Postoperative pancreatic fistula (POPF) is a common complication after pancreaticoduodenectomy (PD). The effect of the location of the main pancreatic duct on POPF development is not completely elucidated. This study aimed to investigate the association between the location of the main pancreatic duct and POPF, and the effect of pancreaticojejunostomy based on the location of the main pancreatic duct on the risk of POPF. This retrospective study enrolled 871 patients who underwent PD between January 2018 and December 2021. Logistic regression analysis was performed to identify the independent risk factors associated with POPF. Predictive performance was evaluated using the receiver operating characteristic curves. In addition, a novel pancreaticojejunostomy strategy that could reduce the risk of POPF was adopted. Based on the multivariate analysis, the pancreatic texture and the location of the main pancreatic duct were the independent risk factors of POPF. A threshold ratio of 0.397 was used to distinguish the central from the eccentric pancreatic ducts. Notably, patients with the central pancreatic duct had a significantly lower incidence rate of POPF than those with the eccentric pancreatic ducts (10.6% vs. 44.8%, P<0.001). The novel group exhibited a significantly lower incidence rate of POPF than the conventional group (13.7% vs. 23.0%, P=0.02), and the incidence rate of other complications was not high. The location of the main pancreatic duct is associated with POPF development. However, implementing the novel pancreaticojejunostomy approach can effectively reduce the risk of POPF while ensuring safety.
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