Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is common. Although multiple pancreatic duct (PD) cannulations are a known risk factor for PEP, the impact of single cannulations remains controversial. We aimed to identify whether single PD cannulation is associated with PEP.We conducted a prospective multicenter study in patients undergoing ERCP for biliary indications during 2021-2024, with third-party intra-procedural data recording and 30-day follow-up. PEP was defined using consensus definitions. Associations between PD cannulations and PEP were evaluated with multivariable logistic regression, with other patient- and procedure-related risk factors and preventative interventions used as covariates. Results were reported as odds ratios (ORs).PEP occurred in 282 (3.8%) of 7430 ERCPs across nine centers. From multivariable analysis, PD cannulation was statistically significantly associated with PEP, with similar odds for single and multiple cannulations in first-time patients (OR 2.03 [95%CI 1.32-3.14] for single, OR 2.18 [95%CI 1.18-4.00] for ≥5 cannulations) and all patients (OR 1.97 [95%CI 1.33-2.93] for single, OR 2.15 [95%CI 1.21-3.82] for ≥5). PD cannulation to the head (OR 2.09 [95%CI 1.36-3.21]) and body (OR 2.43 [95%CI 1.56-3.79]) were both associated with PEP, while side-branch cannulations alone were not (OR 1.18 [95%CI 0.64-2.06]).Single main PD duct cannulation was independently associated with PEP and appeared to be responsible for most of the magnitude of the association with PD cannulation. These data support the use of preventative interventions such as PD stenting in cases where the PD is inadvertently cannulated.
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