Background/Aims: Difficult biliary cannulation is an important risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Therefore, this study aimed to identify the factors that predict difficult cannulation for common bile duct stones (CBDS) to reduce the risk for PEP. Methods: This multicenter retrospective study included 1,406 consecutive patients with native papillae who underwent ERCP for CBDS. Factors predicting difficult cannulation for CBDS were identified using univariate and multivariate analyses. Results: Univariate analysis showed that six factors significantly predicted difficult cannulation: ERCP performed by non-expert endoscopists, low-volume center, absence of acute cholangitis, normal serum bilirubin, intradiverticular papilla, and type of major duodenal papilla. Multivariate analysis identified ERCP performed by non-expert endoscopists (odds ratio [OR], 2.5; p<0.001), low-volume center (OR, 1.6; p<0.001), intradiverticular papilla (OR, 1.3; p=0.007), normal serum bilirubin (OR, 1.3; p=0.038), and absence of acute cholangitis (OR, 1.3; p=0.049) as factors significantly predicting difficult cannulation for CBDS. Conclusions Initial cannulation by an experienced endoscopist, early rescue cannulation, or early takeover by an experienced endoscopist should be considered when performing ERCP for CBDS in the presence of factors predicting difficult cannulation.

Background/Aims: This study aimed to examine the synergistic effect of independent risk factors on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods: This multicenter retrospective study included 1,273 patients with native papillae who underwent ERCP for bile duct stones in Japan. Independent PEP risk factors were identified using univariate and multivariate analyses. Significant risk factors for PEP in the multivariate analysis were included in the final analysis to examine the synergistic effect of independent risk factors for PEP. Results: PEP occurred in 45 of 1,273 patients (3.5%). Three factors including difficult cannulation ≥10 minutes, pancreatic injection, and normal serum bilirubin level were included in the final analysis. The incidences of PEP in patients with zero, one, two, and three factors were 0.5% (2/388), 1.9% (9/465), 6.0% (17/285), and 12.6% (17/135), respectively. With increasing risk factors for PEP, the incidence of PEP significantly increased (1 factor vs. 2 factors, p=0.006; 2 factors vs. 3 factors, p=0.033). Conclusions As the number of risk factors for PEP increases, the risk of PEP may not be additive; however, it may multiply. Thus, aggressive prophylaxis for PEP is strongly recommended in patients with multiple risk factors.