1. Updates on the management of Achalasia
Joint Hospital Surgical Grand Round
21 July 2012
Lok Hon Ting (NDH)
Good monring senior surgeons and colleagues. Today I’m going to talk about the management of achalasia.

2. Pathophysiology Cause unknown, proposed etiology:
Motor disorder of the esophagus characterized by:
Incomplete or absent relaxation of LES
Aperistalsis of esophageal body
Destruction of ganglion cells present in the esophageal wall and LES
> Impaired relaxation of LES
Cause unknown, proposed etiology:
Viral hypothesis (VZV, HSV-1)
Jones DB. J Clin Pathol Robertson CS. Gut 1993
Autoimmune hypothesis
The term Achalasia is a greek term meaning “failure to relax”. It is a rare esophagus motor disorder characterised by two components: Incomplete or absent relaxation of LES and Aperistalsis of esophageal body, rendering ineffective passage of food bolus. The etiology is unknown.
Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal
relationship remains unclear
A preliminary report noted a statistically significant increase in antibody titers against measles virus in patients with achalasia compared with controls.75 Although this study has not been substantiated, another study using DNA hybridization techniques found evidence of varicella-zoster virus in three of nine myotomy specimens from patients with achalasia but none of 20 control specimens.76
Autoimmune Hypothesis
Early descriptions of inflammatory infiltration of the affected regions of the esophagus in achalasia led to speculation of an autoimmune pathogenesis. Inflammatory infiltration of the myenteric plexus was present in 100% of specimens from a histologic analysis of 42 achalasia esophagectomy specimens.11 Immunohistochemical staining characterized the infiltrative cells as T cells positive for CD3 and CD8.81 A significant eosinophilic infiltration has been demonstrated in some patients with achalasia.16, 21 An association between achalasia and class II histocompatability antigen has been described, specifically identifying a higher genotypic frequency of the human leukocyte antigen (HLA)-DQw1, DQA1*0101, DQA1*103, DQB1*0602, and DQB1*0603 alleles in achalasia patients compared with controls.82, 83, 84, 85 Class II antigen expression on myenteric neurons could be targeted as foreign antigens. Storch et al.86 demonstrated antibodies against myenteric plexus in serum of 37 of 58 patients with achalasia and in only four of 54 healthy controls. This study also failed to detect antibodies in the serum of patients with Hirschsprung's disease or esophageal cancer and in only one of 11 patients with peptic esophagitis. A second study detected serum antibodies against myenteric neurons in seven of 18 achalasia patients but not in healthy controls or reflux patients.87 The patients' antibodies bound to neurons in enteric plexuses from tissue sections of both the esophagus and intestine of rats. However, because the defect in primary achalasia is quite specific for the esophagus, the significance of a circulating antibody that targets not only esophageal but also intestinal neurons is unclear. In another recent study, positive immunostaining of the myenteric plexus of the esophagus and ileum of the guinea pig and mouse were detected in the serum samples of 23 out of 45 achalasia patients. However, a similar degree of immunostaining was demonstrated in the serum of eight of 16 patients with gastroesophageal reflux disease. This suggests that the antineuronal antibodies detected may represent nonspecific or secondary phenomena that do not play a causative role in the pathogenesis of achalasia.88

3. Clinical manifestation
Epidemiology
Prevalence 1 per 100,000
No gender predilection
Sadowski DC et al. Neurogastroenterol Motil 2010
Symptoms:
Dysphagia – Both liquids and solids
Regurgitation +/- Pulmonary Aspiration
Chest pain / Heartburn in ~50% patient
Spechler SJ et al. Gut 1995
Weight Loss
16-fold increased risk of Ca Esophagus
Sandler RS et al. JAMA 1995
It is a rare condition, affecting 1 in 100,000. Symptoms include dysphagia (involving both solid and liquid), regurgitation, chest pain, heart burn and weight loss. It was shown that it is associated with a 16-fold increased risk of Ca Esophagus.
Objective.  —To determine more precise and accurate cancer risk estimates for achalasia that could be used to plan surveillance.
Design.  —Cohort.
Setting.  —Swedish population.
Participants.  —All patients with achalasia listed in the population-based Swedish Inpatient Register from 1964 through 1989.
Main Outcome Measures.  —The observed number of cancers in the cohort was compared with expected numbers of cancers (standardized incidence ratio [SIR]) for each 5-year age group and calendar year of observation, calculated using data from the Swedish Cancer Registry.
Results.  —A total of 1062 patients with achalasia accumulated 9864 years of follow-up. The mean age at entry was 57.2 years, and the mean age at cancer diagnosis was 71.0 years. Esophageal cancer occurred in 24 patients. The risk of esophageal cancer in the first year after achalasia diagnosis was extremely high (SIR, 126.3; 95% confidence interval [Cl], 63.0 to 226.1) as a consequence of prevalent cancers leading to distal esophageal obstruction simulating achalasia. During years 1 to 24, the risk was increased more than 16-fold (SIR, 16.6; 95% CI, 8.8 to 28.3). Annual surveillance after the first year would require 406 endoscopic examinations in men and 2220 in women to detect one cancer.
Conclusions.  —Patients with achalasia are at markedly increased risk of developing esophageal cancer. A substantial number of surveillance examinations might be required to screen for cancers, especially in women. It is not known whether surveillance will result in improved survival.(JAMA. 1995;274: )

