Abstract

Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial oesophageal squamous cell carcinoma (ESCC). However, post-procedure stricture is common after ESD for widespread tumours, and multiple endoscopic balloon dilation (EBD) procedures are required. We aimed to evaluate the safety and effectiveness of endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets that had been transported by air over a distance of 1200 km in controlling postprocedural oesophageal stricture. Ten patients who underwent complete circular or semicircular ESD for ESCC were transplanted with cell sheets. The safety of the entire process including cell sheet preparation, transport, ESD and cell sheet transplantation was assessed. The incidence of oesophageal stricture, number of EBD sessions, and time until epithelialization were investigated. Each ESD was successfully performed, with subsequent cell sheet engrafting carried out safely. Following cell sheet transplantation, the luminal stenosis rate was 40%, while the median number of EBD sessions was 0. The median post-ESD ulcer healing period was rather short at 36 days. There were no significant complications at any stage of the process. Cell sheet transplantation and preparation at distant sites and transportation by air could be a safe and promising regenerative medicine technology.

Highlights

  • Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial oesophageal squamous cell carcinoma (ESCC)

  • We reported that oral prednisolone could be effective for aggressive oesophageal ESD even in certain cases of circumferential ESD, reducing the number of endoscopic balloon dilation (EBD) sessions required[2]

  • By follow-up endoscopic and histological examinations, we demonstrated rapid epithelization and reconstruction of oesophageal mucosa following transplantation

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Summary

Introduction

Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial oesophageal squamous cell carcinoma (ESCC). Oesophageal stenosis often occurs after ESD when a widespread lesion involves more than three-fourths of the luminal circumference[2,3] Such situations require frequent endoscopic balloon dilatation (EBD), which compromises quality of life and prolongs hospitalization[1]. Local steroid (triamcinolone) injection has been effective in avoiding luminal stricture in semicircular but not in complete circular ESD3 This treatment still carries potential risks of perforation and mediastinal www.nature.com/scientificreports/. Ohki et al.[7] applied endoscopic transplantation of cultured autologous oral mucosal epithelial cell sheets in 9 patients with superficial oesophageal squamous carcinoma to prevent post-ESD stricture. Endoscopic cell sheet transplantation can be expected to succeed as a new modality for the prevention of post-ESD stenosis This cell-based therapy using autologous oral mucosal epithelial cell sheets has disadvantages. Fabrication of cell sheets is both technically and financially difficult even in a university tertiary hospital setting[4,7,8]

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