effi cacy and safety of pneumatic dilatation
TRANSCRIPT
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nature publishing groupORIGINAL CONTRIBUTIONS
ESOPHA
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TheAmerican Journal ofGASTROENTEROLOGY VOLUME 108 |JULY 2013 www.amjgastro.com
see related editorial on page x
INTRODUCTION
Te short-term results o surgical myotomy or pneumatic dilata-tion are excellent. A recent prospective randomized controlled
trial comparing Heller myotomy to pneumatic dilation as pri-
mary therapy, demonstrated comparable outcomes at 2 years o
90% and 86% respectively (1). However, achalasia is a chronic
relapsing condition, which, irrespective o primary treatment
modality, has a substantial relapse rate ranging rom 2530%
at 5 years ollowing either treatment modality (2,3). Tere is a
paucity o data to guide the clinician as to how best treat symp-
tom recurrence when it occurs ollowing Heller myotomy. Temost requent cause o short-term ailure o Heller myotomy is
an incomplete myotomy either due to incomplete transection o
muscle bers or healing with brosis at the myotomy site ( 4,5).
Other less common causes include a tight undoplication, gas-
troesophageal reux, decompensated megaesophagus beore
surgery and the late occurrence o carcinoma. In this context,
there are no universally accepted management guidelines and in
Efficacy and Safety of Pneumatic Dilatation for
Achalasia in the Treatment of Post-Myotomy SymptomRelapse
Vivek Kumbhari, MBBS, FRACP1, Jason Behary, MBBS1, Michal Szczesniak, PhD1, Teng Zhang, MSc1and Ian J. Cook, MD(Syd), FRACP1
OBJECTIVES: There is no consensus on how best to treat symptom recurrence following previous therapy with
Heller myotomy. Our aim was to determine the safety and the short and long-term efficacy of
pneumatic dilatation to treat symptomatic recurrence in patients previously treated with Heller
myotomy for idiopathic achalasia.
METHODS: We identified 27 eligible patients treated with pneumatic dilatation, for symptom recurrence follow-
ing Heller myotomy as their initial or secondary treatment, from a prospectively acquired databaseof 450 patients with a diagnosis of achalasia seen between 1995 and 2010. Our treatment protocol
involved sequential, graded pneumatic dilatations (303540 mm) over a 26 week period until
an initial therapeutic response was achieved. The subsequent relapse rate, defined as the need for
any subsequent therapy, was determined. Relapsers were offered further pneumatic dilatation
on demand. A cross-sectional analysis was also performed using a validated achalasia severity
questionnaire to determine the overall long-term remission rate.
RESULTS: Of 27 eligible patients, 25 (93%) complied with the institutional dilatation protocol. The two
drop-outs did so after the initial 30 mm dilatation and were deemed treatment failures. One
additional patient did not respond despite protocol compliance. Therefore, 24 of 27 (89%) patients
were responders on intention to treat analysis at 12 months, while the per protocol response rate
was 24 of 25 (96%). Among the 24 responders 16, 25, and 42% relapsed at 2, 3 and 4 years,
respectively. Overall long-term remission, with on demand dilatations as required, was 95%
(median follow-up 30 months). There were no perforations in a total of 50 dilatations in 27 patients.
CONCLUSIONS: In treating symptom recurrence, following prior Heller myotomy, pneumatic dilatation is safe and
yields an excellent short-term response rate. Although the long-term relapse rate is substantial,
subsequent on demand pneumatic dilatation in this population is highly effective with a long-term
remission rate of 95%. These data also highlight the need to keep these patients under long-term
review.
Am J Gastroenterol2013; 108:10761081; doi:10.1038/ajg.2013.32; published online 5 March 2013
1Department of Gastroenterology & Hepatology, The St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia. Correspondence:
Ian J. Cook, MD(Syd), FRACP, Department of Gastroenterology and Hepatology, Gastrointestinal Motility Service, St. George Hospital , Kogarah, Sydney, New
South Wales 2217, Australia. E-mail: [email protected] 4 December 2012; accepted 18 January 2013
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Pneumatic Dilatation Post-Heller Myotomy
light o the technical diffi culties, uncertain results and reux risk
o redo myotomy (6,7) surgeons are ofen reluctant to reoperate.
On the other hand, the effi cacy and saety o pneumatic dilata-
tion in this context is also unclear.
