JNM

J Neurogastroenterol Motil, Vol. 26 No. 2 April, 2020

pISSN: 2093-0879 eISSN: 2093-0887
https://doi.org/10.5056/jnm20014
Journal of Neurogastroenterology and Motility Review

2019 Seoul Consensus on Esophageal Achalasia

Guidelines

Hye-Kyung Jung,1 Su Jin Hong,2 Oh Young Lee,3* John Pandolfino,4 Hyojin Park,5 Hiroto Miwa,6 Uday C Ghoshal,7 Sanjiv
Mahadeva,8 Tadayuki Oshima,6 Minhu Chen,9 Andrew S B Chua,10 Yu Kyung Cho,11 Tae Hee Lee,12 Yang Won Min,13 Chan
Hyuk Park,14 Joong Goo Kwon,15 Moo In Park,16 Kyoungwon Jung,16 Jong Kyu Park,17 Kee Wook Jung,18 Hyun Chul Lim,19 Da
Hyun Jung,20 Do Hoon Kim,18 Chul-Hyun Lim,21 Hee Seok Moon,22 Jung Ho Park,23 Suck Chei Choi,24 Hidekazu Suzuki,25 Tanisa
Patcharatrakul,26 Justin C Y Wu,27 Kwang Jae Lee,28 Shinwa Tanaka,29 Kewin T H Siah,30 Kyung Sik Park,31 and Sung Eun Kim16; The
Korean Society of Neurogastroenterology and Motility
1
Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea; 2Digestive Disease Center and Research Institute,
Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea; 3Department of Internal Medicine, Hanyang
University Hospital, Hanyang University College of Medicine, Seoul, Korea; 4Department of Medicine, Feinberg School of Medicine, Northwestern
University, Chicago, IL, USA; 5Division of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea;
6
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan;
7
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 8Division of Gastroenterology,
Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 9Department of Gastroenterology and Hepatology,
The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; 10Gastro Centre, Ipoh, Malaysia; 11Division of Gastroenterology
and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; 12Department of
Internal Medicine, College of Medicine, Soonchunhyang University Hospital, Seoul, Korea; 13Department of Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Korea; 14Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang
University College of Medicine, Guri, Korea; 15Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea;
16
Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea; 17Department of Internal Medicine, Gangneung Asan
Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea; 18Department of Gastroenterology, Asan Medical Center,
University of Ulsan College of Medicine, University of Ulsan College of Medicine, Seoul, Korea; 19Department of Internal Medicine, Yongin
Severance Hospital, Yonsei University College of Medicine, Yongin, Korea; 20Division of Gastroenterology, Department of Internal Medicine,
Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 21Department of Internal Medicine, Eunpyeong St. Mary's Hospital,
College of Medicine, The Catholic University of Korea, Seoul, Korea; 22Department of Internal Medicine, Chungnam National University School
of Medicine, Daejeon, Korea; 23Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan
University School of Medicine, Seoul, Korea; 24Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University
School of Medicine, Iksan, Korea; 25Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa,
Japan; 26Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; 27Department of Medicine
and Therapeutics, Prince of Wales Hospital, Hong Kong, China; 28Department of Gastroenterology, Ajou University School of Medicine, Suwon,
Gyeonggi-do, Korea; 29Department of Gastroenterology, Kobe University Hospital, Hyogo, Japan; 30Division of Gastroenterology and Hepatology,
National University Health System, Singapore City, Singapore; and 31Department of Internal Medicine, Keimyung University School of Medicine,
Daegu, Korea

Received: January 29, 2020 Revised: None Accepted: March 8, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.
org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work
is properly cited.
*Correspondence: Oh Young Lee, MD, PhD
Department of Internal Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea
Tel: +82-2-2290-8343, Fax: +82-2-2298-8341, E-mail: [email protected]
Hye-Kyung Jung and Su Jin Hong equally contributed to this study.

ⓒ 2020 The Korean Society of Neurogastroenterology and Motility

180 J Neurogastroenterol Motil, Vol. 26 No. 2 April, 2020

www.jnmjournal.org
 Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of
esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent
development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based
on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive
than surgery with comparable efficacy. The present guidelines (the “2019 Seoul Consensus on Esophageal Achalasia Guidelines”)
were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society
of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of
the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines
consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10
pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including
gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could
use these guidelines to make an informed decision on the management of achalasia.
(J Neurogastroenterol Motil 2020;26:180-203)

Key Words
Esophageal achalasia; Esophageal motility disorders; Guideline; Manometry; Myotomy

geons, and general physicians), nurses, and paramedical teams.

The guidelines are intended to help primary physicians and
Introduction general health professionals to make achalasia management de-
Esophageal achalasia is a primary motility disorder character- cisions; the guidelines are also designed to provide educational
ized by incomplete lower esophageal sphincter (LES) relaxation resource for medical students and healthcare providers, and to
and loss of esophageal peristalsis.1 Consequently, the transit of provide patients with the most up-to-date information on their
swallowed food boluses through the esophagus is impaired and the conditions.
patient typically experiences dysphagia. Backflow of saliva or undi-
gested food can cause heartburn, regurgitation or vomiting, chest
pain, and respiratory symptoms such as nocturnal cough, recurrent
Methods
breathing difficulty, and pneumonia. Achalasia is a chronic disease The guideline steering committee consisted of the Presidents
that causes progressive irreversible loss of esophageal motor func- and key members of the Korean Society of Neurogastroenterol-
tion. Achalasia is difficult to diagnose early, but it is important to ogy and Motility (KSNM) and Asian Neurogastroenterology and
identify and treat the condition before irreversible changes occur. Motility Association (ANMA). This committee established the
Over the last decade, novel diagnostic modalities, such as guideline development strategy and approved the project budget.
high-resolution manometry (HRM), as well as treatment advanc- Development of the guidelines began in June 2018. The working
es such as peroral endoscopic myotomy (POEM), have greatly group comprises 38 expert gastroenterologists, surgeons and meth-
improved the success rate of achalasia treatment. However, these odologists, selected from among KSNM and ANMA members
developments remain unknown to most but few gastrointestinal and other experts. Three workshops were conducted while develop-
(GI) motility experts. We need clinical guidelines for the diagnosis ing the revised guidelines and the working group held 8 meetings.
and management of achalasia based on evidence-based medicine The working group identified the most clinically significant
that will help to inform healthcare providers and patients. questions using the nominal group technique.2 The guidelines
The guidelines describe approaches to the practical manage- were developed using both adaptation and de novo methods. The
ment of adult patients with achalasia based on scientific evidence literature was searched for existing guidelines on achalasia. The
and expert consensus. The guidelines cover several options for the search terms used were achalasia-related index words (“achalasia”)
treatment of achalasia, summarize the benefits and harms of each, and guideline-related index words (“clinical protocols” OR “indi-
and provide information on the probable outcomes. cation” OR “therapeutics” OR “therapy” OR “therapeutic use”
The present guidelines provide a practical, evidence-based OR “therapy*” OR “diagnosis” OR “guideline” OR “guidelines
guide for clinicians (gastroenterologists, upper GI tract sur- as topic” OR “guideline adherence” OR “practice guideline” OR

181
Hye-Kyung Jung, et al

“practice guideline as topic” OR “clinical guideline” OR “clinical of evidence for achalasia treatment recommendation was assessed
practice guideline” OR “consensus” OR “recommendation” OR based on the Grading of Recommendations, Assessment, Develop-
“workshop”). The inclusion criteria for the existing guidelines were ment and Evaluation (GRADE) system (Table 1).4 The treatment
as follows: (1) achalasia guidelines pertaining to adults, (2) written recommendations for primary esophageal achalasia were classified as
in English, and (3) published between January 2005 and July 2018. “strong for” “weak for” “weak against” “strong against” or “no rec-
The exclusion criteria were as follows: (1) already developed via the ommendation”. The evidence level, clinical applicability, and benefits
adaptation process and (2) not supported by evidence-based medi- and harms were the evaluation criteria.
cine. Eight guidelines were identified. A systematic review was also Consensus was sought for the draft recommendations devel-
conducted, to identify clinical recommendations requiring an update oped herein using the modified Delphi method.5 An expert panel
due to new evidence, particularly pertaining to POEM and laparo- comprising members of the KSNM and ANMA, and other
scopic Heller myotomy (LHM). The Medline, EMBASE, and experts, reviewed the draft. The first draft consisted of 18 recom-
Cochrane Library databases were searched for all relevant studies mendations with one open question: 2 pertaining to the definition
published during the period 2000-2018. The following index terms and epidemiology of achalasia, 6 pertaining to diagnoses, and 10
were used as search queries: ([POEM] OR [endoscopic myoto- pertaining to treatments. The first draft was sent via e-mail to the
my]) AND ([laparoscopic myotomy] OR [surgical myotomy] OR experts and their responses were anonymized. A score of more than
[Heller myotomy] or [Heller’s myotomy]). The inclusion criteria 4 on a 5-point Likert scale was considered to correspond to “agree”
were as follows: (1) published in English, (2) published between (with the recommendation in question); if more than two-thirds
2000 and 2018, and (3) pertaining to adult patients with achalasia. of all 47 respondents agreed with a recommendation, consensus
The exclusion criteria were as follows: (1) published in languages was considered to have been reached thereon. Consensus was not
other than English, (2) animal studies, and (3) studies of adolescents reached on only 1 of the 18 recommendations on LHM. After the
or children (under the age of 19 years) (Supplementary Figure). We first round of appraisals, the working group presented the draft
critically appraised the quality of the selected studies using the risk recommendations at an ANMA consensus meeting held on April 6,
of bias tools described in the endoscopic treatment section developed 2019. A second round of appraisals, of the modified recommenda-
by a de novo method and the Cochrane Risk of Bias Tool.3 The level tion for LHM, achieved a 93.9% consensus (31/33 experts). Two

