J Gastrointest Surg DOI 10.1007/s11605-014-2610-5

2014 SSAT PLENARY PRESENTATION

Peroral Endoscopic Myotomy (POEM) for Esophageal Primary Motility Disorders: Analysis of 100 Consecutive Patients Ahmed M. Sharata & Christy M. Dunst & Radu Pescarus & Eran Shlomovitz & Aaron J. T. Wille & Kevin M. Reavis & Lee L. Swanström

Received: 15 May 2014 / Accepted: 22 July 2014 # 2014 The Society for Surgery of the Alimentary Tract

Abstract Introduction Peroral endoscopic myotomy (POEM) is a flexible endoscopic approach to the lower esophageal sphincter (LES) providing access for a myotomy to relieve dysphagia. The technique has been adopted worldwide due to reports of excellent short-term clinical outcomes. We report on a consecutive patient cohort with clinical and objective outcomes representing the establishment of a POEM program within a busy esophageal surgical practice. Methods Comprehensive data was collected prospectively on all patients undergoing POEM from October 2010 to November 2013 at a single institution. Patients were classified based on high-resolution manometry (HRM). Operative data and immediate outcomes were reviewed. Symptom scores, HRM, and timed barium swallow (TBS) were performed prior to the procedure. Patients were asked to undergo routine postoperative testing 6–12 months after surgery with the addition of standard 24-h pH to the preoperative protocol. Morbidity was defined as requiring additional procedures or prolonged hospital stay >2 days. Results One hundred POEM patients were included in the final analysis. The mean age was 58 years (18–83 years). Primary presenting symptoms included dysphagia 81, chest pain 10, and regurgitation 9. The mean follow-up was 16 months. HRM diagnoses were 75 achalasia (30 type I, 43 type II, 2 type III), 12 nutcracker esophagus, 5 diffuse esophageal spasm (DES), and 8 isolated hypertensive non-relaxing LES. The mean operative time was 128 min. The median hospital The average LES resting/residual pressure significantlength of stay (LOS) was 1 day. The overall morbidity was 6 %; ly decreased (44.3/22.2 to 19.6/11.7 in millimeters of all were treated endoscopically or with conservative managemercury). Esophageal emptying improved from 40 to ment without further sequelae (three had intra-tunnel leak diag90 % on TBS with 93 % patients demonstrating nosed on routine esophagram and one developed a postoperative >90 % emptying at 1 min. Of the achalasia patients, intra-tunnel hemorrhage, one developed Ogilvie’s, and one re36 % (17/47) showed some return of normal peristalsis quired prolonged intubation for CO2 retention). (≥70 % peristalsis) on post-op HRM. Abnormal acid exposure was present on postoperative testing in 38 % (26/68). Of these, 14 were asymptomatic. This paper was presented at the DDW, May 5th, 2014, Chicago, IL. No reflux patient required additional antireflux procedure. A. M. Sharata : C. M. Dunst : A. J. T. Wille : K. M. Reavis : Eckardt scores decreased from 6 to 1. Dysphagia was L. L. Swanström improved or eradicated in 97 % with a complete resoFoundation for Surgical Innovation and Education, 4805 NE Glisan lution accomplished in 89 %. Complete dysphagia relief St., Suite 6N60, Portland, OR 97213, USA was better for achalasia patients (46/47 patients; C. M. Dunst : K. M. Reavis : L. L. Swanström (*) 97.8 %) vs. non-achalasia patients (17/24; 70.8 %). Of Gastrointestinal and Minimally Invasive Surgery Division, The those with preoperative chest pain, 91.5 % reported Oregon Clinic, 3805 NE Glisan St, Suite 6N60, Portland, OR 97213, complete relief. USA e-mail: [email protected] Four patients have refractory dysphagia. Two nonachalasia patients underwent subsequent laparoscopic Heller C. M. Dunst : R. Pescarus : E. Shlomovitz : L. L. Swanström myotomy and two are improved following serial endoscopic Department of Surgery, Providence Portland Medical Center, 3805 dilatations. NE Glisan St, Suite 6N60, Portland, OR 97213, USA

J Gastrointest Surg

Conclusion This study represents the largest POEM series to date that includes objective data. Despite reflux in one/three of patients, POEM provides excellent relief of dysphagia (97 %) and chest pain (91.5 %) for patients with esophageal spastic disorders with acceptable procedural morbidity. Keywords Esophageal motility disorder . POEM . Endoscopic esophageal myotomy . Achalasia . Long-term follow-up

