Available online at www.sciencedirect.com EJSO 35 (2009) 281e288 www.ejso.com Outcomes and survival after laparoscopic gastrectomy for adenocarcinoma. Analysis on 65 patients operated on by conventional or robot-assisted minimal access procedures R. Pugliese*, D. Maggioni, F. Sansonna, G.C. Ferrari, A. Forgione, A. Costanzi, C. Magistro, J. Pauna, S. Di Lernia, D. Citterio, C. Brambilla Divisione di Chirurgia Generale e Videolaparoscopica, Ospedale di Niguarda Ca’ Granda, Milano, Italy Accepted 4 February 2008 Available online 14 March 2008 Abstract Aims: Despite laparoscopic surgery for gastric cancer has gained worldwide acceptance, long term results and survival are seldom reported. This study was designed to assess long term outcomes after laparoscopic gastrectomy with D2 dissection. The short term results of conventional and robot-assisted minimally invasive procedures were also examined. Patients and methods: The charts of 65 patients who underwent laparoscopic surgery for non-metastatic adenocarcinoma were reviewed retrospectively. This series included 35 patients with early gastric cancer (EGC) and 30 with advanced gastric cancer (AGC). A 4/5 laparoscopic subtotal gastrectomy (LSG) with D2 nodal clearance was the procedure of choice for distal cancers. Laparoscopic total gastrectomy (LTG) with modified D1 lymphadenectomy was performed for mid-proximal EGC. Results: Sixty gastrectomies were carried out laparoscopically, 56 LSG and 4 LTG. Conversion to laparotomy was required in 5 patients with distal cancer. No intraoperative complication was registered. Morbidity included 2 duodenal leaks that healed conservatively. Two postoperative deaths were registered. An average number 31.3  8.8 lymph nodes were collected. The mean hospital stay was 10 days (range 7e24). The mean follow up was 30 months (range 2e86) and the cumulative overall 5 year survival rate was 78%. Survival at 5 years for EGC was 94% and survival at 4 years for AGC was 53% (57% for non-converted patients). Conclusions: Laparoscopic gastrectomy for cancer represents a valid alternative to open surgery with minimal morbidity and acceptable long term survival. Considering the risk of preoperative under diagnoses a D2 lymphadenectomy is suggested also for EGC. This study validated the effectiveness of minimally invasive technique in the management of gastric cancer. Ó 2008 Elsevier Ltd. All rights reserved. Keywords: Gastric cancer; Laparoscopy; Gastrectomy; Lymphadenectomy; Long term survival Introduction The respect for oncological principles is crucial when dealing with gastric cancer. Currently, performance of extended (D2) lymphadenectomy is advocated although in absence of randomized studies.1e7 Some Authors consider also paraortic D3 dissection and adjuvant therapies as potential benefits to survival.7e11 When gastric adenocarcinoma is resected by minimal access procedures the support of endoscopic ultrasonography in the preoperative * Corresponding author. Chirurgia Generale e Videolaparoscopica, Ospedale Niguarda Ca’ Granda, Piazza Ospedale 3, 20162 Milano, Italy. Tel.: þ39 02 6444 2503; fax: þ39 02 6444 2905. E-mail address: chirurgiaurgenza@ospedaleniguarda.it (R. Pugliese). 0748-7983/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejso.2008.02.001 staging plays an important role.12 According to the Guidelines of the Japanese Gastric Cancer Association (JGCA) laparoscopic gastrectomy is a valid alternative to open surgery for early gastric cancer (EGC) but it is controversial for advanced gastric cancer (AGC) in which performance of a correct lymphadenectomy is much more important.3,13 Relapse is generally hematogenous for EGC with a rate of lymph node metastases of 0e10% in mucosal and 11e42% in submucosal carcinomas, hence lymphadenectomy might be regarded as an overtreatment in around two thirds of cases.14e20 Moreover, in patients older than 75 years extended lymphadenectomy may be even unnecessary.21 Despite this data, pre-operative understaging has been reported and enhanced the need for D2 lymphadenectomy also in EGC.22,23 Laparoscopic gastrectomy has been 282 R. Pugliese et al. / EJSO 35 (2009) 281e288 carried out for AGC with good short term outcomes, but large-scale studies are still lacking.24e44 