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Peroral Endoscopic Myotomy for Achalasia in a Thoracic Surgical Practice
Peroral Endoscopic Myotomy for Achalasia in a Thoracic Surgical Practice Stephanie G. Worrell, MD, Evan T. Alicuben, MD, Joshua Boys, MD, and Steven R. DeMeester, MD Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California
Background. Peroral endoscopic myotomy (POEM) is a new option in the treatment of achalasia. It has typically been performed by general surgeons and gastroenterologists familiar with advanced endoscopic procedures. Our objective was to assess the initial experience and outcomes with POEM by a thoracic surgeon. Methods. A retrospective chart review was performed of all patients who underwent POEM from October 2012 until December 2014. Pre- and post-POEM evaluation included upper endoscopy, high-resolution manometry, and a timed barium swallow. Results. There were 35 patients (18 men and 17 women), with a median age of 53 years. Based on highresolution manometry, there were 8 patients (23%) with type I, 21 (60%) with type II, and 5 (14%) with type III achalasia, and 1 patient had hypertensive lower esophageal sphincter. Prior therapy had been performed in 18 patients (51%). The POEM procedure was completed in all but 1 patient. On follow-up, dysphagia was improved in all patients. The Eckardt score was significantly reduced
from 7 before POEM to 0 after POEM (p < 0.0001), and improved similarly for all manometric types of achalasia. Post-POEM upper endoscopy showed esophagitis in 55% of patients, but this condition resolved in all with acid suppression. Timed barium swallow showed a reduction of esophageal retention at 5 minutes from 63% before POEM to 5% after POEM. Ten patients had follow-up at 12 months or greater after POEM and the improvements persisted. Conclusions. Peroral endoscopic myotomy is a safe and effective therapy for achalasia. It provides reliable and persistent palliation of dysphagia and objective improvement in esophageal emptying. Esophagitis is common but resolves with acid suppression therapy. Thoracic surgeons with an interest in esophageal diseases and experience with endoscopy are encouraged to adopt the procedure.
A
relaxation pressure (IRP) but differ based on the presence of esophageal pressurization or spasm in the esophageal body. Type I is classic achalasia, type II has panesophageal pressurization, and type III has evidence of distal esophageal spasm [2]. Achalasia is not curable, but treatment can provide effective palliation of the dysphagia and regurgitation symptoms. All treatments focus on improving the outflow resistance caused by the poorly relaxing LES. The two primary therapies have been pneumatic balloon dilatation (PBD) and laparoscopic Heller myotomy with partial fundoplication. Each approach has advantages and disadvantages, but the reliable and reproducible results with laparoscopic myotomy have made it the gold-standard therapy worldwide. In 2009 Inoue and colleagues [3] first reported an endoscopic myotomy for a patient with achalasia based on an animal study by Pasricha and associates [4]. They termed the procedure peroral endoscopic myotomy (POEM). Subsequently, POEM programs have been initiated by general surgeons and some gastroenterologists in Asia, Europe, and the United States. The aim of this study was to review the initial experience of a thoracic surgeon with the POEM procedure.
chalasia is an esophageal motility disorder that affects approximately 1 per 100,000 people. Interestingly, the prevalence of this disorder has increased more than fourfold during the past two decades [1]. The cause remains uncertain, but patients typically present with progressive dysphagia for both solids and liquids related to destruction of the Auerbach’s plexus. The diagnosis is confirmed by esophageal manometry showing failure of the lower esophageal sphincter (LES) to relax and loss of esophageal body peristalsis. Some patients also have a hypertensive LES resting pressure or evidence of esophageal body pressurization. With the introduction of high-resolution manometry (HRM), achalasia has been divided into three types. Under the Chicago classification system, all types of achalasia have an elevated integrated
Accepted for publication June 8, 2015. Presented at the Fifty-first Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 24–28, 2015. Address correspondence to Dr DeMeester, Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of the University of Southern California, 1510 San Pablo St, Ste 514, Los Angeles, CA 90033; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.06.036
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Abbreviations and Acronyms GEJ HRM IRP LES PBD POEM PPI TBS
= = = = = = = =
gastroesophageal junction high-resolution manometry integrated relaxation pressure lower esophageal sphincter pneumatic balloon dilatation peroral endoscopic myotomy proton pump inhibitor timed barium swallow
Patients and Methods Patients We retrospectively reviewed the charts of all patients who underwent POEM at our center from October 2012 until December 2014. Pre-POEM evaluation in all patients included an Eckardt questionnaire, upper endoscopy with placement of an HRM catheter, and timed barium swallow (TBS) study. Patients were asked to complete the same studies at 3 months after POEM. This study was approved by the institutional review board.
Operation Before the procedure, patients were given nystatin swish and swallow for 7 days and kept on liquids for 5 days (2 days of full liquids followed by 3 days of clears) to cleanse the esophagus and avoid a large food bezoar at the time of the procedure. The procedure was done under general anesthesia with paralysis using an Olympus 190 series endoscope (Olympus Corp, Tokyo, Japan) and carbon dioxide for insufflation, an ERBE generator (ERBE USA Inc, Marietta, GA), and the hybrid knife. The endoscope with an Olympus dissecting cap taped on was inserted without an overtube, and any remaining liquid or debris in the esophagus was suctioned. The esophagus was irrigated with bacitracin solution, and the location of the gastroesophageal junction (GEJ) noted. Orientation was determined by locating the air-fluid level after irrigating the esophagus, and pink tape was applied to the anterior portion of the endoscope 3 cm distal to the measured location of the GEJ (eg, if the GEJ was at 40 cm, the tape was applied at 43 cm). The tape helped to maintain orientation and prevent spiraling during the creation of the submucosal tunnel. Dilute indigo carmine (when available) or methylene blue without added epinephrine was used for injection. The mucosotomy was typically performed at the 2 o’clock position from 8 to 20 cm above the GEJ based on the type of achalasia, with the most proximal mucosotomy in patients with type III achalasia. In the case of a prior laparoscopic myotomy, the tunnel was created at the 5 o’clock position. The distance below the GEJ was confirmed by dye injection and later in the series by visualization of the length of the submucosal tunnel below the GEJ using a pediatric endoscope retroflexed within the stomach (Fig 1). A circular myotomy was initiated 2 to 3 cm distal to the mucosotomy and carried down to the end of the submucosal tunnel 3 cm below the
Fig 1. View of the dissecting endoscope in the distal extent of the submucosal tunnel using a retroflexed pediatric endoscope in the stomach. The 3-cm distance of the tunnel beyond the gastroesophageal junction is nicely verified.
GEJ. After completion of the myotomy and confirmation of homeostasis, the mucosotomy was closed with endoscopic clips or the Apollo OverStitch device (Apollo Endosurgery, Inc, Austin, TX). Typically patients had a contrast swallow the afternoon of the procedure to confirm the integrity of the mucosal closure and were then started on a liquid diet and discharged home the following morning. The liquid diet was continued for 48 hours and then advanced sequentially to full liquids, soft and finally a regular diet at 4 weeks after POEM.
Statistics Statistical comparisons between groups were done using the Mann-Whitney U test for continuous variables and Fisher’s exact test for nominal data. Statistical significance was set at a probability value of less than 0.05. Statistics were performed using GraphPad Prism 4.1 (GraphPad Software, San Diego, CA).