4
Table 1. Levels of Evidence and Support for the Various Primary Esophageal Achalasia Treatment Recommendations

Level of evidence
High At least one RCT or SR/meta-analysis with no concern regarding study quality
Moderate At least one RCT or SR/meta-analysis with minor concerns regarding study quality or,
at least one cohort/case-control/diagnostic test design study with no concern regarding study quality
Low At least one cohort/case-control/diagnostic test study with minor concerns regarding study quality,
or at least one single arm before-after study or, cross-sectional study with no concerns regarding study quality
Very low At least one cohort/case-control/diagnostic test design study with serious concerns regarding study quality,
or at least one single arm before-after study or cross-sectional study with minor/severe concerns regarding study quality
Grade of recommendation
Strong for The benefits of the intervention are greater than the harms based on a high or moderate level of evidence,
such that it can be strongly recommended for clinical practice in most cases.
Weak for The benefits and harms of the intervention may vary depending on the clinical situation or patient characteristics.
Recommended depending to the clinical situation.
Weak against The benefits and harms of the intervention may vary depending on the clinical situation or patient characteristics.
Intervention not be recommended for clinical practice.
Strong against The harms of the intervention are greater than the benefits based on a high or moderate level of evidence,
such that it is not recommended for clinical practice.
No recommendation It is not possible to classify the recommendation owing to a lack of evidence or equivocal results.
Further evidence is needed.
RCT, randomized controlled trial; SR, systematic review.

182 Journal of Neurogastroenterology and Motility

 Seoul Consensus on Achalasia

external experts (Y.T.B. [South Korea] and S.G [Thailand] re- Achalasia is a primary esophageal motor disorder characterized
viewed the recommendations in terms of necessity, appropriateness, by incomplete LES relaxation and an absence of esophageal peri-
health care setting, level of care, and balance between benefits and stalsis.1 The cause of achalasia is not clear yet. Idiopathic achalasia
harms. The final 18 recommendations/guidelines, and a flowchart occurs secondary to destruction of the myenteric plexus, which in-
for the diagnosis and treatment of esophageal achalasia, are pre- volves both peristaltic contraction and LES relaxation.6 The clinical
sented in Table 2 and Figure 1, respectively. presentation includes dysphagia to solids and liquids, regurgitation
This project was funded by the KSNM; there was no external of bland undigested food or saliva, chest pain during eating, and
source of support. All members of the working team confirmed via weight loss. Objective symptom scoring systems, such as the Eck-
e-mail that they had no conflicts of interest related to the develop- ardt score, are important for determining the treatment response
ment of the guidelines, which will be updated every 3 to 5 years to (Table 3).1 A subset of patients with achalasia experience heartburn,
take account of new evidences accumulated. which often leads to misdiagnosis of achalasia as gastroesophageal
reflux disease (GERD).7 Achalasia can be diagnosed based on ma-
nometry, esophagography, or endoscopy findings.1 Pseudoachalasia,
Definition and Epidemiology of Achalasia which shows similar clinical features but is caused by cancer or Try-
panosoma cruzi infection, should be excluded.8
Definition
Epidemiology of Achalasia
Statement 1: Achalasia is a primary motor disorder
of the esophagus characterized by insufficient lower Statement 2: Achalasia is a very rare disorder of the
esophageal sphincter relaxation and loss of esophageal esophagus that affects both sexes equally and is fre-
peristalsis. quently diagnosed in patients aged 40 to 60 years.
(Level of evidence, not applicable; strength of recommenda- (Level of evidence, not applicable; strength of recommenda-
tion, not applicable) tion, not applicable)
Experts’ opinions: agree strongly (78.2%), agree with some Experts’ opinions: agree strongly (34.8%), agree with some
reservations (19.6%), undecided (0.0%), disagree (2.2%), and reservations (54.4%), undecided (6.5%), disagree (4.3%), and
disagree strongly (0.0%) disagree strongly (0.0%)

Suspicious achalasia

Endoscopy (+ CT/EUS) Malignancy, peptic stricture with

acid reflux, structural disorder
such as esophageal webs and
Esophagography (TBE)* rings or eosinophilic esophagitis
High resolution manometry**

Achalasia: subtype I/II/III

Low surgical risk High surgical risk

Subtype I/II Subtype III Botulinum toxin injection/+ oral

pharmaceutical agents

LHM PBD POEM

Failed initial treatment

*For helpful for diagnosis and estimation of the severity and treatment
response of achalasia by time barium esophagograpjy (TBE) Figure 1. Flowchart of the management
PBD/POEM/LHM **Gold standard for diagnosis and classification of subtypes of
achalasia of esophageal achalasia.

Vol. 26, No. 2 April, 2020 (180-203) 183

Hye-Kyung Jung, et al

Table 2. Summary of Recommendations/Guidelines for Primary Esophageal Achalasia

Level of Strength of
Statement
evidence recommendation
Definition and epidemiology of achalasia
1. Achalasia is a primary motor disorder of the esophagus characterized by insufficient lower esophageal NA NA
sphincter relaxation and loss of esophageal peristalsis.
2. Achalasia is a very rare disorder of the esophagus that affects both sexes equally and is frequently NA NA
diagnosed in patients aged between 40 and 60 years.
Diagnosis of esophageal achalasia
Esophageal manometry
3. Esophageal manometry is a gold standard test for diagnosis of achalasia. Low Strong
4. High-resolution manometry is superior to conventional manometry for the diagnosis of achalasia. Low Strong
5. The Chicago classification is a useful tool to define the clinically relevant phenotypes of achalasia. Moderate Strong
Barium esophagography
6. Barium esophagography is recommended to diagnose achalasia in patients with esophageal dysphagia. Low Strong
7. Timed barium esophagography is useful for assessing the severity of achalasia, and for evaluating Moderate Strong
treatment outcomes.
Endoscopy
8. Endoscopic assessment is recommended for achalasia patients to rule out pseudoachalasia caused Low Strong
by cancer or other esophageal diseases (eg, peptic stricture with acid reflux, structural disorders such
as esophageal webs and rings, or esophageal inflammation).
Treatment of esophageal achalasia
Oral pharmacologic treatment
9. Oral pharmacologic therapy can be considered for achalasia whose general condition renders them Low Weak
unsuitable for endoscopic treatment or surgery.
Botulinum toxin injection
10. Botulinum toxin injection is recommended for achalasia patients whose general condition renders them Moderate Strong
unsuitable for endoscopic treatment or surgery.
Pneumatic balloon dilatation
11. Pneumatic balloon dilatation is recommended as an initial treatment for patients with achalasia. Moderate Strong
Peroral endoscopic myotomy
12. The outcomes of peroral endoscopic myotomy are comparable to those of Heller myotomy for Moderate Strong
treatment-naïve patients with achalasia.
13. Peroral endoscopic myotomy, rather than Heller myotomy, should be considered for the treatment of Low Weak
type III achalasia because enables extended myotomy.
14. Acid suppressive therapy is recommended for patients with reflux symptoms or esophageal erosion Low Strong
undergoing peroral endoscopic myotomy, to prevent esophageal stricture.
Surgical treatment
15. Laparoscopic Heller myotomy can be considered as one of first-line therapies for achalasia patients, Moderate Weak
and has similar expected clinical outcomes to pneumatic balloon dilation.
16. Partial fundoplication in addition to LHM is recommended to reduce the risk of subsequent GERD. Low Strong
Management of recurrence of achalasia after initial treatment
17. Peroral endoscopic myotomy is recommended for achalasia patients who failed initial endoscopic treatment. Moderate Strong
18. Peroral endoscopic myotomy can be considered as a rescue treatment for achalasia patients. Low Weak
who were not treated successfully by laparoscopic Heller’s myotomy.
NA, not applicable; LHM, laparoscopic Heller myotomy; GERD, gastroesophageal reflux disease.

