144 POSTER Gastric cancer surgery with intention to treat: value of tumor resection line involvement

Poster session: Oesophageal and gastric cancer cious. For these patients this study evaluated (1) incidence of subsequent invasive intervention for primary-tumour related complications and (2) survival. Methods: This was a cohort study based in an academic tertiary referral centre. During October, 2001-October, 2004, 67 (32%) of 211 consecutive patients with adenocarcinoma of the stomach or gastroesophageal junction (GEJ) had synchronous M1 disease at computed tomography scanning or laparoscopy. 63 patients with M1 disease were managed non-operatively and complete data-sets were available for 40 men and 15 women, median age 73 years. Pre-treatment functional performance status (FPS) was good (ECOG ≤ 1) in 67%. The primary tumour was at the GEJ in 20% and poorly-differentiated in 60%. M1 disease involved peritoneum in 80% or was exclusively non-peritoneal in 20%. Systemic chemotherapy was administered to 67%. Results: 14 patients (25%) had intervention; at median interval of 5 months from diagnosis. 8 patients had more than one intervention, with maximum 3 procedures. Intervention was for gastric obstruction (20%), bleeding (7%) or perforation (2%). No patient had gastrectomy. Laparotomy was performed in 9%; the remainder had endoscopic or radiologic procedures or radiation therapy. There was no intervention-related mortality. Median survival was 7 months (95% CI, 4-10). At Cox regression univariate analysis, good FPS, exclusively non-peritoneal metastasis, non-poor differentiation and chemotherapy predicted significantly longer survival; chemotherapy was the only independently significant predictive factor. Conclusion: Palliative interventional procedures were performed on 25% of patients, with no mortality. Survival characteristics were similar to previous series of non-curative gastrectomy for M1 disease. 142

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Radical perigastric lymphadenectomy with the laparoscopic approach M. Shrotri 1 , V. Upasani 1 , M. Haqqani 2 , W. Taylor 2 . 1 University Hospitals Aintree, Department of Surgery, Liverpool, United Kingdom; 2 University Hospitals Aintree, Directorate of Histopathology, Liverpool, United Kingdom Introduction: Laparoscopic approach upper gastro-intestinal cancer surgery is still not well established in the United Kingdom and the main objection for this approach is the ability to achieve lymphadenectomy as radical as achieved by open surgery. This paper presents the early experience of the author from United Kingdom. Materials & Methods: In the period 27.04.05 – 22.06.06 (14 months) ten cases of gastric (7) and oesophageal (3)cancers underwent laparoscopic radical procedures. In the gastrectomy group there were 2 total, 4 distal and 1 proximal resections (D2 radical resections). In the oesophagectomy group there were 3 gastric mobilisations with intra-abdominal lymphadenectomy (thoracic procedure was done open). The resected specimens were dissected and examined meticulously by specialist upper gastro-intestinal cancer pathologists (two) from the same University Hospital. The number of nodes retrieved was compared to open procedures (radical D2 gastrectomies and oesophagectomies) performed by the same author to regulate quality control. The average hospital stay and mortality after surgery was compared as well. Results: Average lymph-node yield in radical gastrectomy was 40 (range 16-67) and radical oesophagectomy was 38 (range 28-44). This retrieval compares well with that achieved by open surgery i.e. 51 (range 18-95) and 46 (range 22-84). The average hospital stay after laparascopic procedures for upper GI cancers was 16.8 days (8 days for gastrectomies, 35 days for oesophagectomies) as compared to 33 days (42 days for gastrectomies, 28 days for oesophagectomies). The mortality in the laparoscopic group was 10% (1 case) as compared to 18% in the open surgery group. Summary: The laparoscopic approach in radical dissection for upper gastrointestinal cancers appears to be feasible in terms of lymph-node retrieval, which is considered to be the surrogate marker for adequacy of D2 or radical lymphadenectomy in gastric or oesophageal cancer management. At the same time there seems to be shorter hospital stay and lowered mortality in this high risk group of cancer patients. It remains to be seen whether there is parity in long term disease free and overall survival.

