Among high-volume centers, there are variations in the technique of POEM, including in the orientation (e.g., “anterior” vs “posterior”) and thickness of the myotomy (full-thickness vs circular-layer-only myotomy) (see Figs. 8.4 and 8.5), and devices used for dissection (see Fig. 8.7) and for tunnel closure (see Fig. 8.3) [1].

The orientation of POEM can vary depending on the practice of various centers but also depending on esophageal lesions such as diverticula or ulcerations, sigmoidization, or scarring from a prior myotomy that can force a certain orientation independent of the individual preference of the operator. In general a typical anterior myotomy is performed at 2 o’clock using the usual convention (the orientation that results in a myotomy that is centered along the clasp fibers at the lesser curvature of the EGJ and cardia) (see Fig. 8.1). A posterior myotomy is typically performed at 5–6 o’clock (just to the right of the spine) (see Fig. 8.2). A greater curvature myotomy at the 8 o’clock position has also been reported [5]. The anterior, or lesser curvature (LC), approach was initially adopted during the development of POEM as it reflects the surgical Heller myotomy approach, with access to the gastroesophageal junction from the ventral surface. The POEM procedure with this anterior, lesser curvature myotomy (at the 2 o’clock position) has shown excellent results [6–9]. However, excellent results have also been reported by centers that favor a posterior approach [10, 11]. It has been proposed that one of the benefits of the anterior approach is that the sling fibers, a natural reflux barrier supporting the angle of His, are not disrupted, thereby helping to minimize post-procedural gastroesophageal reflux disease (GERD) [5, 12]. However, data supporting the validity of this hypothesis are still lacking. Our group is currently near completion of enrollment of patients in a single-center randomized study comparing anterior and posterior orientation. Furthermore, we recently presented preliminary data from a comparison of anterior and posterior POEMs in our large single-operator series using data from a prospectively maintained database (Stavropoulos SN, et al. Gastrointestinal Endoscopy. 81(5):Supp AB 188–119). In this study we analyzed all POEMs performed at our center, 248 consecutive POEMs (120 anterior, 128 posterior), all successfully completed, with no aborted POEMs or surgical conversions, between 10/2009 and 10/2015. No learning curve bias expected as we performed a similar percentage of anterior POEMs in the first 3 years of our series (48/91, 53 %), as in the last 2 years (72/157 46 %). There were no differences in the Eckardt score, including failures (post-POEM Eckardt score >3, 5/110 A vs 4/117 P, NS), accidental mucosal injuries including nontransmural minor blanching (29 % vs 23 %), with prolonged stay of >5 days (one patient in each group). There was no difference in significant AEs, but it should be noted that there was paucity of such events in our series with no leaks, no tunnel bleeds, and no surgical/IR interventions. Posterior POEM was significantly faster overall (97 min A, 79 min P, P = 0.0007) including a faster closure (suturing 177, clips 71) (9.6 min A, 7.9 min P, P = 0.02). More patients had pain requiring narcotics in posterior POEM (17 % A vs 27 % P, P = 0.007). There was a trend for less acid exposure in anterior POEM: +BRAVO studies 21/58 (36 %) A vs 29/58 (50 %) P, P = 0.13, reflux esophagitis 22/57 (38 %) A vs 33/60 (55 %) P, P = 0.076. Based on these results, we calculated a sample size of 120 (including 20 % dropout) for an anterior vs posterior randomized trial to demonstrate that posterior POEM is faster. However, a larger number may be required to demonstrate a difference in incidence of reflux at 95 % confidence. We have currently enrolled 94 pts in this RCT. Therefore, high-quality data comparing these two approaches should be forthcoming in the near future.