4. Investigation OGD Barium Swallow - Sensitivity 95%
tight cardia and food residual in esophgaus
Barium Swallow - Sensitivity 95%
Ott DJ et al. AJR Am J Roentgenol 1987
Esophageal manometry
absence of any esophageal peristaltic contractions
failure of the LES to relax to less than 8 mm Hg
Gideon RM. Gastrointest Endosc Clin N Am 2005
For patient with suspected Achalasia, OGD is mandatory to rule out mucosal lesion. The barium swallow film on the top left hand corner shows the classical bird’s beak appearance with a dilated esophagus and tapering OGJ. The golden standard for diagnosis is esophageal manometry, showing absence of esophageal peristaltic contraction and failure of LES to relax to less than 8mm Hg during swallowing

5. Treatment Modalities
To treat the condition, the 2 major components of the condition being aperistalsis and Failure LES relaxation are to be tackled. However, up till now there is no effective mehtod to restore effective peristalsis. Thus, multiple treatment modalities have been suggested to decrease LES pressure since the condition was first described in 1913.

6. Pharmacological treatment
Nitrates, Calcium channel blockers
Evidence:
Conclusion: Ineffective
Study
Design
Medication
LES Pressure
Dysphagia symptoms
Traube et al
Am J Gastroenterol 1989
RCT
PO Verapamil
PO Nifedipine ↓
No significant difference
Triadafolopoulos et al
Dig Dis Sci 1991
SL Nifedipine
Pharmacological treatment is basically not effective. Nitrates and Calcium channel blockers have been proposed to relieve dysphagic symptoms. Multiple RCTs in 1980s and 1990s have shown that both agents may have some effect in decreasing LES pressure. Howevere, there is no significant improvement in dysphagia symptoms.
Triadafilopoulos G, Aaronson M, Sackel S, et al. 
Institution
Evans Memorial Department of Clinical Research, University Hospital, Boston, Massachusetts.
Source
Dig Dis Sci 1991 Mar; 36(3) : Abstract
Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebo-controlled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia.
Isosorbide dinitrate and nifedipine treatment of achalasia: a clinical, manometric and radionuclide evaluation.
Gelfond M, Rozen P, Gilat T.
Abstract
The effects of sublingual isosorbide dinitrate (5 mg) and nifedipine (20 mg) were compared in 15 patients with achalasia. The parameters examined included the manometric measurement of the lower esophageal sphincter pressure, the radionuclide assessment of esophageal emptying and the clinical response. The mean basal lower esophageal sphincter pressure fell significantly after both drugs (p less than 0.01), with a maximum fall of 63.5% 10 min after receiving isosorbide dinitrate, but by only 46.7% 30 min after nifedipine. The esophageal radionuclide test meal retention was significantly less (p less than 0.01) only after receiving isosorbide dinitrate. The drug improved initial esophageal emptying by its effect on the lower esophageal sphincter and by relieving the test meal hold-up noted to occur at the junction of the upper and midesophagus. Eight patients cleared their test meal within 10 min after isosorbide dinitrate administration while only two did so after nifedipine. Subjectively, 13 patients had their dysphagia relieved by isosorbide dinitrate and 8 by nifedipine. However, this relief was not confirmed in 4 patients by the radionuclide study and they, as well as the other 3 patients who did not respond to therapy, were referred to pneumatic dilatation. Side effects were more prominent after nitrates. Three of the patients are currently receiving nifedipine and 5 patients received isosorbide dinitrate therapy for 8-14 mo. The radionuclide test meal is currently the best way of objectively evaluating drug therapy in patients with achalasia. Isosorbide dinitrate is more effective than nifedipine in relieving their symptoms.

7. Botulinum toxin injection
Endoscopic injection at 4 quadrants of LES
Inhibit release of acetylcholine in muscle synapse
First used by Pasricha in 1993
With the advancement of endoscopy technique, endoscopic treatment including botulinum toxin injection and dilatation emerged. Botulinum toxin is a chemical that inhibit release of acetylcholine in the msucle synapse. It was to be injected endoscopically into 4 quadrants of LES, so as to paralyze the LES muscle and decreased LES pressure.
Pseudoachalasia: not only esophago-gastric cancer.
Portale G, Costantini M, Zaninotto G, Ruol A, Guirroli E, Rampado S, Ancona E.
Source
Istituto Oncologico Veneto (IOV-IRCCS), University of Padova, School of Medicine, Padova, Italy.
Abstract
Pseudoachalasia is a rare clinical entity which has clinical, radiographic and manometric features often indistinguishable from achalasia. A small primary adenocarcinoma arising at the gastroesophageal junction or a tumor of the distal esophagus are the most frequent causes. Rarely, processes other than esophagogastric cancers may lead to the development of pseudoachalasia. We present three cases of pseudoachalasia in which the primary cause of the disease was not an esophagogastric cancer. The causes were a pancreatic carcinoma, a breast cancer and an histiocytosis X. Aspects of these three patients' diagnostic and therapeutic course are discussed in detail.

