Per-Oral Endoscopic Myotomy

Alireza Sedarat, MD and Mouen Khashab, MD

Introduction

Per-Oral endoscopic myotomy (POEM) is a minimally invasive endoscopic means of performing esophagogastric myotomy to palliate symptoms of achalasia and other spastic motility disorders. It is the first widely adopted Natural Orifice Transluminal Endoscopic Surgery (NOTES) procedure. A direct means of endoscopic myotomy was described in 1980¹ wherein the mucosa of the high-pressure zone was directly incised with an electrosurgical knife to access and cut the deeper muscle fibers. Though the outcomes were remarkably favorable, the method was not adopted. In contrast, POEM in its modern form is the prototypic submucosal endoscopic procedure and seeks to preserve the mucosal flap over the divided esophageal and cardia muscle. Its hallmark is harnessing the submucosa as a working space to safely exit the esophageal lumen and access the muscle layer. The method was built on the early experimental work during the development of NOTES² techniques for safe lumen exit and secure closure.³ The readily accessible muscle layer during these experimental submucosal endoscopy procedures led to the concept of harnessing the technique to emulate a Heller myotomy and was successfully performed in a porcine series.⁴ Subsequently, the method was applied to the first human series in 2010.⁵ Since its introduction into clinical practice, POEM has been performed worldwide by gastroenterologists and surgeons in thousands of patients with remarkable efficacy and safety. The procedure builds on principles of endoscopic submucosal dissection (ESD) and serves as a conceptual bridge between mucosal resection procedures, submucosal endoscopy, and full-thickness resection. The technique has allowed for expanded knowledge and experience with principles of tissue planes, hemostasis, and management of capnoperitoneum. This chapter will describe patient selection, perioperative management, and operative technique of POEM in context of the application to submucosal endoscopy and full-thickness resection techniques.

Patient Selection and Preoperative Management

As in any therapeutic procedure, accurate diagnosis, appropriate preprocedure evaluation, and patient selection are paramount to success.

Indications and Contraindications

POEM is primarily considered in patients with confirmed symptomatic primary idiopathic achalasia. All subtypes of achalasia can be considered for POEM, and there is evidence and growing experience that POEM is more effective for type III achalasia owing to the ability to begin the myotomy more proximally than can be readily achieved with laparoscopic methods. This advantage has also allowed the procedure to be increasingly applied to nonachalasia motility disorders such as jackhammer esophagus or diffuse esophageal spasm.

The procedure can be safely and effectively applied to patients with prior endoscopic treatment for achalasia including pneumatic dilation or botulinum toxin injection. These procedures, however, particularly repeated applications, may result in significant submucosal fibrosis that can make tunnel dissection challenging.

There are now multiple series reporting the technical success, efficacy, and safety of POEM in patients who have undergone a prior Heller myotomy.6 Successful POEM in the setting of a Roux-en-Y gastric bypass has also been reported,⁷ in which the extensive adhesions and altered anatomy could have proven challenging for the laparoscopic approach. POEM has also been studied in patients with sigmoid-type achalasia with similar outcomes as those with a nonsigmoidtype esophagus.⁸ Age is not a contraindication to POEM, and successful procedures have been performed in those at the extremes of age. In particular, several series have reported its successful use in the pediatric population.^9,10

Absolute contraindications to POEM include scenarios that would result in significant fibrosis or obliteration of the submucosal layer, including severe erosive esophagitis, radiation to the mediastinum or upper abdomen, prior endoscopic resection of the esophagus, or mucosal ablation (such as radiofrequency ablation or photodynamic therapy). Conditions that would result in uncontrollable bleeding such as severe uncorrectable coagulopathy, portal hypertension (especially with esophageal varices), or inability to safely withhold anticoagulation or antiplatelet therapy are also considered absolute contraindications. Owing to the potential risks of general anesthesia and possible scenario of tension capnoperitoneum or capnothorax (see later in this chapter), the presence of severe pulmonary disease or pulmonary hypertension has been considered a contraindication as well.

Preoperative Evaluation

Achalasia (or other spastic disorder) is suspected based on history, endoscopy, and esophagram and confirmed and subtyped with high-resolution manometry. In patients at risk for neoplasia (older age, smoking history, family history of malignancy, marked weight loss, short duration of severe symptoms), pseudoachalasia should be excluded with cross-sectional imaging and/or endoscopic ultrasound.

