Successful mucosal transplantation from stomach to esophagus for stricture prevention after widespread circular endoscopic submucosal dissection (ESD) for early esophageal squamous cell carcinoma – report of a first case in man with 1 year transplant survival after preliminary animal experiments in the pig

ESD in the esophagus is an expert technique for ‘en bloc’ resection of mucosal cancers >2cm in size. I can provide a quasi-surgical specimen and significantly reduces the risk of local recurrence compared to piecemeal EMR. However, secondary stricture formation is the major drawback for resections >3cm and of more than 75% of the esophageal circumference. Multiple bouginage sessions or temporary stent placement may be required limiting the QoL. Experimental approches include transplantation of buccal or dermal cell grafts as well as systemic and local steroid applications. However, clinical experience is very limited so far. Since march 2011 be had been performing animal experiments concerning esophageal resection and re-transplantation of esophageal and gastric mucosal patches in pigs under an approved protocol (NLVL No: 33–42502–06/1151) with first preliminary but encouraging results when the following clinical presented.

Case report: A 72 y male pat. with swallowing difficulty; tabacco use of 20 py until >15y ago. Prior rectal resection with sigma anus praeter for a T2 distal rectal cancer. EGD: Suspicion of early squamous cell cancer (Paris IIa; EUS UT1a, m, N0), >75% circum-ferential superficial tumor spread within the cervical esophagus and upper sphincter area (17–25cm aborally). Biopsy: SC HG-IEN. Discussion of the different treatment options in our interdisciplinary tumor board and with the patient: tubular endoscopic resection alone with 80–100% stricture probability, thermal ablation, radical surgery, primary chemoradiation or an experimental approach as compassionate use with primary ESD in the esophagus and secondary gastro-esophageal mucosal patch transplantation. On April 13, 2011 we performed an EGD under general anesthesia with tracheal intubation with first tubular ESD over 10cm from the lower hypopharynx through the UES from 17–27cm followed by a 9×4cm ESD in the gastric antrum. The healthy gastric specimen prelieved was cut longitudinally into 3 mucosal stripes which were attached to the denuded esophageal muscular layer by means of hemoclips. The specimen were gently pressed against the wall by a non-covered self-expanding metal stent to allow luminal and vascular nutrition of the specimen. The sphincter area of 1.5cm length had to be spared in order to not compress the lower larynx with the stent and to avoid unsupportable pain for the patient. After a control the following day the patient could be extubated. The esophageal specimen showed a non-invasive low horny early squamous cell cancer (pT1a G2 L-, V-) and and curative resection (R0; invasion depth of lamina propria max. 150 microns). Stent removal was performed at day 20 pp and was cumbersome due to local mucosal hyperplasia. However, multiple islets of gastric mucosa had successfully grown at the esophageal resection site. The patient was discharged on day 24 and regulary seen as outpatient. We observed a stepwise circular spread out of the reddish layer over an area of 5–6cm within the next 6 month and successful prevention of stenosis. Biopsy proved antral HP-negative mucosa. Unfortunately a 1–1.5cm non-transplant covered segment in the sphincter area showed a repetive tendency to stricture formation serving quasi as ‘natural’ control and requiring multiple ambulatory bouginage treatments but allowing a (semi-) solid diet without restrictions for most food products (DG1).

Conclusions: The so far unique case of a gastro-esophageal endoscopic mucosal transplant with one year follow-up after wide-spread ESD in the esophagus for an early squamous cell cancer opens a new perspective for systematic research in this field.