Abstract
Background. Postoperative pancreatic fistula (POPF) remains the key driver of morbidity after pancreatoduodenectomy (PD). We evaluated anatomical and technical predictors of POPF with emphasis on pancreatic texture and main pancreatic duct (MPD) diameter. Methods. Retrospective analysis of consecutive adults undergoing PD at a single HPB center (2016–Oct 2024). Patients were stratified by intraoperative pancreatic texture (soft vs hard) and MPD diameter (≤5 mm vs >5 mm). Outcomes were graded per ISGPS (2016). Multivariable logistic regression identified independent predictors of POPF. Results. Among 293 patients, overall POPF occurred in 110 (37.5%), including clinically relevant POPF (CR-POPF; grades B/C) in 67 (22.9%). POPF was more frequent with soft than hard pancreas (54.4% vs 17.8%; p<0.001); grade C appeared only in soft glands. In soft pancreas, MPD ≤5 mm vs >5 mm was associated with higher POPF (53.8% vs 23.0%; p=0.013); a similar pattern was seen in hard glands (31.0% vs 9.1%; p=0.002). On multivariable analysis, higher drain amylase on postoperative day (POD) 1 independently predicted POPF (OR 1.011 per 1 IU/L; 95% CI 1.008–1.015; p<0.001), whereas larger MPD diameter reduced risk (OR 0.792 per mm; 95% CI 0.632–0.991; p=0.042). After adjustment, pancreatic texture showed no independent association (OR 1.177; p=0.748). In the soft-gland subgroup, invagination pancreatojejunostomy was linked to more grade C POPF (20.0% vs 6.0%), higher re-operation (20.0% vs 6.1%; p=0.036) and greater in-hospital mortality (24.0% vs 7.5%; p=0.023) compared with duct-to-mucosa anastomosis. Conclusions. Small MPD diameter and soft texture identify patients at heightened risk of POPF after PD; early POD1 drain amylase is a strong independent predictor. When technically feasible—particularly in soft glands with narrow ducts—duct-to-mucosa pancreatojejunostomy is associated with fewer severe fistulas and lower mortality than invagination