Surg Endosc DOI 10.1007/s00464-015-4193-y
and Other Interventional Techniques
A utility of peroral endoscopic myotomy (POEM) across the spectrum of esophageal motility disorders Toshitaka Hoppo1 • Shyam J. Thakkar1 • Lana Y. Schumacher1 • Yoshihiro Komatsu1 Steve Choe1 • Amit Shetty1 • Sara Bloomer1 • Emily J. Lloyd1 • Ali H. Zaidi1 • Mathew A. VanDeusen1 • Rodney J. Landreneau1 • Abhijit Kulkarni1 • Blair A. Jobe1
•
Received: 10 February 2015 / Accepted: 24 March 2015 Ó Springer Science+Business Media New York 2015
Abstract Background Peroral endoscopic myotomy (POEM) has been performed as a novel endoscopic procedure to treat achalasia with favorable outcome. The objective of this study was to assess the outcome of POEM in our initial series and to assess the safety and efficacy of POEM in a variety of esophageal motility-related clinical problems. Methods This is a retrospective cross-sectional study involving all patients with esophageal motility disorders defined by the Chicago classification, who had undergone consideration for POEM at our institution. Validated questionnaires such as gastroesophageal reflux disease healthrelated quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease-specific health-related quality of life were obtained pre- and postoperatively. Results From January 2013 to October 2014, a total of 35 POEMs (achalasia n = 25, non-achalasia n = 10) were performed on 33 patients (female n = 20, male n = 13, mean age 56.9 years). There was no mortality. The rate of inadvertent mucosotomy was 17.1 %. The rate of complications requiring interventions was 5.7 %. During a mean follow-up period of 7 months (range 0.5–17), 92 % of patients with achalasia and 75 % of those with non-achalasia motility disorders had a symptomatic improvement in dysphagia. Chest pain was completely resolved in all patients with achalasia (8/8) and 80 % of patients with non-
& Toshitaka Hoppo [email protected] Blair A. Jobe [email protected] 1
Esophageal and Lung Institute, Allegheny Health Network, 4800 Friendship Avenue, Suite 4600, Pittsburgh, PA 15224, USA
achalasia (4/5). The GERD-HRQL, RSI and dysphagia scores significantly improved after POEM in patients with achalasia. There was a significant improvement in GERDHRQL and RSI scores, and a trend toward lower dysphagia score in patients with non-achalasia. Conclusions The outcome of POEM to treat achalasia and non-achalasia motility disorders is consistent with previous studies. Potential benefit of POEM includes not only its flexibility to adjust the length and location of myotomy but also the ability to extend myotomy proximally without thoracoscopy or thoracotomy. POEM can be combined with laparoscopic procedures and used as ‘‘salvage’’ for localized esophageal dysmotility. Keywords POEM Achalasia Non-achalasia esophageal motility disorders Questionnaires Dysphagia Chest pain
Achalasia is the most common esophageal motility disorder but is relatively rare with a prevalence of 0.5–1 per 100,000 populations per year without a gender predilection [1]. The inflammatory loss of ganglion cells in the myenteric plexus of the esophageal body and lower esophageal sphincter (LES) causes the inability of LES to relax and absence of esophageal body peristalsis, leading to dysphagia, regurgitation of retained food and chest pain [2–4]. Since none of the treatments can restore the impaired muscle activity of esophageal body and LES, the goal of treatment is palliative and aimed at improving esophageal outlet obstruction by dividing the LES while minimizing gastroesophageal reflux. For this purpose, pneumatic dilation and surgical myotomy have been most commonly performed. Although the recent randomized controlled study comparing pneumatic dilation with surgical myotomy demonstrated no difference in the
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short-term efficacy [5], multiple sessions of dilation are often required (with a 4 % perforation risk), and therefore, surgical myotomy has been considered as the most effective treatment in the USA. [6–9] With the advances in minimally invasive surgical techniques, a laparoscopic Heller myotomy with a partial fundoplication (Dor or Toupet) has been most commonly performed since the randomized controlled study by Richards and colleagues demonstrated that the addition of partial fundoplication significantly reduced postoperative gastroesophageal reflux from 47.6 to 9.1 % (p = 0.005) [10]. Since the introduction of high-resolution manometry, nonachalasia esophageal motility disorders such as hypercontractile esophagus and diffuse esophageal spasm have been more readily identified. The Chicago classification criteria have been utilized to define esophageal motility disorders based on several parameters of esophageal pressure topography [11]. Unlike achalasia, the treatment strategy of nonachalasia esophageal motility disorders is still controversial. Esophageal contractility may be secondary to chronic gastroesophageal reflux disease (GERD), and the treatment of GERD has been commonly recommended with unpredictable outcomes. However, esophageal hypercontractilily is often persistent even after the appropriate control of GERD, and a long myotomy over the entire length of intrathoracic esophagus via thoracoscopy or thoracotomy is considered to eliminate the persistent esophageal contractility. Peroral endoscopic myotomy (POEM) has been rapidly accepted by endoscopists and endoscopic surgeons since the promising outcomes of POEM on the initial 17 patients with achalasia [12]. More than 1200 POEMs have been performed worldwide, demonstrating its feasibility and safety with equivalent short-term outcomes to conventional laparoscopic Heller myotomy [13–20]. The indication for POEM has been extended to treat more complicated achalasia (e.g., sigmoid esophagus, failure of previous myotomy) and other spastic esophageal motility disorders. At our institution, we started POEM on patients with simple type II achalasia and successfully applied POEM to a variety of esophageal motility-related clinical problems. The objective of this study was to assess the outcome of POEM in our initial experience and to assess the efficacy and safety of POEM in a variety of esophageal motilityrelated clinical problems.
Materials and methods Study design This retrospective cross-sectional study was performed under the approval of institutional review board of the Allegheny Health Network. Subjects included all patients who
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had undergone consideration for myotomy at our institution from January 2013 to October 2014. All patients underwent esophagram, upper endoscopy, high-resolution manometry and pH testing (if applicable) as a requisite for preoperative assessment. Detailed demographic data (sex, age, BMI), clinical data (pre-/postoperative symptom scores, past medical/surgical history, medication use, duration of symptoms, procedure time, length of hospital stay) and objective data (endoscopic/radiographic findings, manometric findings) were obtained per protocol. To assess the impact of POEM on symptoms and quality of life, all patients were asked to complete validated questionnaires including GERD health-related quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease-specific health-related quality of life, pre- and postoperatively. High-resolution manometry High-resolution manometry (HRM) was performed using a solid-state assembly with 36 circumferential sensors spaced at 1 cm intervals, and manometric data were analyzed using ManoViewTM v2 Analysis software (ManoScan, Given Imaging, Inc. Duluth GA). The preoperative HRM was used to classify patients with esophageal motility disorders according to the Chicago classification v2.0. Clinical perspective was augmented through the calculation of esophageal clearance of swallows of saline liquids and solids (selectively) measured by impedance electrodes coupled with the HRM catheter. Symptom assessment using validated questionnaires All patients were thoroughly interviewed at every clinic visit, and the pre- and postoperative symptoms were previously recorded in the medical charts. Additionally, all patients were asked to fill out validated questionnaires preoperatively, at 6 weeks and at 6 and 12 months postoperatively. The validated questionnaires included GERDHRQL, RSI and achalasia disease-specific health-related quality of life. GERD-HRQL consists of 10 questions which specifically address GERD symptoms [21]. Each question has a score ranging from 0 to 5, and the best possible aggregate score is 0 (asymptomatic), and the worse score is 50 (very severe symptoms). A total score of C 10 is considered abnormal. The RSI was used to assess atypical GERD symptoms [22]. The RSI consists of 9 questions, and each question has a potential score ranging from 0 to 5. A total score [13 is considered abnormal. The severity of dysphagia was scored using the achalasia disease-specific health-related quality of life questionnaire including food tolerance, dysphagia-related behavior modifications, pain, heartburn, distress, lifestyle limitation and satisfaction [23]. Total raw scores were calculated by
Surg Endosc
summing the score for each item to yield a score between 10 and 31 and were recalibrated to interval-level scores from 0 to 100, with higher values indicating greater disease severity. Comparing the postoperative scores with the preoperative scores on each questionnaire, the rate of symptomatic improvement was calculated. Technique of POEM Preoperatively, patients were asked to stay on liquid diet for a 3-day period, and a nystatin swish, swallow solution, was given for 5 days. A single dose of a first-generation cephalosporin and 100 mg of fluconazole were given intravenously 1 h prior to the procedure. POEM was performed as previously published, in the operating room under general anesthesia [12]. Briefly, patients were placed in the supine position and esophagogastroduodenoscopy was performed using a standard upper endoscope (GIFHQ190 or GIF-H190, Olympus USA, Center valley, PA) with CO2 insufflation. The location of anatomic gastroesophageal junction (GEJ) was measured, and the presence of mucosal changes such as esophagitis was recorded. For type I and II achalasia, the mucosotomy was created 15 cm proximal to the GEJ. For other spastic esophageal motility disorders, the location of mucosotomy was selected by correlating with HRM measurement. In these patients, the location for myotomy most commonly occurred 3 cm proximal to the upper border of the endoscopically visualized forceful esophageal contraction. Following submucosal injection of normal saline mixed with indigo carmine to create a submucosal cushion, a 1.5- to 2-cm longitudinal mucosal incision was applied on the anterior esophageal wall (2 o’clock position) using a triangle-tip knife (TT knife, Olympus USA, Center Valley, PA). Once the access to the submucosal space was created, a gastroscope with plastic cap was introduced into the submucosal space, and a submucosal tunnel was created using endoscopic submucosal dissection with the TT knife. Large bridging vessels were carefully cauterized with coagulation graspers. The tunnel was extended at least 3 cm onto the proximal stomach across the GEJ. Myotomy was initiated 2–3 cm proximal to the distal edge of mucosotomy. Once the plane between circular and longitudinal muscles was identified, a proximal-to-distal, circular myotomy was performed, keeping the longitudinal muscle intact. Myotomy was extended 2–3 cm onto the gastric cardia in all patients with achalasia and non-achalasia esophageal motility disorders. At the completion of myotomy, the gastroscope was introduced into the esophageal lumen, and smooth passage through GEJ was confirmed. Hill classification scoring was performed pre- and post-myotomy. Hemostasis within the submucosal space was confirmed, and 80 mg of gentamicin within 20 ml of normal saline
was instilled into the submucosal space. Subsequently, the mucosotomy was closed with serial application of endoscopic clips. On postoperative day 1, an esophagram was obtained to rule out esophageal outlet obstruction and leak. An ‘‘endoleak’’ was defined as a contrast transit into the submucosal space at the site of mucosotomy. If esophagram did not demonstrate esophageal outlet obstruction or leak, a clear liquid diet was initiated and patients were discharged. All patients were asked to take the low dose of proton pump inhibitor (daily) until 48-h pH testing is performed at 6 months postoperatively (off antisecretory medication). Data analysis Values were expressed as either mean with standard deviation or median with intraquartile range when appropriate. Statistical analysis was performed by means of either parametric t test or nonparametric Mann–Whitney U test and Person’s Chi-square test using SPSS (ver. 19) when appropriate, and a p value of \0.05 was considered statistically significant.
