteroinvasive Escherichia Coli (EIEC)-induced NO and S100B
secretion and iNOS protein expression. To achieve this goal, rectal biopsies,
without macroscopic signs of inflammation, obtained from 7 healthy subjects
undergoing screening for colorectal cancer, were stimulated with EIEC and/or
with LC or LC-PB, as the following experimental scheme: A) stimulation with
EIEC from 0h to 5h (0-5h); B) LC or LC-PB 0-5h; C) [LC or LC-PB] 0-5h
EIEC 2.5-5h; D) EIEC 0-5h [LC or LC-PB] 2.5-5h; E) EIEC [LC or LC-PB]
0-5h. After 24 h, S100B release was evaluated by ELISA and NO release and
iNOS expression were evaluated by nitrite assays and Western Blot analysis
respectively, in stimulated compared to un-stimulated biopsies (control). Data
are expressed as meanSD.

RESULTS: EIEC, but not LC or LC-PB, significantly increased S100B secretion


(3.71.1 fold increase vs control; p50.05). When LC or LC-PB were added to
biopsies before, after or together EIEC, S100B secretion was not increased
respect to control and, interestingly, LC-PB were significantly more effective in
reducing S100B expression (-8.10.6, -3.7 0.4, -19.11.1 fold decrease vs viable
LC; p50.05). In parallel, incubation with EIEC led to a significant increase of
iNOS protein expression (5.61.6 fold increase vs control; p50.05) and of NO
secretion (2.40.3 fold increase vs control; p50.05), that was not observed
with LC or LC-PB. When LC or LC-PB were added to biopsy before, after or
together EIEC, iNOS expression and NO secretion were similar to control.
CONCLUSION: We showed that both LC and LC-PB are able to decrease
EIEC-induced S100B and NO secretion in human biopsies and that LC-PB
was more effective in reducing S100B expression than viable LC. Since probiotics
may be detrimental in those pathologies where bacterial translocation is
increased, with this preliminary report we propose postbiotics as a safer and
effective alternative to probiotics.
REFERENCES
1. Mileti E, et al. PLoS One 2009; 4: e7056.
2. Cirillo C, et al. Neurogastroenterol Motil 2011; 23: e372-e382.
Disclosure of Interest: None declared
P1675 XYLOGLUCAN: A NEW AGENT TO PROTECT THE INTESTINAL
MUCOSA AND TO PREVENT BACTERIALLY- MEDIATED
ALTERATION OF TIGHT JUNCTION PERMEABILITY
L. Bueno1,*, V. Theodorou1, S. Sekkal1
NGN Unit, INRA, Toulouse, France
Contact E-mail Address: lbueno@toulouse.inra.fr
1

INTRODUCTION: Xyloglucan (XG) is a water-soluble hemicellulose from vascular plants, indigested by digestive enzyme. This polysaccharide has various
application areas like drug-delivery technology, food technology and textile
industry. It has also been suggested that it may act as a film-forming barrier
distributed on the intestinal mucus layer able to protect the mucosa from chemical or bacterial aggression. However until now, no data has yet been published
to confirm such hypothesis.
AIMS & METHODS: Aims: Our studies aimed to evaluate both in vitro and
in vivo the potency of xyloglucan to prevent the bacterial toxin- induced -increase
permeability and the subsequent epithelial cell bacterial invasion.
Methods: A first series of experiments performed in vitro on co-cultured CaCo2/
Goblets cells submitted to E. coli inoculation, XG was added on the apical site of
the bath both preventively and curatively. Changes in tight junction (TJ) permeability was measured by TEER, Lucifer yellow transfer, E. coli adhesion and
epithelial cell invasion were counted. In a second series performed in vivo, Wistar
rats received orally XG (12.5mg/kg) and 2 h. later were injected IP with LPS
from E. coli. Jejunal strips were collected 6 hours later for in vitro TJ permeability measurement using FITC-dextran and mucosal myelo-peroxidase (MPO)
activity as a marker of inflammation. In a last series, XG was given orally
associated or not with gelatin or co-administered with cholera toxin (CT) into
isolated jejunal loops in anesthetized rats. Evaluation of CT-induced water secretion was performed 2hours later.
RESULTS: In vitro, given preventively XG (2.5mg/200ml), reduced significantly
by 78% the degree of E.coli mucosal colonization after 30min. Added curatively,
1after E.coli inoculation, XG attenuated by 87% the decrease in TEER measured
3h. later. Administered orally 2 hours before LPS, XG (12.5mg/kg) reduced
significantly (P0.01) by 81.8% the LPS-triggered increase in permeability and
subsequently by 63.2% the increase in mucosal MPO activity. When administered orally 4h earlier (12.5mg/kg) or 12h earlier with gelatin (250mg/kg), XG
suppressed CT-induced water secretion. Co-administered locally with CT at dose
of 0.75 and 1.25mg/loop, XG reduced (67%) or suppressed respectively, the
secretory effects of CT.
CONCLUSION: Both in vitro and in vivo data indicate that xyloglucan has
protective effects on intestinal bacterial invasion, alterations of gut permeability
and CT-induced intestinal secretion reaching 12h when associated with gelatin.
These data support that this compound may be of therapeutic interest in the
treatment of infectious diarrhea.
Disclosure of Interest: None declared
P1676 SMALL INTESTINAL BACTERIAL OVERGROWTH
INCREASE THE LIKELIHOOD OF LACTOSE, FRUCTOSE AND
SORBITOL INTOLERANCE FALSE POSITIVE DIAGNOSIS

MAY

T.T. Perets1, D. Hamouda1, E. Shporn1, Y. Niv2, R.M. Dickman2,*


1
Gastroenterology Laboratory, 2Department of Gastroenterology, Rabin Medical
Center - Beilinson Hospital, Petah Tikva, Israel
Contact E-mail Address: kaiser1974@gmail.com
INTRODUCTION: Small intestinal bacterial overgrowth (SIBO) is defined by
the presence of an excessive concentration of bacteria in the small intestine.
Lactose intolerance (LI), fructose intolerance (FI) and sorbitol intolerance (SI)
and SIBO share many gastro-intestinal (GI) symptoms usually attributed to
patients diagnosed with irritable bowel syndrome (IBS).
AIMS & METHODS: To evaluate the role and effect of SIBO in the formation
of LI, FI and SI symptoms in affected patients. A total of 348 patients with
suspected IBS underwent SIBO and LI, FI and SI diagnosis by hydrogen
breath test (HBT). 15 gr of lactulose dissolved in 50 ml of water and 50 gr of
lactose, 25 grams of fructose and 15 grams of sorbitol dissolved in 250 ml of
water were used for SIBO and LI, FI and SI HBT respectively. The test results
were considered positive when hydrogen concentration acceded 10 PPM for
SIBO and 20 PPM for LI, FI or SI above baseline.

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RESULTS: Out of the 348 patients tested for SIBO and LI, 101 (29%) were
positive for both tests. Out of the 197 patients tested for SIBO and FI, 17 were
positive for both tests. And finally, out of the 196 patients tested for SIBO and
SI, 45 were positive for both tests. Out of the 101 SIBO and LI, 17 SIBO and FI
and 45 SIBO and SI positive patients, 82 (81%), 14 (82%) and 23 (53%) respectively had an increase of hydrogen measurement above threshold between 30-90
minutes during their LI/FI/SI-HBT, implying SIBO.
CONCLUSION: The fermentation of lactose, fructose or sorbitol in the small
bowel due to SIBO may increase the likelihood of LI, FI and SI incorrect diagnosis. We suggest that all symptomatic patients will undergo SIBO testing and
eradication if diagnosed positive, prior to LI, FI or SI HBT evaluation.
Disclosure of Interest: None declared
P1677 IS A GLUTEN CHALLENGE REQUIRED TO DIAGNOSE ADULT
COELIAC DISEASE IN EQUIVOCAL CASES: A SINGLE CENTRE
EXPERIENCE OF REAL CLINICAL PRACTICE
S. Raju1, P.D. Mooney1, M. Kurien1,*, D.S. Sanders1
1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, United
Kingdom
Contact E-mail Address: peter.mooney@sth.nhs.uk
INTRODUCTION: Coeliac disease (CD) is under diagnosed which may result in
significant morbidity. The gold standard for diagnosing CD is the demonstration
of villous atrophy. However in some cases there is a strong suspicion of CD but
histology is normal or equivocal. In these cases the gold standard is a 6 week
gluten challenge and repeat duodenal biopsy. To date there is little clinical data
reported in the adult literature for outcomes or effectiveness of a gluten challenge
outside of research studies. This study aims to determine the clinical utility of
gluten challenge and predictive factors that could be used to aid diagnosis.
AIMS & METHODS: We undertook a prospective analysis of all patients who
were asked to undertake a gluten challenge over a 5 year period. Data were
recorded from referral to outcome. Presenting characteristics, baseline haematinics, tissue transglutaminase (tTG) and endomysial antibody (EMA) and HLA
type were recorded prior to gluten challenge. Repeat coeliac serology and biopsy
results were then recorded post gluten challenge. CD diagnosis required an
appropriate HLA phenotype, positive coeliac serology and deterioration in duodenal histology.
RESULTS: 64 patients (46 female, mean age 48.8, SD 16.5) were reviewed. 4
(6.3%) declined gluten challenge. 42/60 (70.0%) of patients challenged were HLA
DQ2 or DQ8 positive (6 homozygous). 21/60 (35.0%) patients were diagnosed
with CD and 32/60 (53.3%) had CD excluded. 7/60 (11.7%) patients were diagnosed with potential CD based on an HLA type compatible with CD and positive
serology but a normal duodenal biopsy on gluten challenge.
6/60 (10%) were unable to complete the full 6 week challenge (median 14.5 days)
due to gluten induced symptoms. A conclusive diagnosis was made in all 6 of
these patients.
Gluten challenge caused an increase in tissue tTG of 50.6% (p 0.034) in
patients with CD. No cut off for tTG prior to gluten challenge could be used
to diagnose CD. Of 30 EMA negative patients prior to endoscopy 6 (20%)
became positive on gluten challenge all of whom were diagnosed with CD. A
combination of tTG 4 20 times the upper limit of normal and a positive EMA
prior to challenge (n 7) had a positive predictive value of 85.7%.
There was no difference in presenting characteristics, baseline bloods or demographics between those diagnosed with CD, potential CD or those who had CD
ruled out.
CONCLUSION: No presenting characteristics, blood results or genotype could
reliably predict a diagnosis of CD. Increased tTG or new EMA positivity on
gluten challenge were associated with CD diagnosis. A gluten challenge will
ensure the best chance of recognition or exclusion of patients with CD. A 2
week gluten challenge may be sufficient to make conclusive diagnosis. A shortened gluten challenge could reduce the length of distress to patients with significant gluten induced symptoms and ensure prompt diagnosis.
Disclosure of Interest: None declared
P1678 INCREASED PREVALENCE OF CHRONIC LIVER
PANCREAS ABNORMALITIES IN PATIENTS WITH CELIAC
DISEASE

AND

M. Basaranoglu1,*, M. Yuksel1, C. Karacaer2, H. Yildiz1, S. Kacar1,


A. Demirbag1
1
Turkiye Yuksek Ihtisas Hospital, Ankara, 2Sakarya Hospital, Sakarya, Turkey
Contact E-mail Address: metin_basaranoglu@yahoo.com
INTRODUCTION: It was reported that involvement of the pancreas, liver and
biliary tract, including the gallbladder is rare in patients with celiac disease (CD).
AIMS & METHODS: Our aim to find the prevalance of these involvements by
using transabdominal ultrasound (US). Additionally, we further characterized
pancreas parancyhmal changes by echoendoscopy (EUS). We evaluated our
CD clinics records which includes 198 patients. We used US to show pancreas,
liver and biliary tract abnormalities. Then, patients with pancreas abnormalities
were further examined by EUS. Patients with recent onset dyspepsia were used as
a control group.
RESULTS: Of the 198 patients with CD, 102 had documented US results. There
were 102 patients without CD as a control group. All of the patients, 25% in CD
and 33% in control were male (p4 0.05). The prevalence of abnormalities as
follows: liver steatosis, 46% in CD vs 48% in controls (p4 0.05); gallbladder
polip, 3.9% in CD vs 6.9% in controls (p4 0.05); gallbladder sludge&stone,
4.9% in CD vs 11.8% in controls (p4 0.05); hepatomegaly, 2.9% in CD vs
28.4% in controls (p5 0.001); gallbladder operation, 5.9% in CD vs 8.8% in
controls (p5 0.001); gastric antrum wall tickness, 4.9% in CD vs 2.0% in

controls (p4 0.05); hepatic simple cyst, 3.9% in CD vs 2.9% in controls (p4
0.05); hemangioma, 3.9% in CD vs 2.9% in controls (p4 0.05); chronic liver
disease findings, 5.9% in CD vs 0% in controls (p: 0.014); hepatoportal sclerosis
1.0% in CD vs 0% in controls (p4 0.05); pancreas parancyhmal changes, 5.9%
in CD vs 0% in controls (p 0.029). EUS investigation was performed in all of
the patients with paranchymal changes that were found by US. EUS showed
major B or minor findings according to the Rosemont classification. None was
autoimmune pancreatitis (AIP). Echoendoscopy findings as follows: main duct
and side branch dilation, small cysts, pancreas atrophy, hyperechogen stria and
foci. Further analysis of the 6 patients with chronic liver disease showed that
none had autoimmune or viral serology. One of them showed grade 1 eosephageal varices with portal hypertensive gastropathy findings.
CONCLUSION: Our results showed that chronic type involvement of the pancreas and liver is significantly frequent in patients with CD. Even, cirrhosis with
varices was seen. So, CD might be a cause of cryptogenic cirrhosis. Thus, we
consider that pancreas and liver abnormalities were underestimated in clinical
practice and should be followed to detect progression.
REFERENCES
1. Burden S, Langley-Evans S, Pounder R, et al. Editorial: coeliac disease pathogenesis, prognosis and management. Aliment Pharmacol Ther 2014; 39: 555-556.
2. Hutchinson JM, Robins G and Howdle PD. Advances in coeliac disease. Curr
Opin Gastroenterol 2008; 24: 129-134.
Disclosure of Interest: None declared
P1679 DEVELOPMENT OF NOVEL T CELL BASED ASSAYS TO
IMPROVE THE DETECTION OF COELIAC DISEASE
M.X. Ma1,*, G.M. Forbes1,2, J. Jessica3, N.M. Keane3, M. John3,4
Gastroenterology, Royal Perth Hospital, 2School of Medicine and Pharmacology,
University of Western Australia, 3Institute for Immunology and Infectious Disease,
Murdoch University, 4Clinical Immunology, Royal Perth Hospital, Perth, Australia
Contact E-mail Address: michael.ma@health.wa.gov.au
1

INTRODUCTION: Coeliac disease (CD) is an immune disorder characterized by


intestinal pathology with systemic manifestations. Accuracy of CD diagnosis is
limited by need for continued ingestion of gluten. Unlike antibodies, memory
CD4 T cells can be stimulated to proliferate after low levels of antigen exposure
in vivo (1,2).
AIMS & METHODS: We developed and compared four in vitro assays to detect
peripheral blood GSTCs in newly diagnosed CD patients. Subjects on a glutencontaining diet had CD diagnosed by positive anti-tissue transglutaminase (tTG)
antibody, appropriate histology and expressed HLA alleles DQ2/DQ8. Whole
blood (WB) and/or peripheral blood mononuclear cells (PBMCs) were stimulated with coeliac associated antigens (whole gliadin [WG], deamidated gliadin
[DG] and tTG) after which cells and supernatants were analysed for: CD4 T cell
expression of lymphocyte activation markers (CD134/CD25), soluble Ox40
ligand (sOx40L) by ELISA, Th1, Th2 and Th17 cytokines (IL-6, TNF, and
IL-17) by Cytokine Bead Array (CBA) and CD antigen specific cytokine secreting cells from cryopreserved PBMCs by TNF ELISpot assay.
RESULTS: Six patients with CD and three patients without CD were studied.
Detection of % CD4CD134CD25 T cell levels above baseline were present
to at least one CD antigen (medians: WG 0.09%, DG 0.04%, tTG 0.11%) in four
patients with CD and one patient without CD to antigens DG (0.11%) and tTG
(0.13%). sOx40L levels were detected in three patients with CD and one patient
without CD. The CBA assay showed increased levels of TNF to DG antigen in
four CD patients (baseline 6.9 pg/ml; stimulated median 13.8 pg/ml, range 7.024.2 pg/ml), increased levels of IL-6 to WG antigen in three CD patients (baseline
98.5 pg/ml; stimulated median 130.7 pg/ml, range 101.8-226.1 pg/ml), and
increased levels of IL-17 to WG antigen in two CD patients (baseline undetectable; stimulated median 26.6 pg/ml, range 23.9-28.6 pg/ml). However in patients
without CD, increased IL-6 and IL-17a levels were also detected whereas TNF
was not, suggesting it may be a more suitable cytokine marker for patients with
CD. DG stimulated T cell secretion of TNFa was detected in three CD patients
by TNFa ELISpot assay (baseline 6.7 SFU/million cells; stimulated median 49.7
SFU/million cells, range 4.7-55.8 SFU/million cells), whilst no patient without
CD had detectable responses.
CONCLUSION: GSTCs can be detected in the peripheral blood of patients with
CD using methods to measure memory T cell responses to coeliac associated
antigens. Such assays have potential for implementation into future CD diagnostics, but will need improved performance characteristics to be clinically useful.
REFERENCES
1. Brottveitt M, Raki M, Bergseng E, et al. Assessing possible coeliac disease by
an HLA-DQ2-gliadin tetramer test. Am J Gastroenterol 2011; 106: 1318-1324.
2. Raki M, Fallang LE, Brottveit M, et al. Tetramer Visualisation of gut-homing
gluten-specific T cells in the peripheral blood of coeliac disease patients. Proc
Natl Acad Sci 2006; 104: 2831-2836.
Disclosure of Interest: None declared
P1680 BONE MINERAL DENSITY DIFFERS ACCORDING TO DISEASE
PHENOTYPE IN CELIAC DISEASE
A. Demirezer Bolat1, M. Tahtaci1,*, F.E. Akin1, O. Tayfur Yurekli1, E. Selvi1,
N.S. Buyukasik1, O. Ersoy2
1
Ankara Ataturk Research and Education Hospital, 2Yildirim Beyazit University
Faculty of Medicine, Ankara, Turkey
Contact E-mail Address: drtahtaci@gmail.com
INTRODUCTION: Coeliac disease (CD) is a genetically determined autoimmune condition, with an estimated worldwide prevalence of 1%. It is believed
to be the result of an abnormal autoimmune response in susceptible individuals
to dietary gluten derived from wheat, rye and barley. Disease phenotype can be

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United European Gastroenterology Journal 2(1S)


mainly classiffied as typical and atypical. Typical CD patients are defined as
patients having diarrhea as predominant symptom.
AIMS & METHODS: The evidence for reduced bone mineral density (BMD) in
CD is well known although it is not known whether there is a difference between
disease phenotypes. This study has aimed to compare bone mineral densities of
typical and atypical CD patients.
Between February 2008 and April 2014, 102 patients with CD were prospectively
included into the study. After serologic screening of CD by antigliadin antibody
(AGA) IgA, AGA IgG and antiendomysium antibody (EMA), duodenal biopsies
were obtained once a positive serology has been reported to confirm the diagnosis. Typical CD patients are patients presenting with diarrhea and patients
referring with complaints other than diarrhea are classified as having atypical
CD. Both groups are evaluated in terms of BMD results and routine
biochemistries.
RESULTS: A total of 102 patients with CD were included in this study. Patients
were assigned into two groups as atypical and typical form of CD. Comparision
of mean biochemistry parameters and bone mineral density in patients with
typical and atypical celiac patients are shown in Table 1.
Table 1: Comparision of mean biochemistry parameters and bone mineral density
in patients with typical and atypical celiac patients.

