10.1177 2050640614548980
10.1177 2050640614548980
10.1177 2050640614548980
OF
EARLY
A133
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
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
A135
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
A136
ON
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
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
A139
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
ACIDS
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
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
A143
PATIENT
IN
A144
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)
99.0(3.2)
n 90
99.1 (6.5)
n 87
96.6
(85/88)
PEARL-IV
Treatment-na ve
GT1a
3D
100.0 (2.6)
n 92
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
3DRBV (N 401)
3D (N 509)
21
13
11
23
4
3
1
2
(5.2)
(3.2)
(2.7)
(5.7)
(0.8)
(0.6)
(0.2)
(0.4)
Region
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)
A146
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)
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
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
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.
A148
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).
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
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
A150
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
Cohort
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
IN
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
A153
OR (95% CI)
P value
0.001
0.012
0.166
0.122
A154
AND
A155
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
A156
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
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.
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
A159
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.
A160
(UPA)-
A161
FOR
EARLY
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
A162
POSTER
EXHIBITION
9:0017:00
HALL
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
FOR
SECONDARY
A163
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
A164
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
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
A166
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
A167
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
A169
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
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
Glycerol (n 10)
0.0127
0.082
50.001
NS
NS
NS
50.001
NS
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
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
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
THE
A172
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
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
A173
COLITIS?
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.
66 (66%)
34 (34%)
87 (87%)
13 (13%)
24 (13 33)
61 (54 69)
Variables
Categories
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
A175
OF
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
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
Number (%)
Perforation
5/107 (5%)
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
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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
POLYPS:
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
189
40
Adenoma, %
of all polyps
Adenoma in Paris I
Adenoma in Paris II
23%
39.5%
51.3%
58%
20%
61%
29%
64%
32%
91%
75%
62%
23%
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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
A181
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
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
A182
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
HEALTH
A183
OF
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
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
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
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
OF
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
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
THE
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
A189
OF
SUSPICIOUS
CAPSULE
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
EXPERIENCE
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
ALICE
IMPROVE
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,
A193
AS
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
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
STENTS
FOR
MALIGNANT
9:0017:00
RECOVERY
PROGRAMME
IN
A197
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
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
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
A199
9:0017:00
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
A201
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
64 (18 to 260)
0.30
1/15 (7%)
27/177 (15%)
0.70
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%]
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
A202
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%
A203
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
FROM
A205
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)
A206
Monozygotic
Dizygotic
Crohns Disease
Ulcerative Colitis
53.3%
10%
25%
19.4%
NON-
n
w
a
r
d
h
t
i
W
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
n
w
a
r
d
h
t
i
W
A207
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
ANTI-TNF
RESPONSE
IN
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)
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
A210
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
p 0.142p50.001
UCR
IBS
(n 25)
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)
A211
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
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%)
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.
BOWEL
A213
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
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.
A215
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
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
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
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.
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
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
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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,
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
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
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*
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.,
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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
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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,
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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.
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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.
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BOWEL
A228
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
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
-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)
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
A231
IN
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
CANCER
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
A232
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).
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
A233
n
P0369 ASSOCIATION BETWEEN COLORECTAL NEOPLASMS AND
METABOLIC SYNDROME IN A PORTUGUESE POPULATION
1,*
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)
PPV
Advanced
neoplasia %
(95% CI)
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
DNA
A235
A236
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
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
A237
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,
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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.
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%)
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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)
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MARKERS
IN
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
A245
Tubular
Adenoma
(TA)
Serrated
Tubulovillous Villous
Adenoma Adenoma
Adenoma
(SA)
Hyperplastic
(VA)
(TVA)
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.
n
w
a
r
d
h
t
i
A246
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.
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A248
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
POSTER
EXHIBITION
9:0017:00
HALL
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
A249
A250
IBS
SAME
GI
A251
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: 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
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
A255
ON
MYOELECTRIC
MOTOR-SECRETORY
LIGAMENTS
OF
A256
Diagnosis (n)
Gastroparesis
Responders
TPGES
(open stim)
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
A257
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%)
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
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
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.
