Risk Factors for Post-ERCP Pancreatitis: Impact of Transpancreatic Septotomy, Needle–Knife Precut, and Duodenal Diverticulum in 1226 Procedures

<b>Background:</b> Post-ERCP pancreatitis (PEP) remains the most common and clinically relevant adverse event following endoscopic retrograde cholangiopancreatography (ERCP). The impact of periampullary duodenal diverticulum and advanced cannulation techniques-particularly needle-knife precut sphincterotomy and transpancreatic septotomy (TPS)-on PEP risk remains debated. This study aimed to evaluate the association of these factors with PEP development in a large tertiary-center cohort. <b>Methods:</b> This retrospective study included 1226 patients who underwent ERCP between January 2018 and October 2022. Demographic, clinical, and procedural variables were recorded. Outcomes included PEP, hyperamylasemia, bleeding, and perforation. Univariable analyses were followed by multivariable logistic regression to identify independent predictors of PEP. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. <b>Results:</b> PEP occurred in 17.3% of the cohort. Needle-knife precut sphincterotomy and transpancreatic septotomy were frequently used advanced cannulation techniques and were both associated with an increased prevalence of PEP, with PEP occurring in 30.3% of patients undergoing needle-knife precut sphincterotomy and 56.9% of those undergoing transpancreatic septotomy. In the multivariable model, needle-knife precut independently increased PEP risk by 2.45-fold (aOR 2.45; 95% CI 1.78-3.36; <i>p</i> < 0.001), whereas TPS demonstrated the strongest association, increasing the risk nearly fivefold (aOR 4.92; 95% CI 2.98-8.11; <i>p</i> < 0.001). Female sex showed a nonsignificant trend toward increased PEP risk (aOR 1.28; 95% CI 0.96-1.69; <i>p</i> = 0.08). Periampullary duodenal diverticulum, pancreatic duct stenting, comorbidities, and age were not independently associated with PEP development (<i>p</i> > 0.05 for all). <b>Conclusions:</b> Needle-knife precut sphincterotomy and transpancreatic septotomy were independent predictors of PEP, with the highest risk observed for transpancreatic septotomy, whereas periampullary diverticulum and pancreatic duct stenting were not associated with increased risk.