Te limited published data on pneumatic dilatation or post-
myotomy symptom recurrence are based on relatively small sam-
ple sizes and short term ollow-up. Te available literature in this
context suggests quite a variable response rate to pneumatic dilata-
tion o 5078% at 1 year (3,4,8). Furthermore, the durability o that
response has been largely unexplored.
Te aim o this study was to determine the saety and the short
and long-term effi cacy o pneumatic dilatation to treat sympto-
matic recurrence in patients who had undergone Heller myotomy
either as primary or secondary therapy or idiopathic achalasia.
METHODS
Patients
Patients selected rom a prospectively acquired database o 450patients with idiopathic achalasia seen by a single gastroenter-
ologist (I.J.C.) in a tertiary reerral center between the years
19952010. Te database comprised patients who had had a
diagnosis o idiopathic achalasia diagnosed on the basis o clini-
cal eatures conrmed by typical manometric ndings or, in
atypical cases, by a combination o the above, as well as radio-
logical ndings. All patients had prior upper gastrointestinal
endoscopy to exclude malignancy and pseudoachalasia. Patients
were included in this study i they had undergone surgical myo-
tomy as either their initial, primary therapy or as secondary
therapy and had subsequent symptomatic recurrence, which
was treated with pneumatic dilatation. Hence inclusion criteriaincluded a mix o patients including those who were either treat-
ment naive, as well as those who had had a pneumatic dilatation
or Botox injection beore their surgical myotomy. Te decision
as to whether a patient had relapsed ollowing Heller myotomy
was based on the patient reporting problematic symptoms, as
well as the judgment o a single experienced clinician (I.J.C.).
Tat clinicians guiding denition o what he considered symp-
tomatic relapse ollowing myotomy was one or more o the ol-
lowing: (a) the presence o dysphagia more than twice per week;
(b) meal-related regurgitation more than once per week; or (c)
any nocturnal regurgitation. Patients were excluded i they had:
any other previous surgery involving the esophagogastric junc-
tion; radiotherapy to the head, neck or thorax; neuromusculardisorders that might impair swallowing or i they had signicant
cognitive impairment.
Pneumatic dilatation and follow-up protocol
All pneumatic dilations were perormed by a single experi-
enced gastroenterologist (I.J.C.) using a standardized protocol.
Gastroscopy was perormed under conscious sedation with
the patient in the oblique lef lateral position. With the aid o
the endoscope and uoroscopy, radio-opaque skin markers
were positioned to identiy the proximal and distal margins
o the gastroesophageal junction. Over a Savary guide wire,
positioned with its tip in the duodenum, a Rigiex balloon dilator
(Microvasive Boston Scientic Corp, Boston, MA, USA) was
passed such that the balloon straddled the gastroesophageal
junction. Te balloon was then inated to 1215 psi or 15 s.
Post procedure, all patients received a Gastrogran esopha-
gram to exclude esophageal peroration. Patients were dis-
charged home afer at least 4 h o observation i they were
stable without signicant chest pain and were tolerating uids
without diffi culty.
In the specic context o post-Heller symptom recurrence,
our protocol is to perorm sequential, graded balloon dilata-
tions routinely commencing with a balloon diameter o 30 mm,
but progressing with subsequent dilatations up to 35 or 40 mm,
at intervals o 24 weeks should it be necessary in the context
o a suboptimal clinical response to smaller balloons. Patients
were assessed 714 days afer each dilatation by a single gastro-
enterologist (I.J.C.) in order to establish whether urther dila-
tation was necessary. Te therapeutic response was dened as
adequate i the patient described: (a) the presence o transientdysphagia 2 times per week or less; (b) meal-related regurgita-
tion once per week or less; and (c) no nocturnal regurgitation. I
a therapeutic response was achieved no urther dilatations were
perormed. Patients were then reviewed afer 12 months, and
thereafer every 2 years, unless they experienced earlier symp-
tom recurrence. Initial responders who subsequently relapsed
were offered on demand pneumatic dilatations in order to
reinstate clinical remission. At that point they were deemed to
have relapsed.
Short-term response
Following pneumatic dilatation, patients were initially classiedas a responder (see above) or nonresponder as assessed by
the same gastroenterologist (I.J.C.). Nonresponders were those
who ailed to achieve adequate symptom relie despite a 40-mm
balloon dilatation. Tese patients received alternate therapy.
Patients who did not comply with or complete the institutional
protocol or who had procedure-related peroration, were deemed
treatment ailures (i.e., nonresponders) as per intention to treat
analysis.
