Association of postoperative acute pancreatitis with clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy: a retrospective cohort study

<title>Abstract</title> <p>Background Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major source of morbidity after pancreaticoduodenectomy (PD). Elevated serum amylase on postoperative day 1, particularly postoperative acute pancreatitis (POAP), may indicate early remnant-pancreas injury, whereas drain fluid amylase on postoperative day 1 (DFA1) is commonly used for early postoperative assessment. However, the relative clinical significance of POAP and DFA1 in early risk stratification for CR-POPF remains unclear. Methods We retrospectively analyzed 327 patients who underwent PD at a single center. According to serum amylase levels on postoperative day 1, patients were classified into a normal group, a postoperative hyperamylasemia (POHA) group, and a POAP group based on the operational definition used in this study. CR-POPF was defined as grade B or C pancreatic fistula according to the 2016 International Study Group of Pancreatic Surgery criteria. The final fistula grade was reconstructed from the source database and mapped to ISGPS Grade B/C for the primary outcome; biochemical leak was not considered CR-POPF. Logistic regression was used to evaluate factors associated with CR-POPF, and supplementary receiver operating characteristic (ROC) analysis was used to assess the discriminative ability of DFA1. Results Among the 327 patients, 45 (13.8%) were classified into the normal group, 104 (31.8%) into the POHA group, and 178 (54.4%) into the POAP group. CR-POPF occurred in 69 patients (21.1%), including 5 patients (11.1%) in the normal group, 13 patients (12.5%) in the POHA group, and 51 patients (28.7%) in the POAP group (P &lt; 0.001). Multivariable analysis identified older age, male sex, and POAP as factors associated with CR-POPF. DFA1 was further evaluated as an adjunctive early postoperative marker. In supplementary ROC analysis, DFA1 showed moderate discriminative ability for CR-POPF in the overall cohort (AUC 0.703, 95% CI 0.637–0.764), whereas its discriminative ability was limited in the POAP subgroup (AUC 0.608, 95% CI 0.523–0.696). Conclusions POAP was significantly associated with CR-POPF after PD. DFA1 showed modest discriminative ability and may provide adjunctive information for early postoperative risk stratification when interpreted within the broader perioperative context.</p>