BRIEF REPORT

GASTROENTEROLOGY 2013;145:309311

BRIEF REPORT
Peroral Endoscopic Myotomy for the Treatment of Achalasia: An
International Prospective Multicenter Study
DANIEL VON RENTELN,1 KARLHERMANN FUCHS,2 PAUL FOCKENS,3 PETER BAUERFEIND,4 MELINA C. VASSILIOU,5
YUKI B. WERNER,6 GERALD FRIED,5 WOLFRAM BREITHAUPT,2 HENRIETTE HEINRICH,4 ALBERT J. BREDENOORD,3
JAN F. KERSTEN,7 TESSA VERLAAN,3 MICHAEL TREVISONNO,5 and THOMAS RSCH1
1
Department of Interdisciplinary Endoscopy, 6Department of Gastroenterology, 7Department of Medical Biometry and Epidemiology, University Hospital HamburgEppendorf, Hamburg, Germany; 2Department of Surgery, Markus-Krankenhaus Frankfurt, Frankfurt, Germany; 3Department of Gastroenterology, Academic Medical
Center, Amsterdam, The Netherlands; 4Department of Gastroenterology, University Hospital Zrich, Zrich, Switzerland; 5Department of Surgery, McGill University,
Montreal, Quebec, Canada

See editorial on page 272.

Pilot studies have indicated that peroral endoscopic
myotomy (POEM) might be a safe and effective treatment for achalasia. We performed a prospective,
international, multicenter study to determine the outcomes of 70 patients who underwent POEM at 5 centers
in Europe and North America. Three months after
POEM, 97% of patients were in symptom remission
(95% condence interval, 89%99%); symptom scores
were reduced from 7 to 1 (P < .001) and lower esophageal sphincter pressures were reduced from 28 to
9 mm Hg (P < .001). The percentage of patients in
symptom remission at 6 and 12 months was 89% and
82%, respectively. POEM was found to be an effective
treatment for achalasia after a mean follow-up period
of 10 months. Clinical Trials Gov Registration number:
NCT01405417.
Keywords: POEM; Peroral Endoscopic Myotomy; Endoscopic Therapy; Esophageal Motility Disorder; LES.

chalasia is a primary esophageal motility disorder

leading to incomplete relaxation of the lower esophageal sphincter (LES), increased LES tone, and aperistalsis
of the esophagus. Typical symptoms are dysphagia,
regurgitation, and chest pain.1 Endoscopic therapy is
facilitated by endoscopic balloon dilatation (EBD) or botulinum toxin injection (BTI) with 1-year remission rates of
68% and 41%, respectively.2 The surgical treatment is
laparoscopic Heller myotomy (LHM) with remission rates
of about 90%.2,3 Based on experimental research,4 an
endoscopic technique to create the esophageal myotomy
was developed5 and named peroral endoscopic myotomy
(POEM).5 Pilot studies from Europe, Asia, and the United
States have shown promising preliminary results for
POEM.511 This prospective study reports outcomes of an
international multicenter POEM study in 70 achalasia
patients from 5 centers in Europe and North America
(Supplementary Tables 1 and 2).

Results
Procedure-Related Parameters and In Hospital
Follow-up Evaluation
Patient data are shown in Supplementary Table 3;
POEM was performed without technical difculties under
general anesthesia in all 70 patients. No conversions to
laparoscopic or open surgery were required. The mean
procedure time for POEM was 105 minutes (range,
54240 min) and the mean length of the myotomy was
13 cm (range, 523 cm). In 57% of cases, full-thickness
dissection into the peritoneal cavity at the cardia
occurred, and in 69% of cases full-thickness dissection
into the mediastinum was observed. After POEM, signicant increases in C-reactive protein level (mean values,
449; P < .001) and leukocyte count (from 7.4 to 9.9;
P < .001), and decreases in hemoglobin levels (from 13 to
12; P < .001) were observed.

