Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis

Br J Surg. 2022 Aug 16;109(9):812-821. doi: 10.1093/bjs/znac074.


Background: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs.

Methods: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power.

Results: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively.

Conclusion: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.

Publication types

  • Meta-Analysis

MeSH terms

  • Humans
  • Length of Stay
  • Pancreas / surgery
  • Pancreatic Fistula* / etiology
  • Pancreatic Fistula* / prevention & control
  • Pancreatic Fistula* / surgery
  • Pancreaticoduodenectomy* / adverse effects
  • Pancreaticojejunostomy
  • Postoperative Complications / prevention & control
  • Postoperative Complications / surgery
  • Retrospective Studies
  • Risk Factors