Tu1621 Prognostic Significance of ZEB1 Expression in Cancer Cells and Cancer Associated Fibroblasts in Pancreatic Head Cancer

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Conclusion. Roux-en-Y drainage of the pancreatic stump by nonstented duct-to-mucosa anastomosis reduced the amylase level in the drainage fluid after DP-CAR (Journal of HepatoBiliary-Pancreatic Sciences In Press.). We are proceeding to examine the evidence of the present study in a multicenter, randomized controlled trial for distal pancreatectomy patients (ClinicalTrials.gov NCT01384617).

MRI Liver in Pancreatic Cancer: A Game Changer Cindy Chew, Hedvig Karteszi, Nigel B. Jamieson, Ross Carter, Euan J. Dickson, Colin McKay Background: Pancreatic cancer is one of the leading causes of cancer mortality. Surgery is the only chance of cure, but is inappropriate for patients with metastasis. Aim: To evaluate the frequency of liver metastasis on MRI in patients with resectable pancreatic cancer and normal liver on contrast enhanced MDCT. Methods: Between April 2012-13, all patients with resectable pancreatic cancer based on CT staging underwent MRI liver - utilising hepatocyte specific contrast agent and diffusion weight imaging. Results: Forty five consecutive patients were examined. Thirty two were male and 13 were female. Median age was 64 years (range 31-76 years). MRI was performed at a median of 2 weeks from CT. Thirteen (29%) patients with normal liver on CT had findings consistent with liver metastases while 4 (9%) had indeterminate liver lesions on MRI. Three of the 4 patients with indeterminate liver lesions demonstrated progression on follow up imaging consistent with metastases. One of the 28 patients with a normal MRI liver underwent palliative bypass on discovering a 5mm subcapsular lesion at laparotomy. At a median follow up of 12 months, 3 of the remaining 27 patients with normal MRI had evidence of liver metastasis (7, 10 and13 months post MRI) while 4 had extrahepatic disease. Survival was significantly reduced in patients with liver metastasis on MRI (p=0.01). Conclusion: MRI identified liver metastases in 36% of patients with resectable pancreatic cancer on MDCT and should be included in the routine staging of these patients.

Tu1619 Socioeconomic Status and Access to Care: Do They Influence Outcomes in Pancreaticoduodenectomy? Gregory C. Wilson, Jeffrey M. Sutton, Koffi Wima, Ian M. Paquette, Jeffrey Sussman, Syed Ahmad, Michael J. Edwards, Shimul A. Shah, Daniel E. Abbott PURPOSE: For pancreatic surgery, high volume (HV) centers have demonstrated superior outcomes. However, the effects of socioeconomic status (SES) and access to care on outcomes in pancreaticoduodenectomy (PD) are unknown. METHODS: The University Healthsystems Consortium (UHC) database was queried to identify 9,883 adult patients undergoing (PD) from 2009-2011. Patients were stratified into quintiles based on a validated SES score. Patient distance to center was calculated using Maptitude Geographic Information System. Logistic regression determined how patient characteristics, including distance to center, influenced center access. RESULTS: Lower SES patients undergoing PD were more likely to be younger (64 years vs. 67 years, p<0.001), black (20.9% vs. 3.4%, p<0.001), and have a higher severity of illness index (p<.001). Lower SES patients also had longer hospital stays (10 d vs. 9 d, p<0.001), increased hospital costs ($20,876 vs. $18,708, p<0.001) and were less likely to receive care at a HV center (37.7% vs. 43.8%, p<.001). Compared to the lowest SES patients, the highest SES patients resided closer to HV centers (36.2 miles [IQR 16.4136.3] vs. 129.8 [IQR 46.0-217.9], p<0.001) and traveled less to undergo PD (18.7 miles [IQR 9.2-35.5] vs. 54.8 miles [IQR 13.6-109.1], p<0.001). Patients in the lowest SES quintile undergoing care at a HV center traveled a median distance of 71.1 miles (IQR 29.0-137.2), significantly further than the closest available center (43.0 [IQR 9.9-78.4], p<0.001) Lowest SES patients, when undergoing surgery at LV vs. HV centers, had longer hospital stays (12d vs. 9d, p<.001), increased hospital cost ($21,914 vs. $19,111, p<.001) and higher readmission rates (21.5% vs. 16.1%, p=0.01). CONCLUSIONS: Low SES patients are less likely to access high volume centers, travel significantly further to do so, and have worse outcomes with disproportionate utilization of care at low volume centers. These data suggest that increased access to HV centers could improve outcomes in low SES patients. Tu1620

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Normal liver staging CT.