Introduction The peroral endoscopic myotomy (POEM) procedure is the latest alternative endoscopic treatment for achalasia. POEM has been rapidly adopted worldwide by expert endoscopic surgeons and gastroenterologists who are interested in profound esophageal motility disorders such as achalasia. The first reported endoscopic myotomy was performed on 17 achalasia patients and was published by Ortega in 1980.1 The technique involved dividing both the mucosa and muscle of the lower esophageal sphincter (LES) with two separate full-thickness incisions proximal to the gastroesophageal junction. The clinical, manometric, and radiological postoperative results of all 17 patients were satisfactory with only three minor bleeding episodes, which were ultimately controlled endoscopically. Despite these results, this technique was not adopted, due to its high potential for esophageal perforation. In 2004, Gostout et al.2 described a submucosal flap technique as a safe transmural transit approach for natural orifice transluminal endoscopic surgery (NOTES). It was not until 2007 that Pasricha and his team utilized the procedure and demonstrated its feasibility for endoscopic myotomy in four pigs.3 The flap provided safe access to the circular muscle layer and allowed a myotomy to be performed; it was in fact the division of only the circular muscle of the esophagus and LES that provided the unique benefit of the procedure they described, as it made this method a potentially more “targeted” treatment. Additional animal studies by others, investigating endoscopic transesophageal or transcervical approaches to the division of the distal esophageal muscle layers, also showed the efficacy of the endoscopic approach.4 The first contemporary series of patients that underwent the modern POEM approach for achalasia was described shortly thereafter in 2008 by Haru Inoue, a surgical endoscopist in Japan who is credited with the development of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). He presented four clinical cases of submucosal myotomy for achalasia at the Digestive Diseases Week (DDW) and subsequently published his early results.5 Initially described for achalasia, indications rapidly expanded to more complex cases (reoperations, sigmoid esophagus, pediatric patients) and non-achalasia primary motility disorders such as diffuse esophageal spasm (DES). Currently, around 4,000

cases have been performed worldwide with growing enthusiasm regarding this endoscopic procedure, and most gastroenterological and surgical societies are now offering educational sessions and postgraduate courses on POEM. In spite of this, relatively few series have been published in the peer-reviewed literature and these have largely concentrated on the technique itself or on immediate clinical outcomes. Herein, we report a symptomatic and objective follow-up on a sequential cohort of 100 patients treated by POEM.

Methods Starting in October 2010, all patients presenting with primary esophageal motility disorders, who were felt to be candidates for treatment by laparoscopic esophageal myotomy or achalasia balloon dilation, were invited to participate in an institutional review board-approved outcomes study regarding POEM. Early exclusion criteria (for the first 18 patients) included previous mediastinal or esophageal surgery, age under 18, inability to tolerate general anesthesia, sigmoid esophagus, and a body mass index greater than 40 kg/m2.6 Once the learning curve was completed, the only contraindications that remained were the inability to undergo general anesthesia and the presence of a hiatal hernia. Preoperative assessment included a standardized, validated symptom assessment form with scores for heartburn, regurgitation, reflux, chest pain, and dysphagia graded frequency (grade 0—absent, grade 1—monthly, grade 2—weekly, grade 3—daily, or grade 4—continuous). In addition, the severity of achalasia-like symptoms was staged according to the Eckardt scoring system. Each patient was given a preoperative and postoperative quality of life survey. Patients before 2011 were given an SF-36 survey. Patients from 2011 on were given the more specific GI quality of life questionnaire. Preoperative testing included high-resolution manometry (HRM), esophagogastroduodenoscopy (EGD), and a timed barium swallow (TBS). These three tests and the GI quality of life questionnaire were repeated at 6 months with the addition of a 24-h pH test for gastroesophageal reflux disease. Moreover, an EGD and a GIQOLQ were performed 1 year after POEM. A postoperative Eckardt score of 3 or less (Eckardt stage 0) was considered a successful outcome.7 p2 days.

J Gastrointest Surg

Fig. 1 POEM protocol (QOL quality of life, EGD esophagogastroduodenoscopy, HRM high-resolution manometry, TBS timed barium swallow)

To differentiate technical complications or operative challenges from morbid complications, we classified esophageal injuries with a newly developed “Portland esophagotomy classification” system. Under this categorization system, injuries are defined as follows: Portland I—full-thickness entry esophagotomy, Portland II—mediastinal exposure (longitudinal fiber split), Portland III—esophageal/gastric mucosal injury, and Portland IV—full-thickness esophageal/gastric perforation not on entry (Table 1).

