High Surface Area Intraluminal Gallbladder Cryoablation with the CholeSafe System: Preclinical Swine Studies as a Minimally Invasive Alternative to Cholecystectomy

Purpose: To investigate the feasibility and safety of high surface area intraluminal gallbladder cryoablation with the CholeSafe System (Ictero Medical, TX, USA) in a swine model, and to evaluate cryogen delivery parameters and identify thresholds for effective ablation.

Materials and Methods: Ten swine underwent high surface area intraluminal gallbladder cryoablation. After laparotomy, thermocouples were sutured to the gallbladder fundus, body, and neck. An 18F introducer sheath was advanced into the lumen, and nitrous oxide freeze cycles were delivered using the CholeSafe System. End-of-cycle intraluminal temperature (EOCT), thaw time to > 10 °C (TT), and minimum external gallbladder temperature (MET) were recorded. After ablation, the sheath was removed and the abdomen closed. Animals were monitored and underwent hepatobiliary MRI at 90 days to assess gallbladder volume, followed by necropsy and histology. Imaging success was defined as gallbladder involution with >90% luminal volume reduction and final volume < 1.5 mL. Histologic success was defined as the absence of viable mucosa.

Results: High surface area intraluminal gallbladder cryoablation was completed in all subjects with a median of 5.5 freeze cycles (IQR 1.75, range 3-7) and mean nitrous oxide delivery of 8.0 ± 3.4 L (range 2.6-12.8). All animals survived without adverse events. Mean EOCT was -34.5 ± 18.8 °C (range -0.1 to -82.1), TT 129.8 ± 78.6 s (27.2–350.0), and MET −3.0 ± 15.7 °C (-41.0 to 30.0). Eight of ten animals (80%) achieved imaging success, with necropsy showing gallbladder involution and histology confirming transmural fibrosis without viable mucosa. Two animals demonstrated incomplete ablation with a persistent lumen and residual mucosa, but these animals had no complications. Compared with incomplete ablation, complete ablation was associated with higher cryogen dose (8.5 vs 5.7 L), colder EOCT (-37.9 vs -20.4 °C) and MET (-5.5 vs 7.6 °C), and longer TT (142.0 vs 78.5 s).

Conclusion: High surface area intraluminal gallbladder cryoablation with the CholeSafe System is a promising minimally invasive alternative to cholecystectomy, with gallbladder involution and complete transmural fibrosis achieved in 80% of subjects with no adverse events. Threshold parameters of cryogen delivery (≥8.5 L), EOCT (< -38 °C), and TT ( >140 s) were identified as potential predictors of successful ablation, warranting further investigation.