Peroral endoscopic myotomy is more effective than balloon dilation in all achalasia

subtypes
Ga Hee Kima†, Kee Wook Junga†, Hwoon-Yong Junga, Min-Ju Kimb, Hee Kyong Naa, Ji Yong
Ahna, Jeong Hoon Leea, Do Hoon Kima, Kee Don Choia, Ho June Songa, Gin Hyug Leea

a
Department of Gastroenterology, Asan Digestive Disease Research Institute, Asan Medical
Center University of Ulsan College of Medicine, Seoul, Korea
b
Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of
Ulsan College of Medicine, Seoul, Korea

†
Ga Hee Kim and †Kee Wook Jung contributed equally to this work as co-first authors.

Running title: POEM vs BD in subtypes of achalasia

Corresponding author: Hwoon-Yong Jung, , MD, PhD, AGAF

Department of Gastroenterology, Asan Digestive Disease Research Institute, Asan Medical
Center, University of Ulsan College of Medicine
88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
E-mail: hyjung@amc.seoul.kr
hwoonymd@gmail.com
Phone: 82-2-3010-3197
Fax: 82-2-476-0824
Guarantor of the article: Hwoon-Yong Jung, M.D., AGAF
Specific author contributions: Ga Hee Kim, Kee Wook Jung, and Hwoon-Yong Jung
designed the study; Min-ju Kim and Kee Don Choi analyzed the raw data and performed
statistical analyses; Hee Kyong Na, Do Hoon Kim, and Jeong Hoon Lee contributed to data
collection; Ji Yong Ahn, Ho June Song, and Gin Hyug Lee interpreted the data; Ga Hee Kim
and Kee Wook Jung drafted the manuscript and prepared the manuscript for submission; all
authors revised the manuscript critically for important intellectual content and gave final
approval of the version to be published.

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/jgh.14616

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Financial support: None for all authors
Potential competing interest: None for all authors
Acknowledgements: None for all authors
Disclosure statement: The authors who have taken part in this study declared that they do
not have anything to disclose regarding funding or conflict of interest with respect to this
manuscript.

Abstract
Background/Aims: Optimal treatment modalities for each of the three subtypes of achalasia
is still under debate. Differences in prognosis and long-term outcomes between peroral
endoscopic myotomy (POEM) and balloon dilation (BD) are also unclear. We aimed to
compare the treatment outcomes of BD and POEM in each subtypes of achalasia by using
information from the manometry database of a tertiary referral center in Korea.
Methods: Data from 5,207 esophageal manometry procedures performed between 1989 and
2016 were analyzed. The medical records and results of esophagography and
esophagogastroduodenoscopy were also reviewed.
Results: We identified 264 patients (116 men and 148 women) with diagnosis of achalasia
during the study period. POEM and BD were carried out on 64 and 177 patients, respectively.
There was a significant difference in the time to relapse between the POEM group and the
BD group (P = 0.002). At the 24-month follow-up, the clinical success rates of POEM and
BD were 91.8% and 68.0%, respectively. The hazard ratio of symptom return was 6.54 for
BD compared with POEM (95% confidence interval 2.12–20.22, P = 0.001). After a follow-
up period of 24 months, the success rate of POEM was significantly higher than that of BD
for all subtypes of achalasia. However, only that of type I and II was statistically significant
(type 1:92.0% vs 51.1%, P=0.004; type 2:92.3% vs 59.8%, P=0.007; type3:91.7% vs 55.6%,
P=0.051).
Conclusions: POEM was more effective than BD in providing mid-long term remission in
patients with all manometric subtypes of achalasia.