Technique Patients were placed on a clear liquid diet for 24 h prior to the procedure. Prophylactic preoperative antimicrobial therapy included a nystatin swish and swallow for 5 days and a single dose of a first-generation cephalosporin within 30 min of mucosotomy. The patients were placed supine, general anesthesia was administered, and a diagnostic esophagogastroduodenoscopy was performed. An overtube was placed, and the site for the anterior esophageal mucosotomy at least 3 to 4 cm proximal to the high-pressure zone was identified. A 1.5- to 2-cm longitudinal mucosotomy in the mid esophagus was performed after a submucosal wheal was raised. The endoscope was inserted and a submucosal tunnel was created using a combination of blunt dissection, carbon dioxide insufflation, hydro-dissection, and careful electrocautery. The tunnel was extended past the gastroesophageal junction (GEJ) and at least 2 cm onto the gastric cardia. A proximal-to-distal, circular myotomy was next performed, taking care to preserve the longitudinal muscle layers of the esophagus and stomach. Smooth passage of the endoscope through the GEJ, a retroflexed evaluation of the valve, and

a blanched gastric mucosa (indicating the distal dissection), confirmed an adequate myotomy (Fig. 2). The mucosotomy was then closed using standard endoscopic clips or endoscopic suturing (Overstitch, Apollo Medical, San Antonio, TX). All patients were evaluated with a water-soluble contrast esophagogram on the first postoperative day. If normal, they were then started on a pureed diet and subsequently discharged. They maintained this diet for one week and then were allowed regular food.8

Results Patient Demographics and Preoperative Symptom Scores Between October 2010 and October 2013, patients with symptomatic manometrically defined esophageal motility disorders (simultaneous esophageal waves and/or spastic LES) , who were felt to be candidates for laparoscopic esophageal myotomy, were offered participation in an institutional review board-approved POEM study. The first 100 POEM patients were included in the final analysis. The mean age was 58 years (18–83 years). There were 51 men and 49 women with a median duration of symptoms of 25 months (range 2–480). The primary symptom on presentation included dysphagia (81), chest pain (10), and regurgitation (9). The mean follow-up was 21.5 months (6–43.3). Thirty patients had previous endoscopic interventions (botulinum toxin injection alone (20 cases), pneumatic dilation alone (5 cases), both (5 cases)). Five achalasia patients had a previous laparoscopic Heller myotomy. The mean body mass index was 26±5 kg/m2 (range 20–32.8) and the median American Society of Anesthesiology grade was 2 (range 1–3). The median Eckardt score before surgery was 6 (range 2–9).

Table 1 Portland esophagotomy classification • Portland I full-thickness entry esophagotomy • Portland II mediastinal exposure (longitudinal fiber split) • Portland III inadvertent mucosotomy • Portland IV full-thickness perforation Fig. 2 Retroflex view of the gastroesophageal junction

J Gastrointest Surg Table 2 Preoperative characteristics

Age, mean years (SD) BMI Eckardt score, mean (SD) Mean symptom duration (SD) months Presenting symptoms Dysphagia Chest pain Regurgitation Previous endoscopic intervention

Post-Heller myotomy Sigmoid esophagus HRM diagnosis

Achalasia n=75

Non-achalasia n=25

POEM N=100

57

61

6 (2–9) 90

5 (1–7) 80

58 (18–83) 26±5 6 (1–9) 87.6 (2–480)

88 % 2% 10 % 14 Botox injection 2 dilatation

72 % 20 % 8% 6 Botox injection 3 dilatation

2 both 5

3 both 0

30 type I 43 type II 2 type III

12 nutcracker 8 hypertensive non-relaxing LES 5 DES

Fifty-seven patients had Eckardt stage 3 achalasia with five of them having an “end-stage” sigmoid esophagus (Table 2). Preoperative Testing HRM was used for the diagnosis and classification of esophageal spastic disorder according to the Chicago classification. Seventy-five patients had achalasia (30 type I, 43 type II, 2 type III), and five of those patients were postHeller myotomy. Twenty-five non-achalasia patients were diagnosed by HRM and classified as 12 with nutcracker esophagus(hypercontractile), 5 diffuse esophageal spasm (DES), and 8 isolated hypertensive non-relaxing LES. The median resting and residual pressures at the lower esophageal

Table 3 Operative details POEM n=100 Operative time (min) Myotomy length (cm) Closing clips Median hospital LOS (days) Esophagotomy Full-thickness entry esophagotomy Esophageal/gastric mucosotomy Full-thickness other than entry Mediastinal exposure (longitudinal fiber split) Capnoperitoneum Returning to regular activities (days)

128 (45–215) 8 (4–23) 5 (3–11) 1 2 21 0 100 11 4 (2–8)

81 % 10 % 9% 30 %

5% 5%

sphincter were 45 mmHg (range 5–74) and 22 mmHg (range 5– 40), respectively. The mean distal esophageal contraction amplitude was 59 mmHg. The median preoperative esophageal emptying was 40 % at 5 min on TBS (range 4–100 %) (Table 2). Perioperative Data The mean operative time was 128 min. The median hospital length of stay (LOS) was 1 day (8 h–2 weeks). All procedures were completed endoscopically and there were no conversions to laparoscopy. The median myotomy length was 8 cm (range 4–23). The median number of clips used to close the mucosotomy was 5 (range 3–11). The average return to regular activity was 4 days post-POEM (range 2–8). According to the Portland esophagotomy classification of non-morbid intraoperative technical events, there were two patients who had full-thickness entry esophagotomy (Portland I injury), which were closed by endoscopic suturing. All patients had some degree of mediastinal exposure