Results Our first POEM was in October 2012, and during the study years a total of 35 patients, 17 women and 18 men, underwent the procedure. The median age was 53 years (range, 25 to 83 years). The median duration of symptoms before POEM was 5 years, and all patients had dysphagia. Additional symptoms included regurgitation and aspiration in 12 patients and chest pain in 10 patients. Based on HRM there were 8 patients (23%) with type I, 21 patients (60%) with type II, and 5 patients (14%) with type III achalasia. One patient had a hypertensive LES with preserved esophageal body peristalsis. The median pre-POEM IRP was 29.1 mm Hg (range,
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0.3 to 67 mm Hg), and the median emptying on TBS at 1 minute was 20% and at 5 minutes was 36%. Prior therapy for achalasia had been performed in 18 patients (50%), most commonly either Botox injection or PBD. In 3 patients both Botox and PBD had been tried, and 1 patient had two prior failed laparoscopic myotomies. The median operative time for all cases was 120 minutes. The operative time decreased from a median of 130 minutes for the first third of cases to 113 minutes in the second third and 100 minutes in the last third (p ¼ 0.57). The median submucosal tunnel length was 18 cm (range, 11 to 25 cm). The procedure was aborted in 2 patients: one because of the presence of mucosal erosions identified before starting the mucosotomy, and one because of large submucosal vessels and a tortuous distal esophagus in a Jehovah’s Witness. The patient with mucosal erosions went on to have a successful POEM at a later date and is included in this series, and the Jehovah’s Witness subsequently had an uneventful laparoscopic myotomy. The remaining 34 cases were completed with no conversions or interruptions. The overall median hospital stay was 1 day (range, 1 to 8 days). Minor complications occurred in 4 patients (11%), but all recovered without incident and there was no mortality (Table 1). Early (3 months) symptomatic follow-up was available for 30 patients after POEM. Dysphagia resolved or was improved in all patients. Heartburn symptoms developed in 4 patients (11%). The Eckardt score went from a median of 7 before POEM to 0 after POEM (p < 0.0001), and no patient had an Eckardt score greater than 2. The symptomatic improvement in Eckardt score did not differ based on preoperative HRM type of achalasia (Fig 2). At early follow-up, 23 patients completed a post-POEM TBS, 22 had an upper endoscopy, and 10 patients had HRM and pH testing. On TBS, all patients had improved esophageal emptying. The median emptying at 1 and 5 minutes was 95% (Fig 3). Upper endoscopy showed that the mucosotomy site was completely healed in all patients. Esophagitis was seen in 55% of patients (12 of 22), but in all but 1 patient was Los Angeles grade A or B. The single patient with severe esophagitis (LA grade D) had a concomitant hiatal hernia (Fig 4). Heartburn symptoms were present in only 3 of the 12 patients with erosive esophagitis on endoscopy. All patients with esophagitis were started on daily proton pump inhibitor (PPI) therapy, and subsequent repeat endoscopy in 4 patients, Table 1. Details of Operative and Postoperative Complications (n ¼ 4) Complication Intraoperative gastric mucosal perforation False positive barium swallow suggesting a leak in the mucosal closure Left pleural effusion Pharyngitis
Treatment Closed with endoscopic clips at the time of the procedure with no postoperative leak Negative on repeat endoscopy
Percutaneous drainage Treated with antibiotics
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including the 1 with LA grade D esophagitis, showed that the esophagitis had resolved. Post-POEM HRM showed that the median IRP was significantly decreased (29.1 mm Hg before POEM to 10.1 mm Hg after POEM; p < 0.0001; Fig 5). The effective disruption of the LES with POEM can be appreciated visibly using high-definition threedimensional manometry (Fig 6). On Bravo pH testing (Given Imaging, Ltd, Yoqneam, Israel), the median DeMeester score on days 1 and 2 was 24.2 and 34.6, respectively, and overall 7 of the 10 patients had increased esophageal acid exposure (Table 2). In most patients (71%), the abnormal score was related to increased esophageal acid exposure during the supine period. No patient had abnormal isolated upright reflux. In the group that had an abnormal pH test, endoscopy showed esophagitis in 43% of patients. None of the 7 patients with an abnormal pH test had heartburn symptoms. There were 10 patients with at least 12 months of follow-up after POEM. Excellent relief of dysphagia persisted in all patients. Intermittent heartburn symptoms were present in 4 patients, but improved with acidsuppression therapy. At a median of 15 months after POEM, 6 patients completed another TBS. The median esophageal emptying was 98% at 1 minute. No patient had worse emptying on TBS at longer follow-up compared with their initial post-POEM study. A single patient has required a reintervention after POEM. This patient had two prior failed laparoscopic myotomies before the POEM procedure. He had initial symptomatic improvement but experienced recurrent dysphagia. His dysphagia improved after progressive PBD up to 40 mm. No other patient has had recurrence of dysphagia or the need for additional intervention.
Comment The primary symptoms in patients with achalasia, dysphagia and regurgitation, are caused by poor esophageal emptying related to outflow obstruction at the LES and loss of esophageal body peristalsis. There is no cure for achalasia, but the symptoms can be palliated by medications or procedures that relax or disrupt the muscle of the LES. The most common procedures are Botox injection, PBD, and surgical myotomy. Botox is temporary, can cause submucosal fibrosis, which can increase the difficulty of other therapies, and should be reserved for select circumstances. Pneumatic dilatation is performed with balloons that start at 30 mm, or 150% of the normal diameter of the esophagus, and can go up to 40 mm or double the normal esophageal diameter. The major advantage of PBD is its endoscopic approach associated with minimal pain, no scar, and rapid recovery. The major disadvantage is the imprecise disruption of the circular fibers of the LES, the risk for full-thickness perforation, and the frequent need for repeat dilatation to accomplish lasting relief of symptoms [6]. Importantly, the outcome of pneumatic dilatation has been shown to vary by HRM subtype, with a reduced likelihood of successful relief of symptoms in patients with type III achalasia [7].
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Fig 2. The change in Eckardt score based on the highresolution manometric type of achalasia.
The major alternative to PBD is a laparoscopic Heller myotomy with partial fundoplication. Laparoscopic myotomy allows precise division of the LES muscle fibers and continuation of the myotomy several centimeters down onto the stomach, which has been shown to increase the efficacy of the procedure [8]. Laparoscopic myotomy is associated with durable, excellent results that have been reproduced at centers around the world [9]. Furthermore, only infrequently are additional procedures necessary, and it is applicable to all HRM subtypes of achalasia [6, 10]. The disadvantage is that it requires abdominal incisions and has more discomfort and a longer recovery compared with PBD. Recently a new procedure for achalasia has been introduced, the peroral endoscopic myotomy or POEM. This procedure is built on techniques developed for endoscopic management of early gastric and esophageal tumors including endoscopic resection and submucosal dissection. In 2007 Pasricha and colleagues [4] showed in an animal model an endoscopic technique to accomplish
Fig 3. Esophageal emptying by timed barium swallow testing increased from a median of 36% at 5 minutes to 95% at 5 minutes after peroral endoscopic myotomy (p < 0.0001).
division of the circular fibers of the LES. The procedure was first used to treat achalasia in a human by Inoue and coworkers [3] a year later, and their initial series of patients was reported in 2010 [11]. The POEM procedure offers precise division of the circular fibers of the LES with the ability to carry the myotomy down several centimeters onto the stomach similar to the laparoscopic approach, but in a scarless, endoscopic fashion. After introduction of the procedure, it was adopted by several centers in Asia, Europe, and the United States, largely by general surgeons and gastroenterologists with
Fig 4. Upper endoscopy after peroral endoscopic myotomy (n ¼ 22) showed esophagitis in 55% of patients. The esophagitis was LA grade A (n ¼ 3) or B (n ¼ 8) in most patients. The single patient with LA grade D esophagitis had a concomitant hiatal hernia.
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Fig 5. The integrated relaxation pressure before (pre) and after (post) peroral endoscopic myotomy (POEM) in 10 patients compared with the normal value [5].
advanced endoscopic procedure experience. We started performing POEM procedures in 2012 and quickly gained experience given patient interest in the procedure. Before starting POEM, we were comfortable with procedures such as endoscopic mucosal resection and ablation, stent placement, and pneumatic balloon dilatation. The learning curve was relatively quick, although it took approximately 20 patients to really feel comfortable with the procedure. Important parts of the learning process included how to maintain orientation during creation of the submucosal tunnel and avoid spiraling, particularly at a tight GEJ, and how to manage bleeding from large submucosal vessels using a combination of the cap to tamponade the vessel, irrigation to identify the exact site of the bleeding, and coagulation graspers to control it. In this series of our first 35 consecutive patients, we have shown a significant improvement in Eckardt score and dysphagia symptoms with a corresponding significant reduction in esophageal retention on TBS and IRP on post-POEM manometry. Despite the inclusion of our first
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patients, we had little morbidity and no mortality or major complications. We found the POEM procedure effective for all HRM types of achalasia, but we adjust the length of the myotomy based on the type of achalasia. The longest myotomies are done in patients with type III achalasia and evidence of esophageal spasm. The POEM approach with long esophageal myotomy has also been reported to be effective for patients with diffuse esophageal spasm [12]. For HRM achalasia types I and II, we are gradually shortening the myotomy because there is likely no benefit to a long myotomy above the LES in these patients. We believe that the distal extent of the myotomy onto the stomach is critical, and have found the most reliable way to confirm an adequate distal extent of the submucosal tunnel is to pass a pediatric endoscope down the true lumen into the stomach while the dissecting scope is kept in the distal extent of the submucosal tunnel. Retroflexing the pediatric scope in the stomach shows the location of the scope in the submucosal tunnel and allows clear delineation of the extent of the tunnel below the GEJ. In our experience, this is much more reliable than other techniques including trying to visualize colored saline that has been injected at the end of the submucosal tunnel. Effective disruption of the LES in patients with achalasia opens the door for gastroesophageal reflux disease. We endoscopically evaluated patients 3 months after POEM and found erosive esophagitis in over half, but in nearly all it was LA grade A or B and reliably resolved with initiation of daily PPI medication. The single patient with severe esophagitis had a concomitant hiatal hernia. From this experience we would recommend that the presence of a hiatal hernia is an indication to perform a laparoscopic myotomy with repair of the hiatal hernia and a partial fundoplication rather than a POEM, particularly in young patients. Furthermore, we recommend that after POEM all patients undergo endoscopy and a pH test. In our series only 11% of patients had
Fig 6. High-definition threedimensional manometry showing the lower esophageal sphincter before and after peroral endoscopic myotomy.