Nevertheless, currently there is no consensus regarding the optimal orientation. The international POEM survey (IPOEMS) [13] revealed that as early as 2013, several pioneering centers performed myotomy in orientations other than the anterior 2 o’clock orientation (see Fig. 8.6). Notably the center with the highest POEM volume and fastest procedure times (Zhongshan Hospital, Shanghai) favored a posterior 5–6 o’clock orientation. The operators at this center favor the posterior approach due to their belief that performing the myotomy posteriorly is technically easier and thus potentially faster and safer. Our data presented above certainly support this contention. In the posterior approach, the muscle incision occurs directly along the long axis of the endoscope since the endoscope lies posteriorly in the esophagus due to gravity and has its therapeutic channel (from which the dissection knife exits) posteriorly (at the 7 o’clock position on the tip of the endoscope). By contrast during an anterior myotomy, the myotomy plane is located across from the endoscope, which, in the usual technique, causes the myotomy to proceed by hooking and cutting sequentially bundles of muscle fibers which results in slower completion of the myotomy [14]. Haruhiro Inoue, one of the operators who has strongly favored an anterior POEM orientation, has noted recently, anecdotally, that he believes that there may be a higher preponderance of large paraesophageal and paragastric vessels in the EGJ and cardia anteriorly, a concern that in at least certain situations may favor a posterior approach.

As noted above in patients with lesions such as large diverticula, these lesions force an orientation located away from the lesion. Similarly, in patients that have previously undergone failed myotomy laparoscopically or perorally, there may be significant scar tissue in the orientation of the prior myotomy making re-do myotomy via POEM more technically difficult. In these cases, a posterior orientation [15] or even a greater curvature (GC) orientation in the 8 o’clock position [5] provides a path that avoids the prior scar tissue. It has also been suggested that a GC orientation allows clear identification of the LES because of the angle of His which is located along the greater curve [5]. In 2015 Onimaru and colleagues reported their experience with 21 achalasia patients who underwent POEM with GC myotomy. They were successful in identifying the angle of His in all patients, and they achieved significant reductions in LES pressures and Eckardt scores after the procedure. They deemed GC POEM to be safe as no adverse events were observed. However, reflux esophagitis was documented in 52 %, with clinical GERD symptoms occurring in 9.5 %, in all of whom they were controlled with proton pump inhibitor (PPI) therapy [5]. It should be noted, however, that a GC myotomy is substantially more challenging than an anterior or posterior myotomy and is also potentially riskier in that it involves dissection of the esophagus in close proximity to the aorta. Therefore, this technique should be employed by expert POEM operators only when an anterior or posterior orientation is not possible due to lesions or scar tissue from prior manipulations.

Another modification in the technique of POEM is to perform a full-thickness myotomy rather than a myotomy limited to the circular muscle as advocated by Haruhiro Inoue (see Figs. 8.4 and 8.5). Preservation of the longitudinal muscle has been recommended to avoid entering the pleural space, but in practice, limiting the myotomy to the circular muscle is challenging, as the longitudinal muscle layer is often very thin and easily breached by air insufflation, mechanical trauma from the endoscope, or electrocautery damage [14]. Further, for long-term reduction in LES pressure, full-thickness myotomy, as is performed with a Heller myotomy, may be beneficial. In the largest series comparing the two techniques, Li et al. in 2013 reported their retrospective study with 103 patients undergoing full-thickness myotomy and 131 patients receiving circular myotomy. Full-thickness procedure times were faster, but short-term symptom relief and manometry outcomes were comparable between the two groups, and there was no difference in complication rates [10]. Similarly, Duan et al. reported faster procedure times, comparable treatment success rates, and no increase in adverse events with full-thickness myotomy [16].