Age (years)
_
Body Mass Index
kg/m2
Hip T score
Vertebral body T score
Serum Calcium (mg/dl)
Serum Phosphorus (mg/dl)
25-hydroxyvitamin D (ng /ml)
Parathyroid Hormone (pg/ml)

Typical (n 38)

Atypical (n 64)

35.4211.31
21.364.02
-1.261.04
-1.641.34
90.62
3.570.55
16.0411.8
100.9278.6

34.7612.15
23.384.64
-0.891.05
-0.991.17
9.090.71
3.390.636
15.968.68
68.446

NS
NS
NS
50.05
NS
NS
NS
50.05

CONCLUSION: Low BMD, osteopenia, and osteoporosis are frequent complications of CD. In this study vertebral T score was found to be significantly lower
and parathyroid hormone levels significantly higher in typical CD patients.
Calcium malabsorption seems to play an important role in low bone mineral
density in CD but the apparent difference between typical and atypical CD
patients suggest there should be another mechanism in typical CD.
REFERENCES
1. Krupa-Kozak U. Pathologic bone alterations in celiac disease: etiology, epidemiology, and treatment. Nutrition 2014; 30: 16-24.
2. Reilly NR, Fasano A and Green PH. Presentation of celiac disease.
Gastrointest Endosc Clin N Am 2012; 22: 613-621.
Disclosure of Interest: None declared
P1681 METABOLIC SYNDROME AND HEPATIC STEATOSIS IN
COELIAC PATIENTS ON GFD
P. Capone1,*, A. Rispo1, G. De Stefano1, N. Imperatore1, N. Gerbino1, M. Leo1,
N. Caporaso1, R. Tortora1
1
Department of Gastroenterology, Endocrinology and Surgery, University Federico
II of Naples, Naples, Italy
Contact E-mail Address: picapo85@gmail.com
INTRODUCTION: BACKGROUND: Several studies have shown that weight
changes are common in patients affected by coeliac disease (CD) after the adoption of a gluten-free diet (GFD). However data on the prevalence of metabolic
syndrome (MS) and hepatic steatosis (HS) in patients with CD on free diet and
after GFD are still scarce.
AIMS & METHODS: 1) to assess the prevalence of MS in CD patients at time of
diagnosis and 1 year after starting GFD 2) to evaluate the prevalence of HS in
CD patients before and after GFD. Between January 2011 and March 2013, we
enrolled all consecutive patients with newly diagnosed CD who were referred to
our third-level CD Unit. All patients were investigated about waist circumference
with BMI, blood pressure, lipid profile (HDL cholesterol, triglycerides), levels of
glucose, aspartate (AST, U/l), alanine aminotransferase (ALT, U/l) and HS. MS
diagnosis was made according to International Diabetes Federation criteria
(IDF) for European countries. HS diagnosis was performed by ultrasonography
(US) in accordance to the current literature. The prevalence of MS and HS was
revaluated after 12 months of GFD. Statistical analysis was performed by using
X2, Mann-Whitney U test, Wilcoxon signed-rank test and odd ratio (O. R.) when
indicated. The differences were considered significant with a p 5 0.05.
RESULTS: Finally, 98 CD patients (29 men, 69 women; mean age: 35.7 years)
were analysed at diagnosis and after 1 year of GFD. At diagnosis, only 2 CD
patients (2%) fulfilled the criteria for MS while 29 patients (29.5%) met the
diagnostic criteria of MS after 12 months of GFD (p50.01; O. R. 20). The
comparison of MS sub-categories 1 year after GFD respect to the baseline
showed that 72 vs 48 patients exceeded waist circumference cut-off (p50.01;
O. R. 2.8), 18 vs 4 patients showed high values of blood pressure (p50.01; O.
R. 5.2), 25 vs 7 patients exceeded glycemic threshold (p 0.01;O. R. 4.4), 34 vs 32
CD patients had reduced levels of HDL cholesterol (p 0.7) and 16 vs 7 patients
had high levels of triglycerides (p 0.05). Mean BMI increased after GFD initiation (22.9 kg/m2 vs 24.1 kg/m2; p 0.01). At time of CD diagnosis, 18 out of 98
patients showed HS at US (18%). One year after starting GFD, 28 out of 98
patients showed HS (18% vs 28.5%; p 0.1); HS was present in 19 out of 29
patients with MS and 9 of 69 CD patients without MS (65% vs 13%;p50.01;O.
R.19).

CONCLUSION: CD patients show a high risk of MS and HS 1 year after


starting GFD. We suggest a deep nutritional assessment at diagnosis and
during the follow-up of patients affect by CD.
Disclosure of Interest: None declared
P1682 LEVEL OF ANTI-TRANSGLUTAMINASES IN PREDICTING THE
MARSH GRADE FOR THE DIAGNOSIS OF ADULT CELIAC
DISEASE
R. Tortora1,*, N. Imperatore1, P. Capone1, G. De Stefano1, G.D. De Palma1,
N. Caporaso1, A. Rispo1
1
Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
INTRODUCTION: The new ESPGHAN guidelines for diagnosis of pediatric
celiac disease (CD) suggest to avoid intestinal biopsy in genetically predisposed
and symptomatic individuals with positive anti-endomysial antibodies (EMA)/
anti-tissue transglutaminases (a-tTG). On the other hand, duodenal biopsy (in
combination with positive a-tTG and EMA) remains the gold standard in adults
with suspected CD.
AIMS & METHODS: To assess the cut-off values of a-tTG able 1) to predict the
presence of a duodenal histology (Marsh 2) diagnostic for CD; 2) to predict the
presence of villous atrophy (Marsh 3) in CD. From September 2011 to March
2014 we performed an observational prospective study including all consecutive
adult patients referred to our third-level centre for suspected CD. All subjects
were tested for EMA (absent/present) and a-tTG (U/ml). All patients with positive antibodies underwent upper endoscopy with duodenal biopsies/histology.
CD diagnosis was made in presence of Marsh  2 histology associated with
both a-tTG IgA 4 7 U/ml and positive EMA. Furthermore, a ROC curve was
constructed in order to detect the best cut-off of specificity of a-tTG level able to
predict the presence of Marsh  2 and Marsh 3 on duodenal histology.
Sensitivity, specificity, PPV and NPV of a-tTG level were calculated by using
SPSS statistical software. In addition, the presence of any disease other than CD
found on upper endoscopy was recorded.
RESULTS: The study included 310 patients with suspected CD (M/F: 35%/
65%; mean age 33.6 years) in presence of both positive EMA and a-tTG.
Final histology showed: Marsh 1 in 27 patients (8.7%), Marsh 2 in 11 subjects
(3.5%) and Marsh 3 in 272 cases (87.7%). The best cut-off value of a-tTG in
predicting Marsh 2 histology was 45 U/ml (sensitivity 70%; specificity 100%;
PPV 100%; NPV 79%) while the best cut-off in predicting villous atrophy
(Marsh 3) was 62.4 U/ml (sensitivity 69%, specificity 100%; PPV 100%; NPV
31%). In addition, we found other endoscopic findings: reflux-related esophagitis
in 38 patients (12%), hiatal hernia in 45 cases (14%), mild/superficial gastritis in
113 subjects (36%), atrophic gastritis in 5 cases (1.6%).
CONCLUSION: CD diagnosis could be performed without biopsy/histology in
adult patients with positive EMA and a-tTG levels 4 45 U/ml. A a-tTG level 4
62.5 is diagnostic for villous atrophy. These results could improve the diagnostic
work-up of CD with a significant reduction of diagnosis-related costs.
Disclosure of Interest: None declared
P1683 PERSISTENCE OF VILLOUS ATROPHY AND IRONDEFICIENCY ANEMIA IS FREQUENTLY OBSERVED IN ADULT
PATIENTS WITH CELIAC DISEASE AFTER AT LEAST ONE YEAR
OF GLUTEN FREE DIET
R. Saadi1,*, G. Malamut1, G. Rahmi1, E. Samaha1, C. Cellier1
1
gastroenterology, hopital europeen georges pompidou, Paris, France
Contact E-mail Address: saaderoula@hotmail.com
INTRODUCTION: Iron-deficiency anemia is a frequent manifestation of celiac
disease (CD), often leading to the diagnosis of the disease. Few studies look at
the evolution of anemia after a gluten free diet (GFD). The persistence of villous
atrophy (VA) and its connection to the improvement of anemia was also rarely
studied.
Goal of our work: to describe the incidence of anemia with hypoferritinemia after
at least a year of GFD in patients with CD, depending on the presence or absence
of persistent VA.
AIMS & METHODS: In a cohort of 655 patients with a diagnosis of CD,
followed at the Hopital Europeen Georges Pompidou in Paris, France between
the year 2000 and 2012, we have analyzed 262 patient records, (40% of the
cohort), of which 158 had duodenal biopsies after at least a year of GFD
(after excluding all patients with refractory celiac disease) and 120 patients had
a hemoglobin level before and after a GFD.
RESULTS: Among the 120 patients with available hemoglobin levels before and
after GFD (98 women, 22 men, mean age of diagnosis 28 yrs.), 46 (38.3%) had
anemia at the time of diagnosis (40.8% of women and 27.27% of men). After a
year of GFD, 27 (22.5%) had persistent anemia.
Among the 158 patients with available duodenal biopsies after at least a year of
GFD (122 women, 36 men, mean age of diagnosis 28 yrs.), 70 (44%) had persistent VA, varying from partial to subtotal, after GFD, and 88 (56%) showed no
more atrophy. Anemia was found in 20 patients (28.57%) with persistent VA,
and in 11 patients (12.5%) who had villous regrowth (p 0.015; OR: 2.78).
Hypoferritinemia was found in 23 patients (33%) with persistent atrophy, and
in 21 patients (24%) with villous regrowth (p 0.217; OR: 1.55). Consistent
observance of GFD was found in 48 patients (69%) with persistent VA, and in
62 patients (71%) without atrophy (NS). Among the 20 patients with residual
atrophy and anemia, 9 patients (45%) had inadequate GFD observance.
CONCLUSION: After at least a year of GFD, 22.5% of the patients in our series
had iron-deficiency anemia, and 44% had persistence of VA (after excluding
refractory CD). Some involuntary errors in GFD might explain this finding in
30% of cases, but there seem to appear a subgroup of patients who have no
villous regrowth and have more frequent iron-deficiency anemia in spite of strict

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United European Gastroenterology Journal 2(1S)

GFD. These patients might beneficiate from intravenous iron therapy. The
future and follow-up of these asymptomatic patients, but with no villous
regrowth, needs to be evaluated, particularly regarding concerns of lymphomatous complications (1).
REFERENCES
1. Lebwohl, et al. Mucosal healing and risk for lymphoproliferative malignancy
in celiac disease; a population-based cohort study. Ann Intern Med 2013; 159:
169-175.
Disclosure of Interest: None declared
P1684 RAISED
INTRAEPITHELIAL
LYMPHOCYTES
IN
THE
PRESENCE OF NORMAL SMALL BOWEL MUCOSA:
CONFIRMATION OF COELIAC DISEASE IN CLINICAL PRACTICE
S. Subramaniam1,*, A. Joshi2, K. Besherdas1
1
Department of Gastroenterology, 2Department of Histopathology, Barnet & Chase
Farm Hospitals NHS Trust, London, United Kingdom
Contact E-mail Address: sharmila.subramaniam@nhs.net
INTRODUCTION: Raised intraepithelial lymphocytes (IEL) (430-40 IEL/100
enterocytes) in small bowel (SB) mucosa is most commonly associated with
coeliac disease (CD) when accompanied by distorted villous architecture. In
addition to CD, there are various other causes of raised IEL including
NSAIDs, autoimmune conditions, tropical sprue, H pylori associated gastritis,
parasitic or viral infections and intestinal lymphoma. It is recommended that
patients who have raised IEL without distorted villous architecture (Marsh classification Stage 1 criteria) undergo further serological testing along with HLA
DQ2/DQ8 genotyping to assist in the diagnosis of CD.
AIMS & METHODS: The aim of the study was to determine the further assessment in clinical practice of patients with raised IEL in otherwise normal SB
biopsies to confirm the diagnosis of CD.
A single centre, retrospective analysis of patients with the histological finding of
raised IELs on distal duodenal (D2) biopsies in a district general hospital in north
London over a two year period between March 2012 and March 2014 was
performed. A database of patients with raised IEL was obtained from the hospital histology database and data on the patients coeliac antibody result, symptoms, diagnosis and management was scrutinized using the hospitals electronic
patient record system.
RESULTS: 121 patients had raised IEL on D2 biopsy specimens. 58 of these
patients had a confirmed diagnosis of CD with villous atrophy. The remainder
(63) had raised IEL with preserved villous architecture. 48/63 patients were
negative for coeliac antibodies, 1 was positive and 14/63 (22.2%) were not
tested. 15/63 (23.8%) were initiated on a gluten free diet and of this, 4 did not
report an improvement in their symptoms despite adherence to the diet. Only 2
patients had HLA DQ2/DQ8 testing to aid in the diagnosis of CD. A final
diagnosis of CD was made in 11/63 (17.5%) patients meeting Marsh 1 criteria.
32/63 (50.8%) patients had a diagnosis of gastrooesophageal reflux disease
(GORD) including 10 patients (15.9%) with H pylori associated gastritis. H
pylori was not tested in 13/32 patients with GORD (40.6%). A third of patients
(20/63 31.7%) with raised IEL and normal SB mucosa did not undergo any
further specific investigation to elucidate the cause of the raised IEL.
CONCLUSION: We conclude that there is marked variability in management of
patients following the findings of raised IEL with normal SB mucosa. A fifth of
patients did not have coeliac antibody tested and only 2 patients had HLA DQ2/
DQ8 genotype assessment to affirm or deny association with CD. Latent CD was
diagnosed in almost a fifth (17.5%) of patients with raised IEL and preserved
villi. GORD and H pylori gastritis were present in half of the patients with this
histological finding. We recommend that all patients in whom raised IEL is
identified have coeliac serology and HLA DQ2 DQ8 testing to exclude CD
prior to entertaining other diagnoses in clinical practice.
Disclosure of Interest: None declared
P1685 PROMOTER REGION
WHIPPLES DISEASE

IL-16

GENE

POLYMORPHISM

Levels of serum IL-16 protein were also tested by means of an ELISA technique
in samples from the same 74 healthy controls; a possible relationship between
genotype and levels of serum IL-16 was investigated.
RESULTS: The wild type T allele was found in 138/160 (86%) patients with WD
and 114/148 (77%) controls (p NS for Chi squared test). TT genotype was
found in 58/80 (72.5%) patients with WD and 44/74 (59.5%) controls
(p 0.08 for Chi squared test); no relationship was found between levels of
serum IL-16 and genotypes.
CONCLUSION: IL-16 gene polymorphisms have already been found associated
with different diseases [5]. Despite this, a relationship has not yet been found
between types of polymorphism and serum levels of IL-16 protein. Although TT
genotype seems to be more frequent in patients with WD than in controls, our
results did not reach statistical significance and do not support an association.
These very preliminary results need to be expanded to hopefully reach statistical
significance.
REFERENCES
1. Schoniger-Hekele M, et al. Appl Environ Microbiol 2007; 73: 2033-2035.
2. Martinetti M, et al. Gastroenterology 2009; 136: 2289-2294.
3. Biagi F, et al. Eur J Clin Microbiol Infect Dis 2012; 31: 3145-3150.
4. Ghigo E, et al. PLoS One 2010; 5: e13561.
5. Lu Y, et al. Thromb Haemost 2012; 107: 30-36.
Disclosure of Interest: None declared
P1686 BIOCHEMICAL DIAGNOSIS OF BILE ACID DIARRHOEA USING
FGF19
C. Borup1,*, C. Syversen1, H.H. Nielsen2, M. Damgaard3, J. Graff4,
J. Rumessen5, L. Munck1,6
1
Internal Medicine, 2Clinical Biochemistry, 3Clinical Pysiology, Kge Hospital,
Kge, 4Clinical Pysiology, Hvidovre hospital, Hvidovre, 5Internal Medicine,
Gentofte Hospital, Hellerup, 6Faculty of Health and Human Sciences, University of
Copenhagen, Copenhagen, Denmark
Contact E-mail Address: lkmu@regionsjaelland.dk
INTRODUCTION: Bile acid diarrhoea (BAD) is a common and less acknowledged cause of chronic watery diarrhoea. The 7-day radiolabled 75Selenium
homocholic acid taurine (SeHCAT) test is not generally available, and it is cumbersome and expensive. Patients suffering from undetected BAD have a poor
quality of life and are withheld effective therapy with sequestrants. New insight
into the regulation of bile acid physiology have identified fibroblast growth
factor FGF19 as one possible marker of BAD and demonstrated a correlation
with SeHCAT. FGF19 concentrations are easily measurable but subject to diurnal variation and postprandial increase. Further studies of FGF19 as a test for
BAD therefore are warranted.
AIMS & METHODS: To confirm the association between SeHCAT and FGF19
in a prospective patient series, to examine the inter- and intra-individual variation and effect of cholecystectomy on FGF19 levels, and to explore whether the
overlap between normal and individuals with BAD could be reduced by measuring the meal induced change in FGF19. FGF19 was measured by commercially
available quantitative sandwich enzyme immunoassay technique before and one
hour after meals and after 1 week in healthy volunteers, in patients with previous
diagnosed BAD or cholecystectomy, and in consecutive patients referred to
SeHCAT. The median (range) FGF 19 values are given as pg/mL. No correction
for cholesterol values or weight was performed. The interassay variation was 9.6
% in our laboratory.
RESULTS: The results are depicted in the table. The median FGF19 was lower
for patients with BAD with a wide overlap. The least squares linear correlation
coefficient r 0.5 for the relation between SeHCAT and FGF19 in the prospective series in which the breakfast induced increase in FGF19 did not differ significantly (Mann-Whitney). Neither single values nor meal induced changes in
FGF19 could predict or rule out BAD. The inter-individual variation of fasting
FGF19 values in all 56 participants was large.

