Extension of early esophageal squamous cell neoplasia into ducts and submucosal glands and the role of endoscopic ablation therapy

Background and Aims: Early esophageal squamous cell neoplasia (ESCN) is preferably treated with en-blocendoscopic resection. Ablation might be an alternative for flat ESCN, but ESCN extension along the epithelial lining of ducts and submucosal glands (SMGs) might jeopardize ablation efficacy. Clinical studies suggest that localrecurrence might arise from such buried ESCN niches after ablation. We studied human endoscopic resectionspecimens of ESCN to quantify ESCN extension into ducts/SMGs and performed a prospective porcine studyto evaluate the depth of radiofrequency ablation (RFA) and CryoBalloon ablation (CBA) into ducts/SMGs.Methods: Endoscopic submucosal dissection specimens of flat-type ESCN from a Japanese (n Z 65) and Dutchcohort (n Z 14) were evaluated for presence and neoplastic involvement of ducts/SMGs. Twenty-seven pigs weretreated with circumferential RFA (c-RFA; n Z 4), focal CBA (n Z 20), and focal RFA (n Z 3) with 4, 60, and 9treatment areas, respectively. After prespecified survival periods (0 hours, 8 hours, 2 days, 5 days, and 28days), treatment areas were evaluated for uniformity and depth of ablation and affected SMGs.Results: Neoplastic extension in ducts/SMGs was observed in most lesions: 58% (38/65) in the Japanese and 64%(9/14) in the Dutch cohort. In the animal study, 33% of SMGs (95% confidence interval, 28-50) were not affectedafter c-RFA, although the overlying epithelium was ablated. Focal RFA and CBA resulted in uniform ablations witheffective treatment of all SMGs.Conclusions: ESCN extends into ducts/SMGs in most patients. In an animal model, focal RFA and CBA effectivelyablated SMGs, whereas c-RFA inadequately ablated SMGs. Given this potential reason for recurrence, endoscopicresection should remain the standard of care. (Gastrointest Endosc 2021;94:832-42.)