Achalasia is a motility disorder of the esophagus, characterized by aperistalsis of the esophageal body and incomplete relaxation of the lower esophageal sphincter (LES). Treatment of achalasia is currently aimed at decreasing the resting pressure in the LES. Peroral endoscopic myotomy (POEM) is an emerging novel endoscopic procedure for the treatment of achalasia with initial data suggesting an acceptable safety profile, excellent short-term symptom resolution, low incidence of postprocedural gastroesophageal reflux (GER), and improvement in manometric outcomes. Further prospective randomized trials are required to evaluate the long-term effectiveness of this promising technique compared to other treatment modalities for achalasia. In this review we outline the technical aspects of POEM, summarize the available data on safety and outcomes, and suggest future directions for further advancement of this minimally invasive approach for the treatment of achalasia. 1. Introduction Achalasia is a motility disorder of the esophagus, characterized by aperistalsis of the esophageal body and incomplete relaxation of the lower esophageal sphincter (LES). In some cases, the underlying pathophysiology has been attributed to the selective loss of inhibitory ganglion cell function in the myenteric plexus [1]. Typical clinical symptoms include dysphagia for solids and liquids, food regurgitation, and retrosternal chest pain. The diagnosis of achalasia is based on clinical, endoscopic, and radiographic findings, with esophageal manometry considered the gold standard [2, 3]. Treatment of achalasia is currently aimed at decreasing the resting pressure in the LES to facilitate the passage of ingested food. Pharmacological therapy with agents that reduce LES pressure, such as nitrates and calcium antagonists, has yielded unsatisfactory results and has been associated with significant side effects [3]. Endoscopic delivery of botulinum toxin into the LES muscle decreases sphincter tone by inhibiting acetylcholine release from smooth muscle excitatory neurons. Unlike nitrates or calcium antagonists, botulinum toxin injection has been widely used because of its adequate immediate response (success rates of over 90%) and overall safety profile. However, long-term results have been disappointing, with only half of all patients benefiting for more than 1 year [4]. Thus, in clinical practice, this therapy is mainly confined to treating older patients or those with unacceptable surgical risks [4, 5]. Given the relatively low efficacy of pharmacological therapies to date, definitive
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