IN

F. Biagi1, A. Schiepatti1,*, C. Badulli2, L. Trotta1, G.E. Feurle3, C. Muller4,


V. Moos5, T. Schneider5, T. Marth6, M. De Amici7, M. Martinetti2,
G.R. Corazza1
1
First Department of Internal Medicine, University of Pavia, 2Immunohematology
and Transfusion Centre, IRCCS Foundation Policlinico San Matteo, Pavia, Italy,
3
DRK Krankenhaus, DRK Krankenhaus, Neuwied, Germany, 4Universitatsklinik
fur Innere Medizin III, Klinische Abteilung Gastroenterologie und Hepatologie,
Medizinische Universitat Wien, Vienna, Austria, 5Medizinische Klinik I, ChariteUniversitatsmedizin Berlin, Berlin, 6Abteilung Innere Medizin, Krankenhaus Maria
Hilf, Daun, Germany, 7Pediatriac Clinic, IRCCS Foundation Policlinico San
Matteo, Pavia, Italy
Contact E-mail Address: f.biagi@smatteo.pv.it
INTRODUCTION: Whipples disease (WD) is a rare chronic systemic disorder
caused, in genetically predisposed subjects, by Tropheryma whipplei, a common
bacterium widespread in the environment [1]. The relevance of genetic predisposition in WD is shown by the association with HLA alleles DRB1*13 and
DQB1*06 and by the demonstration that in patients with WD the cytokine
genetic profile is skewed toward a Th2 and Treg response [2,3]. Since IL-16 is
involved in hampering the development of a protective macrophagic response
against Tropheryma whipplei [4], we investigated whether the genetic background
of IL-16 is different between patients with WD and controls.
AIMS & METHODS: Thanks to the European Consortium on WD (QLG1-CT2002-01049), rs 4778889, a polymorphism of the promoter region of IL-16 gene,
was studied in 80 patients with WD and in 74 healthy controls using the PCRreal time technique; the frequencies of alleles and genotypes were then compared.

Median (range)

Healthy
volunteers

Previous
BAD

Prospective SeHCAT
Cholecystectomy
10%

N
10
Fasting
94 (50 291)
Change after
17 (-153 67)
breakfast
Before lunch
134 (86 236)
Change after lunch26 (-15 105)

8
12
41 (12 130) 71 (25 286)
8 (3 66)
39 (-94 141)

4 10%

9
17
62 (14 91) 103 (24 287)
4 (-30 20) 36 (-136 435)

75 (21 210) 108 (69 1102) n.a.


8 (-71 -51)
7 (-143 76)
n.a.

n.a.
n.a.

Diff. between fast- 44 (-211 294)13 (183 593)10 (-150 245) 4 (-21 135)4 (-220 245)
ing values

CONCLUSION: While the overall results confirm that FGF19 is lower in


patients with BAD, the inter- and intra-individual variation of FGF19 is large.
Neither fasting nor single postprandial values of BAD could identify patients
with BAD. The utility and timing of FGF19 values as a diagnostic test for BAD
using a more powerful and uniform stimulation of the bile acid transporter
should be tested. Analysis of area under the curve of FGF19 values following
stimulation and combination with other markers such as C4 should be included.
REFERENCES
Pattni SS, et al. APT 2013; 38: 967-976.
Lundasen T, et al. J Intern Med 2006; 260: 530-536.
Disclosure of Interest: None declared

A595

United European Gastroenterology Journal 2(1S)


P1687 IN IRRITABLE BOWEL SYNDROME THERE IS
SIGNIFICANT ASSOCIATION BETWEEN FRUCTOSE
MALABSORPTION AND INTOLERANCE AND THE FRUCTOSE
TRANSPORTER, GLUT5 AND GLUT2, PROTEIN OR MRNA
EXPRESSION LEVELS

NO

C.H. Wilder-Smith1,2,*, X. Li1, R.K. Wong1, S.S. Ho3, S.M. Leong3, H.K. Lee3,
E.S. Koay3, R.P. Ferraris4
1
Dep. Medicine, National Univ. Singapore, Singapore, Singapore,
2
Gastroenterology Group Practice, Brain-Gut Research Group, Bern, Switzerland,
3
Dep. Laboratory Medicine, National University Hospital, Singapore, Singapore,
4
Dep Pharmacology & Physiology, New Jersey Medical School, Newark, United
States
Contact E-mail Address: cws@braingut.com
INTRODUCTION: Food intolerances are a major complaint in IBS. Fructose
intolerance prevalence in IBS is up to 70%, but the causative mechanism is
unknown (1). Fructose is transported across the intestinal epithelia by glucose
transporters 5 (GLUT5, Slc2a5) and 2 (GLUT2, Slc2a2) in the apical and basolateral membranes, resp.(2). In mice, deletion of GLUT5 resulted in malabsorption of dietary fructose and typical signs of intolerance (3). Several of the
postulated underlying mechanisms in IBS, e.g. inflammation and stress, reduce
GLUT5 expression (2) Recently, no group differences in GLUT5 and GLUT2
protein and mRNA expression in IBS patients with fructose intolerance and
controls were shown (4).
AIMS & METHODS: To further analyze the relationship between fructoseassociated symptoms in IBS patients with malabsorption, a correlative analysis
with GLUT5 and GLUT2 protein and mRNA expression levels was performed.
Duodenal biopsies were obtained in 11 male or female IBS patients with fructose
malabsorption and intolerance, diagnosed by breath testing after 8h fasting and
ingestion of 35g fructose. Malabsorption was characterized by an increase of
H2420ppm or CH4410ppm in breath and intolerance was defined by a positive
GI-symptom index within 5h of fructose ingestion. 15 matched healthy subjects
aged between 18 and 60 years were used as controls. Coeliacs disease and IBD
were excluded. mRNA for GLUT5 and GLUT2 was quantified by multiplex RTqPCR, and expressed as a ratio of -actin. GLUT5 and GLUT2 protein expression level were determined by Western Blot relative to alpha-tubulin. Analysis
was by Spearman Rank correlation and Mann-Whitney test for group
comparisons.
RESULTS: The maximum H2 and CH4 concentrations across all individuals did
not correlate with either GLUT5 or GLUT2 mRNA or protein expression levels
(r50.14, p40.48). There were no significant group differences in GLUT5
mRNA expression levels between fructose intolerant IBS patients (median:
0.18 (IQR 0.13-0.21)) and controls (0.17 (0.12-0.19))(p40.05). Respective
GLUT2 mRNA expressions were 0.26 (0.20-0.31) and 0.26 (0.190.31)(p40.05). There were also no significant group differences in GLUT5 protein expression between patients (0.95 (0.52-1.68) and controls (0.95 (0.591.15))(p40.05). Respective GLUT2 protein expression levels were 1.56 (1.062.14) and 1.35 (0.96-1.79)(p40.05).
CONCLUSION: Duodenal GLUT5 and GLUT2 mRNA and protein expression
did not correlate with fructose malabsorption characterized by classic breath
testing, and did not differ significantly between fructose-intolerant IBS patients
and healthy controls. Our results suggest that human fructose intolerance or
malabsorption may not be associated with marked changes in GLUT5 and
GLUT2 mRNA and protein expression.
REFERENCES
(1) Wilder-Smith CH. Aliment Pharmacol Ther 2013; 37: 1074.
(2) Douard V and Ferraris RP. Am J Physiol Endocrinol Metab 2008; 295: 227.
(3) Barone S. J Biol Chem 2009; 284: 5056.
(4) Wilder-Smith CH. UEGJ 2014; 2: 14-21.
Disclosure of Interest: None declared

RESULTS: 67 out of 93 (72%) patients result lactose malabsorbers, while 53%


(49 out of 93) referred a headache worsening. Within the group of lactose malabsorbers, headache worsened in 50.7% patients compared to 57.7% in non-malabsorber subjects (p 0.36). More interestingly, we observed that in the subgroup
of patients with a habitual headache (VAS 4 30 mm; 41 subjects) there is a
significant worsening of headache during the test compared to the subgroup with
a non habitual headache VAS 30 mm (70.7% vs 38.5%; p 0.003), regardless
of the breath test result. A significant correlation was observed between habitualheadache VAS and headache-during-the-test VAS (r 0.313; p 0.02). No significant correlations were observed between the VAS increase and H2 nor CH4
excretion.
CONCLUSION: We did not find any correlation between headache and lactose
malabsorption. Although, we observed that the majority of patients undergoing a
LBT complain of headache and the rate dramatically increases among the
patients usually suffering from headache. We are not able to determine whether
the onset of headache or its deterioration are linked to the load of lactose or
prolonged fasting. We think that this data should be taken into account, since we
suppose that the onset of clinically relevant headache during a LBT could affect
compliance in the correct execution of the test and maybe lead to an overestimation of classic LI symptoms. Moreover, the onset of headache might be a cause of
premature suspension of LBT.
Disclosure of Interest: None declared
P1689 PERCEPTION OF LACTOSE INTOLERANCE IMPAIRS HEALTH
RELATED QUALITY OF LIFE
F. Casellas1,*, A. Aparici1, P. Rodr guez1
Digestive System Research Unit, Hospital Universitari Vall dHebron, Barcelona,
Spain
1

INTRODUCTION: Changes in health impacts well-being, which is perceived as


an impaired health related quality of life (HRQOL). It is debated whether adult
lactose malabsorption is a normal situation or a pathological condition. In any
case, the symptoms that people attribute to lactose intolerance or malabsorption
have great relevance as they are associated with a lower consumption of calcium/
vitamin D and a lower bone density. In addition, it is not known if malabsorption or intolerance to dairy products is associated with a loss of HRQOL.
AIMS & METHODS: Our aim was to determine the HRQOL based on the
perception of tolerance to lactose and on the objective determination of the
absorption of lactose. METHODS: Prospective, observational, cross-sectional
study in a cohort of patients referred to assess absorption of lactose. After signing the informed consent, patients completed a validated questionnaire to determine the perception of symptoms of intolerance during their regular
consumption of dairy products at home and a visual analogue scale 0-100 generic
measure of quality of life (VAS). Afterwards, a standardized hydrogen breath test
with 50 g lactose was performed. At the end of the breath test, the questionnaire
was administered again to determine the intensity of symptoms after the lactose
overload in the lab.
RESULTS: 173 patients were included (median age 42 y, F/M 132/41). 77 (44 %)
of patients considered themselves lactose intolerants and that perception was
associated with avoidance of dairy consumption (56 % of self-defined intolerants
avoid dairy intake vs only 6 % of self-defined tolerants). Self-perception of
intolerance was associated with lower scoring of the VAS (median of 60 vs 70
scored by tolerant, p50.01). In contrast, lactose malabsorption established by a
positive hydrogen lactose test was not associated with dairy avoidance (36 % of
malabsorbers avoid dairy vs 32 % of absorbers). However, scoring of VAS was
also significantly lower in malabsorbers than in absorbers (60 vs 70 respectively,
p50.001).
CONCLUSION: Subjective perception of lactose intolerance affects the decision
to avoid dairy even more than objective malabsorption. However, both the selfperception of lactose intolerance and the objective lactose malabsorption are
associated with poorer perceived quality of life.
Disclosure of Interest: None declared

P1688 HEADACHE DURING LACTOSE BREATH TEST: IS THERE ANY


RELATIONSHIP?
F. Del Zompo1,*, F. Mangiola1, D. Feliciani1, T.A. Di Rienzo1, G. DAngelo1,
A. Gasbarrini1, V. Ojetti1
1
Department of Internal Medicine, Gastroenterology Division, Policlinico A.
Gemelli, Rome, Italy
Contact E-mail Address: fabio.delzompo@gmail.com
INTRODUCTION: Lactose malabsorption (LM) consists of the incomplete
absorption of lactose, mainly due to lactase deficiency on the brush border.
While generally well-tolerated, a certain rate of lactose malabsorbers may experience symptoms (diarrhoea, abdominal pain, bloating, and flatulence) characterizing the so-called lactose intolerance (LI). Therefore, LI commonly shows a
clinical overlap with Irritable Bowel Syndrome (IBS). Headache affects IBS
patients with an estimated OR of 2.66 according to previously published studies,
showing a range of similar comorbidities such as fibromyalgia, depression,
insomnia. Thus, several authors support the idea that both headache and IBS
are central pain-related disorders. We investigate the onset of headache during
the LBT, and a possible correlation with lactose malabsorption.
AIMS & METHODS: We enrolled 93 (74 F/19 M; mean age 4215 yrs) outpatients who perform a LBT in our Gastroenterology Unit according to the
guidelines. Patients were asked to report on a Visual Analogue Scale the intensity
of usual headache, before lactose administration and after the end of the test. We
considered as significant an increase of headache in VAS peak during the test
410 mm (dVAS). A positive LBT was considered with a peak 420 ppm in H2
excretion over baseline. Statistical analysis was performed with Pearsons correlation test and with 2 test.

P1690 GALLSTONES,
LACTOSE
MALABSORPTION
METHANOGENIC FLORA: A STRANGE TRIO

AND

F. Mangiola1, F. Del Zompo1, D. Feliciani1, T.A. Di Rienzo1, G. DAngelo1,


C. Sensi2, R. Persiani2, D. DUgo2, A. Gasbarrini1, V. Ojetti1,*
1
Gastroenterology, Gemelli University Hospital, Catholic University of Rome,
2
Department of Surgery, Gemelli University Hospital, Catholic University of
Rome, Roma, Italy
Contact E-mail Address: fra.mangiola@gmail.com
INTRODUCTION: Cholelithiasis, is defined as the presence of stones in the
gallbladder, is one of the most common digestive diseases, affecting 9-19 % of
the general population, with a female prevalence. The most common symptom is
postprandial biliary colic, characteristic for localization, duration and intensity.
Cholecystectomy, usually laparoscopic, is the definitive treatment of choice. The
altered composition and excretion of bile in the duodenum is very irritating to the
lining of the intestines, altering the brush border with a possible interference on
the lactose absorption.
AIMS & METHODS: The aim of this study was to assess the prevalence of
lactose malabsorption through a H2/CH4 lactose breath test (LBT) in subjects
affected by gallstones.
Twenty (4M/16F; mean age 558 yrs) subjects, which would undergo cholecystectomy in the following month for gallstones, have performed a H2/CH4 LBT in
our Gastroenterology Unit according to the guidelines. We have considered a
positive LBT when there was a peak 420 ppm over baseline.
RESULTS: 14 out of 20 (70%) pts resulted lactose malabsorbers with a mean
peak value of H2 of 7323 ppm.

A596

United European Gastroenterology Journal 2(1S)

The most interesting data was that 90% (18/20) of these pts produced high levels
of CH4, with a mean basal value of 85 ppm and a mean peak value of 28  12
ppm.
CONCLUSION: We found a high prevalence of lactose malabsorption in pts
affected by gallstones, confirming the hypothesis that an alteration of bile composition could destroy the lactase enzyme on the brush border.
The high prevalence of methanogenic flora observed in these pts could be a cause
or a consequence of the formation of gallbladder stones. Further studies are
needed to better understand this interesting findings.
Disclosure of Interest: None declared
P1691 THE EFFECT OF GLUTEN ON SOME GASTROINTESTINAL
FUNCTIONS IN HEALTHY VOLUNTEERS: A STUDY OF GASTRIC
AND GALLBLADDER EMPTYING AND COLONIC FERMENTATION
M. Di Stefano1, G. Carneval Maffe`1, M. Bergonzi1,*, C. Mengoli1,
P. Formagnana1, A. Di Sabatino1, G.R. Corazza2
1
1st Department of Internal Medicine, 2IRCCC Policlinico S. Matteo, University
of Pavia, Pavia, Italy
Contact E-mail Address: m.distefano@unipv.it
INTRODUCTION: Gluten is the main protein complex of wheat and represents
a complex substance on both chemical and genetic grounds. The exposure to
gluten in genetically predisposed subject determines the onset of celiac disease, a
frequent condition characterized by increased comorbidity and mortality.
However, gluten exposure may cause a spectrum of disorders, involving different
organs and recently it was suggested to be responsible for a condition characterized by a complex clinical presentation involving both the intestinal tract and
extraintestinal organs defined non celiac gluten sensitivity (NCGS) (1). Besides
un unblinded evaluation of intestinal fermentation (2), in healthy volunteers
(HV) the response to a gluten-containing (GCM) in comparison to a glutenfree meal (GFM) was not yet evaluated.
AIMS & METHODS: Therefore, in a group of HV, we analyzed the effect of a
GCM and a GFM on gastric and gallbladder emptying time and intestinal
fermentation.
In a group of 40 HV a preliminary evaluation of gluten recognition in the meal
was performed. Then 18 HV (6 female, median age 25.72.4 ys, range 21-29) on
separate days at least ten days apart, underwent ultrasonographic measurement
of gastric and gallbladder emptying time after a GCM and a GFM. In 16 HV (11
female, median age 24.53.2 ys, range 21-30) measurement of breath hydrogen
excretion (sampling every 15 min for 7 hours) after a GCM, a GFM and after a
GFM added of powdered gluten was performed in order to evaluate intestinal
fermentation. All the evaluations were performed in a random order, according
to a crossover protocol. Presence and severity of symptoms were monitored
during all the tests with VAS (0-10).
RESULTS: The recognition of GCM and GFM was similar (21/40 versus 23/4,
p NS). After GCM, presence and severity of symptoms was similar than after
GFM. After both meals, the mean parameters of gastric and gallbladder emptying were similar. Hydrogen peak (12.57.3 vs 6.55.1 ppm, p50.01) and cumulative breath excretion (21391720 vs 989680 ppm x min, p50.01) was
significantly higher after GCM than after GFM. Adding gluten powdered to
GFM did not modify intestinal fermentation (peak of breath H2 4.41.8 ppm,
AUC 984342 ppm x min).
CONCLUSION: Gluten doesnt modify gastric and gallbladder kinetics, but
induces differences in the fermentation process at colonic level even if it didnt
increase the symptoms. It is possible that, at least in a subgroup of patient,
alterations of visceral sensitivity may represent a co-factor in the pathophysiology of symptoms after gluten ingestion.
REFERENCES
1. Sapone A, Bai JC, Ciacci C, et al. BMC Med 2012; 7: 13.
2. Anderson IH, Levine AS and Levitt MD. NEJM 1981; 304: 891-892.
Disclosure of Interest: None declared

P1692 FOUR CASES


ENTEROPATHY

OF

SEVERE

OLMESARTAN

SPRUE-LIKE

M. Ble Caso1,*, A. Del Val1, B. Beltran1, A. Valero2, M.D. Higon1, J. Ortuno1,


P. Nos1
1
Gastroenterology, 2Pathology, Hospital la Fe, Valencia, Spain
Contact E-mail Address: delval_ado@gva.es
INTRODUCTION: Olmesartan is an angiotensin-II antagonists use in the treatment of arterial hypertension. In 2012 it was described the first case of spruelike
enteropathy related to this antihypertensive.
AIMS & METHODS: To present 4 cases that are clinical and histological compatible (figure 1) with spruelike enteropathy related to olmesartan. The clinical
characteristics and evolution of patients are summarized in table 1.
RESULTS: The 4 cases presented the clinical features of the entity described as
olmesartan spruelike enteropathy, with chronic diarrhea, associated clinical manifestations, injury to the duodenal mucosa and especially by clinical and histopathologic improvement after the removal of olmesartan.
Clinicians should be aware of olmesartan as a potential drug than can cause
severe chronic diarrhea and severe spruelike enteropathy.
REFERENCES
1. Rubio-Tapia A, Herman ML, Ludvigsson JF, et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc 2012; 87: 732738.
2. Dreifuss SE, Tomizawa Y, Farber, et al. Spruelike enteropathy associated with
olmesartan: an unusual case of severe diarrhea. Case Rep Gastrointest Med 2013;
2013: 618071.
Disclosure of Interest: None declared
P1693 NEGLECTED PREDISPOSING CONDITIONS IN THE CONTEXT
OF BILE ACID DIARRHOEA
N. Mottacki1,*, M. Simren1, K.-A. Ung2, A. Bajor3
1
Dept. of Internal Medicine & Clinical Nutrition, Sahlgrenska Academy, University
of Gothenburg, Gothenburg, 2Department of Gastroenterology, Institute of
Medicine, Karnsjukhuset, Skovde, 3Department of Gastroenterology, Institute of
Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: nima.mottacki@vgregion.se
INTRODUCTION: Bile acid diarrhoea (BAD) associated to diseases other than
those of the ileum is known as BAD type 3. A variety of diseases are known to be
associated with bile acid diarrhoea type 3, though the mechanisms are not always
well understood. There is a degree of awareness of BAD in the context of postcholecystectomy diarrhoea and microscopic colitis, and these predisposing conditions have been included in previous studies. However, where BAD is not
idiopathic, there is less information as to the prevalence of reduced bile acid
turnover rate (as measured by the 75SeHCAT test) in other diseases.
AIMS & METHODS: Our aim was to study a population with BAD, with
special consideration for bile acid turnover rates of those with amyloidosis,
pancreatic disease, upper gastrointestinal (GI) resection (not including the
ileum) and GI radiotherapy. These represent conditions known or suspected to
be associated with BAD, but where the investigation by the 75SeHCAT test is not
commonly considered. Medical records in patients investigated with 75SeHCAT
for chronic diarrhoea at a large tertiary hospital since 1989 were reviewed, and
any patients with the diagnoses above noted. The 75SeHCAT of these patients
was compared to 29 previously published healthy controls, both as a unified
group and as individual diagnostic groups using Mann-Whitney U. 75SeHCAT
retention on day 7 (S7) 5 10% was considered abnormal.
RESULTS: Despite the small number of patients referred with the aforementioned diagnoses, all diagnoses showed significantly lower 75SeHCAT retention
than controls. Median S7 values were significantly lower in all groups other than
amyloidosis. However, the patients with amyloidosis exhibited universally low
retention.