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Table 2. Components of Post–Peroral Endoscopic Myotomy pH Studies (n ¼ 10)a Variable Total number of episodes Supine fraction time (%) Upright fraction time (%) Total fraction time (%) Number of episodes >5 min Longest episode (min) Score a
Day 1
Day 2
Total (both days)
37 7.4 1.9 4.8 2 23.5 24.2
32 18.8 2.8 7.8 4 23 34.6
34.5 13.1 2.3 6.3 3 23 29.4
All values expressed as median.
heartburn, yet 55% had esophagitis and 70% had a positive pH test. Relying only on heartburn symptoms would have missed most patients with objective evidence of reflux, and left untreated, these patients may go on to exhibit strictures or Barrett’s esophagus. An alternative is to start everyone on daily PPI therapy after POEM, but there are long-term side effects with these medications. Our approach now is to start a daily histamine type 2 blocker in all patients after POEM, and escalate therapy to a PPI only when symptoms, endoscopy, or pH testing indicate the need for more aggressive acid suppression. We are also considering offering an endoscopic antireflux procedure to young patients with esophagitis or an abnormal pH test after POEM and await reports of the success of this approach from other centers. Alternatively, young patients with significant reflux after POEM could be offered a laparoscopic partial fundoplication. Thus far we have not had any patient whose symptoms or erosive esophagitis were not readily controlled with PPI therapy or who wished to have a partial fundoplication instead of taking acid-suppression medications. With regard to gastroesophageal reflux disease after POEM, a couple of issues bear consideration. First, all therapies for achalasia open a nonrelaxing valve and thereby create the potential for reflux. Long term, most of the failures after treatment in patients with achalasia are related to complications of reflux. Late (>20 years) after a myotomy and partial fundoplication, Csendes and colleagues [13] showed that 53% of patients had a positive pH test. Furthermore, intestinal metaplasia was found on biopsies in almost 30% of these patients. Reflux also occurs after pneumatic dilatation. A follow-up endoscopy at a mean of 8.9 years after PBD in 331 patients with achalasia showed Barrett’s esophagus in 8.4% and esophageal adenocarcinoma in 2 patients (0.6%). Barrett’s developed at a rate of 1% per year, and the risk was higher in those with lower LES pressures and a hiatal hernia [14]. It is likely that POEM, by virtue of the lack of a partial fundoplication, is associated with more reflux early after therapy compared with a laparoscopic myotomy. However, the myotomy during POEM is done in a different anatomic location compared with a laparoscopic myotomy, and the phrenoesophageal ligament is not disrupted with the POEM procedure. The long-term implications of
these differences remain to be seen, and certainly endoscopic follow-up 5 and 10 years after POEM will be important to evaluate for complications of reflux including development of Barrett’s esophagus in these patients. Our initial results with POEM are comparable to those of other published series. Single center and multicenter studies as well as a recent meta-analysis all confirm the safety and efficacy of POEM [15]. A recent meta-analysis included 29 published studies and showed a significant improvement in the Eckhart score and a reduction of LES pressure after POEM [14]. Compared with a laparoscopic Heller myotomy, the meta-analysis showed a trend toward a lower Eckhart score and shorter operative time with POEM with a similar frequency of adverse events and posttherapy gastroesophageal reflux disease symptoms [15]. The published experience from Portland on POEM in 100 patients who had an esophageal motility abnormality showed relief of dysphagia in 97%, significant improvement in esophageal emptying on TBS, and an overall morbidity of 6%. Post-POEM only 5% of patients had heartburn symptoms, but 27% had esophagitis and 38% had a positive 24-hour pH test for reflux [12]. In a prior series from that center limited to patients with achalasia, 50% had a positive pH test after POEM [5]. The frequency of esophagitis and a positive pH test in our series is higher than in other reports, perhaps related to our effort to carry the myotomy 3 cm down onto the stomach and using the retroflexed pediatric endoscope to confirm the distal extent of the submucosal tunnel. Future studies evaluating the ideal proximal and distal extent and location of the myotomy with POEM to relieve symptoms yet minimize reflux will be useful. There has been concern about the longevity of the myotomy with POEM, particularly because in the multiinstitution study from Europe and North America the success rate with POEM decreased from 97% at 3 months to 82% at 1 year [16]. Success can be assessed subjectively, but perhaps a more objective method is with a TBS evaluating esophageal emptying. Using this method, we had follow-up beyond 1 year in 26% of patients who had completed a TBS earlier, at approximately 3 months, and in this group all patients had similar or further improved emptying compared with their initial post-POEM study. This objective evidence indicates that short-term failure or reclosure of the myotomy is unlikely in patients with an initial good response to POEM. From a mechanistic standpoint, it would seem that myotomy reclosure should be a relatively early event, and thus it appears that the myotomy with POEM is effective and long lasting when done well. Although POEM is a complex endoscopic procedure, this series shows that thoracic surgeons with an interest in esophageal surgery and the necessary endoscopic skillset can readily adopt the procedure. Familiarity with the mediastinum and managing esophageal perforations likely makes thoracic surgeons uniquely qualified to perform POEM and manage periprocedural complications. Some thoughts from our initial POEM experience are that prior interventions, a very high IRP, and
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angulation of the esophagus at the GEJ increase the complexity of the procedure. We would recommend that during the initial several cases when there is a proctor present, some of these difficult patients be included so that tricks for addressing these situations can be demonstrated. On the first 5 to 10 cases without a proctor, these types of patients should be avoided if possible to allow independent experience to accumulate on more straightforward patients. If the procedure is not progressing well, there should be no hesitation to terminate it and avoid a potentially major complication in a patient with benign disease. Depending on how close the submucosal tunnel has come to the GEJ, judgment is necessary to decide whether to convert at that time to another type of therapy or to delay reintervention until sufficient time has passed for the tunnel to heal. Lastly, although closure of the mucosotomy with clips is quite reliable, suturing has become our preference in most patients. The low profile of the sutures is appealing, and there is no possibility of a suture falling off as can occur with a clip. The suture closure has been so secure that moving forward we plan to omit postoperative contrast swallows and to begin offering POEM as an outpatient procedure for patients who live locally. The strengths of our study are that it is a consecutive series of the initial patients who underwent POEM by a thoracic surgeon. It is limited by short and incomplete objective follow-up. However, because most patients had excellent symptomatic relief and had no heartburn symptoms, it is unlikely that the objectively studied population was significantly skewed compared with those who did not return for their scheduled studies. Most of those who did not return had travelled a significant distance for the procedure; however, the importance of objective follow-up in these patients cannot be overemphasized. In conclusion, the POEM procedure represents a paradigm shift in the treatment of achalasia in that high efficacy can now be accomplished with low invasiveness. Previously, low efficacy and low invasive options were Botox injection and a single pneumatic dilatation, whereas more invasive and better efficacy options consisted of multiple pneumatic dilatations and laparoscopic Heller myotomy. The POEM procedure provides the efficacy of a laparoscopic Heller with the invasiveness of a single pneumatic dilatation. It may be the best of both worlds, allowing a precise myotomy with the recovery benefits of no external incisions and no physical restrictions. Even during the learning curve, it is safe and provides reliable palliation of the symptoms of achalasia with objective evidence of improved esophageal emptying. Gastroesophageal reflux occurs after all therapies for achalasia, but may be more prevalent after POEM. Objective evaluation for evidence of reflux is warranted after POEM because symptoms are an unreliable indicator of gastroesophageal reflux disease in these patients. When a hiatal hernia is present in a patient with achalasia, a laparoscopic myotomy, partial fundoplication, and repair of the hernia
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may be a better option than a POEM procedure. However, most patients with achalasia do not have a hiatal hernia, and the safety and efficacy of POEM suggest that it deserves a place in the armamentarium of thoracic surgeons interested in the care of patients with benign esophageal disease.