Total Pancreatectomy With Islet Autotransplantation for Chronic Pancreatitis: the Price Patients Pay for Improvements in Quality of Life Katherine A. Morgan, Stefanie M. Owczarski, Jeffrey J. Borckardt, Wendy Balliet, Hongjun Wang, David B. Adams BACKGROUND: For selected patients with debilitating pain from chronic pancreatitis total pancreatectomy with islet autotransplantation (TPIAT) has been undertaken with recently increased enthusiasm. Safety and efficacy, i.e. "patient-centered cost", of this radical procedure has not been well assessed previously. METHODS: A retrospective review of a prospectively collected database of patients undergoing TPIAT was undertaken. Perioperative morbidity, quality of life (QOL, SF-12), and insulin use were assessed preoperatively and at 12 and 24 months postoperatively. RESULTS: One hundred twenty patients (93 women, mean age 41, mean BMI 26.2) underwent TPIAT. Duration of pancreatitisprior to TPIAT averaged 7.6 years (0.5-40). Mean operative time was 237 minutes (75-395), EBL was 618 cc (50-7800), and median islet equivalents transplanted were256,470(969-1,168,725), or 3640IEQ/kg (14-16010). Average length of hospitalization was 12 days. Twelve patients required reoperation in the 30-day post-operative period (10%). Postoperative morbidity overall was 68% and 23% of patients had a complication requiring intervention (Clavien-DindoIIIa or greater). Perioperative mortality was 1.6%. Five patients (4%) died in the follow-up period. Eightyfivepatients were available for at least 12 monthfollow-up. Physical QOL went from mean 27 preoperatively to 35 and 33 at 12 and 24 months (p=0.001, 0.003)and mental health QOL went from 38 to 42 and 41 (p=0.02, 0.2).Insulin independence was achieved in 26%and 29% at 12 and 24 months respectively. CONCLUSION: Quality of life is significantly improved in patients who undergo TPIAT for chronic pancreatitis, but with notable costsin postoperative morbidity and diabetes. Improvements in physical and mental QOL are sustained up to two years after surgery.

One of multiple lesions seen on MRI consistent with multiple liver metastases (subcapsular location, segment VIII). Follow up CT 4 months later demonstrated increase in the number and size of liver metastases. Tu1618 Roux-en-Y Drainage of the Pancreatic Stump by Nonstented Duct-to-Mucosa Anastomosis Reduced the Amylase Level in the Drainage Fluid After Distal Pancreatectomy With En-bloc Celiac Axis Resection Ken-ichi Okada, Masaji Tani, Manabu Kawai, Seiko Hirono, Motoki Miyazawa, Atsushi Shimizu, Yuji Kitahata, Masaki Ueno, Shinya Hayami, Yoshinobu Shigekawa, Hiroki Yamaue

Tu1621 Prognostic Significance of ZEB1 Expression in Cancer Cells and Cancer Associated Fibroblasts in Pancreatic Head Cancer Peter Bronsert, Ilona Kohler, Dirk Bausch, Martin Werner, Tobias Keck, Ulrich F. Wellner

Background. The pancreatic fistula is a fatal complication especially in distal pancreatectomy with en-bloc celiac axis resection (DP-CAR). Among the literatures about the management of the pancreatic stump after distal pancreatectomy, the most attractive method with low incidence of pancreatic fistula was reported in pancreaticoenteric anastomosis. Methods. Twenty-six consecutive patients who underwent DP-CAR between April 2008 and August 2012 were reviewed retrospectively. The first 13 consecutive patients underwent DP-CAR with no anastomosis, and the subsequent 13 consecutive patients with Roux-en-Y pancreatico-jejunostomy (PJ) by duct-to-mucosa fashion. Results. Median operation time for DPCAR with PJ was 382 compared to 366 minutes for DP-CAR with no anastomosis (p=0.840). Clinically significant pancreatic fistula (ISGPF [The International Study Group on Pancreatic Fistula] classification Grade B/C) occurred in 2 patients (15.4%) with PJ and 5 patients (38.5%) with no anastomosis (p=0.189). The median amylase level in the drainage fluid were decreased in patients with PJ compared to those in patients with no anastomosis at all time points, 315/589 (IU/L) on postoperative day (POD) 1 (p=0.336), 121/286 (IU/L) on POD 3 (p=0.050), and 52/247 (IU/L) on POD4 (p=0.044), respectively. There were no significant differences in regard to mortality and morbidity rates between the groups.