Table to abstract P1692


Table 1 Clinical characteristics and evolution. VA, villous atrophy; CH, crypt hyperplasia; IEL, intraepithelial lymphocytes
Weight Doses Years of Evolution after
Age Sex loss (kg) (mg) treamtent drug withdrawal HLA
78

22

40

Improvement

59

20

40

Improvement

69

15

40

Improvement

53

12

40

1,5

Improvement

Duodenal
histology at
diagnosis

DQ2
Total VA total and IEL
DQ8
DQA1
Total VA, IEl, CH, eosinophilia
DQB1
and lymphoid follicular
hyperplasia
DQA1
Partial VA
DQB1
DQA1
Partial VA, IEL, CH
DQB1

Duodenal histology
after drug
withdrawal

Colon
histology

Partial VA and few IEL

Nonspecific inflammation

Remission of atrophy

Collagenous colitis

Histological improvement

Not performed

Pending outcome

Pending outcome

A597

United European Gastroenterology Journal 2(1S)

Diagnosis
Upper GI surgery
(n 41)
GI radiotherapy
(n 29)
Pancreatic disease
(n 25)
Amyloidosis
(n 6)

Number of
Mannpatients with Median
75SeHCAT 75SeHCAT (10th, Whitney
U
90th percentile)
5 10%

Median age
at investigation RR
(years)
(95% CI)

14

53

17
14
5

15.0*
(3.6, 48.2)
7.0*
(0.1, 30.0)
9.0*
(0.6, 43.8)
1.7
(0.01, n/a)

266
(Z -3.917)**
82.5
(Z -5.258)**
102
(Z -4.520)**
172
(Z 3.722)**

69
54
54

5.0
(1.2-20.1)
8.5
(2.2-33.5)
8.1
(2.0-31.3)
12.1
(3.0-48.2)

CONCLUSION: Patients with amyloidosis, chronic pancreatitis, upper GI surgery and GI radiotherapy showed significantly lower 75SeHCAT retention than
healthy controls. These predisposing conditions remain rare causes of referral for
the 75SeHCAT test, and bile acid diarrhoea may be underdiagnosed in the context of these diseases.
Disclosure of Interest: None declared
P1694 LACTOSE
INTOLERANCE.
URINE
GAXILOSE
TEST,
DIAGNOSTIC PERFORMANCE AND TOLERANCE IN CLINICAL
PRACTICE
P.L. Fernandez Gil1,*, J.A. Gomez Gerique2, B. Castro Senosiain1, M. Rivero
Tirado1, M.J. Garc a Garc a1, S. Llerena Santiago1, P. Hallado Santos1, M.
V. Cena Perez1, M. Lopez Hoyos2, J. Crespo Garc a1
1
GASTROENTEROLOGY AND HEPATOLOGY, 2CLINICAL
BIOCHEMISTRY, MARQUES DE VALDECILLA UNIVERSITY
HOSPITAL. IDIVAL, SANTANDER, Spain
Contact E-mail Address: pedfernandez@humv.es
INTRODUCTION: Recently, a new test has been integrated for the noninvasive
diagnosis of hypolactasia disease. This test analyze urine D-xylose after lactase
cleavage of a lactose analogue 4-galactosylxylose (Gaxilose).
AIMS & METHODS: Evaluate the diagnostic performance of the method compared to the most widely accepted, hydrogen breath test with lactose. Genetic
testing of hypolactasia was also assessed. Determinate the clinical tolerance of
these methods and the patient acceptance.
A prospective study of patients with clinical symptoms suggesting lactose intolerance was performed. Hydrogen breath test was carried out after 50 g of oral
lactose. Malabsorption was considered as an increase of 20 ppm over the basal
level. A Gaxilose test was performed by the measure of five hours urine D-xylose
after 0.45 g of oral Gaxilose. Hypolactasia was considered when the level of Dxylosa was lower than 37.87 mgr. The study was completed with the analysis of
the polymorphism of the gene 13910 (CC associated with hypolactasia).
Furthermore, every patient fulfilled a previously validated symptom score, that
consist of a 5 items-scale from 0 to 10, in relation with milk intake and analyzed
by both diagnostic tests. Finally, each patient chooses their preferred test.
RESULTS: In our study, 31 patients were included (24 women, average age: 34.5
years). Twenty-eight patients who meet all the requirements were analyzed.
According to the hydrogen test, 50% of the patients (14/28) were diagnosed of
malabsorption. The rest of them were negative for the test, five patients were
non-hydrogen producers. A lower percentage of hypolactasia was achieved with
Gaxilose test, 35.7% of the patients (10/28). The same conclusion was obtained
in 22 patients (78.6%) using both tests. Gaxilose test could detect hypolactasia in
one of the five non-hydrogen producer patients and it excluded this possibility in
the other. The results were different in the other five patients (17.9%): two of
them were probably a false positive of the hydrogen test. The other three patients
were false negative of Gaxilose test, with urine D-xylosa level above and close to
the cut-off (39.2-40.2 and 41.9 mg). In our experience the cut-off 41.9 mg
improves the result (100% Sensitivity, 87% Specificity, 87% PPV and 100%
NPV). All the patients who had the 13910 CC genotype, showed malabsorption
in the hydrogen test except one, non-hydrogen producer.
In terms of the clinical expression, every patient had symptoms after drink milk
(average 24 points), 90% while performing the hydrogen test (average 14 points)
and only 33% during Gaxilose test (average 10 points). Gaxilose test was selected
by 89% of patients.
CONCLUSION: Urine Gaxilose test offers an efficient tool for hypolactasia
diagnosis, as well as the hydrogen test. However, this test is inaccurate when
urine xylose level is near over the cut off. In our experience increase the cut-off
would improve the efficacy of the test. Furthermore, the Gaxilose test allows
diagnosis of the non-hydrogen producing patients. It is a well-tolerated test and
the most accepted by the patients.
REFERENCES
Hermida C. J Clin Gastroenterol 2013; 47: 501-508.
Aragon JJ. J Clin Gastroenterol 2014; 48: 29-36.
Disclosure of Interest: None declared

P1695 THE ROLE OF WATCH AND WAIT STRATEGY IN THE


TREATMENT OF INTESTINAL FOLLICULAR LYMPHOMA IN
RITUXIMAB ERA: A RETROSPECTIVE STUDY OF 33 CASES
COMPARED WITH 70 CASES OF NODAL FOLLICULAR
LYMPHOMA
A. Tari1,*, H. Asaoku2, K. Takata3, S. Fujimori4, S. Tanaka5, M. Fujihara6,
T. Koga7, T. Yosino3
1
Department of Internal Medicine, 2Department of Clinical Laboratory, Hiroshima
Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima,
3
Department of Pathology, Okayama University, Okayama, 4Department of
Gastroenterology, Nippon Medical School, Tokyo, 5Department of Endoscopy,
Hiroshima University Hospital, 6Department of Pathology, Hiroshima Red Cross
Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, 7Shin Nippon
Biomedical Laboratories, Ltd., Tokyo, Japan
Contact E-mail Address: 10206regent@gmail.com
INTRODUCTION: The majority of intestinal follicular lymphomas (intestinal
FL) have some distinct clinical features different from those of nodal follicular
lymphomas.
AIMS & METHODS: In this study we compared the clinical course of 33 cases of
FL-GI patients with 70 cases of nodal FL patients both treated by watch and wait
(W&W) strategy in order to evaluate W&W strategy in the era of rituximab being
introduced as a treatment option for intestinal FL. Thirty-three cases of intestinal
FL diagnosed as low-tumour-burden follicular lymphoma (LTB-FL) according to
GELF criteria for LTB, M/F 18/15, age 49-82, clinical stage (CS), Ann Arbor
staging system I: 16, II: 7, IV: 9, WHO grade 1: 32, 2: 1, 3: 0, were followed for over
12 months by W&W, median time period of 46 months. Seventy cases of nodal FL,
M/F 36/34, age 36-92, CS (Ann Arbor) I: 6, II: 10, III: 21, IV: 30, WHO grade 1:
32, 2: 30, 3: 4, followed by watch and wait strategy for median period of 57 months
were compared. The clinical stage at diagnosis was confirmed by blood test, bone
marrow (BM) aspiration, positron emission tomography (PET), contrastenhanced CT scan (from neck to pelvis), esophagogastroduodenoscopy (EGD),
colonoscopy, double balloon enteroscopy. During the period of W&W, EGD and
blood test were performed every four months and PET, colonoscopy and capsule
endoscopy were performed every year.
RESULTS: There was no difference in the age and sex in the patients between
intestinal FL and nodal FL. CS, WHO grade, follicular lymphoma international
prognostic index (FLIPI) grade and the value of sIL-2R were significantly lower in
intestinal FL. The proportion of BM involvement was significantly low in the
patients of intestinal FL. No patient died of disease in intestinal FL while 2
patients of nodal FL died after treatment. The overall survival showed no difference between intestinal FL and nodal FL. The discussion of progression free
survival (PFS) showed significantly better result in intestinal FL compared with
nodal FL. The factors causing the difference in PFS were considered to be BM
involvement, the existence of bulky mass and FLIPI. In all the 28 nodal FL
patients with the progression of the disease, LTB turned into high-tumorburden and they were treated by chemotherapy, rituximab-chemotherapy combinations or peripheral blood stem cell transplantation. Only 6 patients of intestinal
FL showed progression of the disease. Out of these six patients, 2 patients deviated
from the category of LTB-FL and received rituximab-chemotherapy combinations and 4 patients, although the CS progressed (I to II in 3 patients and II to
IV in one), remained in the category of LTB-FL and were followed by W&W.
CONCLUSION: The treatment modality of LTB-FL comprising large proportion of intestinal FL is watch and wait in the era of rituximab as a choice of
treatment.
Disclosure of Interest: None declared
P1696 USEFULNESS OF ULTRASONOGRAPHY FOR DIAGNOSIS OF
SMALL BOWEL TUMORS; A COMPARISON BETWEEN
ULTRASONOGRAPHY AND ENDOSCOPIC MODALITIES
M. Fujita1,*, N. Manabe2, K. Honda3, T. Murao1, M. Ishii1, K.-I. Tarumi1,
T. Akiyama4, A. Shiotani1, J. Hata2, K. Haruma1
1
Gastroenterology, 2Endoscopy and Ultrasonography, 3General Medicine,
4
Pathology, Kawasaki Medical School, Kurashiki, Japan
Contact E-mail Address: minorufu5963@gmai.com
INTRODUCTION: Recently, many papers showed that ultrasonography (US) is
a conventional and non-invasive modality for the examination of abdominal
cavity. The aim of this study was to evaluate the usefulness of US for the detection of small bowel tumors (SBTs).
AIMS & METHODS: The aim of this study was to evaluate the usefulness of US
for the detection of SBTs. Five hundred and fifty eight consecutive patients (295
male, 263 female, mean age 71.1) who underwent capsule endoscopy (CE) and/or
balloon assisted endoscopy (BAE) were enrolled in this study. All patients underwent US prior to CE and BAE. The sensitivity and specificity of US in detecting
SBTs, size of detected SMTs, detection rate of SBTs by US were evaluated.
RESULTS: Ninety three tumors (benign 48, malignant 45) detected by CE and/
or BAE were retrospectively analyzed. The sensitivity and specificity of US in the
detection of SBTs were 50.5% (47/93) and 100% (465/465). Tumor size in
patients with SBTs detected by US (mean 33.2 mm) were significant larger
than those undetected by US (mean 8.7 mm). The ratio of SBTs located in the
ileum was significantly higher in SBTs detected by US (12/17) compared to those
undetected by US (5/17). Body mass index was irrelevant to the detection rate. Of
all patients with SBTs undetected by US, 91.3% (42/46) were benign tumors with
good clinical prognosis.
CONCLUSION: US examination is considered to be a useful modality for
detecting small bowel lesions. We consider that US examination is the first
choice modality for examining SBTs because it is a conventional and non-invasive procedure.

A598
Disclosure of Interest: None declared
P1697 FAMILIAL AND MULTIPLE GASTROINTESTINAL STROMAL
TUMORS WITH FAIR RESPONSE TO HALF DOSE OF IMATINIB
S. Shintani1,*, S. Bamba1, H. Ban2, H. Imaeda1, A. Nishida1, O. Inatomi1,
M. Sasaki3, S. Murata4, S. Hirota5, A. Andoh1
1
Division of Gastroenterology, 2Division of Endoscopy, 3Division of Nutrition,
4
Department of Surgery, Shiga University of Medical Science, Otsu, 5Department
of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan
Contact E-mail Address: sb@belle.shiga-med.ac.jp
INTRODUCTION: GISTs are known as the most common tumor originated
from gastrointestinal (GI) mesenchyme. In 1998, we firstly reported gain-of-function mutations of the c-kit gene in GISTs which appear to originate from interstitial cells of Cajal (ICC)[1]. As we and others have already reported, some
families with multiple GISTs carry a germline gain-of-function mutation of the
c-kit gene. The c-kit gene mutations are reported in approximately 90% of all
sporadic GISTs, and are located most frequently in exon 11. In patients with
familial GISTs, most of the mutations are located in exon 11 as well. We have
experienced a family who has a germline gain-of-function mutation of the c-kit
gene in exon 11 (Del-Val560). Notably, one of the patients has shown fair
response to imatinib. To our knowledge, there are few reports describing the
response to imatinib in familial GISTs. We report here the clinicopathological
features of the patients together with a review of literature.
AIMS & METHODS: A 40-year-old female (case 1) with a history of rheumatoid
arthritis treated with infliximab, complained right lower abdominal dull pain and
underwent contrast enhanced abdominal computed tomography (CT). It
revealed a large mass lesion with the size of 50 x 30 mm at the small intestine.
Single balloon enteroscopy showed a jejunal protruding submucosal tumor with
ulceration on the surface. Partial resection of the jejunum was performed.
Immunohistocheical analysis revealed the tumor was positive for KIT and
CD34 and was diagnosed as GIST. The father of this patient (case 2) had a
previous history of small bowel operation for small bowel perforation due to
mass lesion. He underwent an abdominal CT which revealed multiple mass
lesions at the duodenum and small intestine. EUS-guided fine needle aspiration
(EUS-FNA) biopsy was performed. The tumor showed positivity for KIT and
CD34 and was diagnosed as GIST. To identify germline gain-of-function mutation of the c-kit gene, blood samples were obtained and analyzed for c-kit gene
sequencing.
RESULTS: After obtaining informed consent, blood samples from case 1 and 2
were analyzed. In case 1 and 2, germline c-kit gene mutation was identified in
exon 11, resulting in deletion of codon 560 valine, and they were diagnosed as
familial GIST patients. Imatinib treatment for GISTs was considered in case 2
because of previous history of intestinal perforation. Considering his age, the
dose of imatinib was reduced in half. All GISTs were markedly reduced in size in
one year.
CONCLUSION: Multiple GISTs were more frequently observed in patients with
type 1 neurofibromatosis (NF-1) than in familial GISTs with germline c-kit gene
mutation. Patients who have multiple GISTs without classical symptoms of NF-1
have the possibility of such familial GISTs. Therefore, detailed familial history
should be taken. In patients with sporadic GISTs harboring exon 11 KIT mutations, the partial response rate of imatinib was 83.5%[2]. In our case, half dose of
imatinib was effective. Even in the patients with familial GISTs, imatinib can
become an encouraging therapeutic option.
REFERENCES
[1] Hirota S, et al. Science 1998; 279: 577-580.
[2] Heinrich MC, et al. J Clin Oncol 2003; 21: 4342-4349.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
NUTRITION III POSTER EXHIBITION HALL XL_____________________
P1698 RAPID GASTRIC AND INTESTINAL TRANSIT IS A MAJOR
DETERMINANT OF CHANGES IN BLOOD GLUCOSE,
INTESTINAL HORMONES, GLUCOSE ABSORPTION AND POSTPRANDIAL SYMPTOMS AFTER GASTRIC BYPASS
N.Q. Nguyen1,2,*, T. DEBRECINI2, J. BAMBRICK2, C. RAYNER1,
M. HOROWITZ1
1
MEDICINE, UNIVERSITY OF ADELAIDE, 2GASTROENTEROLOGY,
ROYAL ADELAIDE HOSPITAL, ADELAIDE, Australia
Contact E-mail Address: QUOC. NGUYEN@HEALTH. SA. GOV. AU
INTRODUCTION: Gastric emptying usually regulates the rate of small intestinal (SI) nutrient entry to 1-4 kcal/min. It is hypothesized that Roux-en-Y gastric
bypass (RYGB) augments distal gut hormone release and modifies glycaemia by
uncontrolled transit of liquid nutrients, which should be normalized if nutrient
delivery were controlled.
AIMS & METHODS: To determine the contribution of rapid gastrointestinal
transit of nutrient liquid on blood glucose, incretin hormones, glucose absorption
and gastrointestinal (GI) symptoms after RYGB. 10 RYGB patients were studied twice in random order, separated by at least a week, with either: (i) an oral
glucose drink (50g glucose/ 150ml water with 3g 3-O-methyl-D-glucopyranose (3OMG) and 20MBq 99mTc-sulfur colloid) over 3 min or (ii) the same solution
(without 99mTc-sulfur colloid) infused via an endoscope into the proximal Rouxlimb over 50 min (4kcal/min). 10 healthy control subjects were studied with the
latter solution infused into the duodenum (4kcal/min). GI transit of the glucose
drink was assessed by scintigraphy. On each study, blood glucose, and plasma 3OMG, insulin, glucose-dependent insulinotropic polypeptide (GIP), and

