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Background and Aim: Rectal indomethacin and pancreatic duct stenting (PDS) are recommended for the prevention of post‐endoscopic retrograde cholangiopancreatography pancreatitis (PEP). However, the effects of the combination of the two methods on preventing PEP are controversial. We hypothesized that some group of difficult patients might benefit from the combination of indomethacin plus PDS (IP) compared with indomethacin alone (IN). Methods: Patients with native papilla who underwent endoscopic retrograde cholangiopancreatography in eight tertiary hospitals were screened. They were enrolled if the cannulation proved difficult and post‐procedure indomethacin was administered. Propensity score matching (PSM) was used to balance the baseline characteristics between IP and IN groups. The primary outcome was PEP. Results: Among 4456 patients with available cannulation‐related data, 1889 (42.4%) patients had difficult cannulation and received indomethacin. After PSM, both IP and IN groups included 332 patients. PEP was comparable between the two groups (12.7% vs 10.2%, P = 0.329). By subgroup analysis, the PEP rate was found to be lower in the IP group than in the IN group (7.3% vs 18.2%, P = 0.026) in patients undergoing double‐guidewire technique (DGT). The results of an additional analysis using PSM in DGT patients were consistent with the subgroup analysis results (7.8% vs 19.4%, P = 0.036). Conclusions: The current study indicated that the combined prevention of PEP with indomethacin plus PDS was useful in PEP prevention in patients undergoing DGT. Other groups of patients with difficult cannulation may not benefit from the combination strategy. [ABSTRACT FROM AUTHOR]

Background: Post-ERCP pancreatitis (PEP) is the most common adverse event of ERCP. Rectal indomethacin has been widely administered to decrease the incidence of PEP in high-risk patients. However, it cannot completely prevent the occurrence of PEP. The purpose of the study was to evaluate the risk factors for PEP in high-risk patients receiving post-ERCP indomethacin.Methods: From June 2012 to July 2015, patients undergoing ERCP and at high risk for PEP in three tertiary hospitals in China were enrolled. All patients received indomethacin after the procedure. Patient-related and procedure-related risk factors for PEP were collected. Logistic regression analysis was used to investigate the risk factors.Results: Seven hundred ninety patients at high risk for PEP received post-ERCP indomethacin. The incidence of overall PEP and moderate-to-severe PEP was 8.0 and 1.5%, respectively. In multivariate analysis, suspected sphincter of Oddi dysfunction (SOD) (OR 2.73; 95%CI 1.38-5.43; p = 0.004), the presence of hilar obstruction (OR 4.53; 95%CI 1.60-12.81; p = 0.004), number of cannulation attempts ≥ 13 (OR 2.00; 95%CI 1.07-3.77; p = 0.030), inadvertent pancreatic duct (PD) cannulation ≥ 1 (OR 2.26; 95%CI 1.04-4.90; p = 0.040), and pancreatic contrast injections ≥ 1 (OR 2.30; 95%CI 1.02-5.23; p = 0.046) were high risk factors for overall PEP. For moderate-to-severe PEP, suspected SOD (OR 4.67; 1.19-18.35; p = 0.027), the presence of hilar obstruction (OR 7.95; 1.39-44.97; p = 0.010), and more cannulation attempts (OR 3.71; 1.09-12.65; p = 0.036) were three independent risk factors.Conclusions: A substantial number of high-risk patients had PEP even receiving post-ERCP rectal indomethacin. The independent risk factors included suspected SOD, hilar stricture, more cannulation attempts, inadvertent PD cannulation, and PD contrast injections.Trial Registration: NCT02709421. [ABSTRACT FROM AUTHOR]