Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (−SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with −SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p < 0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04–4.24; p < 0.001) and older age (HR 1.01, 95% CI 1.00–1.03, per year; p = 0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72–1.65; p = 0.70). Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections.

BACKGROUND:Several registry-based analyses suggested a survival advantage for married versus single patients with pancreatic cancer. The mechanisms underlying the association of marital status and survival are likely multiple and complex and, therefore, may be obscured in analyses generated from large population-based databases. The goal of this research was to characterize this potential association of marital status with outcomes in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy on a prospective clinical trial.MATERIALS AND METHODS:This is an ancillary analysis of 367 patients with known marital status treated on NRG Oncology/RTOG 97-04. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model.RESULTS:Of 367 patients, 271 (74%) were married or partnered and 96 (26%) were single. Married or partnered patients were more likely to be male. There was no association between marital status and overall survival (OS) or disease-free survival (DFS) on univariate (hazard ratio [HR], 1.09 and 1.01, respectively) or multivariate analyses (HR, 1.05 and 0.98, respectively). Married or partnered male patients did not have improved survival compared with female or single patients.CONCLUSION:Ancillary analysis of data from NRG Oncology/RTOG 97-04 demonstrated no association between marital and/or partner status and OS or DFS in patients with resected pancreatic cancer who received adjuvant postoperative chemotherapy followed by concurrent external beam radiation therapy and chemotherapy. Clinical trial identification number. NCT00003216.IMPLICATIONS FOR PRACTICE:Several population-based studies have shown an epidemiological link between marital status and survival in patients with pancreatic cancer. A better understanding of this association could offer an opportunity to improve outcomes through psychosocial interventions designed to mitigate the negative effects of not being married. Based on the results of this analysis, patients who have undergone a resection and are receiving adjuvant therapy on a clinical trial are unlikely to benefit from such interventions. Further efforts to study the association between marital status and survival should be focused on less selected subgroups of patients with pancreatic cancer.

369 Background: Diabetes mellitus (DM) has been linked to poor prognosis in pancreatic cancer in numerous retrospective datasets, potentially due to higher levels of insulin and insulin-like growth factor increasing cellular proliferation. Additionally, the hyperglycemic state as well as obesity may lead to a pro-inflammatory state that may enhance tumor progression and metastases. In this analysis, the prognostic significances of diabetes, insulin use, and BMI are evaluated in a prospective, randomized trial of resectable pancreatic ductal adenocarcinoma. Methods: As previously reported, RTOG 9704 pts with resected pancreatic cancer were randomized to 5-fluorouracil (5-FU) or gemcitabine (Gem), given pre and post radiation (RT). Pts in both arms received RT to 50.4 Gy with 5-FU. DM and insulin use were collected on the RTOG 9704 CRFs. BMI was dichotomized as normal/underweight vs. overweight/obese. Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier method and variable levels were compared using log-rank test. Cox models were used for multivariable analyses. Results: 538 pts were enrolled from 1998-2002. 238 pts were eligible with analyzable diabetes and insulin use data, in addition to surgical pathology, and CA19-9 data. 32% and 35% of pts in the 5-FU and Gem arms, respectively, had DM. Of which, 24% and 19% used insulin in the 5-FU and Gem arms, respectively. 55% were overweight/obese. The 4 yr OS was 25% (95% CI: 18, 32) in pts with no diabetes, vs. 18% (10, 27) with DM (HR = 1.3 [0.9, 1.7]; p = 0.11). The 4-yr DFS was 14% (9, 20) in pts with no diabetes, vs. 9% (4, 16) with diabetes (HR = 1.2 [0.9, 1.5]; p = 0.31). Neither insulin use nor BMI was univariately associated with OS or DFS. On multivariate analysis, including nodal status, CA19-9, and other variables, DM, insulin use, and BMI were not associated with OS or DFS. Conclusions: DM, insulin use, and BMI were not associated with OS in pts with resected pancreatic cancer treated with adjuvant chemotherapy and chemoradiation. Node involvement and CA19-9 remain the most significant predictors of OS. Supported by NCI grants U10CA180868, U10CA180822, UG1CA189867 and Eli Lilly Clinical trial information: NCT00003216.