Moreover, the laparoscopic management of gastric malignancies remains open to debate and little data on long term survival is available.31,32,43 The main purpose of this study was to analyze long term results of EGC and AGC treated by minimally invasive technique over a period of 7 years. The endpoints were 5 year survival and disease free intervals. The short term results of LSG by conventional laparoscopy and robot-assisted laparoscopy were analyzed. Our profile of learning curve Patients and methods Study population Since June 2000 through September 2007 a total of 215 patients were referred to our Unit for gastric carcinoma of any stage, including 181 men and 34 women with mean age of 70 years (range 40e85). The overall incidence of EGC in our series was 16% (35/215). The data of 65 patients is illustrated in Table 1. The surgical risk was reckoned by the American Society of Anesthesiology (ASA) score. EGC were 1.84 cm in size (range 0.8e4) and AGC 4.6 cm (range 3e10). Among 35 EGC, 31 were located in the lower third, 68% were Lauren’s intestinal type and 65% were well differentiated. One patient was affected both by EGC and right colonic cancer and underwent LSG and laparoscopy-assisted right hemicolectomy. All of the 30 AGC recruited for laparoscopic excision were located in the lower third of the stomach. Eligibility criteria for laparoscopic surgery Subjects with histologically confirmed EGC or nonmetastatic distal AGC, in good general conditions, were included in this study. Subjects with distant metastases, preoperative evidence of local infiltration, AGC of the upper two thirds of the stomach, anaesthesiologic contraindications and previous laparotomies for major abdominal surgery were not considered eligible for laparoscopic approach. Open gastrectomy was carried out in 124 patients with D2 dissection (D2 þ D3 paraortic in 26 cases). Procedures Sixty-five patients, 40 men and 25 women of mean age of 72 years (range 41e86) were enrolled for laparoscopic procedures, 35 affected by EGC and 30 by AGC. All these patients were asked for informed consent before surgery. Conventional laparoscopy (CL) or robot assisted laparoscopy (RAL) was employed and all the operations were performed by the same surgeon. All of the EGC beneficiated of laparoscopic surgery that until January 2006 was performed only by CL. Laparoscopic subtotal gastrectomy (LSG) was performed for distal EGC or distal AGC with extended D2 dissection according to the latest JGCA classification.13 To date, AGC of cardia or proximal regions of the stomach have been treated by open surgery to ensure a correct D2 or D3 dissection. Laparoscopic total gastrectomy (LTG) with modified D1 dissection was carried out for mid-proximal EGC by CL. The Roux-en-Y loop was the preferred method of reconstruction of the digestive tract. Kodama’s criteria were used for histologic classification of EGC18 and tumor staging was obtained according to UICC-TNM classification (2002) of the International Union Against Cancer. We started by CL in patients >75 years with cancers like EGC not requiring extensive lymphadenectomy,13,14,21 then turned to distal AGC only after developing enough skill maturation in performance of D2 dissection. Then, LTG with modified D1 for EGC ensued, but in the future we aim at approaching mid-proximal AGC by LTG with D2 dissection as the final goal of our learning curve in laparoscopic surgery of the gastric cancer. Preoperative work up and patients’ preparation Preoperative investigations included endoscopy with biopsy and vital staining, abdominal echography and helicalcomputed tomography (CT). In case of EGC the tumor was marked endoscopically with Indian Ink to identify the lesion during laparoscopy, and was staged by ultrasound endoscopy with a 15 MHz probe. All the AGC were staged by endoscopy, biopsy and CT-scan. Preparation consisted in SinaireÒ (Promefarm srl, Milan) 6 tablets a day for 4 days before admission, plus 4 l of Polietilenglycole acid (PEG) 2 days before surgery. SeleparinaÒ (Italfarmaco, Milan) 0.3 ml was given subcutaneously the night before surgery for anti-thrombotic prophylaxis and Cephazoline 6 g i.v. was administered the day of surgery for short term antibioprophylaxis. Statistical analysis