Post-endoscopic retrograde cholangiopancreatography pancreatitis: Mechanistic pathways, diagnostic benchmarks, and emerging and mitochondria-targeted therapies.

This study presents a comprehensive overview of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), detailing its epidemiology, pathophysiology, prevention, and treatment. PEP is the most common complication of ERCP, with an incidence of 3%, 16%, and above 20% in high-risk patients. Proposed mechanisms include mechanical trauma, pancreatic-duct (PD) hypertension, oxidative stress, and dysbiosis-driven inflammation. Mitochondrial oxidative stress is a central pathological driver: It activates the NLRP3 inflammasome and the STING pathway, perpetuating a deleterious "injury-inflammation" cycle. Risk factors encompass patient characteristics, procedural variables, and operator-related factors. Preventive strategies combine pharmacological and procedural measures. Rectal non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, inhibit prostaglandin synthesis. European guidelines report that NSAIDs reduce the overall incidence of PEP, with odds ratios of 0.24-0.63. Subgroup analyses indicate the greatest benefit in high-risk cohorts, with mixed-risk groups also deriving more benefit than average-risk groups. In high-risk patients, prophylactic PD stenting markedly lowers PEP incidence by alleviating ductal hypertension. Aggressive fluid resuscitation enhances pancreatic perfusion and decreases the frequency of moderate-to-severe PEP. Recent therapeutic advances emphasize targeted interventions. Mitochondria-directed nanomedicines cross the blood-pancreas barrier, scavenge reactive oxygen species, and attenuate inflammatory cascades. A multidisciplinary team (MDT) approach optimizes infection control and manages complications in severe PEP, improving clinical outcomes. Future research should focus on addressing genetic susceptibility, developing novel targeted agents, and integrating artificial intelligence-assisted risk stratification to refine personalized prevention and therapy. This article reviews the epidemiological and pathophysiological foundations of PEP, evaluates evidence-based preventive strategies (e.g., NSAIDs, pancreatic duct stenting), and discusses emerging approaches such as gene therapy. It also summarizes advances in treating mild and severe PEP, highlights the role of MDT care, identifies current knowledge gaps, and proposes directions for future research, including the discovery of novel biomarkers and the development of personalized preventive and therapeutic strategies.