Background: Neoadjuvant therapy for pancreatic cancer is being employed more commonly. Most of these patients undergo biliary stenting which results in bacterial colonization and more surgical site infections (SSIs). However, the influence of neoadjuvant therapy on the biliary microbiome has not been studied. Methods: From 2007 to 2017, patients at our institution who underwent pancreatoduodenectomy (PD) and had operative bile cultures were studied. Patient demographics, stent placement, bile cultures, bacterial sensitivities, SSIs and clinically-relevant postoperative pancreatic fistulas (CR-POPF) were analyzed. Patients who underwent neoadjuvant therapy were compared to those who went directly to surgery. Standard statistical analyses were performed. Results: Eighty-three patients received neoadjuvant therapy while 89 underwent surgery alone. Patients who received neoadjuvant therapy were more likely to have enterococci (45 vs 22%, p < 0.01), and Klebsiella (37 vs 19%, p < 0.01) in their bile. Resistance to cephalosporins was more common in those who received neoadjuvant therapy (76 vs 60%, p < 0.05). Neoadjuvant therapy did not affect the incidence of SSIs or CR-POPFs. Conclusion: The biliary microbiome is altered in patients undergoing pancreatoduodenectomy (PD) after neoadjuvant therapy. Most patients undergoing PD with a biliary stent have microorganisms resistant to cephalosporins. Antibiotic prophylaxis in these patients should cover enterococci and gram-negative bacteria.

Controversy exists on accurately grading vascular involvement on preoperative imaging for pancreatic ductal adenocarcinoma. We reviewed the association between preoperative imaging and margin status in 137 patients. Radiologists graded venous involvement based on the Ishikawa classification system and arterial involvement based on preoperative imaging. For patients with both classifications recorded, we categorized vascular involvement as “None,” “Arterial only,” “Venous only,” or “Both” and examined the association of vascular involvement and pathologic margin status. Of 134 patients with Ishikawa classifications, 63%, 17%, 11%, and 9% were graded as I, II, III, and IV, respectively. Of 96 patients with arterial staging, 74%, 16%, and 10% were categorized as stages i, ii, and iii, respectively. Of 93 patients with both stagings, 61% had no vascular involvement, 7% had arterial only, 14% had venous only, and 17% had both involved. Ishikawa classification was strongly associated with a positive SMA and SMV margin (p<0.001). However, for arterial staging, there was no association with SMA or SMV margin. Overall, Ishikawa grading was more predicative of arterial involvement and remained significant on multivariate analysis. The use of diagnostic imaging in predicting positive margins is more accurate when using a venous grading system.