Results Patient demographics and preoperative testing From January 2013 to October 2014, 36 POEMs were attempted on 34 patients. One patient was discovered to have significant metaplastic mucosal change in the distal esophagus, and the procedure was aborted because of severe submucosal scarring and fusion of planes, and this patient was excluded from this study. A total of 35 POEMs (achalasia n = 25, non-achalasia n = 10) were performed on 33 patients (female; n = 20, male; n = 13). The mean age was 56.9 years (range 23–86 years), and the mean BMI was 30.9 (range 20.3–52.1). The primary symptoms included dysphagia (32/33, 97 %), regurgitation (28/33, 84.8 %), heartburn (19/33, 57.6 %), chest pain (13/33, 39.4 %), cough (8/33, 24.2 %), nausea (4/33, 12.1 %) and atypical symptoms such as globus sensation and throat clearing (7/33, 21.2 %). Ten patients (40 %) were symptomatic for greater than 5 years. Esophageal motility disorders included type I achalasia (n = 1), type II achalasia (n = 19), type III achalasia (n = 5), Jackhammer esophagus (n = 5), nutcracker esophagus (n = 2) and diffuse esophageal spasm (n = 1). Eleven patients (33.3 %) had previous interventions including pneumatic dilation (n = 6), Botox injection (n = 3), surgical myotomy (n = 1), POEM (n = 2), gastric bypass (n = 1) and open repair of esophageal perforation caused by pneumatic dilation (n = 1). During a mean follow-up period of 7 months (range 0.5–17), the postoperative 48-h pH testing
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was performed on five patients (15 %), of whom two patients (40 %) had a positive DeMeester score (14.4 and 14.8). Furthermore, five patients (15.2 %) discontinued proton pump inhibitor because they were either asymptomatic or had a negative DeMeester score on the postoperative pH testing (Table 1). Overall procedure data No conversion from POEM to laparoscopic surgery was required (Table 2). The median procedure time was 185 min (range 107–328), and the median length of myotomy was 13 cm (range 6–22). There was a trend toward a shorter procedure time in the most recent 15 cases compared to the initial 20 cases (182 ± 58.0 vs. 190.6 ± 59.5, respectively), although the difference was not statistically significant (p = 0.68). The median length of hospital stay was 3 days (range 1–10). An inadvertent mucosotomy, which was clinically irrelevant, occurred during submucosal dissection in 6 POEMs (17.1 %), and needle decompression to release capnoperitoneum was required during the procedure secondary to increased airway pressure in seven patients (20 %). No patients developed peritonitis or mediastinitis. A small contained endoleak into the submucosal tunnel at the site of mucosotomy, which was not clinically relevant, was identified in five patients (14.3 %), and all were managed with NPO for 48 h. The overall rate of postoperative complications requiring intervention was 5.7 % (n = 2). One patient with type II achalasia developed a right-sided sterile transudative pleural effusion, requiring placement of a pigtail catheter for drainage. A patient with type II achalasia developed mucosal sloughing (6 9 2 cm) in the distal esophagus and mucosotomy closure dehiscence identified on postoperative day 12 (because of pain), requiring endoscopic evaluation (Fig. 1
upper row). This patient did not manifest signs of infection and was successfully treated with proton pump inhibitors, histamine receptor antagonists and topical therapy. Follow-up endoscopy on postoperative day 20 demonstrated a significantly reduced size of mucosal defect (Fig. 1 middle row), and this was completely healed at a 3-month follow-up endoscopy (Fig. 1 bottom row). This patient developed recurrent dysphagia due to the development of a low-grade stricture at the sloughing site and eventually required laparoscopic Heller myotomy with partial fundoplication. Overall clinical symptoms and quality of life assessment Of 25 patients with achalasia, the majority of patients (92 %) had a significant improvement in dysphagia, based on the postoperative interview at clinic. Chest pain was completely resolved in all of eight patients with the preoperative symptom of chest pain. A complete set of pre- and postoperative GERD-HRQL, RSI and dysphagia scores were obtained from 76 % (19/25) of patients with achalasia. Overall, there was a significant improvement in all of GERD-HRQL, RSI and dysphagia scores during a mean follow-up of 7 months (range 0.5–17) (Table 3). The rate of ‘‘abnormal’’ GERD-HRQL and RSI scores was significantly reduced postoperatively (pre-op 74 %/63 % vs. post-op 21 %/11 %, respectively). The majority of patients had an improvement in GERD-HRQL, RSI and dysphagia scores (Fig. 2). In eight patients with non-achalasia, two patients with nutcracker esophagus (25 %) did not have any symptomatic improvement in dysphagia after myotomy over entire length of the esophagus, although one had a shortterm symptomatic improvement. These cases (25 %) were considered ‘‘treatment failures.’’ The remainder of patients
Table 1 Patient demographics Patients who underwent POEM (n = 33) Sex
Male, n = 13; Female, n = 20
Age
56.9 (range 23–86 years)
BMI
30.9 (rage 20.3–52.1)
Symptoms
Dysphagia (97 %), regurgitation (84.8 %), heartburn (57.6 %), chest pain (39.4 %), cough (24.2 %), nausea (12.1 %), atypical symptoms (21.2 %)
Duration of clinic symptoms
C5 years (40 %), 1–5 years (44 %), \1 year (16 %)
Preoperative diagnosis
Type I achalasia (n = 1), type II achalasia (n = 19), type III achalasia (n = 5), Jackhammer esophagus (n = 5), nutcracker esophagus (n = 2), diffuse esophageal spasm (n = 1)
Previous intervention Mean follow-up period
33.3 % (11/33): Pneumatic dilation (n = 6), Botox injection (n = 3), surgical myotomy (n = 1), POEM (n = 2), gastric bypass (n = 1), open repair of esophageal perforation (n = 1) 7 months (range 0.5–17)
Post-POEM pH testing (n = 5)
Positive DeMeester score 40 % (2/5)
Proton pump inhibitor
Off 15.2 % (5/33), On 84.8 % (28/33)
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Surg Endosc Table 2 Overall procedure data
POEMs (n = 35) Conversion to laparoscopic surgery
0 % (n = 0)
Median procedure time (min)
185 (range 107–328)
Median length of myotomy (cm)
13 (range 6–22)
Median length of hospital stay
3 (range 1–10)
Inadvertent mucosotomy
n = 6 (17.1 %)
Veress needle decompression
n = 7 (20 %)
Contained endoleak
n = 5 (14.3 %)
Complications requiring intervention
n = 2 (5.7 %): chest tube (n = 1), upper endoscopy (n = 1)
pre- and postoperative GERD-HRQL, RSI and dysphagia scores were obtained from 75 % (6/8) of patients with nonachalasia. There was a significant improvement in GERDHRQL and RSI scores, and a trend toward lower scores in dysphagia score (Table 3). All patients had abnormal GERD-HRQL and RSI scores preoperatively. Although GERD-HRQL and RSI scores improved postoperatively in the majority of patients (67 % and 86 %, respectively), more than a half of patients still had abnormal GERDHRQL and RSI scores (Fig. 2). Perioperative course of POEMs for achalasia
Fig. 1 Postoperative complication requiring endoscopy for endoscopic evaluation. Upper row on day 12, a large mucosal sloughing and mucosotomy dehiscence was found. Middle row on day 20, the size of mucosal sloughing was significantly reduced and mucosotomy dehiscence was closed. Bottom row at 3 months, a mucosal sloughing was completely healed with scar tissue
(75 %) had a significant symptomatic improvement, based on the postoperative interview at clinic. Chest pain was completely resolved in four of five patients with preoperative symptom of chest pain (80 %). A complete set of
A total of 25 POEMs were performed on 25 patients with achalasia (type I n = 1, type II n = 19, type III n = 5) (Table 4). The preoperative, mean resting LES pressure was 53.6 mmHg, and the mean residual LES pressure was 33.0 mmHg. Preoperative esophagram showed sigmoid esophagus (n = 3) and moderately dilated esophagus without sigmoidization (n = 8). The median procedure time was 187 min (range 107–328), and the median length of myotomy was 13 cm (range 6–17). Seven patients (28 %) had previous interventions including dilation and/or Botox injection (n = 5) and surgical procedures such as gastric bypass (n = 1) and repair of esophageal perforation after pneumatic dilation (n = 1). The patient, who previously underwent gastric bypass for obesity and presented with nausea without dysphagia, was found to have type III achalasia, and a 17-cm anterior myotomy including a 2-cm myotomy onto the gastric pouch was performed without complications (Fig. 3). Postoperatively, nausea was completely resolved. The patient who had previously undergone multiple sessions of dilation for achalasia and then developed esophageal perforation was emergently repaired with primary repair and partial fundoplication via laparotomy. This patient underwent a 6-cm anterior POEM without complication, and dysphagia was completely resolved postoperatively.