Table 4 Morbidity details POEM n=100 Overall morbidity Mucosotomy dehiscence (intra-tunnel contained leak) Intra-tunnel hemorrhage Prolonged intubation for CO2 retention Ogilvie’s syndrome

6% 3 1 1 1

J Gastrointest Surg

Fig. 3 Timed barium swallow

(longitudinal fiber split—Portland II injury), 21 patients had esophageal/gastric mucosal injuries (Portland injury III) that were closed by one or two endoscopic clips. There were no full-thickness esophageal/gastric perforations (Portland injury IV) other than the tunnel entry site. These events were felt to be technical issues related to a learning curve and none had an impact on the clinical outcome or required additional intervention (Table 3). Eleven of 100 patients developed clinically significant capnoperitoneum and underwent Veress needle decompression during the surgery. The overall morbidity was 6 %, and all were treated endoscopically or managed conservatively without further sequelae. Three patients had an intra-tunnel leak (mucosotomy dehiscence) diagnosed on routine postoperative esophagogram and managed by repeat endoscopy and additional endoscopic clip application. None of these were associated with clinical signs of sepsis. Another patient developed an intra-tunnel hemorrhage

on postoperative day 3, which resolved with re-admission and conservative treatment. One patient with multiple medical comorbidities developed Ogilvie’s syndrome, which was treated medically, and one patient with chronic lung disease required overnight intubation for excessive CO2 retention (Table 4). Objective Outcomes All patients were asked to come back at 6 months for objective testing. In all, objective follow-up tests were available for 87 % of patients. Ten patients refused to have any further objective testing since they were feeling well or lived long distances away, and three patients died several months after POEM from unrelated pathologies: drug overdose, brain lymphoma, and bleeding disorder. Timed Barium Swallow Postoperative TBS was available on 55 of 100 patients. The median percent of emptying at 1 min significantly improved preoperatively from 40 % (range 4–100 %) to 90 % (range 70– 100 %) at 6 months (p=0.003). Only four patients failed to completely empty their esophagus at 1 min (80 % emptying) (Fig. 3). Esophagogastroduodenoscopy

Fig. 4 High-resolution manometry pre- and post-POEM results

Seventy-three patients had a 6-month postoperative EGD. Twenty patients had esophagitis classified using the Los Angeles classification: 15 patients had grade A, 3 patients

J Gastrointest Surg

Fig. 5 High-resolution manometry showing post-POEM recovered peristaltic activity

had grade B, and 2 patients had grade C esophagitis. On endoscopic retroflexion, 18 patients had a valve of Hill grade 1, 35 patients had Hill grade 2, 14 had a Hill grade 3, and 6 had a Hill grade 4 valve.

High-Resolution Manometry Postoperative HRM has been performed so far in 65 patients. Significant decreases were seen postoperatively in the median values of lower esophageal sphincter pressure characteristics. The median lower esophageal sphincter resting pressure significantly decreased from 44.3 to 19.6 mmHg (p=0.0001). More importantly, the median lower esophageal sphincter residual pressures decreased significantly from 22.2 to 11.7 mmHg (p=0.0001) (Fig. 4). There were also significant reductions in esophageal pressurization both during swallows and between swallows. Of the achalasia patients, 36 % (17/47) recovered some degree of peristaltic activity with median peristaltic swallows of 70 %, with a range of 40–100 % (Fig. 5).

Twenty-four-hour pH Testing A total of 68 patients have had postoperative 24-h pH testing. Twenty-six had acid exposure >14.7 of DeMeester score, giving an objective evidence of gastroesophageal reflux disease in 38.2 % of patients. Of these, 13 (50 %) were asymptomatic. All patients with abnormal pH studies were placed on daily H2 blockers or PPI. No patients have required an antireflux procedure for persistent symptoms (Fig. 6).

Subjective Follow-Up The mean Eckardt scores decreased from 6 to 1 with only eight patients having a score greater than 3. Dysphagia was improved or eradicated in 97 % with complete resolution (Eckardt=0) accomplished in 89 %. Complete dysphagia relief was better for achalasia patients (46/47 patients; 97.8 %) than for non-achalasia patients (17/24; 70.8 %). Of those with preoperative chest pain, 91.5 % reported complete relief (Table 5). Four patients had refractory dysphagia. Two of them were non-achalasia patients who, after failing several dilations, eventually underwent laparoscopic Heller myotomy. Interestingly, their symptoms remained refractory even after laparoscopic myotomy. The other two were achalasia patients who showed improvement with one to three endoscopic dilations.

