Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis
PARANOIA Study Group:, Writing group:, James Halle‐Smith, Rupaly Pandé, Lewis Hall, James Hodson, Keith J Roberts, Ali Arshad, Saxon Connor, Kevin C. Conlon, Euan J. Dickson, Francesco Giovinazzo, Ewen M. Harrison, Nicola de Liguori Carino, Todd Hore, Stephen R Knight, Benjamin Loveday, Laura Magill, Darius Mirza, Anubhav Mitta, Sanjay Pandanaboyana, Rita Perry, Thomas Pinkney, Jas Samra, Ajith K. Siriwardena, Sohei Satoi, James Skipworth, Stefan Stättner, Robert P. Sutcliffe, Bobby Tingstedt, Keith J Roberts
Abstract
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.