Evolving field of third-space endoscopy: Derivatives of peroral endoscopic myotomy

Third-space endoscopy, also known as submucosal endoscopy, allows for a wide range of therapeutic interventions within the submucosal layer and even into the muscular or subserosal layers of the gastrointestinal lumen. The technical development of peroral endoscopic myotomy (POEM) for achalasia has revolutionized the field of therapeutic endoscopy and the method has been continuously refined and modified. Although POEM has been applied to treat primary achalasia, it shows a favorable clinical response in other esophageal motility disorders and as a salvage treatment after previously failed intervention. Gastroesophageal reflux after POEM has drawn considerable attention and there have been major advancements in its prevention and management. POEM has led to advantageous derivatives such as peroral endoscopic tumor resection or submucosal tunneling endoscopic resection for resection of subepithelial lesions, Zenker POEM for hypopharyngeal diverticula, diverticular POEM for epiphrenic esophageal diverticula, and gastric POEM for refractory gastroparesis. These techniques have a similar concept, which constitutes submucosal tunneling with a mucosal flap valve and secure mucosal incision closure. The submucosal tunneling technique is widely accepted and continues to evolve. This study aimed to review in detail the indications, outcomes, and technical variations in POEM and explore several emerging submucosal tunneling procedures. This review will benefit future studies by providing a summary of recent developments in this field.