Data was derived retrospectively from the database and elaborated by SPSS statistical analysis software package (version 11.0). Continuous variables were analyzed by Student t-test and discrete variables by Chi square test or Fisher’s Exact Test. Values of P < 0.05 were considered significant within a confidence interval (CI) of 95%. Long term actuarial survivals were determined by KaplaneMeier estimator and were elaborated by JMP 5.1.1 version of SAS Institute. Statistical differences in survival between groups were identified by the log-rank test. The patients operated on by RAL were all included in the statistical elaboration of long term results. R. Pugliese et al. / EJSO 35 (2009) 281e288 Table 1 Laparoscopic procedures in early gastric cancer (EGC) and advanced gastric cancer (AGC) ECG (¼35) AGC (¼30) Age Gender Mean (range) Men Women 68 years (41e84) 77 years (71e86) 21 19 14 11 ASA score I II III 5 19 11 0 17 13 Location Upper Middle Lower 2 2 31 0 0 30 pTNM pT1mN0M0 (IA) 29 (UICC 2002) pT1smN0M0 (IA) 4 (2 Pen B, 2 small mucosal SM) pT1smN1M0 (IB) 1 Pen A pT2N0M0 (IB) pT1smN2M0 (II) 1 Pen A pT2N1M0 (II) pT2N2M0 (IIIA) pT3N1M0 (IIIA) pT2N3M0 (IV) 15 6 5 3 1 Data of 65 patients. Niguarda Hospital, Milan (2000e2007). Pen B ¼ penetrating B, Pen A ¼ penetrating A, SM ¼ small mucosal, according to Kodama’s classification of submucosal early gastric cancers.18 Surgical technique of conventional LSG and LTG The surgical techniques of conventional LSG and LTG are the same described in a previous issue of ours,23 using trocars of 10 mm (X-celÒ Ethicon Endo-Surgery Inc, Cincinnati, OH). All the dissecting manoeuvers are conducted by ultrasonic scalpel either with a shaft of 10 mm (UltracisionÒ Ethicon, Cincinnati, OH) or with a shaft of 5.5 mm (Harmonic AceÒ Ethicon, Cincinnati, OH). Titanium clips (LigaclipÒ12-L endowed with rotating clip applier, Ethicon Endosurgery Inc, Cincinnati, OH) or absorbable clips (LaproclipÒ, Tyco Healthcare Group, Norwalk, USA) are used on vessels. Gastric dissection, D2 lymphadenectomy and closure of duodenum are the first steps of operations. For LTG a side-to-side esophagojejunal anastomosis is fashioned reproducing Orringer’s model.45 We shortly describe the technique of LSG by RAL. Robot assisted LSG The patient is in supine position the same as for conventional LSG. The telesurgery robotic cart is a 3-armed Robotic Surgical System (Robot da VinciÒ Intuitive Surgical, Mountain View, CA, USA) controlled from a remote console. Robot and optic system setup are prepared. Electric cables connect the robotic system and after a self-test the 3 arms are wrapped with covers and fixed by supports. A 3D image is selected, then a 12 mm cannula 283 is inserted in supraumbilical site for open laparoscopy and optic view. Then under direct vision 3 ports of 12 mm are inserted in the upper quadrants. One robotic port of 7 mm is created for other instruments. The robotic cart is installed. For the first steps a wide view is necessary, thus they are conducted under CL: omentectomy, coloepiploic detachment, opening the lesser sac, gastroduodenal dissection and ablation of inphrapyloric nodes (tiers 4 and 6). Then, the second jejunal loop is prepared to fashion the side-to-side stapled anastomosis at the foot of the Rouxen-Y loop. When the robotic system is ready, lymphadenectomy is conducted on the anterior aspect of hepatic artery (group 12a), then the right gastric artery is cut, the suprapyloric nodes are removed (group 5) and the duodenum is transected by a 45 mm linear cutting stapler reinforced with SeamguardÒ bioabsorbale policarbonate material (W.L. Gore & Associates, Inc. Flagstaff, Arizona) for reinforcement of the staple line. Lymphadenectomy is completed by ablation of nodal tiers 8, 9, 11p followed by division of left gastric artery with removal of group 7 and tiers 1, 3 and 5 along the lesser curvature. The stomach is transected by linear stapler to obtain a 4/5 gastrectomy leaving temporarily the specimen in the peritoneal cavity. A 50 cm. Roux-en-Y jejunal limb is chosen for restoration of the digestive tract. A transmesocolic gastro-jejunal anastomosis is fashioned with a linear cutting stapler on the posterior wall of the gastric stump. The access openings are