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Prognostic value of cox-2 expression in gastric cancer A. Tamburini 2 , V. Tomajer 1 , L. Albarello 1 , E. Orsenigo 2 , M. Carlucci 2 , R. Castoldi 2 , S. Di Palo 1 , C. Staudacher 2 . 1 San Raffaele Hospital, General Surgery, Milan, Italy; 2 Vita-Salute University, San Raffaele Hospital, Milan, Italy Background: Cyclooxygenase (COX) is the rate –limiting enzyme in prostaglandin synthesis and the target of non steroidal anti-inflammatory drugs. A direct link between the isoenzyme COX-2 and carcinogenesishas been demonstrated by studies showing that the intestinal polyp growth is suppressed by pharmacologic inhibition and genetic deletion of COX-2 in mice. Moreover, the ransgenic expression of COX-2 and microsomal prostaglandin E syntase induces hyperplastic tumor growth in mouse, and that celecoxib reduces chemically induced gastric carcinogenesis in rat. COX-2 expression seems to have a role in early gastric carcinogenesis. Aim: The aim of this study was to evaluate the correlation between COX-2 expression and prognosis of gastric cancer (any pN, any pT) without distant metastasis. Methods: 194 gastric carcinoma patients (123 males, 87 women) without distant metastasis (pM0, any T) who underwent R0 gastric resection were enrolled in this study. Immunohistochemical staining has been employed for detecting the expression of COX-2. Cytoplasmic COX-2 immunoreactivity was assessed by the intensity of staining and percentage of positivity areas. Associations between factors, including clinico-pathologic variables and COX-2 scores, were assessed by χ2 and Student t test. Survival rates were calculated using the Kaplan-Meier method and the differences between the groups were analysed by log-rank test. Results: A correlation between COX-2 expression, grading and advanced penetration depth (mean cox-2 expression 74% in early gastric cancer vs 52% in non-EGC, p = 0, 017). There was an association between Cox2 expression and the presence of lymph-node metastasis ( p<0, 0001, χ2 ). We also observed a significant association between COX-2 expression and relapse of disease ( p = 0, 05, Kaplan Meier), but not with poor survival. Conclusion: High COX-2 protein expression, serosal invasion (pT3-pT4) and presence of lymph-node metastasis are poor prognostic factor in patients with gastric carcinoma without distant metastasis. Cox-2 expression in any percentage strongly correlates with lymph-node invasion and penetration depth, so it may be indicate tumor aggressiveness. 144

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Gastric cancer surgery with intention to treat: value of tumor resection line involvement V. Tomajer, E. Orsenigo, T. Casiraghi, M. Carlucci, R.R. Castoldi, S. Di Palo, C. Staudacher. San Raffaele Hospital, General Surgery, Milan, Italy Background: prognostic value of resection line involvement after curative gastrectomy for cancer is still debated. It always has been considered as a negative prognostic factor, but it seems to lack its significance in stage III and IV tumor with microscopic involvement of section line (R1), in which local relapse occours before distant metastases. In these patients, a more aggressive surgical approach could raise morbidity without any improvement in long term survival and patients quality of life. Methods: 1118 gastric adenocarcinoma patients (654 males, 464 women) without distant metastasis (pM0, any T) who underwent gastric resection for carcinoma at San Raffaele Hospital between 1990 and 2005 were enrolled in our study. Mean age was 65 years old. All patients were treated with curative resection intent. Patient were divided in two groups: R0 patients (no resection line involvement, R0: 978 pts) and R+ patients (R+ 139 pts: R1 117 pts; R2 22 pts respectively). Associations between factors, including clinicopathologic variables, were assessed by χ2 and Student t test. Survival rates were calculated using the Kaplan-Meier method and statistical significance between the groups was analyzed by log-rank test. Results: there was no diffenence in sex and age between the two groups. Percentage of positive resection margin (R+) was higher in patients who underwent total gastrectomy (TG) (15,7% vs 9,2% respectively, p = 0, 049). R+ percentage significally correlated to TNM stage ( p<0, 001), depth of tumoral invasion (pT) ( p<0, 001) and lymph-node involvement (pN) ( p<0, 001). There was a correlation between R and tumor diameter [R+ 6,26 cm (SD 2,9) vs R0 4,36 cm (SD 2,6) respectively ( p<0, 001)]. Long