ESOPHAGITIS
CORRELATED
WITH
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
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
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%)
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
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
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
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
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%)
A263
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
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
AFTER
A265
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
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.
A267
LASER
METABOLIC
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
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
OF
TUMOR
A271
40
#2
78
#3
58
#4
49
Diagnosis
cancer
of
gastric
Locali-zation
Time of occurrence
after diagnosis of type
IGC, months (years) Outcome
17 (1.4)
156 (13)
80 (6.7)
63 (5.2)
61 (5.1)
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
ARAB
A273
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
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
A275
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%
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
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
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
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
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
A279
A280
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
IN
ELDERLY
Angiodysplasias
Apthoid ulcers
Ulcerations
Polyps
Tumors
86.3%
0.9%
5.4%
2,7%
4,6%
59.2%
13.0%
12.0%
9.9%
5.8%
A281
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
A282
all (113)
19-35 y (37)
36-45 y (36)
46-60 y (40)
Protein
Animal Protein
Fat
PUFA
64 (59, 66)
74 (55, 100)
136 (112, 165)
10 (7, 13)
95 (75, 108)
241 (171, 316)
151 (113, 175)
-35 (-53, -15)
!-3
!-6
!-6/!-3
Total CHO
Simple CHO
-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
A283
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
A285
ASYMPTOMATIC
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
A286
WITH
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
BOWEL
A287
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
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
healthy 4 patients
patients 4 healthy
Anatomical region
No. of
voxels
0
12
-9
-15
66
24
0
63
9
30
36
6
4.16
4.25
4.08
4.06
9
5
6
8
A289
OF
IRRITABLE
BOWEL
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
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.
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
SYSTEM
FOR
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
50.001
0.728
0.002
50.001
NA
A293
HIGH
LIVER
IRON
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
A295
NAFLD
NAFLDML-7 NASH
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
NASHML-7
26.61.200* 14.900.666#
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
A296
n
w
a
r
d
h
t
i
W
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
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
A297
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
A298
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
A299
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)
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.
A301
IN
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
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
ACTIVE
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.
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.
A305
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
A306
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
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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
RISK
A309
n
w
a
ithdr
A310
n
w
a
r
d
h
t
i
W
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
LIVER
DISEASE
USING
A311
348991
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
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
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
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OF
TEMPORARY
A314
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
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
A315
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
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
A317
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
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
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
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: 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
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
A321
II
POSTER
EXHIBITION
9:0017:00
HALL
n
w
a
ithdr
P0692 CHARACTERISTIC
ENDOSCOPIC
FINDINGS
HELICOBACTER PYLORI-NEGATIVE EARLY GASTRIC
UNDIFFERENTIATED ADENOCARCINOMA
OF
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
A323
P0698 DEVELOPMENT
OF
PROPOFOL
SEDATION
THERAPEUTIC ENDOSCOPY UNDER DEEP SEDATION WITH
SPONTANEOUS RESPIRATION
FOR
ACID-
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
FOR
THE
A325
Age
Weight
75 years 81 4
Propofol
ASA I/II/III
Colonoscopy dose EGD /
(%)
EGD n n (%)
Colonoscopy
AE (%)
Desaturation/
Bradycardia
307
72.99 37.4/
80.5934
307
2.6/0.3
56-71
53-85
53-85
3 (23%)
4 (57%)
7 (35%)
3 (23%)
1 (14%)
4 (20%)
7 (54%)
2 (29%)
9 (45%)
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
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
A328
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)
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
A329
GASTRIC
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
HIATUS
HERNIAS
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%
A331
COLONIC
POLYPS.
IS
VISUAL
39
1014
1519
2024
2529
430
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
A333
AND
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
A335
Ileoscopy normal
Indication (n)
Diarrhoea (67)
Abdo pain (39)
IBD assessment (29)
Other* (18)
Total6 (129)
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?
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.
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)
A336
Group 1
High
confidence
Group 2
High confidence
Diminutive
High
lesions
confidence
High
confidence
Diminutive
lesions
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
A337
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
A338
INCIDENTAL
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
A339
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
A340
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
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: 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
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.