Keywords: Achalasia; Manometry; Peroral endoscopic myotomy; Balloon dilation

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INTRODUCTION

Achalasia is an uncommon disorder of esophageal motility with an yearly incidence of 0.03–

1.63 cases per 100,000 population in Western countries.1,2 In the management of achalasia,
the main goal of therapy is alleviating esophagogastric junction (EGJ) outflow obstruction
and subsequent obstructive symptoms.3,4 Current treatment options for achalasia included
pneumatic balloon dilation (BD), botulinum toxin injection, surgical myotomy and peroral
endoscopic myotomy (POEM).3
BD is currently the most commonly used treatment modality because it is relatively easy to
perform, noninvasive, and does not require special training.4 However, because the shearing
effect of BD is localized to the EGJ, BD is recommended for treatment of achalasia types I
and II, albeit merely by expert opinions only and without definite evidence.4-6
For type III achalasia, peroral endoscopic myotomy (POEM) is recommended.5,6 Introduced
in 2010, POEM uses an endoscopic knife to make mucosal incision inside the esophagus and
submucosal tunnel up to the gastric cardia.7 In POEM, the exact length of esophageal
hypercontractility and EGJ outflow obstruction can be dissected in a tailored manner, thus
making it ideal for type III achalasia, which involves both the EGJ and the esophageal body.6
Although POEM now represents one of the most advanced treatment methods for achalasia,
only a limited number of studies based on small number of patients have compared the
treatment outcomes of patients treated with either BD or POEM.8 No randomized trial has
been conducted on comparing POEM with BD for each subtype achalasia, therefore, optimal
treatment modalities for each of the three subtypes of achalasia are still under debate.
Moreover, differences in prognosis and long-term outcomes between POEM and BD are also
unclear.
We therefore aimed to compare the treatment outcomes of BD and POEM in patients with
achalasia using information from the manometry database of a tertiary referral center.

METHODS
We performed a retrospective analysis of the esophageal manometry database records of adult
patients (age >18 years) diagnosed with achalasia at a single center in Korea between June
1989 and December 2016. The following clinical data were collected and analyzed: age, sex,
presenting symptom, and pre and post Eckardt scores. Upper endoscopy and esophagography

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results were also reviewed. The present study was approved by the institutional review board
of the treating institute (approval no. 2017-1161).

Esophageal manometry
From 1989 to 2010, esophageal manometry was performed using an 8-channel water-
perfused manometry catheter (Synectics Medtronics, Stockholm, Sweden) in a standardized
manner, as previously described in detail by Richter et al.9 After 2011, esophageal manometry
was performed using high-resolution manometry (HRM) with 32 solid-state sensors spaced at
1-cm intervals (InSIGHTTMHRiM·system; Sandhill Scientific, Highlands Ranch, CO, USA).
Manometric data were analyzed using the BioView software (Sandhill Scientific Inc.).
Manometric tracings were classified according to the three subtypes according to the Chicago
classification version 3.010: type I = with impaired LES relaxation during swallowing and
aperistalsis of the esophageal body, type II = with pan-esophageal pressurization, type III =
with no peristalsis but with evidence of esophageal spasm. The following metrics were
recorded: integrated relaxation pressure (IRP) and LES resting pressure (LESP). The
diagnosis of achalasia was double checked with barium esophagography, which was
performed at the same time according to the patients’ symptoms. Secondary achalasia was
excluded if patients were diagnosed with any malignancy within 1 year of the achalasia
diagnosis.

BD technique
Patients in the BD group underwent esophagogastroduodenoscopy (EGD) under conscious
sedation with midazolam and pethidine. A guidewire was placed in the stomach, and a
balloon dilator (Rigiflex; Boston Scientific, Natick, MA, USA) was inserted into the stomach
along the guidewire. We checked the location of the balloon using EGD. We then inflated
with either air or contrast medium for few seconds until the curve in the unrelaxed LES was
obvious. We attempted dilation for 60–180 s with a maximum pressure of 15 psi (Boston
Scientific). During the first BD a 30-mm balloon was used, followed by dilation with a 35-
mm balloon after 2-4 weeks.

