Expanding Role of Third Space Endoscopy in the Management of Esophageal Diseases

“Third space” endoscopy, also commonly referred as submucosal endoscopy, is founded on the principle that the deeper layers of the gastrointestinal (GI) tract can be accessed by tunneling in the submucosal space without compromising the integrity of the overlying mucosa. Peroral endoscopic myotomy (POEM), endoscopic submucosal dissection (ESD), and submucosal tunneling endoscopic resection (STER) are innovative techniques within the field of third space endoscopy in the management of esophageal disorders. POEM has become an accepted minimally invasive therapy for achalasia and related motility disorders with excellent short-term results, with early studies yielding similar efficacy to surgical myotomy and increased durability when compared to pneumatic balloon dilation (PBD). Data are needed to establish long-term outcomes with POEM, with particular interest on the incidence of gastroesophageal reflux, which appears to be higher than initially anticipated. ESD, a mature endoscopic resection technique in Asia, has recently gained traction in the West as a viable option for the management of early Barrett’s esophagus (BE) neoplasia. Compared to standard endoscopic mucosal resection (EMR), ESD allows the en bloc resection of lesions irrespective of size, which may facilitate histological interpretation and reduce recurrence rates. Large prospective randomized controlled trials are needed to validate the efficacy and safety of this technique and to further define its role in the endoscopic armamentarium in early BE neoplasia. STER is an attractive technique that theoretically permits the resection of subepithelial esophageal tumors (SETs) arising from the deeper GI layers. Initial studies from highly experienced endoscopic centers support its technical feasibility and safety, although these results should be interpreted with caution due to variability arising from small numbers and heterogeneity among studies. Overall, third space endoscopy is an expanding field within endoscopic therapeutics for the treatment of esophageal diseases. While initial results have been very promising, large prospective studies, long-term data, and structured training programs with the establishment of competency parameters are needed before third space endoscopy can be advocated outside of highly specialized centers.