Background: Gallbladder cancer (GBC) and cholangiocarcinoma (CCA) are rare entities with relatively poor prognoses. We compared treatment outcomes of definitive resection with or without neoadjuvant therapy in GBC and CCA patients. Methods: All non-metastatic GBC and CCA patients at a single institution who underwent definitive resection from 1992-2016 were analyzed. We compared overall survival (OS), locoregional failure (LRF) and distant failure (DF) in patients who received neoadjuvant therapy (chemotherapy and/or radiation) versus those who did not receive neoadjuvant treatment. OS was analyzed using the Kaplan-Meier method and log rank tests. Cox proportional hazard models were used to analyze time to recurrence. Results: Out of 128 patients, 90 had GBC and 38 had CCA, 25 patients (27%) among GBC and 8 patients (21%) with CCA were T3, T4 or node positive. Overall, 52 (58%) GBC and 25 (66%) CCA patients received neoadjuvant treatment, chemotherapy alone 60 patients (47%) or radiation with or without chemotherapy 17 patients (13%). Chemotherapy was single agent in 44 patients (34%) and multi-agent in 25 (20%). The median OS for GBC patients was 3.1 years with 2.6 years for no neoadjuvant group and 3.1 years for neoadjuvant group (P=0.6786). Median OS was 2.6 years for CCA patients, 3.6 years for no neoadjuvant therapy versus 2.0 years for neoadjuvant group (P=0.1613). There was a trend towards increased DF in patients with CCA and GBC receiving neoadjuvant therapy: HR 2.74, 95% CI, 0.73-10.3, P=0.14 and 0.92, 95% CI, 0.44-1.93, P=0.82 respectively. The hazard ratio for time to LRF in CCA patients receiving neoadjuvant treatment was 3.17, 95% CI, 0.62-16.31, P=0.16 whereas HR was 0.15, 95% CI, 0.10-1.76, P=0.23 for GBC patients. Among GBC patients, the pattern of first failure was locoregional in 8 (10%) having 3 LRF in neoadjuvant group (2 with chemotherapy, 1 with CRT, 0 with RT alone) as compared to 5 in adjuvant group. Among 28 (35%) patients with DF first, 15 patients received neoadjuvant therapy versus 13 patients in non-neoadjuvant group. In CCA patients, LRF occurred first in 6 patients receiving neoadjuvant treatment (3 with chemotherapy, 1 with CRT, 2 with RT alone) as compared to 2 patients who were treated with non-neoadjuvant CRT. DF was the first site of failure in 9 patients treated with neoadjuvant CRT (8 with chemotherapy, 0 with CRT and 1 with RT alone) as compared to 4 patients without neoadjuvant treatment. Conclusions: In this retrospective data set, a trend towards better survival was seen in adjuvantly treated CCA patients, but not in GBC patients. Recurrence patterns also appear different among the two, which might be attributed to treatment modality used, patient selection or unmeasured factors.

# 01. Laparoscopic splenectomy with management of intraoperative hemorrhage {#article-title-2} This video demonstrates a laparoscopic splenectomy for ITP with safe management of intraoperative hemorrhage. YouTube video link: [www.youtube.com/watch?v=6vYkOy3UePQ][1] # 02. Incisional hernia after

Desmoplasia, a fibrotic mass including cancer-associated fibroblasts (CAFs) and self-sustaining extracellular matrix (D-ECM), is a puzzling feature of pancreatic ductal adenocarcinoma (PDACs). Conflicting studies have identified tumor-restricting and tumor-promoting roles of PDAC-associated desmoplasia, suggesting that individual CAF/D-ECM protein constituents have distinguishable tumorigenic and tumor-repressive functions. Using 3D culture of normal pancreatic versus PDAC-associated human fibroblasts, we identified a CAF/D-ECM phenotype that correlates with improved patient outcomes, and that includes CAFs enriched in plasma membrane-localized, active α5β1-integrin. Mechanistically, we established that TGFβ is required for D-ECM production but dispensable for D-ECM-induced naïve fibroblast-to-CAF activation, which depends on αvβ5-integrin redistribution of pFAK-independent active α5β1-integrin to assorted endosomes. Importantly, the development of a simultaneous multi-channel immunofluorescence approach and new algorithms for computational batch-analysis and their application to a human PDAC panel, indicated that stromal localization and levels of active SMAD2/3 and α5β1-integrin distinguish patient-protective from patient-detrimental desmoplasia and foretell tumor recurrences, suggesting a useful new prognostic tool.