United European Gastroenterology Journal 2(1S)


glucagon-like peptide-1 (GLP-1) concentrations, and GI symptoms, were measured over 270 min.
RESULTS: In RYGB subjects, the glucose drink emptied rapidly into the distal SI
(pouch emptying (PE), t50 31min; caecal arrival time (CAT) 2610min).
CAT, but not PE, was inversely correlated with peak plasma GLP-1 (r -0.73,
p 0.01). Compared to oral glucose, 4kcal/min SI glucose infusion in RYGB
subjects was associated with substantially lower plasma GLP-1, GIP, insulin
and GI symptoms, similar to those observed in healthy subjects. Both plasma 3OMG and blood glucose were higher in RYGB subjects during SI glucose infusion
than after oral glucose, and higher than in healthy subjects. Peak plasma 3-OMG
correlated closely with peak blood glucose (r 0.94, P50.0001) in RYGB subjects
during SI infusion, but not after oral glucose or in healthy subjects.
CONCLUSION: After RYGB, reducing intestinal glucose delivery to 4kcal/min
is associated with higher blood glucose, greater glucose absorption, lower incretin
responses and less GI symptoms, supporting rapid transit contribution to the
exaggerated incretin responses and dumping symptoms.
Disclosure of Interest: None declared
P1699 VEGETAL VERSUS ANIMAL FOOD PROTEINS: A DIFFERENT
IMPACT IN 1-H POST-PRANDIAL IMPEDANCE AND PH
ANALYSIS IN GERD PATIENTS
N.de Bortoli1,*, G. Guidi1, I. Martinucci1, E. Savarino2, A. Stella1, M. Furnari3,
L. Bertani1, R. Franchi1, S. Russo1, M. Bellini1, V. Savarino3, S. Marchi1
1
Gastroenterology Unit, University of Pisa, Pisa, 2Gastroenterology Unit,
University of Padua, Padua, 3Gastroenterology Division, University of Genoa,
Genoa, Italy
Contact E-mail Address: nick.debortoli@gmail.com
INTRODUCTION: Gastroesophageal reflux disease (GERD), affecting up to
20% of the general population in Western countries, develops when the reflux
of gastric contents causes troublesome symptoms and/or complications.
Behaviors changes and lifestyle modifications are considered the first line treatment for GERD with the least possibility of side effects.
Although few data are available on eating habits, in clinical practice different
foods (i.e., chocolate, peppermint, wine, tomato, spicy food, coffee) and, generally, high-fat diet are indicated as triggering reflux symptoms. However, the role
of dietary behavior, mainly in terms of specific dietary components, in influencing GERD clinical manifestations remains controversial.
AIMS & METHODS: By means of impedance and pH monitoring, we aimed to
evaluate the effect of two meals with a bromatological-balanced composition:
one with a prevailing component of animal food protein and the other with
vegetable food protein.
We enrolled 30 consecutive patients with typical reflux symptoms and negative
endoscopy, who had been proposed for esophageal manometry and 24-h impedance and pH monitoring (MII-pH) (OFF-therapy) during their scheduled diagnostic program.
All patients were allocated to receive a scheduled diet with a caloric intake of
about 1200 Kcal, divided into two meals of 600 Kcal: one with a prevailing
component of animal protein and the other with vegetable protein. Breakfast
was free and not considered during the 1-h postprandial analysis.
According to MII-pH analysis, we evaluated total reflux number, acid exposure
time (AET) and symptom-reflux association. Moreover, during the first postprandial hour (both lunch and dinner), we evaluated: total reflux number,
number of acid and weakly-acidic refluxes, AET, presence of symptoms.
A student t-test for paired data was performed and the differences were considered significant when p values were 50.05.
RESULTS: Male/female ratio was 0.5 (10/20). Mean age was 53.412.7 yrs. All
patients had heartburn. Twenty-four hour MII-pH analysis showed that 14/30
patients had pathological AET (non-erosive reflux disease, NERD), and 16/30
had normal AET but positive symptom-reflux association (hypersensitive esophagus, HE). The comparison between the first postprandial hour analysis
showed a higher total reflux number (7.63.9 vs 4.73.1) and acid reflux
number (42.7 vs 1.92.2), and greater AET (33 vs 0.71.3) after the
animal protein meal than after the vegetable protein meal. Moreover, more
symptoms were reported after the animal protein meal (2.31.8 vs 0.80.7)
(p50.05).
CONCLUSION: Vegetable proteins are associated with a lower number of
refluxes, particularly acid refluxes, and thus with a reduced number of symptoms
during the first postprandial hour. This is a pilot study and future investigations
are warranted to confirm these results.
Disclosure of Interest: None declared
P1700 IRON, B12, AND FOLIC ACID. HAVE WE FORGOTTEN ABC?
R. Weisshof1,*, T. Mashiach2, I. Chermesh1
1
Gastroenterology department, 2Quality assurance unit, Rambam Health Care
Campus, Haifa, Israel
Contact E-mail Address: r_weisshof@rambam.health.gov.il
INTRODUCTION: Micronutrient deficiency including B12, Folic Acid (FA)
and Iron (Fe) are frequent in Inflammatory Bowel Diseases (IBD). Laboratory
manifestations of these deficiencies are evident on blood count. B12 and/or FA
may present as macrocytosis, and Fe as microcytosis. Combined deficiencies can
present as normo/macro or micro-cytosis with a large Red Cell Distribution
Width (RDW). These laboratory abnormalities should lead to investigation of
these deficiencies.
AIMS & METHODS: The aim of this study is to check the awareness for
investigation of these deficiencies.
Data regarding all IBD patients hospitalized for exacerbation during 2010-3.2014
with mean corpuscular volume (MCV)  75 fL; MCV  100 fL; RDW  17%

A599

United European Gastroenterology Journal 2(1S)


was retrieved from the electronic files. Deficiencies were defined in accordance to
our local laboratory values.
RESULTS: Three hundred and seventy-three patients; 46% males; age 38.9/17.7 years. Relevant abnormal laboratory results were found in 90 (24%)
patients. 28 and 22 of 56 patients with low MCV had high and normal RDW
respectively. Four and three of ten patients with high MCV had normal and high
RDW respectively. 41/56, 4/7 and 11/27 of patients with laboratory findings
mandating investigation for Fe, B12 and Folic acid, and combined deficiencies
according to the above criteria had complete evaluation. A stratified tendency
towards higher awareness for investigation was noted as highest for Fe, and
lowest for combined deficiencies (p NS). 55/59; 2/7 of patients who underwent
investigation for Fe and B12 and FA, were found to be deficient. Almost 40%
did not undergo full evaluation. 86% of investigated patients were found to be
deficient. 56% of patients diagnosed with Fe deficiency were prescribed
treatment.
CONCLUSION: Deficiency of Fe and/or B12 and/or FA is suggested in almost a
quarter of hospitalized IBD patients, but is far too often overlooked. Untreated
deficiencies can cause significant morbidity. Measures to increase awareness are
needed.
Disclosure of Interest: None declared
P1701 DIETARY
MANIPULATION
OF
GASTROINTESTINAL
FUNCTION CAN MODIFY POSTPRANDIAL ENDOTHELIAL
DYSFUNCTION IN HEALTHY HUMANS
S.S. Thazhath1,2,*, T. Wu1,2, M. Bound1,2, H. Checklin1,2, K. Jones1,2,
S. Willoughby1,3, M. Horowitz1,2, C. Rayner1,2
1
Discipline of Medicine, 2Centre of Research Excellence (CRE) in Translating
Nutritional Science to Good Health., 3Cardiac Research Centre, Royal Adelaide
Hospital, University of Adelaide, Adelaide, Australia
Contact E-mail Address: chris.rayner@adelaide.edu.au
INTRODUCTION: Endothelial function, measured by flow-mediated dilatation
(FMD), predicts cardiovascular events, and is known to be impaired after meals.
The rate of gastric emptying and nutrient delivery to the small intestine has a
substantial influence on postprandial glycaemic excursions in health and type 2
diabetes, but its impact on endothelial function is unclear.
AIMS & METHODS: Our aim was to evaluate the effects of dietary modifications designed to slow gastric emptying and/or small intestinal nutrient exposure
on postprandial endothelial function in healthy humans.12 healthy subjects (6
male, 6 female: 33  5.6 years) were studied on 3 occasions each, in a randomised, crossover design. After an overnight fast, subjects consumed a mashed
potato meal (meal 1) or the same meal mixed with 9 g guar (meal 2) within 10
min, or the mashed potato meal divided into 12 equal portions over 60 min (meal
3), each labelled with 13C-octanoic acid. Brachial artery FMD was measured
every 30 min for 120 min. Blood glucose and serum insulin concentrations,
and gastric emptying (breath test), were evaluated for 240 min. Data are
means  SE.
RESULTS: Addition of guar to the meal (meal 2 vs meal 1) slowed gastric
emptying (half-emptying time 285  27 vs. 208  15 min, p 50.05), lowered postprandial glycaemia and insulin (P50.001 for each), and was associated with a
delayed but sustained suppression of FMD (P 5 0.005). With meal 3, the
glycaemic excursion was modestly suppressed (P50.001), but the insulin
response was more marked after the first 30 min (P50.001) compared with
meal 1, while the reduction in FMD was markedly attenuated (P50.05). The
magnitude of reduction in FMD at t 30 min was inversely related to the cumulative 13CO2:12CO2 ratio (r -0.53 P 5 0.01), suggesting a relationship to small
intestinal nutrient delivery, but FMD did not correlate with postprandial
glycaemia.
CONCLUSION: These observations indicate that gastrointestinal function can
be manipulated by dietary means to regulate postprandial endothelial function.
The underlying physiology potentially reflects interplay of multiple factors
including gastric volume, rate of small intestinal nutrient exposure, and insulin
secretion. Further studies are warranted to develop therapeutic strategies to
reduce postprandial endothelial dysfunction in high-risk populations (eg. type
2 diabetes).
Disclosure of Interest: None declared
P1702 THE EFFECT OF CONSUMING SMALL VOLUMES OF BEER ON
GASTRIC MOTILITY AND SMALL INTESTINAL FUNCTION AND
THE INVOLVEMENT OF GENE POLYMORPHISMS
T. Shibata1,*, I. Hirata1, H. Yamashita1, M. Nakao2, T. Omori1, Y. Jodai1,
T. Kawamura3, Y. Ichikawa1, M. Okubo1, T. Ishizuka1, T. Tahara1,
Y. Nakagawa1, M. Nagasaka1, N. Ohmiya1
1
Gastroenterology, FUJITA HEALTH UNIVERSITY, Toyoake, 2College of
Pharmacy, Kinjo Gakuin University, Nagoya, 3College of Pharmacy, FUJITA
HEALTH UNIVERSITY, Toyoake, Japan
Contact E-mail Address: shibat03@fujita-hu.ac.jp
INTRODUCTION: The effects of alcoholic beverages such as small amount of
wine have been proposed for keeping healthy conditions.
AIMS & METHODS: The aim of this study was to investigate the effect of
consuming small amounts of beer or a non-alcoholic beer taste beverage (nonbeer) on internal organ functions, including gastric motility.
The subjects included 20 male healthy volunteers. All subjects were questioned
regarding their alcohol consumption status. Blood was collected for DNA extraction prior to the test, and the genetic polymorphisms in ADH1B (rs1229984,
Arg47His) and ALDH2 (rs671 Glu487Lys) was analyzed using the TaqMan
assay method. The subjects consumed 150 ml of beer (5.0 % v/v contain ethanol)
or non-beer once per week, followed by the ingestion of 200 ml of the test

nutrient containing 13C-acetate 15 min later, after which the subjects exhalations were collected in a breathing bag at 0, 5, 10, 15, 20, 30, 40, 50, 60, 90, and
120 min. The concentration peak of 13C was measured as Tmax. The volunteers
was measured their body weight, height, body mass index (BMI), body surface
area (BSA), basal metabolic rate. Diamine oxidase activity (DAO) for the marker
of small intestinal function activity was measured in a fasting blood sample
collected the day after the test. Statistical analyses were performed with
Wilcoxon signed-rank test, and F-test.
RESULTS: Gastric motility was significantly slower in the group that consumed
a small amount of beer (Tmax 49.0 vs. 38.3, respectively, p 0.00137). Similar
results were found in the ADH1B *2/*2, ALDH2 *1/*2, and daily beer consumption groups. BMI, BSA were not related with gastric empting time. DAO values
were significantly variable in beer drinking group compared with non-alcoholic
beer drinking group (P 50.0001).
CONCLUSION: The consumption of even a small amount of beer affects gastric
motility and small intestinal function. And the polymorphisms in alcohol metabolism-related enzyme-encoding genes are related to gastric motility and small
intestinal function.
Disclosure of Interest: None declared
P1703 THE
ROLE
OF
PROPHYLACTIC
PERCUTANEOUS
ENDOSCOPIC GASTROSTOMY TUBE PLACEMENT IN PATIENTS
WITH HEAD-AND-NECK CANCER TREATED WITH DEFINITIVE
CHEMORADIATION THERAPY
R. V. Rodrigues1,*, S. Faias1, J. Moleiro1, M. Serrano1, M. Femenia1,
S. Severiano1, V. Machado1, A. Dias-Pereira1
1
Gastroenterology, Instituto Portugues de Oncologia de Lisboa, Franscisco Gentil,
Lisboa, Portugal
INTRODUCTION: Head-and-neck cancer (HNC) patients have a high-risk of
malnutrition and swallowing dysfunction, particularly during chemoradiation
therapy (CRT) that justifies prophylactic percutaneous endoscopic gastrostomy
(PEG) placement for nutritional support.
AIMS & METHODS: Evaluate the utility, duration of use and nutritional outcome of prophylactic PEG tube placement in patients with HNC undergoing
definitive CRT, with a follow-up longer than 1 year.
Prospective analysis of consecutive patients with HNC refered for prophylactic
PEG placement in a 6-month period, between July/2012-December/2012, in a
single center. Demographic data, tumor location and stage, body mass index
(BMI), duration of PEG usage (exclusive and complementary) and weight evaluation before, during and after treatment were assessed.
RESULTS: PEGs were placed in 47 patients with HNC (41M/6W), mean
age 58 year old (40-76). TNM: T1/2 11, T3/4 36 N0/1 20, N2/3 27.
BMI 24kg/m2 (15-33). Of the 47 PEGs placed, only 2 were not used. Average
length of PEG usage: 7 months (0.1-20 months). After one-year of follow-up, of
the 45 patients who used PEG: 27 were in remission, 3 had persistent disease, 15
died (13 of disease progression; 2 of respiratory infection). Of the 27 in remission:
22 removed PEG on average after 7 months (3-15) and 5 still use PEG on average
after 17 months (14-20). Of the 15 deceased patients only 2 removed PEG.
Average length of exclusive use of PEG: 3 months (0-18). Use of PEG (exclusive/partial/null): during treatment (15/29/2); after treatment (6/26/9); six months
after treatment (7/5/23). Mean weight (before/during/after treatment): 65/62/
60Kg. Weight reduction occurred in 31 patients during treatment and in 24
after treatment even using PEG for nutritional support.
CONCLUSION: Enteral nutritional support is essential in patients with HNC
during and after treatment with definitive CRT. Prophylactic PEG placement
allowed enteral intake but did not prevent weight loss. Almost all patients
required PEG not only during but also after treatment. One fifth of the patients
in remission required long-term PEG usage for nutritional support.
Disclosure of Interest: None declared
P1704 TRANSNASAL
PERCUTANEOUS
ENDOSCOPIC
GASTROSTOMY (TN-PEG) IN HEAD AND NECK CANCER
PATIENTS: COMBINED APROACH WITH GASTROENTEROLOGY
AND PNEUMOLOGY
S. Faias1,*, D. Costa2, J. Dion sio2, P. Mota2, I. Rosa1, J. Pereira Silva1,
S. Ferreira1, S. Mao Ferro1, A. Dias Pereira1
1
Gastroenterology, 2Pneumology, INSTITUTO PORTUGUES DE
ONCOLOGIA DE LISBOA, Lisboa, Portugal
Contact E-mail Address: sandrarfaias@hotmail.com
INTRODUCTION: Head and neck cancer patients (HNCP) are prone to malnutrition due to malignancy and side efects of treatment. The placement of a
percutaneous endoscopic gastrostomy (PEG) is necessary for most of these
patients. In some situations, oropharyngeal obstruction or trismus preclude a
transoral aproach and a transnasal (TN) route with a thin scope is the available
option. Adaptation of a bronchofiberoscope for PEG placement in this context
has been previously described.
AIMS & METHODS: Retrospective analysis of all TN-PEG tubes placed in
HNCP in a single institution, over a 5-year period, using the pull method, in
a combined aproach by a gastroenterologist in the abdominal side and a pneumologist in the head side, employing an adapted bronchofiberscope.
Demography, indication (prophylatic versus palliative), TN-PEG procedure outcome, complications and treatment, and overall survival were reviewed.
RESULTS: Between 2009-201, 23/649 (3,5%) consecutive HNCP patients
referred for PEG placement, underwent a TN-PEG procedure. TN-PEGs were
successfully placed in 22/23 patients, 17 men and 6 women, with a mean age of 56
years old (26-74) and a mean BMI 20 (15-27). Only one TN-PEG technical
failure due to missing transillumination. Palliative TN-PEGs in 14/23 and