Achalasia is a rare esophageal motility disorder. Population- differ according to ethnicity. The incidence of achalasia is 0.03-0.27
based epidemiological data on achalasia are sparse and most existing per 100 000 persons per year in developing countries (Fig. 2).10,11 A
studies used a retrospective design.9 According to studies conducted recent large cohort study based on Dutch healthcare insurance data
in the 2000s, the incidence of achalasia is increasing and does not revealed an incidence of achalasia of 2.2 per 100 000 persons per

184 Journal of Neurogastroenterology and Motility

 Seoul Consensus on Achalasia

Table 3. Eckardt Score for Clinical Classification of Achalasia Severity

Score Dysphagia Regurgitation Retrosternal pain Weight loss (kg)

0 None None None None
1 Occasional Occasional Occasional <5
2 Daily Daily Daily 5-10
3 Each meal Each meal Each meal > 10

Iceland
Canada 0.55/8.7
1.6/2.5 10.8
Netherlands
2.2/15.3
Korea
Italy 0.4/6.3
Chicago, USA Israel
1.59/NA
1.1/4.7 14.4 0.95/7.9 12.6
Algeria
0.3/3.2 Singapore
0.3/1.8

Zimbabwe
0.03/NA South Australia Figure 2. Reported incidence and
2.5/NA
prevalence rates of achalasia. Data are
expressed as rates per 100 000 persons
per year (incidence/prevalence).

year,9 compared to 2.9 per 100 000 persons in a study using tertiary mentary tests to manometry in the diagnosis and management of
hospital data.12 The prevalence of achalasia also appears to be in- achalasia.17,18 However, neither EGD nor barium esophagography
creasing slightly. A Dutch study reported a prevalence rate of 15.3 alone is sensitive enough to achieve a definitive diagnosis. EGD
per 100 000 persons,9 and other studies have reported prevalence can be used as a supportive tool for diagnosis of achalasia in only
rates of 2.5-32.6 per 100 000 persons.12,13 However, Kim et al14 one-third of patients, and esophagography in up to two-thirds of
reported that the incidence and prevalence of achalasia were 0.4 and patients. Thus, patients suspected to have achalasia but who have
6.3 per 100 000 persons, respectively, in population-based studies shown normal results in EGD or esophagography studies must
based on a Korean national healthcare database. undergo esophageal motility tests. However, in patients with EGD
The numbers of male and female patients with achalasia or esophagography findings typical of achalasia, esophageal motility
were similar in several large-scale epidemiological studies.9,11,14,15 tests should be performed to confirm the diagnosis.
Although achalasia can occur at any age, it is most prevalent in pa-
tients aged 40 to 60 years.9,11,16 Asian epidemiological studies have Statement 3: Esophageal manometry is a gold standard
reported similar data to Western studies. test for the diagnosis of achalasia.
(Level of evidence, low; strength of recommendation, strong)
Experts’ opinions: agree strongly (76.1%), agree with some
Diagnosis of Achalasia reservations (23.9%), undecided (0.0%), disagree (0.0%), and
disagree strongly (0.0%)
Esophageal Manometry
Esophageal manometry is essential for assessing esophageal Manometric findings of aperistalsis and incomplete LES re-
motor function in patients with achalasia.1 Barium esophagography laxation without evidence of mechanical obstruction supports the
and esophagogastroduodenoscopy (EGD) are used as comple- diagnosis of achalasia (Fig. 3A). Other findings, such as increased

Vol. 26, No. 2 April, 2020 (180-203) 185

Hye-Kyung Jung, et al

A B Achalasia type I Achalasia type II Achalasia type III

mmHg
150

30
20

10

Figure 3. Manometric findings of esophageal achalasia. A. Conventional esophageal manometry findings of achalasia. Achalasia is characterized by
incomplete lower esophageal sphincter (LES) relaxation upon deglutition, defined as a residual pressure > 10 mmHg, and aperistalsis in the body
of the esophagus. In addition, the resting tone of the LES will often be elevated. B. Subtypes of esophageal achalasia identified by high-resolution
manometry: type I, classic achalasia with no evidence of pressurization; type II, panesophageal pressurization; and type III, vigorous achalasia or
spastic contractions of the distal esophageal segment.

basal LES and baseline esophageal body pressure with simultaneous into 3 subtypes, which has implications for treatment outcomes.20
non-propagating contractions, are also suggestive of achalasia, but Although these achalasia subtypes can be defined by careful analysis
are not required for its diagnosis. Though rare, variants of achalasia of conventional tracings, they can be distinguished more easily and
differing in the degree of incomplete LES relaxation and aperistalsis, reproducibly by HRM.21
as well as some characterized by complete LES relaxation, have been
described.19 Aperistalsis has been defined as a lack of esophageal Statement 5: The Chicago classification is useful for
body peristalsis and can present with different pressure patterns, such defining the clinically relevant phenotypes of achalasia.
as a “quiescent” esophageal body, isobaric panesophageal pressuriza- (Level of evidence, moderate; strength of recommendation,
tion, and simultaneous contractions. Achalasia variants presenting strong)
with propagating contractions, which could represent either early Experts’ opinions: agree strongly (50.0%), agree with some
achalasia or, most commonly, a subclinical mechanical obstruction at reservations (45.7%), undecided (4.3%), disagree (0.0%), and
the esophago-gastric junction, have also been described. This het- disagree strongly (0.0%)
erogeneity demonstrates the need for motility studies, where motor
patterns can affect diagnosis and management. Based on the relaxation pressure and propagation and pressur-
ization parameters, the Chicago classification 3.0 is a system for clas-
sifying achalasia into distinct subtypes (I-III) and variants, ie, early
Statement 4: High-resolution manometry is superior to
achalasia with esophagogastric junction (EGJ) outflow obstruction
conventional manometry for the diagnosis of achalasia.
(Level of evidence, low; strength of recommendation, strong) (EGJOO) and achalasia associated with hypotonic LES (absence
Experts’ opinions: agree strongly (71.8%), agree with some of contractility) (Fig. 3B).19-21 Type I achalasia, called classic acha-
reservations (23.9%), undecided (4.3%), disagree (0.0%), and lasia, is characterized by an absence of esophageal body smooth
disagree strongly (0.0%) muscle contractility and no esophageal pressurization. These find-
ings are more typical of late-stage achalasia, in which there is loss of
Data are emerging suggesting that HRM may have greater muscle tone and subsequent dilation of the esophageal body. Type
sensitivity for diagnosing achalasia than conventional manom- II achalasia, which is the most common type, is characterized by pe-
etry.20 Conventional manometric techniques and tracing analysis riods of esophageal pressure and compression; the smooth muscle
(interval of 3-5 cm) can be utilized to depict the pressure profile of the esophagus retains its tone and there is absent peristalsis with
of the smooth muscle esophagus; however, with HRM, the whole abnormal pan-esophageal high-pressure patterns. If 20.0% or more
esophagus can be analyzed, which is useful for predicting not only of the patient’s swallows are characterized by this panesophageal
the presence of achalasia, but also the treatment response. Esopha- pressurization, the achalasia is classified as type II. Type III acha-
geal pressure topography enables the differentiation of achalasia lasia, which is the least common type, is characterized by spastic

186 Journal of Neurogastroenterology and Motility

 Seoul Consensus on Achalasia

contraction of the distal esophagus in at least 20.0% of swallows. (Level of evidence, low; strength of recommendation, strong)
The achalasia subtypes have been linked to the treatment re- Experts’ opinions: agree strongly (39.1%), agree with some
sponse in multiple studies, including a recent systematic review and reservations (54.4%), undecided (6.5%), disagree (0.0%), and
meta-analysis of manometric findings.22 These findings should be disagree strongly (0.0%)
used to guide treatment decisions. Multiple studies have reported
different treatment success rates among the 3 achalasia subtypes, Barium esophagography is recommended to assess esophageal
particularly, type III showing a higher likelihood of treatment failure emptying and EGJ morphology in those with equivocal motility test
compared to type II achalasia.22,23 The inferior response of type III results.32 The diagnosis of achalasia can be supported by esopha-
patients is often attributed to spastic contractions in the esophageal gographic findings, including dilation of the esophagus, a narrow
body. Pratap and colleagues found that type II predicted a good EGJ with a “bird-beak” appearance, aperistalsis, and poor empty-
response to pneumatic dilatation.24 The European Achalasia Trial ing of the barium (Fig. 4A).33 In advanced cases, a dilated esopha-
showed that treatment success rates for type II achalasia were high geal body and high air-fluid level, in the absence of an intragastric
for both LHM (93.0%) and pneumatic balloon dilation (PBD; air bubble or even a sigmoid-like appearance of the esophagus, may
100.0%).25 The follow-up data of the same trial confirmed that type be present.
III achalasia is indeed an important predictor of treatment failure, at
least for PBD. Studies of LHM also found type III achalasia to be Statement 7: Timed barium esophagography enables
predictive of a poor treatment outcome. Patients with type III acha- assessment of the severity of achalasia and evaluation of
lasia had the highest incidence of failure (22.2% vs 3.0% and 3.4% the treatment outcome.
for types I and type II, respectively; P = 0.01).26-28 Finally, four (Level of evidence, moderate; strength of recommendation,
studies reported that type III achalasia was associated with failure of strong)
POEM treatment.23,29-31 Experts’ opinions: agree strongly (34.8%), agree with some
reservations (58.7%), undecided (6.5%), disagree (0.0%), and
Barium Esophagography disagree strongly (0.0%)
Statement 6: Barium esophagography is recom-
Timed barium esophagography (TBE) is a reproducible tech-
mended to diagnose achalasia in patients with esopha-
nique for estimating esophageal emptying with very high inter-
geal dysphagia.
observer agreement (Fig. 4B). Esophageal emptying is assessed with

1 min 2 min 5 min

A B

130.0 mm 113.5 mm 116.3 mm

59.8 mm
59.5 mm
57.1 mm

272.9 mm 284.2 mm
282.0 mm

Figure 4. Esophagographic findings of esophageal achalasia. A. Barium swallow typically reveals a “bird-beak” appearance of the esophagogastric
junction, with a dilated esophageal body and an air-fluid level in the absence of an intragastric air bubble, or even a sigmoid-like appearance (in
advanced cases). B. Timed barium esophagography for measuring esophageal emptying at 1, 2, and 5 minutes. The barium column height is mea-
sured from the end of the esophagus.

