Post by Simon Sirtl

How do small gallstones cause acute pancreatitis without occluding the pancreaticobiliary outflow tract? Until now, only assumptions and hypotheses existed, but no conclusive pathomechanism had been established. The PICUS-1 trial demonstrated in 2023, using endoscopic ultrasound, that around 24% of patients with presumed idiopathic acute pancreatitis actually had pancreatitis triggered by microlithiasis or biliary sludge. However, it remained unclear how microlithiasis, in the absence of a sufficient ductal obstruction, could nevertheless trigger acute pancreatitis. We were now able to demonstrate for the first time that papillary biopsies from patients with microlithiasis-induced acute pancreatitis showed a significantly higher infiltration of CD45-positive leukocytes and increased NLRP3 expression compared with patients with alcohol-induced acute pancreatitis and with control subjects. Together with our in vitro data and findings from a microlithiasis mouse model, these results allow us to propose, for the first time, a pathomechanism explaining how small gallstones can trigger acute pancreatitis: via the intermediate step of acute papillitis, leading to a transient obstruction of the pancreaticobiliary outflow tract. Full paper read: https://lnkd.in/dfH-kE6E A huge thank you goes to our incredible co-authors and friends, who made this project possible and supported it throughout the nearly six years since its beginning. A special thanks also to the Medical and Clinician Scientist Program (MCSP), whose funding made this project possible in the first place. Mahmood Ahmad, Prince Allawadhi, Thomas Metzler, Oliver Buchstab, Steffen Ormanns, Martina Rudelius, Georg Beyer, Lukasz Krupa, Robert Staron, Christian Schulz, Lisa Fahr, Andrea Sendelhofert, Christian Schulz, Katja Steiger, Matthias Sendler, Markus M. Lerch, Ivonne Regel, Michał Żorniak, Julia Mayerle, Ujjwal Mukund Mahajan UEG - United European Gastroenterology UEG Journal Albrecht Neesse LMU Klinikum München Ludwig-Maximilians-Universität München European Pancreatic Club Pancreatitis Werkgroep Nederland / Dutch Pancreatitis Study Group Enrique de Madaria Gabriele Capurso Marc Besselink Giovanni Marchegiani DGVS Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten