Achalasia is a type of esophageal motility disorder, consisting of relaxation dysfunction of the lower esophagus and disturbed esophageal peristalsis. Related clinical symptoms include dysphagia, regurgitation, chest pain, and weight loss. Traditional treatment options include endoscopic botulinum toxin injection, endoscopic pneumatic dilation, and laparoscopic Heller's myotomy. These therapies mainly relieve symptoms by reducing the pressure on the lower esophageal sphincter and reducing blood flow resistance at the esophagogastric junction. Based on endoscopic submucosal dissection and natural orifice transluminal endoscopic surgery, peroral endoscopic myotomy (POEM) is a purely endoscopic method of myotomy with minimal invasiveness and a low rate of adverse events when performed by experienced operators. Since then, numerous studies have shown the significant clinical efficacy and safety of POEM. The purpose of this article is to introduce different modified POEMs, special indications for different POEMs, and their advantages as well as disadvantages.

The field of third space endoscopy (TSE), also called submucosal endoscopy using a mucosal flap valve, allows secure access to the submucosal and deeper layers of the gastrointestinal tract without the risk of a full-thickness perforation. Since the first description of per-oral endoscopic myotomy (POEM) for the treatment of achalasia cardia 10 years ago, this field has expanded rapidly. Several new procedures, submucosal tunneling endoscopic resection, gastric-POEM, Zenker POEM, per-rectal endoscopic myotomy, diverticular POEM, and recanalization for complete esophageal obstruction (per-oral endoscopic tunneling for restoration of the esophagus), have been performed. All TSE procedures employ a similar technique-after a mucosal incision, a submucosal tunnel is created, a myotomy is performed, or a subepithelial tumor is resected distal to the site of mucosal incision, after which the mucosal incision is closed. Potential indications for TSE include resection of subepithelial tumors in the esophagus, gastroesophageal junction, or stomach; refractory gastroparesis; Zenker diverticulum; Hirschsprung disease or other forms of megacolon; and recanalization for complete esophageal obstruction. Data are currently available for POEM, submucosal tunneling endoscopic resection, and gastric-POEM, although mainly in the form of retrospective studies, and randomized trials and long-term follow-up data are limited. Submucosal endoscopy has an excellent safety profile with very few intraoperative adverse events, the majority being related to insufflation, although bleeding, perforation, and sepsis have been reported. TSE procedures require special training and have demonstrated a learning curve.