Comparative Study Between Laparoscopic Heller Myotomy Versus Pneumatic Dilatation for Treatment of Early Achalasia: A Prospective Randomized Study

Abstract

Introduction:

Achalasia is an incurable primary motor disorder of the esophagus. The best treatment modality for achalasia is still controversial. This study compared the short- and intermediate-term outcome between endoscopic pneumatic dilatation (EPD) versus laparoscopic esophageal myotomy (LEM) for the management of adult patients with early-stage achalasia.

Patients and Methods:

This was a prospective randomized controlled study of adult patients (20–50 years old) who presented with early-stage achalasia (esophageal diameter of <3.5 cm on contrast esophagography). Patients were classified into two groups according to the method of management: Group A patients were treated with LEM, whereas Group B patients were treated with EPD. Follow-up evaluations were conducted at 1 week, 3 months, 6 months, and then 1 year.

Results:

In total, 50 patients were managed for a manometrically confirmed diagnosis of achalasia. The median age of presentation was 31.5 years, with a male-to-female ratio of 0.4:1. Both groups were comparable regarding patient demographics and preoperative severity of the condition. The rate of symptoms relief was 76% in EPD compared with 96% in LEM (P=.04). There was a significant lowering of lower esophageal sphincter in the LEM group (P=.0001). Perforation of the esophagus occurred in 8% of the patients during EPD, whereas mucosal tears occurred in 4% of the patients during LEM. Reflux symptoms developed in 28% and 16% of the patients in the EPD and LEM groups, respectively.

Conclusions:

LEM was more effective clinically and manometrically for patients with early-stage achalasia than EPD. There was no significant difference between the two procedures regarding complications.

Introduction

Achalasia is an incurable primary motor disorder of the esophagus.¹ Its characteristic manometric features are esophageal body aperistalsis and insufficient relaxation of a frequently hypertensive lower esophageal sphincter in response to swallowing.² As the pathogenesis of achalasia is not well understood, the treatment is palliative, aiming at relieving the obstruction at the gastroesophageal junction.³ Variable treatment modalities for achalasia include pharmacological treatment, injection of botulinum toxin, endoscopic pneumatic dilatation (EPD), and Heller's cardiomyotomy.⁴ The laparoscopic approach in performance of Heller's cardiomyotomy in the early 1990s rendered it comparable to EPD in the management of achalasia with a shorter hospital stay and less postoperative pain.⁵

The best treatment modality for achalasia is still controversial. Studies comparing EPD with laparoscopic esophageal myotomy (LEM) reported contradicting results. Some authors reported similar long-term outcome for both EPD and LEM, whereas other studies showed superiority of LEM.^2,6–9 There is practical conflict corresponding to the contradiction found in these studies. LEM is the first line of treatment for achalasia in the United States, and EPD reversed for cases with surgical failure.³ On the other hand, surgery has a secondary role in most European and Canadian centers.^3,10

Direct comparison between EPD and LEM was difficult because of the confounding bias caused by variability in patient age and degree of achalasia and the performance bias caused by heterogeneity in the procedures of EPD and LEM. This study was designed to minimize this bias as the procedures of both the EPD and the LEM were performed by the same group of surgeons who are experienced in laparoscopy and endoscopy. The study also compared the short- and intermediate-term outcome between EPD versus LEM for management of adult patients with early-stage achalasia through a randomized controlled trial.

Patients and Methods

This was a prospective randomized controlled study of adult patients (20–50 years old) who presented with early-stage achalasia (esophageal diameter of <3.5 cm on contrast esophagography) to be managed by the Mansoura Gastrointestinal Surgical Center, Mansoura University, Mansoura, Egypt, in the period between January 2005 and January 2010. Patients were classified into two groups according to the method of management: Group A patients were treated with LEM and Dor fundoplication, whereas Group B patients were treated with EPD. Exclusion criteria included extremes of age (less than 20 years and more than 50 years), previous endoscopic treatment for achalasia or previous upper abdominal surgery, grade II or III esophageal dilatation on contrast esophagography, sigmoid esophagus, and patients who were unfit for surgery.

Informed consent was obtained from all patients to be included in the current study, after a careful explanation of the disease and possible modalities of treatment with its morbidity. The study was approved by the local ethical committee.