Three-Month Follow-up Symptom Scores and

Manometry Outcomes
Symptom scores at 3 months were available for
all 70 study patients. Treatment success was achieved in
97% of cases (95% condence interval, 8999). The mean
pretreatment and post-treatment Eckhardt scores
decreased from 7 to 1 (P < .001). Manometry assessments
at 3 months were available for 61 of 70 study patients.
Nine patients refused to undergo follow-up manometry
because of discomfort related to the manometry procedure. Mean pretreatment compared with post-treatment
LES pressures were 28 vs 9 mm Hg (P < .001).
Study outcomes are summarized in Supplementary
Table 4.

Abbreviations used in this paper: BTI, botulinum toxin injection; EBD,

endoscopic balloon dilatation; LES, lower esophageal sphincter; LHM,
laparoscopic Heller myotomy; POEM, peroral endoscopic myotomy; PPI,
proton pump inhibitor.
2013 by the AGA Institute
0016-5085/$36.00
http://dx.doi.org/10.1053/j.gastro.2013.04.057

310

VON RENTELN ET AL

BRIEF REPORT

Six-Month Follow-up Evaluation, 1-Year

Follow-up Evaluation, Reux, and
Complication Rates
Contact was established with all patients at the
required follow-up periods for up to 1 year. No patient
was lost to follow-up evaluation. The available number of
patients at each of the follow-up intervals at the time of
manuscript preparation was 70 (at 3 months), 61 (at
6 months), and 51 (at 1 year). The mean follow-up period
for the entire patient group (n 70) was 10.1 months
(range, 312 mo). Follow-up evaluation at 6 and
12 months showed sustained treatment success of 88.5%
and 82.4%, respectively (Figure 1). The mean Eckhardt
score pretreatment was 6.9 compared with 1.3 at 6 months
and 1.7 at 12 months (P < .001 for both comparisons).
The incidence of gastroesophageal reux after POEM is
shown in Table 1. Multivariate analysis showed that
neither age, previous treatment (Botox/dilatation), length
of the myotomy, pre-procedure LES pressure, initial Eckardt score, sex, procedure duration, nor full-thickness
dissection during POEM were signicant predictors of
treatment failure at 1 year. Complication rates are
described in Supplementary Table 5.

Discussion
This international prospective multicenter study
was able to reproduce the promising results of a POEM
pilot series57,10 in a substantially larger cohort and with a
longer follow-up period. POEM appears to be a safe and
effective treatment for achalasia, resulting in equivalent
short-term symptom relief compared with LHM.2,3 With
POEM it seems possible to emulate the surgical principles
of LHM without the need for skin incisions and to reduce
the procedural trauma. Treatment success for POEM
declined moderately during follow-up evaluation with
remission rates of 82% at 12 months. Thus, in the long
term, POEM may be slightly less effective than LHM,2,3
but nal conclusions can be drawn only after direct
comparison in a randomized controlled trial.

Figure 1. Three-month to 1-year remission rates after POEM with 95%

condence intervals (n 70).

GASTROENTEROLOGY Vol. 145, No. 2

Table 1. Gastroesophageal Reux After POEM Treatment

Clinical symptoms, %
Overall rate
Daily
Occasionally
PPI use, %
Overall rate
Daily
Occasionally
Endoscopic erosions, %
Overall rate
Grade A
Grade B
Grade C
Grade D

