Searching for a better mousetrap for ablation of Barrett’s esophagus

I am pleased to share some insights on the article by Gotink et al. in this issue of Endoscopy: “Nonthermal resection device for ablation of Barrett’s esophagus: a feasibility and safety study” [1]. The authors are experts in both endoscopic therapy and clinical trials, making this an ideal team to evaluate the novel nonthermal resection device (EndoRotor Mucosal Resection device; Interscope Inc., Northbridge, Massachusetts, USA) for patients with Barrett’s esophagus. Well-meaning endoscopists must consider the risks of new technologies over the standard-of-care when they act as early adopters. Thus, I applaud the editors for choosing this well-performed clinical trial. We are cognizant of bias against reporting ineffective treatments and poor outcomes, especially with a trend toward industry funding, and publishing positive outcomes [2].

“The study revealed a relatively high complication rate with the novel device and deemed the procedure to be technically demanding.”

The current study included 30 consecutive patients with flat high grade dysplasia, low grade dysplasia, or residual neoplasia after mucosal resection (2–5 cm). Results revealed a relatively high complication rate with the novel device and deemed the procedure to be technically demanding. Although all patients received submucosal injection of epinephrine, one patient suffered post-procedural bleeding and another suffered a perforation. The stricture rate was 4/30 (13 %) and severe pain was reported in 60 % of patients. Only one patient had complete eradication after the initial ablation session and their segment was relatively small (C0M3).

Endoscopic ablation remains one of the most common treatments for Barrett’s esophagus and neoplasia [3]. The search for ablation techniques started with therapies used to cauterize blood vessels (heater probe and bipolar electrocautery), then progressed to more advanced forms of thermal ablation with radiofrequency energy and cryotherapy. Developers have referred to the former devices as “point and shoot” or focal therapy, and the latter as wide area application of ablative energy. Focal technologies are not only tedious to use but also result in uneven treatment, with residual tissue and high recurrence rates. Additionally, experts widely accept using focal technologies such as argon plasma coagulation at appropriate energy settings for small residual areas of neoplasia after mucosal resection or wide area ablation. Not all modalities have proven successful, and some (e. g. photodynamic therapy with porphyrin sodium) have gone to the wayside owing to their cumbersome nature or untoward adverse effects.

Therefore, the question remains: is there more going on with the accepted ablation technologies than meets the eye? To evaluate potential reasons for their continued use, let us diverge and discuss Laplace’s law as it applies to distension of the esophageal wall and its target lesion. Focal technologies rely on the endoscopist aligning the treatment catheter to the Barrett’s mucosa with the esophagus generally in a decompressed state. Wide area applications generally distend the esophageal wall, which thins the layers and associated neoplasia according to Laplace’s law of the relationship between wall thickness and wall tension. This is one of the most important factors in determining efficacy of ablation technologies. With the wall distended, the distance between the thermal interface and the submucosal layer decreases.

Regarding cryotherapy, the principle of wall distension may even account for the similar efficacy of the two commercially available devices in different microenvironments. The standard ablation dose for Barrett’s esophagus with flat dysplasia is one application of nitrous oxide in a distended balloon or two applications of liquid nitrogen during constant decompression.

Future technologies should focus on the underlying principles of Laplace’s law with regard to wall thinning in order to properly treat the entire mucosal layer. Radiofrequency ablation and cryotherapy have excellent efficacy and safety profiles. Cryotherapy is favored for radiofrequency failures when endoscopic resection is not feasible [4] [5]. The outcome of this study is more than the fact that the EndoRotor device fell short of the expectations of experts in Barrett’s ablation with respect to ease of use, safety, and efficacy. In my opinion, the principal outcome is that a well-conducted clinical trial can educate early adopters and avoid unnecessary harm when suitable alternatives are widely available.

Publication History

Article published online:
01 February 2022

• References

• 1 Gotink AW, Peters Y, Bruno MJ. et al. Nonthermal resection device for ablation of Barrett’s esophagus: a feasibility and safety study. Endoscopy 2022; 54: 545-552 DOI: 10.1055/a-1644-4326.
• 2 Brown A, Kraft D, Schmitz SM. et al. Association of industry sponsorship to published outcomes in gastrointestinal clinical research. Clin Gastroenterol Hepatol 2006; 4: 1445-1451
• 3 Shaheen NJ, Falk GW, Iyer PG. et al. ACG Clinical Guideline: Diagnosis and management of Barrett’s esophagus. Am J Gastroenterol 2016; 111: 30-50
• 4 Tariq R, Enslin S, Hayat M. et al. Efficacy of cryotherapy as a primary endoscopic ablation modality for dysplastic Barrett’s esophagus and early esophageal neoplasia: a systemic review and meta-analysis. Cancer Control 2020; DOI: 10.1177/1073274820976668.
• 5 Visrodia K, Zakko L, Singh S. et al. Cryotherapy for persistent Barrett’s esophagus after radiofrequency ablation: a systematic review and meta-analysis. Gastrointest Endosc 2018; 87: 1396-1404