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Poster session: Oesophageal and gastric cancer

term survival correlated to surgical clearance [R0 61,15%, 60,5%, 51,61% (3, 5, 10 years respectively); R1 31,87% (3 years); R2 0% (2 years) respectively ( p<0, 001)]. Disease free survival also correlated to absence of resection line involvement [R0 62,51% and 51,48% (3 and 5 years) vs R1 17,7% (3 years) respectively ( p<0, 001)]. Cox regression showed serosal invasion, lymph-nodal metastases and resection line tumor involvement in I and II stage patients as independent negative prognostic factors ( p = 0, 018). Concluions: tumor resection line involvement after gastric cancer surgery with intention to treat significantly correlates with a worse prognosis in univariate analysis and in multivariate analysis in Stage I and II patients, in which we consider aggressive surgery as the treatment of choice. 145

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High complete response rates with a novel neoadjuvant chemoradiation regimen for stage II-III oesophageal cancer G. Nieuwenhuijzen 1,5 , L. van de Schoot 1 , M. van der Sangen 2 , G. Creemers 3 , O. Repelaer-van Driel 4 , H. Rutten 1 . 1 Catharina Hospital, Surgery, Eindhoven, The Netherlands; 2 Catharina Hospital, Radiation Oncology, Eindhoven, The Netherlands; 3 Catharina Hospital, Medical Oncology, Eindhoven, The Netherlands; 4 Maxima Medical Centre, Surgery, Eindhoven, The Netherlands; 5 Comprehensive Cancer Centre South, Eindhoven, The Netherlands Introduction: The outcome for patients with oesophageal cancer undergoing surgical resection alone is poor. We studied the feasibility and efficacy of a new neo-adjuvant chemoradiation protocol with moderate toxicity and potential high reponse rates followed by surgery in patients with stage II-III oesophageal cancer. Methods: In the period from jan 2002 – nov 2004, 50 patients with a potential resectable stage II-III oesophageal cancer received chemotherapy with paclitaxel 175 mg/m2 iv and carboplatin AUC 5 iv on day 1 and 22, 5FU 200 mg/m2 ci on day 1 to 42 in combination with radiotherapy 45 Gy in 25 fractions starting on day 1. Surgery followed 6-8 weeks after completion of neoadjuvant treatment. Results: 50 patients have completed neoadjuvant therapy. Patient characteristics: M/F:44/6, median age 60 yrs (34-75), median WHO 1 (0-2), adenoca (n=42), squamous cell cancer (n=8). Toxicity: no treatment related deaths due to chemoradiation. One patient died after completion of neoadjuvant therapy due to a myocardial infarction. Uncomplicated grade 3 leucopenia in 23 pts (46%). All patients experienced oesophagitis, usually mild (≤ gr 2), however 13 pts needed nasogastric enteral feeding during therapy. 2 patients showed metastatic disease at surgery, hence 47 pts underwent surgery with a curative intention (transhiatal n= 44, transthoracic n=3). Pathologic complete response was achieved in 20 of 47 operated patients (43%). R0 resection was achieved in 45 of 47 operated patients (96%) There were 4 post-operative deaths (8.5%), due to major anastomotic complications of the gastric tube (n=3) and a progressive chylothorax (n=1). Post-operative complications: anastomotic leakage (major n=5, minor n=11), pulmonary (n=15), recurrent nerve palsy (temporary n=3, permanent n=1) and cardiac dysrhythmias (n=3). After a relative short median follow-up of 2.6 years (1.3-4.5) actuarial 3 year survival on an intention to treat basis was 68%. Actuarial 3 year survival in complete responders was 81%. Actual survival data after a median follow up 3 years can be presented at the meeting. Conclusions: This novel combined-modality neoadjuvant approach for treatment of patients with stage II-III oesophageal cancer is feasible and preliminary assessment of efficacy is encouraging, with 43% of the patients having a pCR and 96% R0 resection rate with an acceptable morbidity and mortality. Preliiminary survival data are very promising. 146

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Esophagectomy in rural hospital without ICU care facilities R. Karwasra, S. Singh. Regional cancer Centre, PGIMS, Surgery and Surgical Oncology, Rohtak, India Background: Cancer of esophagus is an extremely lethal malignancy and surgery is the most effective modality of treatment, but associated with high morbidity and mortality and therefore traditionally esophagectomy is performed at high volume center having ICU facilities. Aim: Focus to compare results of esophagectomy performed without ICU care.