A600
prophylatic in 9/23 patients. TN-PEG route due to trismus (22/23) and oropharyngeal obstruction (1/23), in patients with tumors of oropharynx (8), oral cavity
(7), tongue (5) e maxillary sinus (3). TN-PEG was the only way of nutrition in the
22 patients for a mean time of 242 days (31-1115). On follow-up, 15 patients died
of disease progression, 2 died of other causes and 5 are alive in remission. None
of the patients removed TN-PEG. The 5 patients in remission were using TNPEG for exclusive enteral nutrition for a mean time of 378 days (110-730). Minor
complications ocurred in 8/22: 1 burried bumper syndrome; 1 PEG extrusion;
and 6 infections, 3 early (5 7 days after TN-PEG placement) and 5 late (47
days after TN-PEG placement). Neither immediate, major complications ocurred
nor mortality associated with the procedure.
CONCLUSION: Combined TN-PEG placement by a Gastroenterologist and a
Pneumologist using an adapted bronchofiberoscope is a safe and useful option
for HNCP in witch transoral PEG placement is not possible.
REFERENCES
Adaptation of a bronchofiberoscope for percutaneous endoscopic gastrostomy.
GI Endosc 1986; 32: 245.
Disclosure of Interest: None declared
P1705 HEPATOPATHY IN CHRONIC INTESTINAL FAILURE AND
PARENTERAL NUTRITION: OUTCOME AND PROGNOSTIC
FACTORS
T. Krafft1,*, R. Muckelbauer2, U. Gerlach3, M. Karber1, K.H. Weylandt1,
B. Wiedenmann1, P. Neuhaus3, J. Muller-Nordhorn2, A. Pascher3, U.-F. Pape1
1
Hepatology and Gastroenterology, Campus Mitte & Virchow Klinik, 2Berlin
School of Public Health, 3General, Visceral and Transplantation Surgery,
CHARITE, UNIVERSITY MEDICINE BERLIN, Berlin, Germany
Contact E-mail Address: ulrich-frank.pape@charite.de
INTRODUCTION: Chronic intestinal failure (CIF), mostly caused by short
bowel syndrome (SBS), frequently - through malabsorption - leads to malnutrition which requires parenteral nutrition (PN). PN, particularly long-term PN, is
frequently complicated by a form of hepatopathy (intestinal failure associated
liver disease, IFALD), which is not well understood in pathogenesis, diagnosis
and consequences for CIF-patient-management.
AIMS & METHODS: The incidence, severity and outcome of IFALD were
studied in a retrospective fashion in a cohort of 142 patients with CIF from an
interdisciplinary team at an acedemic referral center. Statistical analysis was
performed using SPSS 19.0.
RESULTS: 142 patients from 2004 - 2013 with CIF due to SBS were analyzed; 88
(62%) of them had a non-malignant cause of CIF due to venous (11%) or arterial
(28%) mesenteric ischemia, Crohns disease (14%), adhesions or volvlus (23%),
radiation enteritis (2%) or other causes. 80 (91%) patients of non-malignant CIF
required PN. 52% had a type I (end-jejunostomy), 24% a type II (jejunocolostomy) and 24% a type III (ileocolostomy) SBS-anatomy. Elevated liver
enzymes were detected in all patients during the initial 24 months (hypersecretive
and adaptive period) of SBS and in 90% beyond 24 months (during stabilization
period). After stabilization period was reached, an elevation of ASAT, ALAT
and total bilirubin (but not AP or GGT) indicated a significantly worse prognosis
by Cox regression analysis. A combined score considering a more than 2-fold
elevation of at least two of these 3 parameters indicated a statistically worse longterm outcome as indicated by decreases overall survival by Kaplan-Meier analysis (p50.001); this was idependent from other statistically significant prognostic factors such as type of SBS or presence and number of catheter-related blood
stream infections.
CONCLUSION: In CIF-patients IFALD as defined by elevated liver enzymes
ASAT, ALAT and elevated total bilirubin is highly prevalent even after intestinal
stabilization has been achieved independently from type of SBS and other complications. A simple assessment score based on these lab values may indicate
poorer long-term outcome and should thus direct medical and surgical CIFand PN-management.
Disclosure of Interest: None declared
P1706 A
MULTICENTRE,
RANDOMISED
CLINICAL
TRIAL
COMPARING OUTCOMES OF GASTROSTOMY TUBES PLACED
USING THE MIC INTRODUCER KIT OR THE TRADITIONAL
PERCUTANEOUS ENDOSCOPIC GASTROSTOMY PUSH/PULL
TECHNIQUE
V. Iori1,*, C. Guatti Zuliani2, V.G. Mirante3, D. Vasta4, G. Iori1, L. Casoni5,
A. Mazzocchi6, L. Rossi6, R. Conigliaro3, R. Sacchero7, R. Sassatelli1,
L. Camellini1
1
Gastroenterology and Endoscopy Unit, Santa Maria Hospital, Reggio Emilia,
2
Gastroenterology and Endoscopy Unit, Endoscopy Unit AUSL, Reggio Emilia,
3
Gastroenterology and Endoscopy Unit, S. Agostino-Estense Hospital, Modena,
4
Pharmaceutical Department, AUSL, 5Stoma center, Santa Maria Hospital,
Reggio Emilia, 6Nutritional Team, AUSL, 7Endoscopy Unit AUSL, reggio emilia,
Italy
Contact E-mail Address: iori.veronica@asmn.re.it
INTRODUCTION: Different techniques for direct insertion of a gastric feeding
tube (g-tube), are reported. Advantages are:easy and safe positioning in upper
tract stenosis;reduced incidence of peristomal infections;possibility to place, as
first choice, a balloon type g-tube, which is easy to be changed at bed-side.
AIMS & METHODS: To compare the push/pull endoscopic method (PEG) to
the MIC introducer kit (KIT; Kimberly-Clark Corporation, Roswell, GA, USA)
for placing g-tubes. From September 2010 to April 2013,206 consecutive patients
(age:18-85) without upper tract stenosis randomly received a 20 French g-tube by
push/pull PEG method (106), or by direct insertion using the KIT (100). Primary
enpoints were complication rates during tube placement and at 30-days and Jain

United European Gastroenterology Journal 2(1S)


score-based1 peristomal infection severity. Secondary endpoints were time necessary for the placement, longevity of the g-tube until first change and the need of
endoscopic substitution. Patients were planned to be followed for 13 months.
Data were analysed using the Mann-Whitney test, while frequencies were analysed by the Chi-squared test with Yates correction or Fisher exact test, when
appropriate. Significant differences between means were indicated by p0.05.
RESULTS: Placement was successful in 106/106 PEG and in 99/100 KIT
patients. Complication rates were not significantly different in the two arms.
Major complications were 2 fistulas and 1 death in PEG,1 respiratory arrest in
KIT. Minor complications were only in KIT patients (2 superficial lesion of
gastric mucosa;2 pneumoperitoneum;1 deformation of dilator device).
Complications at 30-days included infection (4 cases in both groups), death
(PEG:10;KIT:11) minor bleeding (PEG:2;KIT:1), leakage (PEG:1), and ab-ingestis pneumonia (KIT:1). Peristomal infection severity scores were similar at 30days (0.28 vs 0.31). G-tube substitutions occurred in 62% and 95% (p50.01) of
PEG and KIT patients, with a greater incidence of these procedures occurring in
endoscopy unit for PEG (58% vs. KIT:22%; p50.01). The mean time required
to place tube was shorter by PEG (10.4  4.5 min vs. KIT: 14.8  5.2; p50.001).
Time prior to first change exceeded 90-days (PEG:230 vs KIT:124).
CONCLUSION: These results suggest that KIT is a feasible and safe alternative
to PEG. Furthermore, patients with g-tubes placed using the KIT were significantly less likely to require a second endoscopic procedure to have their g-tubes
removed, whith a reduction of endoscopic suite costs.
REFERENCES
Jain NK, et al. Ann Intern Med 1987; 107: 824-828.
Disclosure of Interest: V. Iori Other: The KITs were obtained free of charge from
Innova Medica Ltd. Innova Medica is the official Italian importer., C. Guatti
Zuliani Other: The KITs were obtained free of charge from Innova Medica Ltd.
Innova Medica is the official Italian importer., V. Mirante Other: The KITs were
obtained free of charge from Innova Medica Ltd. Innova Medica is the official
Italian importer., D. Vasta: None declared, G. Iori: None declared, L. Casoni:
None declared, A. Mazzocchi: None declared, L. Rossi: None declared, R.
Conigliaro: None declared, R. Sacchero: None declared, R. Sassatelli: None
declared, L. Camellini: None declared
P1707 ARE NUTRITION ASSESSMENT TOOLS OF ANY USE IN THE
MANAGEMENT OF THE SURGICAL PATIENT?
W. Arshad1,*, D. Longbotham1, J. Sarveswaran1, G. Kaur1
1
Surgery, SCUNTHORPE GENERAL HOSPITAL, Scunthorpe, United
Kingdom
Contact E-mail Address: geeta.kaur@email.com
INTRODUCTION: Nutrition is an important biological factor in the holistic
approach towards management of the surgical patient. The MUST (Malnutrition
Universal Scoring Tool) is a tool used in many studies to assess the nutritional
status of patients. In 2012, we performed an audit of the MUST scoring tool,
comparing it with with a trust devised tool. In 2013, we repeated the audit to
complete the audit cycle, following recommendations implemented from the previous audit.
AIMS & METHODS: Aims: We aimed to assess the accuracy of these assessment
tools, and the value of the concerted education of our nursing staff regarding the
use of these tools.
Methods: Data was prospectively collected over a 2 month period, including both
elective and acute admissions to surgical wards. The same audit tool was used
this year, as was used in the previous year, to allow for comparative analysis.
Education was given to the nurses on how best to implement the MUST tool.
RESULTS: The 2013 cohort included 140 patients (32 elective and 108 acute
admissions) as compared with 120 patients in the 2012 cohort (24 elective and 96
acute admissions). In 2012 86% of patients had nutrition assessment completed
on admission, compared to 94% in 2013. 52% of patients assessed by MUST
were deemed to have low, 12% had moderate and 36% had high risk of malnutrition in 2012, compared to 54% low, 13% moderate and 40% high respectively in 2013. 56% of these were reviewed by dietitian/ had appropriate
nutritional support started by their medical team in 2012, compared to 76% in
2013. Higher re-admittance rates were also reflected in different MUST score
groups. Low risk group readmission rates were 7.9% (8.6% in 2013), moderate
33.3% (33.3% in 2013) and 14.2% (14.8% in 2013) in high risk MUST groups.
Wound infections occurred in 8.6% of patients in 2012, and 7.2% of patients in
2013.
CONCLUSION: Conclusions: Both years audits reveals a direct correlation
between MUST scores and the length of stay in hospital, readmission rate, risk
of wound infection and risk of death. Promisingly, after the education of nursing
staff on the wards, there appears to have been an increase in the number of
surgical patients receiving adequate care in regards to nutrition/ nutrition
assessment.
Disclosure of Interest: None declared
P1708 SAFETY OF UNSEDATED PEG PLACEMENT
TRANSORAL ULTRATHIN ENDOSCOPY IN PATIENTS WITH
AMYOTROPHIC LATERAL SCLEROSIS

USING

Y. Sato1,*, Y. Nishigaki1
1
Gastroenterology, Niigata University Graduate School of Medical and Dental
Sciences, Niigata, Japan
Contact E-mail Address: yuichi@med.niigata-u.ac.jp
INTRODUCTION: In patients with amyotrophic lateral sclerosis (ALS), percutaneous endoscopic gastrostomy (PEG) placement under sedition often causes
apnea or hypoventilation. To prevent complications of sedation, unsedated
transnasal PEG placement using small diameter endoscopy (SDE) has been

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United European Gastroenterology Journal 2(1S)


performed. However, even with SDE, transnasal intubation sometimes fails due
to the impossibility of crossing the nasal cavity or results in epistaxis and/or
nasomucosal injury. Moreover, a recent study revealed that transoral insertion
using SDE is superior to transnasal insertion using SDE in endoscopy
procedures.
AIMS & METHODS: The aim of the present study was to assess whether
unsedated PEG placement in ALS patients using ultrathin endoscopy (UTE)
via the transoral route can improve safety. Between 2003 and 2012, PEG placement was identified and reviewed in 42 patients with ALS. PEG was performed in
11 patients using transoral UTE without sedation (UTE group), 17 patients using
conventional normal-diameter esophagogastroduodenoscopy (C-EGD) without
sedation (unsedated C-EGD group) and 14 patients using C-EGD with sedation
(sedated C-EGD group). We compared the clinical features, cardiopulmonary
data before and during PEG placement, and complications related to PEG placement among the three groups.
RESULTS: There were no significant differences in age, M/F ratio, forced vital
capacity (FVC), blood pressure, oxygen saturation before and during PEG or
major complications among the three groups. With regard to complications, no
major complications such as adverse events requiring surgery, permanent adverse
sequelae or death, were observed in any patient. However, among the three
groups, there were differences in the incidence of minor complications, including
apnea and/or hypoventilation, aspiration pneumonia and peristomal infection.
No minor complications were observed in the UTE group, whereas, aspiration
pneumonia was observed in the unsedated C-EGD group (3/17, 7.6%) and apnea
and/or hypoventilation were observed in the sedated C-EGD group (3/14,
21.4%). The proportion of patients whose BP was elevated by more than 20%
compared with that observed before the PEG procedure was 7.1% (1/14) in the
UTE group, 23.5% (4/17) in the unsedated C-EGD group and 14.2% (2/14) in
the sedated C-EGD group. In the UTE group, PEG placement was successfully
performed in all patients, and no patients required sedation during the procedure.
However, among the three patients complicated with apnea and/or hypoventilation due to sedation in the sedated C-EGD group, PEG placement could not be
successfully performed due to apnea and/or hypoventilation in two patients.
CONCLUSION: Unsedated PEG placement using transoral UTE in ALS
patients is a safe method.
Disclosure of Interest: None declared

WEDNESDAY, OCTOBER 22, 2014


9:0014:00
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE
III POSTER EXHIBITION HALL XL_____________________
P1709 COLITIS-ASSOCIATED COLORECTAL CANCER INDUCES
PHENOTYPE INSTABILITY AND EFFECTOR FUNCTIONS IN
TUMOR-INFILTRATING REGULATORY T CELLS
A. Rizzo1,*, V. De Mare1, C. Stolfi1, F. Pallone1, G. Monteleone1, M.C. Fantini1
1
System Medicine, University of Rome "Tor Vergata", Rome, Italy
Contact E-mail Address: m.fantini@med.uniroma2.it
INTRODUCTION: Regulatory T cells are critical to maintain the immune
system homeostasis in the gut and Treg malfunctioning is associated with chronic
colitis. At the same time, accumulating evidence indicates that proinflammatory
stimuli can downregulate the Treg lineage commitment transcription FoxP3
leading to Treg phenotype instability. Although Tregs have been shown to accumulate in the stroma of sporadic colorectal cancers suppressing the intratumoral
immune response, the role and functional stability of Tregs in colitis associated
colorectal cancer is unknown.
AIMS & METHODS: Aim of the study was to characterize Treg phenotype and
stability in a model of colitis-associated colorectal cancer. To address this issue a
Tregs fate mapping reporter mouse was generated where Tregs and ex-Tregs,
which have lost FoxP3 expression are identified by the emission of specific combinations of green and red fluorescences. Treg fate mapping reporter mice underwent the Azoxymethane/Dextrane Sulphate Sodium model of colitis-associated
colorectal cancer. At the end of the experiment, the expression of Th1- and Th17specific markers (i.e. Tbet and IFN-gamma for Th1 and RORgamma-t and
IL17A for Th17) were analyzed by flow cytometry in Treg and ex Treg cells
isolated from tumors and tumor-surrounding lamina propria.
RESULTS: The frequency of both Tregs but not ex-Tregs among CD4 T
cells isolated from the lamina propria of treated mice was higher as compared to
untreated mice (45% vs 28% Tregs treated vs untreated respectively) while the
absolute number of both Tregs and ex-Tregs was increased in treated as compared to untreated mice. In inflammatory conditions, in the peritumoral areas,
both Tregs and ex-Tregs upregulated the transcription factors Tbet and
RORgamma-t and expressed the proinflammatory cytokines IL17A and IFNgamma. However in the tumor Tregs and ex-Tregs were characterized by the
expression of Th17- but not Th1-related markers.
CONCLUSION: Tregs and ex-Tregs characterized by the expression of Th1 and
Th17 effector molecules represent a sizable fraction of CD4 T cells accumulating in the peritumoral lamina propria and in the tumor stroma. The exclusive
expression of Th17 markers by Tregs and ex-Tregs infiltrating the tumor stroma
suggest that Tregs phenotypic plasticity might enhance rather than suppress the
intratumoral Th17 immune response.
Disclosure of Interest: None declared

P1710 ACRYLAMIDE,
A
DIETARY
GLYCATED
IMPLICATED IN INTESTINAL INFLAMMATION

PRODUCT

C. Vignal1,*, N. Grossin2, M. Djouina1, P. Desreumaux1,3, E. Boulanger2,


M. Body-Malapel1
1
inserm/Lille 2 university unit 995, 2EA2693, lille 2 university, 3Gastroenterology,
CHRU Lille, Lille, France
Contact E-mail Address: cecile.vignal@univ-lille2.fr
INTRODUCTION: A strong body of evidence supports the role of environmental influence in the development of Inflammatory Bowel Diseases (IBD). The
increase in incidence of IBD during the 50s in Europe and United States and
since about 10 years in developing countries parallel the modification of alimentary habits and in particular, the consumption of refined food.
Acrylamide is a chemical compound considered a potential carcinogen in
humans. Acrylamide is produced naturally in food as a result of cooking
starch rich food at high temperature (4120 C, baking, frying or grilling).
High amounts of acrylamide are present in Western diet (in potato chips,
pizza, French fries or pastries) with unknown effects on intestinal inflammation.
AIMS & METHODS: The aim of our study was to determine the effects of
acrylamide on intestinal homeostasis in mice. C57bl6 mice were given increasing
doses of acrylamide in their drinking water (25; 50 et 100mg/kg of body weight/
day) for 9 months, control mice receiving water only. Colon was then harvested
and assessed for macroscopic, structural and histological modifications. Markers
of intestinal barrier, inflammatory and immune responses were also quantified.
RESULTS: No macroscopic lesions were observed in mice receiving acrylamide.
However, the 3 doses of acrylamide induced structural abnormalities of the colon
with a modification of the intestinal permeability compared to control mice.
Crypts depth (148mm for control mice, 215mm for 25mg of acrylamide, and
211mm for 50mg, p 0.0317), number of goblet cells per crypt (respectively x3
for 25mg and 50mg, and x2 for 100mg, p 0.0195) and Muc 2 expression (75%
for 100mg, p 0 .04) were higher in mice receiving acrylamide. Acrylamide also
induced expression of inflammatory markers; a significant increase of myeloperoxidase activity (48%, p 0.03 for 50mg, and 50%, p 0.04 for 100mg), and
of oxidative stress (103% for 50mg, p 0.03 and 52% for 100mg, p 0.009 for
iNOS expression, and 32% for 25mg, p 0.04 and 37% for 100mg, p 0.009
for NADPH oxydase expression) were observed in mice receiving acrylamide
compared to control mice. The immune response was also disturbed; with an
increased expression of Th1 cytokines (57% for 50mg, p 0.02, for TNF
expression, and 477%, p 0.009, 443%, p 0.01, and 408%, p 0.009,
for 25mg, 50mg and 100mg of acrylamide respectively for IFNg expression), Th2
cytokines (291%, p 0.02, 81%, p 0.03, and 82%, p 0.03 for 25mg, 50mg
et 100mg respectively for IL-4 expression) and a decreased expression of Th17
cytokines (-24% for 100mg, p 0.02 for IL17f) in mice receiving acrylamide
compared to control mice.
CONCLUSION: At low doses, acrylamide disturbed intestinal homeostasis with
architectural modifications, altered permeability, increased inflammation and
mucosal immune response. More studies are now needed to evaluate the role
of acrylamide in IBD.
Disclosure of Interest: None declared
P1711 LIVING
WITH
CROHNS
DISEASE:
EXPECTATIONS,
EXPERIENCES AND DECISION-MAKING IN RELATION TO BEST
CONVENTIONAL AND AUTOLOGOUS STEM CELL TREATMENTTHE DECIDES STUDY
J. Cooper1,*, I. Blake1
Nottingham University Hospitals, Nottingham, United Kingdom
Contact E-mail Address: joanne.cooper3@nuh.nhs.uk
1