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Surg Endosc Table 3 Clinical symptom assessment (mean ± SD) Patients with achalasia Pre-op
Post-op
Patients with non-achalasia p value
Pre-op
Post-op
p value
Symptomatic improvement Dysphagia
92 % (23/25)
75 % (6/8)
Chest pain
100 % (8/8)
80 % (4/5)
Questionnaires GERD-HRQL
16.3 ± 11.6
6.7 ± 8.1
0.003*
33.6 ± 9.0
16.4 ± 14.1
0.02*
RSI
20.1 ± 12.4
6.4 ± 4.8
\0.001*
30 ± 11.1
19.5 ± 11.7
0.02*
Dysphagia score Abnormal scores
60 ± 15.1
28.3 ± 20.4
\0.001*
70 ± 17.2
44.5 ± 21.7
0.15
Abnormal GERD-HRQL score
74 % (14/19)
21 % (4/19)
100 % (7/7)
57 % (4/7)
Abnormal RSI score
63 % (12/19)
11 % (2/19)
100 % (7/7)
86 % (6/7)
Improvement in scores GERD-HRQL
90 % (17/19)
67 % (5/7)
RSI
100 % (19/19)
86 % (6/7)
Dysphagia score
95 % (18/19)
86 % (6/7)
* p \ 0.05 is considered significant
Fig. 2 Pre- and postoperative GERD-HRQL, RSI and dysphagia scores on each patient. Bold black line the cutoff score for an ‘‘abnormal’’ in GERD-HRQL and RSI
Perioperative course of POEMs for non-achalasia A total of 10 POEMs were performed on eight patients with non-achalasia esophageal motility disorders (Table 4). Nonachalasia esophageal motility disorders included Jackhammer esophagus (n = 5), nutcracker esophagus (n = 2) and diffuse esophageal spasm (n = 1). Of these, a patient with
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Jackhammer esophagus had concomitant GERD as evidenced by Los Angeles Classification grade C esophagitis and a positive DeMeester score (20.3 on day 1 and 53.3 on day 2). In this patient, a laparoscopic long myotomy with partial fundoplication followed by POEM to extend the myotomy proximally was performed. The remainder of patients with non-achalasia motility disorders did not have
Surg Endosc Table 4 Comparison of patients with achalasia and non-achalasia
Preoperative diagnosis
Patients with achalasia (n = 25)
Patients with non-achalasia (n = 8)
Type I (n = 1), type II (n = 19), type III (n = 5)
Jackhammer (n = 5), Nutcracker (n = 2), DES (n = 1)
Pre-op manometry Resting LES pressure
53.6 ± 14.3
44.5 ± 11.8
Residual LES pressure
33.0 ± 7.6
13.0 ± 4.4
Pre-op esophagram
Sigmoid esophagus (n = 3), moderate dilation (n = 8)
Corkscrewed appearing esophagus (n = 1)
Median procedure time (min)
187 (range 107–328)
182 (range 113–257)
Median length of myotomy (cm)
13 (range 6–17)
15 (range 6–22)
Median length of hospital stay
2 (range 1–10)
3 (range 3–7)
Previous interventions
28 % (7/25): Pneumatic dilation (n = 5), Botox injection (n = 3), gastric bypass (n = 1), open repair of esophageal perforation (n = 1)
POEM (n = 2), surgical myotomy (n = 1), dilation (n = 1)
No sigmoid or dilated esophagus
Fig. 3 Type III achalasia on patients with gastric bypass. Upper row preoperative manometry showed type III achalasia. Left middle row preoperative esophagram showed spastic esophageal contractions. Right middle row postoperative esophagram showed a completely relaxed esophagus with good esophageal emptying
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evidence of GERD. One patient with Jackhammer esophagus also had an epiphrenic diverticulum (2.8 9 1.6 cm) without GERD. In this patient, a POEM was performed in conjunction with a laparoscopic resection of the diverticulum and partial fundoplication. The preoperative, mean resting LES pressure for this group of patients was 44.5 mmHg, and the mean residual LES pressure was 13.0 mmHg. One patient with diffuse esophageal spasm had a cork-screwed appearing esophagus, but none of patients with non-achalasia motility disorders had a dilated or sigmoid esophagus. The median procedure time was 182 min (range 113–257), and the median length of myotomy was 15 cm (range 6–22). The median length of hospital stay was 3 days (range 3–7). Three patients (42.9 %) had previous interventions including POEM (n = 2), dilation (n = 1) and laparoscopic and thoracoscopic myotomy (n = 1). One patient, who had manometric findings of multiple simultaneous contractions with relaxation of LES and radiographic findings of a cork-screwed appearing esophagus along the entire length of intrathoracic esophagus, was diagnosed with diffuse esophageal spasm and underwent a 21-cm myotomy with excellent symptomatic resolution (Fig. 4). Two patients (1 Jackhammer, 1 nutcracker) had persistent dysphagia after POEM and were found to have remaining esophageal hypercontractility in the proximal and middle of the esophageal body (Fig. 5 middle row). Subsequently, they underwent posterior redo-POEM, targeting the remaining esophageal contractions. Postoperative HRM demonstrated that redo-POEM successfully eliminated the remaining esophageal hypercontractility and the symptoms resolved (Fig. 5 bottom row). One patient with nutcracker esophagus, who previously underwent laparoscopic and thoracoscopic long myotomy, was found to have a 1-cm region of persistent esophageal contraction 4 cm proximal to the GE junction; a 6-cm, posterior POEM targeting that site was performed. During the procedure, a significantly thickened circular muscle band was identified and completely divided. Postoperative esophagram demonstrated no remaining esophageal contractions and symptoms resolved (Fig. 6).
