Surgery-related factors for pancreatic fistula after pancreatectomy: an umbrella review

Background: Multiple risk or protective factors for postoperative pancreatic fistula (POPF) have been suggested in the literature of surgical specialities. We aimed to map existing evidence regarding the risk factors for POPF to help guide future clinical treatment. Methods: We performed an umbrella review by searching the Web of Science, PubMed, Embase, and Cochrane databases until June 19, 2023. Meta-analyses (MAs) that included >= 2 studies were included. Methodological quality was assessed using AMSTAR2 scores and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools were used to quantify the strength of the evidence. Results: Of the 42 MAs, 1 was rated as having high methodological quality, and 4 were rated as moderate. Among the 82 outcomes, 6 were supported by high-quality evidence. Moderate-quality evidence was found for 13 outcomes. The remaining outcomes had either low- or very low-quality evidence. In pancreaticoduodenectomy (PD), protective factors for all-grade POPF include pancreaticogastrostomy (PG) [ vs. pancreaticojejunostomy (PJ), moderate quality], external pancreatic ductal stent ( vs. no stents, high quality). Risk factors for all-grade POPF in PD include pancreatic duct occlusion ( vs. no occlusion, moderate quality) and sealant ( vs. no sealant, moderate quality). Polyglycolic acid mesh [ vs. no mesh, moderate quality] was a protective factor for clinically relevant POPF (CR-POPF) in PD, omental/falciform ligament wrapping ( vs. no wrapping, low quality), and artery-first PD ( vs. standard, low quality). In distal pancreatectomy (DP), no factors for all-grade POPF were rated as high- or moderate-quality evidence. Polyglycolic acid mesh ( vs. no mesh, moderate quality) was a protective factor for CR-POPF in DP. No factors were rated as high- or moderate-quality evidence in other types of pancreatectomy. In addition, high- and moderatequality evidence showed that there was little difference in the incidence of pancreatic fistula in PD between minimally invasive and open surgery, duct-to-mucosa and invaginated PJ, Roux-en-Y and conservative reconstruction, extended and standard lymphadenectomy, and in the incidence of pancreatic fistula in DP between fibrin sealant patch and no patch. Conclusions: This umbrella review found varying levels of evidence for the associations between different surgery-related risk factors for POPF. Given the wealth of existing evidence of relatively low quality, future research should focus on improving its credibility.