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Introduction: Circumferential endoscopic esophageal submucosal dissection (EESD) for high grade dysplasia or early cancer provides an intact specimen for histology, offers less-invasive therapy than esophagectomy and potentially allows one-step en bloc eradication of Barrett’s esophagus. As such, the technique holds potential for staging, treating and preventing esophageal cancer. However, aggressive stricture formation after EESD has limited its clinical use. We hypothesized that an in vivo esophageal stricture model could be developed to assess endoscopic interventions designed to prevent stricture formation following EESD.
Methods: Five swine were utilized in this study. Under anesthesia, a flexible endoscope with a band ligator and snare was used to circumferentially incise the mucosal layer 20 cm proximal to the lower esophageal sphincter. An approximately 10 cm circumferential segment of tissue was dissected free from the underlying muscle and excised using electrocautery and snare. Weekly barium esophagograms evaluated for reduction in esophageal diameter and assessed stricture length and proximal dilation. Animals were followed clinically and were euthanized when the stricture exceeded 80% and they were unable to gain weight (despite high-calorie liquid diet). A blinded pathologist evaluated EESD and necropsy specimens.
Results: Resected specimens ranged from 90-110 mm in length. Histology confirmed uniform en bloc mucosal resection down to the superficial submucosa. All five animals rapidly developed strictures following EESD. At one week, animals demonstrated a 62.2±12.9% reduction in luminal diameter, longitudinal shortening to 77.6±12.4% of the original resected length with dilation in the proximal esophagus to 128±6.2% baseline diameter. By two weeks, animals demonstrated a 77.7±12.1% reduction in luminal diameter, longitudinal shortening to 62.7±12.3% of the original resected length with dilation in the proximal esophagus to 174.8±27.3%. Based on criteria, no animal survived beyond the third week of study. There was no correlation between resected specimen length and the degree of luminal narrowing or survival. Stricture zone histology showed unepitheliazed submucosa with abundant PMNs, fibrosis and neovascularization.
Conclusions: We describe the successful development of an esophageal stricture model. EESD in the porcine esophagus removes specimens of uniform length and depth without damaging the underlying muscule. Circumferential EESD results in clinically significant stricture formation within weeks. Esophagograms demonstrated uniform reduction in luminal diameter in the area of resection with concomitant proximal esophageal dilation. Histology confirmed the presence of inflammation and fibrosis. Future areas of investigation will focus on endoscopic methods to alleviate or prevent stricture formation following EESD.