3 months

6 months

12 months

33
1.5
31.3

30
6.6
23.4

37
7.8
29.4

34
11.9
22.4

39
24.6
14.8

29
19.6
9.8

42
29.2
12.3
None
None

Comparing POEM with EBD also will require prospective randomized studies. Here, results will depend on the
dilatation protocol: if only one initial EBD is performed
then remission rates for POEM are likely to be higher.2
With an extended dilatation protocol that includes early
re-treatments in therapy-naive patients, EBD can be
equivalent to LHM at 2 years.3 In our study, approximately
half of the patients had received previous endotherapies
such as EBD or EBTI before POEM. This shows that
POEM is safe and efcient after previous treatments.
Studies have shown that treatment using EBD or BTI can
be associated with decreased outcomes for subsequent
LHM.12 However, after applying a multivariate analysis,
neither previous Botox nor EBD treatment were identied
as predictors of treatment failure after POEM. However,
this might be owing to the limited number of POEM
failures. Treatment failures after POEM underwent LHM
(n 3) or balloon dilatation (n 5), and treatments were
safe and effective. Because the target area for the myotomy
during POEM is lateral (on the lesser curvature side) and
the myotomy during LHM is anterior, subsequent LHM
seem to be a feasible second-line treatment if POEM fails.
Complications remain a matter of concern as with every
new technique. Visible complete transmural openings into
the mediastinum and into the peritoneal cavity occurred in
the majority of patients. Therefore, POEM potentially carries
the risk of mediastinitis/peritonitis and/or damage to surrounding organs. Full-thickness dissection into the mediastinum occurred because of the extremely thin layer of the
longitudinal muscle and adventitia, and into the peritoneum
because of intentional deep dissection and disappearance of
the circular/longitudinal layer structure at the cardia.
Occurrence of pneumoperitoneum and subcutaneous
emphysema was not associated with any infectious complications. However, use of corrective procedures (ie, transabdominal relief of CO2 with a 16G needle) was required in a
signicant proportion of cases, and it is mandatory to secure
the integrity of the overlying mucosal layer and to achieve
sufcient closure of the mucosal entry site. Furthermore,
precautions such as preoperative cleansing, sterile uids, and
perintervention antibiotics were used.

The rate of gastroesophageal reux appears to be higher

compared with published literature for LHM and EBD,
which is in the range of approximately 20%.3 At 3 months
after POEM, esophagitis was observed in 42% of cases.
However, the severity of esophagitis was only minor (grade
A or B) and all patients could be managed adequately with
proton pump inhibitor (PPI) therapy. At 3 months, 22%
of patients required occasional and 12% required daily
PPI therapy. The 1-year follow-up evaluation showed
slightly increased clinical reux rates (overall, 37%) but
slightly reduced PPI use (overall, 29%). However, further
assessment, especially pH-metry studies, comparing reux
rates after POEM with LHM and EBD remain warranted.
Such study limitations are addressed in the randomized
controlled trials that have been initiated.
Another potential benet of POEM is the option to
extend the myotomy into the proximal esophagus. This
could make POEM the preferred treatment approach for
type III achalasia13 or for patients with spastic disorders
(ie, nutcracker esophagus). However, only classic achalasia
patients were included in this study and the subgroup for
patients identied with type III achalasia was too small to
draw any conclusions on the efcacy of a very long
myotomy. Studies evaluating POEM for such patient
groups remains to be assessed in subsequent studies.
In conclusion, this international prospective multicenter study showed that POEM is a safe and effective
treatment for esophageal achalasia. Short- and long-term
symptomatic relief is adequate and associated with an
acceptable rate of gastroesophageal reux.

Supplementary Material
Note: To access the supplementary material
accompanying this article, visit the online version of

POEM FOR ACHALASIA 311

Gastroenterology at www.gastrojournal.org, and at http://

dx.doi.org/10.1053/j.gastro.2013.04.057.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.

Francis DL, et al. Gastroenterology 2010;139:369374.

Campos GM, et al. Ann Surg 2009;249:4557.
Boeckxstaens GE, et al. N Engl J Med 2011;364:18071816.
Pasricha PJ, et al. Endoscopy 2007;39:761764.
Inoue H, et al. Endoscopy 2010;42:265271.
Costamagna G, et al. Dig Liver Dis 2012;44:827832.
von Renteln D, et al. Am J Gastroenterol 2012;107:411417.
Hungness ES, et al. J Gastrointest Surg 2013;17:228235.
Ren Z, et al. Surg Endosc 2012;26:32673272.
Swanstrom LL, et al. Ann Surg 2012;256:659667.
Zhou P, et al. Endoscopy 2013;45:161166.
Smith CD, et al. Ann Surg 2006;243:579584.
Pandolno JE, et al. Gastroenterology 2008;135:15261533.

