Peroral endoscopic myotomy (POEM) opens the door of third-space endoscopy
29 October 2019 (online)
Over the last few years, some of the first movers in gastrointestinal endoscopy decided to stretch the limits of the gut lumen. The rapid development of minimally invasive procedures encouraged the concept of natural orifice transluminal endoscopic surgery (NOTES). In 2007, Sumiyama et al. reported, for the first time, access to the peritoneal cavity through the gastric lumen using the mucosal flap valve concept . This technique also enabled successful submucosal endoscopic myotomy to be carried out in living porcine experiments by Pasricha et al. .
These initial steps paved the way for the first NOTES procedure ever attempted on humans: peroral endoscopic myotomy (POEM). It was on 8 September 2008, in Japan, that Inoue et al. carried out the first POEM procedure; 2 years later, the first series of POEM procedures was reported in patients affected by achalasia (Fig. 1s, see online-only Supplementary material) . In fact, now it is routinely possible to reach the esophageal muscular layer by creating a submucosal tunnel. Proper creation of a submucosal cushion, mucosotomy, and dissection of the submucosal layer are paramount steps for navigating inside the third space. Once the tunnel is made, myotomy or other procedures can be carried out ([Fig. 1]).
From the beginning, POEM was clinically well accepted by both endoscopists and patients     . Large numbers of clinical series were reported worldwide with excellent results: a success rate higher than 85 %. Nowadays, depending on a patient’s anatomy or previous surgical scars, it is possible to choose different approaches, such as anterior (from 11 to 1 oʼclock), posterior (from 5 to 7 o’clock), lesser curve (2 o’clock), and lateral greater curve (8 o’clock)   . POEM has also shown excellent results in patients with a previous surgical myotomy, and patients who have had surgery for other reasons or pneumatic balloon dilation. Furthermore, this procedure is now applicable to patients with type I, II, and III achalasia (according to the Modified Chicago Classification), Jackhammer esophagus, and diffuse esophageal spasm where the length of myotomy is tailored depending on the characteristics of the disease. Moreover, efforts have been made to refine the POEM procedure to reduce post-POEM gastroesophageal reflux disease (GERD), for instance by selective myotomy and the preservation of sling fibers     .
To address this issue of post-POEM GERD, Inoue et al. recently reported POEM combined with fundoplication (POEM + F) (Fig. 2s). This is a pure NOTES procedure. The technique consists of a routine POEM procedure followed by entry into the peritoneal cavity and performance of fundoplication using a curved needle. The anterior wall of the fundus can be grasped and tied onto either the abdominal esophagus or the diaphragmatic crus in the submucosal tunnel. Pilot data were promising, but further evaluation needs to be done .
Even if POEM is still the most popular NOTES procedure, it was just the first of a long series of procedures that followed. Using the same initial steps as POEM, there are now many different procedures with multiple target therapies, such as tumor excision by peroral endoscopic tumor excision (POET) (Fig. 3s), which is also known as submucosal tunneling endoscopic dissection (STER)   ; gastric POEM (G-POEM) (Fig. 4s) for gastroparesis  ; lumen recanalization ; and treatment of esophageal diverticula . The applications are not confined to the upper gastrointestinal tract, as POEM has also been used in the lower gastrointestinal tract, for example for the treatment of Hirschsprung’s disease  or when performing rectal STER .
One of the other smart applications of third-space endoscopy is Zenker’s POEM (Z-POEM) or epiphrenic POEM (E-POEM). Zenker’s diverticulum is a prolapse of the mucosal and submucosal layer in Killian’s triangle. It was traditionally treated surgically, but some endoscopic approaches have been developed in the last few years. In this case, the application of third-space endoscopy requires the creation of two tunnels on both sides of the muscular septum. The creation of these tunnels permits the visualization of the septum, which thereby allows complete myotomy to be performed. As is well known, deeper myotomy is associated with lower recurrence of symptoms and higher clinical success rates, which is the reason why Z-POEM showed better results when compared with other endoscopic procedures. Moreover, the closure of the tunnels with endoclips seems to be correlated with a lower risk of post-procedural infections   .
In conclusion, NOTES procedures like third-space endoscopy remain the last frontier of interventional endoscopy. These innovative procedures must however go hand-in-hand with high levels of endoscopic skill and a deep knowledge of anatomy . Future efforts should now be focused on selecting the most appropriate indications and minimizing the risks.
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