The conventional technique of POEM uses standard injection needle for creation of the submucosal space and a cutting knife, such as the triangle-tip (TT) knife (Olympus Corp, Tokyo, Japan) (see Fig. 8.7a) for submucosal dissection and myotomy. The injection needle and knife are repeatedly exchanged through the working channel of the scope to allow for adequate submucosal cushioning and subsequent dissection [6]. Another technical modification that has been made to the original POEM procedure is the water-jet-assisted POEM, using a combined injection/cutting knife (HybridKnife (HK), ERBE, Tubingen, Germany) (see Fig. 8.7b). This device allows injection and dissection in a single instrument [17]. In their randomized controlled trial of 100 patients comparing POEM performed with the TT knife versus the HK, Zhou’s group reported that the hybrid knife produced significant decreases in POEM procedure time (22.9 vs 35.9 min (p < 0.0001) and fewer minor bleeding episodes, with no differences in complications of treatment success [17]. This improvement in procedure times was mostly attributed to less replacement of accessories. Even though our group has consistently used the hybrid knife to perform tunnel dissection and full-thickness myotomy for all but the first 18 cases of our series (currently numbering 290 POEMs), in our initial POEMs in 2009, when no specialized ESD knives were available in the USA, we employed a balloon inflation technique for submucosal tunnel creation. This technique was described in detail at our 2010 GIE case report with video demonstration of our first POEM (and also the first POEM to be performed anywhere outside of Japan) [18]. In brief, after initial submucosal saline injection and mucosal incision to allow entry into the submucosal space, we performed blunt insertion of a 5.5 cm long, 12 mm diameter dilation balloon (CRE wire-guided dilator; Boston Scientific, Marlborough, MA, USA) followed by dilation of the submucosa to 12 mm. The endoscope was then inserted to the distal terminus of the tunnel created by the dilation, and the process was repeated two or three additional times extending the tunnel to the gastric cardia. This technique results in rapid creation of the tunnel within 5–10 min (much faster than what can be achieved by the standard electrosurgical dissection using an ESD knife). However, this technique carries the risk of inadvertent insertion of the balloon through the mucosa or muscularis propria during the blunt insertion stage, which would result in perforation. Because of this risk, we rapidly transitioned to electrosurgical dissection after the first few POEMs. The technique however does carry promise as it results in rapid and relatively bloodless submucosal tunneling and could provide a superior alternative with properly designed balloons that lack the stiffness of CRE balloons and allow more precise and safe dissection through submucosal tissue and do so even in settings with significant submucosal fibrosis (e.g., POEM after extensive prior Botox injections). Christopher Gostout has been a stalwart advocate of this technique even for ESD [19]. Anecdotally the Oregon Clinic group has used this technique for the initial portion of the tunnel to facilitate endoscope insertion into the submucosal space, and some other groups reportedly use biliary balloons or even biopsy forceps (repeatedly inserting the forceps and opening its jaws) to create the submucosal tunnel without any electrosurgical energy, but peer-reviewed publications are lacking.

Closure of the submucosal flap is another area of modification from the original POEM procedure. Reliable closure of the mucosal site is critical in preventing leakage of esophageal contents into the peritoneal space. Most groups use hemostatic clips to approximate the edges of the tunnel entry site [6, 7, 20, 21]. Saxena et al. describe their experience using an over-the-scope clipping device (OTSC, Ovesco Endoscopy AG, Tubingen, Germany) in two patients. In both patients, initial attempt at closure using hemostatic clips was unsuccessful but OTSC closure was successful [22]. Swanstrom’s group at the Oregon Clinic reported a retrospective case-controlled study evaluating closure with hemostatic clips versus endoscopic suturing using the Apollo OverStitch device [23]. Of the 124 POEM cases assessed, endoscopic suturing was employed in 10 (8 %). Five cases were included in the study and were matched to five cases using conventional clip methods. No complications were noted in either group, and postoperative contrast esophagrams were negative in all patients. Closure time was shorter for the endoscopic clip group (16 +/− 12 min) as compared to the OverStitch device group (33 +/− 11 min), p = 0.044. The very long median closure time with endoscopic suturing is not explained and was the main reason for a cost advantage with endoscopic clips (the device costs were not too dissimilar with the OR time difference accounting for most of the cost difference according to the authors). The authors concluded that endoscopic suturing seems best suited for cases of difficult mucosotomy closure [23]. A larger, retrospective study by our group at Winthrop, to avoid learning curve bias from early cases, compared the most recent 25 consecutive closures of the mucosotomy with clips to the most recent 25 consecutive closures with OverStitch. There were no significant differences in closure time (8.8 min for endoclips and 10.1 min for OverStitch), cost ($916 versus $818), and hospital stay (1.9 days versus 1.7 days) [24].

