Difficult biliary cannulation during ERCP: techniques and an evidence-informed practical algorithm.

Difficult biliary cannulation remains the pivotal technical barrier in therapeutic endoscopic retrograde cholangiopancreatography (ERCP) and is a major modifiable driver of post-ERCP pancreatitis (PEP). Contemporary practice has moved from prolonged standard attempts toward earlier recognition of difficult access, guidewire-based primary cannulation, targeted rescue techniques, and routine pancreatitis prophylaxis. This review summarizes current evidence and proposes a practical, evidence-informed algorithm for native papilla ERCP. Difficult cannulation is best recognized using objective procedural thresholds, including more than five papillary contacts, more than 5 min after papillary visualization, or more than one unintended pancreatic duct (PD) cannulation or opacification. Primary cannulation should use a wire-guided approach with careful control of papillary trauma and contrast injection. Once difficulty is declared, rescue technique selection should follow procedural anatomy and clinical context rather than a rigid sequence: repeated PD access favors double-guidewire (DGW), transpancreatic biliary sphincterotomy (TPBS), or PD stent-assisted approaches; a bulging or favorably oriented papilla favors early needle-knife fistulotomy (NKF); and failed access despite endoscopist expertise should prompt escalation rather than continued trauma. Rectal nonsteroidal anti-inflammatory drugs should be administered before or during ERCP in patients without contraindications; prophylactic PD stenting should be used after repeated or deep PD access and according to the rescue technique and overall PEP risk, with appropriate hydration in suitable patients. Local postprocedural cryoprevention with papillary ice-water irrigation is an emerging adjunct supported by one multicenter randomized trial, although its incremental benefit alongside standard prophylaxis remains uncertain. When ERCP fails, repeat expert ERCP, endoscopic ultrasound-guided rendezvous (EUS-RV) or biliary drainage (EUS-BD), and percutaneous transhepatic biliary drainage (PTBD) should be selected according to indication, urgency, anatomy, patient stability, and local expertise. The algorithm distinguishes guideline-supported decision nodes from areas in which comparative evidence is limited and sequencing represents a practical expert synthesis.