closed by separated extracorporeal slipknots. The endobag (Endocatch IIÒ 15 mm Ethicon Endo-Surgery Inc, Cincinnati, OH) containing the resected stomach with D2 lymphatic stations is retrieved through the enlarged umbilical port. A drain is placed near duodenal stump in Morrison’s pouch and closure of port incisions ends the operation. Results Short term results A 4/5 LSG with D2 dissection was carried out in 56 distal cancers, totally intracorporeal in 55 (Tables 2 and 3) and video-assisted in 1 in which the gastrojejunal anastomosis was fashioned through a small midline incision. Intracorporeal LTG was carried out by CL in 4 EGC with no conversion. Conversion was required in 5 distal cancers (7.6%) for difficult dissection of 4 AGC and anatomical problems in 1 EGC. The conversion rate for LSG was 6.5% by CL and 18% by RAL. No intraoperative complication was registered. Overall, the mean operating time of LSG was 254  16 min. Mean duration of LTG was 275  22 min (range 165e410). The estimated mean blood loss was 146  55 ml for LSG and 180  94 ml for LTG. Specific morbidity was 4.6%, comprising 2 duodenal stump leaks after CL (incidence 3%): both leaks healed conservatively and occurred at the very start of this study, when the stump was just stapled, but after enclosing the staple line by separated stitches or reinforcing it by SeamguardÒ stump leaks weren’t observed 284 R. Pugliese et al. / EJSO 35 (2009) 281e288 Table 2 Outcomes of 65 laparoscopic procedures for early and advanced gastric adenocarcinoma EGC (n ¼ 35) AGC (n ¼ 30) Surgical procedure Mean number of nodes harvested (range) Resection margin 4 LTG 30 LSG 29.7  7 (20e40) 34 free of disease 1 LSG converted 33 1 free of disease 26 LSG 32.5  9.7 (28e45) 25 free of disease 1 infiltrated 4 LSG converted 34.6  8 (30e48) 3 free of disease 1 infiltrated A preoperative diagnosis of mucosal EGC was made in 38 patients. The histologic examination on the surgical specimen disclosed an AGC in 3 cases and a submucosal EGC in 6 (Table 1). Hence, under diagnosis occurred in 23.7% of cases (9/38). Sensitivity for any EGC was 100% and accuracy 95%. Sensitivity for mucosal EGC was 100% and accuracy 86%, with a positive predictive value of 76.3% for pT1m. Anyway, subtotal gastrectomy with D2 dissection was routinely carried out also in cases underestimated by preoperative investigations. Short term result of robot assisted LSG Niguarda Hospital, Milan (2000e2007). any more. One pancreatic leak, but no duodenal leak occurred in the RAL group. Mortality rate (within 30 days) was 3%, due to 1 anastomotic bleeding in a patient with cirrhosis after LSG by CL and to 1 haemorragic stroke after LSG by RAL, both carried out for EGC. The mean LOS (length of hospital stay) was 10  3 days (range 7e24). The mean LOS for LTG was 11.6  2 days and the difference with the mean hospital stay of LSG (Table 3) was not statistically relevant (P > 0.05). The average distance of the resection margin was 6.7  0.68 cm (range 4e8.5 cm) with no significant difference between CL and RAL. The resection margin was involved in 2 cases of Lauren’s infiltrating carcinoma (Table 2). In the first ten procedures for EGC were retrieved 20 nodes and in the first ten procedures for AGC 25 nodes. An average number of 31.3  8.8 lymph nodes (range 18e45) was collected by laparoscopic gastrectomies, as detailed in Table 2; the mean number of nodes harvested by LTG was 35  4. Nodal metastases were found in 2 Pen A type distal EGC (incidence 6.4%): all the nodes involved were collected from the lesser curvature, with a ratio (number of metastatic nodes/number of nodes retrieved) respectively of 3/40 (N1) and 10/25 (N2). In this study subtotal gastrectomy by RAL was attempted in 11 patients (6 women and 5 men) of mean age 68 years (range 45e82). The mean size of lesions was 3.2  2.6 cm (range 0.8e10 cm). Conversion was required in 2 cases for difficulties in dissection (conversion rate 18%): in one EGC owing to a hepatic artery of 7 mm in diameter arising from the left gastric artery, and in one AGC (pT2N2) for tumor size. No intraoperative complication was registered. The mean time for robot system setup dropped from 40 to 15 min within 2 years. The robotic system was prepared in 23  8 min on