Mitigation Strategies: A Standardized Multimodal Pathway to Reduce the Severity of Clinically Relevant Pancreatic Fistula After Pancreaticoduodenectomy

Background Pancreaticoduodenectomy (PD) carries significant morbidity, primarily due to clinically relevant postoperative pancreatic fistula (CR-POPF). This study investigated the clinical impact of a multimodal mitigation strategy in patients undergoing PD, encompassing prehabilitation, standardized surgical techniques, and optimized postoperative management. The secondary aim was to identify factors associated with grade C POPF. Methods A single-center retrospective analysis was conducted using a prospective database of 520 patients who underwent pancreatic surgery at our hospital between January 2016 and December 2025. One hundred eighty-four patients who underwent PD were selected and divided into two cohorts using 2022 as a cutoff, the year in which our multimodal mitigation strategy was introduced. Results In the after-2022 cohort, a significant reduction in CR-POPF was observed (39% vs 55%, P = .036), with specific decrease in grade C POPF cases (5% vs 23%, P < .001). A statistically significant reduction in PPH was also observed in the after-2022 cohort (3% vs 17%, P < .001). Furthermore, in after-2022 cohort, there were a reduction of reoperation rate (8% vs 25%, P = .001) and LOS (23.0 days vs 14.5 days, P < .001). For the secondary aim, the multivariate analysis identified the after-2022 period and the occurrence of cardiac and pulmonary complications as factors associated with grade C POPF (respectively P < .001, P = .017 and P < .001). Conclusions This study highlights the potential of a structured, multi-level mitigation strategy in improving outcomes after pancreatoduodenectomy, in particular, the severity of pancreatic fistula and its consequences.