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POEM operative technique
POEM was performed under general anesthesia by three expert endoscopists (H.Y.J., K.D.C.,
and D.H.K.). An upper gastrointestinal endoscope equipped with a clear plastic cap and
carbon dioxide insufflation were used for all procedures. Landmarks such as the LES,
gastroesophageal junction, and site of incision in the mid-esophagus were identified
endoscopically. After the creation of a submucosal bleb, through injection of saline solution
or starch-based solution, a 2–3 cm longitudinal mucosal incision was made with a hook knife
(Olympus, Tokyo, Japan) using the dry cut mode at 60 W on effect 5 (ERBE, Tübingen,
Germany). The orientation of the mucosal incision and subsequent submucosal tunneling and
myotomy were performed in a posterior fashion at the discretion of the endoscopist. Once
entry into the esophageal submucosal space was achieved, a submucosal tunnel was created
using an insulated-tip knife nano (Olympus) in spray coagulation mode at 80 W on effect 7.
Once the submucosal tunnel was established and beyond 2 cm from the LES, myotomy was
performed starting 2 cm caudally from the mid-esophageal incision with the hook knife and
spray coagulation at 80 W. Myotomy was performed in a selective inner circular manner at
the discretion of the endoscopist. Once the myotomy was completed, the mucosal incision
site was closed with endoclips.

Definitions
Symptom scores were assessed using the Eckardt score. Clinical response was defined as a
decrease in Eckardt score to 3 or lower. Relapse was defined as recurrence of dysphagia
symptom with increase in Eckardt score to 4 or higher. Initial and late clinical outcomes were
determined according to clinical response at 6 months and at least 2 years of follow-up,
respectively.
The secondary outcomes included procedure-related adverse events, LES pressure, IRP on
manometry, clinical reflux adverse events (grade-0 = absent, grade-1 = less than 2 days a
week, grade-2 = 2 to 4 days a week, grade-3 = more than 4 days a week),11 reflux esophagitis
on EGD and other procedure-related parameters.

Statistical analysis
The baseline characteristics of the included patients were compared between the BD and
POEM groups by using Fisher’s exact test, whereas continuous variables were assessed using

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the Mann-Whitney U-test. The long-term clinical success rate and risk of recurrence were
estimated and graphed using the Kaplan-Meier curve and assessed with the log rank test. The
mean values between baseline and follow-up were compared using the Wilcox signed rank
test for paired samples. The Cox proportional hazards model was used to evaluate
independent risk factors for clinical recurrence. All P-values were two sided, with P < 0.05
indicating statistical significance. The Cochran-Armitage trend test was used for trend
analysis according to period.
All statistical analyses were performed using SPSS version 21.0 (IBM Corp., Armonk, NY,
USA).

RESULTS
Diagnostic trend
We identified 264 patients who were diagnosed with achalasia during the study period,
including 116 men and 148 women. Among them, 177 patients initially underwent BD and 64
patients underwent POEM initially.
Table 1 provides an overview of the number of esophageal manometry procedures performed
at our institution during the course of the study period (1989–2016), as well as of the number
of patients diagnosed with achalasia through these procedures. To determine the variation in
the achalasia diagnosis rate, we divided the 27-year period into five separate periods. The
number of esophageal manometry cases appeared to have increased only slightly during the
course of the study period. However, the number of patients with achalasia appeared to
increase significantly during the 27-year period (P < 0.001, Cochran-Armitage trend test).
There was a notable increase in the number of patients diagnosed as with achalasia after 2008,
following the implementation of HRM, and again in 2012, following the implementation of
POEM.

General characteristics of patients

Of the 264 patients, 64 initially underwent POEM and 177 patients underwent initially BD.
The two groups were similar at baseline in sex, body mass index (BMI), symptom, Eckardt
score, and type of HRM (Table 2). Patients who underwent POEM were significantly older,
had lower post Eckardt scores, more proton pump inhibitor (PPI) use, higher IRP than
patients who underwent BD. Patients who underwent POEM were significantly older

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(49.48±17.2 vs 44.08±16.82, P=0.033) And the base line LES pressure higher in BD group
than POEM group (49.01±32.5 vs 39.28±25.91, P=0.018).