Though the procedure is minimally invasive and often entertained in patients subjectively or objectively considered unfit for traditional surgery, there are important caveats to this approach that must be considered. General anesthesia with endotracheal intubation and paralysis is the norm and thus patients must be fit to tolerate this. As such, preoperative cardiopulmonary risk assessment and optimization is necessary prior to proceeding. Although not formally studied or compared, the cardiopulmonary risk may be similar to laparoscopy and the patient should be expected to tolerate 1 to 2 hours of general anesthesia with possible fluctuation of blood pressure or ventilation parameters that will require active management by the anesthesiologist. In particular, the potential development of capnoperitoneum must be anticipated and managed effectively with needle decompression if needed; consequences of tension capnoperitoneum or capnothorax can be significant and result in hemodynamic compromise; the consequences of these derangements are likely to be exaggerated in patients with baseline inadequate cardiopulmonary function.

Operative Management

Preoperative Preparation and Equipment

Patients are asked to maintain a liquid diet for 48 hours prior to POEM to minimize risk of aspiration of retained esophageal contents during induction of anesthesia. Some practitioners routinely provide prophylaxis against esophageal candidiasis with topical nystatin, though this has not been formally evaluated. The procedure can be safely performed both in the operating room and in an appropriately equipped endoscopy suite.

General anesthesia is induced and paralysis is maintained so that all ventilation is positive pressure. When the esophageal wall is compromised, negative intrathoracic pressure (as during inspiration) may augment gas escape into the mediastinum and thorax and increase risk of significant gas-related adverse events. Though aspiration is minimized with standard endotracheal intubation, it is not eliminated. Thus, a specialized endotracheal tube with an additional subglottic suction port can be employed to further minimize this risk. Sequential compression devices are employed for deep venous thrombosis prophylaxis. Urinary catheter and arterial line placement can be considered for urine output monitoring and management of intraprocedural hemodynamic changes if desired in high-risk cases and in expected long procedures. The abdomen is left exposed for periodic examination to detect capnoperitoneum.

The procedure is generally performed in the supine position using a high-definition, standardcaliber gastroscope with a clear cap distal attachment. An endoscope with jet irrigation is highly desirable (if not mandatory). The esophageal lumen is thoroughly cleansed and lavaged. An antibiotic solution is commonly employed to cleanse the esophageal and proximal gastric surface, though this has not been well studied. Generally, a single dose of preprocedure antibiotics are given, though this also has not been standardized or well studied.

Carbon dioxide insufflation is mandatory and early series have reported increased gas-related complications when air insufflation was used.11 An electrosurgical knife is the main accessory, and different operators have different preferences for their practice. Availability of a coagulation forceps is beneficial for precise hemostasis.

Operative Technique

The procedure is divided into 4 sequential steps: mucosotomy and tunnel entry, creation of submucosal tunnel, myotomy, and mucosotomy closure.

Mucosotomy

After measurement of landmarks and confirmation of the relevant anatomy (such as position of esophagogastric junction/squamous columnar junction, presence of hiatal hernia, impression of the spine, etc) a site is chosen in the esophagus for mucosal entry. Usually either an anterolateral (2 o’clock) or posterolateral (5 o’clock) position is chosen so the cardia is approached toward the lesser curvature side and the dissection of the angle of His can be avoided (though there are case reports of this being performed successfully).12 Generally, a location 10 to 12 cm above the high-pressure zone of the lower esophageal sphincter (LES) is selected and a submucosal bleb is created with injection of normal saline tinted with either methylene blue or indigo carmine. A small amount of dilute epinephrine can be added (1:100,000 dilution) to minimize initial oozing related to mucosotomy. Usually approximately 10 cc is injected; an adequate lift is crucial to avoiding full-thickness esophagotomy. A 1 to 2 cm incision is made using the electrosurgical knife using a blended cutting current (such as DRY CUT or ENDO CUT [Erbe]). Usually a longitudinal incision is made to facilitate closure, though some operators employ variations including a transverse incision.

