Introduction Because of the morbidity associated with esophagectomy, there has been an impetus to move towards esophageal preservation in patients with Barrett’s esophagus (BE) with dysplasia or superficial malignancy. The introduction and success of endoscopic approaches such as endoscopic mucosal resection and radiofrequency ablation has resulted in a consumer demand for definitive endoscopic therapy. However, the primary limitations of these techniques are missed metachronous lesions, compromised histologic assessment, the need for subsequent procedures and stricture formation. Resection of the entire mucosal-submucosal complex (MSC) followed by an extracellular matrix scaffold substitution could potentially address these concerns. The objective of this study was to determine technical feasibility of transoral endoscopic sleeve resection of the esophageal MSC in an animal model. MethodsSix adult female swine underwent transoral endoscopic esophagectomy (TEE). Beginning at 20 cm from the dental arch, a 1 cm circumferential plane was created between the MSC and the muscularis propria (MP) using cap endoscopic resection and insulated needle knife dissection. A vein stripper was passed retrograde into the esophagus through an endoscopic gastrostomy and secured to the MSC sleeve. Drawing back on the vein stripper facilitated MSC inversion and enabled dissection away from the MP over the entire length of the esophagus. MSC tissue specimens were retrieved and autopsy was performed. Endpoints included procedure time, number of cap resections, MSC and MP mural integrity with leak testing, hemorrhage events requiring intervention, resection length and residual MSC adherent to MP.ResultsIn all animals TEE was successfully completed. Mean procedure time was 195 minutes (range 135-320). Mean number of cap resections to reach a circumferential plane was 2.8 (range 1-5). No transmural MSC or MP perforations occurred. A mean of 2 (range 1-3) hemorrhage events per procedure required endoscopic intervention. Macroscopic and histological assessment demonstrated 100% longitudinal resection in 5 of 6 animals and complete resection margin depth in 97% (range 90-100) of the total surface area removed.ConclusionTEE is feasible in this animal model and results in an intact and unaltered specimen. This natural orifice surgical technique may lead to a one step diagnostic and/or therapeutic approach in the treatment of BE and early stage malignancy, which will enable esophageal preservation and avoid the morbidity associated with traditional esophagectomy.