Post-Pancreatectomy Acute Pancreatitis Drives Fistula Formation After Pancreatoduodenectomy

Bhandare MS, Nandy K, Parray AM, et al. Interplay of Post-Pancreatectomy Acute Pancreatitis, Postoperative Pancreatic Fistula, and Mortality After Pancreatoduodenectomy: Insights from a Comprehensive Cohort Study of 1594 Patients and Development of Predictive Nomograms. J Am Coll Surg. January 2026.

Complications following pancreatoduodenectomy (PD) remain a major determinant of postoperative mortality, with clinically relevant pancreatic fistula (POPF) representing the most consequential event. In this large single-center cohort study, Bhandare and colleagues examined whether post-pancreatectomy acute pancreatitis (PPAP) functions as an upstream driver of fistula formation and death, rather than a parallel postoperative finding, and developed predictive tools to aid perioperative risk stratification.

The authors analyzed outcomes from 1,594 consecutive patients undergoing PD at a high-volume hepatopancreatobiliary center. PPAP was identified using standardized ISGPS criteria and evaluated in relation to clinically relevant POPF and mortality. Multivariable regression modeling was performed to isolate independent predictors of PPAP and POPF while accounting for established technical and patient-level risk factors. These variables were subsequently incorporated into nomograms designed to estimate individualized postoperative risk.

Patients who developed PPAP experienced substantially worse postoperative courses, including higher rates of grade B/C POPF, increased overall morbidity, and significantly higher mortality compared with patients without PPAP. Importantly, PPAP remained independently associated with both fistula formation and death after adjustment for known predictors such as pancreatic gland texture, duct size, and operative factors. Outcomes were poorest in patients in whom PPAP and POPF coexisted, demonstrating a compounded effect on mortality rather than an additive one.

Based on these findings, the authors constructed predictive nomograms capable of estimating the likelihood of PPAP, POPF, and postoperative mortality following PD. These models showed strong discriminatory performance and can provide surgeons with a practical framework for early postoperative risk recognition, escalation of monitoring, and informed discussions with patients and families.

The study supports the concept that PPAP is a clinically meaningful pathophysiologic event that precedes and amplifies pancreatic fistula–related complications after pancreatoduodenectomy. Incorporation of PPAP into postoperative risk assessment may improve surgical decision-making and identify patients who could benefit from intensified surveillance or early intervention.