Introduction Acute kidney injury (AKI) is a well-recognized negative prognostic factor for morbidity and mortality in acute pancreatitis (AP).Although several studies have documented a markedly increased incidence of AKI complicating AP, these studies are relatively small and include a limited number of outcomes, with mortality rates ranging from 5% to 80%.As such, quantification of AKI's effect on AP outcomes is challenging.The aim of this study was to assess the impact of AKI on mortality, morbidity and resource utilization among patients with AP over the past decade using a large national database.Materials and Methods This is a retrospective cohort study using the National Inpatient Sample, the largest publically available inpatient database in the USA, from 2004 to 2013.All patients with an ICD-9 CM code for a principal diagnosis of AP were included.There were no exclusion criteria.The primary outcome was in-hospital mortality.Secondary outcomes were morbidity measured by intensive care unit (ICU) admission, shock and multi-organ failure; resource utilization measured by abdominal CT, total parenteral nutrition (TPN) use, length of hospital stay (LOS) and total hospitalization costs.Patients who had a concomitant diagnosis of AKI were identified using the appropriate ICD-9 CM codes.Using multivariate regression analysis, odds ratios and means were adjusted for age, sex, race, income in the patient's zip code, Charlson Comorbidity Index, hospital region, urban location, size and teaching status.Results 2,690,774 patients with AP were included in the study, of which 182,448 (6.8%) had a diagnosis of AKI.Mean age was 52 years and 48% were female.For the primary outcome, mortality in patients with AP and AKI was significantly higher compared to patients without AKI (adjusted OR: 11.94, p<0.01).For the secondary outcomes, patients with AKI displayed increased odds of shock, multi-organ failure and ICU admission when compared to patients without AKI.For resource utilization, patients with AKI had higher odds of TPN use and a longer mean LOS compared to patients without AKI.Total hospital costs were also significantly increased in patients with AKI.Table 1 displays all adjusted odds rations and means with p-values.Conclusion Patients with acute pancreatitis who develop acute kidney injury have an almost 12-fold greater in-hospital mortality rate compared with patients without acute kidney injury.In addition, acute kidney injury development is associated with significant morbidity in acute pancreatitis, as measured by greater rates of shock, ICU admission and multi-organ failure.Finally, acute kidney injury in acute pancreatitis has a profound effect on resource utilization, with increased TPN use as well as longer length of stay and higher total hospitalization costs.Table 1 -Adjusted means and odds ratios for patients with acute pancreatitis with and without acute kidney injury Tu1399

Nadler, Ashlie MD; Goel, Neha MD; Selesner, Leigh; Ward, William H. MD; Hoffman, John; Reddy, Sanjay S. MD; Pitt, Henry A. MD, FACS Author Information

thus large series outcomes are unknown.Methods ACS-NSQIP was reviewed for all nontraumatic pancreatic resections (DP -distal pancreatectomy, PD -pancreaticoduodenectomy, or TP-total pancreatectomy) in patients with pancreatico-biliary or duodenal neoplastic disease from 2005-2013.Emergent operation was defined as NSQIP criteria for emergent case and/or one of the following: ASA Class 5, preoperative ventilator dependency, preoperative sepsis, or requirement of >4 units RBCs in 72 hours prior to resection.Chi-square tests, Fisher's exact tests were performed to compare postoperative outcomes Results Of 21,452 patients who underwent pancreatectomy for neoplastic indications, we identified 534 (2.5%) patients that underwent emergent pancreatectomy.Preoperative systemic sepsis (66.3%) and bleeding (17.9%) were most common indications for emergent operation.Overall 30day mortality (9.4% vs. 2.7%), major morbidity (46.1% vs. 25.6%),perioperative PRBC transfusion (47.6% vs. 23.4%),return to OR (14% vs. 5.6%), any SSI (26.6% vs. 19.6%),UTI (8.8% vs. 4.6%), unplanned intubation (9% vs. 4.1%), pneumonia (9.6% vs. 4.2%), length of stay (14 days vs. 11 days), and discharge to skilled facility (22% vs. 11.7%)were expectedly higher in the emergent cohort.For emergent cases, PD was performed more often (76.5% vs. 68.8%),DP was less common (21.5% vs. 29.0%),and TP was similar (1.9% vs. 2.1%) compared to elective cohorts.Similar worse outcomes persisted when stratified by type of pancreatic resection (DP, PD, TP), with the highest mortality found for emergent TP (20.0%).Conclusion Emergent pancreatic resection for neoplastic disease results in substantial mortality and morbidity.The results of this large series of modern national data may assist surgeons in making emergent operative decisions in select cases and provide more informed risk counseling on expected outcomes after such rare unanticipated procedures.