Vol. 26, No. 2 April, 2020 (180-203) 187

Hye-Kyung Jung, et al

the patient in the upright position. The patient is instructed to drink eosinophilic esophagitis. A tumor infiltrating the gastroesophageal
100-250 mL of low-density barium and the barium column height is junction and cardia can mimic the clinical, radiological, and mano-
measured from the end of the esophagus; the height at 5 minutes is metric findings of achalasia, resulting in impaired LES relaxation,
used to determine the completeness of emptying.34 TBE predicts the esophageal dilatation, and absence of peristalsis. This condition is
likelihood of symptom recurrence after PD or surgical myotomy.35 defined as “secondary achalasia” or “pseudoachalasia.” Similar to
Rohof et al34 found that esophageal retention was a good predictor the manometric features of achalasia, mechanical obstruction can
of treatment failure in cases of long-standing achalasia and proposed result in both impaired EGJ relaxation and abnormal esophageal
basing the decision for retreatment on the TBE rather than manom- body function (aperistalsis or spastic contractions).
etry. Moreover, studies using TBE showed that it improved diagno- Dysphagia to solids and liquids, short-duration dysphagia (< 1
sis and prediction of treatment outcome. In a recent study including year), serious weight loss (> 6.8 kg), and age over 55 years should
achalasia patients, and those with EGJOO or dysphagia of other lead to suspicion of secondary achalasia; however, these signs are
origin, a barium column height of 5 cm after 1 minute showed the neither sensitive nor specific.37 Thus, in patients with HRM or
highest sensitivity and specificity (of 94.0% and 71.0%, respectively) esophagography findings of achalasia, endoscopic evaluation of the
for differentiating untreated achalasia from EGJOO and non- EGJ and cardia is needed to ensure that there is no infiltration of
achalasia based on receiver operating characteristic analysis.36 cancer. Mucosal ulceration or nodularity, reduced compliance of the
EGJ, or an inability to pass the endoscope into the stomach are the
Endoscopy most common endoscopic findings of pseudoachalasia. Endoscopic
Statement 8: Endoscopic assessment is recommended mucosal biopsy is used to diagnose secondary pseudoachalasia.
for achalasia patients to rule out pseudoachalasia When biopsy is negative but secondary achalasia is suspected, com-
caused by cancer and other esophageal diseases (eg, puted tomography or endoscopic ultrasonography can help to rule
peptic stricture with acid reflux, structural disorders out pseudoachalasia.38,39
such as esophageal webs and rings, or esophageal in- In idiopathic achalasia, the endoscopic findings at the EGJ
flammation). range from normal-appearing (in about 40% of patients) to a thick-
(Level of evidence, low; strength of recommendation, strong) ened muscular ring that may have a rosette configuration on retro-
Experts’ opinions: agree strongly (78.2%), agree with some flexion, accompanied by signs of esophagitis such as friability, thick-
reservations (19.6%), undecided (2.2%), disagree (0.0%), and ening, and even erosion secondary to food stasis (Fig. 5), as well
disagree strongly (0.0%) as mild-to-moderate resistance to intubation of the EGJ.40 Saliva,
liquid, and undigested food material may be seen in the esophagus
EGD has a low diagnostic yield for achalasia; its primary role in the absence of mucosal abnormality or tumor.1 As the disease
is exclusion of mechanical obstruction secondary to a peptic stric- progresses, luminal dilation and tortuosity make the diagnosis more
ture or cancer in patients with dysphagia.16 EGD can also rule out obvious.41,42 Although endoscopy may suggest achalasia, other tests
reflux esophagitis, structural lesions (strictures, webs, or rings), and must be performed to confirm the diagnosis.

Figure 5. Endoscopic findings of esopha-

geal achalasia. A dilated esophagus show-
ing food stasis, saliva and some resistance
at the gastroesophageal junction.

188 Journal of Neurogastroenterology and Motility

 Seoul Consensus on Achalasia

Botulinum Toxin Injection

Treatment of Esophageal Achalasia
Statement 10: Botulinum toxin injection is recom-
The goal of achalasia treatment is to promote relief of dyspha-
mended for achalasia patients whose medical condition
gia and related complications. Several treatments can be tailored
is unsuitable for endoscopic treatment or surgery.
according to the patient’s overall health status. However, there is no
(Level of evidence, moderate; strength of recommendation,
specific therapy targeting the underlying disease process, because
strong)
the pathogenesis of the impaired esophageal peristalsis and poor
Experts’ opinions: agree strongly (42.5%), agree with some
esophageal sphincter relaxation are unclear.
reservations (42.5%), undecided (10.7%), disagree (4.3%), and
PBD, POEM, and LHM provide similarly effective long-
disagree strongly (0.0%)
term results for esophageal achalasia. In patients whose condition is
too poor for endoscopic treatment or surgery, botulinum injection Injection of botulinum toxin into the LES has been shown
or oral medication might be helpful. to improve the symptoms of achalasia (dysphasia, regurgitation,
and chest pain), decrease the LES pressure, improve esophageal
Oral Pharmacologic Treatment emptying, and increase the size of the LES aperture compared to
injection of placebo (Table 4).50,51 However, although multiple trials
Statement 9: Oral pharmacologic therapy can be con-
have demonstrated short-term benefits of botulinum toxin injection,
sidered for achalasia patients whose medical condition
a single injection of botulinum toxin has only short-duration clinical
is unsuitable for endoscopic treatment or surgery.
(Level of evidence, low; strength of recommendation, weak) effects with relapses within several months occurring frequently.51-59
Experts’ opinions: agree strongly (21.8%), agree with some Typically, 100 U of botulinum toxin is injected into 4 quadrant
reservations (50%), undecided (21.8%), disagree (6.5%), and of LES each as 4 divided doses. There is wide variability in the
disagree strongly (0.0%) timing of the botulinum toxin injections. A multicenter randomized
study found no clear dose-response effect (doses of 50, 100, or 200
Uncontrolled and small studies reported that a number of U) after 1 month, but 2 injections of 100 U botulinum toxin, 30
pharmacological agents, including calcium channel blockers, ni- days apart, was the most effective therapeutic schedule.60 According
trates, anticholinergics, phosphodiesterase inhibitors, and ß-adren- to a 9-year retrospective chart review, botulinum toxin was used in
ergic agonists, have been used for treating achalasia. These agents 21.0% of achalasia patients. Symptom improvement persisted for a
are effective in reducing LES pressure and temporarily relieving mean of 6.2 months, with a need for repeated injections (mean, 1.7;
dysphagia, but do not improve LES relaxation or peristalsis.43 range: 1-7), and about 43.0% of patients required different, addi-
Calcium channel blockers transiently decrease LES pressure by tional treatments.61
13.0-49.0%, facilitate esophageal emptying and improve symptom Botulinum toxin injection can induce esophageal perforation
severity by 0.0-77.0%.44-47 Calcium channel blockers are associated or, inflammatory mediastinitis62 and chest pain (4.3%) or heartburn
with side effects, such as headache, hypotension, and peripheral (0.7%),58 but it is a relatively safe treatment because of the low
edema.48 Anticholinergics (eg, cimetropium bromide) decrease probability of complications. Botulinum toxin injection is less effica-
LES pressure and accelerate esophageal transit. A double-blind, cious than PBD and myotomy in inducing long-term remission of
placebo-controlled trial showed that cimetropium bromide reduced achalasia.51,63 However, if myotomy or PBD cannot be performed
LES pressure by 70.0% for about 45 minutes, and improved because the patient is in poor general condition, repeated botulinum
esophageal transit.49 The clinical response to pharmacologic agents toxin injection should be considered. Following repeated botulinum
is short-lived; they do not provide complete relief of symptoms and toxin injection, 50.0% of patients were asymptomatic. The median
efficacy decreases substantially over time.45 Thus, these agents are duration of the symptom-free period was 11.5 months after the first
commonly reserved for patients who cannot, or refuse to, undergo botulinum injection, and 10.5 months after the second.63
endoscopic or surgical therapy, and for those who have failed endo-
scopic or surgical therapy.