Relapse rate and time to relapse

Eighty-five patients (35.0%) had recurrence of dysphagia. Of the 64 patients who underwent
POEM, five (7.8%) patients developed symptom recurrence compared to 80 of 177 (45.2%)
patients who underwent BD. Concerning short- and long-term efficacy, the treatment success
rates of POEM at 6, 12, and 24 months after the primary treatment were higher than those of
BD (95% vs. 83.2%, 95% vs. 77.6%, and 91.8% vs. 68%; P = 0.002) (Figure 1a).
Subsequently, we compared the treatment success rates of BD and POEM for the different
manometric subtypes. In type I and II the success rate for BD was significantly higher than
that for POEM after 24 months ( type I;P =0.004 , type II;P=0.007, Figure 1b,c) For type III,
the success rates after 24 months were 91.7% and 55.6% for POEM and BD, respectively
(Figure 1d). However, because of the low number of patients in this subgroup, this difference
was not statistically significant (P =0.051).
In the BD group, 80 patients (45.2%) had a recurrence of symptoms. Subsequently,
redilation was performed in 27 patients. A total of 11 patients underwent POEM. However, it
was not successful in two patients, who were then referred for surgery. Moreover, two
patients underwent surgery because of perforation after dilation.
Of the 64 patients treated with POEM, five patients were considered to have had treatment
failure and three patients were subsequently treated with redo POEM. Additionally, two
patients were placed under close observation without further procedures.

Treatment outcome predictors

We used multivariate Cox proportional hazard models to predict risk factors for relapse in the
study patients (Table 3). We tested factors such as treatment method, age, sex, BMI,
symptom, pre and post Eckardt score, PPI use, baseline LES pressure, and IRP. The hazard
ratio (HR) of symptom return was 6.54 for BD compared with POEM (P = 0.001). Moreover,
the presence of chest pain at diagnosis predicted the recurrence of dysphagia (HR 1.53, P =
0.036).

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Comparison of treatment outcomes according to manometric subtypes
In the POEM group, type I achalasia was present in 26 (40.6%), type II achalasia was present
in 25 (39.1%), and type III achalasia was present in 13 (20.3%) patients. All three groups of
patients who underwent POEM showed significantly improved post POEM Eckardt scores
(Figure 2a). Furthermore, the LES pressure (from 34.48 ± 19.6 to 12.28 ± 5.72 mmHg in
type I, from 41.07 ± 6.4 to 18.89 ± 9.38 mmHg in type II, and from 45.48 ± 23.97 to 20.3 ±
10.32 mmHg in type III; all P < 0.05) and IRP (from 21.22 ± 9.73 to 8.5 ± 6.43 mmHg in type
I, from 33.72 ± 15.44 to 12.53 ± 8.68 mmHg in type II, and from 24.38 ± 8.76 to 16.73 ± 8.62
mmHg in type III; all P < 0.05) significantly decreased after POEM in all three groups
(Figure 2b,c). IRP decreased the most in patients with type II achalasia.
In the BD group, only 83 patients (46.9%) were tested using HRM. Among them, type I
achalasia was present in 33 (45.2%), type II achalasia was present in 34 (46.2%), and type III
achalasia was present in six (8.2%) patients. All three groups of patients who underwent BD
showed significantly improved post BD Eckardt scores (Figure 3a). The LES pressure (from
35.91 ± 29.1 to 10.59 ± 7.18 mmHg in type I, from 42.13 ± 22.16 to 27.52 ± 11.42 mmHg in
type II, and from 50.86 ± 42.24 to 19.58 ± 13.01 mmHg in type III; all P < 0.05) and IRP
(from 17.88 ± 12.04 to 7.64 ± 6.1 mmHg, P=0.007 in type I, from 21.91 ± 9.12 to 6.82 ± 6.85
mmHg, P=0.099 in type II, and from 17.0 ± 10.24 to 11.65 ± 6.15 mmHg, P=0.993 in type III)
decreased after BD in all three groups of patients (Figure 3b,c).
We evaluated subgroups of risk factors for relapse in study patients according to treatment
modality for manometric subtypes (Table 4). In patients with type I achalasia, the HR of
symptom return was 4.69 for BD compared with POEM (P = 0.02). In patients with type II
and III achalasia, no statistically significant difference was observed between the two
therapies in the multivariate analysis of symptom return (type II: HR 7.08, P = 0.066; type III:
HR 11.88, P = 0.082).