References 1. Sadowski DC, Ackah F, Jiang B, Svenson LW. Achalasia: incidence, prevalence and survival. A population-based study. Neurogastroenterol Motil 2010;22:e256–61. 2. Pandolfino JE, Kwiatek MA, Nealis T, Bulsiewicz W, Post J, Kahrilas PJ. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology 2008;135: 1526–33. 3. Inoue H, Minami H, Satodate H, Kudo S-E. First clinical experience of submucosal endoscopic myotomy for esophageal achalasia with no skin incision. Gastrointest Endosc 2009;69:AB122; Abstract. 4. Pasricha PJ, Hawari R, Ahmed I, et al. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy 2007;39:761–4. 5. Swanstrom LL, Kurian A, Dunst CM, Sharata A, Bhayani N, Rieder E. Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure. Ann Surg 2012;256: 659–67. 6. Boeckxstaens GE, Annese V, des Varannes SB, et al, European Achalasia Trial Investigators. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med 2011;364:1807–16. 7. Rohof WO, Salvador R, Annese V, et al. Outcomes of treatment for achalasia depend on manometric subtype. Gastroenterology 2013;144:718–25. 8. Oelschlager BK, Chang L, Pellegrini CA. Improved outcome after extended gastric myotomy for achalasia. Arch Surg 2003;138:490–7. 9. Ross SW, Oommen B, Wormer BA, et al. National outcomes of laparoscopic Heller myotomy: operative complications and risk factors for adverse events. Surg Endosc 2015 Jan 15; [epub ahead of print]. 10. Greene CL, Chang EJ, Oh DS, Worrell SG, Hagen JA, DeMeester SR. High resolution manometry subclassification of achalasia: does it really matter? Does achalasia sub-classification matter? Surg Endosc 2015;29:1363–7. 11. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010;42:265–71. 12. Sharata AM, Dunst CM, Pescarus R, et al. Peroral endoscopic myotomy (POEM) for esophageal primary motility disorders: analysis of 100 consecutive patients. J Gastrointest Surg 2015;19:161–70. 13. Csendes A, Braghetto I, Burdiles P, Korn O, Csendes P, Henríquez A. Very late results of esophagomyotomy for patients with achalasia: clinical, endoscopic, histologic, manometric, and acid reflux studies in 6 patients for a mean follow-up of 190 months. Ann Surg 2006;243:196–203. 14. Leeuwenburgh L, Scholten P, Calj e TJ, et al. Barrett’s esophagus and esophageal adenocarcinoma are common after treatment for achalasia. Dig Dis Sci 2013;58:244–52. 15. Talukdar R, Inoue H, Reddy DN. Efficacy of peroral endoscopic myotomy (POEM) in the treatment of achalasia: a systematic review and meta-analysis. Surg Endosc 2014 Dec 25; [epub ahead of print]. 16. Von Renteln D, Fuchs KH, Fockens P, et al. Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study. Gastroenterology 2013;145:309–11.e1; e3.
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DISCUSSION DR KAMAL G. KHALIL (Houston, TX): Just curious if we adopt this as our primary approach, and those of us who do VATS (video-assisted thoracoscopic surgery) myotomy usually combine it with an antireflux procedure. Have you noticed any increase in reflux in those few patients that you followed postoperatively?
DR MATTHEW G. BLUM (Colorado Springs, CO): I was curious, do you do myotomy through just the inner circular muscle, or are you going all the way through the longitudinal muscle as well? And did you have any issues with pneumoperitoneum or pneumothorax?
DR WORRELL: Symptomatic reflux postoperatively was present in about 15% of patients. However, there was a 55% incidence of patients with esophagitis on follow-up endoscopy. Doctor Inoue recently reported on a review of all reported literature on the POEM (peroral endoscopic myotomy), and overall there’s been a 10% incidence of postoperative reflux, which is in line with postlaparoscopic myotomy reflux. The endoscopic myotomy is performed at a different location on the esophagus, potentially maintaining the angle of His; therefore, we propose that there may be a decreased risk of reflux with this procedure compared to what is expected.
DR WORRELL: To minimize the pneumoperitoneum and pneumothorax we exclusively use CO2. We have had about 4 patients who have developed some pneumoperitoneum during the procedure. This was decompressed easily with an 18-gauge catheter into the abdomen. The catheter is removed at the end of the procedure and without sequelae. And then the first part of your question, we intentionally only do a circular muscle myotomy. However, the longitudinal muscles often split just because they’re so thin, and many times it ends up being a full-thickness myotomy.
DR SCOTT I. REZNIK (Dallas, TX): It’s a great presentation. How were you choosing or counseling patients when they’re coming specifically for POEM? Is this your treatment of choice now or is it just something you’re introducing? DR WORRELL: The POEM is our treatment of choice. However, we acknowledge that there are some more complex cases that may benefit from a laparoscopic myotomy. Specifically, patients with hiatal hernias should undergo surgical intervention with repair of the hiatal hernia. Some tortuous distal esophaguses make the POEM more complex. However, with experience there are techniques that can be used to complete the POEM procedure without conversion to a laparoscopic or open procedure. In a surgeon’s initial experience, it is probably best to avoid these kind of patients for POEM. DR REZNIK: Are you routinely putting these patients on PPIs (proton pump inhibitors) or only if they have symptoms of esophagitis or reflux? DR WORRELL: Our current practice is to put all patient on H2 (histamine type 2) blockers post-POEM. All patients then have an endoscopy at 3 months. If esophagitis is present at that time, then we convert them over to a PPI. DR K. ROBERT SHEN (Rochester, MN): What’s the current follow-up long term at your institution for these patients who are undergoing some sort of surgical intervention for achalasia? Do you see them back once postoperative[ly] and then that’s it, or do you see them yearly? DR WORRELL: For the POEM patients, we are routinely seeing them at 3 months to undergo a timed barium swallow and endoscopy. If they have no evidence of esophagitis, then we see them back at a year to assess their symptomatic outcome. DR SHEN: Okay. In the abstract it mentioned that there was follow-up data available on only 56% of the patients, so what happened to the others? DR WORRELL: Our follow-up has increased, many of the patients reported in the initial abstract are now over 6 months out from their operation.
DR BLUM: And you’ve kind of advocated that thoracic surgeons pick this up. I would see probably half a dozen achalasia patients in a year. Is that a sufficient volume to become familiar with the techniques, and would you shy away from any of the patients that had been intervened on before based on your experience especially early on, or did that actually make any difference? DR WORRELL: With our experience, we believe proficiency occurs around 15 to 20 cases. There was a recent publication by a gastroenterologist looking at mastery of the POEM, which they concluded occurred at 60 cases. Additionally, there has been no difference in outcomes or complications based on preoperative therapy, such as Botox or dilation. DR SHEN: Back when laparoscopic Heller myotomy was first gaining traction among the surgical community, it was not uniform to perform an antireflux procedure until the group from Seattle, Washington, with Dr Pellegrini performed a prospective randomized study looking at patients who received some sort of an antireflux procedure versus just the myotomy. And it clearly showed there was a reduction in symptomatic and asymptomatic reflux that could be documented with either endoscopy or pH studies. And that, then, has become sort of the widely adopted standard of care, to combine some sort of antireflux procedure with the myotomy. So in light of that experience, are we really stepping back in time now with doing a myotomy again alone without an antireflux procedure? DR WORRELL: I think that is a very good point. Time will definitely tell us if that is true. At the same time, there has been an increase in the development and use of endoscopic antireflux operations, which may serve as an adjunct therapy for these patients. Additionally, the POEM is performed in a different location along the esophagus, in theory allowing the angle of His to be maintained, and therefore, potentially decreasing the expected incidence of reflux. DR MELANIE A. EDWARDS (St. Louis, MO): I have a quick question. Regarding your esophagitis, how many of them did not resolve with PPI therapy? DR WORRELL: All patients who stuck with the daily PPI regimen had resolution of their esophagitis.