SSAT Abstracts

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor ZEB1 in epithelial-mesenchymal transition, invasion and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue. Methods: Patient baseline and follow-up data was extracted from a prospectively maintained database. After clinicopathological re-review, serial sliced tissue slides were immunostained for ZEB1 and Pan-Cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathological parameters and survival after resection. Results: N=117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer associated fibroblasts (CAF) was significantly associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of over 0.10. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection. Conclusions: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after

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resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting CAF.

impaired pancreatic exocrine function following PPPD compared to the younger patients, and that cumulative 7-hour 13CO2 exhalation of 13C-mixed triglyceride breath test is an important predictive marker of exocrine pancreatic insufficiency, even in a subclinical condition. These findings may have potential implications for the selection of therapeutic strategies in the clinical setting.

Tu1622 Portal Venous Resection in Cancer of the Pancreatic Head: What Are the Relevant Predictors of Survival? Hryhoriy Lapshyn, Ulrich F. Wellner, Birte Kulemann, Jens Hoeppner, Peter Bronsert, Dirk Bausch, Ulrich T. Hopt, Frank Makowiec, Tobias Keck, Uwe A. Wittel

Tu1625 Increased Bacterial Translocation in Aging Animals Is Not Related to Decreased Intestinal Antimicrobial Peptide Expression in Acute Pancreatitis Debora G. Cunha, Fabiano Pinheiro da Silva, Denise F. Barbeiro, Marcia K. Koike, Marcel C Machado, Irineu T. Velasco

Introduction: When tumors are found to be adherent to the superior mesenteric or portal vein during pancreatoduodenectomy, en bloc portal venous resection (PVR) is an option to achieve complete tumor resection. It has also been reported that PVR without confirmed histopathologic portal venous infiltration (PVI) is associated with significantly better survival. The aim of this study was to evaluate oncologic outcome and prognostic factors in patients receiving PVR for pancreatic cancer. Methods: A unicenter retrospective study was performed on the basis of a prospectively maintained database. IBM SPSS Version 21 was used for all calculations with the significance level set to p=0.05. Results: From 2001 to 2013, 103 patients received pancreatoduodenectomy with PVR for pancreatic head cancer. Median survival in patients with PVR without PVI was 25 months, whereas confirmed PVI was associated with poor median survival of 14 months (p<0.05). In patients with PVR, only PVI and lymph node ratio, but not margin status, T or N stage, grading, lymphatic, microvessel or perineural infiltration, age or gender were independent prognostic factors in a multivariate Cox proportional hazards model. Conclusion: Portal venous resection for tumor adherence in pancreatic cancer is associated with equal median survival as in patients without PVR when there is no histopathologic infiltation of the large veins. Additional prognostic information is only provided by lymph node ratio, whereas margin status and other standard histopathologic parameters have no additional predictive value in this situation.

Introduction/background:Acute pancreatitis (AP) in elderly patients in spite of similar occurrence of local complications is followed by a substantial increase in organ failure and mortality rates. We have recently demonstrated that aging is related to increased bacterial translocation and distant organ damage in acute pancreatitis. Enteric antimicrobial peptides are key effectors of innate immunity and therefore could have reduced expression in aging animals with acute pancreatitis. The aim of the present study was to evaluate the effect of aging on intestinal expression of antimicrobial peptides in acute pancreatitis Methods :AP was induced in male Wistar rats by an intraductal 2.5% taurocholate injection and divided in 2 experimental groups(20 rats each group) G-1 young 3 month old rats and older (18 month old rats). Twelve hours after AP fragments of distal ileum were collected for evaluation of the gene expression of alfa defensins 5 and 7 ,Cramp, IL-1 beta , IL-10 and TNF -alpha. Results : A significant increase in the intestinal expression of alpha defensins 5 and 7 was observed in older group compared to the young animals with AP (p< 0.05).Cramp gene expression was similar in both groups .Also a significant increase in intestinal TNF-alpha expression was observed in older group compared to young rats (P<0.05). The expression of IL-1 beta was similar in both groups of animals. Intestinal IL-10 gene expression was increased in young animals compared to the older group Conclusions The increased bacterial translocation in aging animals is not related to a decreased production of antimicrobial peptides but could be related to imbalance between intestinal pro- inflammatory and anti -inflammatory cytokine production