average (range 15e40) and the mean duration of RAL was 170  45 min (range 120e240). Average LOS was 11 days. The differences between short term results of CL and RAL, excluding converted patients (Table 3), were not statistically relevant (P > 0.05). The post-operative morbidity consisted in 1 pancreatic leak that healed conservatively in 40 days. Mortality concerned 1 patient with EGC who died from haemorragic stroke. The resection margin was 6.7 cm on average and margins were all free of disease on histologic examination; the mean number of nodes retrieved by robot assisted LSG was 27.5  5 (range 18e40). Outline of follow up Conventional LSG Robot assisted LSG n ¼ 46 n¼9 The follow-up included controls scheduled on a 6 month basis for 5 years, including clinical examination, abdominal echography and monitoring of CEA and CA 19/9 cancer antigens serum levels. Endoscopy or CT scan were required when the suspicion of relapse was raised by clinical examination, echography or laboratory findings. (25 EGC, 21 AGC) values (range) (4 EGC, 5 AGC) values (range) Long term results and survival 236  20 (145e360) 156  57 (45e250) 1.2  0.7 350  71 (240e460) 92  58 (50e200) 1.2  0.5 5  0.8 10  2.5 (7e24) 31.5  9.5 (20e45) 5  1.1 11  1 (10e13) 27.5  5 (18e40) Table 3 Short term outcomes of 55 patients after conventional and robot assisted subtotal gastrectomy by thorough intracorporeal technique Operating time (minutes) Blood loss (ml) Times to mobilization (p.o. day) Oral intake (p.o. day) Hospital stay (days) Mean number of nodes harvested by D2 Accuracy of preoperative staging Niguarda Hospital, Milan (2000e2007). The mean follow up after surgery was 35  20.7 months (range 2e86). Excluding 2 postoperative deaths, survival was reckoned on 63 patients: 4 of them were lost to follow up. The 5 year cumulative overall survival (OS) was 78% as shown in Fig. 1. The follow up span was 7 years for EGC and 4 years for AGC: stratified survivals are illustrated in Fig. 2 and the differences were statistically significant R. Pugliese et al. / EJSO 35 (2009) 281e288 285 Comment Short term results Figure 1. Cumulative long term survival of laparoscopic gastrectomy for adenocarcinoma (2000e2007). with the log rank test (Mantel-Cox). Four year OS of patients with distal AGC was 53%, but it was 57% for those not converted. Eleven patients had recurrence (18.6%) and 6 of them died of disease, one affected by EGC and 5 by AGC (Table 4). One patient undergoing video-assisted LSG for EGC Pen A type died for carcinosis (n 1 in Table 4). Another patient with EGC Pen A type was alive and disease free 2 months after RAL. Two patients had the resection margin involved by Lauren’s infiltrating type carcinoma and were reoperated on (n 8 and 9 in Table 4). Fourteen patients with N1eN3 advanced cancer underwent postoperative adjuvant chemotherapy, while one patient converted (pT3N1) could not beneficiate of adjuvant therapy for medical contraindications (n 2 in Table 4). Four patients affected by poorly differentiated AGC died from disease after totally intracorporeal LSG by CL (n 3, 4, 5, 6 in Table 4). No port site metastasis was observed in this study. The mean disease free interval of the 6 patients deceased was 17 months (range 3e30) with a mean survival of 22 months (range 8e38). These periods were respectively 20 months (range 9e30) and 25 months (range 12e38) for the 4 patients beneficiating of totally intracorporeal LSG. To date, no death for disease was registered after totally intracorporeal LSG by RAL in 8 patients after a mean follow up of 8 months (range 2e18). Disease free OS was 94% for EGC and 51% for AGC (P ¼ 0.0048 with the log-rank test). Figure 2. Gastric cancer by laparoscopic approach: survival for EGC (at 5 years) and for AGC (at 4 years). Our short term results compared favourably with those of other series. No intraoperative complication was registered. The overall conversion rate was 7.6% (6% for CL), with a 0%e10% rate reported in other series.28,30,34e36,41e44 The mean operating time of LSG by CL was 236 min, ranging between 200 and 320 min in the literature.24,29e36,41 The mean operating time of LSG by RAL was 350 min, ranging from 420 to 656 min in other reports.39e41 Estimated mean blood loss was 148 