Third Space Endoscopic Therapies for Benign Motility Disorders: A Narrative Review.

Objectives: To review the evidence base, evolution, outcomes, adverse events (AEs), and management for third-space endoscopy (TSE) procedures for management of benign motility disorders. Methods: This review examines TSE procedures for motility disorders, reviewing the current available techniques, success, outcomes, and long-term outcomes from the literature. Results: Peroral endoscopic myotomy (POEM) for achalasia cardia is now established as first-line therapy, endorsed by the American Society for Gastrointestinal Endoscopy, American College of Gastroenterology, Society of American Gastrointestinal and Endoscopic Surgeons, and international expert bodies, with long-term clinical success exceeding 90% at 7 years. Since 2010, the technique has evolved considerably, with refinements in myotomy length, orientation, and depth, along with intraoperative use of an endoluminal functional lumen imaging probe to optimize outcomes and reduce post-procedure gastroesophageal reflux (GER). The TSE platform has since expanded to spastic esophageal disorders, esophagogastric junction outflow obstruction, Zenker's and epiphrenic diverticula (Z-POEM/D-POEM), refractory gastroparesis (gastric per-oral endoscopic pyloromyotomy), and Hirschsprung's disease. Techniques have also been modified along the way to achieve better results while minimizing AEs. Post-POEM GER, occurring objectively in 40%-55% of patients, remains the principal long-term challenge, and multiple modalities have been explored to address it. Conclusions: TSE has fundamentally transformed the management of benign gastrointestinal motility disorders, with POEM serving as the paradigm for the shift from surgical to endoscopic treatment. Ongoing technical refinement, GER mitigation strategies, and emerging innovations are poised to further advance the field. Trial Registration: N/A.