Stricture prevention after extended circumferential endoscopic mucosal resection by injecting autologous keratinocytes in the sheep esophagus

Abstract

During the past decades, endoscopic mucosal resection (EMR) has been developed to treat early intramucosal esophageal cancers and dysplastic Barrett's esophagus. The primary drawback of this method is severe postsurgical esophageal stricture formation. The purpose of this preclinical study was to assess strategies for prevention of this major complication by injecting autologous keratinocytes in the EMR mucosal defect in the sheep model. Circumferential, 6-cm-long EMRs were performed in the esophagus of nine sheep. Autologous keratinocytes were harvested 2 weeks before EMR and cultured. Circumferential resection consisted of two opposite hemicircumferential mucosectomies allowing a widespread resection of 24 cm(2). Immediately after EMR, autologous keratinocytes were endoscopically injected in the mucosal defect. Animals were sacrificed after 6 months. Circumferential EMRs were successfully performed in all animals. There were no intra- or postoperative complications. None of the animals developed strictures. All animals were sacrificed at 6 months as planned. Histological examinations showed fibrotic changes in 10 % (range 0-25 %) of the circumferential muscularis propria interna layer and 7.2 % (range 0-25 %) in the muscularis propria externa layer at the midportion of the EMR. No circumferential transmural fibrosis was identified. Prevention of stricture formation after extensive (6-cm long) circumferential EMR of the sheep esophagus can be achieved by injecting autologous keratinocytes into the wound of the resected mucosal segment.