Received February 20, 2013. Accepted April 30, 2013.

Reprint requests
Address requests for reprints to: Daniel von Renteln, MD, Department
of Interdisciplinary Endoscopy, University Medical Center HamburgEppendorf, Martinistr. 52, 20246 Hamburg, Germany. e-mail:
renteln@gmx.net; fax: (49) 040-7410-40004.
Acknowledgments
The authors would like to thank Tania Noder for data management
and study follow-up evaluation, H. Inoue and H. Minami for training and
helping to introduce peroral endoscopic myotomy for this study, Guy
Boeckxstaens for advice with manuscript preparation, and John Cobain/
Olympus Corp for invaluable technical and organizational assistance
during the study.
Conicts of interest
The authors disclose no conicts.
Funding
Supported by the Euro-NOTES foundation and Olympus (Hamburg/
Germany and Canada) by providing material support (endotherapeutic
supplies) and supporting training and travel between centers.

BRIEF REPORT

August 2013

311.e1 VON RENTELN ET AL

Supplementary Materials and Methods

Patient Recruitment, Inclusion and Exclusion
Criteria
Adult patients with classic primary achalasia,
diagnosed by standard methods (contrast studies,
manometry and esophagogastroduodenoscopy) were
enrolled into this multicenter study at 5 centers in Europe
and North America (Hamburg n33, Frankfurt n12,
Amsterdam n14, Zurich n7, and Montreal n4). The
inclusion and exclusion criteria are listed in the
Supplementary Table 1. The study protocol was approved
by the Ethics Committee of each institution (registration
number PV3725 at the Hamburg Chamber of Physicians)
and written informed consent was obtained from all
patients.

POEM Procedures, Management Pre- and

Post-Procedure
All patients underwent a preoperative assessment
prior to peroral endoscopic myotomy (POEM) and were
considered eligible to undergo general anesthesia. Before
performing a POEM procedure independently, the endoscopist had to perform at least two procedures under
direct guidance of an endoscopist with extensive POEM
experience. The steps of the procedure, and the postoperative protocol have been previously described.1 All
study sites used the exact same operative protocol and
endotherapeutic material that has been described by our
group previously.1

Primary Outcome
The primary outcome was treatment success
dened as Eckhardt score of 3 at 3 months. Any patient
requiring additional treatment after POEM for recurrent
symptoms was dened as a treatment failure.

Follow-up and Secondary Outcomes

All patients were scheduled for follow-up visits
according to the schedule in Supplementary Table 2.
Secondary outcomes included: procedure related adverse
events, lower esophageal sphincter pressure (LESP),
symptomatic reux, and use of antacid medication. These
data were obtained at 3 months, with further clinical
follow-up conducted at 6 and 12 months. At 3 months,
patients were re-assessed by endoscopy, manometry, and
contrast radiography. Additional endoscopy, manometry,
and contrast radiography was offered to patients in

GASTROENTEROLOGY Vol. 145, No. 2

situations of persistent or recurrent symptoms. Procedurespecic parameters such as duration of the procedure, hospital stay, and length of the myotomy were also
noted. A serious adverse event (SAE) incidence of less than
2% was established as the minimum safety standard. SAEs
were dened as death, mediastinitis, peritonitis, or any
complication requiring emergency/salvage surgery. The
Ethics Comittee in Hamburg functioned as the safety
monitoring board and received a report after each
10 consecutive patients completed the 3 month follow-up.