INTRODUCTION: The DECIDES study involved an in-depth qualitative investigation into experiences of living with severe Crohns Disease (CD), exploring
expectations, decision-making and perceived risk within the context of the
Autologous Stem Cell Transplantation International Crohns Disease (ASTIC)
trial. The ASTIC trial examines the role of haematopoietic stem cell treatment
(HSCT) for Crohns sufferers. Although the study examines quality of life and
disease-specific measures of patient response, feedback from participants indicated other important issues impacting on their experiences of CD and specifically on decision-making and experience of trial participation.
AIMS & METHODS: The DECIDES study used semi-structured interviews to
investigate the experiences, expectations, decision-making and perceptions of risk
taking of participants who, a) took part in the ASTIC trial, b) considered participation by did not take part, and c) patients with matched severity of CD.
Research questions investigated the impact of CD on life, attitudes towards
current best conventional treatment, expectations, risk taking, perceived decision
making towards radical treatments, and information needs. Interviews were analysed using thematic analysis informed by a framework analysis approach.
RESULTS: 1. Running out of options and time. The majority of participants
described having exhausted all available treatment options prior to considering
ASTIC, often stating they had nowhere else to go. This decision making process
was driven by a sense of limited time and options, but with the knowledge of
possible randomisation to delayed or early treatment arms.
2. Fertility- Decision-making about fertility emerged as an important and emotive factor to consider for participants. Perceptions varied on how this issue was
initially mentioned in consultations. Regardless, a number of participants
reported that fertility and family planning was an unexpected, unconsidered,
yet important issue to consider during the decision making process.
3. Shared decision-making and control- Participants described the relationship
with their specialist IBD consultant and research nurse as essential factors in
their decision making process, valuing expert opinion and advice. The majority of
participants stated that the recommendation to participate in the trial by their

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United European Gastroenterology Journal 2(1S)

IBD Consultant strongly influenced their decision, in addition to media/internet


resources.
4. Balancing risks and benefits- Perceived benefits of the ASTIC trial such as
buying more time or being a potential lifeline outweighed the risks of the
trial. With the understanding that the treatment procedure was very severe and
there was a realistic risk of death, the risks were negated by the potential
enhancement of their quality of life.
CONCLUSION: This research provides new insights into the decision making
processes of patients with severe Crohns disease faced with potential participation in a trial of a radical treatment option. The research indicates a variety of
external influences and critical moments or touch points in the decision making
journey, providing opportunities for additional support, information and a suite
of decision making support tools.
Disclosure of Interest: None declared
P1712 IMPROVEMENT
OF
ULCERATIVE-COLITIS-ASSOCIATED
MICROBIOTA DIYSBIOSIS AFTER TREATMENT WITH
MESALAZINE-MMX (MEZAVANTTM) USING MUCOSAL F.
PRAUSNITZII/E. COLI INDEX AS A MARKER
J.O. Miquel Cusachs1,2,*, D. Busquets Casals2, M. Serra Page`s3, J. Garcia-Gil4,
X. Aldeguer Mante`2
1
Gastroenterology and endoscopy, Hospital General de Vic, Vic, 2Gastroenterology
and endoscopy, Hospital Josep Trueta de Girona, 3Metabolic disorders, Institut de
Investigacio biomedica de Girona (IdIBGi), 4Biology and microbiology, University
of Girona, Girona, Spain
Contact E-mail Address: uriolmiquel@gmail.com

Methods: The study was performed on 40 Wistar rats. Animals were divided into
4 groups. Group 1 received saline intraperitoneally (1ml/kg), group 2 - received
saline and Melatonin 100mg/kg/day, groups 3 and 4 were given 1% DSS in the
drinking water for 14 days. In group 3 during last seven days of DSS administration rats were receiving saline intraperitoneally. Group 4 during last seven
days of DSS administration were receiving saline intraperitoneally and melatonin
in dose of 100mg/kg/day. Histological changes in all goups were evaluated. Level
of Il-1, Il-6, Il-10, TNF-, paraoxonase (PON-1), reduced glutathione (GSH)
and oxidized glutathione (GSSG) in intestinal homogenate was determined in
enzyme linked immunosorbent (ELISA) assay.
RESULTS: Melatonin administration to rats with DSS-dependent colitis significantly reduced the severity of histopathological inflammation features. The use
of melatonin resulted in a reduction in the level of IL-1 (7.53 in group 1) from
(17.86 pg/mg in the group 3) to the (9.24 pg/mg group 4), IL-6 (8.39 in group 1)
from (16.92 pg/mg in the group 3) to the (8.66 pg/mg in the group 4) and TNF-,
(7.21 in the group 1) from (14.57 pg/mg in the group 3) to the (6.76 pg/mg group
4), and had no significant effect on the level of anti-inflammatory IL-10 (p4
0.05). Experimental colitis resulted in reduced levels of antioxidant agents (GSH
and PON-1), melatonin reversed this adverse event (p 50.05).
CONCLUSION: Melatonin by anti-inflammatory and antioxidant effect reduces
the severity of experimental colitis in rats.
Disclosure of Interest: None declared
P1714 REMISSION IN CROHNS DISEASE AND THE MANAGEMENT
OF RELAPSES: A REVIEW OF REAL WORLD PATIENT CASES
L. Chanroux1,*, J. Casellas1
The Research Partnership, London, United Kingdom
Contact E-mail Address: laurentc@researchpartnership.com
1

INTRODUCTION: Microbiota (MI) in Cohns diseases (CD) and Ulcerative


Colitis (UC) are structurally different from healthy ones. We assume that the
inflammation on colon mucosa may disrupt the normal MI ecosystem. Thus, any
treatment given to curb the inflammation process has to be expressed by a
recovery of the lost healthy equilibrium. In this study, our research group has
developed a bacterial marker to evaluate treatment effectiveness on UC. We
designed a specific index of Fp/Ec (FEI), based on the disappearance of
Faecalobacterium prausnitzi (Fp) and the different abundance of E.coli (Ec). In
previous studies, it has been established that the lower the value the more disturbed is the MI ecosystem.
We designed a study to assess Mesalazine-MMX (MZX) clinical response on
mild/moderate UC and how that correlates on MI dysbiosis changes by examining FEI, previous (T0) and after (T1) treatment (TM).
AIMS & METHODS: We obtained rectal biopsy from mild/moderate UC
patients on MZX (4,8 gr once daily) given with intention to treat and resample them 4 wks after. We included 8 patients in total. Biopsies are obtained
from first 5 cm of rectum by flexible gastroscope with standard procedures.
Inclusion criteria were: Patient 418yo. UC diagnosed histologically, na ve to
treatment, with a mild/moderate flare (Mayo index  5) and histological criteria;
and signed informed consent. We excluded patients with previous antibiotic and/
or any concomitant drugs aimed to IBD TM given in the previous 6 months. All
samples were analyzed using DNA real-time PCR methods.
RESULTS: All patients but one (number 5) in this study showed an improvement on disease activity as measured by Mayo Index. At T0, patients showed an
FEI under 2,6 (previously established cut-off point, COP, for major dysbiosis)
and in T1 the median was 3,150. That increase on value is related to the improvement on MI dysbiosis. In T1, the number of EC was reduced (in average 55%) of
patients. There were no differences in the total number of Fp after TM. MZX is
able to significantly (p 0.035) change the FEI above the COP. The FEI detects,
with 83% of accuracy, the MI dysbiosis improvement. Coefficient of variation
after TM of the FEI is 0.34%.
CONCLUSION: TM on mild/moderate UC flare with MZX contributes to an
improvement on dysbiosis situation as shown by a clear increase in the FEI. FEI
looks as a good marker to measure MI dysbiosis and thus, it is a promising new
tool to assess response to TM on UC. This study has been supported by Shire, Inc.
REFERENCES
1: Mart n R, Chain F, Miquel S, et al. The commensal bacterium
Faecalibacterium prausnitzii is protective in DNBS-induced chronic moderate
and severe colitis models. Inflamm Bowel Dis 2014 Jan 10.
2-. Lopez-Siles M, Mart nez-Medina M, Aldeguer X, et al. Real-time PCR quantification of mucosa-associated Escherichia coli and Faecalibacterium prausnitzii
to support Crohns disease diagnostics. Gastro week 2009 UEGW/WCOG.
Disclosure of Interest: None declared
P1713 USE
OF
MELATONIN
IN
THE
TREATMENT
EXPERIMENTAL DSS-DEPENDENT COLITIS IN RATS
1,*

OF
1

K. Celinski , G. Czechowska , A. Korolczuk , T. Dworzanski , A. Ma dro ,


E. Dworzanska3, P. Konturek4
1
Gastroenterology, 2Pathomorphology, 3Pediatric Neurology, MEDICAL
UNIVERSITY OF LUBLIN, Lublin, Poland, 4Internal Medicine, ThueringenClinic, Saalfeld, Germany
INTRODUCTION: Melatonin is known as a factor regulating daily activity, but
it is also a powerful antioxidant and a substance with an anti-inflammatory
properties. Significant amounts of melatonin is produced in the mucous membrane of the digestive tract and liver. Melatonin has a protective effect on oxidative stress dependent damage of proteins, lipids and DNA. Melatonin reduces
the inflammatory response by blocking the NF-B signal pathway which is
responsible for the expression of proinflammatory cytokines. These mechanisms
are involved in the pathogenesis of ulcerative colitis.
AIMS & METHODS: Evaluation of Melatonin possible influence on severity
and the course of rats large intestine inflammation induced DSS.

INTRODUCTION: Biologic agents have improved the outlook for many


patients with moderate to severe Crohns disease (CD). However, clinical data
suggest that many patients may still not be attaining remission.
AIMS & METHODS: Our aim was to better understand disease remission in CD
by reviewing real-world patient cases and assessing the management of
relapses. We used patient data collected as part of an online treatment survey
conducted among a panel of gastroenterologists between November 2012 and
December 2013 across the five largest EU countries (France, Germany, Italy,
Spain and the UK) and analysed the treatment history of 4284 patients (2879 bio
pts and 1405 pts receiving immunosuppressants). We then analysed the characteristics of 1229 patients who at their most recent visit were not experiencing any
flares in their disease. We also examined the records of 1064 biologic experienced
patients who were currently in remission or had experienced it in the past.
RESULTS: 29% of patients were said to be experiencing no flares in their CD at
the time of their visit, with the highest levels seen in France and Spain where 37%
and 35% of patients were free from flares, respectively. There were no statistically significant differences in the age or gender of these patients compared to all
other patients (pts with an increase, decrease or stabilisation of flares) though
they were more likely to have a CDAI 5 150 (97% vs. 45% for other pts).
Patients in remission were also less likely to have fistulising disease (19% vs. 28%
for all other pts) although the proportion of patients with mucosal lesions
remained similar in all groups (55% - 57%). Patients in remission were less
commonly treated with steroids and biologics although use of the latter stayed
high. 3% of patients received a steroid (22% for other pts) and 60% received a
biologic (70% for other pts). Among current biologic patients, 41% had
experienced remission in the past with an average of 3 episodes and 36% experiencing remission for 4 12 months. At relapse doctors immediately initiated
biologic therapy in 57% of patients and in 71% of cases elected to re-start the
biologic the patient had been receiving prior to remission. There was little correlation between these decisions and the number or duration of remission episodes.
However, 90% of patients who had experienced  3 remissions had undergone 01 surgical interventions for their disease vs. 76% for those who had experienced
 4. 9% of all patients cases reviewed had discontinued biologic therapy and
disease remission was the most common reason for this change (52%, no statistically significant differences between bios). However, while 66% of patients had
been in remission for 4 12 months, 57% had experienced remission before
(average of 3 episodes).
CONCLUSION: Our data show that both the induction and maintenance of
remission are common but also highlight that while patients may see a reduction
in the number of drugs they receive and an improvement in their CDAI and
fistulae, drug-free remission and deep-remission with mucosal healing are not
guaranteed. Additional analysis is required to assess how treatment strategies
may optimise outcomes by maximising the duration of remission and minimising
relapses, delaying or halting the progression of CD to increasing damage and
disability.
Disclosure of Interest: L. Chanroux: None to report, J. Casellas: None declared

A603

United European Gastroenterology Journal 2(1S)


P1715 REDUCED MONOCYTE ACTIVATION AND RECRUITMENT
TWO WEEKS AFTER TREATMENT START REFLECT EARLY
INFLIXIMAB THERAPY RESPONSE IN PATIENTS WITH
ULCERATIVE COLITIS
M.K. Magnusson1,2,*, H. Strid2, S. Isaksson1,2, A. Lasson3, K.-A. Ung4,
A. Bajor2, L. Ohman1,2
1
Dept of Microbiology and Immunology, Inst for Biomedicine, 2Dept of Internal
Medicine and Clinical Nutrition, Inst for Medicine, Gothenburg, 3Dept of Internal
Medicine, Sodra Alvsborg Hospital, Boras, 4Dept of Internal Medicine,
Karnsjukhuset, Skovde, Sweden
Contact E-mail Address: maria.magnusson@microbio.gu.se
INTRODUCTION: The cellular mechanisms leading to infliximab therapy
response in patients with ulcerative colitis (UC) are still incompletely known.
Also, it is difficult to assess early therapy response during treatment.
AIMS & METHODS: The aim was to determine effects of infliximab therapy on
monocytes and monocyte related chemokines in UC patients during their first 4
months of therapy, and to evaluate early immunological effects linked to therapy
response.
Blood, biopsies and stool samples were obtained before treatment (baseline), 2
weeks and 4 months after infliximab therapy start from 42 previously anti-TNF
therapy-na ve UC patients. Therapy response was defined as decreased Mayo
score  3 after 4 months (20 responders and 22 non-responders). The expression
of CD86 and CD14 on monocytes in serum and in lysed biopsies was measured
by FACS and ELISA, respectively. Expression of the chemokines CCL2, CCL3,
CCL4, CX3CL1 and CXCL10 in serum and biopsies was determined by cytokine
bead array. Data are presented as median (range).
RESULTS: At baseline there were no differences in monocyte phenotype, chemokine secretion, CRP levels, fecal calprotectin or Mayo score between therapy
responders and non-responders. However, in therapy responders, infliximab
reduced blood monocyte expression (median fluorescent intensity) of CD86
(2904 (2043-9862) vs. 2826 (1351-5618), p 0.02) and CD14 (4004 (1492-23164)
vs. 3008 (798-9872), p 0.02), 2 weeks after therapy start, relative to baseline. In
contrast, therapy non-responders showed increased levels of CD86 (2628 (14204848) vs. 3828 (1527-7568), p 0.01) and similar levels of CD14 (3518 (115111631) vs. 5312 (3530-17163), p 0.1) at 2 weeks post therapy start, relative to
baseline. In intestinal tissue, CD14 (0.36 ng/ml (0.14-0.57) vs. 0.63 ng/ml (0.540.85), p 0.006) and CD86 (0.43 ng/ml (0.23-0.89) vs. 1.35 ng/ml (1-3.09),
p 0.01) was lower in therapy responders compared to non-responders 4
months after therapy start.
Two weeks after therapy start, serum CCL2 decreased in therapy responders (169
pg/ml (69-663) vs. 132 pg/ml (43-241), p 0.03) but not in non-responders (118
pg/ml (34-637) vs. 133 pg/ml (44-364), p 0.22), relative to baseline. At 4 months
after therapy start, serum CCL2 was still decreased in therapy responders (169
pg/ml (69-663) vs. 126 pg/ml (49-403), p 0.009) but not in non-responders (118
pg/ml (34-637) vs. 128 pg/ml (60-174), p 0.16) relative to baseline. This correlated with lower levels of CCL2 in intestinal tissue in responders as compared to
non-responders after 4 months of treatment (12.6 pg/ml (1.4-56.9) vs. 755 pg/ml
(465-862), p 0.006). Serum CCL3, CCL4 and CX3CL1 were not linked to
therapy response while CXCL10 was only decreased in therapy responders
after 4 months (241 pg/ml (75-552) vs. 157 pg/ml (68-608), p50.05), relative to
non-responders.
CONCLUSION: Infliximab therapy response in UC patients is associated with
reduced monocyte expression of CD86 and CD14 and serum levels of CCL2 two
weeks after therapy start. A similar pattern was observed in intestinal tissue 4
months after therapy start. Thus, reduced monocyte activation and recruitment
two weeks after treatment start may reflect early infliximab therapy response in
UC patients.
Disclosure of Interest: None declared
P1716 THE INTESTINAL ENVIRONMENT OF PATIENTS WITH
ULCERATIVE COLITIS IMPAIRS THE ABILITY OF
MACROPHAGE AND DENDRITIC CELL SUBSETS TO PRODUCE
RETINOIC ACID
M.K. Magnusson1,2,*, S.F. Brynjolfsson1, A. Dige3, L. Ohman1,2, L. Borjesson4,
J. Bengtsson4, J. Agnholt3, H. Sjovall2, M.J. Wick1
1
Dept of Microbiology and Immunology, Inst for Biomedicine, 2Dept of Internal
Medicine and Clinical Nutrition, Inst for Medicine, Gothenburg, Sweden,
3
Department of Medicine V (Hepatology and Gastroenterology), Gastro-Immuno
Research Laboratory (GIRL), Aarhus University Hospital, Aarhus, Denmark,
4
Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
Contact E-mail Address: maria.magnusson@microbio.gu.se
INTRODUCTION: Intestinal dendritic cells (DCs) and macrophages (MQs)
have pivotal roles in intestinal homeostasis, and disruption of this balance can
culminate in ulcerative colitis (UC). Relatively little is known about human DC
and MQ subsets in the intestinal mucosa in health versus disease. Also, not much
is known about retinoic acid, a vitamin A metabolite that can influence the
generation of tolerance, and its role in UC.
AIMS & METHODS: Our aim was to study the population dynamics and
retinoic acid production of DC and MQ subsets in UC patients with active
inflammation and in clinical remission compared to non-inflamed control tissue.
Colonic biopsies and surgical samples were collected from patients with active
UC (inflamed tissue, n 28), UC in remission (non-inflamed tissue, n 6) and
non-inflamed control subjects (non-inflamed tissue, n 28). Blood samples were
collected from UC patients in remission (n 6) and non-inflamed control subjects (n 7). Characterization of DCs and MQs was performed by flow cytometry. Lamina propria DCs were grouped into lin-HLADRCD14-CD1c cells
(CD1cDCs) and lin-HLADRCD14-CD141 cells (CD141DCs) and