Submucosal Tunnel

Immediately after the mucosotomy is performed, the submucosal fibers must be carefully trimmed toward the muscle layer so the endoscope has a “space” into which it can be insinuated vertically to enter the submucosa. During the early part of the learning curve, operators often find efficient entry into the submucosal space to be challenging, especially in the posterior approach. Patience, adequate submucosal injection, efficient movements, and careful and adequate trimming of submucosal fibers deep to the mucosotomy will allow for successful entry. The distal attachment is crucial in allowing the tip of the endoscope to maneuver into the submucosal space and maintain visualization. Once the submucosal space is entered, stepwise dissection is performed distally with the plane of dissection just above the circular muscle layer. Unlike in mucosal resection procedures, the therapeutic intent of POEM is to divide the muscle layer and preservation of the mucosal layer is paramount to preserving the integrity of the esophageal wall. As such, the dissection is directed as close to the muscle layer as possible. Submucosal expansion is created to allow for a safe dissection plane with additional injection of normal saline solution (tinted as desired with blue dye). In contrast to the initial submucosal bleb, epinephrine should be avoided during submucosal tunnel dissection. The dissection is generally one-third the circumference of the wall of the esophagus and is directed perpendicularly to the circular muscle fibers to avoid “tunnel wander.” Dissection in a tortuous or sigmoid esophagus can be challenging. Dissection is continued until an adequate distance is achieved distally—usually 2 to 3 cm into the cardia. Whereas the dissection of the esophageal body is usually relatively rhythmic and straightforward, dissection at the level of the high-pressure zone becomes tedious and slow. The spasm of the LES narrows the tunnel and the risk of inadvertent mucosotomy is higher. Vascularity also tends to increase at the esophagogastric junction and further complicates safe dissection.

Myotomy

Once the submucosal tunnel is completed, the division of the muscle layer is performed starting proximally and extending distally. The myotomy can be initiated 1 to 2 cm distal to the end of the mucosotomy to allow a margin of safety from the mucosal flap. If necessary, the myotomy and mucosotomy may overlap if subsequent closure of the mucosotomy is robust. During the initial muscle division, dissection is performed slowly to define the thickness of the muscle and access the intermuscular plane. The myotomy is then extended caudally until completed.

Closure

After the myotomy is completed into the cardia, appropriate relaxation of the LES is confirmed endoscopically. The submucosal tunnel is irrigated and closely inspected for undivided muscle fibers, persistent bleeding, or inadvertent mucosotomy. The lumen side is also closely inspected for mucosal injury, which should be repaired as soon as recognized. Mucosal closure is then performed with either clips or endoscopic suturing.

Variations in Operative Technique

The upper limit of the final length of the myotomy depends on the length of the submucosal tunnel and thus the chosen location of mucosal entry is important. This is primarily of concern in cases with spasm of the esophageal body (type III achalasia or jackhammer esophagus, for example), where the therapeutic success (and indeed the strength of POEM) lies in the ability to adequately extend the proximal extent of the esophageal myotomy. Careful review of prior high-resolution manometry and esophagram, and observation of endoscopic areas of spasm can guide the endoscopist regarding appropriate mucosal entry position. In addition, it is important to recognize individual variations (such as prominent submucosal veins, impingement from the spine, lumen shape) that may make either submucosal entry or subsequent mucosotomy closure more difficult. It is often advisable to anticipate these difficulties and adjust the location of the mucosal entry if needed; it is preferable to dissect a slightly longer tunnel than to create a mucosotomy in a location that is untenable for closure.

An anterior vs posterior approach is usually selected based on operator experience/preference or presence of prior intervention (typically an anterior Heller myotomy would necessitate a posteriorly performed POEM). Based on prior surveys, most POEM operators seem to prefer an anterior approach,13 although some large-volume, well-known centers prefer the posterior approach. Relative strengths and weaknesses of either approach have not been definitively determined, though there are ongoing studies seeking to answer this question.

The initial description of endoscopic tunneling in the animal model used blunt dissection of the submucosal fibers using endoscopic balloons. The original human description and most current POEM operators seem to opt for electrosurgical dissection. The advantage of blunt dissection is primarily possible reduced procedure time and possibly a reduced risk of cautery-related mucosotomy. Unlike the porcine model, there is increased vascularity in the human esophagus and blunt dissection is not routinely recommended given the risk of bleeding. The advantage of cautery knife dissection is the hemostasis it provides during dissection. Variations of dissection method also include use of different current modes of the electrosurgical generator.