Sample Size Calculation and Statistical

analysis
We performed a prospective pilot study to establish
the safety and preliminary efcacy for POEM1 and to
determine the sample size calculation for this study. The
sample size was calculated to demonstrate the noninferiority of POEM compared with alternative therapies
(LHM and EBD) with published success rates of about
90% for LHM and 68% for EBD.2 Calculations were based
on the results of our POEM pilot study resulting in a
93.8% success rate after POEM. To demonstrate noninferiority with a margin of equivalence of 14% and a
power of 80% (a .025 one-sided), 58 patients were
required for the study. To account for possible attrition of
up to 20%, 70 patients were recruited as per protocol.
Prior to analysis the data were plotted to determine
their distribution. Mean and 95% condence intervals
(95% CI) are shown. Mean values between baseline and
follow-up were compared using Students t-test for paired
samples. Success rates along with exact 95% CIs were
calculated. Between groups comparisons were calculated
with t-tests or Fishers exact test as appropriate. Logistic
regression with backward selection was used to identify
predictors of treatment failure. Nominal P values are reported; P < .05, two-sided, were considered signicant. In
case of treatment failure requiring any second-line therapy, the last Eckhardt score prior to the second-line
therapy is used for statistical assessment at all subsequent time points. R 2.15.2 was used for statistical analysis. All authors had access to the study data and have
reviewed and approved the nal manuscript.

References
1. Von Renteln D, et al. Gastrointest Endosc 2012;75:160160.
2. Campos GM, et al. Ann Surg 2009;249:4557.

August 2013

POEM FOR ACHALASIA

Supplementary Table 1. Study inclusion and exclusion criteria

Inclusion criteria
 Patients with symptomatic achalasia and pre-op barium
swallow, Manometry, and esophagogastroduodenoscopy which
are consistent with the diagnosis
 Age >18 years with medical indication for surgical myotomy or EBD
 Signed written informed consent.
Exclusion criteria
 Patients with previous surgery of the stomach or esophagus
 Patients with known coagulopathy
 Previous surgical achalasia treatment
 Patients with liver cirrhosis and/or esophageal varices
 Active esophagitis
 Eosinophilic esophagitis
 Barretts esophagus
 Pregnancy
 Stricture of the esophagus
 Malignant or premalignant esophageal lesion
 Severe Candida esophagitis
 Hiatal hernia > 1cm
 Extensive, tortuous dilatation (>7cm luminal diameter, S shape)
of the esophagus

311.e2

Supplement Table 3. Patient and procedural characteristics of

POEM
POEM (n70)
Age (y, CI)
Female gender (n, %)
Previous treatment (n, %)
OR time (min, CI)
Length of myotomy (cm, CI)

45
30
24
105
13

(40.548.8)
(42.9%)
(34.3%)
(95.1114.2)
(11.913.5)

Supplement Table 4. Outcomes of POEM Pre- vs Post Treatment

Pre-Treatment

Supplement Table 2. Study follow-up

Baseline 3 months 6 months 12 months 2 years
Eckhardt Score
EGD
Manometry
GERD Score
PPI use

O
O
O
O
O

O
O
O
O
O

O
O

O
O

O
O

O
O

Weight
Eckhardt Score
LESP
CRP
WBC
Hb

Post-Treatment

Mean

95% CI

Mean

95% CI

P value

72.8
6.9
27.6
4.1
7.4
13

(68.876.9)
(6.47.4)
(24.231.0)
(2.55.7)
(6.18.6)
(12.313.7)

75.6
1
8.9
58.7
9.9
12

(71.379.8)
(0.71.2)
(7.310.5)
(50.467.0)
(8.910.8)
(11.412.6)

.005
<.001
<.001
<.001
<.001
<.001

311.e3 VON RENTELN ET AL

GASTROENTEROLOGY Vol. 145, No. 2

Supplement Table 5. Complications of POEM

n (%)

Required additional treatment (n)

Clip dislocation at mucosal closure

Peroration into mediatinum at mucosal entry site

3 (4%)
1 (1%)

Mucosal injury through electrocautery or laceration

Bleeding requiring intervention
Cap detached in submucosal tunnel
Delayed bleeding leading to mediastinal hematoma

3
1
1
1

Endoscopic re-clipping (3)

Endoscopic clipping, creation of a more distal entry into
the submucosal tunnel (1)
Endoscopic clipping (3)
Endoscopic hemostatis (1)
Endoscopic removal (1)
Hospital admission, monitoring, conservative management (1)

Comlication

(4%)
(1%)
(1%)
(1%)

Sequela
none
none
none
none
none
none