Background. Peroral endoscopic myotomy (POEM) is a new option in the treatment of achalasia. It has typically been performed by general surgeons and gastroenterologists familiar with advanced endoscopic procedures. Our objective was to assess the initial experience and outcomes with POEM by a thoracic surgeon. Methods. A retrospective chart review was performed of all patients who underwent POEM from October 2012 until December 2014. Pre- and post-POEM evaluation included upper endoscopy, high-resolution manometry, and a timed barium swallow. Results. There were 35 patients (18 men and 17 women), with a median age of 53 years. Based on highresolution manometry, there were 8 patients (23%) with type I, 21 (60%) with type II, and 5 (14%) with type III achalasia, and 1 patient had hypertensive lower esophageal sphincter. Prior therapy had been performed in 18 patients (51%). The POEM procedure was completed in all but 1 patient. On follow-up, dysphagia was improved in all patients. The Eckardt score was significantly reduced
from 7 before POEM to 0 after POEM (p < 0.0001), and improved similarly for all manometric types of achalasia. Post-POEM upper endoscopy showed esophagitis in 55% of patients, but this condition resolved in all with acid suppression. Timed barium swallow showed a reduction of esophageal retention at 5 minutes from 63% before POEM to 5% after POEM. Ten patients had follow-up at 12 months or greater after POEM and the improvements persisted. Conclusions. Peroral endoscopic myotomy is a safe and effective therapy for achalasia. It provides reliable and persistent palliation of dysphagia and objective improvement in esophageal emptying. Esophagitis is common but resolves with acid suppression therapy. Thoracic surgeons with an interest in esophageal diseases and experience with endoscopy are encouraged to adopt the procedure.
A
relaxation pressure (IRP) but differ based on the presence of esophageal pressurization or spasm in the esophageal body. Type I is classic achalasia, type II has panesophageal pressurization, and type III has evidence of distal esophageal spasm [2]. Achalasia is not curable, but treatment can provide effective palliation of the dysphagia and regurgitation symptoms. All treatments focus on improving the outflow resistance caused by the poorly relaxing LES. The two primary therapies have been pneumatic balloon dilatation (PBD) and laparoscopic Heller myotomy with partial fundoplication. Each approach has advantages and disadvantages, but the reliable and reproducible results with laparoscopic myotomy have made it the gold-standard therapy worldwide. In 2009 Inoue and colleagues [3] first reported an endoscopic myotomy for a patient with achalasia based on an animal study by Pasricha and associates [4]. They termed the procedure peroral endoscopic myotomy (POEM). Subsequently, POEM programs have been initiated by general surgeons and some gastroenterologists in Asia, Europe, and the United States. The aim of this study was to review the initial experience of a thoracic surgeon with the POEM procedure.
chalasia is an esophageal motility disorder that affects approximately 1 per 100,000 people. Interestingly, the prevalence of this disorder has increased more than fourfold during the past two decades [1]. The cause remains uncertain, but patients typically present with progressive dysphagia for both solids and liquids related to destruction of the Auerbach’s plexus. The diagnosis is confirmed by esophageal manometry showing failure of the lower esophageal sphincter (LES) to relax and loss of esophageal body peristalsis. Some patients also have a hypertensive LES resting pressure or evidence of esophageal body pressurization. With the introduction of high-resolution manometry (HRM), achalasia has been divided into three types. Under the Chicago classification system, all types of achalasia have an elevated integrated
Accepted for publication June 8, 2015. Presented at the Fifty-first Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 24–28, 2015. Address correspondence to Dr DeMeester, Division of Thoracic Surgery, Department of Surgery, Keck School of Medicine of the University of Southern California, 1510 San Pablo St, Ste 514, Los Angeles, CA 90033; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.06.036
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Abbreviations and Acronyms GEJ HRM IRP LES PBD POEM PPI TBS
= = = = = = = =
gastroesophageal junction high-resolution manometry integrated relaxation pressure lower esophageal sphincter pneumatic balloon dilatation peroral endoscopic myotomy proton pump inhibitor timed barium swallow
Patients and Methods Patients We retrospectively reviewed the charts of all patients who underwent POEM at our center from October 2012 until December 2014. Pre-POEM evaluation in all patients included an Eckardt questionnaire, upper endoscopy with placement of an HRM catheter, and timed barium swallow (TBS) study. Patients were asked to complete the same studies at 3 months after POEM. This study was approved by the institutional review board.
Operation Before the procedure, patients were given nystatin swish and swallow for 7 days and kept on liquids for 5 days (2 days of full liquids followed by 3 days of clears) to cleanse the esophagus and avoid a large food bezoar at the time of the procedure. The procedure was done under general anesthesia with paralysis using an Olympus 190 series endoscope (Olympus Corp, Tokyo, Japan) and carbon dioxide for insufflation, an ERBE generator (ERBE USA Inc, Marietta, GA), and the hybrid knife. The endoscope with an Olympus dissecting cap taped on was inserted without an overtube, and any remaining liquid or debris in the esophagus was suctioned. The esophagus was irrigated with bacitracin solution, and the location of the gastroesophageal junction (GEJ) noted. Orientation was determined by locating the air-fluid level after irrigating the esophagus, and pink tape was applied to the anterior portion of the endoscope 3 cm distal to the measured location of the GEJ (eg, if the GEJ was at 40 cm, the tape was applied at 43 cm). The tape helped to maintain orientation and prevent spiraling during the creation of the submucosal tunnel. Dilute indigo carmine (when available) or methylene blue without added epinephrine was used for injection. The mucosotomy was typically performed at the 2 o’clock position from 8 to 20 cm above the GEJ based on the type of achalasia, with the most proximal mucosotomy in patients with type III achalasia. In the case of a prior laparoscopic myotomy, the tunnel was created at the 5 o’clock position. The distance below the GEJ was confirmed by dye injection and later in the series by visualization of the length of the submucosal tunnel below the GEJ using a pediatric endoscope retroflexed within the stomach (Fig 1). A circular myotomy was initiated 2 to 3 cm distal to the mucosotomy and carried down to the end of the submucosal tunnel 3 cm below the
Fig 1. View of the dissecting endoscope in the distal extent of the submucosal tunnel using a retroflexed pediatric endoscope in the stomach. The 3-cm distance of the tunnel beyond the gastroesophageal junction is nicely verified.
GEJ. After completion of the myotomy and confirmation of homeostasis, the mucosotomy was closed with endoscopic clips or the Apollo OverStitch device (Apollo Endosurgery, Inc, Austin, TX). Typically patients had a contrast swallow the afternoon of the procedure to confirm the integrity of the mucosal closure and were then started on a liquid diet and discharged home the following morning. The liquid diet was continued for 48 hours and then advanced sequentially to full liquids, soft and finally a regular diet at 4 weeks after POEM.
Statistics Statistical comparisons between groups were done using the Mann-Whitney U test for continuous variables and Fisher’s exact test for nominal data. Statistical significance was set at a probability value of less than 0.05. Statistics were performed using GraphPad Prism 4.1 (GraphPad Software, San Diego, CA).