Adequate extension of the submucosal tunnel into the cardia is necessary for an adequate cardiomyotomy to be performed. As in the Heller myotomy experience, an inadequate cardiomyotomy may lead to persistent symptoms of dysphagia. Thus, a reliable estimation of adequate extension of the submucosal tunnel is crucial for procedure success. A variety of methods to achieve this have been described, including insertion tube measurement, anatomic changes of the tunnel, fluoroscopy, double-scope transillumination, and impedance planimetry measurement.^14,15

Fibrosis due to prior intervention can make submucosal dissection difficult and risky because of the close proximity of the mucosa to the cutting plane. Areas of spasm (such as the high-pressure zone of the LES or spastic segments of a jackhammer esophagus) can similarly make dissection difficult. Generally in these locations, the dissection proceeds very slowly and deliberately. Alternately, a method of combined submucosa and muscle layer division has been described wherein the myotomy is performed without a submucosal tunnel.

Although the relative merits of full-thickness myotomy vs selective circular myotomy of the LES and cardia can be debated,¹⁶ in the esophageal body most practitioners preserve the longitudinal muscle layer and selectively dissect and divide the circular muscle layer. The longitudinal muscle layer thereby serves as a “safety” layer so that the procedure is performed intramurally. This principle is also important in full-thickness resection procedures and resection of muscle-layer subepithelial tumors. Selective dissection achieves 2 major goals. First, the risk of injury to vital extramural structures is virtually eliminated; in fact, injury to even small extramural blood vessels could be problematic or impossible to manage endoscopically. Second, this principle maximizes the chance of preservation of the adventitia and thus minimizes issues of extraluminal gas escape.

Postoperative Care

After completion of the procedure, the patient is admitted for overnight observation and kept “nothing by mouth” overnight. Intravenous antibiotics can be continued prophylactically at the operator’s discretion. Some centers give no antibiotics after the initial preoperative dose. Most centers perform an esophagram on postoperative day 1 to exclude a leak, although the utility of this practice in the absence of worrisome clinical signs has been questioned. The patient is then discharged on a limited diet (liquid or soft) for 2 weeks with instructions to slowly advance to regular food as tolerated. Although not standardized, our center discharges patients with proton pump inhibitor therapy until follow-up endoscopy and pH studies have excluded postmyotomy reflux.

Outcomes

Efficacy for Achalasia Patients

Since its introduction into clinical practice, there have been multiple studies demonstrating the efficacy of POEM for palliation of symptoms associated with achalasia. It should be noted that the definition and measurement of efficacy is variable (clinical dysphagia scores, timed barium esophagram, LES pressure reduction, quality of life, etc) among studies and most are retrospective and uncontrolled. The initial white paper 17 summarized the available short-term data from 14 studies with 804 patients showing a clinical success of 82% to 100%. A multicenter European trial of 80 patients with a minimum 2-year follow-up confirmed an initial high (96.3%) response rate, but clinical recurrence in 14 cases that initially responded (midterm recurrence rate 17.7%).¹⁸ In a large retrospective Japanese study¹⁹ of 500 patients in which 61% had 3 or more years of follow-up, clinical success was 91% at 2 years and 88% at 3 years. A single-center American study²⁰ of 29 patients with a median follow-up of 65 months showed sustained improvement in 19/23 (83%) patients with achalasia. In summary, the existing and emerging literature suggest an impressively high short-term response rate with sustainability in the majority of patients in the medium term. An important minority may have recurrent symptoms, emphasizing the need for long-term follow-up post-POEM. Long-term efficacy (> 5 to 10 years) is not yet known. These initial results and some comparative data suggest outcomes are favorable compared to Heller myotomy.²¹

