A novel cryoballoon ablation system for eradication of dysplastic Barrett’s esophagus: a first-in-human feasibility study

Abstract

Background Endoscopic cryoablation for Barrett’s esophagus (BE) might offer advantages over heat-based ablation. Focal cryoballoon ablation has been promising for short-segment BE, whereas the novel 90°-swipe cryoballoon ablation system (CbSAS⁹⁰) ablates larger areas in a single step (90° over 3 cm). The system allows for dose adjustment. CbSAS⁹⁰ has been feasible and safe in animal and pre-esophagectomy studies. This is the first clinical study to assess feasibility, safety, and efficacy of CbSAS⁹⁰ for eradication of dysplastic BE.

Methods In this prospective study in dysplastic BE patients, dose finding started with semi-circumferential treatment at 0.8 mm/s (dose 1). The dose was escalated by reducing speed by 0.1 mm/s in six patients until BE surface regression was ≥ 80 % without complications (“effective dose”). The effective dose was subsequently confirmed with circumferential treatment in 12 new patients. Post-procedural pain (0 – 10) and dysphagia (0 – 4) were evaluated. Outcomes were feasibility, safety, and BE surface regression.

Results 25 patients were included, with technically successful treatment in 92 % (95 %CI 73 % – 99 %). Median (95 %CI) BE surface regression was 78 % (50 % – 85 %) for dose 1 and 85 % (55 % – 95 %) for dose 2 (0.7 mm/s), which was defined as the effective dose. Circumferential treatment resulted in 93 % (88 % – 96 %) regression. Two of 12 patients with circumferential treatment developed strictures that required dilation. Median pain and dysphagia scores were low (0 – 3 and 0, respectively).

Conclusions CbSAS⁹⁰ was feasible and effective for ablating larger BE areas. The optimal dose for circumferential treatment that balances safety and efficacy requires further evaluation.