8. Botulinum toxin injection
Farnoosh Farrokhi etal. Orphanet Journal of Rare Diseases 2007
This pooled data, consisting of 4 RCTs and 4 prospective studies, showed that botox injection does decrease LES pressure in various degree and have very good short term result. Remission rate is more than 70% at 1 month FU. However, the majority of patients have symptom recurrence at 6 and 12 months FU. Although the response rate of 2nd injection is up to 76%, response rate decreased significantly in subsequent injection, possibly due to antibody formation against botox protein.
Promising short term effect
Symptoms recurrence beyond 6 months follow up
76% response to 2nd injection, but not to further injection

9. Botulinum toxin injection
Side effects 0 – 33%
Chest pain, reflux symptoms and rash
D Gui. Aliment Pharmacol Ther 2003
Subsequent myotomy more difficult
Pehlivanov N. Neurogastroenterol Motil 2006
Conclusion:
Safe and effective in short term symptoms relief
For elderly or frail patient only
Mild post-procedure symptoms of chest pain, reflux and allergic rashes were reported in 33% patients. Concern has been raised that subsequent myotomy may be more difficult after botox injection. It was concluded that botulinum toxin injection is safe and effective in short term only. It is recommended for elderly or frail patient only.

10. Pneumatic dilatation
To disrupt circular muscle fiber of LES without full thickness perforation
First used by Sir Thomas Willis since the condition was first recognized
Rigiflex Polyethylene balloon
(30, 35, 40mm diameter)
Another endoscopic treatment modality is endoscopic dilatation. The aim is to disrupt circular muscle fibers of the LES without full thickness perforation. Different dilatation devices have been developed. Rigidflex Polyethylene balloon with various sizes is most commonly used.

11. Pneumatic dilatation Guilherme M. Campos et al. Annals of Surgery 2009
This pool data consist of 7 Prospective and 8 retrospective study, using various dilatation protocol (in terms of dilator size, duration and pressure). It was shown that the rate of symptoms improvement is excellent in the short term follow-up, but the remission rate declined gradually beyond 6 months FU.
Guilherme M. Campos et al. Annals of Surgery 2009

12. Pneumatic dilatation A pool of 1065 patients in 15 controlled series
Mean follow-up 30.8 months (6 – 111 months)
Rate of symptom improvement decreases with FU duration
Perforation rate: 1.6% (0 – 8%)
Subsequent treatment after index dilatation:
Repeated dilatation 25%
Myotomy 5%
With a mean FU of 30.8 months, the rate of symptoms improvement rates decrease from 84.8% to 58% as shown in this diagram. 25% required repeated diltation while 5% of patients were referred to surgical unit for myotomy. Perforation rate was reported to be 1.6%. Although repeated dilatation or subsequent surgery is common, pneumatic dilatation became a popular choice of treatment because of minimal invasively in contrary to myotomy which was performed in an open manner before 1990s

13. Heller’s myotomy First described by Ernest Heller in 1914
Cutting the anterior and posterior aspect of LES
Current practice: myotomy over anterior aspect only
Minimally invasive approach 1990s
Thoracoscopic versus laparoscopic
Laparoscopic approach: less morbidity and quicker recovery
Richter JE. Gastroenterol hepatol 2008
> standard approach
Cardiomyotomy was first described by Heller in It involved cutting anterior and posterior aspect of LES via an open approach when it was first described. Laparoscopic approach was introduced in 1991 and laparoscopic cardiomyotomy soon became the standard of treatment. Only the anterior aspect of LES was in current practice.