Vol. 26, No. 2 April, 2020 (180-203) 189

 Table 4. Summary of the Evidence Supporting Botulinum Toxin Injection in Patients With Achalasia

190
Follow-up
Study Country Study design Participants Intervention Comparator Outcome
duration
1996, USA Prospective Treatment-naïve Botox, n = 31 None Median 2.4 yr Sustained improvement (beyond 3 mo): 53.0%
Hye-Kyung Jung, et al

Pasricha et al52 cohort study patients with Symptom relapse (within a median of 1.3 yr): 95.0%
achalasia
1999, Germany RCT Patients with Botox, n = 12 PBD, n = 12 2.5 yr Symptom remission: Botox vs PBD, 0.0% vs 60.0%
Muehldorfer et al53 achalasia with/without
prior treatment
1999, USA RCT Treatment-naïve Botox, n = 22 PBD, n = 20 1 yr Symptom remission: Botox vs PBD, 32.0% vs 70.0%, P = 0.017
Vaezi et al54 patients with
achalasia
2000, Italy Prospective Treatment-naïve Botox 100 U, Botox 50 U, 2 2 yr Symptom relapse: Botox 100 U vs 50 U vs 200 U,
Annese et al51 cohort study patients with 2 injection, injection, n = 40 19.0% vs 47.0% vs 43.0%
achalasia n = 38 Botox 200 U, 2
injection, n = 40
2001, Iran RCT Treatment-naïve Botox, n = 20 PBD, n = 20 1 yr Symptom remission: Botox vs PBD, 15.0% vs 53.0%, P < 0.01
Mikaeli et al55 patients with
achalasia
2002, Italy Prospective Treatment-naïve Botox, n = 37 None 1 yr Symptom remission period: mean 15.6 mo (range, 2-30 mo)
D'Onofrio et al56 cohort study patients with
achalasia
2003, USA RCT Treatment-naïve Botox, n = 16 PBD, n = 18 4 mo Symptom remission: Botox vs PBD, 38.0% vs 89.0%
Bansal et al57 patients with
achalasia
2004, Italy RCT Treatment-naïve Botox, n = 40 Heller myotomy, 6 mo Symptom score improvement rate: Botox vs Heller myotomy,

Journal of Neurogastroenterology and Motility

Zaninotto et al58 patients with n = 40 65.0% vs 82.0%, P < 0.05
achalasia Symptom relapse rate in Botox group: 65.0%
Symptom remission (2 yr): Botox vs Heller myotomy,
34.0% vs 88.0%, P < 0.05
2009, China RCT Treatment-naïve Botox, n = 29 PBD, 2 yr Symptom remission: Botox vs PBD vs PBD + Botox,
Zhu et al59 patients with n = 28 14.0% vs 36.0% vs 57.0%
achalasia PBD + Botox,
n = 30
PBD, pneumatic balloon dilatation; RCT, randomized controlled trial.
 Seoul Consensus on Achalasia

(Level of evidence, moderate; strength of recommendation,

Pneumatic balloon dilatation strong)
Statement 11: Pneumatic balloon dilatation is recom- Experts’ opinions: agree strongly (63.0%), agree with some
mended as an initial treatment for patients with achalasia. reservations (37.0%), undecided (0.0%), disagree (0.0%), and
(Level of evidence, moderate; strength of recommendation, disagree strongly (0.0%)
strong)
LHM is a first-line treatment for achalasia that achieved
Experts’ opinions: agree strongly (26.1%), agree with some
excellent outcomes in 91.8% of patients after a follow-up of 83.2
reservations (54.4%), undecided (13.0%), disagree (6.5%), and
months.75,76 However, LHM is an invasive and expensive proce-
disagree strongly (0.0%)
dure that requires general anesthesia.77,78 Previous meta-analyses of
One of the most frequently used treatments for achalasia is POEM showed a clinical success rate of 98.0%.79,80 In meta-analy-
PBD of the LES.59,64-72 Treatment parameters such as balloon size, sis of the present guidelines, the clinical efficacy rate of POEM was
number of dilations, inflation pressure, and duration vary according 92.8% (95% confidence interval [CI], 91.1-94.1%) for the naïve
to the specialists or institutions. Depending on the general condi- and prior treatment-failed patients combined, and 93.7% (95%
tion of the patient, graded PBD (with 30-mm, 35-mm, or 40-mm CI, 86.7-97.1%) for naïve patients. Additionally, in another meta-
balloons) is considered one of the primary options for achalasia.73 analysis, the postoperative Eckardt score was better for patients who
According to a retrospective analysis of 209 patients, management underwent POEM versus those who underwent LHM (Fig. 6).81-
86
of achalasia with initial dilation can provide good or excellent long- Recent guidelines for achalasia stated that POEM has an efficacy
term results and high patient satisfaction rates.74 A prospective similar to that of LHM.87 A study with a 3-year follow-up showed
randomized European study of PBD and LHM reported that the that POEM was comparable to LHM in terms of the postopera-
therapeutic success rate was not significantly different between the tive Eckardt score and quality of life.88 A large, recently published
1- and 2-year follow-ups (P = 0.46). Also, there was no significant large cohort study, with long-term follow-up, showed that the
difference in the pressure at the LES (P = 0.27) or esophageal clinical success rate of POEM was 87.0% after a median follow-
emptying, as assessed by the height of the barium column (P = up of 49 months.89 Reflux-related adverse events can occur with
0.21) (Table 5).59,64-72 both POEM and LHM. However, in contrast to LHM, which
requires partial fundoplication to reduce pathologic acid reflux,
Peroral endoscopic myotomy POEM is typically performed without any anti-reflux procedure.90
Statement 12: The outcomes of peroral endoscopic Previous meta-analyses reported that acid reflux occurs more fre-
myotomy are comparable to those of laparoscopic quently after POEM than after LHM.91,92 However, there was
Heller myotomy for treatment-naïve patients with no difference in the rate of reflux symptoms, pathologic acid reflux,
achalasia. or the requirement for proton pump inhibitors (PPIs) between the
POEM and LHM groups.84

POEM heller myotomy Std. Mean difference Std. Mean difference

Study or Subgroup Std. Mean difference SE Total Total Weight IV, Random, 95% CI IV, Random, 95% CI
1.1.1 Post-operative eckardt score
2013, Ujiki 0.669 0.33 18 21 20.0% 0.67 [ 1.32, 0.02]
2014, Bhayani 0.84 0.215 37 63 26.2% 0.84 [ 1.26, 0.42]
2016, Schneider 0 0.283 25 25 22.4% 0.00 [ 0.55, 0.55]
2017, Leeds 1.435 0.468 12 11 14.1% 0.44 [ 2.35, 0.52]
2017, Peng 0.144 0.388 12 15 17.3% 0.14 [ 0.90, 0.62]
Subtotal (95 % CI) 2 104 135 100.0% 0.58 [ 1.03, 0.13]
2 2
Heterogeneity: Tau = 0.16; Chi = 10.34, df = 4 (P = 0.04); I = 61%
Test for overall effect: Z = 2.52 (P = 0.01)
2 1 0 1 2
Favour [POEM] Favour
[Heller myotomy]

Figure 6. Meta-analysis comparing peroral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM). During the 3-year follow-
up, POEM is comparable to LHM in terms of the postoperative Eckardt score.

Vol. 26, No. 2 April, 2020 (180-203) 191

 Table 5. Summary of the Evidence Supporting Pneumatic Balloon Dilatation in Patients with Achalasia

192
Follow-up
Study Country Study design Participants Intervention Comparator Outcome
duration
2016, China Retrospective Treatment-naïve PBD, POEM, POEM group; Treatment success (Eckardt score ≤ 3) rate
Hye-Kyung Jung, et al

Tan et al64 cohort study patients with n=9 n = 12 26.0 mo Treatment success rate at 24 mo and 36 mo
achalasia PBD group; POEM vs PBD: 100.0% vs 44.4%, 100.0% vs 33.3%, P < 0.05
70.7 mo
2013, Hong Kong Retrospective Patients with PBD, LHM, LHM group; Recurrent dysphagia: PBD vs LHM,
Chan et al65 cohort study achalasia without n = 50 n = 18 34.0 mo 55.1% vs 26.7%, P = 0.235
prior treatment PBD group; Reintervention rate was needed:
64.0 mo PBD vs LHM, 42.1% vs 9.1%, P = 0.045
2008, Iran Retrospective Treatment-naïve PBD, Myotomy, Myotomy group; Patient satisfaction scores of the myotomy vs PBD groups:
Emami et al66 cohort study patients with n = 45 n = 20 34.9 mo 8.05 ± 2.37 and 7.67 ± 2.49, respectively (P = NS)
achalasia PBD group;
25.3 mo
2014, Korea Retrospective Patients with PBD, Botox (n = 25) Median 61.0 mo The symptom-free period was significantly longer in the PBD
Jung et al67 cohort study achalasia without n = 12 group (P = 0.036) than the Botox group.
prior treatment
2007, Sweden RCT Treatment-naïve PBD, LHM, 1 yr Pneumatic dilatation was associated with significantly
Kostic et al68 patients with n = 26 n = 25 more treatment failures (P = 0.04).
achalasia
2016, Netherlands Retrospective Recurrent or PBD, None 6.5 yr Success rate of 57.0% using 30-mm and 35-mm balloons.
Saleh et al69 analysis of persistent n = 24
prospective symptoms of
database. achalasia after
Heller myotomy