Discussion Following the first report of successful endoscopic submucosal myotomy in a porcine model by Pasricha and colleagues [24], Inoue and colleagues established POEM and reported the promising outcomes of POEM in 17 patients with achalasia [12]. Since then, the concept of POEM has been quickly accepted, and several uncontrolled series of POEM have demonstrated that therapeutic success can be achieved in [80 % of patients, and serious adverse
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events such as mediastinitis and abscess formation are extremely rare (\0.1 %) [13]. Furthermore, previous studies have suggested that the outcome of POEM in patients with non-achalasia esophageal motility disorders is not as effective in alleviating the symptom of chest pain compared to dysphagia, and our results support this evidence [19, 25]. In the present study, dysphagia significantly improved in greater than 90 % of patients with achalasia and 70 % of patients with non-achalasia esophageal motility disorder. Furthermore, chest pain significantly improved in the majority of patients with both achalasia and non-achalasia motility disorders. There was no mortality or major complications such as peritonitis or mediastinitis, and the rate of postoperative complications requiring intervention was 5.7 %. These data suggest that the efficacy of POEM in the alleviation of dysphagia is consistent with previous studies, and the outcome of POEM in patients with non-achalasia esophageal motility disorders is less favorable when compared to those with achalasia. Hemorrhage can occur during the procedure but can be controlled with coagulation using the tip of TT knife, coagulation graspers or compression using the cap attached on the tip of endoscope. Initially, we used a diluted epinephrine solution to assist with hemostasis; however, one patient developed mucosal sloughing due to mucosal necrosis, which was possibly caused by ischemia of mucosal flap due to epinephrine. The patient ultimately had recurrent dysphagia due to scar formation at the site of mucosal sloughing and required laparoscopic Heller myotomy several months after POEM. Stent placement could be fatal in this setting and potentially cause esophageal rupture or erosion into the great vessels or airway. In the present study, the rate of inadvertent mucosotomy was 17 %, with the majority occurring in the first 20 cases. In a recent study, Kurian and colleagues demonstrated that the learning curve appears to plateau in about 20 cases for experienced endoscopists [26]. Further experience should improve the POEM technique and decrease the incidence of inadvertent mucosotomy. Since no antireflux procedure is added in POEM, the initial concern was postoperative GERD; however, POEM preserves patients’ antireflux barrier structure such as the phrenoesophageal membrane and the angle of His, theoretically reducing the risk of postoperative GERD. Accumulating data have suggested that objective evidence of GERD such as esophagitis and/or abnormal pH testing is found in 20–46 % of post-POEM patients [12, 13, 16, 17, 19, 20]. Previous prospective studies have demonstrated that this prevalence appears to be comparable with that in patients who had Heller myotomy with partial fundoplication [27, 28]. These data were further supported by the most recent comparative study involving 101 patients who had either laparoscopic Heller myotomy (n = 64) or POEM (n = 37), demonstrating that 39 % of patients with POEM
Surg Endosc Fig. 4 Diffuse esophageal spasm. Upper row preoperative manometry showed multiple simultaneous contractions with relaxation of LES. Middle row preoperative esophagram showed a cork-screw appearing esophagus. Bottom row postoperative esophagram showed a completely relaxed esophagus with good esophageal emptying
and 32 % of those with Heller myotomy had abnormal acid exposure, and there was no significant difference in DeMeester scores, proportion of patients with abnormal DeMeester score or the median number of reflux events based on 24-h pH testing between the groups (p = 0.7) [14].
In the present study, the data of postoperative pH testing or endoscopy were not sufficient to support this data; however, there was a significant improvement in GERD-HRQL and RSI scores, suggesting that POEM does not aggravate typical or atypical GERD symptoms.
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Fig. 5 Hypercontractile esophagus. Upper row preoperative manometry showed hypercontractile esophagus. Middle row post-first POEM manometry showed the remaining esophageal hypercontractility in the middle and proximal esophagus. Bottom row post-second POEM manometry showed a totally atonic esophagus
The International POEM Survey (IPOEMS) has demonstrated slightly less efficacy of POEM in patients with DES and type III achalasia but excellent efficacy in hypertensive LES and nutcracker esophagus and suggested that POEM may be superior to laparoscopic Heller myotomy in patients
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with spastic esophageal motility disorders as the myotomy can be extended proximally in the esophageal body [25]. In the present study, three patients with hypercontractile esophagus required redo-myotomy via a ‘‘salvage’’ POEM for incomplete myotomy, who otherwise would have required thoracoscopic surgery. In these cases, the previous myotomy was performed anteriorly, and redo-POEM was successfully performed posteriorly. Of them, two patients with nutcracker esophagus eventually did not respond to extensive myotomy, although one had a short-term symptomatic relief. Both patients were diabetic and found to have irritable bowel syndrome and/or gastroparesis. Esophageal motility disorders may be a part of entire GI functional disorders, possibly affecting the outcome of POEM, and the probability of procedure failure should be discussed with patients prior to POEM. Introduction of high-resolution manometry has highlighted a group of patients who has hypercontractile esophagus with other esophageal disease such as GERD and epiphrenic diverticulum. The optimal treatment strategy for this population remains unclear. Since hypercontractile esophagus may be secondary to GERD, antireflux surgery to treat the underlying cause is expected to eliminate hypercontractility of esophageal body. However, persistent esophageal hypercontractility is often observed even after appropriate treatment of GERD. In the present study, we successfully performed POEM combined with a laparoscopic procedure on two patients with Jackhammer esophagus and either severe GERD or epiphrenic diverticulum. The laparoscopic approach followed by POEM and POEM followed by laparoscopic approach both worked well and resulted in excellent outcomes. In both cases, POEM was used to extend a laparoscopically created myotomy proximally. POEM may offer the ability to easily extend myotomy proximally without thoracoscopy or thoracotomy, possibly reducing the postoperative cardiopulmonary complications and length of hospital stay. There are some limitations in the present study. The follow-up period is short, and there is a lack of postoperative esophageal objective testing. Many patients with post-POEM GERD may be entirely asymptomatic [14]. Furthermore, the prevalence of GERD as evidenced by objective testing appears to be higher than that measured by symptom scores or questionnaires [12, 13, 16, 17, 19, 20]. These data suggest that clinical symptoms alone are not sufficient to assess the outcome of POEM, and postoperative evaluation using objective testing should be employed to prevent chronic injury from subclinical GERD and/or unnecessary antisecretory medication use, The outcome of POEM to treat achalasia and non-achalasia esophageal motility disorders in the present study is consistent with previous reports. We started POEM on patients with simple type II achalasia and successfully applied POEM to a variety of esophageal motility-related clinical
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Fig. 6 ‘‘Salvage’’ POEM. The patient who previously underwent laparoscopic and thoracoscopic myotomy complained persistent dysphagia. Right upper row preoperative esophagram showed a short, persistent esophageal contraction in the distal esophagus. Left upper row postoperative esophagram showed no remaining
esophageal contraction. Left middle row during POEM, a short, thickened muscular band was identified and completely divided. Right middle row after POEM, a segmental contraction disappeared. Bottom row the esophagus was completely atonic
scenarios. The benefit of POEM includes not only its flexibility to adjust the length and location of myotomy but also the ability to extend the myotomy proximally without thoracoscopy or thoracotomy. POEM can be combined with a laparoscopic procedure and used as ‘‘salvage’’ for localized areas of esophageal dysmotility. Further evaluation using objective testing with long-term follow-up is required.
2. Goldblum JR, Rice TW, Richter JE (1996) Histopathologic features in esophagomyotomy specimens from patients with achalasia. Gastroenterology 111(3):648–654 3. Goldblum JR, Whyte RI, Orringer MB, Appelman HD (1994) Achalasia. A morphologic study of 42 resected specimens. Am J Surg Pathol 18(4):327–337 4. Birgisson S, Richter JE (1997) Achalasia: What’s new in diagnosis and treatment? Dig Dis 15(Suppl 1):1–27 5. Boeckxstaens GE, Annese V, des Varannes SB et al (2011) Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med 364(19):1807–1816 6. Campos GM, Vittinghoff E, Rabl C et al (2009) Endoscopic and surgical treatments for achalasia: a systematic review and metaanalysis. Ann Surg 249(1):45–57 7. Bonatti H, Hinder RA, Klocker J et al (2005) Long-term results of laparoscopic Heller myotomy with partial fundoplication for the treatment of achalasia. Am J Surg 190(6):874–878 8. Costantini M, Zaninotto G, Guirroli E et al (2005) The laparoscopic Heller-Dor operation remains an effective treatment for esophageal achalasia at a minimum 6-year follow-up. Surg Endosc 19(3):345–351
Disclosures Toshitaka Hoppo, Shyam J. Thakkar, Lana Y. Schumacher, Yoshihiro Komatsu, Steve Choe, Amit Shetty, Sara Bloomer, Emily J. Lloyd, Ali H. Zaidi, Mathew A. VanDeusen, Rodney J. Landreneau, Abhijit Kulkarni and Blair A. Jobe have no conflicts of interest or financial ties to disclose.