14. Heller’s myotomy
The long-term efficacy of pneumatic dilatation and Heller myotomy for the treatment of achalasia.
Vela MF, Richter JE, Khandwala F, Blackstone EH, Wachsberger D, Baker ME, Rice TW.
Source
Department of Gastroenterology, Center for Swallowing and Esophageal Disorders, The Cleveland Clinic Foundation, Cleaveland, Ohio, USA.
Abstract
BACKGROUND & AIMS:
Studies comparing long-term success after pneumatic dilatation (PD) and laparoscopic Heller myotomy (HM) are lacking. This study compares long-term outcome of PD (single dilatation and graded approach) and laparoscopic HM and identifies risk factors for treatment failure.
METHODS:
A cross-sectional follow-up evaluation of an achalasia cohort treated between 1994 and 2002 was followed-up for a mean of 3.1 years. There was a total of 106 patients treated by graded PD (1-3 dilatations with progressively larger balloons) and 73 patients treated by HM (20 had failed graded PD and crossed over to HM). A symptom assessment (structured telephone interview or clinic visit) was performed and patients were given freedom from alternative therapies to determine treatment outcome. Endoscopy, manometry, and timed barium esophagram were performed to determine the cause of treatment failure.
RESULTS:
The success of single PD was defined as freedom from additional PDs: 62% at 6 months and 28% at 6 years (risk factors for failure: younger age, male sex, wider esophagus, and poor emptying on posttreatment timed barium esophagram). Freedom from subsequent PDs increased with each dilatation (graded PD). The success of graded PD and HM, defined as dysphagia/regurgitation less than 3 times/wk or freedom from alternative treatment, was similar: 90% vs 89% at 6 months and 44% vs 57% at 6 years (no risk factors for failure were identified). Causes of symptom recurrence were incompletely treated achalasia (96% after PD vs 64% after HM) and gastroesophageal reflux disease (4% after PD vs 36% after HM).
CONCLUSIONS:
No treatment cures achalasia. Short- and long-term success is similar for graded PD and laparoscopic HM. Therapeutic success decreases steadily over time. Achalasia patients need careful long-term follow-up evaluation.
Gastroenterology Apr;80(4):
A prospective randomized study comparing forceful dilatation and esophagomyotomy in patients with achalasia of the esophagus.
Csendes A, Velasco N, Braghetto I, Henriquez A.
A prospective and randomized study was performed comparing pneumatic forceful dilatation and surgical esophagomyotomy as primary treatment of patients with achalasia of the esophagus. Eighteen dilated and 20 operated patients were studied before and after treatment with 1 patient lost. Clinical, radiologic, and manometric evaluations were performed before and after treatment and acid reflux test in the late follow-up period. Immediately after treatment, a significant improvement was seen clinically, by radiologic studies and after manometric evaluation. In the late follow-up period, operated patients showed a permanent improvement in all of them, but dilated patients remained a symptomatic in about 50% of the cases. The rest had to be redilated or reoperated on due to a failure of primary dilatation leading to final good or excellent results in 60% and failure in 40% of patients. Acid reflux test showed a positive test in 31% of the operated patients and in 7% of the dilated patients. This controlled study suggests that surgical treatment of achalasia, used as primary treatment, is accompanied by significantly better long-term results compared with pneumatic dilatation according to the technique utilized by us.
Context Pneumatic dilatation and surgical (Heller) myotomy are the 2 principal methods
for treatment of achalasia. There are no population-based studies comparing outcomes
of these 2 treatments in typical practice settings.
Objective To compare the outcomes of pneumatic dilatation and surgical myotomy
for achalasia.
Design, Setting, and Participants Retrospective longitudinal study using linked
administrative health data in Ontario. A total of 1461 persons aged 18 years or older
received treatment for achalasia between July 1991 and December 2002, 1181 (80.8%)
of whom had pneumatic dilatation and 280 (19.2%) of whom had surgical myotomy
as the first procedure.
Main Outcome Measures Use of subsequent interventions for achalasia (pneumatic
dilatation, surgical myotomy, or esophagectomy) following the first treatment
during the study period, subsequent physician visits, and use of gastrointestinal medications
among persons aged 65 years or older. We adjusted for confounding variables
using regression models.
Results The cumulative risk of any subsequent intervention for achalasia after 1, 5,
and 10 years, respectively, was 36.8%, 56.2%, and 63.5% for persons treated initially
with pneumatic dilatation and was 16.4%, 30.3%, and 37.5% for persons treated
initially with surgical myotomy (adjusted hazard ratio [HR], 2.37; 95% confidence interval
[CI], ; P.001). Differences in risk were observed only when subsequent
pneumatic dilatation was included as an adverse outcome; there was no statistical
difference between the 2 groups with respect to the risk of subsequent surgical
myotomy or esophagectomy. Compared with persons treated initially with surgical
myotomy, those treated with pneumatic dilatation were not statistically different with
respect to subsequent physician visits (adjusted rate ratio, 1.01; 95% CI, ),
or time to use of histamine-2 receptor blockers (adjusted HR, 1.19; 95% CI, 0.79-
1.80), proton pump inhibitors (HR, 1.02; 95% CI, ), and prokinetic medications
(HR, 0.92; 95% CI, ).
Conclusions Subsequent intervention after the initial treatment of achalasia is common.
Although the risk of subsequent interventions among persons treated with surgical
myotomy in typical practice settings is higher than previously thought, the risk of
subsequent intervention is greater among persons treated with pneumatic dilatation
than with surgical myotomy. This difference is attributable to the use of subsequent
pneumatic dilatation rather than surgical procedures.
Bresadola et al. Surg Laparosc Endoscc Percutan Tech 2012

