The capabilities of interventional gastrointestinal endoscopy have significantly increased over the past several decades. Improvements in devices and techniques have eased the transfer of novel concepts from bench to bedside. The concept of submucosal endoscopy with mucosal flap safety valve has enabled endoscopists to securely use submucosal space, or third space. Peroral endoscopic myotomy was the initial procedure performed utilizing submucosal space in patients with achalasia. Subsequently, this technique has been used successfully for removal of subepithelial tumors from the esophagus and the stomach. All third-space endoscopy procedures use a similar technique—a submucosal tunnel is created, and then a myotomy is performed or a sub-epithelial tumor is dissected away from the initial site of the mucosal incision. The other potential indications for third-space endoscopy include refractory gastroparesis, Zenker diverticulum, andrestoration of completely obstructed esophageal lumen. Although the emerging data look promising for peroral endoscopic myotomy and pyloromyotomy, randomized studies with long-term follow-up are lacking. Submucosal endoscopy is largely safe, and the occurrence of major adverse events is uncommon. Therefore, the majority of third-space endoscopy procedures can be performed in an endoscopy suite. The most frequently encountered adverse events during submucosal endoscopy include those related to insufflation, bleeding, and perforations.
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