Results Our first POEM was in October 2012, and during the study years a total of 35 patients, 17 women and 18 men, underwent the procedure. The median age was 53 years (range, 25 to 83 years). The median duration of symptoms before POEM was 5 years, and all patients had dysphagia. Additional symptoms included regurgitation and aspiration in 12 patients and chest pain in 10 patients. Based on HRM there were 8 patients (23%) with type I, 21 patients (60%) with type II, and 5 patients (14%) with type III achalasia. One patient had a hypertensive LES with preserved esophageal body peristalsis. The median pre-POEM IRP was 29.1 mm Hg (range,
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0.3 to 67 mm Hg), and the median emptying on TBS at 1 minute was 20% and at 5 minutes was 36%. Prior therapy for achalasia had been performed in 18 patients (50%), most commonly either Botox injection or PBD. In 3 patients both Botox and PBD had been tried, and 1 patient had two prior failed laparoscopic myotomies. The median operative time for all cases was 120 minutes. The operative time decreased from a median of 130 minutes for the first third of cases to 113 minutes in the second third and 100 minutes in the last third (p ¼ 0.57). The median submucosal tunnel length was 18 cm (range, 11 to 25 cm). The procedure was aborted in 2 patients: one because of the presence of mucosal erosions identified before starting the mucosotomy, and one because of large submucosal vessels and a tortuous distal esophagus in a Jehovah’s Witness. The patient with mucosal erosions went on to have a successful POEM at a later date and is included in this series, and the Jehovah’s Witness subsequently had an uneventful laparoscopic myotomy. The remaining 34 cases were completed with no conversions or interruptions. The overall median hospital stay was 1 day (range, 1 to 8 days). Minor complications occurred in 4 patients (11%), but all recovered without incident and there was no mortality (Table 1). Early (3 months) symptomatic follow-up was available for 30 patients after POEM. Dysphagia resolved or was improved in all patients. Heartburn symptoms developed in 4 patients (11%). The Eckardt score went from a median of 7 before POEM to 0 after POEM (p < 0.0001), and no patient had an Eckardt score greater than 2. The symptomatic improvement in Eckardt score did not differ based on preoperative HRM type of achalasia (Fig 2). At early follow-up, 23 patients completed a post-POEM TBS, 22 had an upper endoscopy, and 10 patients had HRM and pH testing. On TBS, all patients had improved esophageal emptying. The median emptying at 1 and 5 minutes was 95% (Fig 3). Upper endoscopy showed that the mucosotomy site was completely healed in all patients. Esophagitis was seen in 55% of patients (12 of 22), but in all but 1 patient was Los Angeles grade A or B. The single patient with severe esophagitis (LA grade D) had a concomitant hiatal hernia (Fig 4). Heartburn symptoms were present in only 3 of the 12 patients with erosive esophagitis on endoscopy. All patients with esophagitis were started on daily proton pump inhibitor (PPI) therapy, and subsequent repeat endoscopy in 4 patients, Table 1. Details of Operative and Postoperative Complications (n ¼ 4) Complication Intraoperative gastric mucosal perforation False positive barium swallow suggesting a leak in the mucosal closure Left pleural effusion Pharyngitis
Treatment Closed with endoscopic clips at the time of the procedure with no postoperative leak Negative on repeat endoscopy
Percutaneous drainage Treated with antibiotics
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including the 1 with LA grade D esophagitis, showed that the esophagitis had resolved. Post-POEM HRM showed that the median IRP was significantly decreased (29.1 mm Hg before POEM to 10.1 mm Hg after POEM; p < 0.0001; Fig 5). The effective disruption of the LES with POEM can be appreciated visibly using high-definition threedimensional manometry (Fig 6). On Bravo pH testing (Given Imaging, Ltd, Yoqneam, Israel), the median DeMeester score on days 1 and 2 was 24.2 and 34.6, respectively, and overall 7 of the 10 patients had increased esophageal acid exposure (Table 2). In most patients (71%), the abnormal score was related to increased esophageal acid exposure during the supine period. No patient had abnormal isolated upright reflux. In the group that had an abnormal pH test, endoscopy showed esophagitis in 43% of patients. None of the 7 patients with an abnormal pH test had heartburn symptoms. There were 10 patients with at least 12 months of follow-up after POEM. Excellent relief of dysphagia persisted in all patients. Intermittent heartburn symptoms were present in 4 patients, but improved with acidsuppression therapy. At a median of 15 months after POEM, 6 patients completed another TBS. The median esophageal emptying was 98% at 1 minute. No patient had worse emptying on TBS at longer follow-up compared with their initial post-POEM study. A single patient has required a reintervention after POEM. This patient had two prior failed laparoscopic myotomies before the POEM procedure. He had initial symptomatic improvement but experienced recurrent dysphagia. His dysphagia improved after progressive PBD up to 40 mm. No other patient has had recurrence of dysphagia or the need for additional intervention.
Comment The primary symptoms in patients with achalasia, dysphagia and regurgitation, are caused by poor esophageal emptying related to outflow obstruction at the LES and loss of esophageal body peristalsis. There is no cure for achalasia, but the symptoms can be palliated by medications or procedures that relax or disrupt the muscle of the LES. The most common procedures are Botox injection, PBD, and surgical myotomy. Botox is temporary, can cause submucosal fibrosis, which can increase the difficulty of other therapies, and should be reserved for select circumstances. Pneumatic dilatation is performed with balloons that start at 30 mm, or 150% of the normal diameter of the esophagus, and can go up to 40 mm or double the normal esophageal diameter. The major advantage of PBD is its endoscopic approach associated with minimal pain, no scar, and rapid recovery. The major disadvantage is the imprecise disruption of the circular fibers of the LES, the risk for full-thickness perforation, and the frequent need for repeat dilatation to accomplish lasting relief of symptoms [6]. Importantly, the outcome of pneumatic dilatation has been shown to vary by HRM subtype, with a reduced likelihood of successful relief of symptoms in patients with type III achalasia [7].
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Fig 2. The change in Eckardt score based on the highresolution manometric type of achalasia.
The major alternative to PBD is a laparoscopic Heller myotomy with partial fundoplication. Laparoscopic myotomy allows precise division of the LES muscle fibers and continuation of the myotomy several centimeters down onto the stomach, which has been shown to increase the efficacy of the procedure [8]. Laparoscopic myotomy is associated with durable, excellent results that have been reproduced at centers around the world [9]. Furthermore, only infrequently are additional procedures necessary, and it is applicable to all HRM subtypes of achalasia [6, 10]. The disadvantage is that it requires abdominal incisions and has more discomfort and a longer recovery compared with PBD. Recently a new procedure for achalasia has been introduced, the peroral endoscopic myotomy or POEM. This procedure is built on techniques developed for endoscopic management of early gastric and esophageal tumors including endoscopic resection and submucosal dissection. In 2007 Pasricha and colleagues [4] showed in an animal model an endoscopic technique to accomplish
Fig 3. Esophageal emptying by timed barium swallow testing increased from a median of 36% at 5 minutes to 95% at 5 minutes after peroral endoscopic myotomy (p < 0.0001).
division of the circular fibers of the LES. The procedure was first used to treat achalasia in a human by Inoue and coworkers [3] a year later, and their initial series of patients was reported in 2010 [11]. The POEM procedure offers precise division of the circular fibers of the LES with the ability to carry the myotomy down several centimeters onto the stomach similar to the laparoscopic approach, but in a scarless, endoscopic fashion. After introduction of the procedure, it was adopted by several centers in Asia, Europe, and the United States, largely by general surgeons and gastroenterologists with
Fig 4. Upper endoscopy after peroral endoscopic myotomy (n ¼ 22) showed esophagitis in 55% of patients. The esophagitis was LA grade A (n ¼ 3) or B (n ¼ 8) in most patients. The single patient with LA grade D esophagitis had a concomitant hiatal hernia.
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Fig 5. The integrated relaxation pressure before (pre) and after (post) peroral endoscopic myotomy (POEM) in 10 patients compared with the normal value [5].
advanced endoscopic procedure experience. We started performing POEM procedures in 2012 and quickly gained experience given patient interest in the procedure. Before starting POEM, we were comfortable with procedures such as endoscopic mucosal resection and ablation, stent placement, and pneumatic balloon dilatation. The learning curve was relatively quick, although it took approximately 20 patients to really feel comfortable with the procedure. Important parts of the learning process included how to maintain orientation during creation of the submucosal tunnel and avoid spiraling, particularly at a tight GEJ, and how to manage bleeding from large submucosal vessels using a combination of the cap to tamponade the vessel, irrigation to identify the exact site of the bleeding, and coagulation graspers to control it. In this series of our first 35 consecutive patients, we have shown a significant improvement in Eckardt score and dysphagia symptoms with a corresponding significant reduction in esophageal retention on TBS and IRP on post-POEM manometry. Despite the inclusion of our first
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patients, we had little morbidity and no mortality or major complications. We found the POEM procedure effective for all HRM types of achalasia, but we adjust the length of the myotomy based on the type of achalasia. The longest myotomies are done in patients with type III achalasia and evidence of esophageal spasm. The POEM approach with long esophageal myotomy has also been reported to be effective for patients with diffuse esophageal spasm [12]. For HRM achalasia types I and II, we are gradually shortening the myotomy because there is likely no benefit to a long myotomy above the LES in these patients. We believe that the distal extent of the myotomy onto the stomach is critical, and have found the most reliable way to confirm an adequate distal extent of the submucosal tunnel is to pass a pediatric endoscope down the true lumen into the stomach while the dissecting scope is kept in the distal extent of the submucosal tunnel. Retroflexing the pediatric scope in the stomach shows the location of the scope in the submucosal tunnel and allows clear delineation of the extent of the tunnel below the GEJ. In our experience, this is much more reliable than other techniques including trying to visualize colored saline that has been injected at the end of the submucosal tunnel. Effective disruption of the LES in patients with achalasia opens the door for gastroesophageal reflux disease. We endoscopically evaluated patients 3 months after POEM and found erosive esophagitis in over half, but in nearly all it was LA grade A or B and reliably resolved with initiation of daily PPI medication. The single patient with severe esophagitis had a concomitant hiatal hernia. From this experience we would recommend that the presence of a hiatal hernia is an indication to perform a laparoscopic myotomy with repair of the hiatal hernia and a partial fundoplication rather than a POEM, particularly in young patients. Furthermore, we recommend that after POEM all patients undergo endoscopy and a pH test. In our series only 11% of patients had
Fig 6. High-definition threedimensional manometry showing the lower esophageal sphincter before and after peroral endoscopic myotomy.