Tu1623 Impact of Pancreatic Fistula on Recurrence and Long-Term Prognosis of Periampullary Adenocarcinomas After Pancreaticoduodenectomy Dowan Kim, Pablo E. Serrano, Peter T. Kim, Paul D. Greig, Carol-Anne Moulton, Steven Gallinger, Alice C. Wei, Sean Cleary

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Background: The impact of pancreatic fistulas (PF) on cancer-specific survival and recurrence patterns is not well understood. The objective of this study was to evaluate the impact of PF on disease-free-survival (DFS) and overall-survival (OS) after pancreaticoduodenectomy in patients with periampullary adenocarcinomas, including pancreatic, distal bile duct, duodenal and ampullary adenocarcinoma, Methods: This is a retrospective cohort study of patients undergoing pancreaticoduodenectomy for periampullary adenocarcinomas from 2000-2012. Univariate and multivariate survival analyses were performed to determine the impact of PF on DFS and OS, while controlling for pathologic and clinical factors. Results: There were 634 PD (pancreas: 347 - other periampullary: 287); median age: 65 (range: 2484) years; 424/634, 68% had node positive disease; 61/634, 10% had positive margins and 98/634, 16% were poorly differentiated. There were 81/634, 13% patients with PF. Perioperative mortality rate was 1.7% (11/634), higher in patients with PF (10 vs. 0.5%, P < 0.001). In the multivariate analysis, PF significantly reduced DFS [Hazard ratio (HR): 1.6, 95% confidence-interval (CI): 1.1-2.6] in pancreatic but not in other periampullary cancer patients. Other factors associated with decreased DFS and OS were: node, margin-positive, and higher-grade cancers. Adjuvant therapy was associated with improved OS in pancreatic cancer patients (HR: 0.7, 95% CI=0.5-0.9, P=0.02). PF was not associated with decreased OS in pancreatic or other periampullary cancer patients. Conclusion: PF increase the risk of pancreas cancer recurrence after pancreaticoduodenectomy. Low tumor grade, negative lymph nodes, and negative resection margin are associated with improved DFS and OS.

Introduction: Walled off pancreatic necrosis (WOPN) is a potentially lethal complication of acute necrotic pancreatitis occurring in 5-10% of patients. We hypothesized that minimally invasive surgical cystgastrostomy and necrosectomy is a safe and feasible approach with comparable results to endoscopic management. Method: A retrospective review of a prospectively maintained data base of patients who underwent minimally invasive surgical (laparoscopic and robotic) cystgastrostomy and necrosectomy for WOPN was compared to a retrospective cohort of patients who underwent endoscopic cystgastrostomy and necrosectomy. Periprocedural outcomes were analyzed. Failure for the surgical group was defined as the need for any reintervention due to persistence of WOPN, whereas it was defined as the need for surgery in the endoscopic group. Results: Between 2008 and 2013, 15 patients underwent minimally invasive necrosectomy (robotic =10, laparoscopic=5) and 22 patients underwent endoscopic cystgastrosotomy and necrosectomy. The surgical cohort had a larger median cyst size compared to the endoscopic group (16 cm vs 12 cm P=0.03). There were no differences in age, sex, race, BMI, Charlson Comorbidity Index (CCI), etiology of pancreatitis, and location of WOPN between both groups (all P=NS). For the surgical cohort, average OR time was 195 min, average EBL was 67 cc and 60% underwent concomitant cholecystectomy for biliary etiology. There was no mortality in either group and no statistical difference in the frequency of post procedural complications; surgical group (pulmonary embolus(1);splenic artery pseudoaneurysm (1), infected collection (2)) and endotherapy group (perforation (1), bleeding (1),infected collection (2)). Failure of WOPN to resolve occurred in 3 patients (20%) in the surgical group compared to 3 patients (13.6%) in the endoscopic group (P=0.66). Reintervention was less common in the surgical group versus the endotherapy (20% versus 59%, P= 0.041) with a median re-intervention rate of 0 (range 0-2) for the surgical group versus 1(range 0-10) for the endoscopic group (p=0.02).Mean total length of stay-inclusive of readmissions and reinterventions- was similar between both groups (Surgical group= 9 days, Endoscopy =18.1 days, P=0.087) Conclusion. Minimally invasive cystgastrostomy and necrosectomy is safe and feasible for the management of WOPN with similar success and complication rates compared to the endoscopic approach. It may be considered as the intervention of choice when combined with cholecystectomy for biliary etiology.

