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

Anouk Overwater, Sanne N. van Munster, G. Johan A. Offerhaus, Cees A. Seldenrijk, G. Mihaela Raicu, Arjun D. Koch, Jacques J.G.H.M. Bergman, Roos E. Pouw, Lodewijk A.A. Brosens, Marnix Jansen, Bas L.A.M. Weusten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


Background and Aims: Early esophageal squamous cell neoplasia (ESCN) is preferably treated with en-bloc
endoscopic 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 local
recurrence might arise from such buried ESCN niches after ablation. We studied human endoscopic resection
specimens of ESCN to quantify ESCN extension into ducts/SMGs and performed a prospective porcine study
to 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 Dutch
cohort (n Z 14) were evaluated for presence and neoplastic involvement of ducts/SMGs. Twenty-seven pigs were
treated with circumferential RFA (c-RFA; n Z 4), focal CBA (n Z 20), and focal RFA (n Z 3) with 4, 60, and 9
treatment areas, respectively. After prespecified survival periods (0 hours, 8 hours, 2 days, 5 days, and 28
days), 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 affected
after c-RFA, although the overlying epithelium was ablated. Focal RFA and CBA resulted in uniform ablations with
effective treatment of all SMGs.
Conclusions: ESCN extends into ducts/SMGs in most patients. In an animal model, focal RFA and CBA effectively
ablated SMGs, whereas c-RFA inadequately ablated SMGs. Given this potential reason for recurrence, endoscopic
resection should remain the standard of care. (Gastrointest Endosc 2021;94:832-42.)
Original languageEnglish
Pages (from-to)832-842
JournalGastrointestinal Endoscopy
Issue number4
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
We thank the National Cancer Center Hospital in Tokyo, Drs Ryoji Kushima and Ichiro Oda in particular, for sharing data of the Japanese cohort. We also thank Koen Vaessen, Nico Attevelt, and Hester de Bruin for their support in the animal lab and Pentax Medical and Olympus for placing the required endoscopy equipment in the animal lab for the duration of the study free of charge.

Publisher Copyright:
© 2021 American Society for Gastrointestinal Endoscopy


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