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Table 2. Components of Post–Peroral Endoscopic Myotomy pH Studies (n ¼ 10)a Variable Total number of episodes Supine fraction time (%) Upright fraction time (%) Total fraction time (%) Number of episodes >5 min Longest episode (min) Score a
Day 1
Day 2
Total (both days)
37 7.4 1.9 4.8 2 23.5 24.2
32 18.8 2.8 7.8 4 23 34.6
34.5 13.1 2.3 6.3 3 23 29.4
All values expressed as median.
heartburn, yet 55% had esophagitis and 70% had a positive pH test. Relying only on heartburn symptoms would have missed most patients with objective evidence of reflux, and left untreated, these patients may go on to exhibit strictures or Barrett’s esophagus. An alternative is to start everyone on daily PPI therapy after POEM, but there are long-term side effects with these medications. Our approach now is to start a daily histamine type 2 blocker in all patients after POEM, and escalate therapy to a PPI only when symptoms, endoscopy, or pH testing indicate the need for more aggressive acid suppression. We are also considering offering an endoscopic antireflux procedure to young patients with esophagitis or an abnormal pH test after POEM and await reports of the success of this approach from other centers. Alternatively, young patients with significant reflux after POEM could be offered a laparoscopic partial fundoplication. Thus far we have not had any patient whose symptoms or erosive esophagitis were not readily controlled with PPI therapy or who wished to have a partial fundoplication instead of taking acid-suppression medications. With regard to gastroesophageal reflux disease after POEM, a couple of issues bear consideration. First, all therapies for achalasia open a nonrelaxing valve and thereby create the potential for reflux. Long term, most of the failures after treatment in patients with achalasia are related to complications of reflux. Late (>20 years) after a myotomy and partial fundoplication, Csendes and colleagues [13] showed that 53% of patients had a positive pH test. Furthermore, intestinal metaplasia was found on biopsies in almost 30% of these patients. Reflux also occurs after pneumatic dilatation. A follow-up endoscopy at a mean of 8.9 years after PBD in 331 patients with achalasia showed Barrett’s esophagus in 8.4% and esophageal adenocarcinoma in 2 patients (0.6%). Barrett’s developed at a rate of 1% per year, and the risk was higher in those with lower LES pressures and a hiatal hernia [14]. It is likely that POEM, by virtue of the lack of a partial fundoplication, is associated with more reflux early after therapy compared with a laparoscopic myotomy. However, the myotomy during POEM is done in a different anatomic location compared with a laparoscopic myotomy, and the phrenoesophageal ligament is not disrupted with the POEM procedure. The long-term implications of
these differences remain to be seen, and certainly endoscopic follow-up 5 and 10 years after POEM will be important to evaluate for complications of reflux including development of Barrett’s esophagus in these patients. Our initial results with POEM are comparable to those of other published series. Single center and multicenter studies as well as a recent meta-analysis all confirm the safety and efficacy of POEM [15]. A recent meta-analysis included 29 published studies and showed a significant improvement in the Eckhart score and a reduction of LES pressure after POEM [14]. Compared with a laparoscopic Heller myotomy, the meta-analysis showed a trend toward a lower Eckhart score and shorter operative time with POEM with a similar frequency of adverse events and posttherapy gastroesophageal reflux disease symptoms [15]. The published experience from Portland on POEM in 100 patients who had an esophageal motility abnormality showed relief of dysphagia in 97%, significant improvement in esophageal emptying on TBS, and an overall morbidity of 6%. Post-POEM only 5% of patients had heartburn symptoms, but 27% had esophagitis and 38% had a positive 24-hour pH test for reflux [12]. In a prior series from that center limited to patients with achalasia, 50% had a positive pH test after POEM [5]. The frequency of esophagitis and a positive pH test in our series is higher than in other reports, perhaps related to our effort to carry the myotomy 3 cm down onto the stomach and using the retroflexed pediatric endoscope to confirm the distal extent of the submucosal tunnel. Future studies evaluating the ideal proximal and distal extent and location of the myotomy with POEM to relieve symptoms yet minimize reflux will be useful. There has been concern about the longevity of the myotomy with POEM, particularly because in the multiinstitution study from Europe and North America the success rate with POEM decreased from 97% at 3 months to 82% at 1 year [16]. Success can be assessed subjectively, but perhaps a more objective method is with a TBS evaluating esophageal emptying. Using this method, we had follow-up beyond 1 year in 26% of patients who had completed a TBS earlier, at approximately 3 months, and in this group all patients had similar or further improved emptying compared with their initial post-POEM study. This objective evidence indicates that short-term failure or reclosure of the myotomy is unlikely in patients with an initial good response to POEM. From a mechanistic standpoint, it would seem that myotomy reclosure should be a relatively early event, and thus it appears that the myotomy with POEM is effective and long lasting when done well. Although POEM is a complex endoscopic procedure, this series shows that thoracic surgeons with an interest in esophageal surgery and the necessary endoscopic skillset can readily adopt the procedure. Familiarity with the mediastinum and managing esophageal perforations likely makes thoracic surgeons uniquely qualified to perform POEM and manage periprocedural complications. Some thoughts from our initial POEM experience are that prior interventions, a very high IRP, and
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angulation of the esophagus at the GEJ increase the complexity of the procedure. We would recommend that during the initial several cases when there is a proctor present, some of these difficult patients be included so that tricks for addressing these situations can be demonstrated. On the first 5 to 10 cases without a proctor, these types of patients should be avoided if possible to allow independent experience to accumulate on more straightforward patients. If the procedure is not progressing well, there should be no hesitation to terminate it and avoid a potentially major complication in a patient with benign disease. Depending on how close the submucosal tunnel has come to the GEJ, judgment is necessary to decide whether to convert at that time to another type of therapy or to delay reintervention until sufficient time has passed for the tunnel to heal. Lastly, although closure of the mucosotomy with clips is quite reliable, suturing has become our preference in most patients. The low profile of the sutures is appealing, and there is no possibility of a suture falling off as can occur with a clip. The suture closure has been so secure that moving forward we plan to omit postoperative contrast swallows and to begin offering POEM as an outpatient procedure for patients who live locally. The strengths of our study are that it is a consecutive series of the initial patients who underwent POEM by a thoracic surgeon. It is limited by short and incomplete objective follow-up. However, because most patients had excellent symptomatic relief and had no heartburn symptoms, it is unlikely that the objectively studied population was significantly skewed compared with those who did not return for their scheduled studies. Most of those who did not return had travelled a significant distance for the procedure; however, the importance of objective follow-up in these patients cannot be overemphasized. In conclusion, the POEM procedure represents a paradigm shift in the treatment of achalasia in that high efficacy can now be accomplished with low invasiveness. Previously, low efficacy and low invasive options were Botox injection and a single pneumatic dilatation, whereas more invasive and better efficacy options consisted of multiple pneumatic dilatations and laparoscopic Heller myotomy. The POEM procedure provides the efficacy of a laparoscopic Heller with the invasiveness of a single pneumatic dilatation. It may be the best of both worlds, allowing a precise myotomy with the recovery benefits of no external incisions and no physical restrictions. Even during the learning curve, it is safe and provides reliable palliation of the symptoms of achalasia with objective evidence of improved esophageal emptying. Gastroesophageal reflux occurs after all therapies for achalasia, but may be more prevalent after POEM. Objective evaluation for evidence of reflux is warranted after POEM because symptoms are an unreliable indicator of gastroesophageal reflux disease in these patients. When a hiatal hernia is present in a patient with achalasia, a laparoscopic myotomy, partial fundoplication, and repair of the hernia
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may be a better option than a POEM procedure. However, most patients with achalasia do not have a hiatal hernia, and the safety and efficacy of POEM suggest that it deserves a place in the armamentarium of thoracic surgeons interested in the care of patients with benign esophageal disease.