Preoperative evaluation of patients was done by a thorough history-taking with regard to age, sex, duration of illness, and the achalasia symptoms, which included dysphagia, regurgitation, weight loss, chest pain, heartburn, and respiratory complications. Dysphagia was classified by Demeester's grading into mild dysphagia with occasional episodes, moderate dysphagia that required fluid to clear, and severe grade with solid food impaction that required medical or endoscopic treatment.¹¹ Barium contrast study of the esophagus was done for all patients. Patients were divided into four groups according to the esophageal dilatation into first degree (esophageal diameter <3.5 cm), second degree (esophageal diameter from 3.5 to 6 cm), third stage (esophageal diameter >6 cm), and fourth stage, with marked esophageal dilatation, angulation, and tortuousness.¹² Moreover, all patients were evaluated by upper gastrointestinal endoscopy to confirm the diagnosis and exclude pseudoachalasia. Finally, the esophageal manometric study was mandatory to confirm the diagnosis.

Randomization

Patients with early achalesia included in this study were randomized into two groups using the closed envelope method. The envelopes were drawn and opened by a nurse. The patients were randomized into two groups: Group A patients were treated with LEM and Dor fundoplication, whereas Group B patients were treated with EPD.

Intervention

Laparoscopic esophageal cardiomyotomy and Dor fundoplication

The standard approach for performance of the procedure is the laparoscopic approach. The distal esophagus is mobilized anteriorly and laterally, bringing adequate length of the intraabdominal esophagus. The anterior vagus is identified and dissected from the distal esophagus to allow adequate length of myotomy. The myotomy incision starts at the midline just above the point of apparent constriction until the plane between the muscle and the mucosa is identified. Then, the myotomy is extended for 6 cm in the lower esophagus and 2 cm in the stomach below the cardia. Mucosal integrity is ensured by saline injection through a nasogastric tube with distal occlusion of the stomach. If mucosal injury is detected, it is repaired with simple interrupted stitches by polyglactin 910 (Vicryl^® 4/0; Ethicon, Somerville, NJ). Afterward, anterior 180° Dor fundoplication covering the myotomy is done with interrupted 2/0 silk sutures approximating the seromuscular layer of the fundus to the edge of the myotomy.

The patient is ambulant on the evening of the operation. Oral fluids are started on the first postoperative day. Patients are discharged on postoperative Day 3 if the postoperative course is uneventful. We do not perform diatrizoate meglumine and diatrizoate sodium solution (Gastrografin^®; Bayer, Leverkusen, Germany) swallow as a routine proceudre after surgery. If mucosal injury occurs during the operation, the nasogastric tube is not removed, and a Gastrografin swallow is performed, usually on Day 4. If it is free, the patient starts oral feeding, and the patient is discharged, usually on Day 5 or 6 postoperatively.

Endoscopic pneumatic balloon dilatation

Pneumatic dilatation is performed after an overnight fasting with the patient under conscious sedation in the left lateral position. Esophageal lavage through a large-bore nasogastric tube is performed if needed. A noncompliant pneumatic balloon is passed over a guidewire to be positioned at the cardia under direct vision by upper endoscopy alone. The balloon is inflated up to a pressure of 15 psi for 60–90 seconds. Dilatation is gradually done by 3-cm, 3.5-cm, and 4-cm-diameter balloons unless mucosal ulceration occurs. Gastrografin study of the esophagus is performed to exclude esophageal perforation. The patient is put under close observation for 6 hours after the procedure and then discharged. After a pneumatic dilatation, patients are started on a proton pump inhibitor for 1 week.

Assessment

The primary outcome was the successful symptomatic relief, which evaluated carefully using the aforementioned Demeester's grading of dysphagia.¹¹

If the patients complained of recurrent symptoms after surgery, the surgical treatment was deemed to be a failure. If the patient required more than three sets of dilatation, the pneumatic dilatation was deemed a failure.

Secondary outcomes were the length of postoperative hospital stay, postoperative morbidities including esophageal perforation and reflux symptoms, esophageal manometery, and recurrence of symptoms.

Follow-up

Follow-up was carried out 1 week, 3 months, 6 months, and then 1 year postprocedure. Patients with suspected recurrence were evaluated by esophageal manometry, barium swallow, and endoscopy. After 1 year, all patients underwent a follow-up endoscopy, manometry, and barium swallow.

Statistics

Patient data were recorded in a prospectively maintained database in a standardized manner. Descriptive data were expressed as median with ranges for continuous data. Categorical variables were described using frequency distributions. A P value <.05 was considered statistically significant. Comparison of variables was done by independent Student's t test for continuous variables and the chi-squared test for categorical variables. Statistical analysis was done with the help of IBM (Armonk, NY) SPSS version 20 software.