Efficacy for Nonachalasia Patients

Emerging data specific to nonachalasia spastic disorders of the esophagus (such as jackhammer esophagus or diffuse esophageal spasm) suggest that a long myotomy (often tailored to the manometric findings) with POEM is feasible and effective. Perhaps not surprisingly, there appears to be superior response to dysphagia symptoms vs chest pain symptoms. One meta-analysis was performed in an attempt to pool the available data for efficacy and safety of POEM in spastic disorders of the esophagus. The efficacy for type III achalasia, diffuse esophageal spasm, and jackhammer esophagus was 92%, 88%, and 72%, respectively, with pooled adverse events of 14% (3% mucosotomy requiring clip closure). This study and others suggest that POEM is efficacious for spastic esophageal disorders when compared to medical therapy with acceptable safety.^22,23

Per-Oral Endoscopic Myotomy for Patients With Previous Heller Myotomy

Studies have shown that up to 10% to 15% of patients with achalasia will not respond to Heller myotomy. These patients warrant special attention as they represent a special challenge, and the causes for unsuccessful Heller myotomy may vary. It is important to reevaluate the esophageal physiology completely with multimodal testing to determine the likely pathophysiology of symptoms and recommend appropriate therapy. This evaluation usually includes endoscopy, esophagram, high-resolution manometry, and selected use of pH testing. The goal of this testing is to identify patients with nonrelaxing LES or incompletely treated esophageal body spasm that will likely benefit from POEM.

It is first important to distinguish a patient who has recurrence from one who had an initial inadequate response. Patients with recurrence can be defined as those who had an initial resolution or near resolution of dysphagia symptoms but recurrence of symptoms after some period of time (usually > 1 year). This delayed recurrence is thought to be due to fibrosis of the myotomy site resulting in functional restoration of the nonrelaxing LES and associated typical symptoms: manometry, esophagram, and endoscopy similar or identical to patients with de novo achalasia. The main goal of endoscopy (± pH studies) is to exclude reflux, peptic stricture, or neoplasia as a cause for the recurrent symptoms. Patients with early recurrence (especially less than a few months) may have less robust fibrosis of the myotomy site or fundoplication and may respond to through-the-scope dilation up to 18 to 20 mm. Patients with documented recurrent achalasia may be treated with pneumatic dilation (30 to 40 mm), surgical revision, or POEM. Surgical revision is feasible but generally more technically difficult and associated with higher operative complications.

In contrast, patients who have had a Heller myotomy but have failed to improve within 1 to 2 months postsurgery may have an inadequate cardiomyotomy, unrecognized esophageal body spasm (ie, incompletely treated type III achalasia), or a fundoplication that is too tight. The latter scenario is difficult to differentiate with certainty from inadequate cardiomyotomy (they can be manometrically identical), but patients with type I achalasia or sigmoid achalasia are more likely to have persistent symptoms caused by a tight wrap. Discussion with the surgeon or review of the operative report may provide clues to the presence of a tight wrap. If a tight wrap is suspected, pneumatic dilation or POEM can be offered, but surgical revision and wrap takedown may be necessary.

Cases of inadequate cardiomyotomy can be suspected on the basis of higher than expected resting and residual LES pressures on high-resolution manometry. These patients can be effectively treated with a POEM directed at the opposite wall of the esophagus with attention focused on extending the myotomy well into the cardia. On the other hand, when high-resolution manometry reveals residual esophageal body spasm (as in incompletely treated type III achalasia), the POEM is focused on providing an adequate length of myotomy of the esophageal body (usually as directed by distances above the LES or diaphragm measured by manometry). In general, the myotomy is extended through the LES and cardia (as in standard POEM) with an adequate cardiomyotomy performed opposite the initial surgery to minimize the risk of delayed recurrence of symptoms.

The operative approach for POEM in a post-Heller patient is nearly identical to those who have not had surgery except that the tunnel is by necessity directed to the opposite wall of the esophagus as the prior surgery to avoid fibrosis. There are a few caveats. First, it is crucial to review the operative report of the initial surgery when available to confirm the location and length of myotomy, type of fundoplication (if any), and operative details such as inadvertent mucosotomy that required repair. In general, a laparoscopic Heller myotomy will result in an anterior full-thickness myotomy of 6 to 10 cm including ~2 to 3 cm of the cardia. This will generally mean that the POEM will be of the posterior wall. However, variations of technique exist and review of the operative report may identify exceptions or variations. Furthermore, although an anterior myotomy is performed anatomically, the dissection of the hiatus, mobilization of the esophagogastric junction, reduction of a hiatal hernia, and/or performance of the fundoplication may result in a “twist” of the distal esophagus so the anterior-posterior orientation is distorted. This may be difficult or impossible to determine pre-POEM, but selective use of endoscopic ultrasound or optical coherence tomography may help to identify the location of the muscle defect and guide selection of the POEM tunnel.