319 Background: The use of neoadjuvant therapy has been widely used for borderline resectable pancreatic cancer (BLRPC). Controversy exists on the definition of BLRPC, and because of this, we examined the association of vascular involvement and margin status in patients who had initial resection. Methods: Records of 137 patients who had surgery for resectable or BLRPC were collected. Included were radiologist grading of venous/arterial involvement based on preoperative imaging. For patients with both staging recorded, we categorized vascular involvement as none, arterial only, venous only, or both. We examined the association of vascular involvement and margin status using Chi-square tests, and logistic regression. Results: Of 137 patients, all underwent surgery first. 85% had a Whipple without vascular resection, and 13% with. Of 134 patients with Ishikawa staging, there were 63% stage I, 17% stage II, 11% stage III, and 9% stage IV. Of 96 patients with arterial staging, there were 74% stage i, 16% stage ii, and 10% stage iii. Of 93 patients with both Ishikawa and arterial staging recorded, 61% had no vascular involvement, 7% arterial, 14% venous, and 17% had both. Ishikawa stage I-IV was associated with a positive SMA margin, and was seen in 14%, 44%, 53%, and 58%, respectively (p < 0.001). However, for arterial staging the association was weaker, and for arterial stages i-iii, a positive SMA margin was seen in 20%, 40%, and 40%, respectively (p = 0.06). Therefore, Ishikawa staging was more predicative of arterial involvement. Higher Ishikawa staging was associated with increased positive SMV margins; 5%, 26%, 33%, respectively (p < 0.001), while preoperative arterial staging was not predictive (p = 0.63). In logistic regression for any positive margin, only venous staging was significant in predicting a positive margin. Conclusions: The use of imaging in predicting positive margins is more accurate when using a venous grading system as opposed to an arterial one. With a more standard approach of designating degree of vein involvement, and better preoperative imaging, further studies will be needed to substantiate these findings.

415 Background: Sarcopenia (Sp) or severe loss of muscle mass is a prognostic factor in cancer patients. We assessed the association between Sp and outcomes in borderline resectable or locally advanced/unresectable pancreatic cancer patients undergoing chemoradiation (CRT). Methods: We reviewed all patients who underwent CRT at an NCI-designated cancer center between 2007-2012. Patients with available pre-treatment imaging were included in the analysis. Sp was defined as a lumbar skeletal muscle area/height of < 55.4 cm2/m2 for males and < 38.9 cm2/m2for females. Sp was correlated to treatment toxicity, cause specific survival (CSS), and overall survival (OS). Analysis was performed using chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Kaplan-Meier method and Cox regression was used for survival analysis. Results: A total of 86 patients met the inclusion criteria with 32 (37%) patients being sarcopenic. The median age was 70 (range 46-91) with a median follow-up of 14 months (3-68). The majority of patients were male (57%), had T3 disease (47%), or were borderline resectable (63%). Twenty nine (33.7%) patients underwent surgery. Sarcopenic patients were less likely to undergo surgery (p = 0.024) versus non-sarcopenic patients. Otherwise there was no difference in clinical or treatment factors. The 12-month actuarial OS for patients with and without Sp was 47.9% and 70.7%, respectively (p = 0.047). The 12-month actuarial CSS for patients with and without Sp was 48% and 76%, respectively (p = 0.007). On multivariable analysis, after controlling for T-stage, N-stage, resectability, gender, pre-treatment CA 19-9, and surgery, Sp was no longer associated with CSS (HR 0.284 95% CI 0.774-2.398) or OS (HR 1.077 95% CI 0.626-1.853). Surgery remained associated with CSS (HR 0.205 95% CI = 0.102-0.412) and OS (HR 0.187 95% CI 0.096-0.363). T-stage also remained associated with both CSS (HR 0.616 95% CI 0.410-0.925) and OS (HR 0.649 95% CI 0.440-0.957). Conclusions: The presence of Sp decreases the likelihood of undergoing curative surgery for pancreatic cancer. This may be another useful tool to identify poor prognosis patients.