Journal of Neurogastroenterology and Motility

2010, Japan Prospective Treatment-naïve PBD, None 28.0 mo Successful in 41 of 55 cases (74.5%)
Tanaka et al70 study patients with n = 55
achalasia
2001, Germany RCT Patients with PBD, Botox, Botox group; Overall response rate: Botox vs PBD, 82.6% vs 92.9%
Allescher et al71 achalasia with/ n = 14 n = 23 1375 day Symptom remission rate at 2 yr for Botox = 30.0%.
without prior PBD group; After 24 mo, a single balloon dilation was superior to a single
treatment 1477 day botulinum toxin injection.
2009, China RCT Treatment-naïve PBD, Botox, n = 29 2 yr Symptom remission rate: Botox vs PBD vs PBD + Botox,
Zhu et al59 patients with n = 28 PBD + Botox, 14.0% vs 36.0% vs 57.0%
achalasia n = 30
2011, EU RCT Treatment-naïve PBD, LHM, 43 mo Rate of the therapeutic success: PBD vs LHM,
Boeckxstaens et al72 patients with n = 95 n = 106 90.0% vs 93.0% (at the 1-yr follow-up) and 86.0% vs 90.0%
achalasia (at the 2-yr follow-up) (P = 0.46)
PBD, pneumatic balloon dilatation; POEM, peroral endoscopic myotomy; LHM, laparoscopic Heller myotomy; NS, not significant; RCT, randomized controlled trial.
 Seoul Consensus on Achalasia

In summary, the high clinical efficacy of POEM, and the ac-

ceptable adverse event rate, are similar to those of LHM for treat-

POEM, 98.0% (n = 48); LHM, 80.8% (n = 21)

ment-naïve patients with achalasia. Nevertheless, long-term follow-

POEM, 102 (43-345); LHM, 264 (189-331)

up studies are required to define the role of POEM in the initial
endoscopic treatment of achalasia.

Statement 13: Peroral endoscopic myotomy, rather

Clinical success rate (8 studies):

91.6% (95% CI, 84.3-95.7%)
Adverse event rate (8 studies):
Median procedure time, min:

11.2% (95% CI, 6.3-19.0%)

than laparoscopic Heller myotomy, can be considered

Outcome
for the treatment of type III achalasia because it can of-

Clinical response rate:

fer extended myotomy.
(Level of evidence, low; strength of recommendation, weak)
Experts’ opinions: agree strongly (43.4%), agree with some
reservations (37.0%), undecided (17.4%), disagree (2.2%), and
disagree strongly (0.0%)

mean 21.5 mo
mean 8.6 mo;
Previous studies reported different success rates among the 3

3 mo-3 yr
Follow-up

POEM,
achalasia subtypes; in particular, type III achalasia was associated

duration

LHM,

Range,
with an increased risk of treatment failure compared to type II acha-

Table 6. Summary of the Evidence Supporting Peroral Endoscopic Myotomy in Patients With Type III Achalasia
lasia.22,23 Type III achalasia is characterized by pathological mecha-

Intervention Comparator
nisms involving the esophageal body and the LES.93 Therefore, the

n = 26
LHM,

None
response rate to PBD or botulinum toxin injection is relatively low
in patients with type III achalasia. In a study that reported treatment
response according to achalasia subtype, the clinical success rate of

n = 179
Retrospective Type 3 achalasia patients POEM,

Meta-analysis Eight studies on type 3 POEM,

the first session of PBD was 38.0% (3/8) for type I achalasia, 73.0% n = 49

POEM, peroral endoscopic myotomy; LHM, laparoscopic Heller myotomy; CI, confidence interval.
(19/26) for type II achalasia, and 0.0% (0/11) for type III achalasia.34

who underwent POEM

Botulinum toxin injection also showed low efficacy in patients with
type III achalasia (type I, 0.0% [0/2]; type II, 86.0% [6/7]; type
POEM or LHM

achalasia patients
cohort study who underwent

III, 22.0% [2/9]). In another study, the treatment response of PBD

Participants

was 63.0% in type I achalasia, 90.0% in type II achalasia, and 33.0%

in type III achalasia.24 Myotomy may have greater efficacy for the
treatment of type III achalasia compared to PBD. A study involving
18 patients with type III achalasia demonstrated that LHM tended
Study design

to have a clinical success rate superior to that of PBD, although the

difference was not significant (86.0% vs 40.0%, P = 0.12).94
Although the treatment response rate of type III achalasia pa-
tients undergoing LHM is higher than that of those undergoing
and 1 European centers)

PBD, the efficacy of LHM for type III achalasia is inferior to that
Kumbhari et al92 (4 USA, 3 Asian,

for other types of achalasia. In a previous study on LHM in pa-

tients with achalasia, the clinical success rate was 85.0%, 95.0%, and
International

70.0% for type I, type II, and type III achalasia, respectively (P <
Country

USA

0.001).31
Unlike conventional treatments, such as PBD and LHM,
POEM enables extended myotomy in patients with type III acha-
Khan et al95

lasia. Meta-analysis of studies comparing POEM and LHM

showed that the length of myotomy was significantly greater for
Study

2015,

2017,

Vol. 26, No. 2 April, 2020 (180-203) 193

Hye-Kyung Jung, et al

POEM than LHM. Also, operation time and length of hospital tively. However, there is no significant difference of development of
stay tended to be shorter for POEM than LHM. Another meta- GERD between POEM and LHM (Fig. 7).
analysis, of 8 studies on POEM for type III achalasia, demonstrat- Although the definitions of symptoms, abnormal pH, and
ed an overall clinical success rate of 91.6% (Table 6).92,95 Moreover, abnormal endoscopic findings were not standardized across the
a multi-center retrospective cohort study including 75 patients with studies, POEM is clearly associated with an increased risk of post-
type III achalasia showed that the clinical response rate was higher procedural reflux. Therefore, acid suppressive therapy is recom-
in patients who underwent POEM than in those who underwent mended after POEM for patients with reflux symptom or esopha-
LHM (98.0% vs 81.0%, P = 0.01).92 gitis. Also, there is a dissociation among the rate of abnormal acid
The overall rate of adverse events in type III achalasia patients exposure and the rates of reflux symptoms and reflux esophagitis
who underwent POEM was 11.2% in the meta-analysis discussed based on endoscopic examinations. Therefore, clinicians should
above.96 More than 70.0% of adverse events could be managed evaluate asymptomatic patients via regular endoscopy examinations
conservatively without further intervention. In some patients, the or pH monitoring.
length of hospital stay was prolonged due to adverse events includ- In a previous meta-analysis, the rate of PPI use after POEM
ing pulmonary embolism, pneumothorax, capnoperitoneum, and ranged from 2.6% to 27.8% (pooled estimate, 10.6%; 95% CI, 6.5-
bleeding. Inadvertent mucosotomies occurred in 3.0% of patients, 17.3%).90 However, the optimal duration and dose of PPI use are
who were managed by clipping.96 The rate of adverse events in controversial. Most patients with post-procedural gastroesophageal
patients with type III achalasia undergoing POEM seems to be ac- reflux can be treated using a standard PPI dose. Also, the long-
ceptable. term effects of an abnormal pH in asymptomatic participants are
Although large-scale randomized controlled trials (RCTs) unclear. Therefore, a short course of PPIs is recommended after
are lacking, current evidence supports superior clinical efficacy of POEM, although a more tailored approach based on symptoms,
POEM over LHM in patients with type III achalasia, where the pH and endoscopy findings appears to be more appropriate.
length of myotomy is greater for the former treatment modality.
Given that, for patients with type III achalasia, the clinical success Surgical Treatment
rate of POEM is good and the adverse event rate is acceptable,
Statement 15: Laparoscopic Heller myotomy can be
we recommend POEM over LHM for the treatment of type III
considered a first-line therapy for achalasia patients,
achalasia.
and has similar expected clinical outcomes to pneu-
Statement 14: Acid suppressive therapy is recommend- matic balloon dilation.
ed for patients with reflux symptoms or esophageal (Level of evidence, moderate; strength of recommendation,
erosion after peroral endoscopic myotomy, to prevent weak)
esophageal stricture. Experts’ opinions: agree strongly (18.2%), agree with some
(Level of evidence, low; strength of recommendation, strong) reservations (75.8%), undecided (3.0%), disagree (3.0%), and
Experts’ opinions: agree strongly (47.8%), agree with some disagree strongly (0.0%)
reservations (50.0%), undecided (2.2%), disagree (0.0%), and
disagree strongly (0.0%) Surgical myotomy, also known as Heller myotomy, disrupts
the muscle fibers of the LES. LHM is the preferred surgical
One of the main adverse events associated with POEM is technique because of its low morbidity rate and the rapid rate of re-
gastroesophageal reflux. Unlike LHM, in POEM no anti-reflux covery.97,98 In a systematic review involving 3086 patients, symptom
procedure is performed; however, no alteration of the diaphragmatic improvement after LHM was achieved in 89.3% after a mean of
and gastroesophageal anatomy occurs in POEM, which potentially 35.4 months (range: 8-83 months).97 Two prospective, randomized
reduces the risk of reflux. Gastroesophageal reflux is evaluated after trials have compared PBD and LHM.99,100 Although LHM was
POEM according to symptoms, pH, and endoscopic findings. In more effective for symptom relief, these were small, low-quality
meta-analysis of the present guidelines, the overall rates of reflux trials and one failed to meet its recruitment target. Borges et al101
symptoms, abnormal pH, and reflux esophagitis, according to en- reported that LHM and PBD for achalasia were equally effective,
doscopic examinations, were 20.3% (95% CI, 16.9-24.3%), 24.7% even at the 2-year follow-up. In a large, high-quality, multicenter
(95% CI, 20.0-30.0%), and 42.6% (95% CI, 34.1-51.5%), respec- randomized trial involving 201 patients, there was no significant