Complications and adverse events

Esophageal perforation occurred in 3 of 177 patients (1.7%) in the BD group. Perforations
were managed surgically in two patients and conservatively in one patient.
In the POEM group, mucosal injuries occurred in two patients and delayed bleeding
occurred in two patients. Gastroesophageal reflux was evaluated in 64 patients in the POEM
group; 25 patients reported the presence of reflux symptoms, with 28 grade-1 cases and one

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grade-2 case. Of the 27 patients who received follow-up EGD, only four patients showed
mild esophagitis (Los Angeles classification grade A) (Table S1).
DISCUSSION
In this single-center retrospective study, we evaluated and compared the efficacy and
manometry outcomes between BD and POEM as treatments for achalasia. The major finding
of this study is that POEM provided better long-term efficacy. This is the first study to
demonstrate the comparative efficacy of POEM and BD with a long-term follow-up period.
Achalasia is a progressive disorder that results in an impaired LES.12 The various modalities
for the management of achalasia include pharmacological treatment, endoscopic pneumatic
BD, botulinum injection, Heller’s myotomy, and, more recently, POEM.13 BD uses air
pressure to intraluminally dilate and disrupt the circular muscle fibers of the LES. For many
years, repeated endoscopic BD has been the treatment of choice, leading to therapeutic
success rates of 86% and 85% at 2 and 5 years, respectively.14,15 Although not considered a
failure of therapy, 25% of patients require at least one repeat dilation within a 5-year follow-
up.15 The optimal treatment of primary achalasia remains unclear. There have been no
randomized trials comparing the efficacy of BD and POEM. A pooled analysis of several
cohort studies comparing POEM and laparoscopic Heller’s myotomy showed similar
outcomes. However, there was a trend toward reduced hospital stay in the POEM group.16-18
Pre- and post-treatment physiological evaluation of esophageal function in achalasia patients
using HRM is essential to assess the improvement after treatment and to predict long-term
response.19 HRM parameters such as IRP were shown to correlate with symptom scores of
achalasia. In the present study, LES pressure and IRP decreased significantly after treatment
in both groups. Even in the subgroup analysis for three different subtypes, we found that both
BD and POEM produced significant improvements in both LES pressure and IRP. POEM
showed significantly better sustained symptom improvement than BD.
In a previous study, the response to BD was the highest in type II achalasia and somewhat
lower in type I achalasia; patients with type III achalasia had a poor response to all forms of
therapy.20 These results were similar to those of laparoscopic Heller’s myotomy.21 All
enrolled patients showed significant improvements in Eckardt score, LESP, and IRP after BD
or POEM regardless of achalasia subtype (Figure 2 and 3). And we did not use a 40-mm
balloon, as for most Asian patients 30-mm or 35-mm-diameter dilators are the most
appropriate. Hence, the 40-mm Rigiflex dilator was not used in our study, which was

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performed in the Asian countries22-24.
In this study, because of the small sample size, no statistically significant difference was
observed between the two therapies in the multivariate analysis of symptom return in types II
and III achalasia. However, in multivariate analysis, POEM tended to show better outcomes
than BD in type III achalasia (HR 11.88, P = 0.082; the difference was not statistically
significant because of the small number of patients) rather than in type I (HR 4.69, P = 0.02)
or type II (HR 7.08, P = 0.066) achalasia (Table 4). This is the first study to compare 2
different treatment modalities in 3 achalasia types.
During the last three decades, the number of patients who were newly diagnosed with
achalasia significantly increased in 2008 and 2012 (Table 1). We postulated that the use of
HRM and POEM was one of the reasons for this. The same results were also found in
Western countries. However, this finding should be verified using a large number of cases in
a nationwide study.
This study has several potential limitations. First, this was a retrospective study, and it was
difficult to ensure that all clinical manifestations were accounted for in the reports. Only 83
of 177 (46.9%) patients underwent HRM test in the BD group, contrast to the POEM group.
The remaining patients in the BD group underwent conventional manometry. Therefore, we
performed an additional analysis which displays data on the oldest patients who were
excluded from the study, with a diagnosis made using conventional manometry (Table S2,
S3). The results were similar to those of the previous analysis. In our study, a novel treatment
method, peroral endoscopic myotomy (POEM), was started in 2012. We recognize that the
different time periods in the two groups (BD -earlier, poem -later) is a limitation of our study.
records about symptoms or Furthermore, an exact comparison between the clinical outcomes
of manometric subtype groups was difficult because only 19 patients with type III achalasia
were enrolled. However, our study makes a significant contribution to the literature because
this is the first study to compare the efficacies of POEM and BD in large number of patients.
We expect that our study will provide both momentum and direction to future prospective
studies on achalasia treatment options.
In conclusion, POEM appears to be more effective than BD for providing mid-long term
remission in Korean patients with all manometric subtypes of achalasia. Based on the results
of our study even type I or II achalasia patients need to be considered as an initial treatment
of POEM.

