IMPORTANCE The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.OBJECTIVE To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.

Background Many studies have explored factors relating to post‐operative pancreatic fistula (POPF); however, the original definition (All‐POPF) was revised to include only ‘clinically relevant’ (CR) POPF. This study identified variables associated with the two International Study Group on Pancreatic Surgery definitions to identify which variables are more strongly associated with CR‐POPF. Methods A systematic review identified all studies reporting risk factors for POPF (using both International Study Group on Pancreatic Fistula definitions) following pancreatoduodenectomy. The primary outcome was factors associated with CR‐POPF. Meta‐analyses (random effects models) of pre‐, intra‐ and post‐operative factors associated with POPF in more than two studies were included. Results Among 52 774 patients All‐POPF (n = 69 studies) and CR‐POPF (n = 53 studies) affected 27% (95% confidence interval (CI95%) 23–30) and 19% (CI95% 17–22), respectively. Of the 176 factors, 24 and 17 were associated with All‐ and CR‐POPF, respectively. Absence of pre‐operative pancreatitis, presence of renal disease, no pre‐operative neoadjuvant therapy, use of post‐operative somatostatin analogues, absence of associated venous or arterial resection were associated with CR‐POPF but not All‐POPF. Conclusion In conclusion this study demonstrates wide variation in reported rates of POPF and that several risk factors associated with CR‐POPF are not used within risk prediction models. Data from this study can be used to shape future studies, research and audit across ethnic and geographic boundaries in POPF following pancreatoduodenectomy.

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Background: Positive margins in pancreatoduodenectomy (PD) for pancreatic cancer, specifically the superior mesenteric artery (SMA) margin, are associated with worse outcomes. Local therapies targeting these margins could impact on recurrence. This study analysed recurrence-patterns to identify whether strategies to control local disease could have a meaningful impact. Methods: (I) Systematic review to define recurrence patterns and resection margin status. (II) Additional retrospective study of PD performed at our centre.Results: In the systematic review, 23/617 evaluated studies were included (n = 3815). Local recurrence was observed in 7-69%. SMA margin (6 studies) was positive in 15-35%. In the retrospective study (n = 204), local recurrence was more frequently observed with a positive SMA margin (66 vs.45%; p = 0.005). Furthermore, in a multivariate cox-proportional hazard model, only a positive SMA margin was associated with disease recurrence (HR 1.615; 95%CI 1.127-2.315; p = 0.009). Interestingly, median overall survival was 20 months and similar for patients who developed local only, metastases only or simultaneous recurrence (p = 0.124). Conclusion:Local recurrence of pancreatic cancer is common and associated with similar mortality rates as those who present with simultaneous or metastatic recurrence. Involvement of the SMA margin is an independent predictor for disease progression and should be the target of future adjuvant local therapies.

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Background Many studies evaluate interventions to reduce POPF following PD, but often report conflicting results. Previous meta-analyses have generally included non-randomised trials and not considered novel interventions.  Aim To evaluate interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) with level 1 data. Methods A systematic review and meta-analysis assessed randomised controlled trials (RCTs) evaluating interventions to reduce All-POPF or clinically relevant (CR)-POPF after PD. A post-hoc analysis of negative RCTs assessed whether these had appropriate levels of statistical power. Results Among 22 interventions (n = 7,512 patients, 55 studies), 12 were assessed by multiple studies, and subject to meta-analysis. Of these, external pancreatic duct drainage was the only intervention found to be associated with significantly reduced rates of CR- and all-POPF. In addition, Ulinastatin was associated with significantly reduced rates of CR-POPF, whilst invagination (vs duct to mucosa) pancreatojejunostomy was associated with significantly reduced rates of all-POPF. Review of negative RCTs found the majority to be underpowered, with post-hoc power calculations indicating that interventions would need to reduce the POPF rate to ≤ 1% in order to achieve 80% power in 16/34 (All-POPF) and 19/25 (CR-POPF) studies, respectively.   Conclusions Meta-analysis supports a role for several interventions to reduce POPF after PD, although data is often inconsistent and/or based on small trials. Systematic review identifies other interventions which may benefit from further study. However, underpowered trials appear to be a fundamental problem, inherently more so with CR-POPF. Larger trials, or new directions for research are required to further understanding in this field.

Background Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. Methods This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012–2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. Results The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5–8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34–42 months) for BRPC and 33 months (95% CI 27–45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20–2.20) and tumor differentiation (HR 1.43; 95% CI 1.08–1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. Conclusions This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.