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Supplemental Digital Content is available in the text Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. Methods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial. Results: There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9–27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6–30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2–21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence. Conclusions: R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence. [ABSTRACT FROM AUTHOR]

Objectives: We tested cytoplasmic HuR (cHuR) as a predictive marker for response to chemotherapy by examining tumor samples from the international European Study Group of Pancreatic Cancer-3 trial, in which patients with resected pancreatic ductal adenocarcinoma (PDA) received either gemcitabine (GEM) or 5-fluorouracil (5-FU) adjuvant monotherapy. Background: Previous studies have implicated the mRNA-binding protein, HuR (ELAVL1), as a predictive marker for PDA treatment response in the adjuvant setting. These studies were, however, based on small cohorts of patients outside of a clinical trial, or a clinical trial in which patients received multimodality therapy with concomitant radiation. Methods: Tissue samples from 379 patients with PDA enrolled in the European Study Group of Pancreatic Cancer-3 trial were immunolabeled with an anti-HuR antibody and scored for cHuR expression. Patients were dichotomized into groups of high versus low cHuR expression. Results: There was no association between cHuR expression and prognosis in the overall cohort [disease-free survival (DFS), P = 0.44; overall survival, P = 0.41). Median DFS for patients with high cHuR was significantly greater for patients treated with 5-FU compared to GEM [20.1 months, confidence interval (CI): 8.3-36.4 vs 10.9 months, CI: 7.5-14.2; P = 0.04]. Median DFS was similar between the treatment arms in patients with low cHuR (5-FU, 12.8 months, CI: 10.6-14.6 vs GEM, 12.9 months, CI: 11.2-15.4). Conclusions: Patients with high cHuR-expressing tumors may benefit from 5-FU-based adjuvant therapy as compared to GEM, whereas those patients with low cHuR appear to have no survival advantage with GEM compared with 5-FU. Further studies are needed to validate HuR as a biomarker in both future monotherapy and multiagent regimens. [ABSTRACT FROM AUTHOR]

Objective: To examine the outcomes from minimal access retroperitoneal pancreatic necrosectomy (MARPN) and open pancreatic necrosectomy (OPN) for severe necrotizing pancreatitis in a single center. Background: The optimal management of severe pancreatic necrosis is evolving with a few large center single series. Methods: Between 1997 and 2013, patients with necrotizing pancreatitis at the Liverpool Pancreas Center were reviewed. Outcome measures were retrospectively analyzed by intention to treat. Results: There were 394 patients who had either MARPN (274, 69.5%) or OPN (120, 30.5%). Complications occurred in 174 MARPN patients (63.5%) and 98 (81.7%) OPN patients (P<0.001). OPN was associated with increased postoperative multiorgan failure [42 (35%) vs 56 (20.4%), P=0.001] and median (inter-quartile range) Acute Physiology and Chronic Health Evaluation II score 9 (6-11.5) vs 8 (5-11), P<0.001] with intensive care required less frequently in MARPN patients [40.9% (112) vs 75% (90), P<0.001]. The mortality rate was 42 (15.3%) in MARPNs and 28 (23.3%) in OPNs (P=0.064). Both the mortality and the overall complication rates decreased between 1997-2008 and 2008-2013 [49 (23.8%) vs 21 (11.2%) P=0.001, respectively; and 151 (73.3%) vs 121 (64.4%), P=0.080, respectively). Increased mortality was independently associated with age (P<0.001), preoperative intensive care stay (P=0.014), and multiple organ failure (P<0.001); operation before 2008 (P<0.001) and conversion to OPN (P=0.035). MARPN independently reduced mortality odds risk (odds ratio=0.27; 95% confidence interval= 0.12-0.57; P<0.001). Conclusions: Increasing experience and advances in perioperative care have led to improvement in outcomes. The role of MARPN in reducing complications and deaths within a multimodality approach remains substantial and should be used initially if feasible. [ABSTRACT FROM AUTHOR]

Comparison of minimal access retroperitoneal pancreatic necrosectomy (MARPN) versus open necrosectomy in the treatment of infected or nonresolving pancreatic necrosis.Infected pancreatic necrosis may lead to progressive organ failure and death. Minimal access techniques have been developed in an attempt to reduce the high mortality of open necrosectomy.This was a retrospective analysis on a prospective data base comprising 189 consecutive patients undergoing MARPN or open necrosectomy (August 1997 to September 2008). Outcome measures included total and postoperative ICU and hospital stays, organ dysfunction, complications and mortality using an intention to treat analysis.Overall 137 patients underwent MARPN versus open necrosectomy in 52. Median (range) age of the patients was 57.5 (18-85) years; 118 (62%) were male. A total of 131 (69%) patients were tertiary referrals, with a median time to transfer from index hospital of 19 (2-76) days. Etiology was gallstones or alcohol in 129 cases (68%); 98 of 168 (58%) patients had a positive culture at the first procedure. Of the 137 patients, 34 (31%) had postoperative organ failure in the MARPN group, and 39 of 52 (56%) in the open group (P < 0.0001); 59/137 (43%) versus 40/52 (77%), respectively, required postoperative ICU support (P < 0.0001). Of the 137 patients 75 (55%) had complications in the MARPN group and 42 of 52 (81%) in the open group (P = 0.001). There were 26 (19%) deaths in the MARPN group and 20 (38%) following open procedure (P = 0.009). Age (P < 0.0001), preoperative multiorgan failure (P < 0.0001), and surgical procedure (MARPN, P = 0.016) were independent predictors of mortality.This study has shown significant benefits for a minimal access approach including fewer complications and deaths compared with open necrosectomy. [ABSTRACT FROM AUTHOR]