Materials and methods: 406 patients of carcinoma esophagus presented from 1999-2003. Out of which 66 patients explored & 14 patients were found inoperable. Total 52 esophagectomy performed out of which 45 were Transhiatal and 7 were Transthoracic. Results: Intra-operative complications occurred in 5 (9.6%) patients out of which airway injury in 3 (5.7%) patients, injury to recurrent laryngeal nerve in 1 (1.9%) patient and massive bleeding in 1 (1.9%) patient. Postoperatively pulmonary complications were most common & occurred in 18 (34.62%), post operative wound infection in 3 (5.77%) and anastmotic leakage in 3 (5.77%) cases. 2 (3.85%) patients died in the peri-operative period due to pulmonary complications. Mean duration of post-operative hospital stay was 18.16 days. All the patients had excellent swallowing status. Distant metastasis was the most common cause of death in operated patients. 2 patients had recurrence at supraclavicular node while recurrence at anastmotic site was not found in any of the patients. 1 year & 2 year survival was 72.22% & 27.22% respectively. Conclusion: Results and complication rate of esophagectomy at our center were comparable to the leading World Series despite non-availability of ICU care. 147

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Laparoscopic partial gastrectomy with D2 lymph-node dissection for pT1-pT2 gastric cancer: result in a single Institute V. Tomajer, E. Orsenigo, M. Carlucci, R. Castoldi, S. Di Palo, C. Staudacher. San Raffaele Hospital, General Surgery, Milan, Italy Background: Despite evidence that minimally invasive treatment for many benign conditions has led to a reduction in perioperative morbidity and mortality, with a resultant decrease in hospital stay and accelerated return to normal activities, critics have expressed the view that the benefit for patients with cancer is more limited. However, others have argued that for diseases, such as upper gastrointestinal cancer, minimally invasive techniques have a clear benefit even for curative therapy. Aim: to evaluate the feasibility of totally laparoscopic subtotal resection for T1-T2 gastric cancer. Methods: 120 gastric adenocarcinoma patients (69 males, 51 women) pM0, pT1-pT2 who underwent R0 gastric resection at San Raffaele Hospital between 2000 and 2005 were enrolled. All patients underwent subtotal gastrectomy for distal stomach neoplasia; we divided them in two groups (LPS: laparoscopic group, 50 pts; LPT: laparotomic group, 70 pts). Associations between factors, including clinico-pathologic variables, morbidity and postoperative mortality, were assessed by χ2 and Student t test. Results: mean age was 64,69 in LPS and 60,00 in LPT group (p=NS). Percentage of pT1 and pN0 was higher in LPS group ( p = 0, 029 and p = 0, 016 respectively), but there was no difference of mean tumor diameter (3,21 LPS vs 4,09 LPT, p=NS) and R0 percentage between the two groups. Mean operating time was higher in LPS group (190,48 min LPS vs 112,35 min LPT, p=NS). Conversion rate was 6%. Mean number of retrieved lymph-node was higher in LPS group (27,82 vs 23,75, p=NS). Morbidity was 26% in LPS group and 10% in LPT group, not statistically different, and similar were mortality rate and re-operation rate (3,4% and 6% in LPS group, 3,7% and 5,7% in LPT group respectively (p=NS). Post-operative hospital stay was similar, with a mean of 11,88 for LPS and 11,73 in LPT group (p=NS). We divided LPS group in two period (Group A from 2000 to 2002, Group B from 2003 to 2005), with reduction of post-operative hospital stay, (14,5 vs 11,27, p=NS). Concluions: subtotal totally laparoscopic gastrectomy for gastric cancer is technically feasible, and it must be done by skilled surgeon. Reduction of post-operative stay represent the importance of a learning curve in laparoscopic surgery for cancer. Further investigation are necessary to assess long term survival, but similar R0 percentage and number of retrieved lymphnode can support the oncological value of laparoscopy. 148

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Long-term results following D1 and D2 gastrectomy A. Tentes, C. Mirelis, I. Bougioukas, A. Xanthoulis, K. Bekiaridou, E. Tsalkidou, I. Nikas, K. Balaxidis, A. Dimoulas. Didimotichon General Hospital, Surgical Department, Didimotichon, Greece The purpose of the study is to report the long-term results of patients with