Clinical Evaluation of Postoperative Day 3 Serum Lipase in Relation to Clinically Relevant Pancreatic Fistula After Distal Pancreatectomy: A Retrospective Cohort Study

Background/Objectives: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major complication after distal pancreatectomy. Postoperative pancreatic enzyme elevation is increasingly recognized as a marker of pancreatic remnant injury, but serum lipase after distal pancreatectomy has been less well characterized than serum amylase and drain-fluid markers. This study evaluated postoperative day 3 (POD3) serum lipase as a routine biochemical marker associated with CR-POPF. Methods: We retrospectively analyzed 202 consecutive adults who underwent distal pancreatectomy between 2016 and 2026. CR-POPF was defined as International Study Group on Pancreatic Surgery grade B or C. POD3 lipase was available in 157 patients, including 17 CR-POPF events. Results: POD3 lipase was higher in patients with CR-POPF than in those without it (median 74 vs. 31 U/L; p < 0.001). Each doubling of lipase was associated with higher odds of CR-POPF (OR 2.59, 95% CI 1.54–4.37). The AUC was 0.79 (95% CI 0.67–0.90) and remained 0.79 after bootstrap optimism correction. At 64 U/L, the negative predictive value was 96%; at 3 × ULN, specificity was 99%. Conclusions: POD3 serum lipase provides a readily available serum biochemical marker, not requiring drain-fluid sampling, associated with CR-POPF after distal pancreatectomy. The findings are exploratory and require external validation before clinical implementation.