Quality of Life

Fig. 6 DeMeester score results of pH test 6 months post-POEM

Forty-one patients completed pre- and post-quality of life (QOL) questionnaires. The SF-36 questionnaire showed improvements in all eight categories, but the only statistically significant change was in the “vitality” summary score of the SF-36 questionnaire as shown in Table 6 and Fig. 7. GI quality of life questionnaires showed significant increases in their mean quality of life pre- and post-POEM from 84.7 to 110.5 (p=0.0012) as shown in Table 7 and Fig. 8.

J Gastrointest Surg Table 5 Subjective outcomes Symptoms

Achalasia

Non-achalasia

POEM n=100

Mean follow-up (months) Eckardt score Dysphagia relief

20.1 1 97 %

23

Chest pain relief Heartburn Regurgitation

100 % 5 % (3/59) 6.7 % (4/59)

75 % 18 % (4/22) 18 % (4/22)

Discussion All treatments currently available for achalasia target the LES with the goal of palliating the patient's symptoms of dysphagia. POEM has been shown to be a good alternative to surgical myotomy or balloon dilation as it is less morbid than surgery and more effective than pneumatic dilation or Botox treatments. Our series, together with a growing international experience, confirms that the POEM technique is safe, effective, and can be applied to a wide range of spastic esophageal motility disorders. It is also a teachable procedure, with a learning curve of around 20 cases.9 After our early experience, we felt comfortable with the technique and have expanded our indications to include more challenging indications and anatomies (multiple previous interventions, sigmoid esophagus, small diverticuli, etc.). As POEM is a refluxogenic procedure for at least one in three patients, patients with concurrent hiatal hernia should only be offered the procedure cautiously and we prefer a laparoscopic approach to allow concomitant hernia repair and partial fundoplication. Currently, we believe that the only absolute contraindication to POEM remains an inability to undergo general anesthesia. The theoretical benefit of POEM is that it allows a selective myotomy, dividing only the diseased circular and sling muscles of the LES and proximal stomach. In fact, animal studies have specifically shown that the preservation of the longitudinal muscle layer does not compromise the effectiveness of the myotomy.10 The practical advantage of POEM is that, by avoiding body wall trauma and extensive dissection of the esophageal hiatus,11 the procedure is mostly pain-free and allows patients to resume normal activities a couple of days after the surgery. In our series, improvement in dysphagia was seen in 97 % of patients and complete resolution of dysphagia was noted in 89 %. This is in line with the excellent 82–100 % dysphagia relief from other treatments presented in the literature.21,22 As might be anticipated, complete dysphagia relief was better in achalasia patients (97.8 %) as compared to the non-achalasia (70.8 %) patients. The median hospital stay was 1 day and the average return to regular activities was 4 days; in line with the

70 %

21.5 (43–5.6) 1 89 % complete 97 % complete 91.5 % complete 8 % (7/81) 10 % (8/81)

minimally invasive character of endoscopic surgery. There was an acceptably low failure rate of 2 %. This emphasizes another advantage of POEM, which is that if it does fail, other surgical options are still available and as easily performed as a “virgin” case, as opposed to a risky and difficult redo case.12 Conversely, we and other colleagues have successfully performed POEM on patients who had a failed previous Heller myotomy, which is a complex and – difficult procedure when approached laparoscopically.13 15 POEM also provides an excellent avenue for performance of a long myotomy (up to 23 cm length in this series) for diffuse esophageal spasm which otherwise requires a thoracic approach.16 In our series, 25 patients underwent POEM for non-achalasia neuromuscular disorders (NAND). Twelve had nutcracker esophagus with/without non-relaxing LES, eight had hypertensive non-relaxing LES, and five patients had DES. Although symptom control was not as good as for achalasia patients, complete resolution of dysphagia was seen in 70.8 % and complete resolution of chest pain in 71.5 % of these NAND patients. As with any technique, POEM is not devoid of intraoperative technical difficulties, particularly injury to the esophagus during dissection. We struggled with how to characterize some of these

Table 6 SF-36 quality-of-life data SF-36 quality of life Domain

PF RP BP GH VT SF RE MH

Pre-POEM

Post-POEM

p value

Mean

Std. dev.

Mean

Std. dev.

