Traditional surgeries involve accessing body cavities, such as the abdomen and thorax, via incisions that divide skin and muscle. These operations result in postoperative pain and convalescence, and a risk of complications such as wound infection and hernia. The development of flexible endoscopy allowed diseases as varied as gastrointestinal bleeding and colon adenomas to be treated without incisions, but this technique is restricted by its endoluminal nature. A novel category of surgical endoscopic procedures has recently been developed that uses flexible endoscopic techniques to enter and access the submucosa of the gastrointestinal tract. Through this approach, the advantages of incisionless endoscopy can be applied to areas of the body that previously could only be reached with surgery. This Review introduces this new class of interventions by describing two examples of such submucosal surgeries for the treatment of benign gastrointestinal disease: per-oral endoscopic myotomy and per-oral pyloromyotomy. The approach to pre-procedure patient evaluation, operative technique, and the published outcomes are discussed, as well as potential future applications of similar techniques and procedures in this so-called third space.
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