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REFERENCES

1 Birgisson S, Richter JE. Achalasia in Iceland, 1952-2002: an epidemiologic study. Dig.

Dis. Sci. 2007; 52: 1855-1860.
2 Samo S, Carlson DA, Gregory DL, Gawel SH, Pandolfino JE, Kahrilas PJ. Incidence
and prevalence of achalasia in central Chicago, 2004-2014, since the widespread use
of high-resolution manometry. Clin. Gastroenterol. Hepatol. 2017; 15: 366-373.
3 Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and
management of achalasia. Am. J. Gastroenterol. 2013; 108: 1238-1249; quiz 1250.
4 Pandolfino JE, Kahrilas PJ. Presentation, diagnosis, and management of achalasia.
Clin. Gastroenterol. Hepatol. 2013; 11: 887-897.
5 Kahrilas PJ, Pandolfino JE. Treatments for achalasia in 2017: how to choose among
them. Curr. Opin. Gastroenterol. 2017; 33: 270-276.
6 Kahrilas PJ, Bredenoord AJ, Carlson DA, Pandolfino JE. Advances in management of
esophageal motility disorders. Clin. Gastroenterol. Hepatol.
7 Inoue H, Minami H, Kobayashi Y et al. Peroral endoscopic myotomy (POEM) for
esophageal achalasia. Endoscopy 2010; 42: 265-271.
8 Tan Y, Zhu H, Li C, Chu Y, Huo J, Liu D. Comparison of peroral endoscopic
myotomy and endoscopic balloon dilation for primary treatment of pediatric achalasia.
J. Pediatr. Surg. 2016; 51: 1613-1618.
9 Richter JE, Wu WC, Johns DN et al. Esophageal manometry in 95 healthy adult
volunteers. Variability of pressures with age and frequency of "abnormal" contractions.
Dig. Dis. Sci. 1987; 32: 583-592.
10 Kahrilas PJ, Bredenoord AJ, Fox M et al. The Chicago Classification of esophageal
motility disorders, v3.0. Neurogastroenterol. Motil. 2015; 27: 160-174.
11 Vigneri S, Termini R, Leandro G et al. A comparison of five maintenance therapies
for reflux esophagitis. N. Engl. J. Med. 1995; 333: 1106-1110.
12 Chuah SK, Hsu PI, Wu KL, Wu DC, Tai WC, Changchien CS. 2011 update on
esophageal achalasia. World J. Gastroenterol. 2012; 18: 1573-1578.
13 Banks M, Sweis R. POEM and the management of achalasia. Frontline Gastroenterol.
2017; 8: 143-147.
14 Boeckxstaens GE, Annese V, des Varannes SB et al. Pneumatic dilation versus
laparoscopic Heller's myotomy for idiopathic achalasia. N. Engl. J. Med. 2011; 364:

This article is protected by copyright. All rights reserved.