194 Journal of Neurogastroenterology and Motility

 Seoul Consensus on Achalasia

Population

This recommendation applies to almost all patients with achalasia

Patients dignosed using conventional or high resolution
manometry
Treatment-naive patients or patients who failed to the
Patients with achalasia prior treatment
However the recommendation is not applicable to patients with:
Sigmoid achalasia
Surgically high-risk patients

Comparison of benefits and harms

Favours POEM No important difference Favours LHM

Evidence quality
Postoperative Eckardt score 0.58 SMD lower Very low

Length of myotomy 0.63 SMD longer Moderate

Operation time No important difference Very low

Length of hospital stay No important difference Very low

Reflux symptom No important difference Very low

Erosive esophagitis on endoscopy No important difference Very low

Pathologic acid reflux on pH monitoring No important difference Very low

Considerations and interpretation

Although sufficiently long-term follow-up data are limited in comparison between POEM and LHM, both clinical efficacies of POEM and LHM
have been demonstrated in many single-arm cohort studies (moderate level of evidence for both POEM and LHM).
Patients may be recommended for POEM over LHM because POEM is a less invasive procedure than LHM (strong recommendation for POEM
and weak recommendation for LHM).

Figure 7. Comparison of peroral endoscopic myotomy and laparoscopic Heller myotomy in patients with achalasia. POEM, peroral endoscopic
myotomy; SMD, standard mean difference; LHM, laparoscopic Heller myotomy.

difference in treatment success rate after 1, 2, and 5 years of follow- Statement 16: Partial fundoplication in addition to
up.25,72 Rohof et al94 reported differences in outcomes according to LHM is recommended to reduce the risk of subsequent
the achalasia subtype. The success rate of PBD was significantly GERD.
higher than that of LHM for type II achalasia (100.0% vs 93.0%, (Level of evidence, low; strength of recommendation, strong)
P < 0.05).94 However, the largest difference in symptom remis- Experts’ opinions: agree strongly (23.9%), agree with some
sion rates between PBD and LHM was observed in type III reservations (56.5%), undecided (17.4%), disagree (2.2%), and
achalasia, although the difference was not statistically significant disagree strongly (0.0%)
due to the small number of patients in this subgroup. In addition,
type III achalasia patients treated by PBD had significantly greater The antireflux barrier function of the LES is lost after my-
esophageal stasis compared to type III patients treated by LHM. otomy, and the need to add an antireflux procedure to LHM has
Therefore, patients with type III seem to respond better to LHM long been debated. In a meta-analysis, the rate of gastroesophageal
than to PBD. However, RCTs comparing the outcomes of LHM reflux symptoms was reduced when fundoplication was added to
and PBD in the various achalasia subtypes are needed to draw myotomy (8.8% vs 31.5%, P = 0.001).97 However, the rate of post-
definitive conclusions. It should also be noted that PBD is a more operative dysphagia was higher after LHM plus Nissen fundopli-
cost‑effective treatment option than LHM for achalasia.102,103 cation than after LHM plus Dor fundoplication (15.0% vs 2.8%,
P = 0.001).104 In contrast, the relief of dysphagia after LHM plus
Dor fundoplication was shown to be comparable to LHM alone.105
In addition, 2 types of partial fundoplication (Dor and Toupet) were

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Hye-Kyung Jung, et al

comparable in terms of the degree of improvement in symptoms prior treatment showed a longer procedure time and higher rate of
after LHM.106 Partial fundoplication reportedly decreases reflux af- clinical failure after POEM compared to those without prior treat-
ter LHM.107 Finley et al108 reported no difference in the frequency ment.120 POEM has a reported efficacy rate of > 90% based on
or severity of reflux symptoms between patients with and without short-term follow-up data. Persistence or recurrence of symptoms
anterior fundoplication. However, that study was limited by the may occur after POEM. Two studies showed that redo POEM
significant difference in preoperative upright esophageal clearance is feasible for patients in whom POEM failed, as a salvage option
between the 2 groups. To draw definitive conclusions, additional with a 100.0% technical success rate and an 85.0-100.0% clinical
large randomized trials are needed. success rate based on short-term follow-up data.121,122 For patients
with persistent or recurrent symptoms after POEM, redo POEM
Management of Achalasia Recurrence After Initial seems to be an efficacious and safe technique.123
Treatment In summary, POEM appears to be a safe and effective option
If PBD fails as a first-line treatment, additional treatment with for patients who failed initial endoscopic treatment. Long-term
PBD may be considered.67,109 PBD is also an option when symp- follow-up and randomized studies comparing other treatment op-
toms recur after botulinum toxin injection.69 In cases showing per- tions are required to define the role of POEM for cases of achalasia
sistent or recurrent symptoms after LHM, retreatment with PBD in which initial endoscopic treatment failed.
may be considered.110,111 LHM is an effective treatment for the
majority of achalasia patients. However, a small proportion of pa- Statement 18: Peroral endoscopic myotomy can be
tients suffer persistent or recurrent symptoms after surgery. In such considered as a rescue treatment for achalasia patients
cases, the success rate of PBD after surgery was reported to vary who were not treated successfully by Heller myotomy.
from 50.0% to 78.0%.108-110 If the symptoms persist after POEM, (Level of evidence, low; strength of recommendation, weak)
PBD may be considered as salvage therapy depending on the clini- Experts’ opinions: agree strongly (28.3%), agree with some
cal symptoms of the patient, although there are relatively few studies reservations (47.8%), undecided (17.4%), disagree (6.5%), and
supporting this.75,76,112 disagree strongly (0.0%)

Recurrent or persistent symptoms occurred in about 10.0-

Statement 17: Peroral endoscopic myotomy is recom-
20.0% of patients who underwent LHM.25 For such patients,
mended for achalasia patients who failed initial endo-
treatment options include repeat LHM, PD, or POEM. Recently,
scopic treatment.
(Level of evidence, moderate; strength of recommendation, POEM has been used as a rescue treatment for patients who
strong) failed LHM. Clinical studies have reported success rates of 92.0-
Experts’ opinions: agree strongly (60.9%), agree with some 98.0%.124-126 Thus, POEM could be a feasible salvage treatment
reservations (34.8%), undecided (4.3%), disagree (0.0%), and for patients with persistent symptoms after LHM. However, ad-
disagree strongly (0.0%) ditional large studies with longer follow-up periods are necessary.

The endoscopic treatment options for achalasia treatment with Esophagectomy

durable outcomes are PBD and POEM. Although PBD showed In patients with end-stage achalasia, when repeated endoscopic or
a long-term success rate of 72.0-86.0%, re-dilation was required by surgical treatments are not effective, some patients may require esopha-
up to one-third of patients with recurrent symptoms.25,70,72,75 Young gectomy to relieve their symptoms. Indeed, the presence of a mega-
age, residual LES pressure > 10 mmHg, stasis on TBE, and male esophagus (maximum esophageal diameter > 6 cm), could be a pre-
sex have been reported as predictive factors for symptom recur- dictive factor for the need of esophagectomy.127-129 In a recent systemic
rence after PBD.113-114 POEM is a treatment option in cases for review, the postoperative morbidity ranged from 19.0% to 50.0% and
which PBD failed, as well as an initial treatment for achalasia (Table the mortality ranged from 0.0% to 5.4%.129 Given the high morbidity
7).77,109,115-122 Large-scale observational studies including patients in and mortality, esophagectomy should be performed in patients with a
whom PBD failed have reported that POEM is a safe and effective megaesophagus who are fit for major surgery, complain of long-lasting
treatment option.96,117,120 Prior treatment did not increase the risk disabling symptoms not responding to multiple endoscopic and surgi-
of POEM-related adverse events.116,119,120 However, patients with cal interventions, preferably in specialized centers.

