Third-Space Endoscopy in Gastrointestinal Disease: Techniques, Outcomes, and Future Directions: A Narrative Review.

BACKGROUND: Third-space endoscopy uses the submucosal layer as an intentional working corridor to enable dissection, myotomy, or enucleation while preserving organ integrity. The aim of this article was to provide a concise, procedure-based overview of established third-space endoscopic tunneling techniques - peroral endoscopic myotomy (POEM) including major variants, endoscopic submucosal tunnel dissection (ESTD) and submucosal tunneling endoscopic resection (STER) - while discussing endoscopic submucosal dissection (ESD) as the foundational submucosal dissection technique and endoscopic intermuscular dissection as an advanced intermuscular extension. SUMMARY: ESD established the principles of controlled submucosal entry, dissection and hemostasis that enabled subsequent tunneling techniques. ESTD adapts these principles to a mucosal flap-valve/tunnel approach for selected large esophageal neoplastic lesions. POEM has become a standard platform for achalasia and has been adapted to diverticular and gastric pyloric myotomy, whereas STER allows enucleation of selected muscularis propria subepithelial tumors with preserved mucosal integrity. Adoption remains limited by technical complexity, learning curves and infrastructure requirements, structured training and standardized outcome reporting are key enablers. KEY MESSAGES: Third-space endoscopy represents a shift toward endoscopic organ preservation. Continued innovation, transparent outcome reporting, and competency-based training pathways are essential for safe dissemination.