Interventions to reduce post-operative pancreatic fistula after pancreaticoduodenectomy - do we need a change of direction? a systematic review and meta-analysis

Abstract

Introduction: Various perioperative interventions designed to reduce postoperative pancreatic fistula (POPF) rate after pancreaticoduodenectomy (PD) have been evaluated, but most are unsuccessful. The aim of this study was to provide a contemporary report of the efficacy of different interventions and identify areas for future investigation in this complex field. Method: A systematic review of the literature for RCTs evaluating perioperative interventions to reduce POPF after PD was performed according to the PRISMA guidelines. Meta-anlayses were performed for each intervention. Results: Some 20 interventions (n=6,628 patients, 56 studies) were identified. Four interventions reduced POPF after PD on MA: external pancreatic stent vs. no stent (OR 0.42; 95%CI: 0.25-0.70); p< 0.005); invagination PJ vs. duct to mucosa PJ (OR 0.60; 95%CI: 0.40-0.90; p=0.01); pancreaticogastrostomy (PG) vs. PJ (OR 0.69; 95%CI: 0.49-0.99; p=0.04) and omission of intraabdominal drains in patients with low risk PJ anastomoses (OR 0.52; 95%CI: 0.34-0.81; p< 0.005). Two interventions with data available from only one RCT were shown to reduce POPF: end to side vs. classic pancreaticojejunostomy (PJ) (OR 0.25; 95%CI 0.07-0.96; p=0.041) and closed suction drainage of pancreatic duct (OR 0.44; 95%CI: 0.2-0.99; p=0.045). One intervention, acute normovolaemic haemodilution, increased POPF rate in one RCT (OR 3.29 95%CI:1.11-9.77; p=0.045). Conclusions: Current evidence for perioperative interventions to reduce POPF after PD is heterogenous and frequently from underpowered RCTs. To further clinical knowledge in this complex field future RCTs should be better powered and flexible enough to involve evaluation of the promising novel strategies identified in this review.