Endoscopic UltraSound guided-Gallbladder Drainage (EUS-GBD) is an established non-invasive approach for gallbladder drainage in elderly/comorbid patients. Technical guidelines suggest that a transduodenal versus transgastric route should be preferred due to the lower risk of stent occlusion and migration, despite the absence of any head-to-head comparison.

This is a single tertiary center prospective study conducted between Jan-2021 and Mar-2025. Allconsecutive patients treated with EUS-GBD with Lumen Apposing Metal Stents (LAMS) were enrolled in a Prospective Registry of Therapeutic EUS (PROTECT, ClinicalTrials.gov NCT04813055), with daily follow‐upduring admission and every 60 days after discharge. Baseline characteristics and Technical / Clinical outcomes were compared between the transduodenal versus transgastric access.

A total of 57 patients were enrolled, 47 (82.5%) and 10 receiving respectively transduodenal versus transgastric drainage. There was no difference in background characteristics between the groups. However, there were more EUS-GBD performed for biliary drainage in the transgastric (40%) versus transduodenal (2.1%) route, which also resulted in a higher prevalence of 8 mm LAMS use (30% versus 2.1%).Technical Success (100%) was similar between groups. However, the transgastric route showed lower rate of Clinical Success (70% versus 95.7%, p=0.01) and higher rate of Adverse Events (50% versus 14.9%,p=0.01). In this group, all adverse events were severe/fatal according to ASGE lexicon, and included 4 clinical failures of EUS-GBD for biliary drainage (of which 2 with endoscopic finding of buried  LAMS). After a median follow-up of 215 [61-404] days, there was no significant difference in the rate of recurrence of biliary events, despite the risk tended to be higher in the transgastric route (14.3% versus 6.7, p=0.5). Median estimated survival was shorter in the transgastric route (p=0.0045).

Despite the small sample size and the likely selection bias, this prospective comparison suggests that thetransgastric route for EUS-GBD is more prone to clinical failure and adverse events, such as LAMS occlusion or burial. The transuodenal route should be preferred, whenever feasible, for long-term LAMS indwell.