In 2015 Liu reported on a new technique for accomplishing the POEM procedure that combines the steps of submucosal tunneling and myotomy. The procedure was performed in two patients, with an average procedure time of 24 min with less bleeding. The authors hypothesized based on these very preliminary findings that the simultaneous cutting of the submucosa and muscularis propria may result in a more efficient procedure [25].

The conventional POEM is performed in antegrade fashion: the submucosal tunnel is created several centimeters proximal to the GEJ and extended beyond the GEJ into the cardia. The subsequent myotomy is similarly initiated proximally and extended distally into the cardia. Ponsky and colleagues reported on their experience with “retrograde myotomy” in five patients, initiating the myotomy at the distal end of the submucosal tunnel, in the cardia, and proceeding in “retrograde” fashion to perform the myotomy across the GEJ extending it to approximately 3 cm distal to the mucosotomy forming the entry to the tunnel [26]. The authors felt that this approach resulted in an easier, faster procedure. We have occasionally utilized this technique in patients with extremely tight LES in whom the sphincter could “shut the endoscope out of the cardia” during proximal to distal myotomy, requiring forceful forward pressure which may not be as effective in the presence of a partially completed proximal myotomy that may allow “buckling” of the endoscope into the mediastinum. We do not recommend this “retrograde” myotomy technique for routine use due to its increased risk as the knife is cutting away from the esophageal lumen (toward the mediastinum/peritoneum) and there is limited visualization of the tissue to be cut since the leading edge of the incision is hidden by the muscle tissue yet to be cut.

One of the key issues in the POEM procedure is ensuring that the submucosal tunnel has been extended 2–3 cm beyond the GEJ into the cardia to ensure complete ablation of the LES high-pressure zone. A variety of indicators that suggest that the GEJ or cardia has been reached include:

A transillumination auxiliary technique, initially described by Baldaque-Silva and colleagues, allows confirmation that the tunnel was extended into the cardia by inserting transnasally an ultrathin endoscope, in parallel with the orally inserted gastroscope used to perform the POEM procedure. The ultrathin scope is advanced to the level of the stomach and placed in the retroflexed position with visualization of the cardia, while the gastroscope is kept within the tunnel with its tip at the tunnel terminus. The light intensity of the thin endoscope is diminished, and the light from the gastroscope within the submucosal tunnel is identified, thereby confirming its position in the cardia [27]. Inoue’s group compared this technique to conventional identification of the cardia by the indicators listed above in a prospective randomized controlled trial with 100 consecutive achalasia patients undergoing POEM. POEM was completed with high rates of technical and clinical success in both groups, with low adverse events, but the double-scope transillumination group had myotomy extension in 34 % of cases, which led to an increase in the length of the cardiomyotomy from 2.6 to 3.2 cm (p = 0.01) [28]. Despite the extension of the myotomy in a third of the patients in the transillumination group (suggesting that the final length of the cardiomyotomy of the control group may have not been of adequate length in a third of patients), there were no differences in clinical success rates, and no differences in post-procedure GERD, thus raising doubts about the clinical significance of these findings. Some drawbacks of this technique are that it may require two operators, is cumbersome, requiring a second endoscopy tower and endoscope, and adds significant time to the procedure (17 min in this study). However, this technique may be beneficial for difficult cases such as those on patients with sigmoid end-stage achalasia or for operators early on the POEM learning curve.

