OBJECTIVE:To provide a composite endpoint in pancreatic surgery. BACKGROUND:Single endpoints in prospective and randomized studies have become impractical due to their low frequency and the marginal benefit of new interventions. METHODS:Data from prospective studies were used to develop (n=1273) and validate (n=544) a composite endpoint based on postoperative pancreatic fistula, postpancreatectomy hemorrhage, as well as reoperation and reinterventions. All patients had pancreatectomies of different extents. The association of the developed PAncreatic surgery Composite Endpoint (PACE) with prolonged length of hospital stay >75th percentile and mortality was assessed. A single-institution database was used for external validation (n=2666). Sample size calculations were made for single outcomes and the composite endpoint. RESULTS:In the internal validation cohort, the PACE demonstrated an area under the curve of 78.0%, a sensitivity of 90.4%, and a specificity of 67.6% in predicting a prolonged length of hospital stay. In the external cohort, the area under the curve was 76.9%, a sensitivity of 73.8%, and a specificity of 80.1%. The 90-day mortality rate was significantly different for patients with a positive versus a negative PACE both in the development and internal validation cohort (5.1% vs 0.9%; P < 0.001), as well as in the external validation cohort (8.5% vs 1.2%, P < 0.001). The PACE enabled sample size reductions of up to 80.5% compared to single outcomes. CONCLUSIONS:The PACE performed well in predicting prolonged hospital stays and can be used as a standardized and clinically relevant endpoint for future prospective trials enabling lower sample sizes and therefore improved feasibility compared to single outcome parameters.

BACKGROUND Multimodal treatment concepts enhance options for surgery in locally advanced pancreatic ductal adenocarcinoma (PDAC). This review provides an overview of technical advances to facilitate curative-intent resection in PDAC. METHODS A review of the literature addressing current technical advances in surgery for PDAC was performed, and current state-of-the-art surgical techniques summarized. RESULTS Artery-first and uncinate-first approaches, dissection of the anatomical triangle between the coeliac and superior mesenteric arteries and the portomesenteric vein, and radical antegrade modular pancreatosplenectomy were introduced to enhance the completeness of resection and reduce the risk of local recurrence. Elaborated techniques for resection and reconstruction of the mesenteric-portal vein axis and a venous bypass graft-first approach frequently allow resection of PDAC with venous involvement, even in patients with portal venous congestion and cavernous transformation. Arterial involvement does not preclude surgical resection per se, but may become surgically manageable with recent techniques of arterial divestment or arterial resection following neoadjuvant treatment. CONCLUSION Advanced techniques of surgical resection and vessel reconstruction provide a toolkit for curative-intent surgery in borderline resectable and locally advanced PDAC. Effects of these surgical approaches on overall survival remain to be proven with high-level clinical evidence.

Abstract Objective Some studies have indicated that resecting the pylorus during partial pancreatoduodenectomy (PD) may lead to reduced delayed gastric emptying (DGE). Randomized controlled trials (RCTs) showed conflicting results regarding superiority of pylorus-resecting PD (prPD) compared to the pylorus-preserving procedure (ppPD). The aim of this individual patient data meta-analysis was to investigate risk factors on an individual patient level which may explain the observed differences between the existing RCTs. Methods RCTs comparing ppPD and prPD were searched systematically in MEDLINE, Web of Science and CENTRAL. Individual patient data (IPD) from existing RCTs were included. The primary endpoint was DGE according to the International Study Group of Pancreatic Surgery (ISGPS) adjusted for age, sex and body-mass-index (BMI). The meta-regression model was applied to the IPD of the RCTs. Mixed effects models were applied to perform meta-analyses. Results IPD from 418 patients (three RCTs) were used for quantitative synthesis. There was no significant statistical difference between ppPD and prPD regarding DGE adjusted for age, sex and BMI (OR 0.72; 95%-CI: 0.41 to 1.22) and DGE grade (RR 1.01; 95%-CI: 0.64 to 1.57). Regarding other relevant perioperative and postoperative outcome parameters, there were also no significant differences among the two techniques. Conclusion This IPD meta-analysis comparing preservation and resection of the pylorus during PD confirmed that the resection of the pylorus is not superior to the pylorus-preserving procedure regarding DGE. The pylorus should therefore be preserved whenever possible. Further RCT are futile, because their results are unlikely to change the pooled estimate for DGE.

ImportanceThe patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.ObjectiveTo define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and ParticipantsProspectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.InterventionsRandomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and MeasuresOverall survival, recurrence, and sites of recurrence.ResultsOf the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03).Conclusions and RelevanceThere were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial RegistrationClinicaltrials.gov Identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.

Incidence of wound complications after kidney transplantation (KTx) is still considerable. Here, we report the impact of prophylactic absorbable polyglactin (Vicryl (R)) mesh reinforcement on the incidence of short-term post-KTx wound complications. Sixty-nine patients were analyzed; 23 with and 46 without preventive onlay mesh reinforcement. Surgical site infections (SSI) were seen in six (26%) patients in the mesh group and in 17 (37%) patients in no-mesh group. A lower, but not statistically significant, rate of early postoperative wound complications occurred in the mesh group. Wound complications were observed in seven (30%) patients in the mesh group and in 23 (50%) patients in the no-mesh group. There was no association between mesh placement and SSI incidence (odds ratios [OR] 0.60, 95% confidence interval [CI] 0.20-1.82, p = 0.369) and wound complications (OR 0.44, 95% CI 0.15-1.26, p = 0.126). Therefore, we conclude that mesh reinforcement does not increase the risk of SSI and overall wound complications. Long-term outcomes have to be evaluated in a randomized trial setting. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:67-72, 2020.