Long-term outcome measures
Tis was determined in two ways. (1) Relapse rate by dened
endpoints, and (2) Point prevalence o remission by validated
questionnaire in June 2010. Among the post-procedure respond-ers, the subsequent relapse rate was dened as the time to any
subsequent therapy including urther pneumatic dilatation,
Botox injection or repeat Heller myotomy. o determine the
overall long-term remission rate, all responders to the initial
treatment protocol were asked to complete a 10-item sel-report
symptom inventory, which has been validated previously as a
measure o achalasia disease-specic heath-related quality o
lie (9). Te questionnaire sampled the concepts o ood toler-
ance, dysphagia-related behavior modications, pain, heartburn,
distress, liestyle limitation, and satisaction. Te individual
scores ranged rom 0 to 100. A score o 0 indicates the complete
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absence o symptoms and unaffected quality o lie. A score o
100 represents debilitating symptoms at each meal with a totally
unsatisactory quality o lie. Te questionnaire was mailed to all
responders, and those who had not returned it within a month
were contacted via telephone and asked to return the completed
questionnaire. Scores were deemed valid only i there were no
missing responses. Tose with an achalasia symptom score < 50
were considered to be in remission at that time. Briey, patients
who scored < 50 could eat and drink most oods, were able to
swallow with little diffi culty, rarely had pain and had minimal
impairment o quality o lie (9).
Ethics
At the time o receipt o the ollow-up symptom questionnaire,
all participants gave written, inormed consent to participate
in the study and or their data to be used. Te study protocol
was approved by Human Ethics Committees o the South Eastern
Sydney and Illawarra Area Health Service.
Statistical analysis
All statistical analyses were perormed by using SPSS, version
19.0 (SPSS Inc., Chicago, IL, USA). Disease-ree survival esti-
mates were calculated by the KaplanMeier method and survival
comparisons were perormed using the log-rank test. Inerences
regarding any differences in proportions o responders between
subgroups o patients were made using a Fishers Exact test.
RESULTS
Patient characteristics
Te database identied 27 (10 M, 17F) patients with median ageo 51 years (range 1679 years) who met the inclusion criteria
or the study. Te median interval between the Heller myotomy
and subsequent salvage pneumatic dilation was 7 years (range
145 yrs). O these 27 patients, 16 had been treatment naive; 10
had ailed pneumatic dilatation and one had had Botox beore
their Heller myotomy.
Short-term response to pneumatic dilatation
O the 27 patients who commenced the sequential dilations, 25
(93%) complied with the ull protocol (see above). Te two non-
compliant patients were deemed treatment ailures as per inten-
tion to treat analysis. One o the 25 patients who completed the
protocol also ailed to respond to pneumatic dilatation. Hence,24 o 27 patients (89%) were considered initial responders on
intention to treat analysis while 24 o 25 (96%) responded as per
protocol analysis (Figure 1). welve o 27 patients (44%) ailed to
respond to the 30-mm balloon. O these, 2 did not proceed (i.e.,
noncompliant) while 10 proceeded to 35 mm dilatation. Tree
patients (11%) progressed to the 40 mm balloon dilatation.
A subgroup analysis was perormed to compare the pre-Hel-
ler myotomy treatment group (n= 11) and pre-Heller myotomy
naive group (n= 16). Patients who had had treatment beore their
Heller myotomy had a trend toward a higher nonresponse rate to
pneumatic dilatation (3 o 11), when compared with those who
were treatment naive (none o 16) (P= 0.056) although this did not
reach statistical signicance.
Relapse rate post-pneumatic dilatation
Te relapse rate was determined in the 24 patients who had
responded to pneumatic dilatation(s). No patient had relapsed
within 12 months o dilatation. Te annual relapse rates are
shown in the KaplanMeier curve (Figure 2). Relapse rates were
16%, 25% and 42% at 2 year, 3 years and 4 years respectively. At
the time o assessment, with median ollow-up time o 30 months
PD 30 mm (n=27)
Nonresponder
n=12
Nonresponder
n=3
Nonresponder
n=1
PD 35 mm
n=10
PD 40 mm
n=3
Dropouts
n=2
Responder
n=15
Responder
n=7
Responder
n=2
Figure 1. Response rates following initial sequential pneumatic dilata-
tions. Note that 44% needed more than one (i.e., > 30 mm) dilatationwhile 11% required three dilatations (i.e., up to 40 mm). PD, pneumatic
dilatation.
