Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM-1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex. BRM suppression can be reversed pharmacologically.(1) Our group and others have reported associations with lung, head and neck, hepatocellular cancer risk,(1-3) and with lung and esophageal cancer prognosis (ASCO 2013; abstract 11057 & 4077). Herein, we assessed risk and survival associations with pancreatic cancer. A provincial population-based case-control study was conducted with 623 histologically confirmed pancreatic adenocarcinoma cases and 1,192 age/gender distribution-matched controls.(4) Survival of cases was obtained through the Ontario Cancer Registry. Logistic and Cox proportional hazard regression models were fitted, adjusting for relevant covariates. Median age was 65 y; 52% were male; Stage I (8%), II (55%), III (14%), IV (23%); 53% after curative resection, 79% after chemotherapy; and 83% had died. In the risk analysis, adjusted odds ratios (aOR) were 1.01 (95% CI: 0.1-2.0) and 0.96 (95% CI: 0.7-1.3) for the homozygotes of BRM-741 and BRM-1321, respectively; aOR of double-homozygotes was 1.11 (95% CI: 0.80-1.53), compared to the double-wildtype. For the survival analysis, adjusted hazard ratios (aHR) were 2.19 (95% CI: 1.9-2.5) for BRM-741 and 1.94 (95% CI: 1.7-2.2) for BRM-1321, per unit increase in variant alleles. Compared with the double-wildtype, aHR for carrying no, one, and two double-homozygotes were 2.14 (95% CI: 1.6-2.8), 4.17 (95% CI: 3.0-5.7), 8.03 (95% CI: 5.7-11.4), respectively. In conclusion, two functional promoter BRM polymorphisms were not associated with pancreatic adenocarcinoma risk, but are strongly associated with survival.

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Background: Timely surgical resection in patients with suspected or diagnosed pancreas adenocarcinoma is an essential part of care. We hypothesized that longer surgical wait time was associated with worse oncologic outcomes.Methods: A retrospective cohort of patients (N = 144) with resectable pancreas adenocarcinoma was divided into four wait time groups (<4, 4-8, 8-12, and >12 weeks), defined from the time of diagnosis on cross-sectional imaging. Overall and recurrence-free survival were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. A higher rate of conversion to palliative bypass in patients waiting over 4 weeks was observed and further analyzed using post-hoc multivariate regression.Results: On multivariable analysis, longer wait time was associated with improved overall (HR 0.49, 95% CI: 0.28-0.85) and recurrence-free survival (HR 0.29, 95% CI: 0.15-0.56) in >12 weeks compared to <4 weeks group. On post-hoc analysis, longer wait time over 8 weeks was positively associated with palliative bypass (OR 5.33,. Conclusion:Wait time over 8 weeks was associated with a higher rate of palliative bypass. There was an improvement in overall and recurrence-free survival in patients who waited over 12 weeks, likely due to selection bias.

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Background:We aimed to define the appropriateness of interventions for the prevention of postoperative pancreatic fistulas (POPF) after pancreatectomy, given the lack of consistent data on this topic.Methods: Using the RAND/UCLA appropriateness method, we assembled an expert panel to rate clinical scenarios for interventions to prevent POPF after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). Results:The following interventions were rated appropriate: individualized risk prediction for all patients; perioperative pasireotide administration for patients undergoing PD who have a soft pancreatic gland and a pancreatic duct size of less 3 mm and for patients undergoing DP; pancreaticogastrostomy for patients undergoing PD who have a soft pancreatic gland and pancreaticojejunostomy for PD for patients with a pancreatic duct size of 6 mm or greater regardless of pancreatic gland texture; duct-to-mucosa anastomosis for all patients undergoing PD and dunking anastomosis for patients undergoing PD who have a pancreatic duct size of less than 3 mm with a firm pancreatic gland; simple stapled and reinforced stapled transection for all DP; surgical drains for PD and DP in patients with a soft pancreatic gland; and open and minimally invasive surgery for DP and open surgery for PD. The following were rated inappropriate: gastrointestinal anastomosis for stump closure in all DP and omission of surgical drain in PD for patients with a pancreatic duct diameter less than 3 mm and a soft pancreatic gland. Conclusion:The expert panel identified appropriate and inappropriate scenarios for POPF prevention following pancreatectomy, to provide guidance to clinicians. However, the appropriateness of the interventions in the majority of the clinical scenarios was rated as uncertain, demonstrating equipoise. Contexte :Nous avons voulu clarifier le bien-fondé des interventions de prévention des fistules pancréatiques postopératoires (FPPO) après la pancréatectomie, car on déplore un manque de données cohérentes à ce sujet.Méthodes : Nous avons formé un comité d'experts qui a appliqué la méthode de consensus RAND/UCLA pour évaluer les scénarios cliniques d'interventions de prévention des FPPO après la pancréatoduodénectomie (PD) et la pancréatectomie distale, ou gauche (PG).Résultats : Les interventions suivantes ont été jugées appropriées : évaluation systématique du risque chez tous les patients; administration périopératoire de pasiréotide chez les patients soumis à une PD qui ont un pancréas mou et un canal pancréatique de moins de 3 mm de diamètre et chez les patients soumis à une PG; pancréatogastrostomie chez les patients soumis à une PD qui ont un pancréas mou et pancréatojéjunostomie chez les patients soumis à une PD dont le canal pancréatique mesure 6 mm ou plus de diamètre, indépendamment de la texture du pancréas; anastomose canal-muqueuse chez tous les patients soumis à une PD et anastomose en « dunking » chez les patients soumis à une PD qui ont un canal pancréatique de moins de 3 mm de diamètre et un pancréas fe...