References 1. Sadowski DC, Ackah F, Jiang B, Svenson LW. Achalasia: incidence, prevalence and survival. A population-based study. Neurogastroenterol Motil 2010;22:e256–61. 2. Pandolfino JE, Kwiatek MA, Nealis T, Bulsiewicz W, Post J, Kahrilas PJ. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology 2008;135: 1526–33. 3. Inoue H, Minami H, Satodate H, Kudo S-E. First clinical experience of submucosal endoscopic myotomy for esophageal achalasia with no skin incision. Gastrointest Endosc 2009;69:AB122; Abstract. 4. Pasricha PJ, Hawari R, Ahmed I, et al. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy 2007;39:761–4. 5. Swanstrom LL, Kurian A, Dunst CM, Sharata A, Bhayani N, Rieder E. Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure. Ann Surg 2012;256: 659–67. 6. Boeckxstaens GE, Annese V, des Varannes SB, et al, European Achalasia Trial Investigators. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med 2011;364:1807–16. 7. Rohof WO, Salvador R, Annese V, et al. Outcomes of treatment for achalasia depend on manometric subtype. Gastroenterology 2013;144:718–25. 8. Oelschlager BK, Chang L, Pellegrini CA. Improved outcome after extended gastric myotomy for achalasia. Arch Surg 2003;138:490–7. 9. Ross SW, Oommen B, Wormer BA, et al. National outcomes of laparoscopic Heller myotomy: operative complications and risk factors for adverse events. Surg Endosc 2015 Jan 15; [epub ahead of print]. 10. Greene CL, Chang EJ, Oh DS, Worrell SG, Hagen JA, DeMeester SR. High resolution manometry subclassification of achalasia: does it really matter? Does achalasia sub-classification matter? Surg Endosc 2015;29:1363–7. 11. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010;42:265–71. 12. Sharata AM, Dunst CM, Pescarus R, et al. Peroral endoscopic myotomy (POEM) for esophageal primary motility disorders: analysis of 100 consecutive patients. J Gastrointest Surg 2015;19:161–70. 13. Csendes A, Braghetto I, Burdiles P, Korn O, Csendes P, Henríquez A. Very late results of esophagomyotomy for patients with achalasia: clinical, endoscopic, histologic, manometric, and acid reflux studies in 6 patients for a mean follow-up of 190 months. Ann Surg 2006;243:196–203. 14. Leeuwenburgh L, Scholten P, Calj e TJ, et al. Barrett’s esophagus and esophageal adenocarcinoma are common after treatment for achalasia. Dig Dis Sci 2013;58:244–52. 15. Talukdar R, Inoue H, Reddy DN. Efficacy of peroral endoscopic myotomy (POEM) in the treatment of achalasia: a systematic review and meta-analysis. Surg Endosc 2014 Dec 25; [epub ahead of print]. 16. Von Renteln D, Fuchs KH, Fockens P, et al. Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study. Gastroenterology 2013;145:309–11.e1; e3.
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WORRELL ET AL POEM FOR ACHALASIA
Ann Thorac Surg 2015;-:-–-
DISCUSSION DR KAMAL G. KHALIL (Houston, TX): Just curious if we adopt this as our primary approach, and those of us who do VATS (video-assisted thoracoscopic surgery) myotomy usually combine it with an antireflux procedure. Have you noticed any increase in reflux in those few patients that you followed postoperatively?
DR MATTHEW G. BLUM (Colorado Springs, CO): I was curious, do you do myotomy through just the inner circular muscle, or are you going all the way through the longitudinal muscle as well? And did you have any issues with pneumoperitoneum or pneumothorax?
DR WORRELL: Symptomatic reflux postoperatively was present in about 15% of patients. However, there was a 55% incidence of patients with esophagitis on follow-up endoscopy. Doctor Inoue recently reported on a review of all reported literature on the POEM (peroral endoscopic myotomy), and overall there’s been a 10% incidence of postoperative reflux, which is in line with postlaparoscopic myotomy reflux. The endoscopic myotomy is performed at a different location on the esophagus, potentially maintaining the angle of His; therefore, we propose that there may be a decreased risk of reflux with this procedure compared to what is expected.
DR WORRELL: To minimize the pneumoperitoneum and pneumothorax we exclusively use CO2. We have had about 4 patients who have developed some pneumoperitoneum during the procedure. This was decompressed easily with an 18-gauge catheter into the abdomen. The catheter is removed at the end of the procedure and without sequelae. And then the first part of your question, we intentionally only do a circular muscle myotomy. However, the longitudinal muscles often split just because they’re so thin, and many times it ends up being a full-thickness myotomy.
DR SCOTT I. REZNIK (Dallas, TX): It’s a great presentation. How were you choosing or counseling patients when they’re coming specifically for POEM? Is this your treatment of choice now or is it just something you’re introducing? DR WORRELL: The POEM is our treatment of choice. However, we acknowledge that there are some more complex cases that may benefit from a laparoscopic myotomy. Specifically, patients with hiatal hernias should undergo surgical intervention with repair of the hiatal hernia. Some tortuous distal esophaguses make the POEM more complex. However, with experience there are techniques that can be used to complete the POEM procedure without conversion to a laparoscopic or open procedure. In a surgeon’s initial experience, it is probably best to avoid these kind of patients for POEM. DR REZNIK: Are you routinely putting these patients on PPIs (proton pump inhibitors) or only if they have symptoms of esophagitis or reflux? DR WORRELL: Our current practice is to put all patient on H2 (histamine type 2) blockers post-POEM. All patients then have an endoscopy at 3 months. If esophagitis is present at that time, then we convert them over to a PPI. DR K. ROBERT SHEN (Rochester, MN): What’s the current follow-up long term at your institution for these patients who are undergoing some sort of surgical intervention for achalasia? Do you see them back once postoperative[ly] and then that’s it, or do you see them yearly? DR WORRELL: For the POEM patients, we are routinely seeing them at 3 months to undergo a timed barium swallow and endoscopy. If they have no evidence of esophagitis, then we see them back at a year to assess their symptomatic outcome. DR SHEN: Okay. In the abstract it mentioned that there was follow-up data available on only 56% of the patients, so what happened to the others? DR WORRELL: Our follow-up has increased, many of the patients reported in the initial abstract are now over 6 months out from their operation.
DR BLUM: And you’ve kind of advocated that thoracic surgeons pick this up. I would see probably half a dozen achalasia patients in a year. Is that a sufficient volume to become familiar with the techniques, and would you shy away from any of the patients that had been intervened on before based on your experience especially early on, or did that actually make any difference? DR WORRELL: With our experience, we believe proficiency occurs around 15 to 20 cases. There was a recent publication by a gastroenterologist looking at mastery of the POEM, which they concluded occurred at 60 cases. Additionally, there has been no difference in outcomes or complications based on preoperative therapy, such as Botox or dilation. DR SHEN: Back when laparoscopic Heller myotomy was first gaining traction among the surgical community, it was not uniform to perform an antireflux procedure until the group from Seattle, Washington, with Dr Pellegrini performed a prospective randomized study looking at patients who received some sort of an antireflux procedure versus just the myotomy. And it clearly showed there was a reduction in symptomatic and asymptomatic reflux that could be documented with either endoscopy or pH studies. And that, then, has become sort of the widely adopted standard of care, to combine some sort of antireflux procedure with the myotomy. So in light of that experience, are we really stepping back in time now with doing a myotomy again alone without an antireflux procedure? DR WORRELL: I think that is a very good point. Time will definitely tell us if that is true. At the same time, there has been an increase in the development and use of endoscopic antireflux operations, which may serve as an adjunct therapy for these patients. Additionally, the POEM is performed in a different location along the esophagus, in theory allowing the angle of His to be maintained, and therefore, potentially decreasing the expected incidence of reflux. DR MELANIE A. EDWARDS (St. Louis, MO): I have a quick question. Regarding your esophagitis, how many of them did not resolve with PPI therapy? DR WORRELL: All patients who stuck with the daily PPI regimen had resolution of their esophagitis.