15. Heller myotomy A pool of 1708 patients in 19 publications
Follow-up duration: 4.78 year (range: years)
Symptom response rate: 79.3% (range: 47 – 97%)
GERD:
With fundoplication: 15.2% (range: 0 – 44%)
Without fundoplication: 37% (range: 11 – 60%)
Response rates decreased in patients with longer FU
> 7 years: 80% > 10 years: 74% > 20 years 65%
Csendes. Ann Surg 2006
This pool data consists of 1700 patient in 19 publications. With a mean FU of 4.78 year, symptoms response rate was about 80%, ranging from 47 – 97%. Apparently, cardiomyotomy renders a more sustainable symptom improvement. However, it was also found that the procedure was associated with gastroesophageal reflux. For those without concomitant fundoplication the average rate of fundoplication was 37%.
first report of laparoscopic Heller myotomy in 1991 by Shimi
thoracoscopic Heller myotomy by Pellegrini et al2 in 1992

16. Heller’s myotomy and anti reflux surgery
Study
Design
Patient no.
Acid Reflux
Dysphagia / Esophageal emptying
Richards et al. Ann Surg 2004
Prospective double-Blind RCT
H: 21
H: 47.6%
No significant difference in dysphagia score
H + D: 22
H + D: 9.1% (p = 0.005)
Rice et al.
J Thorac Cardiovasc Surg 2005
Retrospective non-randomized study
H: 61
H + D:
↓ exposure time
↓ number of episode
↓ longest episode time
(p < 0.05)
H + D did not impair esophageal emptying
(p = 0.6)
H + D: 88
Conclusion:
Heller’s myotomy with concomitant Dor’s fundoplication is the procedure of choice
D Falkenback et al
Dis Eso 2003
RCT
H: 10
H: 47.6%
No significant difference in dysphagia score
(p = 0.82)
H + N: 10
H + D: 9.1%
(p = 0.005)
In view of this, studies have been performed to compare Cardiomyotomy alone and Cardiomyotomy plus Dor’s Fundoplication. This table summarized the results trials about concomitant antireflux surgery. It was found that both Dor’s and Nissen’s fundoplication effectively decreased GERD without affecting dysphagia symptoms when compared to heller’s myotomy alone. RCT comparing Dor’s and Nissen’s fundoplication shows that both contribute to decreased GERD incidence, but patient with nissen fundoplication has more dysphagia after operation. Thus, it is concluded that Dor’s fundoplication is the procedure of choice
ler’s myotomy alone
versus
heller’s myotomy + Dor’s Fundoplication
Rebecchi et al
Ann Surg 2008
RCT
H + D: 72
5.6%
2.8%
H + N: 72
0% (p = 0.07)
15%
(p < 0.001)

17. Pneumatic Dilatation versus Heller’s Myotomy
A Csendes et al. Guts 1989
Randomized controlled trial
Subjects: Pneumatic dilatation (n = 39)
Open Heller’s myotomy + Dor’s fundoplication (n =42)
Conclusion:
The study shows that surgical treatment offers a better final clinical result than pneumatic dilatation with the Mosher bag
With the above result, it seems that laparoscopic heller’s myotomy with concomitant partial fundoplication render a more sustained symptoms improvement in comparison to pneumatic dilatation whereas pneumatic dilatation offers a less invasive approach with a reasonable effectiveness in reducing dysphagic symptoms. Study has been performed since 1980s to compare these two modalities of treatment. Csendes performed a RCT and the result was published in 1989, it was found that with a median FU of 58 months, only 54% of patient in the dilatation group remains symptoms free whereas 95% patient who received myotomy remains symptoms free
Late results of a prospective randomised study
comparing forceful dilatation and oesophagomyotomy
in patients with achalasia
A CSENDES, I BRAGHETTO, A HENRIQUEZ, AND C CORTES
From the Department of Surgery and Radiology, University of Chile, Santiago, Chile
SUMMARY Late results in 81 patients with achalasia treated in a prospective randomised study
comparing forceful pneumatic dilatation with the Mosher bag and surgical anterior oesophagomyotomy
by abdominal route, are reported. There were no deaths from either of the treatments.
Two patients (5*6%) had a perforation of the abdominal oesophagus after pneumatic dilatation and
were excluded from late follow up. In patients having surgery at radiological evaluation there was
gullet diameter significantly increased at the oesophagogastric junction and decreased at the middle
third of the oesophagus. One patient was lost from follow up and one died of an oesophageal
carcinoma, leaving 95% of excellent results at the late follow up (median 62 months). Resting
gastro-oesophageal sphincter pressure decreased significantly to approximately 10 mmHg; this was
maintained five years after surgery. By contrast, in patients having pneumatic dilatation, there were
good results in only 65% (follow up median 58 months), with 30% failures. One patient was lost from
follow up and one developed oesophageal carcinoma. Measurement of resting gastro-oesophageal
sphincter pressure after dilatation was highly predictive of the outcome. The study shows that
surgical treatment offers a better final clinical result than pneumatic dilatation with the Mosher bag.
After 6 months, the results in the 2 groups were comparable, although symptom scores improved more in surgical patients (82% confidence interval [CI] 76–89 vs. 66% CI 57–75, P 0.05). The drop in lower esophageal sphincter pressure was similar in the 2 groups; the reduction in esophageal diameter was greater after surgery (19% CI 13–26 vs. 5% CI 2–11, P 0.05). Later on, symptoms recurred in 65% of the BoTx-treated patients and the probability of being symptom-free at 2 years was 87.5% after surgery and 34% after BoTx (P 0.05). Conclusion: Laparoscopic myotomy is as safe as BoTx treatment and is a 1-shot treatment that cures achalasia in most patients. BoTx
should be reserved for patients who are unfit for surgery or as a
bridge to more effective therapies, such as surgery or endoscopic
dilation.
Surg Endosc May 19. [Epub ahead of print]
Perioperative management and treatment for complications during and after peroral endoscopic myotomy (POEM) for esophageal achalasia (EA) (data from 119 cases).
Ren Z, Zhong Y, Zhou P, Xu M, Cai M, Li L, Shi Q, Yao L.
Source
Endoscopy Center, Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, , China,
Abstract
BACKGROUND:
The aim of this study was to investigate the management and treatment for complications during and after peroral endoscopic myotomy (POEM) for patients suffering from esophageal achalasia (EA).
METHODS:
The data of 119 cases of EA patients who underwent POEM from October 2010 to July 2011 and the complications that arose during the operation, after the operation, and during follow-up were analyzed.
RESULTS:
Complications that occurred during the operation included cutaneous emphysema (22.7 %, 27/119) and pneumothorax (2.5 %, 3/119). Postoperative complications included pneumothorax (25.2 %, 30/119), subcutaneous emphysema (55.5 %, 66/119), mediastinal emphysema (29.4 %, 35/119), delayed hemorrhage (0.8 %, 1/119), pleural effusion (48.7 %, 58/119), minor inflammation or segmental atelectasis of the lungs (49.6 %, 59/119), and gas under diaphragm or aeroperitoneum (39.5 %, 47/119). Complications that occurred during follow-up included one case of difficulty eating caused by the stricture of mucosa and one case of dehiscence at the mouth of the tunnel created during surgery, with food retention. No deaths occurred. All complications were resolved through traditional treatment. No additional surgery was needed.
CONCLUSION:
Complications arising during and after POEM should be treated quickly and can be resolved by using traditional treatment. POEM can be expected to become the preferred treatment for EA. 17