Results

In total, 50 patients were managed for a manometrically confirmed diagnosis of achalasia in the period between January 2005 and January 2010 in the Gastrointestinal Surgical Center of Mansoura University. The median age of presentation was 31.5 years, with a male-to-female ratio of 0.4:1. The median duration of illness was 44 months, ranging from 4 to 96 months. Dysphagia was the main presenting symptom (100%) with varying degree of severity according to Demeester's grading system.¹¹ The study population was randomly assigned to treatment by either EPD (n=25) or LEM (n=25). Both groups were comparable regarding patient demographics and preoperative severity of the condition (Table 1).

Table 1.

Comparison of Preoperative Symptoms and Manometric Features Between the Laparoscopic Esophageal Myotomy Group and the Endoscopic Pneumatic Dilatation Group

	LEM	EPD	P value
Age (years)	32	30.8	.35
Sex (male:female)	8/17	5/20	.33
Dysphagia			.71
Mild	13	15
Moderate	8	6
Severe	4	4
Heartburn	7/25	12/25	.15
Regurgitation	8/25	9/25	.77
Weight loss	7/25	11/25	.24
Manometry
LESP	39.8	37.4	.6
% relaxation	68%	65.6%	.82
Simultaneous waves	58.2%	59.2%	.55
Nontransmitted waves	35.2%	36.5%	.78

EPD, endoscopic pneumatic dilatation; LEM, laparoscopic esophageal myotomy; LESP, lower esophageal sphincter pressure

The standard approach in surgery was laparoscopy, and there was no need to convert to open exploration in the study population. Injury of the mucosa occurred in 3 cases (12%) and was managed by either simple repair only or simple repair with the addition of Dor fundoplication. The mean duration of hospital stay after surgery was 3±1 days. A postoperative leak occurred in 1 case (4%), which was managed nonoperatively (antibiotics, intravenous fluid, and total parenteral nutrition). Mild wound infection was encountered in 3 cases (12%). One patient (4%) did not show symptomatic improvement after LEM. This case was managed by EPD, which showed poor response despite repeated sets of dilatation, and the patient is refusing undergoing another surgical myotomy (Table 2).

Table 2.

Comparison of Postoperative Outcome Between the Laparoscopic Esophageal Myotomy Group and the Endoscopic Pneumatic Dilatation Group

	LEM	EPD	P value
Esophageal perforation	1/25 (4%)	2/25 (8%)	.55
Improvement of dysphagia after
3 months	24/25 (96%)	19/25 (76%)	.04
1 year	22/25 (96%)	14/25 (56%)	.01
Developing reflux symptoms	7/25 (28%)	4/25 (16%)	.3
Recurrent symptoms after 1 year	2/24 (8.3%)	5/19 (26.3%)	.1
Manometeric features
LESP	11.04±2.62	16.01±2.88	.0001
% relaxation	79.72±4.12%	75.08±4.31%	.0001
Simultaneous waves	44.4±4.56%	43.04±5.05%	.3
Nontransmitted waves	38.04±5.33%	41.3±6.78%	.67
Cost (USD) of the procedure	580	228	.0001

EPD, endoscopic pneumatic dilatation; LEM, laparoscopic esophageal myotomy; LESP, lower esophageal sphincter pressure; USD, U.S. dollars.

In the dilatation group, 12 patients (48%) had one set, 8 patients (32%) had two sets, and 5 patients (20%) had three sets of EPD. EPD is an outpatient procedure that does not require a hospital stay for more than 6 hours of observation. Esophageal perforation occurred in 2 patients (8%) who were managed nonoperatively after hospital admission. Chest pain and fever are infrequent complications (20%). Failure of the EPD was encountered in 6 patients (24%) who did not show symptomatic improvement after the third set of EDP; these 6 cases were managed by LEM and showed a dramatic response.

The median duration of follow-up after the procedure was 48 months, ranging from 3 to 144 months. The rate of symptoms relief was 76% in EPD compared with a rate of 96% in LEM (P=.04). There was a significant lowering of the lower esophageal sphincter in the LEM group (P=.0001). Perforation of the esophagus occurred in 8% of patients during EPD, whereas mucosal tears occurred in 4% of patients during LEM. Reflux symptoms developed in 28% and 16% of the patients in the EPD and LEM groups, respectively (Table 2).