Another technique for reliably identifying an adequate myotomy extension into the cardia involves the use of fluoroscopy. Kumbhari reported using either a hemoclip attached to the GEJ or the fluoroscopically guided placement of a 19-gauge needle on the skin at the level of the GEJ to help accurately assess the length of the myotomy in 24 consecutive patients undergoing the POEM procedure. Based on the fluoroscopic information, the submucosal tunnel was extended in 21 % of patients, with minor increases in procedure time (4 min for the hemoclip group and 2 min for the 19-gauge needle group) [29]. Others have used fluoroscopy for reorienting the submucosal tunnel in a downward direction, particularly in cases of sigmoid achalasia esophagus [30]. It should be noted, however, that these techniques require performing POEMs in a fluoroscopy room tying up this room for at least 2 h. Given the small benefit of this technique, which would be expected to be even smaller after the early portion of the POEM learning curve, it is unclear whether this would represent appropriate resource utilization in busy endoscopy suites with one or two fluoroscopy rooms.

Real-time measurement of the GEJ distensibility with a balloon-based imaging probe that uses impedance planimetry has been used intraprocedurally to assess the adequacy of the myotomy [31]. The device EndoFLIP (Crospon Ltd, Galway, Ireland) provides measurements that include cross-sectional area (CSA), minimal diameter, compliance, and distensibility indices. The device had previously been used to assess the GEJ pre-procedurally and on follow-up evaluation 3 months after the POEM [32]. Rieder used the EndoFLIP device on four patients undergoing POEM and compared values to healthy volunteers. Pre- and post-myotomy data were obtained. In the group undergoing POEM, pre-procedure diameter, CSA, and distensibility were lower than in healthy volunteers. These parameters improved significantly during the intraprocedural (immediate post-myotomy) assessment, becoming more like those of the healthy volunteers [31]. The device was used intraprocedurally during POEM and laparoscopic Heller procedures demonstrating similar improvements in GEJ distensibility intraoperatively [33]. Unlike other objective measurements of the adequacy of the myotomy, the EndoFLIP device has the ability to give a real-time assessment of the myotomy, potentially allowing for optimization of the myotomy at the time of the POEM. Recently, EndoFLIP was used to assess the degree that each of the POEM stages (submucosal tunnel dissection, esophageal body myotomy, short cardiomyotomy, long cardiomyotomy) contributed to improved GEJ physiology [34]. Interestingly, this study found that submucosal tunnel dissection prior to any myotomy resulted in a marked improvement in EGJ physiology. Myotomy extension across the LES to 2 cm distal to the EGJ onto the gastric wall resulted in normalization of EGJ distensibility, whereas subsequent extension and additional centimeter to 3 cm distal to the EGJ did not increase compliance further. These data suggest no further improvement in GEJ; patency would be expected from extending the myotomy more than 2 cm into the cardia [34]. The same group has examined the use of proprietary software to analyze real-time pre-POEM EndoFLIP data to obtain insights in achalasia pathophysiology. They found that esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography, and they speculated that the presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course [35].

The POEM procedure has been successfully expanded to non-achalasia motility disorders of the esophagus, namely, spastic disorders such as diffuse esophageal spasm (DES), nutcracker esophagus, and jackhammer esophagus [36–38]. In these disorders, the length of the myotomy is substantially longer, up to 20 cm or so, owing to the pathophysiology of these motility disorders which involves spasticity or hypercontractility of as much as 2/3 s of the esophagus. Sharata and colleagues reported on 25 non-achalasia patients within a larger cohort of 100 patients undergoing POEM [39]. Twelve had nutcracker esophagus, five had DES, and there were eight cases of hypertensive non-relaxing LES. When compared to their counterparts with achalasia, this non-achalasia group had somewhat less dysphagia relief (70 % versus 97 % in the achalasia group), less chest pain relief (75 % versus 100 %), and higher rates of heartburn and regurgitation [39]. A multicenter retrospective analysis of outcomes in 73 patients with DES, Jackhammer, and type 3 achalasia that had POEM at 12 different centers revealed mildly lower efficacy in pain relief than dysphagia relief (not statistically significant however) and significantly lower efficacy in Jackhammer compared to DES and spastic achalasia [40].