196 Journal of Neurogastroenterology and Motility

 Table 7. Summary of the Evidence Supporting Peroral Endoscopic Myotomy After Prior Treatment Failure in Patients With Achalasia

Study Design Population Intervention Comparator Follow-up Outcome

duration
2015, Prospective Patients with POEM after None 3 yr Technical success rate: 100.0%
Inoue et al115 cohort study achalasia with/without prior treatment, Adverse event rate: 3.2%
prior treatment n = 195 Two-month outcome, pre- vs post-op: Eckardt score, 6.0 ± 3.0 vs 1.0 ± 2.0, P < 0.0001,
LES pressure (persisting at 3 yr post-POEM), 25.4 ± 17.1 vs 13.4 ± 5.9 mmHg
, P < 0.0001
Gastroesophageal reflux rate: 16.8% at 2 mo and 21.3% at the 3-yr follow-up
2018, Prospective Patients with POEM after POEM without 23.0 mo Clinical success rate: 88.9%
Liu et al116 cohort study achalasia with/without prior treatment, prior treatment, Reflux rate: 23.9 %, symptomatic reflux rate: 15.9%, GERD rate: 19.0%
prior treatment n = 262 n = 604 POEM-related major adverse event rate: 4.0%
POEM after prior treatment was associated with a longer operation
time (P = 0.001), longer hospital stay (P = 0.001),
and increased rate of clinical failure during follow-up (hazard ratio, 1.90; P = 0.002
[Cox regression]).
2014, Prospective Patients with POEM after POEM without 14.0 mo Operation time: prior PBD vs no prior PBD, 42.4 ± 8.3 vs 34.3 ± 7.4, P = 0.01
Ling et al117 case–control achalasia with/without prior PBD, prior PBD, Subcutaneous emphysema: prior PBD vs no prior PBD, 13.3% vs 14.3%
study prior PBD n = 21 n = 30 Pneumothorax: prior PBD vs no prior PBD, 4.8% vs 6.7%
Post-POEM Eckardt score: prior PBD vs no prior PBD, 0.7 ± 0.6 vs 0.5 ± 0.8, P = 0.11
Post-POEM Eckardt score: prior PBD vs no prior PBD, 7.1 ± 6.8 vs 6.7 ± 5.4, P = 0.23
2017, Prospective Patients with POEM after POEM without 1 yr Operation time, min: prior treatment vs no prior treatment, 60.8 ± 30.9 vs 62.0 ± 21.0,
Tang et al118 cohort study achalasia with/without prior treatment, prior treatment, P = 0.863
prior treatment n = 22 n = 39 Treatment success (Eckardt score ≤ 3), n (%): prior treatment vs no prior
treatment, 21 (95.5%) vs 36 (92.3%), P = 0.624
Pre-POEM Eckardt score: prior treatment vs no prior treatment, 7.4 ± 2.4 vs 7.3 ± 1.8
Post-POEM Eckardt score: prior treatment vs no prior treatment, 1.2 ± 1.1 vs 1.2 ± 1.1
Pre-/post-POEM D-value: prior treatment vs no prior treatment,

Vol. 26, No. 2 April, 2020 (180-203)

6.2 ± 2.2 vs 6.4 ± 1.8, P = 0.840
Pre-LES pressure: prior treatment vs no prior treatment, 41.1 ± 15.7 vs 39.9 ± 14.4
Post-LES pressure: prior treatment vs no prior treatment, 13.4 ± 5.3 vs 14.5 ± 5.6
Pre-/post-LES pressure D-value: prior treatment vs no prior treatment,
27.9 ± 17.6 vs 24.9 ± 15.2, P = 0.569
Cases with adverse events: prior treatment vs no prior treatment,
5 (22.7%) vs 8 (20.5%), P = 0.958
Cases of gastroesophageal reflux: prior treatment vs no prior treatment,
4 (23.5%) vs 7 (20.0%), P = 0.771
based on symptoms and endoscopy
2017, Prospective Patients with POEM after POEM without Median Technical success rate: prior treatment vs no prior treatment, 96.8% vs 97.3%, P = 0.795
Nabi et al119 cohort study achalasia with/without prior treatment, prior treatment, 17.0 mo Clinical success rate: prior treatment vs no prior treatment, 92.6% vs 95.7%, P = 0.275
prior treatment n = 189 n = 216 Mean Eckardt score: pre- vs 1-year post-op, 7.07 ± 1.6 vs 1.27 ± 1.06, P = 0.001
Mean LES pressure: pre- vs post-op, 45 ± 16.5 mmHg vs 15.6 ±  6.1 mmHg, P = 0.001
Significant improvement in esophageal emptying on TBE (> 5  0 %): 1-year post-op, 93.8 %
Abnormal acid reflux on pH monitoring: 28.3 %
Erosive esophagitis: 18.5 %
Seoul Consensus on Achalasia

197
 Table 7. Continued

198
Study Design Population Intervention Comparator Follow-up Outcome
duration
2018, Prospective Patients with POEM after POEM without Median Mean operation time, min: prior treatment vs no prior treatment,
Nabi et al120 cohort study achalasia with/without prior treatment, prior treatment, 20.0 mo 74.9 ± 30.6 vs 67.0 ± 27.1, P = 0.002
Hye-Kyung Jung, et al

prior treatment n = 242 n = 260 Technical success rate: prior treatment vs no prior treatment: 97.1% vs 98.1%, P = 0.56
Adverse events rate: prior treatment vs no prior treatment: 33.1% vs 35.8%, P = 0.57
Clinical success rate at 6 months: prior treatment vs no prior treatment:
92.5% vs 92.4%, P = 0.95
Rate of elevation of DeMeester score: prior treatment vs no prior treatment:
32.1% vs 25.0%, P = 0.50
Rate of esophagitis diagnosed by EGD (247 /342):
prior treatment vs no prior treatment: 20.7% vs 22.1%, P = 0.88
24-hour pH study (n  =  97), DeMeester score > 14.7:
prior treatment vs no prior treatment: 32.0% vs 25.0%, P = 0.50
2017, Retrospective Patients with POEM after None 2-4 wk Adverse event rate: 7.5% (mild, 6.4%; moderate, 1.7%; severe, 0.5%)
Haito-Chavez matched achalasia with/without prior Mucosoctomy: 2.8%
et al96 case-control prior treatment treatment, Factors associated with adverse events: sigmoid-type esophagus
study n = 112 (OR = 2.28, P = 0.05), less surgeon experience (< 20 cases) (OR = 1.98, P = 0.04),
use of a triangular tip knife (OR = 3.22, P = 0.05), use of an electrosurgical technique
other than spray coagulation (OR = 3.09, P = 0.02)
2016, Prospective Prior POEM failure Redo POEM, None 11.3 mo Technical success rate: 100.0%
Li et al121 cohort study n = 15 Mean operation time, min: 41.5 (range: 28-62)
Mean symptom score: pre- vs post-op, 5.6 (range: 4-8) vs 1.2 (range: 0-3), P < 0.001
Mean LES pressure, mmHg: pre- vs post-op. 25.0 vs 9.5, P < 0.001
Clinical reflux rate: 33.3%
2017, Prospective Prior POEM failure Redo POEM, None At least Technical success rate: 100.0%
Tyberg et al122 cohort study n = 46 6.0 mo Clinical success rate: 85.0%
Mean Eckardt score: pre- vs post-op, 4.3 ± 2.48 vs 1.64 ± 1.67, P < 0.00001

Journal of Neurogastroenterology and Motility

Procedural bleeding rate: 17.0% (managed successfully by endoscopy)
2018, Prospective Prior POEM failure Redo POEM, PBD after Median Clinical success rate: POEM, 63.0%; PBD, 20.0%; HM 45.0%
van Hoeij et al110 cohort study n=8 prior POEM 39.0 mo
failure, n = 15 (range,
HM after 6-59)
prior POEM
failure, n = 11
POEM, peroral endoscopic myotomy; op, operation; LES, lower esophageal sphincter; GERD, gastroesophageal reflux disease; PBD, pneumatic balloon dilatation; TBE, timed barium esophagogram;
EGD, esophagogastroduodenoscopy; OR, odds ratio; HM, Heller myotomy.
 Seoul Consensus on Achalasia

Y Wu, Kwang Jae Lee, Shinwa Tanaka, and Kewin T H Siah have
contributed in the systematic review, the extraction of recommenda-
Conclusions tions, and writing the paper; Chan Hyuk Park, Da Hyun Jung, Do
The 2019 Seoul Consensus on Esophageal Achalasia Guide- Hoon Kim, Chul-Hyun Lim, Hee Seok Moon, and Su Jin Hong
lines for esophageal achalasia introduced herein are designed to performed the meta-analysis; and Hye-Kyung Jung and Oh Young
serve as a practical, evidence-based guide for clinicians (including Lee have designed the development of guideline as the chairman of
primary physicians, gastroenterologists, upper GI tract surgeons, the guideline committee and KSNM.
medical students, nurses, and paramedical teams) and patients.
Esophageal manometry is the gold standard for diagnosing achala-
sia, while the Chicago classification for HRM is useful for defining
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