ml, 156 ml for CL and 92 ml for RAL, ranging from 65 to 300 ml in other series.32e36,39,40 Specific morbidity was 4.6%, ranging from 3.8% to 26.7% in the literature.22,25,30e35,36,43 Mortality was 3%, varying between 0% and 9% in laparoscopic reports.30,31,33,35,36,41e44 Recently, a mortality rate of 4e6% has been reported in a large study on open gastrectomy.10 Average LOS was 10 days, comparable to the 7e17 days LOS reported in other studies.24,29,30e44 Compared to CL, RAL did not result in higher morbidity or in longer LOS. Long term results The main endpoints of our study have been long term results after laparoscopic gastrectomy. To authors’ knowledge this is the third issue including both EGC and AGC and reporting survival rates. However, Huscher’s and Tanimura’s studies31,32 reported only cumulative survival rates which are biased by the proportion of EGC included, while this study reported also the stratified survivals of EGC and AGC. The 5 year cumulative OS was 78% in our series, consisting of EGC in more than half cases. Focusing only on antropyloric AGC, the 4-year OS was 53% (Fig. 2) but it was 57% excluding converted patients, a result consistent with other reports.6,31,32,46 To date, it has been described only one case of port-site recurrence after laparoscopic gastrectomy,47 but no port site metastasis was observed in this study. Lymph node harvest Shimizu and Adachi reported in the year 2000 that there was no difference in nodal clearance between laparoscopic and open surgery.22,48 The mean number of nodes collected in our study was 31, ranging from 15 to 43 in the literature.22,24,30e36,42 Thus, D2 dissection complied with JGCA criteria and also with Western criteria of a minimum of 25 nodes retrieved.49 The mean number of nodes collected by RAL was 27, comparable to that reported in a recent issue.40 At the outset of our experience with CL the mean number of nodes collected was even smaller: in the first ten procedures for EGC were retrieved 20 nodes and in the first ten procedures for AGC 25 nodes. We are confident that with progression of the learning curve RAL will afford the same number of nodes 286 R. Pugliese et al. / EJSO 35 (2009) 281e288 Table 4 Long term results of 11 patients with recurrence of disease Tumor Operation Disease free interval (months) Reoperation for relapse 1 2 pT1N1 pT3N1 D2 LSG Converted 21 3 3 4 5 6 7 pT2bN2 pT2bN1 pT2bN2 pT2bN0 pT2bN2 D2 LSG D2 LSG D2 LSG D2 LSG RA converted (TG) 8 19 21 30 6 8 9 10 11 pT2bN0 pT3N1 pT3N1 pT2N1 Converted (TG) D2 LSG D2 RA LSG D2 RA LSG 42 13 12 5 No Exploratory laparotomy No No No No Exploratory laparotomy Oesophagectomy Degastrectomy Hysteroadnexectomy No Alive (months after gastrectomy) Deceased (months after gastrectomy) 27 8 12 24 27 38 8 57 21 12 10 LSG ¼ laparoscopic subtotal gastrectomy; TG ¼ total gastrectomy; RA ¼ robot-assisted. Follow-up span June 2000eSeptember 2007. retrieved by CL. On the other hand, the role of extended lymphadenectomy still is debated.2,14,20,21 A randomized study comparing extended D2 versus super extended D3 lymphadenectomy has been conducted in Japan, but apart from short term results, to the best of authors’ knowledge survival and long term results of this study still await publication.3,7,8 Some Japanese Authors maintain that JGCA classification is more suitable than UICC-TNM classification for estimating prognosis of patients with AGC.4 Lymphadenectomy in EGC can identify the high-risk population with worse prognosis, independent of its influence on survival,50 although in the vast majority of mucosal EGC a D1 dissection with removal of 1, 3e6 stations according to JGCA would suffice13 and D2 for well differentiated mucosal EGC <4.5 cm in size has been considered unnecessary.14 Despite this data, there are still good reasons to suggest a routine D2 dissection for EGC, i.e. under diagnoses. Extent of resection mucosal were submucosal on histologic examination.22 In this study preoperative misdiagnosis occurred in 23.7% of cases, leaving 3 AGC undiagnosed and 6 submucosal EGC under staged. Anyway, D2 dissection was carried out routinely in all distal cancers and because the frequency of nodal involvement of distal EGC was 6.4% with hindsight it must be emphasized how D2 has