Discussion

LEM and EPD are the mainstays of treatment for achalasia.¹³ However, both modalities carry a variable risk of perforation, gastroesophageal reflux disease, and recurrence of symptoms.¹⁴ Although achalasia is the most common motility disorder of the esophagus, few randomized studies have compared LEM and EPD on a large sample size with standardization of surgical and endoscopic procedure.¹⁵ Moreover, to our knowledge the comparison between the efficacy of LEM and EPD in early-stage achalasia in adult patients has never been examined.

There is no standard technique for EPD. Katzka and Castell¹⁶ analyzed 25 studies on EPD and concluded that there is no identical method of EPD regarding the type of the balloon, pressure, and duration of dilatation except between two studies only. Besides, EPD is usually performed by gastroenterologists, whereas LEM is performed by surgeons, and that renders comparing the two procedures difficult. The technique of EPD is similar to that reported by Wong and Maydonovitch.¹⁷ At our center, EPD and LEM are both done by expert surgeons who have been performing both procedures for at least 10 years.

Decision-making regarding management of adult patients with early-stage achalasia represents a real challenge. Both LEM and EPD have shown comparable results in patients with minor illness severity.¹⁸ Endoscopic treatment carries the advantages of being an outpatient procedure, fewer procedure-related complications, and the presence of the second line of surgical treatment in case of failure.^2,19 On the other hand, laparoscopic myotomy shows better short- and long-term outcome with better quality of life due to the absence of the need for repeated sets of endoscopic dilatation.^2,20

Definition of failure after EPD is crucial in its comparison with LEM regarding efficiency and cost. This study defined failure after EPD when the patient had persistent dysphagia after the third set of dilatation in accordance with the recommendation of the American Gastroenterological Association.²¹ According to this definition, the failure rate was higher in the EPD group, but it did not reach statistical significance (P=.42). If the failure was deemed with persistent dysphagia after one set of dilatation, the failure rate would have been significantly higher in the EPD group (n=16, P=.0001).

To avoid biased cost-effectiveness analysis, Yaghoobi et al.¹⁵ recommended consideration of repeated sets of dilatation and the need for surgical treatment during assessment of the cost of EPD. However, consideration of these recommendation did not affect the significantly lower cost of EPD ($228 U.S.) in comparison with LEM ($580 U.S.) (P=.0001). Thus, repeated sets of dilatation affected the assessment of the effectiveness of the EPD but did not affect the lower cost of the procedure when compared with LEM. The cost of LEM does not take into consideration the mandatory hospital stay, which would presumably make it far more costly.

In this series, the significant improvement of manometric features in the LEM group (P=.0001) was not reflected in a significant clinical improvement (P=.42). This is can be partially explained by the ongoing controversy regarding the relation between the pressure of the lower esophageal sphincter and the degree of clinical manifestation of achalasia.²² This finding can be also justified by the small sample size of both groups, which did not show a significant difference between the two groups. The small sample size is due to the small proportion of adult patients who presented in the early stage of achalasia.

Despite limiting the study to early-stage achalasia in adult patients, the results regarding complications and response rate are comparable to those of studies comparing EPD and LEM in achalasia patients in general. A European multicenter comparative study found the response rate to be 90% and 86% 2 years after LEM and EPD, respectively.²³ Similarly, this study reported better outcome in LEM, but it did not reach statistical significance in comparison with EPD. The perforation rate was similar to studies reported by previous studies.^8,16

The long-term remission after LEM is reported to occur in 95% of patients.⁵ Nevertheless, the management of patients with recurrent achalasia after surgery is a surgical challenge. Some studies recommended remyotomy as the best treatment modality for patients with recurrence after LEM, but this requires a high level of experience in esophageal surgery and patients' acceptance of an increased likelihood of morbidities.^19,24 On the other hand, younger age is reported as a risk factor for failure after EPD.^25,26 However, failure of EPD can be successfully managed by further sets of dilatation or switching to LEM.¹⁶

Conclusions

EPD and LEM are comparable treatment strategies for adult patients with early-stage achalasia. There was no significant difference between the two procedures regarding complications and response rate. Improvement of manometric features was better in the LEM, whereas the expenses were less in EPD. Failure after EPD showed a good response to surgical treatment. Difficult management of failure after LEM should be clarified during patient counseling. There is a need for more multicenter and randomized studies comparing EPD and LEM in adult patients with early-stage achalasia.

Footnotes

Disclosure Statement

No competing financial interests exist.

E.H. and A.E.N. designed the research. E.H., A.E.N., E.E.H., M.E.H., T.S., H.H., and N.G.E.H. performed the research. E.H., A.E.N., and H.H. analyzed the data. A.E.N. and H.H. wrote the manuscript.

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