Does neoadjuvant therapy reduce pancreatic fistula after pancreatoduodenectomy and distal pancreatectomy?-a systematic review and meta-analysis

Abstract

BACKGROUND: Postoperative pancreatic fistula (POPF) is a major complication after pancreatic resection. This systematic review and meta-analysis investigated the impact of neoadjuvant therapy (NAT) on POPF rates after pancreatoduodenectomy (Whipple procedure) and distal pancreatectomy. METHODS: A systematic search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Central Register of Controlled Trials was conducted for studies published since 2016 using the updated International Study Group of Pancreatic Fistula (ISGPF) definition for POPF. Random-effects models were used to pool data. RESULTS: Thirty studies (22,048 patients) were included. Of those, 24 were comparative studies between neoadjuvant and upfront surgery (UPS) groups, while 6 reported POPF rates only in the neoadjuvant group. NAT significantly reduced POPF rates after Whipple procedure [risk ratio (RR) 0.44, 95% confidence intervals (CI): 0.38-0.52, P<0.01]. A harder pancreatic texture was more common after NAT compared to UPS (RR 1.27, 95% CI: 1.23-1.32, P<0.001). There were no significant differences between the neoadjuvant and upfront surgery groups regarding pancreatic duct size or body mass index (BMI). CONCLUSIONS: NAT reduces POPF after Whipple procedure, likely by altering pancreatic texture. The exact mechanisms by which the pancreas becomes harder during neoadjuvant treatment remain unclear. This finding could be implemented to improve surgical outcomes in patients with a soft pancreas. However, accurately predicting tumor response to NAT is a prerequisite for such an approach to avoid potential disease progression. Advances in personalized medicine, where tumor response could be predicted, offer hope for tailoring treatment strategies and maximizing outcomes.