0
0 2 4
Years
6 8
20
40%Remission
60
80
100
Figure 2. KaplanMeier survival curve showing remission rates in the
initial 24 responders. While none had relapsed at 12 months, the relapse
rate thereafter was substantial with 58% in remission at 4 years.
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Pneumatic Dilatation Post-Heller Myotomy
(range 1228 months) a cumulative total o 6 o 24 patients had
relapsed.
A subgroup analysis was again perormed to compare the pre-
Heller myotomy treatment group and pre-Heller myotomy naive
group. Patients who had had treatment beore their Heller myo-
tomy had a comparable relapse rate (4 o 8) when compared with
those who were treatment naive (2 o 16) (P= 0.13).
Long-term outcome
wenty-two (92%) o the 24 initial responders to pneumatic
dilatation returned their symptom questionnaires. wo ques-
tionnaires were not returned despite ollow-up contact by tel-
ephone. At the time o survey (June 2010), 21 o 22 (95%) had
a questionnaire score < 50, and were deemed to be in clinical
remission with median ollow-up interval o 30 months (range
1228 months). O note, out o the 21 patients in remission,
5 o 6 patients who had relapsed during the ollow-up
interval had had interval relapses successully treated with on
demand pneumatic dilatation. None had undergone alterna-tive therapies.
Procedure safety
A total o 50 pneumatic dilatations in 27 patients were perormed
throughout the entire study period; 40 at the time o initial post-
surgical treatment and 10 subsequently perormed on demand
or symptomatic relapse. Tere were no perorations sustained in
either group.
DISCUSSION
Tis single center retrospective study o 27 patients is the largestto date evaluating the effi cacy and saety o pneumatic dilatation
to treat symptomatic recurrence in patients who had been treated
with Heller myotomy, either as primary or secondary therapy, or
idiopathic achalasia. Te major nding rom this study is that
pneumatic dilatation in this context has an excellent short-term
response rate but a substantial relapse rate in the ollowing years.
Te response rate 12 months ollowing pneumatic dilatation on
intention to treat analysis was 89%. In those patients compliant
with the ull protocol o sequential dilatations, up to a maximum
balloon diameter o 40 mm where necessary, the response rate was
96% at 12 months. Pneumatic dilatation in this context appears to
be sae with no perorations afer 50 dilatations. However, deter-
mination o the true peroration rate would require a greater sam-ple size. We also report substantial longer-term relapse rates o
16, 25 and 42% at 2, 3 and 4 years respectively. Tis observation
is compatible with extensive existing data indicating that achala-
sia is a chronic relapsing condition with a substantial long-term
relapse rate afer primary treatment with either surgical myotomy
(3,4,1012) or ollowing pneumatic dilatation (2,3,13,14) How-
ever, our data also show that salvage treatment o post-myotomy
recurrence combined with subsequent on demand subsequent
pneumatic dilatations, yields an excellent long-term outcome with
95% o patients in remission at a median ollow-up o 2.5 years
using this approach.
Subgroup analysis suggests that those who had ailed primary
therapy beore their myotomy tended to show a poorer imme-
diate response and a tendency toward a higher relapse rate
ollowing pneumatic dilatation than those who had been treat-
ment naive beore their myotomy. However, the numbers in the
pre-Heller myotomy treatment naive group (n= 16) and
the group who had had some treatment beore their myo-
tomy (n= 11) are relatively small and this trend ailed to reach
statistical signicance.
reatment success in achalasia has been usually dened on the
basis o symptom improvement (13,15). Valid comparison across
studies is diffi cult as denitions vary rom strict criteria (symp-
toms once per week or less) (13) to more liberal endpoints, such
as 50% decrease in symptoms or lack o need or repeat treatment
(16). Tere are only a ew published studies, all with < 10 patients,
that have evaluated the response to pneumatic dilation (with the
now standard Rigiex balloon dilator) in patients with symptom
relapse ollowing Heller myotomy. Zaninotto et al. (4) reported
that 56% o nine patients remained clinically asymptomatic at amedian ollow-up o 14.5 (360) months. wo studies reporting
the Cleveland Clinic experience evaluated response rates to pneu-
matic dilatation in this context (3,8). Guardino et al.(8) reported
50% o 10 patients had symptomatic improvement (less than 24
episodes o dysphagia and regurgitation per week) at a mean ol-
low-up o 10.8 months. Vela et al.(3), using the same outcome
measures, reported 67% o three patients (mean ollow-up 11.5
months (178 months) improved symptoms with pneumatic dila-
tation used in the context o recurrence ollowing myotomy as
the primary initial treatment.Te discrepancy among these stud-
ies relates to several actors: (a) differences in the denition o
relapse; (b) small sample sizes; (c) lack o distinction betweeninitial relapse and relapse despite on demand pneumatic dilata-
tion; and (c) limited ollow-up duration (typically 12 months).
