Non-Invasive Pancreas Ablation Using Histotripsy: Pre-clinical Safety Study in an In Vivo Porcine Model

Pancreatic cancer is an aggressive disease that is typically diagnosed late, leading to poor prognosis and overall survival. Even with advances in treatment, the 5-year survival rate for patients is only 12.5%. Histotripsy is a non-invasive, non-thermal and non-ionizing focused ultrasound treatment method that has recently been US FDA approved for treating liver tumors and is currently being investigated for other applications. This study expands on prior work investigating the feasibility of pancreas ablation using ultrasound-guided histotripsy in pigs. Here, we applied histotripsy to healthy pancreas in nine pigs using a therapy system with treatments guided by real-time ultrasound imaging. After treatment, subjects survived for 1 week (n = 3) or 5 weeks (n = 6). Damage to the pancreas and surrounding tissue was characterized using gross morphology, histological analysis, and computed tomography imaging. Treatment zones were visible on immediate post-procedure computed tomography, with lesion dimensions measuring 1.4 ± 0.6 cm, 1.2 ± 0.3 cm, and 1.5 ± 0.4 cm in the anteroposterior, transverse, and craniocaudal planes, aligning with the planned 1.5 cm-diameter spherical treatment volume. At 5 weeks, lesion size reduction was observed in three subjects, decreasing by 49%, 98%, and 100%, respectively. Histotripsy was well-tolerated, with successful pancreas targeting in six of nine subjects. Two cases of potential pancreatitis were noted. Three pigs experienced bowel damage due to poor ultrasound visualization, leading to off-target effects including septic peritonitis and gastrointestinal blockage. These findings suggest histotripsy is a viable approach for pancreatic treatment when the organ is clearly visualized and bubble clouds remain within the tissue.