80.588 72.059 69.882 69.294 52.647 83.088 98.041 72.235

21.7861 34.4081 17.8286 17.6024 18.6344 22.5092 8.0764 18.6800

85.294 72.059 69.235 74.176 64.118 91.912 90.194 77.647

18.6640 38.4081 26.2191 18.4229 15.8346 15.2717 22.8747 15.8782

0.336 0.436 0.903 0.282 0.003 0.062 0.104 0.060

J Gastrointest Surg

Fig. 7 SF-36 quality of life questionnaire (PF physical functioning, RP role limitation (physical), BP bodily pain, GH general health, VT vitality, SF social functioning, RE role limitation (emotional), MH mental health)

operative injuries as most do not result in clinical problems as long as they are recognized and treated at the time of the intervention. Given the potential confusion in the terminology of these events we have proposed a new “Portland classification” (Table 1) that differentiates “inadvertent mucosal injury” from “mediastinal exposure” from “full-thickness perforation.” We find that some degree of mediastinal exposure, or longitudinal muscle fiber splitting, happens in almost all cases and should not be considered a complication of the technique as it results in no adverse clinical outcomes. Inadvertent mucosal injuries, burns or small perforations, also happen often (21 % in the current series) and are also clinically irrelevant but, as they happened mostly early on in our experience, they are something we have described as a learning curve marker.9 Less frequent were full-thickness entry esophagotomy (2 %). Though all three patients who had this did well, these are more concerning technical problems as they would have presumably caused problems if not carefully repaired during the procedure. The incidence of symptomatic capnoperitoneum necessitating Veress needle placement was 11 % in this series. It seems to occur even when there is no full-thickness breach of the esophageal wall and therefore is not presented as a complication. Capnoperitoneum was twice as likely in patients with a history of weight loss more than 20 lb (odds ratio of 2) compared to patients without a history of weight loss. Our overall true complication rate was low, at just 6 %, and includes three cases of mucosal closure dehiscence, a case of an intra-tunnel bleed, a

patient with prolonged CO retention, and a 6th who developed Ogilvie’s syndrome. No deaths or major morbidities were encountered. The mucosotomy closure failures were detected on our routine post-op day 1 contrast studies. Some have advocated against routine postoperative contrast studies, and, while it is true that these intra-tunnel contrast leaks were completely asymptomatic, we believe it is still too early in the experience to recommend against routine studies, especially early in one’s learning curve. We show that the rate of GERD post-POEM is not insignificant. This rate in our current series is 38 %. However, this is not substantially different than the objective reflux rate following laparoscopic Heller and partial fundoplication. In a recent multi-institutional study, there was 21–42 % of abnormal pH studies at long-term follow-up of a series of laparoscopic myotomies with fundoplication.23 This has been confirmed in – multiple other studies.23 28 It is important to note that 50 % of the post-POEM patients who were shown to be refluxing were asymptomatic, which highlights the importance of objective long-term follow-up to avoid potential consequences from this iatrogenic GERD. For patients who did have symptoms, these symptoms were mostly mild and all were easily controlled medically. Currently, we highly recommend objective testing to identify reflux (EGD and or pH) rather than empiric antisecretory medications as such a strategy would result in unnecessarily medicating the majority of patients. Lastly, we have experienced that the POEM technique can be successfully taught to less-experienced individuals without a significant sacrifice in outcomes. At our institution, most POEM cases are now performed by senior level surgical trainees under faculty supervision. However, it is true that POEM remains an advanced flexible endoscopic procedure requiring precise maneuvers and knowledge of an array of endoscopic tools such as endoscopic suturing devices is

Table 7 GI quality of life data

Mean SD

Pre-POEM

Post-POEM

p value

74.71 25.030

110.50 26.825

0.0012 Fig. 8 Gastrointestinal quality of life questionnaire

J Gastrointest Surg

absolutely necessary. Proper patient selection is also critical, and preoperative evaluation with comprehensive physiologic testing should be mandatory, including a review of the raw manometric data. Therefore, we feel that at this point, POEM should be restricted to interventionalists with regular endoscopic experience and detailed knowledge of esophageal physiologic testing.

Conclusion In our first 100 POEM patients, subjective and objective follow-up demonstrates excellent relief of dysphagia, particularly for achalasia patients. Even in the traditionally difficultto-treat esophageal spasm patients, a clinical resolution of dysphagia and chest pain is seen in two out of three patients. An acceptable 38 % incidence of GERD is seen, with all these patients having good symptomatic control with medical treatment. We stress the need for long-term objective follow-up to better understand the long-term success rate of the procedure as well as any long-term effects of POEM-induced GERD.

Conflict of Interest No support or funding was obtained for this study.