References 1. Francis DL, Katzka DA (2010) Achalasia: update on the disease and its treatment. Gastroenterology 139(2):369–374
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Surg Endosc 9. Gockel I, Junginger T, Eckardt VF (2006) Long-term results of conventional myotomy in patients with achalasia: a prospective 20-year analysis. J Gastrointest Surg 10(10):1400–1408 10. Richards WO, Torquati A, Holzman MD et al (2004) Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: a prospective randomized double-blind clinical trial. Ann Surg 240(3):405–412 discussion 412–405 11. Kahrilas PJ, Ghosh SK, Pandolfino JE (2008) Esophageal motility disorders in terms of pressure topography: the Chicago classification. J Clin Gastroenterol 42(5):627–635 12. Inoue H, Minami H, Kobayashi Y et al (2010) Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 42(4):265–271 13. Stavropoulos SN, Desilets DJ, Fuchs KH et al (2014) Per-oral endoscopic myotomy white paper summary. Gastrointest Endosc 80(1):1–15 14. Bhayani NH, Kurian AA, Dunst CM, Sharata AM, Rieder E, Swanstrom LL (2014) A comparative study on comprehensive, objective outcomes of laparoscopic Heller myotomy with per-oral endoscopic myotomy (POEM) for achalasia. Ann Surg 259(6):1098–1103 15. Costamagna G, Marchese M, Familiari P, Tringali A, Inoue H, Perri V (2012) Peroral endoscopic myotomy (POEM) for oesophageal achalasia: preliminary results in humans. Dig Liver Dis 44(10):827–832 16. Hungness ES, Teitelbaum EN, Santos BF et al (2013) Comparison of perioperative outcomes between peroral esophageal myotomy (POEM) and laparoscopic Heller myotomy. J Gastrointest Surg 17(2):228–235 17. Inoue H, Tianle KM, Ikeda H et al (2011) Peroral endoscopic myotomy for esophageal achalasia: technique, indication, and outcomes. Thorac Surg Clin 21(4):519–525 18. Sharata AM, Dunst CM, Pescarus R et al (2015) Peroral endoscopic myotomy (POEM) for esophageal primary motility
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disorders: analysis of 100 consecutive patients. J Gastrointest Surg 19(1):161–170 Swanstrom LL, Kurian A, Dunst CM, Sharata A, Bhayani N, Rieder E (2012) Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure. Ann Surg 256(4):659–667 von Renteln D, Inoue H, Minami H et al (2012) Peroral endoscopic myotomy for the treatment of achalasia: a prospective single center study. Am J Gastroenterol 107(3):411–417 Velanovich V (2007) The development of the GERD-HRQL symptom severity instrument. Dis Esophagus 20(2):130–134 Belafsky PC, Postma GN, Koufman JA (2002) Validity and reliability of the reflux symptom index (RSI). J Voice 16(2):274–277 Urbach DR, Tomlinson GA, Harnish JL, Martino R, Diamant NE (2005) A measure of disease-specific health-related quality of life for achalasia. Am J Gastroenterol 100(8):1668–1676 Pasricha PJ, Hawari R, Ahmed I et al (2007) Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy 39(9):761–764 Stavropoulos SN, Modayil RJ, Friedel D, Savides T (2013) The international per oral endoscopic myotomy survey (IPOEMS): a snapshot of the global POEM experience. Surg Endosc 27(9):3322–3338 Kurian AA, Dunst CM, Sharata A, Bhayani NH, Reavis KM, Swanstrom LL (2013) Peroral endoscopic esophageal myotomy: defining the learning curve. Gastrointest Endosc 77(5):719– 725 Khajanchee YS, Kanneganti S, Leatherwood AE, Hansen PD, Swanstrom LL (2005) Laparoscopic Heller myotomy with Toupet fundoplication: outcomes predictors in 121 consecutive patients. Arch Surg 140(9):827–833 discussion 833–824 Rawlings A, Soper NJ, Oelschlager B et al (2012) Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomizedcontrolled trial. Surg Endosc 26(1):18–26
and Other Interventional Techniques
A utility of peroral endoscopic myotomy (POEM) across the spectrum of esophageal motility disorders Toshitaka Hoppo1 • Shyam J. Thakkar1 • Lana Y. Schumacher1 • Yoshihiro Komatsu1 Steve Choe1 • Amit Shetty1 • Sara Bloomer1 • Emily J. Lloyd1 • Ali H. Zaidi1 • Mathew A. VanDeusen1 • Rodney J. Landreneau1 • Abhijit Kulkarni1 • Blair A. Jobe1
•
Received: 10 February 2015 / Accepted: 24 March 2015 Ó Springer Science+Business Media New York 2015
Abstract Background Peroral endoscopic myotomy (POEM) has been performed as a novel endoscopic procedure to treat achalasia with favorable outcome. The objective of this study was to assess the outcome of POEM in our initial series and to assess the safety and efficacy of POEM in a variety of esophageal motility-related clinical problems. Methods This is a retrospective cross-sectional study involving all patients with esophageal motility disorders defined by the Chicago classification, who had undergone consideration for POEM at our institution. Validated questionnaires such as gastroesophageal reflux disease healthrelated quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease-specific health-related quality of life were obtained pre- and postoperatively. Results From January 2013 to October 2014, a total of 35 POEMs (achalasia n = 25, non-achalasia n = 10) were performed on 33 patients (female n = 20, male n = 13, mean age 56.9 years). There was no mortality. The rate of inadvertent mucosotomy was 17.1 %. The rate of complications requiring interventions was 5.7 %. During a mean follow-up period of 7 months (range 0.5–17), 92 % of patients with achalasia and 75 % of those with non-achalasia motility disorders had a symptomatic improvement in dysphagia. Chest pain was completely resolved in all patients with achalasia (8/8) and 80 % of patients with non-
& Toshitaka Hoppo [email protected] Blair A. Jobe [email protected] 1
Esophageal and Lung Institute, Allegheny Health Network, 4800 Friendship Avenue, Suite 4600, Pittsburgh, PA 15224, USA
achalasia (4/5). The GERD-HRQL, RSI and dysphagia scores significantly improved after POEM in patients with achalasia. There was a significant improvement in GERDHRQL and RSI scores, and a trend toward lower dysphagia score in patients with non-achalasia. Conclusions The outcome of POEM to treat achalasia and non-achalasia motility disorders is consistent with previous studies. Potential benefit of POEM includes not only its flexibility to adjust the length and location of myotomy but also the ability to extend myotomy proximally without thoracoscopy or thoracotomy. POEM can be combined with laparoscopic procedures and used as ‘‘salvage’’ for localized esophageal dysmotility. Keywords POEM Achalasia Non-achalasia esophageal motility disorders Questionnaires Dysphagia Chest pain
Achalasia is the most common esophageal motility disorder but is relatively rare with a prevalence of 0.5–1 per 100,000 populations per year without a gender predilection [1]. The inflammatory loss of ganglion cells in the myenteric plexus of the esophageal body and lower esophageal sphincter (LES) causes the inability of LES to relax and absence of esophageal body peristalsis, leading to dysphagia, regurgitation of retained food and chest pain [2–4]. Since none of the treatments can restore the impaired muscle activity of esophageal body and LES, the goal of treatment is palliative and aimed at improving esophageal outlet obstruction by dividing the LES while minimizing gastroesophageal reflux. For this purpose, pneumatic dilation and surgical myotomy have been most commonly performed. Although the recent randomized controlled study comparing pneumatic dilation with surgical myotomy demonstrated no difference in the
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short-term efficacy [5], multiple sessions of dilation are often required (with a 4 % perforation risk), and therefore, surgical myotomy has been considered as the most effective treatment in the USA. [6–9] With the advances in minimally invasive surgical techniques, a laparoscopic Heller myotomy with a partial fundoplication (Dor or Toupet) has been most commonly performed since the randomized controlled study by Richards and colleagues demonstrated that the addition of partial fundoplication significantly reduced postoperative gastroesophageal reflux from 47.6 to 9.1 % (p = 0.005) [10]. Since the introduction of high-resolution manometry, nonachalasia esophageal motility disorders such as hypercontractile esophagus and diffuse esophageal spasm have been more readily identified. The Chicago classification criteria have been utilized to define esophageal motility disorders based on several parameters of esophageal pressure topography [11]. Unlike achalasia, the treatment strategy of nonachalasia esophageal motility disorders is still controversial. Esophageal contractility may be secondary to chronic gastroesophageal reflux disease (GERD), and the treatment of GERD has been commonly recommended with unpredictable outcomes. However, esophageal hypercontractilily is often persistent even after the appropriate control of GERD, and a long myotomy over the entire length of intrathoracic esophagus via thoracoscopy or thoracotomy is considered to eliminate the persistent esophageal contractility. Peroral endoscopic myotomy (POEM) has been rapidly accepted by endoscopists and endoscopic surgeons since the promising outcomes of POEM on the initial 17 patients with achalasia [12]. More than 1200 POEMs have been performed worldwide, demonstrating its feasibility and safety with equivalent short-term outcomes to conventional laparoscopic Heller myotomy [13–20]. The indication for POEM has been extended to treat more complicated achalasia (e.g., sigmoid esophagus, failure of previous myotomy) and other spastic esophageal motility disorders. At our institution, we started POEM on patients with simple type II achalasia and successfully applied POEM to a variety of esophageal motility-related clinical problems. The objective of this study was to assess the outcome of POEM in our initial experience and to assess the efficacy and safety of POEM in a variety of esophageal motilityrelated clinical problems.