18. Pneumatic Dilatation versus Lap Heller’s Myotomy
S Kostic et al. World J Surg 2006
Randomized controlled trial
Subjects: Graded pneumatic dilatation (n = 26)
Heller’s myotomy + toupet’s fundoplication (n =25)
Primary outcome: Treatment failure rate
2 Perforations after pneumatic dilatation
Kostic performed a RCT which was published in World J Surg patients were randomised and follow up for an year. It was found that the treatment failure rate is significantly higher for dilatation group at 1 year FU. 18

19. Pneumatic Dilatation versus Lap Heller’s Myotomy
Lopushinsky SR et al. JAMA 2006
Retrospective longitudinal study
Subjects: Pneumatic dilatation 1181 (80.8%)
Surgical myotomy 280 (19.2%)
Primary outcome: use of subsequent intervention
Differences in risk were observed only when subsequent pneumatic dilatation was included as an adverse outcome
Another Retrospective longitudinal study was published in A total of 1461 received either pneumatic dilatation and surgical myotomy was studied for risk of subsequent intervention (either repeated dilatation or surgery). It was found that risk of subsequent intervention is higher in dilatation group. However, if repeated dilatation is not considered as treatment failure, there is no difference in subsequent intervention risk.
Main Outcome Measures Use of subsequent interventions for achalasia (pneumatic
dilatation, surgical myotomy, or esophagectomy) following the first treatment
during the study period, subsequent physician visits, and use of gastrointestinal medications
among persons aged 65 years or older. We adjusted for confounding variables
using regression models.
Results The cumulative risk of any subsequent intervention for achalasia after 1, 5,
and 10 years, respectively, was 36.8%, 56.2%, and 63.5% for persons treated initially
with pneumatic dilatation and was 16.4%, 30.3%, and 37.5% for persons treated
initially with surgical myotomy (adjusted hazard ratio [HR], 2.37; 95% confidence interval
[CI], ; P.001). Differences in risk were observed only when subsequent
pneumatic dilatation was included as an adverse outcome; there was no statistical
difference between the 2 groups with respect to the risk of subsequent surgical
myotomy or esophagectomy. Compared with persons treated initially with surgical
myotomy, those treated with pneumatic dilatation were not statistically different with
respect to subsequent physician visits (adjusted rate ratio, 1.01; 95% CI, ),
or time to use of histamine-2 receptor blockers (adjusted HR, 1.19; 95% CI, 0.79-
1.80), proton pump inhibitors (HR, 1.02; 95% CI, ), and prokinetic medications
(HR, 0.92; 95% CI, )
Clin Gastroenterol Hepatol May;4(5):580-7.
The long-term efficacy of pneumatic dilatation and Heller myotomy for the treatment of achalasia.
Vela MF, Richter JE, Khandwala F, Blackstone EH, Wachsberger D, Baker ME, Rice TW.
Source
Department of Gastroenterology, Center for Swallowing and Esophageal Disorders, The Cleveland Clinic Foundation, Cleaveland, Ohio, USA.
Abstract
BACKGROUND & AIMS:
Studies comparing long-term success after pneumatic dilatation (PD) and laparoscopic Heller myotomy (HM) are lacking. This study compares long-term outcome of PD (single dilatation and graded approach) and laparoscopic HM and identifies risk factors for treatment failure.
METHODS:
A cross-sectional follow-up evaluation of an achalasia cohort treated between 1994 and 2002 was followed-up for a mean of 3.1 years. There was a total of 106 patients treated by graded PD (1-3 dilatations with progressively larger balloons) and 73 patients treated by HM (20 had failed graded PD and crossed over to HM). A symptom assessment (structured telephone interview or clinic visit) was performed and patients were given freedom from alternative therapies to determine treatment outcome. Endoscopy, manometry, and timed barium esophagram were performed to determine the cause of treatment failure.
RESULTS:
The success of single PD was defined as freedom from additional PDs: 62% at 6 months and 28% at 6 years (risk factors for failure: younger age, male sex, wider esophagus, and poor emptying on posttreatment timed barium esophagram). Freedom from subsequent PDs increased with each dilatation (graded PD). The success of graded PD and HM, defined as dysphagia/regurgitation less than 3 times/wk or freedom from alternative treatment, was similar: 90% vs 89% at 6 months and 44% vs 57% at 6 years (no risk factors for failure were identified). Causes of symptom recurrence were incompletely treated achalasia (96% after PD vs 64% after HM) and gastroesophageal reflux disease (4% after PD vs 36% after HM).
CONCLUSIONS:
No treatment cures achalasia. Short- and long-term success is similar for graded PD and laparoscopic HM. Therapeutic success decreases steadily over time. Achalasia patients need careful long-term follow-up evaluation.
Comment in
The long-term efficacy of pneumatic dilation and Heller myotomy for the treatment of achalasia. [Clin Gastroenterol Hepatol. 2006] 19

20. Pneumatic Dilatation versus Lap Heller’s Myotomy
Design
Patient no.
Symptom improvement (% patient)
GERD
Perforation
6 – 12 months
2 years
6 years
Vela MF et al
Clin gastroenterol hepatol 2006
Cross sectional study
Single PD: NR
62%
28% 4%
Graded PD: 106
90%
44%
HM: 73
89%
57%
36%
GE Boechxstaens et al
N Engl J Med 2011
RCT
Graded PD: 95
86%
15%
HM + Dor: 106
93%
23%
(p=0.28)
12%
mucosal tear
A cross sectional study involving 179 patients published in 2006 show that the rate of symptom improvement is actually similar between graded PD and HM at 6 years FU. Another RCT involving 201 patients was published in NEJM in It shows that the rate of symptoms improvement is actually similar at 2 year FU.
Clin Gastroenterol Hepatol May;4(5):580-7.
The long-term efficacy of pneumatic dilatation and Heller myotomy for the treatment of achalasia.
Vela MF, Richter JE, Khandwala F, Blackstone EH, Wachsberger D, Baker ME, Rice TW.
Source
Department of Gastroenterology, Center for Swallowing and Esophageal Disorders, The Cleveland Clinic Foundation, Cleaveland, Ohio, USA.
Abstract
BACKGROUND & AIMS:
Studies comparing long-term success after pneumatic dilatation (PD) and laparoscopic Heller myotomy (HM) are lacking. This study compares long-term outcome of PD (single dilatation and graded approach) and laparoscopic HM and identifies risk factors for treatment failure.
METHODS:
A cross-sectional follow-up evaluation of an achalasia cohort treated between 1994 and 2002 was followed-up for a mean of 3.1 years. There was a total of 106 patients treated by graded PD (1-3 dilatations with progressively larger balloons) and 73 patients treated by HM (20 had failed graded PD and crossed over to HM). A symptom assessment (structured telephone interview or clinic visit) was performed and patients were given freedom from alternative therapies to determine treatment outcome. Endoscopy, manometry, and timed barium esophagram were performed to determine the cause of treatment failure.
RESULTS:
The success of single PD was defined as freedom from additional PDs: 62% at 6 months and 28% at 6 years (risk factors for failure: younger age, male sex, wider esophagus, and poor emptying on posttreatment timed barium esophagram). Freedom from subsequent PDs increased with each dilatation (graded PD). The success of graded PD and HM, defined as dysphagia/regurgitation less than 3 times/wk or freedom from alternative treatment, was similar: 90% vs 89% at 6 months and 44% vs 57% at 6 years (no risk factors for failure were identified). Causes of symptom recurrence were incompletely treated achalasia (96% after PD vs 64% after HM) and gastroesophageal reflux disease (4% after PD vs 36% after HM).
CONCLUSIONS:
No treatment cures achalasia. Short- and long-term success is similar for graded PD and laparoscopic HM. Therapeutic success decreases steadily over time. Achalasia patients need careful long-term follow-up evaluation.
Comment in
The long-term efficacy of pneumatic dilation and Heller myotomy for the treatment of achalasia. [Clin Gastroenterol Hepatol. 2006]