• References

• 1 Desai TK, Krishnan K, Samala N. et al. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett’s oesophagus: a meta-analysis. Gut 2012; 61: 970-976
• 2 Weusten B, Bisschops R, Coron E. et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 2017; 49: 191-198
• 3 Baust JG, Gage AA. The molecular basis of cryosurgery. BJU Int 2005; 95: 1187-1191
• 4 Spechler SJ, Sharma P. American Gastroenterological Association. et al. American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology 2011; 140: 1084-1091
• 5 Baust JG, Gage AA, Bjerklund Johansen TE. et al. Mechanisms of cryoablation: clinical consequences on malignant tumors. Cryobiology 2014; 68: 1-11
• 6 van Munster SN, Overwater A, Haidry R. et al. Focal cryoballoon versus radiofrequency ablation of dysplastic Barrett’s esophagus: impact on treatment response and postprocedural pain. Gastrointest Endosc 2018; 88: 795-803.e2
• 7 Solomon SS, Kothari S, Smallfield GB. et al. Liquid nitrogen spray cryotherapy is associated with less postprocedural pain than radiofrequency ablation in Barrett’s esophagus. J Clin Gastroenterol 2019; 53: e84-e90
• 8 Overwater A, Weusten BLAM. Cryoablation in the management of Barrett’s esophagus. Curr Opin Gastroenterol 2017; 33: 261-269
• 9 Johnston MH, Eastone JA, Horwhat JD. et al. Cryoablation of Barrett’s esophagus: a pilot study. Gastrointest Endosc 2005; 62: 842-848
• 10 Xue H, Tan H, Liu W. et al. A pilot study of endoscopic spray cryotherapy by pressurized carbon dioxide gas for Barrett’s esophagus. Endoscopy 2011; 43: 379-385
• 11 Schölvinck DW, Friedland S, Triadafilopoulos G. et al. Balloon-based esophageal cryoablation with a novel focal ablation device: dose-finding and safety in porcine and human models. Dis Esophagus 2017; 30: 1-8
• 12 Canto MI, Shaheen NJ, Almario JA. et al. Multifocal nitrous oxide cryoballoon ablation with or without EMR for treatment of neoplastic Barrett’s esophagus (with video). Gastrointest Endosc 2018; 88: 438-446.e2
• 13 Künzli H, Schölvinck D, Meijer S. et al. Efficacy of the CryoBalloon Focal Ablation System for the eradication of dysplastic Barrett’s esophagus islands. Endoscopy 2016; 49: 169-175
• 14 Schölvinck D, Künzli H, Kestens C. et al. Treatment of Barrett’s esophagus with a novel focal cryoablation device: a safety and feasibility study. Endoscopy 2015; 47: 1106-1112
• 15 Louie BE, Hofstetter W, Triadafilopoulos G. et al. Evaluation of a novel cryoballoon swipe ablation system in bench, porcine, and human esophagus models. Dis esophagus 2018;
• 16 Swager A-F, Curvers WL, Bergman JJ. Diagnosis by endoscopy and advanced imaging of Barrett’s neoplasia. In: Jansen M, Wright NA. , eds. Stem cells, pre-neoplasia, and early cancer of the upper gastrointestinal tract. Cham: Springer; 2016: 81-98
• 17 Dische S, Saunders M, Barrett A. et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol 1997; 44: 123-136
• 18 Nederlandse Vereniging van Maag-darm-leverartsen. Richtlijn Barrett-Oesofagus. 2018 Available from: https://www.mdl.nl/sites/www.mdl.nl/files/richlijnen/Richtlijnen%20Barrett%20oesofagus%20-%20jan%202018%20-%20tbv%20website.pdf Accessed: 15 April 2019
• 19 Pouw RE, Seewald S, Gondrie JJ. et al. Stepwise radical endoscopic resection for eradication of Barrett’s oesophagus with early neoplasia in a cohort of 169 patients. Gut 2010; 59: 1169-1177
• 20 Trindade A, Canto M. Circumferential treatment of long-segment Barrett’s esophagus using the next-generation cryoballoon. Endoscopy 2019; 51: E69-E70
• 21 Belghazi K, Pouw RE, Koch AD. et al. Self-sizing radiofrequency ablation balloon for eradication of Barrett’s esophagus: results of an international multicenter randomized trial comparing 3 different treatment regimens. Gastrointest Endosc 2019; 90: 415-423
• 22 Zemlyak AY, Pacicco T, Mahmud EM. et al. Radiofrequency ablation offers a reliable surgical modality for the treatment of Barrett’s esophagus with a minimal learning curve. Am Surg 2012; 78: 774-778
• 23 Peerally MF, Bhandari P, Ragunath K. et al. Radiofrequency ablation compared with argon plasma coagulation after endoscopic resection of high-grade dysplasia or stage T1 adenocarcinoma in Barrett’s esophagus: a randomized pilot study (BRIDE). Gastrointest Endosc 2019; 89: 680-689
• 24 Shaheen NJ, Sharma P, Overholt BF. et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 2009; 360: 2277-2288
• 25 van Vilsteren FGI, Alvarez Herrero L, Pouw RE. et al. Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett’s esophagus with early neoplasia: a prospective multicenter study. Endoscopy 2013; 45: 516-525
• 26 Belghazi K, Pouw R, Sondermeijer C. et al. A single-step sizing and radiofrequency ablation catheter for circumferential ablation of Barrett’s esophagus: Results of a pilot study. United Eur Gastroenterol J 2018; 6: 990-999
• 27 van Vilsteren FGI, Phoa KN, Alvarez Herrero L. et al. Circumferential balloon-based radiofrequency ablation of Barrett’s esophagus with dysplasia can be simplified, yet efficacy maintained, by omitting the cleaning phase. Clin Gastroenterol Hepatol 2013; 11: 491-498.e1
• 28 Chadwick G, Groene O, Markar SR. et al. Systematic review comparing radiofrequency ablation and complete endoscopic resection in treating dysplastic Barrett’s esophagus: a critical assessment of histologic outcomes and adverse events. Gastrointest Endosc 2014; 79: 718-731.e3
• 29 Pouw RE, Wirths K, Eisendrath P. et al. Efficacy of radiofrequency ablation combined with endoscopic resection for Barrett’s esophagus with early neoplasia. Clin Gastroenterol Hepatol 2010; 8: 23-29
• 30 Sharma VK, Jae Kim H, Das A. et al. Circumferential and focal ablation of Barrett’s esophagus containing dysplasia. Am J Gastroenterol 2009; 104: 310-317