Te apparent higher relapse rate observed by Zaninotto et al.(4),
could be accounted or by a less vigorous initial dilatation pro-
tocol. For example, that study ound in those reporting a air
response, that none had received a 40-mm dilatation and one had
not received dilatation with balloon larger than 30 mm. It is note-
worthy that 11% o the patients in the current study and 4059%
in the Cleveland Clinic experience required a 40-mm balloon
dilatation beore an adequate initial response was achieved (3,8).
Tis highlights the need or a more aggressive approach in the
context o prior ailed myotomy when compared with untreated
cases o achalasia.Intuitively it could be argued that pneumatic dilatation in
patients who have undergone prior surgery might carry a greater
risk o peroration than does dilatation or untreated achalasia
in whom the peroration risk varies rom 2 to 5% (1,8,17). In
the present study o a total o 50 dilatations in 27 patients, there
were no perorations. However, the true peroration rate is di-
cult to determine even rom the current study, which is the larg-
est reported to date. Despite the act that a 40-mm dilatation is
required more requently in this population than in untreated
achalasia (8) none o the previously published studies reporting
pneumatic dilatation using Rigiex balloons in this context have
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pneumatic dilatations and patient ollow up. Te author has read and
approved the nal draf o the manuscript submitted: Ian Cook.
Financial support: None.
Potential competing interests: None.
Study HighlightsWHAT IS CURRENT KNOWLEDGE
3Achalasia is a chronic relapsing condition, irrespective ofprimary therapy.
3The optimal management of patients with symptom relapsefollowing Heller myotomy is unknown.
3Published reports of outcome and safety of pneumaticdilatation to treat symptom recurrence following Heller
myotomy are few and studied small numbers.
WHAT IS NEW HERE
3In this, the largest series reported to date, we reportpneumatic dilatation to be highly effective in treating
post-Heller myotomy symptom recurrence with an initial
response rate of 89% intention to treat analysis or
96% (per protocol).
3Pneumatic dilatation appears to be acceptably safe inthis context with no perforations after 50 dilatations in
27 patients.
3While long term relapse rates are substantial (42% at 4 yrs),on demand future pneumatic dilatation is highly effec-
tive salvage therapy yielding a long term overall remission
rate of 95% (median follow-up 2.5 years).
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versus laparoscopic Hellers myotomy or idiopathic achalasia. New Engl JMed. 2011;364:180716.2. Zerbib F, Tetiot V, Richy F. Repeated pneumatic dilations as long-term
maintenance therapy or esophageal achalasia. Am J Gastroenterol2006;101:69297.
3. Vela MF, Richter JE, Wachsberger D. Complexities o managing achalasia ata tertiary reerral center: use o pneumatic dilatation, Heller myotomy, andbotulinum toxin injection. Am J Gastroenterol. 2004;99:102936.
4. Zaninotto G, Costantini M, Portale G et al.Etiology, diagnosis, and treat-ment o ailures afer laparoscopic Heller myotomy or achalasia. Ann Surg2002;235:18692.
5. Ellis FH Jr. Failure afer esophagomyotomy or esophageal motor disorders.Causes, prevention, and management. Chest Surg Clin N Am 1997;7:47787; (discussion 88).
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7. Costatini M, Di Giunta M, Salvador R et al.Remedial laparoscopic myo-
tomy or recurrent esophageal achalasia afer ailed surgical treatment. DisEsophagus 2012;25 (Suppl 1): 56A.
8. Guardino JM, Vela MF, Connor J et al.Pneumatic dilation or the treat-ment o achalasia in untreated patients and patients with ailed Hellermyotomy. J Clin Gastroenterol 2004;38:85560.
9. Urbach DR, omlinson GA, Harnish JL et al.A measure o disease-specic health-related quality o lie or achalasia. Am J Gastroenterol.2005;100:166876.