been appropriate in cases underestimated preoperatively. In a study by Kitano the frequency of nodal involvement after distal gastrectomy for EGC, in absence of a routine D2 dissection, was 6.6%,43 a value comparable to that of our study in which for distal EGC a routine D2 was performed although nodal metastases were all from the lesser and the greater curvature, that is, within the reach of D1 dissection. To summarize, because under diagnosis left undetected 3 AGC and understaged 6 submucosal EGC in our experience, we maintain that, until accuracy of preoperative staging is 100%, performance of LSG with D2 lymphadenectomy remains justified. Conclusions Distal gastrectomy has been generally carried out for EGC of the lower third.25e29,32,33,36,43 However, subtotal gastrectomy with a 6 cm margin has been recommended for distal cancers, also for EGC.19,30,31,40,51 It has been reported a 2.2e23.1% incidence of multifocal EGC and this factor regards especially elderly patients affected by intestinal or differentiated type of carcinoma of the lower third.15,19,52,53 In our series 68% of EGC were intestinal type, 65% were well differentiated and the mean age of patients was 68 years (Table 1), hence a minimum safety margin of 6 cm was warranted. Moreover, subtotal gastrectomy yields the performance of a correct D2 dissection including the right paracardial nodes (tier 1). The problem of preoperative under diagnoses Under diagnoses do represent a major problem: Shimizu reported that 29% of EGC diagnosed preoperatively as This study reported survivals after laparoscopic gastrectomy stratified for EGC and AGC, a data seldom found in other reports today. Oncologic principles of lymph node harvest and extent of resection were respected. Our long term results confirmed that laparoscopic surgery represents a reliable alternative to open procedure in the treatment of gastric cancer. Conflict of interest We hereby declare that there is no potential or actual personal, financial or political interest related to this article. References 1. Adachi Y, Shiraishi N, Kitano S. Modern treatment of early gastric cancer: review of the Japanese experience. Dig Surg 2002;19:333–9. R. Pugliese et al. / EJSO 35 (2009) 281e288 2. Hartgrink HH, van de Velde CJH, Putter H, et al. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch Gastric Cancer Group Trial. J Clin Oncol 2004;22:2069–77. 3. Nakajima T. Gastric cancer treatment guidelines in Japan. Gastric Cancer 2002;5:1–5. 4. Ikeguchi M, Murakami D, Kanaji S, et al. Lymph node metastasis of gastric cancer: comparison of Union International Contra Cancer and Japanese systems. ANZ J Surg 2004;74:852–4. 5. Roukos DH, Kappas AM. Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol 2005;2:98–107. 6. Pesic M, Karanikolic A, Dordevic N, et al. The importance of primary gastric cancer location in 5-year survival rate. Arch Oncol 2004; 12(Suppl 1):51–3. 7. Kodera Y, Sasako M, Yamamoto S, et al. on behalf of the Gastric Cancer Surgery Study Group of Japan Clinical Oncology Group. Identification of risk factors for the development of complications following extended and superextended lymphadenectomies for gastric cancer. Br J Surg 2005;92:1103–9. 8. Sasako M, Saka M, Fukugawa T, et al. Surgical treatment of advanced gastric cancer: Japanese perspective. Dig Surg 2007;24:101–7. 9. Marrelli D, Pedrazzani C, Neri A, et al. Complications after extended (D2) and superextended (D3) lymphadenectomy for gastric cancer: analysis of potential risk factors. Ann Surg Oncol 2007;24: 25–33. 10. Smith JK, McPhee JT, Hill JS, et al. National outcomes after gastric resection for neoplasm. Arch Surg 2007;42:387–93. 11. Kulig J, Popiela T, Kolodziejczyk P, et al. Polish Gastric Cancer Study Group. Standard D2 versus extended D2 (D2þ) lymphadenectomy for gastric cancer: an interim safety analysis of a multicenter, randomized, clinical trial. Am J Surg 2007;193:10–5. 12. Ganpathi IS, So JBY, Ho KY. Endoscopic ultrasonography for gastric cancer: does it influence treatment? Surg Endosc 2006;20: 559–62. 13. Japanese Classification of Gastric Carcinoma. 2nd English ed. Gastric Cancer 1998;1:10–24. 14. Hochwald SN, Brennan MF, Klimstra DS, et al. 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