21. Pneumatic Dilatation versus Heller’s Myotomy
Emerging evidence showing comparable result between pneumatic dilatation and Heller’s Myotomy
Improvement of dilatation devices and technique
Definition of treatment failure
Some of the latest studies accept repeated dilatation as part of the dilatation program, instead of treatment failure
Both pneumatic dilatation and Heller’s Myotomy are reasonable choices of treatment if patients accept repeated dilatation
As you can see from the above studies, there seems to be emergence of evidence showing comparable results between HM group and pneumatic dilatation group. This maybe due to the improvement in dilatation devices and technique with well decided dilatation protocol. Another reason for improved outcome of pneumatic dilatation is that some of the latest studies accept repeated dilatation as part of the dilatation program, instead of treatment failure. It seems that with the currently available evidence, both pneumatic dilatation and laparoscopic cardiomyotomy are reasonable choices of treatment provided that the patient understand risk of repeated dilatation.

22. Per Oral Endoscopic Myotomy
Natural orifice transluminal endoscopic surgery -> Novel approach for Achalasia
The concept of Submucosal tunneling and procedure was described by Samiyama K in 2007
Endoscopic myotomy was first reported by Pasricha et al. in a porcine model
Endoscopy 2007
Per Oral endoscopic Myotomy is a novel approach for treatment of achalasia. It was first reported by Pasricha in a porcine model in The photoes on the right are intra-operative pictures in porcine model. the procedure basically involves raising the mucosa by injecting saline into submucosa. Then the overlying mucosa is incised and submucosal tunnel was developed down to the LES where myotomy was performed. Significant decrease in LES pressure was demonstrated.
Fig. 1 The endoscopic myotomy procedure.
a Normal saline was first injected into the submu−
cosa. b An incision was made using an electrocau−
tery knife to provide entry for the balloon catheter.
c Balloon dilation was performed to accentuate the
submucosal space. d The endoscope was then in−
serted into the submucosal space. e We then per−
formed a myotomy of the circular muscle (the ar−
rows point to the edges of the cut muscle). f The
mucosal defect was finally closed with clips.

23. Per Oral Endoscopic Myotomy
First series of 17 patients with achalasia treated by P.O.E.M., reported by Inoue et al
Endoscopy 2010
The first human series involving 17 subjects was published in 2010 by Inoue

24. Per Oral Endoscopic Myotomy
17 patients
seven women, ten men
mean age 41.4 years, range 18–62
Long submucosal tunnel created (mean 12.4cm)
Mean myotomy length = 8.1cm
Dysphagia symptoms score: 10  1.3 (p = )
LES pressure: 52.4mmHg  19.8mmHg (p = )
In the series, both dysphagia score and LES pressure was significantly decreased whereas no major complication was reported

25. Per Oral Endoscopic Myotomy
Experience from various centers
Study
Patient no.
Myotomy length (cm)
Dysphagia score
LES Pressure
(mmHg)
Morbidity
Inoue et al. Endoscopy 2010 17
8.1
Pre: 10
Post: 1.3
(p = )
Pre: 52.4
Post: 19.9
(p = )
Penetration of cardiac mucosa in 2 patients, no clinical manifestation
Zhou PH et al.
Chi J Gastroint Surg 2011 42
9.5
Significant symptoms improvement
Not reported
Nil
Costamagna et al
Digestive and Liver Disease 2012 7
10.2
Eckardt Score
Pre: 7.1
1 month: 1.1
(p = 0)
Pre: 45.1
Post: 16.9
This table summarized the available published series. They show promising short term result. However, long term results are lacking.

26. Conclusion
Laparoscopic cardiomyotomy + partial fundoplication is the standard treatment for achalasia
Pneumatic dilatation is reasonable alternative if patient accepts risk of repeated dilatation
Botox injection is only recommended for elderly and frail patients
To conclude, with the current available evidence, laparoscopic cardiomyotomy plus fundoplication remains the treatment of choie. Pneumatic dilatation is resonable alternative provided patient accepts risk of repeated dilatation. Botox injection is reserved for those elderly or frail patients.

27. Conclusion
POEM is a novel approach showing promising short term results
Long term follow up needed
rate of symptoms recurrence
need for subsequent intervention
incidence of GERD
complication profile
POEM is a novel approach for the treatment of achalasia with promising short term result. However long term follow up is needed to define the rate of symptoms recurrence, need for subsequent intervention and incidence of GERD.

28. Thank you