Based on available series with short- and medium-term follow-up, it appears that efficacy of POEM in post-Heller patients is comparable or slightly lower compared with patients who undergo POEM without prior surgery with similarly low adverse events.24,25 It should be noted that 5% to 10% of achalasia patients may have progressive dysphagia and weight loss despite adequate myotomy. In these patients, the esophagus is general dilated and very tortuous (also known as sigmoid) and there is retained food or contrast despite a patulous esophagogastric junction. These patients are characterized as “end-stage” and may ultimately require esophagectomy to restore alimentation.

Postmyotomy Acid Reflux Disease

Possibly the greatest area of controversy in the expanding field of POEM remains the risk of gastroesophageal reflux disease (GERD) after POEM and how this compares to the risk after Heller myotomy. During most laparoscopic Heller myotomy procedures, the normal attachments of the esophagogastric junction (such as phrenoesophageal ligament, angle of His, and hiatal fat pad) are dissected to expose the distal esophagus and cardia to allow for a safe and effective myotomy. These structures are important in the natural antireflux mechanism and their disruption may account for some of the GERD seen after laparoscopic myotomy. Performance of a partial fundoplication seems to compensate for this disruption and appears to decrease the risk of GERD (at least in the short to medium term). In POEM, a fundoplication is not performed. Despite this, a significantly higher risk for post-POEM GERD has not been observed; possibly this can be attributed to the preservation of the angle of His and phrenoesophageal ligament. This theory is supported by a small series in which postmyotomy GERD was reduced in patients who underwent laparoscopic myotomy with minimal dissection of the esophagogastric junction and without a fundoplication.²⁶ In available comparative series the risk of postmyotomy GERD appears comparable for POEM vs Heller myotomy. The risk of reflux post-POEM appears to be variable depending on how GERD is defined; one multicenter study²⁷ found rates GERD to be 57%. It should be noted that about half of achalasia patients with positive pH studies postmyotomy might not have symptoms of reflux. The ideal management of patients with positive pH studies and minimal or no symptoms and/or minimal or no reflux esophagitis is not clearly established. Results of ongoing prospective randomized trials are awaited to more definitively compare the risk of postmyotomy reflux in endoscopic vs laparoscopic myotomy.

Adverse Events

The overall rate of serious adverse events appears to be less than 1% to 2%. The most feared complication is inadvertent mucosotomy. Since the submucosa and muscle layers are dissected, even a small mucosal defect can result in a clinically significant perforation and morbidity. As such, mucosotomies should be identified and repaired effectively. Minor bleeding may be common and easily managed with the dissection knife. Careful dissection and meticulous hemostasis is paramount, but cautery injury from aggressive hemostasis may result in mucosal compromise. This can be minimized by careful identification of bleeding points (often under water immersion) and judicious use of coagulation forceps. If the bleeding source appears to originate from the underside of the mucosa, often mechanical tamponade with the scope tip or forceps (without coagulation) is sufficient. Delayed bleeding has been described in < 1% of patients and presents with chest pain, dysphagia, hematemesis, and anemia. There have been a few descriptions of management of delayed bleeding including conservative management, emergency endoscopy with tunnel reentry and hemostasis, and use of mechanical means of tamponade (such as a Blakemore tube).28

Summary

POEM is a recently described, minimally invasive, effective, and safe way of achieving esophagogastric myotomy to palliate the symptoms of achalasia and other spastic disorders of the esophagus. In the short time since its introduction into clinical practice, it has been widely adopted with a remarkable safety and efficacy record. It is the prototypical submucosal endoscopy and NOTES procedure and has set the stage to expand the role of interventional endoscopy. Lessons learned from the POEM experience—submucosal dissection, recognition of tissue planes, hemostasis, management of capnoperitoneum, mucosotomy closure—have been crucial in allowing the interventional endoscopist to push the boundaries of therapeutics beyond the lumen to safely perform advanced resection procedures such as submucosal tunneled resection and full-thickness resection.

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