More Than Just a Complication: Post-ERCP Pancreatitis and Its Clinical Determinants in over 800 Procedures

<b>Background:</b> Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) remains the most frequent and clinically significant complication of ERCP, with a multifactorial etiology involving patient- and procedure-related risk factors. Despite preventive measures such as NSAIDs and peri-procedural stenting, the incidence of PEP has not substantially declined. We aimed to assess clinical determinants of PEP in a large real-world cohort treated with standardized procedural protocols. <b>Materials and Methods:</b> This retrospective single-center study analyzed 806 patients who underwent ERCP between January 2019 and December 2021. All procedures were performed by a single operator under general anesthesia with standardized prophylaxis (diclofenac 100 mg per rectum and cefazolin 2 g intravenously). Patients with delayed ERCP (>48 h from admission) or active acute pancreatitis were excluded. Logistic regression was used to identify independent predictors of PEP, hospital stay, and in-hospital mortality. <b>Results:</b> PEP occurred in 60 patients (7.4%). Independent risk factors included stenosis of the papilla of Vater (OR = 2.45; <i>p</i> = 0.025), gallbladder stones (OR = 2.66; <i>p</i> = 0.001), prior acute pancreatitis (OR = 2.72; <i>p</i> = 0.005), and sphincterotomy (OR = 2.53; <i>p</i> = 0.016). PEP was associated with longer hospitalization (MD = 4.5 days; <i>p</i> < 0.001) and increased in-hospital mortality (6.7% vs. 1.7%; <i>p</i> = 0.032). <b>Conclusion:</b> Stenosis of the papilla, gallbladder stones, prior acute pancreatitis, and sphincterotomy independently increased the risk of PEP, whereas older age, previous ERCP, and pancreaticoduodenal tumors were associated with a reduced risk. Despite standardized prophylaxis, PEP remains a relevant clinical concern. Identification of high-risk patients and individualized procedural planning are essential to minimizing complications.