 1807-1816.
15 Moonen A, Annese V, Belmans A et al. Long-term results of the European achalasia
trial: a multicentre randomised controlled trial comparing pneumatic dilation versus
laparoscopic Heller myotomy. Gut 2016; 65: 732-739.
16 Bhayani NH, Kurian AA, Dunst CM, Sharata AM, Rieder E, Swanstrom LL. A
comparative study on comprehensive, objective outcomes of laparoscopic Heller
myotomy with per-oral endoscopic myotomy (POEM) for achalasia. Ann. Surg. 2014;
259: 1098-1103.
17 Leeds SG, Burdick JS, Ogola GO, Ontiveros E. Comparison of outcomes of
laparoscopic Heller myotomy versus per-oral endoscopic myotomy for management
of achalasia. Proc. (Bayl. Univ. Med. Cent.) 2017; 30: 419-423.
18 Marano L, Pallabazzer G, Solito B et al. Surgery or peroral esophageal myotomy for
achalasia: a systematic review and meta-analysis. Medicine (Baltimore) 2016; 95:
e3001.
19 Tang Y, Xie C, Wang M, Jiang L, Shi R, Lin L. Association of high-resolution
manometry metrics with the symptoms of achalasia and the symptomatic outcomes of
peroral esophageal myotomy. PLoS One 2015; 10: e0139385.
20 Pratap N, Kalapala R, Darisetty S et al. Achalasia cardia subtyping by high-resolution
manometry predicts the therapeutic outcome of pneumatic balloon dilatation. J.
Neurogastroenterol. Motil. 2011; 17: 48-53.
21 Salvador R, Costantini M, Zaninotto G et al. The preoperative manometric pattern
predicts the outcome of surgical treatment for esophageal achalasia. J. Gastrointest.
Surg. 2010; 14: 1635-1645.
22 Yamashita H, Ashida K, Fukuchi T et al. Predictive factors associated with the
success of pneumatic dilatation in Japanese patients with primary achalasia: a study
using high-resolution manometry. Digestion 2013; 87: 23-28.
23 Jeon HH, Youn YH, Rhee K, Kim JH, Park H, Conklin JL. For patients with primary
achalasia the clinical success of pneumatic balloon dilatation can be predicted from
the residual fraction of radionuclide during esophageal transit scintigraphy. Dig. Dis.
Sci. 2014; 59: 375-382.
24 Meng F, Li P, Wang Y et al. Peroral endoscopic myotomy compared with pneumatic
dilation for newly diagnosed achalasia. Surg. Endosc. 2017; 31: 4665-4672.

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Table 1. Diagnostic trend of achalasia over the last 27 years with respect to the number of
esophageal manometry cases
Year of diagnosis

1989- 1997- 2002- 2007- 2012- P-valuea

1996 2001 2006 2011 2016

Number of achalasia cases 13 19 39 65 128

Number of esophageal
604 703 938 1363 1597
manometry tests performed <0.001

Achalasia per
2.1 2.7 4.1 4.8 8.0
manometry (%)
a
P-value was estimated using the Cochran-Armitage trend test

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Table 2. Baseline characteristics of patients in the POEM and BD groups
POEM (n=64) BD (n=177) P-value
Sex (M : F) 25 (29.1): 39 (60.9) 76 (43.0): 101 (57.0) 0.658
Age (years, mean±SD) 49.48±17.2 44.08±16.82 0.033
BMI (kg/m2, mean±SD) 21.94±3.76 21.56±3.89 0.491
Type of
Solid 7 (10.9) 42 (23.7) 0.081
dysphagia
Liquid 2 (3.1) 3 (1.7)
Both 55 (85.9) 132 (74.6)
Dysphagia 2.91±0.29 2.81±0.49 0.062
Regurgitation 1.56±1.11 1.69±1.02 0.392
Chest pain 1.36±0.96 1.30±1.02 0.457
Weight loss 1.09±1.12 0.83±1.06 0.613
Pre Eckardt score 6.88±1.59 6.56±1.64 0.189
Post Eckardt score 1.14±1.66 1.79±1.75 0.007
PPI use (n) 60 (93.7) 120 (67.8) <0.001
LES pressure (mmHg,
39.28±25.91 49.01±32.50 0.018
mean±SD)
IRP (mmHg, mean±SD) 27.26±12.95 19.25±10.62 0.001
Follow-up, mo, mean±SD 21.98 ± 17.62 49.23±52.77 0.009
Type of HRM Type 1 26 (40.6) 33 (45.2) 0.122
Type 2 25 (39.1) 34 (46.2)
Type 3 13 (20.3) 6 (8.2)