Purpose: This study was undertaken to identify parameters associated with hematologic toxicity or chemotherapy dose modification in patients undergoing concurrent chemoradiation (CRT) with gemcitabine for localized pancreatic cancer.Methods and materials: We reviewed patients with localized pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of nongemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. The T11-L3 vertebrae were contoured as bone marrow region at risk. Linear and logistic regression models were used to test associations between dosimetric parameters and gemcitabine dose modification or hematologic toxicity during or within 3 months following CRT. Receiver operator curves were generated to identify threshold doses for hematologic toxicity.Results: Forty-nine patients were included. During CRT, the maximum thoracolumbar dose was associated with grade 2+ neutropenia during CRT (P = .017) and the volume receiving 5 Gy (V5) was associated with grade 2+ leukopenia (P = .041). Post-CRT, thoracolumbar mean dose (P = .015), V5 (P = .01), and V10 (P = .012) were associated with increased grade 2+ neutropenia. On multivariable analysis, the thoracolumbar maximum dose (P = .045) and V5 (P = .045) were associated with grade 2+ neutropenia and grade 2+ leukopenia during CRT, respectively. Post-CRT, the mean dose (P = .046), V5 (P = .019), and V10 (P = .037) were associated with increased grade 2+ neutropenia. A maximum dose of 48.02 Gy and V5 of 57.6% were identified as predictors of toxicity during CRT. A V5 of 56.6%, V10 of 47.05%, and mean dose of 11.67 Gy were identified as predictors of post-CRT hematologic toxicity. Post-CRT, there was a trend toward increased dose modifications with increased V5 (P = .065).Conclusions: In our dataset, the thoracolumbar mean dose, maximum dose, V5, and V10 correlated with hematologic toxicity during CRT and post-CRT in patients with localized pancreatic cancer. Because of the high rates of distant failure and importance of systemic therapy in these patients, this may be an important consideration during treatment planning. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Nadler, Ashlie MD; Zih, Francis S.W.; Hoffman, John; Sigurdson, Elin R. MD, FACS; Reddy, Sanjay MD Author Information

Tsai et al make a strong case for total neoadjuvant therapy in the treatment of patients with clearly resectable cancer. They enumerate the advantages (guaranteed treatment of micrometastatic disease and early discovery of resection-obviating chemoresistant disease) and mention most of the disadvantages (rare local tumor progression, biliary stent, and difficulties with travel to a tertiary center) of this sequencing approach. Besides treating micrometastatic disease, it also allows the physician to select out from surgery those patients who have metastatic disease unresponsive to chemotherapy.

IMPORTANCE:Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported.OBJECTIVE:To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting.DESIGN, SETTING, AND PARTICIPANTS:A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50-76 years]; 55% female). Patients registered between May 29, 2013, and February 7, 2014.INTERVENTIONS:Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy.MAIN OUTCOMES AND MEASURES:Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate.RESULTS:The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%-83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%-88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration.CONCLUSIONS AND RELEVANCE:The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial's completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients.TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01821612.