Materials and methods Study design This retrospective cross-sectional study was performed under the approval of institutional review board of the Allegheny Health Network. Subjects included all patients who
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had undergone consideration for myotomy at our institution from January 2013 to October 2014. All patients underwent esophagram, upper endoscopy, high-resolution manometry and pH testing (if applicable) as a requisite for preoperative assessment. Detailed demographic data (sex, age, BMI), clinical data (pre-/postoperative symptom scores, past medical/surgical history, medication use, duration of symptoms, procedure time, length of hospital stay) and objective data (endoscopic/radiographic findings, manometric findings) were obtained per protocol. To assess the impact of POEM on symptoms and quality of life, all patients were asked to complete validated questionnaires including GERD health-related quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease-specific health-related quality of life, pre- and postoperatively. High-resolution manometry High-resolution manometry (HRM) was performed using a solid-state assembly with 36 circumferential sensors spaced at 1 cm intervals, and manometric data were analyzed using ManoViewTM v2 Analysis software (ManoScan, Given Imaging, Inc. Duluth GA). The preoperative HRM was used to classify patients with esophageal motility disorders according to the Chicago classification v2.0. Clinical perspective was augmented through the calculation of esophageal clearance of swallows of saline liquids and solids (selectively) measured by impedance electrodes coupled with the HRM catheter. Symptom assessment using validated questionnaires All patients were thoroughly interviewed at every clinic visit, and the pre- and postoperative symptoms were previously recorded in the medical charts. Additionally, all patients were asked to fill out validated questionnaires preoperatively, at 6 weeks and at 6 and 12 months postoperatively. The validated questionnaires included GERDHRQL, RSI and achalasia disease-specific health-related quality of life. GERD-HRQL consists of 10 questions which specifically address GERD symptoms [21]. Each question has a score ranging from 0 to 5, and the best possible aggregate score is 0 (asymptomatic), and the worse score is 50 (very severe symptoms). A total score of C 10 is considered abnormal. The RSI was used to assess atypical GERD symptoms [22]. The RSI consists of 9 questions, and each question has a potential score ranging from 0 to 5. A total score [13 is considered abnormal. The severity of dysphagia was scored using the achalasia disease-specific health-related quality of life questionnaire including food tolerance, dysphagia-related behavior modifications, pain, heartburn, distress, lifestyle limitation and satisfaction [23]. Total raw scores were calculated by
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summing the score for each item to yield a score between 10 and 31 and were recalibrated to interval-level scores from 0 to 100, with higher values indicating greater disease severity. Comparing the postoperative scores with the preoperative scores on each questionnaire, the rate of symptomatic improvement was calculated. Technique of POEM Preoperatively, patients were asked to stay on liquid diet for a 3-day period, and a nystatin swish, swallow solution, was given for 5 days. A single dose of a first-generation cephalosporin and 100 mg of fluconazole were given intravenously 1 h prior to the procedure. POEM was performed as previously published, in the operating room under general anesthesia [12]. Briefly, patients were placed in the supine position and esophagogastroduodenoscopy was performed using a standard upper endoscope (GIFHQ190 or GIF-H190, Olympus USA, Center valley, PA) with CO2 insufflation. The location of anatomic gastroesophageal junction (GEJ) was measured, and the presence of mucosal changes such as esophagitis was recorded. For type I and II achalasia, the mucosotomy was created 15 cm proximal to the GEJ. For other spastic esophageal motility disorders, the location of mucosotomy was selected by correlating with HRM measurement. In these patients, the location for myotomy most commonly occurred 3 cm proximal to the upper border of the endoscopically visualized forceful esophageal contraction. Following submucosal injection of normal saline mixed with indigo carmine to create a submucosal cushion, a 1.5- to 2-cm longitudinal mucosal incision was applied on the anterior esophageal wall (2 o’clock position) using a triangle-tip knife (TT knife, Olympus USA, Center Valley, PA). Once the access to the submucosal space was created, a gastroscope with plastic cap was introduced into the submucosal space, and a submucosal tunnel was created using endoscopic submucosal dissection with the TT knife. Large bridging vessels were carefully cauterized with coagulation graspers. The tunnel was extended at least 3 cm onto the proximal stomach across the GEJ. Myotomy was initiated 2–3 cm proximal to the distal edge of mucosotomy. Once the plane between circular and longitudinal muscles was identified, a proximal-to-distal, circular myotomy was performed, keeping the longitudinal muscle intact. Myotomy was extended 2–3 cm onto the gastric cardia in all patients with achalasia and non-achalasia esophageal motility disorders. At the completion of myotomy, the gastroscope was introduced into the esophageal lumen, and smooth passage through GEJ was confirmed. Hill classification scoring was performed pre- and post-myotomy. Hemostasis within the submucosal space was confirmed, and 80 mg of gentamicin within 20 ml of normal saline
was instilled into the submucosal space. Subsequently, the mucosotomy was closed with serial application of endoscopic clips. On postoperative day 1, an esophagram was obtained to rule out esophageal outlet obstruction and leak. An ‘‘endoleak’’ was defined as a contrast transit into the submucosal space at the site of mucosotomy. If esophagram did not demonstrate esophageal outlet obstruction or leak, a clear liquid diet was initiated and patients were discharged. All patients were asked to take the low dose of proton pump inhibitor (daily) until 48-h pH testing is performed at 6 months postoperatively (off antisecretory medication). Data analysis Values were expressed as either mean with standard deviation or median with intraquartile range when appropriate. Statistical analysis was performed by means of either parametric t test or nonparametric Mann–Whitney U test and Person’s Chi-square test using SPSS (ver. 19) when appropriate, and a p value of \0.05 was considered statistically significant.
Results Patient demographics and preoperative testing From January 2013 to October 2014, 36 POEMs were attempted on 34 patients. One patient was discovered to have significant metaplastic mucosal change in the distal esophagus, and the procedure was aborted because of severe submucosal scarring and fusion of planes, and this patient was excluded from this study. A total of 35 POEMs (achalasia n = 25, non-achalasia n = 10) were performed on 33 patients (female; n = 20, male; n = 13). The mean age was 56.9 years (range 23–86 years), and the mean BMI was 30.9 (range 20.3–52.1). The primary symptoms included dysphagia (32/33, 97 %), regurgitation (28/33, 84.8 %), heartburn (19/33, 57.6 %), chest pain (13/33, 39.4 %), cough (8/33, 24.2 %), nausea (4/33, 12.1 %) and atypical symptoms such as globus sensation and throat clearing (7/33, 21.2 %). Ten patients (40 %) were symptomatic for greater than 5 years. Esophageal motility disorders included type I achalasia (n = 1), type II achalasia (n = 19), type III achalasia (n = 5), Jackhammer esophagus (n = 5), nutcracker esophagus (n = 2) and diffuse esophageal spasm (n = 1). Eleven patients (33.3 %) had previous interventions including pneumatic dilation (n = 6), Botox injection (n = 3), surgical myotomy (n = 1), POEM (n = 2), gastric bypass (n = 1) and open repair of esophageal perforation caused by pneumatic dilation (n = 1). During a mean follow-up period of 7 months (range 0.5–17), the postoperative 48-h pH testing
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was performed on five patients (15 %), of whom two patients (40 %) had a positive DeMeester score (14.4 and 14.8). Furthermore, five patients (15.2 %) discontinued proton pump inhibitor because they were either asymptomatic or had a negative DeMeester score on the postoperative pH testing (Table 1). Overall procedure data No conversion from POEM to laparoscopic surgery was required (Table 2). The median procedure time was 185 min (range 107–328), and the median length of myotomy was 13 cm (range 6–22). There was a trend toward a shorter procedure time in the most recent 15 cases compared to the initial 20 cases (182 ± 58.0 vs. 190.6 ± 59.5, respectively), although the difference was not statistically significant (p = 0.68). The median length of hospital stay was 3 days (range 1–10). An inadvertent mucosotomy, which was clinically irrelevant, occurred during submucosal dissection in 6 POEMs (17.1 %), and needle decompression to release capnoperitoneum was required during the procedure secondary to increased airway pressure in seven patients (20 %). No patients developed peritonitis or mediastinitis. A small contained endoleak into the submucosal tunnel at the site of mucosotomy, which was not clinically relevant, was identified in five patients (14.3 %), and all were managed with NPO for 48 h. The overall rate of postoperative complications requiring intervention was 5.7 % (n = 2). One patient with type II achalasia developed a right-sided sterile transudative pleural effusion, requiring placement of a pigtail catheter for drainage. A patient with type II achalasia developed mucosal sloughing (6 9 2 cm) in the distal esophagus and mucosotomy closure dehiscence identified on postoperative day 12 (because of pain), requiring endoscopic evaluation (Fig. 1