A343
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
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
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
A346
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
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
A348
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
A349
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
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
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
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
A351
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
A352
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
A353
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
A355
RECOMMENDED:
IN
A356
P0818 SURGICAL
CHALLENGES
AND
ITS
CURRENT
A357
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
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
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
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
9:0017:00
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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
A361
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-
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
A363
RENAL
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.
OF
A365
ITS
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
A366
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
A367
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
AMONG
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
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)
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.
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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
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
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
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%)
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
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
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
A375
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)
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.
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
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:
A377
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
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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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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
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(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
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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
NOT
A380
(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 %
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
A381
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)?
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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
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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
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.
A385
A386
OPEN
A387
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
68 / 23
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
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
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
FROM
WITH
A389
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
OF
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
AND
THE
RISK
OF
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,*
A390
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
60.5%
21.5%
55.6%
6.2%
0%
1.8%
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
TO
A393
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
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
A395
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
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
A397
Linaclotide (10-300nM)
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
COLON
A399
A400
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)
AND
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
A401
WITH
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
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
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
A404
II
POSTER
EXHIBITION
9:0017:00
HALL
A405
A406
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
Pre vs
Maintenance Maintenance
5 0.0001
5 0.0001
NERVE
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
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
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
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
A409
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)
A410
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(%)
All
(n 191)
CD 4 200
cells/mm
(n 146)
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)
CPR (Scores)
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
0.67)
0.73)
0.66)
1.00)
0.72)
A411
GBS
GBS
Hemoglobin alone
Outcome
AUC
95%CI
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
A412
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
A413
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%)
PATIENTS
WITH
DENTAL
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).
A415
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
A416
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 2rhK (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
A417
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
HE (N 30)
FHPPI
(N 30)
FH-PPI
(N 30)
HV
(N 20)
P
(FHPPI
vs HE)
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
A419
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
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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
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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
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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
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IN
A424
IN
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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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
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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.
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
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
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
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
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
LESIONS
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
CONCLUSION: It can be concluded that a marked density of H. pylori colonization significantly increases the gastritis severity.
Disclosure of Interest: None declared
A429
THE
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
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,
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
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
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.
A434
DISEASE
IN
CASES
OF
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
AVAILABLE
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
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%
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
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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
MORTALITY
FOLLOWING
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OF
ESOPHAGEAL
STRICTURES
IN
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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
OF
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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
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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.
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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
A444
These findings suggest that TSA and SSA have different genetic alterations from
TA or HP.
Disclosure of Interest: None declared
00
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
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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.
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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
A447
GOJ
Cardia
Fundus
Body
Incisura
Antrum
Pylorus
Landmark 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
A449
THE
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
n
w
a
r
d
h
t
i
W
A451
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
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
A453
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%
HEPATIC
A454
n
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i
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
A455
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
Hematological alterations
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*
A457
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
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
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,*
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
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
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
A459
Years
Diagnosis
alfa-fetoprotein
(ng/mL)
Year of LT /
aetiology
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
Male / 45
2 / 17
Female / 68
Diagnosis
method
Treatment
Cause of death /
survival time
after diagnosis
Sorafenib (5
months)
Palliative
Dead of multiorgan
failure / 2 weeks
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
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)
NPV PLR
NLR Accuracy
0.7273
0.3625
0.32
0.9394
0.325
0.9697
0.1375
0.9697
0.3625
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
WHO
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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
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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
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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
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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
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w
a
r
d
h
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i
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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.
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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
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
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
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
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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
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
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
OF
RE-
A471
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)
A472
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
CANCER
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
A473
WITH
ASSOCIATED
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
A474
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
NO
DRAIN
FOR
A475
EUS-FNA
EUS-FNA (overall)
MDCT
PET/CT
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
28
30
31
27
3
3
0
0
0
0
3
3
3
1
0
4
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
A476
TO
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
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
A477
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
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
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
A478
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
3
2
22
1
6
1
1
1
1
P1271 PER-ORAL
ENDOSCOPIC
MYOTOMY
(POEM)
ACHALASIA CARDIA, CASE SERIES FROM SINGLE TERTIARY
CARE CENTRE
FOR
A479
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
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
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%
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
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
FOR
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.