Tu1624 Postoperative Fat Absorptive Function and Glucose Metabolism: Does Age Affect Outcomes Following Pancreatoduodenectomy? Masahiko Morifuji, Yasushi Hashimoto, Naoya Nakagawa, Kenichiro Uemura, Yoshiaki Murakami Background: Postoperative exocrine pancreatic insufficiency and resultant maldigestion is multifactorial in nature, mainly influenced by patient-specific features of the pancreas; however, the impact of advancing age is less well understood. The aim was to evaluate the effect of aging on postoperative digestive and fat absorptive disturbances following pyloruspreserving pancreatoduodenectomy (PPPD). Methods: A prospectively collected, IRB approved database at a single institution was reviewed. Patients with an aged greater than or equal to 75 (elderly group) were compared to those with an aged less than 75 prior to surgery (control group). An optimized 13C-mixed triglyceride breath test [13C-MTG-T] using a labeled long-chain triglyceride mixture was performed to assess postoperative fat absorptive function after PPPD. Pancreatic exocrine insufficiency was defined as cumulative 7-hour 13CO2 exhalation [% dose 13C cum 7h] < 5%. Pre and postoperative HbA1c levels were measured in blood samples to assess glucose metabolism function. Diabetic patients were identified as those treated with insulin, oral hypoglycemic medications, or having an HbA1c level ≥ 6.9% (NGSP). Data pertaining [13C-MTG-T], HbA1c levels, oral pancreatic enzyme requirements, and body mass index (BMI) were measured at 1 year following surgery. Post-operative fat absorptive function was compared with pre- and post-operative patient's characteristics and glucose metabolism. Results: Consecutive 51 patients were identified from April 2005 to 2009. The elderly group ( ≥75 years) included 18 patients, while the remaining 33 patients were assigned as the control group (<75 years). The % dose 13C cum 7h was significantly higher in the elderly group (6.5 ± 5.1%) compared to the control group (3.3 ± 2.4%; P<0.05). The number of patients requiring oral pancreatic enzyme was significantly higher in the elderly group (12 of 18; 83%) comparing to the control group (11 of 33; 33%; P<0.05). The difference in either HbA1c or body mass index (BMI) between the two groups is not statistically significant. Conclusion: Aging is not associated with

Tu1627 Maturation of Robot-Assisted Pancreaticoduodenectomy Program Within an Established Pancreatic Surgery Unit Noaman Ali, Mihir M. Shah, Kevin M. El-Hayek, Jane Wey, Sricharan Chalikonda, Matthew Walsh Background: There are potential advantages to the application of minimally invasive techniques to pancreaticoduodenectomy (PD). Technical feasibility and patient selection are important factors that will impact outcomes. We present a single center experience focusing on trends in patient selection and outcomes of robot-assisted pancreaticoduodenectomy (RAPD) Methods: Retrospective review of a prospectively maintained database of all open and robotic pancreaticoduodenectomy from March 2009 to July 2013. Results: 65 patients underwent attempted RAPD at a single institution during the study period. Concurrently,

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Minimally Invasive Surgical Cystgastrostomy and Necrosectomy for the Management of Walled Off Pancreatic Necrosis; Comparison With Endoscopic Approach At a High Volume Pancreatic Center Mohammad Khreiss, Georgios Papachristou, Mustapha Daouadi, Mazen Zenati, Kenneth Lee, Melissa E. Hogg, Adam Slivka, Jennifer Chennat, Andres Gelrud, Herbert Zeh, Amer H. Zureikat