upper row). This patient did not manifest signs of infection and was successfully treated with proton pump inhibitors, histamine receptor antagonists and topical therapy. Follow-up endoscopy on postoperative day 20 demonstrated a significantly reduced size of mucosal defect (Fig. 1 middle row), and this was completely healed at a 3-month follow-up endoscopy (Fig. 1 bottom row). This patient developed recurrent dysphagia due to the development of a low-grade stricture at the sloughing site and eventually required laparoscopic Heller myotomy with partial fundoplication. Overall clinical symptoms and quality of life assessment Of 25 patients with achalasia, the majority of patients (92 %) had a significant improvement in dysphagia, based on the postoperative interview at clinic. Chest pain was completely resolved in all of eight patients with the preoperative symptom of chest pain. A complete set of pre- and postoperative GERD-HRQL, RSI and dysphagia scores were obtained from 76 % (19/25) of patients with achalasia. Overall, there was a significant improvement in all of GERD-HRQL, RSI and dysphagia scores during a mean follow-up of 7 months (range 0.5–17) (Table 3). The rate of ‘‘abnormal’’ GERD-HRQL and RSI scores was significantly reduced postoperatively (pre-op 74 %/63 % vs. post-op 21 %/11 %, respectively). The majority of patients had an improvement in GERD-HRQL, RSI and dysphagia scores (Fig. 2). In eight patients with non-achalasia, two patients with nutcracker esophagus (25 %) did not have any symptomatic improvement in dysphagia after myotomy over entire length of the esophagus, although one had a shortterm symptomatic improvement. These cases (25 %) were considered ‘‘treatment failures.’’ The remainder of patients
Table 1 Patient demographics Patients who underwent POEM (n = 33) Sex
Male, n = 13; Female, n = 20
Age
56.9 (range 23–86 years)
BMI
30.9 (rage 20.3–52.1)
Symptoms
Dysphagia (97 %), regurgitation (84.8 %), heartburn (57.6 %), chest pain (39.4 %), cough (24.2 %), nausea (12.1 %), atypical symptoms (21.2 %)
Duration of clinic symptoms
C5 years (40 %), 1–5 years (44 %), \1 year (16 %)
Preoperative diagnosis
Type I achalasia (n = 1), type II achalasia (n = 19), type III achalasia (n = 5), Jackhammer esophagus (n = 5), nutcracker esophagus (n = 2), diffuse esophageal spasm (n = 1)
Previous intervention Mean follow-up period
33.3 % (11/33): Pneumatic dilation (n = 6), Botox injection (n = 3), surgical myotomy (n = 1), POEM (n = 2), gastric bypass (n = 1), open repair of esophageal perforation (n = 1) 7 months (range 0.5–17)
Post-POEM pH testing (n = 5)
Positive DeMeester score 40 % (2/5)
Proton pump inhibitor
Off 15.2 % (5/33), On 84.8 % (28/33)
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POEMs (n = 35) Conversion to laparoscopic surgery
0 % (n = 0)
Median procedure time (min)
185 (range 107–328)
Median length of myotomy (cm)
13 (range 6–22)
Median length of hospital stay
3 (range 1–10)
Inadvertent mucosotomy
n = 6 (17.1 %)
Veress needle decompression
n = 7 (20 %)
Contained endoleak
n = 5 (14.3 %)
Complications requiring intervention
n = 2 (5.7 %): chest tube (n = 1), upper endoscopy (n = 1)
pre- and postoperative GERD-HRQL, RSI and dysphagia scores were obtained from 75 % (6/8) of patients with nonachalasia. There was a significant improvement in GERDHRQL and RSI scores, and a trend toward lower scores in dysphagia score (Table 3). All patients had abnormal GERD-HRQL and RSI scores preoperatively. Although GERD-HRQL and RSI scores improved postoperatively in the majority of patients (67 % and 86 %, respectively), more than a half of patients still had abnormal GERDHRQL and RSI scores (Fig. 2). Perioperative course of POEMs for achalasia
Fig. 1 Postoperative complication requiring endoscopy for endoscopic evaluation. Upper row on day 12, a large mucosal sloughing and mucosotomy dehiscence was found. Middle row on day 20, the size of mucosal sloughing was significantly reduced and mucosotomy dehiscence was closed. Bottom row at 3 months, a mucosal sloughing was completely healed with scar tissue
(75 %) had a significant symptomatic improvement, based on the postoperative interview at clinic. Chest pain was completely resolved in four of five patients with preoperative symptom of chest pain (80 %). A complete set of
A total of 25 POEMs were performed on 25 patients with achalasia (type I n = 1, type II n = 19, type III n = 5) (Table 4). The preoperative, mean resting LES pressure was 53.6 mmHg, and the mean residual LES pressure was 33.0 mmHg. Preoperative esophagram showed sigmoid esophagus (n = 3) and moderately dilated esophagus without sigmoidization (n = 8). The median procedure time was 187 min (range 107–328), and the median length of myotomy was 13 cm (range 6–17). Seven patients (28 %) had previous interventions including dilation and/or Botox injection (n = 5) and surgical procedures such as gastric bypass (n = 1) and repair of esophageal perforation after pneumatic dilation (n = 1). The patient, who previously underwent gastric bypass for obesity and presented with nausea without dysphagia, was found to have type III achalasia, and a 17-cm anterior myotomy including a 2-cm myotomy onto the gastric pouch was performed without complications (Fig. 3). Postoperatively, nausea was completely resolved. The patient who had previously undergone multiple sessions of dilation for achalasia and then developed esophageal perforation was emergently repaired with primary repair and partial fundoplication via laparotomy. This patient underwent a 6-cm anterior POEM without complication, and dysphagia was completely resolved postoperatively.
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Post-op
Patients with non-achalasia p value
Pre-op
Post-op
p value
Symptomatic improvement Dysphagia
92 % (23/25)
75 % (6/8)
Chest pain
100 % (8/8)
80 % (4/5)
Questionnaires GERD-HRQL
16.3 ± 11.6
6.7 ± 8.1
0.003*
33.6 ± 9.0
16.4 ± 14.1
0.02*
RSI
20.1 ± 12.4
6.4 ± 4.8
\0.001*
30 ± 11.1
19.5 ± 11.7
0.02*
Dysphagia score Abnormal scores
60 ± 15.1
28.3 ± 20.4
\0.001*
70 ± 17.2
44.5 ± 21.7
0.15
Abnormal GERD-HRQL score
74 % (14/19)
21 % (4/19)
100 % (7/7)
57 % (4/7)
Abnormal RSI score
63 % (12/19)
11 % (2/19)
100 % (7/7)
86 % (6/7)
Improvement in scores GERD-HRQL
90 % (17/19)
67 % (5/7)
RSI
100 % (19/19)
86 % (6/7)
Dysphagia score
95 % (18/19)
86 % (6/7)
* p \ 0.05 is considered significant
Fig. 2 Pre- and postoperative GERD-HRQL, RSI and dysphagia scores on each patient. Bold black line the cutoff score for an ‘‘abnormal’’ in GERD-HRQL and RSI
Perioperative course of POEMs for non-achalasia A total of 10 POEMs were performed on eight patients with non-achalasia esophageal motility disorders (Table 4). Nonachalasia esophageal motility disorders included Jackhammer esophagus (n = 5), nutcracker esophagus (n = 2) and diffuse esophageal spasm (n = 1). Of these, a patient with
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Jackhammer esophagus had concomitant GERD as evidenced by Los Angeles Classification grade C esophagitis and a positive DeMeester score (20.3 on day 1 and 53.3 on day 2). In this patient, a laparoscopic long myotomy with partial fundoplication followed by POEM to extend the myotomy proximally was performed. The remainder of patients with non-achalasia motility disorders did not have
Surg Endosc Table 4 Comparison of patients with achalasia and non-achalasia
Preoperative diagnosis
Patients with achalasia (n = 25)
Patients with non-achalasia (n = 8)
Type I (n = 1), type II (n = 19), type III (n = 5)
Jackhammer (n = 5), Nutcracker (n = 2), DES (n = 1)
Pre-op manometry Resting LES pressure
53.6 ± 14.3
44.5 ± 11.8
Residual LES pressure
33.0 ± 7.6
13.0 ± 4.4
Pre-op esophagram
Sigmoid esophagus (n = 3), moderate dilation (n = 8)
Corkscrewed appearing esophagus (n = 1)
Median procedure time (min)
187 (range 107–328)
182 (range 113–257)
Median length of myotomy (cm)
13 (range 6–17)
15 (range 6–22)
Median length of hospital stay
2 (range 1–10)
3 (range 3–7)
Previous interventions
28 % (7/25): Pneumatic dilation (n = 5), Botox injection (n = 3), gastric bypass (n = 1), open repair of esophageal perforation (n = 1)
POEM (n = 2), surgical myotomy (n = 1), dilation (n = 1)
No sigmoid or dilated esophagus
Fig. 3 Type III achalasia on patients with gastric bypass. Upper row preoperative manometry showed type III achalasia. Left middle row preoperative esophagram showed spastic esophageal contractions. Right middle row postoperative esophagram showed a completely relaxed esophagus with good esophageal emptying
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evidence of GERD. One patient with Jackhammer esophagus also had an epiphrenic diverticulum (2.8 9 1.6 cm) without GERD. In this patient, a POEM was performed in conjunction with a laparoscopic resection of the diverticulum and partial fundoplication. The preoperative, mean resting LES pressure for this group of patients was 44.5 mmHg, and the mean residual LES pressure was 13.0 mmHg. One patient with diffuse esophageal spasm had a cork-screwed appearing esophagus, but none of patients with non-achalasia motility disorders had a dilated or sigmoid esophagus. The median procedure time was 182 min (range 113–257), and the median length of myotomy was 15 cm (range 6–22). The median length of hospital stay was 3 days (range 3–7). Three patients (42.9 %) had previous interventions including POEM (n = 2), dilation (n = 1) and laparoscopic and thoracoscopic myotomy (n = 1). One patient, who had manometric findings of multiple simultaneous contractions with relaxation of LES and radiographic findings of a cork-screwed appearing esophagus along the entire length of intrathoracic esophagus, was diagnosed with diffuse esophageal spasm and underwent a 21-cm myotomy with excellent symptomatic resolution (Fig. 4). Two patients (1 Jackhammer, 1 nutcracker) had persistent dysphagia after POEM and were found to have remaining esophageal hypercontractility in the proximal and middle of the esophageal body (Fig. 5 middle row). Subsequently, they underwent posterior redo-POEM, targeting the remaining esophageal contractions. Postoperative HRM demonstrated that redo-POEM successfully eliminated the remaining esophageal hypercontractility and the symptoms resolved (Fig. 5 bottom row). One patient with nutcracker esophagus, who previously underwent laparoscopic and thoracoscopic long myotomy, was found to have a 1-cm region of persistent esophageal contraction 4 cm proximal to the GE junction; a 6-cm, posterior POEM targeting that site was performed. During the procedure, a significantly thickened circular muscle band was identified and completely divided. Postoperative esophagram demonstrated no remaining esophageal contractions and symptoms resolved (Fig. 6).