407 Background: Many studies have associated a R0 resection to have significantly improved survival compared with a R1 resection in PAC. Patients (pts) who undergo NACRT often go to surgery 4-8 weeks after the end of therapy, before the effects of NACRT can be fully manifested. The goal of this study is to evaluate if a positive SM (+SM) after NACRT has the same poor prognosis as a +SM after upfront surgery. Methods: After IRB approval, we retrospectively reviewed all cases of surgically resected PAC at a single institution from Dec 1996 to Jan 2014. Pts were stratified by receipt of NACRT as well as by SM status. We excluded pts treated with palliative intent, metastatic disease at presentation, death within 90 days of surgery, and biliary or ampullary tumors. The primary endpoint was overall survival (OS). We assessed the relationship between pt and tumor variables with treatment/margin combination using Chi-squared tests. OS was examined using Kaplan-Meier curves, and we tested association with treatment/margin using log-rank tests. Results: A total of 213 pts met inclusion criteria; 111 received upfront surgery (group I) with 94 (85%) receiving adjuvant chemotherapy or CRT and 102 received NACRT (group II) with either concurrent 5-fluorouracil (n=18) or gemcitabine (n=84). There were 31 pts with +SM in group I and 29 pts in group II. Pt demographics were balanced. There was more vessel involvement in group II (81%) at diagnosis than group I (11%) (p<0.01) with a trend towards improved OS in group II vs group I (p=0.09). Pathological evaluation revealed more PNI (61% vs 42%, p<0.01) and more lymph node positivity (71% vs 33%, p<0.01) in group I vs group II, respectively. Median OS for group I SM+/SM- and group II SM+/SM- were 15/25 months and 26/32 months respectively. OS is significantly improved with a negative SM (-SM) compared with a +SM (p<0.01). If the SM is positive, pts in group II had improved OS compared with group I (p=0.02). OS was not significantly different for group II +SM vs group I –SM (p=0.34). Conclusions: The negative impact of a +SM on survival is partially mitigated by NACRT. This data further supports the use of NACRT, although it is limited by its retrospective nature and small sample size.

Introduction: The mainstay of treatment for pancreatic and gastric cancers is surgical resection. Unfortunately many of these patients present with locally advanced, unresectable or distant disease and therefore medical management may be of more benefit. Accurate staging of patients with pancreatic and gastric cancer is essential in determining the best treatment strategy. Despite preoperative imaging there remains a group of patients that have clinically occult metastatic disease. Positive peritoneal cytology is a poor prognostic indicator for survival in both gastric and pancreatic cancer. Surgical resection may not be of benefit in those with positive peritoneal cytology. At our institution, a diagnostic laparoscopy with peritoneal washings is performed prior to surgical resection. We performed a retrospective review to evaluate the accuracy of immediate peritoneal washing interpretation in both gastric cancer and pancreatic cancer. Results: There were 51 patients that underwent immediate peritoneal washing interpretations. There were 5 patients with gastric adenocarcinoma, 2 patients with cholangiocarcinoma, and 44 patients with pancreatic adenocarcinoma. Four of the patients had positive cytology for tumor cells with immediate interpretation, and 47 patients had cytology negative for tumor cells with immediate interpretation. There was only one patient with negative cytology on immediate interpretation with cytology positive for malignant cells on final pathologic results. There were many RBCs noted within the peritoneal fluid specimen, which is probably why the cancer cells were missed. Immediate peritoneal cytology results had a 100% positive predictive value, and a 97% negative predictive value. There were no false positive results. Discussion: Positive peritoneal cytology is considered a poor prognostic factor for survival in both gastric and pancreatic cancer. In pancreatic and gastric cancer, previous studies have shown resection in the presence of metastatic disease does not improve survival. Diagnostic laparoscopy has been used as an adjunct to help stage patients before proceeding with a radical resection that has an associated significant morbidity andmortality rate is futile and potentially harmful, delaying or obviating systemic therapy that may be of more benefit to the patient. Our results show that utilizing immediate interpretation of peritoneal cytology is reliable and accurate. There was only one patient with a false negative result and there were no false positive results. Therefore, prior to surgical resection immediate interpretation can be utilized. Conclusion: Diagnostic laparoscopy with peritoneal washings and immediate interpretation of cytology can be used prior to proceeding with surgical resection. A futile operation can potentially be avoided with the use of immediate interpretation of the peritoneal fluid.

Introduction: Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report: A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroen-docrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G.A). Discussion: Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G.A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. Conclusion: To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that this presentation may be due to the novel menin gene mutation recently described.