References 1. Ortega JA, Madureri V, Perez L. Endoscopic myotomy in the treatment of achalasia. Gastrointest Endosc. 1980 Feb;26(1):8–10. 2. Rajan E, Gostout CJ, Feitoza AB, Leontovich ON, Herman LJ, Burgart LJ, Chung S, Cotton PB, Hawes RH, Kalloo AN, Kantsevoy SV, Pasricha PJ. Widespread EMR: a new technique for removal of large areas of mucosa. Gastrointest Endosc. 2004;60(4): 623–7. 3. Pasricha PJ, Hawari R, Ahmed I, Chen J, Cotton PB, Hawes RH, Kalloo AN, Kantsevoy SV, Gostout CJ. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy. 2007;39(9):761–4. 4. Swanström LL, Perretta S. Interventional endoscopy and single incision surgery. Ann N Y Acad Sci. 2011;1232:411–7. doi:10.1111/j. 1749-6632.2011.06058.x. 5. Inoue H, Minami H, Kobayashi Y, Sato Y, Kaga M, Suzuki M, Satodate H, Odaka N, Itoh H, Kudo S. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010;42(4):265–71. doi: 10.1055/s-0029-1244080. Epub 2010 Mar 30. 6. 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(4):659–67. doi: 10.1097/ SLA.0b013e31826b5212. 7. Gockel I, Junginger T. The value of scoring achalasia: a comparison of current systems and the impact on treatment–the surgeon’s viewpoint. Am Surg. 2007;73(4):327–31. 8. Sharata A, Kurian AA, Dunst CM, Bhayani NH, Reavis KM, Swanstrom LL. Technique of per-oral endoscopic myotomy (POEM) of the esophagus (with video). Surg Endosc. 2014;28(4): 1333. doi: 10.1007/s00464-013-3332-6. 9. Kurian AA, Dunst CM, Sharata A, Bhayani NH, Reavis KM, Swanström LL. Peroral endoscopic esophageal myotomy: defining

the learning curve. Gastrointest Endosc. 2013;77(5):719–25. doi: 10. 1016/j.gie.2012.12.006. 10. Bonin EA, Moran E, Bingener J, Knipschield M, Gostout CJ. A comparative study of endoscopic full-thickness and partial-thickness myotomy using submucosal endoscopy with mucosal safety flap (SEMF) technique. Surg Endosc. 2012;26(6):1751–8. doi: 10.1007/ s00464-011-2105-3. 11. Simić AP, Radovanović NS, Skrobić OM, Raznatović ZJ, Pesko PM. Significance of limited hiatal dissection in surgery for achalasia. J Gastrointest Surg. 2010;14(4):587–93. doi: 10.1007/s11605-0091135-9. 12. Teitelbaum EN, Soper NJ, Hungness ES. Per-oral esophageal myotomy (POEM) and subsequent salvage laparoscopic heller myotomy. Gastroenterology. 2012;142:S1031–S1032. 13. Vigneswaran Y, Yetasook AK, Zhao JC, Denham W, Linn JG, Ujiki MB. Peroral Endoscopic Myotomy (POEM): Feasible as Reoperation Following Heller Myotomy. J Gastrointest Surg. 2014 Mar 22. 14. Onimaru M, Inoue H, Ikeda H, Yoshida A, Santi EG, Sato H, Ito H, Maselli R, Kudo SE. Peroral endoscopic myotomy is a viable option for failed surgical esophagocardiomyotomy instead of redo surgical Heller myotomy: a single center prospective study. J Am Coll Surg. 2013;217(4):598–605. Doi:10. 1016/j.jamcollsurg.2013.05.025. 15. Zhou PH, Li QL, Yao LQ, Xu MD, Chen WF, Cai MY, Hu JW, Li L, Zhang YQ, Zhong YS, Ma LL, Qin WZ, Cui Z. Peroral endoscopic remyotomy for failed Heller myotomy: a prospective single-center study. Endoscopy. 2013;45(3):161–6. doi: 10.1055/s-0032-1326203. 16. Minami H, Isomoto H, Yamaguchi N, Ohnita K, Takeshima F, Inoue H, Nakao K. Peroral endoscopic myotomy (POEM) for diffuse esophageal spasm. Endoscopy. 2014;46 Suppl 1:E79-81. doi: 10. 1055/s-0032-1309922. 17. Ling TS, Guo HM, Yang T, Peng CY, Zou XP, Shi RH. Effectiveness of peroral endoscopic myotomy in the treatment of achalasia: A pilot trial in Chinese Han population with a minimum of 1-year follow-up. J Dig Dis. 2014. doi: 10.1111/1751-2980.12153. 18. Swanström LL, Rieder E, Dunst CM. A stepwise approach and early clinical experience in peroral endoscopic myotomy for the treatment of achalasia and esophageal motility disorders. J Am Coll Surg. 2011;213:751–756. 19. ZHOU PH, CAI MY, YAO LQ, ZHONG YS, REN Z, XU MD, CHEN WF, QIN XY. [Peroral endoscopic myotomy for esophageal achalasia: report of 42 cases]. Zhonghua Wei Chang Wai Ke Za Zhi. 2011;14(9):705–8. 20. Inoue H, Tianle KM, Ikeda H, Hosoya T, Onimaru M, Yoshida A, Minami H, Kudo SE. Peroral endoscopic myotomy for esophageal achalasia: technique, indication, and outcomes. Thorac Surg Clin. 2011;21(4):519–25. Doi: 10.1016/j.thorsurg.2011.08.005. 21. Stavropoulos SN, Modayil RJ, Friedel D, Savides T. The International Per Oral Endoscopic Myotomy Survey (IPOEMS): a snapshot of the global POEM experience. Surg Endosc. 2013;27(9): 3322–38. doi: 10.1007/s00464-013-2913-8. 22. Von Renteln D, Fuchs KH, Fockens P, Bauerfeind P, Vassiliou MC, Werner YB, Fried G, Breithaupt W, Heinrich H, Bredenoord AJ, Kersten JF, Verlaan T, Trevisonno M, Rösch T. Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study. Gastroenterology. 2013;145(2):309–11.e1-3. doi: 10.1053/j.gastro.2013.04.057. 23. Rawlings A, Soper NJ, Oelschlager B, Swanstrom L, Matthews BD, Pellegrini C, Pierce RA, Pryor A, Martin V, Frisella MM, Cassera M, Brunt LM. Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomized-controlled trial. Surg Endosc. 2012;26(1):18–26. doi: 10.1007/s00464-011-1822-y. 24. Khajanchee YS, Kanneganti S, Leatherwood AE, Hansen PD, Swanström LL. Laparoscopic Heller myotomy with Toupet