Discussion Following the first report of successful endoscopic submucosal myotomy in a porcine model by Pasricha and colleagues [24], Inoue and colleagues established POEM and reported the promising outcomes of POEM in 17 patients with achalasia [12]. Since then, the concept of POEM has been quickly accepted, and several uncontrolled series of POEM have demonstrated that therapeutic success can be achieved in [80 % of patients, and serious adverse
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events such as mediastinitis and abscess formation are extremely rare (\0.1 %) [13]. Furthermore, previous studies have suggested that the outcome of POEM in patients with non-achalasia esophageal motility disorders is not as effective in alleviating the symptom of chest pain compared to dysphagia, and our results support this evidence [19, 25]. In the present study, dysphagia significantly improved in greater than 90 % of patients with achalasia and 70 % of patients with non-achalasia esophageal motility disorder. Furthermore, chest pain significantly improved in the majority of patients with both achalasia and non-achalasia motility disorders. There was no mortality or major complications such as peritonitis or mediastinitis, and the rate of postoperative complications requiring intervention was 5.7 %. These data suggest that the efficacy of POEM in the alleviation of dysphagia is consistent with previous studies, and the outcome of POEM in patients with non-achalasia esophageal motility disorders is less favorable when compared to those with achalasia. Hemorrhage can occur during the procedure but can be controlled with coagulation using the tip of TT knife, coagulation graspers or compression using the cap attached on the tip of endoscope. Initially, we used a diluted epinephrine solution to assist with hemostasis; however, one patient developed mucosal sloughing due to mucosal necrosis, which was possibly caused by ischemia of mucosal flap due to epinephrine. The patient ultimately had recurrent dysphagia due to scar formation at the site of mucosal sloughing and required laparoscopic Heller myotomy several months after POEM. Stent placement could be fatal in this setting and potentially cause esophageal rupture or erosion into the great vessels or airway. In the present study, the rate of inadvertent mucosotomy was 17 %, with the majority occurring in the first 20 cases. In a recent study, Kurian and colleagues demonstrated that the learning curve appears to plateau in about 20 cases for experienced endoscopists [26]. Further experience should improve the POEM technique and decrease the incidence of inadvertent mucosotomy. Since no antireflux procedure is added in POEM, the initial concern was postoperative GERD; however, POEM preserves patients’ antireflux barrier structure such as the phrenoesophageal membrane and the angle of His, theoretically reducing the risk of postoperative GERD. Accumulating data have suggested that objective evidence of GERD such as esophagitis and/or abnormal pH testing is found in 20–46 % of post-POEM patients [12, 13, 16, 17, 19, 20]. Previous prospective studies have demonstrated that this prevalence appears to be comparable with that in patients who had Heller myotomy with partial fundoplication [27, 28]. These data were further supported by the most recent comparative study involving 101 patients who had either laparoscopic Heller myotomy (n = 64) or POEM (n = 37), demonstrating that 39 % of patients with POEM
Surg Endosc Fig. 4 Diffuse esophageal spasm. Upper row preoperative manometry showed multiple simultaneous contractions with relaxation of LES. Middle row preoperative esophagram showed a cork-screw appearing esophagus. Bottom row postoperative esophagram showed a completely relaxed esophagus with good esophageal emptying
and 32 % of those with Heller myotomy had abnormal acid exposure, and there was no significant difference in DeMeester scores, proportion of patients with abnormal DeMeester score or the median number of reflux events based on 24-h pH testing between the groups (p = 0.7) [14].
In the present study, the data of postoperative pH testing or endoscopy were not sufficient to support this data; however, there was a significant improvement in GERD-HRQL and RSI scores, suggesting that POEM does not aggravate typical or atypical GERD symptoms.
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Fig. 5 Hypercontractile esophagus. Upper row preoperative manometry showed hypercontractile esophagus. Middle row post-first POEM manometry showed the remaining esophageal hypercontractility in the middle and proximal esophagus. Bottom row post-second POEM manometry showed a totally atonic esophagus
The International POEM Survey (IPOEMS) has demonstrated slightly less efficacy of POEM in patients with DES and type III achalasia but excellent efficacy in hypertensive LES and nutcracker esophagus and suggested that POEM may be superior to laparoscopic Heller myotomy in patients
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with spastic esophageal motility disorders as the myotomy can be extended proximally in the esophageal body [25]. In the present study, three patients with hypercontractile esophagus required redo-myotomy via a ‘‘salvage’’ POEM for incomplete myotomy, who otherwise would have required thoracoscopic surgery. In these cases, the previous myotomy was performed anteriorly, and redo-POEM was successfully performed posteriorly. Of them, two patients with nutcracker esophagus eventually did not respond to extensive myotomy, although one had a short-term symptomatic relief. Both patients were diabetic and found to have irritable bowel syndrome and/or gastroparesis. Esophageal motility disorders may be a part of entire GI functional disorders, possibly affecting the outcome of POEM, and the probability of procedure failure should be discussed with patients prior to POEM. Introduction of high-resolution manometry has highlighted a group of patients who has hypercontractile esophagus with other esophageal disease such as GERD and epiphrenic diverticulum. The optimal treatment strategy for this population remains unclear. Since hypercontractile esophagus may be secondary to GERD, antireflux surgery to treat the underlying cause is expected to eliminate hypercontractility of esophageal body. However, persistent esophageal hypercontractility is often observed even after appropriate treatment of GERD. In the present study, we successfully performed POEM combined with a laparoscopic procedure on two patients with Jackhammer esophagus and either severe GERD or epiphrenic diverticulum. The laparoscopic approach followed by POEM and POEM followed by laparoscopic approach both worked well and resulted in excellent outcomes. In both cases, POEM was used to extend a laparoscopically created myotomy proximally. POEM may offer the ability to easily extend myotomy proximally without thoracoscopy or thoracotomy, possibly reducing the postoperative cardiopulmonary complications and length of hospital stay. There are some limitations in the present study. The follow-up period is short, and there is a lack of postoperative esophageal objective testing. Many patients with post-POEM GERD may be entirely asymptomatic [14]. Furthermore, the prevalence of GERD as evidenced by objective testing appears to be higher than that measured by symptom scores or questionnaires [12, 13, 16, 17, 19, 20]. These data suggest that clinical symptoms alone are not sufficient to assess the outcome of POEM, and postoperative evaluation using objective testing should be employed to prevent chronic injury from subclinical GERD and/or unnecessary antisecretory medication use, The outcome of POEM to treat achalasia and non-achalasia esophageal motility disorders in the present study is consistent with previous reports. We started POEM on patients with simple type II achalasia and successfully applied POEM to a variety of esophageal motility-related clinical
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Fig. 6 ‘‘Salvage’’ POEM. The patient who previously underwent laparoscopic and thoracoscopic myotomy complained persistent dysphagia. Right upper row preoperative esophagram showed a short, persistent esophageal contraction in the distal esophagus. Left upper row postoperative esophagram showed no remaining
esophageal contraction. Left middle row during POEM, a short, thickened muscular band was identified and completely divided. Right middle row after POEM, a segmental contraction disappeared. Bottom row the esophagus was completely atonic
scenarios. The benefit of POEM includes not only its flexibility to adjust the length and location of myotomy but also the ability to extend the myotomy proximally without thoracoscopy or thoracotomy. POEM can be combined with a laparoscopic procedure and used as ‘‘salvage’’ for localized areas of esophageal dysmotility. Further evaluation using objective testing with long-term follow-up is required.
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Disclosures Toshitaka Hoppo, Shyam J. Thakkar, Lana Y. Schumacher, Yoshihiro Komatsu, Steve Choe, Amit Shetty, Sara Bloomer, Emily J. Lloyd, Ali H. Zaidi, Mathew A. VanDeusen, Rodney J. Landreneau, Abhijit Kulkarni and Blair A. Jobe have no conflicts of interest or financial ties to disclose.
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