A484
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.
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
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
A485
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
A486
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)
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
A487
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
A488
P1304 CLINICOPATHOLOGICAL
CHARACTERISTICS
LATERALLY SPREADING TUMORS WITH SKIRT
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.
N
Size (mm)
Rate of SM
invasion (%)
Total
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
A491
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
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
A493
COLONOSCOPY:
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
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
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
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
A496
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
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
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%)
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
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
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
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ENDOSCOPIC
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.
A502
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
A503
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%
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
FOR
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
Number
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
A507
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).
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.
FOR
A509
FOR
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
AS
A511
SURGERY:
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
A513
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
9:0014:00
A514
VEGFA
Ang1
Ang2
Tie2
Affected mucosa
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
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-
PRO-
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
IS
ASSOCIATED
WITH
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
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
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
BMI 35 BMI30
Average age
Female: Male
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
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
A521
OF
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
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AND
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(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
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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
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
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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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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 (%)
IS
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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
A528
POTENTIAL
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%
A529
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
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
A530
FOR
THE
TREATMENT
OF
PERIANAL
P1463 IDENTIFICATION
ANTIBODIES
OF
NEUTRALIZING
ANTI-INFLIXIMAB
A531
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
A532
IBD Centres
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
A533
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
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
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
DISEASE
2,3
FECAL
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
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
A538
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
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,
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
TO
ULCERATIVE
COLITIS
TREATMENT:
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
ADA
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
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
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
FOR
TOLL-LIKE
A542
[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)
(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.
A543
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
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
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
A544
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
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
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,
1
2
3
4
5
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)
(0.01-0.05)
(0.08-1.24)
(0.10-0.57)
(0.04-0.08)
(0 0.20)
Low
A547
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
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
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
COLON
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
A551
A552
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
0.9
0.1
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
A553
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.
A555
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: 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
WITH
Abdominal pain/discomfort
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
A559
Study
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)
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
A561
IS
NEGATIVELY
A562
III
POSTER
EXHIBITION
9:0014:00
HALL
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
A563
FS in
FS in
FS in
DDV
DDV
DDV
MTV
MTV
MTV
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
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
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
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
BODY
A567
TUMOUR-
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
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
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
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
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
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.
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
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
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
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
Patients (n )
Age (years)
Thyroiditis (%)
PG1 (ug/L)
PG2 (ug/L)
PG1/PG2
G17 (pmol/L)
Hp Abs (EIU)
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
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
A575
Study Two
ESO-20mg
Placebo
ESO-20mg
Placebo
18
19
22
21
43
29
47
31
43
35
43
39
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
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
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
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
A579
AND
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
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,
A581
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
0.03-0.33
0.34-0.74
0.75-1.49
1.5-10.09
1.7%
5.0%
4.2%
8.3%
(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
A583
WITH
SIGNIFICANCE
OF
EZRIN
A584
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.
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
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
A586
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
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
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.
A589
ON
A590
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
A591
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
A592
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
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
A593
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).
A594
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
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)
n.a.
n.a.
Diff. between fast- 44 (-211 294)13 (183 593)10 (-150 245) 4 (-21 135)4 (-220 245)
ing values
A595
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
P1690 GALLSTONES,
LACTOSE
MALABSORPTION
METHANOGENIC FLORA: A STRANGE TRIO
AND
A596
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
OF
SEVERE
OLMESARTAN
SPRUE-LIKE
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
Nonspecific inflammation
Remission of atrophy
Collagenous colitis
Histological improvement
Not performed
Pending outcome
Pending outcome
A597
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
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
A599
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
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
A601
P1710 ACRYLAMIDE,
A
DIETARY
GLYCATED
IMPLICATED IN INTESTINAL INFLAMMATION
PRODUCT
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
A602
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
OF
1
A603
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
WITH
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)
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