studied for their expression of CD103. Lamina propria MQs were grouped
into
lin-HLADRCD14HLADRint
MQs
(DRintMQs)
and
linHLADRCD14HLADRhi MQs (DRhiMQs). Blood monocytes were grouped
into classical (CD14CD16-), intermediate (CD14CD16) and non-classical (CD14CD16) monocytes. The ability of cells to produce retinoic acid
was analyzed using the Aldefluor assay, which measures aldehyde dehydrogenase
(ALDH) activity. Data are presented as median (range).
RESULTS: The inflamed intestinal mucosa of UC patients is characterized by an
increased number per 105 lamina propria cells of DRintMQs (1472 (160-4066) vs.
138 (1-1947), p50.0001) and a decrease in CD103CD1cDCs (4 (1-26) vs. 19
(2-59), p 0.002) and CD103CD141DCs (7 (1-38) vs. 24 (4-54) p 0.0009)
compared to non-inflamed controls. The frequency of ALDH cells was reduced
in CD1cDCs (13 % (6-28) vs. 47 % (18-61), p 0.003), CD141DCs (16 % (729) vs. 33 % (14-64), p 0.006), DRintMQs (8 % (7-24) vs. 24 % (21-33),
p 0.002) and DRhiMQs (18 % (9-33) vs. 56 % (47-69), p 0.0002) from the
inflamed lamina propria of UC patients compared to healthy controls.
Interestingly, when studying ALDH activity in lamina propria of UC patients
in remission, the frequency of ALDH cells was also lower among CD1cDCs
(18 % (8-30) vs. 47 % (21-61), p 0.005), CD141DCs (18 % (13-26) vs. 41 %
(17-64), p 0.003) and DRhiMQs (33 % (19-56) vs. 57 % (45-69), p 0.01),
compared to controls. In contrast, no difference in the frequency of ALDH
cells among classical, intermediate or non-classical blood monocytes was
detected between UC patients and controls.
CONCLUSION: The inflamed intestinal mucosa in UC is characterized by an
influx of DRintMQs and reduced numbers of CD103CD1cDCs and
CD103CD141DCs. Colonic myeloid cells of UC patients are imprinted by
the intestinal environment to display low ALDH activity, regardless of disease
activity, which may influence the delicate balance between inflammation and
tolerance.
Disclosure of Interest: None declared
P1717 OSTEOPATHY IMPROVES THE SEVERITY OF IBS-LIKE
SYMPTOMS ASSOCIATED WITH CROHN DISEASE IN REMISSION
D. Pishvaie1, D. Tirouvaziam1, R. Dainese1, A. Setien1, J.L. Payrouse1,
X. Hebuterne1, P. Thierry1,*
1
CHU Nice, Universite de Nice Sophia Antipolis, Nice, France
INTRODUCTION: Osteopathy may improve the severity of the irritable bowel
syndrome (IBS) (1). About 35% of patients with quiescent Crohn Disease (CD)
continue to suffer from IBS-like symptoms (2).
AIMS & METHODS: We aimed to evaluate the effect of osteopathy on the
severity of IBS-like symptoms in CD patients on remission. We prospectively
assigned 38 patients with CD on remission over 12 months while receiving infliximab every 8 weeks. Twenty-five patients received 3 sessions of standardized
osteopathy 15, 30 and 45 days after the last infusion of infliximab. Ten patients
were followed at same interval for clinical interview. IBS-like symptoms were
evaluated according to Rome III criteria. The impact of IBS-like and abdominal
pain associated with CD on quality of life was evaluated using the Francis score
and the Inflammatory Bowel Disease Questionnaire (IBDq). The severity of
psychological factors was appreciated by evaluating anxiety, depression and fatigue with HAD, Beck and Fatigue Impact scale questionnaires. All patients were
evaluated at day 0, 30, 45 and 60. Comparisons from baseline values were performed between groups and during time in each group.
RESULTS: Compared with baseline, the severity of IBS-like symptoms was
significantly reduced in patients receiving osteopathy. Compared with controls,
this decrease was significantly more pronounced in patients treated with osteopathy at day 30 (-38.443.9 vs 37.749.1, p 0.005) and day 45 (-38.443.9 vs
37.749.1). Compared with controls, the clinical benefit of osteopathy was not
sustained at day 60 (-30 43.3 vs -1336.8, p 0.4). The quality of life was
significantly greater during osteopathy (p 0.09 at day 30, p 0.02 at day 45),
being not significantly different at day 60 (p 0.3). The severity of fatigue was
significantly improved in patients receiving osteopathy with a persisting effect at
the end of the study. The effect of osteopathy on depression scores was less
marked, being statistically significant only at day 30. However, anxiety was
not affected by osteopathy.
CONCLUSION: Three sessions of osteopathy improve the severity of IBS-like
symptoms and quality of life associated with CD in remission, with no sustained
clinical benefit after stopping treatment. Osteopathy improves fatigue and
depression traits whereas anxiety is not changed. Osteopathy should therefore
be considered in future clinical trials aimed at reducing the severity of abdominal
pain and discomfort in patients with CD considered in remission.
REFERENCES
1 Piche T, et al. Neurogastroenterol Motil 2010.
2 Florance BM, et al. Eur J Gastroenterol Hepatol 2012.
Disclosure of Interest: None declared

A604

United European Gastroenterology Journal 2(1S)

P1718 ANTI-TNF THERAPY RESPONSE IS ASSOCIATED


LOWER MUCOSAL EXPRESSION OF INFLAMMATORY
CYTOKINES BEFORE THERAPY START IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE

WITH

R. Dahlen1,*, M.K. Magnusson2, H. Strid1, A. Bajor1, A. Lasson3, K.-A. Ung4,


L. Ohman1
1
Medicine, Internal medicine and clinical nutrition, 2Biomedicine, Immunology &
Microbiology, Gothenburg, 3Sodra Alvsborgs sjukhus, Boras, 4Karnsjukhuset,
Skovde, Sweden
INTRODUCTION: The mechanisms of action of therapy response to anti-TNF
treatment in IBD patients are currently not completely known. Therefore, we
aimed to determine the mucosal immunopathology in IBD patients before antiTNF treatment and four months after therapy start, in therapy responders and
non-responders, respectively.
AIMS & METHODS: Mucosal biopsies from 37 IBD patients (UC 27,
CD 7, unclassified 3), (28 males, median age 36) were collected before antiTNF antibody (infliximab or adalimumab) treatment start and at evaluation of
therapy response, four months after therapy start. Therapy response was evaluated by comparing one or several of the following parameters before treatment
start and after four months of therapy; CRP, fecal calprotectin, partial or complete Mayo score (UC) and HBI (CD). Biopsies were obtained from 24 therapy
responders (UC 17, CD 5, unclassified 2) before therapy start, and at four
months post therapy start from 11 of these patients. Among non-responders,
biopsies were obtained from 13 patients (UC 10, CD 2, unclassified 1) at
baseline, and at four months post treatment start from five of these patients.
Total mRNA from biopsies was analyzed with real-time PCR. Expression of
TNF, IL-1b, IL-17A, IFN-, IL-6, IL-13, FOXP3, TNFR1, and TNFR2 was
determined. Results were normalized to the expression level of GAPDH and
expressed as 2^-Target-GAPDH. Data are shown as median arbitrary units, 25-75
percentile.
RESULTS: At baseline, there was no difference between UC and CD patients in
any of the targets analyzed; therefore patients were not subdivided according to
UC or CD-phenotype in subsequent analyses. At baseline, patients responding to
therapy had lower levels of TNF (responders 36*10-5(24*10-5-56*10-5) vs. nonresponders 59*10-5 (45*10-5-76*10-5); p 0.046)), and IL-1 (200*10-5 (110*10-5510*10-5) vs. 510*10-5 (370*10-5-800*10-5); p 0.03) as compared to non-responders. Similar trends were seen for the expression of IL-17A, IFN-g and FOXP3.
Among anti-TNF therapy responders, a reduced expression of TNF, IL-1b, IL-6
and FOXP3 was demonstrated, comparing baseline to four months post treatment start (Table 1). Among the patients not responding to the therapy, four out
of five patients had reduced expression of IL-17A, IFN-g and IL-1b (p n.s.) at
baseline as compared to after four months of therapy.
Table 1. Mucosal RNA expression in therapy responders at baseline and four
months after therapy start.

Target gene

Baseline
(x10-5)

4 months post
treatment start (x10-5)

p-value

TNF
IL-1
IL-6
FOXP3

54 (33-91)
360 (180-1200)
130 (66-240)
37 (19-70)

19
93
11
18

0.03
0.006
0.03
0.007

(11-72)
(49-180)
(4.7-40)
(8.7-40)

CONCLUSION: The expression of several mucosal cytokine RNA decreases


after four months of anti-TNF therapy among both responders and non-responders, although the cytokines regulated by the therapy may differ between the two
groups. Before therapy start, therapy responders have lower mucosal cytokine
expression of TNF and IL-1b than non-responders, indicating that non-responding patients might have a more severe immunopathology than responders.
Disclosure of Interest: None declared
P1719 CHARACTERIZATION OF APPENDICEAL LYMPHOCYTES IN
ULCERATIVE COLITIS PATIENTS
S. Sahami1,*, J. Bernink2, A. te Velde2, P. Tanis1, W. Bemelman1, C. Buskens1
1
Surgery, 2Tytgat Institute for Liver and Intestinal Research, AMC, Amsterdam,
Netherlands
INTRODUCTION: An increasing body of literature reported on the negative
correlation between an appendicectomy and the development of ulcerative colitis
(UC). Extensive infiltration of CD4 T cells has been observed in the inflamed
mucosa of UC patients, and it has been suggested that aberrant activation of Tlymphocytes in the appendix could serve as a priming site. Furthermore, appendiceal mucosal tissue of UC patients showed an increased CD4/CD8 ratio that
correlated with the disease activity in the colon. However, which T helper subsets
accumulated in the appendix that might account for the enhanced susceptibility
to develop UC, remains to be investigated.
AIMS & METHODS: In this study we aimed to characterize the T cell populations in appendiceal mucosal tissues of UC patients with inactive and active
disease and compared them to Crohns disease (CD) and acute appendicitis
(AA).
Surgical samples of the appendix were obtained from UC patients and compared
to patients with Crohns disease (CD) and acute appendicitis (AA). UC patients
were either in remission (inactive, median mayo score 1) or therapy refractory
(active, median mayo score 3). The appendix was histologically evaluated by
assessing the degree of inflammation and compared to a retrospective cohort

of patients with unaffected appendices (operated upon for cancer). In order to


determine the T-cell composition of the appendix in these patients, we took the
advantage of multicolour flow cytometric analysis. Both freshly isolated mucosal
appendix resection specimens and peripheral blood were stained with a cocktail
of antibodies to discriminate between the cytotoxic T cells and T helper subsets.
RESULTS: In contrast to the transmural infection seen in appendices of CD and
AA patients, resection specimens of UC patients appeared macroscopically
normal. However, histological evaluation showed increased mucosal lymphocyte
infiltration, which was not significantly different between inactive and active
disease.
We observed in the appendix of UC patients a significantly lower proportion of
pro-inflammatory CCR6 CD4 T helper cells when compared to CD.
Furthermore, although no significant difference was observed in CCR6 CD4
T helper cells between inactive and active UC resection specimens, the proportion
of CCR6 CD4 T helper cells in peripheral blood of UC patients was significantly higher for inactive disease when compared to active disease.
CONCLUSION: Our results demonstrate that despite a macroscopically normal
appearing appendix, there is an increased infiltration of T lymphocytes in appendices of UC patients, irrespective of disease activity. Although no difference was
seen between inactive and active UC, the lower frequency of pro-inflammatory
CD4 CCR6 T cells in the appendix of UC patients compared to CD patients
is possibly a result of enhanced efflux of these cells to the affected colon.
Disclosure of Interest: None declared
P1720 NARROW SPECTRUM KINASE INHIBITORS (NSKI) TARGET
KINASES INVOLVED IN BOTH INNATE AND ADAPTIVE IMMUNE
RESPONSES LEADING TO POTENT AND HIGHLY EFFICACIOUS
EFFECTS IN EXPERIMENTAL MODELS OF INFLAMMATORY
BOWEL DISEASE
S. Sirohi1,*, Y. Solanke1, M. Butler1, M. Foster1, M.C. Fyfe1, P. Biancheri2,
T.T. MacDonald2, S. Webber1, C.A. Walshe1
1
Topivert Pharma Ltd, 2Centre for Immunology and Infectious Disease, Blizard
Institute, Barts and the London School of Medicine and Dentistry, London, United
Kingdom
Contact E-mail Address: sameer.sirohi@topivert.com
INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohns disease (CD), is a complex disease involving both the
adaptive and innate immune responses. Here we demonstrate that NSKI
TOP1210 can modulate kinases (P38 & Lck) leading to inhibition of pro-inflammatory cytokine release from cells involved in both arms of the immune response.
Furthermore, in vitro, in vivo, and patient explants demonstrate the potent and
efficacious effects of NSKIs and their superiority to corticosteroids in these
models.
AIMS & METHODS: Inhibition of phospho- P38 (pP38) & phospho-Lck
(pLck) were assessed in vitro in either an ATP-based biochemical assay or in
human T cells and macrophages by flow cytometry or spectrophotometry methods. In vivo efficacy and target engagement of TOP1210 was investigated in an
adoptive T cell transfer colitis model with modulation of pP38 and pLck in the
mucosal tissue assessed by immunohistochemistry (IHC). Biopsies and cells isolated from IBD patients were cultured ex-vivo in the presence or absence of
TOP1210 or Budesonide and assessed for pro-inflammatory cytokine release.
Cytokine release for all models was assessed by ELISA.
RESULTS: In the in vitro assays, TOP1210 exhibited sub-100nM IC50 against
both pP38 and pLck. Inhibition of pP38 was linked to a reduction of IL-8
release from stimulated human macrophages and inhibition of pLck correlated
with a similar inhibition profile of IFN release from stimulated human T cells.
Oral administration of TOP1210 (5 mg/kg) in an adoptive transfer T cell colitis
model led to down modulation of pP38 and pLck in the mucosa of these
animals and linked to a reduction in IL-8 and IFN release in colon homogenates. Furthermore, TOP1210 was superior compared to a maximum tolerated
dose of Budesonide (1 mg/kg) in efficacy end points in the model (histopathology
scores). Consistent with the in vitro and in vivo data, TOP1210 was also found to
be a highly efficacious and a potent inhibitor of pro-inflammatory cytokine
release from IBD patient biopsies and isolated cells (LPMC and myofibroblasts)
with effects comparable, and in some cases superior, to Budesonide.
CONCLUSION: TOP1210 targets key kinases involved in the inflammatory
signalling cascades of IBD pathogenesis. Down-modulation of these kinases in
both a mouse in vivo colitis model and UC patient explants led to a significant
reduction in pro-inflammatory cytokine release. TOP1210s efficacy, relative to
budesonide, suggests NSKIs may provide an important alternative to corticosteroids in the treatment of IBD.
Disclosure of Interest: S. Sirohi: None declared, Y. Solanke: None declared, M.
Butler: None declared, M. Foster: None declared, M. C. Fyfe: None declared, P.
Biancheri Financial support for research from: Topivert Pharma Ltd, T. T.
MacDonald Consultancy for: Topivert Pharma Ltd, S. Webber: None declared,
C. A. Walshe: None declared
P1721 GENETIC POLYMORPHISM IN TRAF3IP2 GENE COULD BE
PREDICTIVE FACTOR OF LONG-TERM EFFECT OF INFLIXIMAB
AGAINST CROHNS DISEASE
S. Urabe1,*, H. Isomoto1, K. Maeda2, T. Ishida3, Y. Fukuda4, C.C. Chen1,
F. Takeshima1, H. Machida1, K. Nakao1, K. Tsukamoto2
1
Department of Gastroenterology and Hepatology, Nagasaki University Hospital,
2
Department of Pharmacotherapeutics, Nagasaki University Graduate School of
Biomedical Sciences, Nagasaki City, 3Department of Gastroenterology, Oita Red
Cross Hospital, Oita City, 4Department of Gastroenterology, Nagasaki Harbor
Medical Center City Hospital, Nagasaki City, Japan

United European Gastroenterology Journal 2(1S)


INTRODUCTION: Infliximab (IFX) is a TNF- monoclonal antibody which
have substantial effects for remission induction and maintenance for Crohns
disease (CD). However, there are primary failure patients who could not get
remission and secondary failure patients who once got remission but the effect
of IFX was lost later. In this regard, the identification of biomarkers to predict
the therapeutic effect is important. The present study was conducted to elucidate
the association of genetic polymorphisms in IL17RA, IL17RC, TRAF3IP2,
IL17A, and IL17F in interleukin-17 signaling pathway with therapeutic effects
of IFX against CD.
AIMS & METHODS: CD patients who were treated with infliximab in Oita Red
Cross Hospital, Nagasaki University Hospital and Nagasaki Harbor Medical
Center City Hospital were enrolled in this study. The study was approved by
each ethics committee and informed consent was obtained from each subject. For
correlation analysis of the short-term treatment effect, we extracted 112 patients
who have been assessed treatment effect of 10 weeks after infliximab administration, and for analysis of long-term effect, extracted 104 patients assessed 1
year after, and 93 patients assessed 2 years after administration, and in each
treatment period, the patients were divided into two groups whether the treatment was effective or not. In each period, significance tests were performed

A605
between sensitive group and resistance group about the frequency of occurrence
of genetic polymorphism of IL17RA, IL17RC, TRAF3IP2, IL17A and IL17F.
RESULTS: There were significant differences in the frequency of occurrence of
rs10872070 which is single nucleotide polymorphism (SNP) in TRAF3IP2
between the sensitive group and the resistance group two years after IFX administration (p 0.022, OR 0.068). Sensitivity as a biomarker to predict the treatment-resistance was 16.7%, and the specificity was 98.7%. In addition, the
positive predictive value was 75.0%, and negative predictive value was 83.1%.
CONCLUSION: We for the first time found that TRPF3IP2 could be the treatment-resistant gene in IFX therapy for CD. This gene polymorphism could be a
biomarker to predict the treatment-resistance and secondary failure of IFX.
Moreover, IL-17 signaling pathway suggested that participating in the treatment-resistance of IFX would involve the pathogenesis of CD, and it could be
a target molecule for novel therapeutics combined with a TNF- monoclonal
antibody.
Disclosure of Interest: None declared

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