10. Berch BR, Nava RD, orquati A et al.Myotomy: ollow-up study o50 patients. J Gastrointest Surg. 2005;9:132631.
11. Bessell JR, Lally CJ, Schloithe A et al.Laparoscopic cardiomyotomy orachalasia: long-term outcomes. ANZ J Surg. 2006;76:55862.
12. Csendes A, Braghetto I, Burdiles P et al.Very late results o esophago-myotomy or patients with achalasia: clinical, endoscopic, histologic,manometric, and acid reux studies in 67 patients or a mean ollow-up o190 months. Annal Surg 2006;243:196203.
reported any perorations, albeit with a relatively small combined
experience o 19 cases (3,4,8).
Te alternative to pneumatic dilatation or most patients who
require urther therapy afer ailed Heller myotomy is a redo myo-
tomy. Redo myotomy is technically challenging, with mean operat-
ing times o 3 h and prolonged post operative stay o up to 5 days
(6,7). Gorecki et al.(6), in a small study o six patients, reported good
short-term results in 83% ollowing laparoscopic redo myotomy.
A recent study o 30 patients undergoing redo laparoscopic myotomy
also reported the operative diffi culties encountered and a response
rate o 73%. O some concern also, was that, 20% o patients in that
study developed troublesome reux (7). In a condition that has been
shown to have a high relapse rate, the problems become even more
diffi cult in the context o urther recurrences ollowing repeat sur-
gery. In this context, esophagectomy becomes increasingly likely.
An important secondary nding in the present study was that
longer term relapses ollowing pneumatic dilatation or post-
myotomy recurrence were successully treated by on demand
pneumatic dilatation. At a mean ollow-up interval o 30 months,95% o the original cohort o patients remained in remission. Tis
observation matches that o others who ollow a similar long-
term strategy o on demand pneumatic dilatation with a remis-
sion rate o at least 95% with mean ollow-up o 45 months (2).
In summary, graded pneumatic dilatation, up to 40 mm bal-
loon diameter i necessary, together with on demand dilatation
thereafer, is a sae and effective treatment or post-Heller myo-
tomy symptom relapse in patients with idiopathic achalasia. Te
available evidence indicates that redo myotomy is technically di-
cult and has a signicant ailure rate and complication rate. On
this background, and given the effi cacy and saety demonstrated
in the present study, there is a strong argument or pneumaticdilatation in preerence to repeat surgery, particularly in a con-
dition, which is known to be chronic and relapsing. Te need
or repeated treatments over the liespan o these patients also
emphasizes the need to keep these patients under review long
term in order to pick up recurrent obstruction and, hopeully
avoids the development o megaesophagus (3,18).
CONFLICT OF INTEREST
Guarantor of the article: Ian J. Cook, MD(Syd), FRACP.
Specic author contributions:Study design, database review, data
collection, analysis and interpretation o data, statistical analysis,
creation o gures and manuscript preparation. Te author
has read and approved the nal draf o the manuscript submitted:Vivek Kumbhari; study design, interpretation o data, statistical
analysis, creation o gures and manuscript preparation.
Te author has read and approved the nal draf o the manuscript
submitted: Jason Behary; statistical analysis, editing gures and
drafing o the manuscript. Te author has read and approved
the nal draf o the manuscript submitted: Michal Szczesniak;
collation o reerences and drafing o the manuscript. Te author
has read and approved the nal draf o the manuscript submitted:
ang Zhang; study hypothesis and design, database creation,
database review, analysis o results, interpretation o data,
statistical analysis, manuscript preparation. Perormance o
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Pneumatic Dilatation Post-Heller Myotomy
13. West RL, Hirsch DP, Bartelsman JF et al.Long term results o pneumaticdilation in achalasia ollowed or more than 5 years. Am J Gastroenterol2002;97:134651.
14. Karamanolis G, Sgouros S, Karatzias G et al.Long-term outcome opneumatic dilation in the treatment o achalasia. Am J Gastroenterol2005;100:27074.
15. Spiess AE, Kahrilas PJ. reating achalasia: rom whalebone to laparoscope.JAMA 1998;280:63842.
16. Vaezi MF. Quantitative methods to determine effi cacy o treatmentin achalasia. Gastrointest Endosc Clin N Am 2001;11:40924,(viii-ix).
17. Spechler SJ. AGA technical review on treatment o patients with dysphagiacaused by benign disorders o the distal esophagus. Gastroenterology1999;117:23354.
18. Richter JE, Boeckxstaens GE. Management o achalasia: surgery orpneumatic dilation. Gut 2011;60:86976.