Canadian Association of General Surgeons Canadian Association of Thoracic Surgeons Canadian Society of Colon and Rectal Surgeons

of presentations to the Annual Meetings of the Canadian Association of General Surgeons Canadian Association of Thoracic Surgeons Canadian Society of Colon and Rectal Surgeons Canadian Hepato-Pancreato-Biliary Society Canadian Society of Surgical Oncology RÉSUMÉS des communications présentées aux congrès annuels de l’Association canadienne des chirurgiens généraux l’Association canadienne des chirurgiens thoraciques la Société canadienne des chirurgiens du côlon et du rectum la Canadian Hepato-Pancreato-Biliary Society la Société canadienne d’oncologie chirurgicale Vol. 51, Suppl., August / août 2008 www.cma.ca/cjs CANADIAN SURGERY FORUM Halifax, NS September 11–14, 2008 FORUM CANADIEN DE CHIRURGIE Halifax, N.-É. du 11 au 14 septembre 2008 Canadian Association of General Surgeons © 2008 Canadian Medical Association Can J Surg, Vol. 51, Suppl., August 2008 — Abstracts 3 AUTOCRINE MOTILITY FACTOR RECEPTOR EXPRESSION PREDICTS RECTAL CANCER PATIENT OUTCOMES. M.R.C. Dickeson, S.K. Chan, O.L. Griffith, P.T. Phang, H. Masoudi, S.J.M. Jones, I.R. Nabi, S.M. Wiseman. Department of Surgery, St. Paul’s Hospital, Departments of Medical Genetics, Cell Biology and Pathology, University of British Columbia, Genetic Pathology Evaluation Centre, Prostate Research Centre, Vancouver General Hospital, British Columbia Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, BC. The identification of molecular markers that aid in predicting outcomes for individuals diagnosed with rectal adenocarcinoma could provide important prognostic information beyond that of clinical and pathological characteristics alone. The purpose of this study was to identify molecular markers that predict outcomes for individuals diagnosed with rectal cancer. A retrospective analysis was carried out for 130 consecutive patients undergoing resection for rectal adenocarcinoma at a single institution over a 6-year period. Clinical characteristics evaluated were: age, sex, tumour location, preand postoperative chemoand radiotherapy, and surgical procedure. Pathologic variables evaluated included: margin status, TNM stage and the presence of vascular and lymphatic invasion. Significant variables were identified by Kaplan–Meier survival analysis and log-rank test. The tumour specimens from these 130 patients were used to prepare a tissue microarray (TMA) that was stained for 10 molecular markers involved in tumourigenesis. The markers evaluated were: autocrine motility factor receptor (AMF-R), Aurora-A, Aurora-C, Cav-1, HER2, HER3, HER4, MDM2, MRAS and PGI. Statistical analysis was used to compare the expression of the markers and correlate their expression with the clinical and pathologic variables. The clinicopathologic variables and virtually all molecular markers analyzed in the study did not significantly predict patient outcomes. However, increased expression of AMF-R did significantly predict decreased overall survival (p < 0.001), disease-free survival (p = 0.036) and disease-specific survival (p = 0.005). The failure of clinical and pathologic variables to predict patient outcomes reemphasizes the need for better tools to predict rectal cancer prognosis. AMF-R warrants further study as a molecular prognosticator, and potential target for therapy, for rectal cancer. 2 SHORT-TERM BLOCKADE OF T CELL COSTIMULATORY AND ADHESION PATHWAYS PREVENTS NEONATAL PORCINE ISLET XENOGRAFT REJECTION. D.C.M. Mok, H. Arefanian, R.V. Rajotte, G.R. Rayat. Alberta Diabetes Institute, Department of Surgery, University of Alberta, Edmonton, Alta. The objective of this study was to determine if a combination of short-term blockade of the CD28/B7 costimulatory pathway using CTLA4-Ig in combination with short-term blockade of other costimulatory, or the LFA-1/ICAM-1 adhesion pathway using monoclonal antibody (mAb) therapy could lead to long-term neonatal porcine islet (NPI) xenograft survival. Sixto 8-week-old, male streptozotocin-induced diabetic (≥ 17 mmol/L) C57BL/6J mice were transplanted with 2000 NPIs under the kidney capsule. Transplanted mice were treated with an intraperitoneal injection of CTLA4-Ig (50 μg on days –1 to 15) either alone or in combination with antiLFA-1 (200 μg on days 0, 1, 7, 14), anti-ICOS (200 μg on days 0–14) or anti-CD45RB (300 μg on day –1 and 100 μg on days 0–5) mAbs. Upon graft rejection or > 100 days posttransplantation in long-term functioning grafts, mice were euthanized and their graft examined by immunohistochemical staining. Flow cytometry was used to phenotype systemic immune cell populations. Single therapy of CTLA4-Ig (0/6), anti-CD45RB (0/10) and anti-ICOS (0/6) mAbs did not prevent rejection of NPI xenografts in mice. Single therapy with anti-LFA-1 mAb, however, resulted in long-term graft function in 67% (4/6). Meanwhile, combination therapy of CTLA4-Ig with antiLFA-1 mAb, anti-CD45RB mAb or anti-ICOS mAb prolonged graft survival in 67% (4/6), 33% (2/6) and 50% (3/6) of mice, respectively, but immune cell infiltration of the graft was still detected. Immune cell infiltration in functioning islet xenografts were predominantly CD4+ T cells. In contrast, systemic CD4+ T cell populations in combination therapy-treated islet xenograft recipients were reduced to levels found in naive nontransplanted B6 mice. Simultaneously targeting the CD28-B7 costimulatory pathway and the LFA-1/ICAM-1 adhesion pathway was most effective in preventing NPI xenograft rejection and controlled systemic CD4+ T cell expansion. Combination therapy targeting T cell costimulatory and adhesion pathways may form a future component of antirejection therapy for islet xenotransplantation with the potential to induce xenograft tolerance. 3 THE ROLE OF SCREENING EVALUATIONS IN PATIENTS WITH GERMLINE MUTATIONS OF THE E-CADHERIN/CDH1 GENE (HEREDITARY DIFFUSE GASTRIC CANCER). P. Hebbard, D. Fontaine, J. McCarthy, K. Laing, F. Bursey, N. Wadden, Canadian Surgery Forum 2008 Forum canadien de chirurgie 2008 Canadian Association of General Surgeons Association canadienne des chirurgiens généraux