Esophageal preservation in five male patients after endoscopic inner-layer circumferential resection in the setting of superficial cancer: a regenerative medicine approach with a biologic scaffold

Abstract

As a result of injury caused by chronic gastroesophageal reflux, Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma are rapidly increasing problems in the United States. The current standard of care involves esophagectomy, a procedure associated with a high morbidity, a negative impact on long term quality of life, and a mortality rate of 1-6 percent. An entirely endoscopic technique for circumferential, long segment en bloc removal of the mucosa and submucosa with subsequent placement of a biologic scaffold material that promotes a constructive remodeling response and minimizes stricture is described herein. The results of this approach are reported for five patients with 4-24-month follow-up. Restoration of normal mature, K4+/K14+, squamous epithelium, and return to a normal diet without significant dysphagia is reported for all patients. Two of five patients show a small focus of recurrent Barrett's esophagus at the gastroesophageal junction, but the entire length and circumference of the reconstituted esophageal mucosa remains free of disease. This experience provides evidence that a regenerative medicine approach may, for the first time, enable aggressive endoscopic resection of early stage neoplasia without the need for esophagectomy and its associated complications.

Figures

FIG. 1.

Left panel shows the inversion technique. Drawing back on the plastic cable at the site of the gastrostomy facilitates inversion of a sleeve of attached mucosal and submucosal layers. Using this technique, the remaining attachments are stripped away from the muscularis externa, thereby freeing the entire sleeve of tissue. The sleeve is then retrieved and exited through the mouth. The right panel demonstrates a 13-cm-long sleeve of esophageal inner layers removed from patient no. 3. The tube shaped sleeve was split longitudinally for subsequent fixation and histopathologic processing. Color images available online at www.liebertonline.com/tea

FIG. 2.

Representative endoscopic views of each stage in the procedure and follow-up. (Upper row) Left: 8-cm-long circumferential muscularis externa was exposed after inversion and resection of the entire sleeve of mucosal and submucosal layers. Middle: the stent was deployed resulting in the gentle compression of ECM against the entire exposed mucsularis externa. Right: 2-week follow-up, immediately after the stent removal. ECM could be seen firmly attached to the area of resection. (Bottom row) Left: 5-week follow-up, the ECM was no longer visible and the resected area was completely covered by squamous epithelium. Middle: 10-month follow-up. The entire esophageal mucosa appeared normal with soft, short segment circumferential strictures. Right: 13-month follow-up. The entire resected area was covered by normal esophageal epithelium without stricture formation. ECM, extracellular matrix. Color images available online at www.liebertonline.com/tea

FIG. 3.

Diagnostic biopsy (top row), postoperative biopsy (second row), K4 immunolabeling (third row), and K14 immunolabeling images from each of the four patients. The number of weeks indicated at the bottom of the figure represents the time at which the postoperative biopsy was taken. The diagnostic biopsies all show adenocarcinoma. The postoperative biopsies show replacement of the ECM scaffold with mature, differentiated squamous epithelium. Scale bars represent 100 μm. Color images available online at www.liebertonline.com/tea