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Table 3. Univariate and multivariate analyses of factors affecting relapse
Univariate analysis Multivariate analysis
HR* (95% CI) P-value HR* (95% CI) P-value
Treatment
POEM 1 1
BD 3.89 (1.55-9.76) 0.004 6.54 (2.12-20.22) 0.001
Age (years) 0.99 (0.98-1.01) 0.342
Sex
Male 1
Female 1.08 (0.87-1.34) 0.486
BMI (kg/m2) 1.01 (0.95-1.07) 0.793
Dysphagia 1.09 (0.70-1.67) 0.705
Regurgitation 0.88 (0.72-1.08) 0.238
Chest pain 1.46 (1.18-1.81) <0.001 1.53 (1.03-2.3) 0.036
Weight loss 1.02 (0.84-1.23) 0.844
Pre Eckardt score 1.06 (0.94-1.2) 0.352
Post Eckardt score 1.37 (1.24-1.5) <0.001 1.36 (1.24-1.5) 0.697
PPI use 1.11 (0.67-1.85) 0.681
LES pressure 0.99 (0.98-1.0) 0.196
IRP 0.96 (0.92-1.0) 0.026 0.97 (0.93-1.01) 0.156
Type of HRM
Type 1 1
Type 2 0.61 (0.34-1.11) 0.108
Type 3 0.71 (0.25-2.1) 0.534
HR, hazard ratio; CI, confidence interval; POEM, peroral endoscopic myotomy; BD, balloon
dilation; BMI, body mass index; PPI, proton pump inhibitor; LES, lower esophageal
sphincter; IRP, integrated relaxation pressure; HRM, high-resolution manometry.

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Table 4. Univariate and multivariate analyses of factors affecting relapse for each achalasia type.
Type 1 (n=59) Type 2 (n=59) Type 3 (n=19)
Univari Multivariate analysis Univari Multivariate analysis Univari Multivariate analysis
ate P- HR* (95% P- ate P- HR* (95% P- ate P- HR* (95% CI) P-
value CI) value value CI) value value value
Treatment
POEM - 1 1 - 1
BD 0.013 4.69 (1.27- 0.02 0.035 7.08 (0.88- 0.066 0.092 11.88 (0.73- 0.082
0.181 17.25) 0.215 57.17) 0.928 193.43)
Age (years) 0.86 0.222 0.45 -
Sex, Female 6 0.246 0 -
BMI (kg/m2) 0.121 0.759 0.776
Dysphagia 0.436 0.314 0.710

Regurgitation 0.939 0.02 0.969

Chest pain 0.075 1.49 (0.96- 0.073 0.129 1.81 (1.06- 0.03 0.528
0.724 2.28) 0.812 3.09) 0.91

Weight loss 0.342 0.03 0.582 1.84 (0.48-7.11) 0.376

Pre Eckardt 0.045 0.331 0.405

score 0.355 1.04 (0.87- 0.680 0.545 1.2 (0.9-1.6) 0.212 NA

0.422 0.237 0.76

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Post Eckardt 0.346 1.23) 0.733
score
PPI use
LES pressure
IRP

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Figure 1. Kaplan-Meier curves of time to treatment failure for BD (blue line) and POEM (red
line) during the 5 years after treatment. BD, balloon dilation; POEM, peroral endoscopic
myotomy. (a) All type, (b) type I, (c) type II, (d) type III

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Figure 2. (a) Eckardt scores before and after POEM. *P < 0.001, †P < 0.001,‡P = 0.001. (b)
Lower esophageal sphincter resting pressures before and after POEM. *P < 0.001,†P =
0.002,‡P = 0.01. (c) Integrated relaxation pressures before and after POEM. *P < 0.001, †P <
0.001,‡P = 0.007. POEM, peroral endoscopic myotomy.

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 Figure 3. (a) Eckardt scores before and after BD. *P < 0.001, †P = 0.0260,‡P = 0.1. (b) Lower
esophageal sphincter resting pressures before and after BD. *P < 0.001, †P = 0.001,‡P = 0.001.
(c) Integrated relaxation pressures before and after BD. *P = 0.007, †P = 0.099,‡P = 0.993. BD,
balloon dilation.

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