J Gastrointest Surg

25.

26.

27.

28.

fundoplication: outcomes predictors in 121 consecutive patients. Arch Surg. 2005;140(9):827–33; discussion 833–4. 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 67 patients for a mean follow-up of 190 months. Ann Surg. 2006;243(2):196–203. Wright AS, Williams CW, Pellegrini CA, Oelschlager BK. Longterm outcomes confirm the superior efficacy of extended Heller myotomy with Toupet fundoplication for achalasia. Surg Endosc. 2007;21(5):713–8. Boeckxstaens GE, Annese V, des Varannes SB, Chaussade S, Costantini M, Cuttitta A, Elizalde JI, Fumagalli U, Gaudric M, Rohof WO, Smout AJ, Tack J, Zwinderman AH, Zaninotto G, Busch OR; European Achalasia Trial Investigators. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med. 2011;364(19):1807–16. doi: 10.1056/ NEJMoa1010502. Richards WO, Torquati A, Holzman MD, Khaitan L, Byrne D, Lutfi R, Sharp KW. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: a prospective randomized double-blind clinical trial. Ann Surg. 2004;240(3):405–12; discussion 412–5.

Discussant Dr. Eric S Hungness (Chicago, IL): I would like to first offer congratulations on a fine presentation, although the title is a little misleading since type 1 and type 2 achalasia really are not “spastic” esophageal disorders. The Oregon Clinic group is to be commended for taking the US lead for POEM and continuing to offer the surgical community updates on their experience with this promising procedure. This presentation outlines 2-year data demonstrating outstanding clinical improvement and low morbidity on par with that of Heller myotomy. I have 3 questions: The first is regarding recognized full-thickness and mucosal perforations (23 % of your cases), which seem quite high, and your training program. In your previously published learning curve manuscript, there was a 40 % mucosal injury rate during your first 25 cases which then appropriately dropped to 6 % for the last part of that study up to patient

40. If my calculations are correct, the mucosal or full-thickness injury rate has increased to 22 % for the last 60 cases where fellows have been the primary surgeon. What do you think has contributed to the higher rate recently, and if so, what is being done to address it? Does it even really matter? Second, were you able to evaluate your POEM achalasia outcomes, such as reflux rates, in regard to the Chicago classification subtype? Lastly, are there any contraindications to POEM or any subset of patients that would benefit more from a laparoscopic myotomy instead of POEM, such as those with hiatal hernia or obesity?

Closing Discussant Dr. Sharata: Thank you Dr. Hungness for your comments. The answer for the first question regarding inadvertant mucosotomy is it is truly a learning curve marker. Our previously published learning curve paper represented our early experience showed this clearly; since then, we have trained an additional six fellows. The fellows were the primary surgeons for most of the POEM procedures, and as expected, their learning curve contributed to the increased mucosotomy injury rate. In general, we recommend training for POEM on porcine explants and live porcine models to shorten the learning curve. We have shown that the mucosotomy injuries do not affect the clinical outcomes of the POEM patients. Therefore, mucosotomy injury is not included as one of the morbid complications according to the Portland esophagotomy classification of POEM and remains just a learning curve marker. Unfortunately, I am unable to tell you the clinical outcomes of our POEM achalasia patients according to the Chicago classification since we have only 3 patients with type III achalasia compared to the larger number of patients for achalasia types I and II. Since POEM is a refluxogenic procedure for at least one/three of patients, we feel hiatal hernia is a contraindication except under very specific circumstances. Generally, we prefer a laparoscopic myotomy to allow concomitant hernia repair and partial fundoplication. Currently, the only absolute contraindication to POEM is a lack of ability to undergo general anesthesia. In contrast, we believe that obese patients and non-achalasia patients can obtain great benefits from having the POEM procedure as compared with a laparoscopic myotomy.