S446 Nano-Pulse Stimulation Technology Is a Promising New Energy Modality for Barrett’s Esophagus

Abstract

Introduction: Barrett’s esophagus greatly increases risk of esophageal adenocarcinoma. Various technologies can address Barrett’s but are limited in adoption by post-ablation stricture formation and pain. Nano-Pulse Stimulation™ (NPS™) technology disrupts normal cellular organelle functions, inducing apoptotic-like regulated cell death (RCD), without destroying the cell membrane or causing collateral damage to acellular collagen-rich tissues. NPS is a non-thermal modality that utilizes a nano-second duration pulsed electric field offering an alternative to thermal ablation. We performed an animal dose-response feasibility study to assess NPS treatment effect on esophageal epithelium, submucosal glandular structures and fibrosis. Methods: Using 10 female Yorkshire swine, fifty 1.6-cm long distal esophageal treatments were performed with a novel NPS catheter. Energy delivered during NPS treatment averaged 10.85 ± 0.29 J, with an average power of 0.56 ± 0.05 W. Results: Histopathology performed on treatments from 8 hours to 2 days revealed complete epithelial cell death, mild exudate, and caspase 3 epithelial and submucosal gland activity, indicating initiation of RCD. Evidence of reepithelization began at day 2 and was completed by day 8. At day 17, submucosal glands and muscularis mucosa had been eliminated with no evident damage to the muscularis propria, demonstrating controlled depth of treatment effect. Also, by 17 days, complete esophageal reepithelialization was observed. Esophagoscopy performed at the end of each study timepoint provided no evidence of stricture formation. Conclusion: NPS treatment at the prescribed energy and power results in apoptotic-like regulated cell death and total elimination of the esophageal mucosa and submucosal glands while sparing structural collagen and avoiding stricture. No evidence of thermal damage was present at any timepoint after NPS treatment, and complete mucosal reepithelialization occurred within 17 days. These results support the potential value of NPS technology as a novel treatment modality for Barrett’s esophagus.Figure 1.: Formalin fixed paraffin embedded histology samples of the esophagus stained with H&E and acquired at 1.5x magnification. Images show (A) untreated, (B) acute, (C) 2 days, (D) 8 days, and (E) 17 days post NPS treated esophageal tissue.