JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Volume 25, Number 6, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/lap.2014.0682
Full Report
Comparative Study Between Laparoscopic Heller Myotomy Versus Pneumatic Dilatation for Treatment of Early Achalasia: A Prospective Randomized Study Emad Hamdy, MD, Ayman El Nakeeb, MD, Ehab El Hanfy, MD, Mohamed El Hemaly, MD, Tarek Salah, MD, Hosam Hamed, MD, and Nabil Gad El Hak, MD
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.
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
Introduction
A
chalasia 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
Gastroenterology Surgical Center, Mansoura University, Mansoura, Egypt.
1
2
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 earlystage 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.
HAMDY ET AL.
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
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.
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.
Intervention
Follow-up
Laparoscopic esophageal cardiomyotomy and Dor fundoplication. The standard approach for performance of the
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.
Randomization
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
MANAGEMENT OF EARLY-STAGE ACHALASIA
3
Table 1. Comparison of Preoperative Symptoms and Manometric Features Between the Laparoscopic Esophageal Myotomy Group and the Endoscopic Pneumatic Dilatation Group
Age (years) Sex (male:female) Dysphagia Mild Moderate Severe Heartburn Regurgitation Weight loss Manometry LESP % relaxation Simultaneous waves Nontransmitted waves
LEM
EPD
P value
32 8/17
30.8 5/20
.35 .33 .71
13 8 4 7/25 8/25 7/25
15 6 4 12/25 9/25 11/25
.15 .77 .24
39.8 68% 58.2% 35.2%
37.4 65.6% 59.2% 36.5%
.6 .82 .55 .78
EPD, endoscopic pneumatic dilatation; LEM, laparoscopic esophageal myotomy; LESP, lower esophageal sphincter pressure
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 presen-
tation 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). 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). 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
Table 2. Comparison of Postoperative Outcome Between the Laparoscopic Esophageal Myotomy Group and the Endoscopic Pneumatic Dilatation Group LEM Esophageal perforation Improvement of dysphagia after 3 months 1 year Developing reflux symptoms Recurrent symptoms after 1 year Manometeric features LESP % relaxation Simultaneous waves Nontransmitted waves Cost (USD) of the procedure
1/25 (4%) 24/25 22/25 7/25 2/24
(96%) (96%) (28%) (8.3%)
11.04 – 2.62 79.72 – 4.12% 44.4 – 4.56% 38.04 – 5.33% 580
EPD 2/25 (8%) 19/25 14/25 4/25 5/19
(76%) (56%) (16%) (26.3%)
16.01 – 2.88 75.08 – 4.31% 43.04 – 5.05% 41.3 – 6.78% 228
P value .55 .04 .01 .3 .1 .0001 .0001 .3 .67 .0001
EPD, endoscopic pneumatic dilatation; LEM, laparoscopic esophageal myotomy; LESP, lower esophageal sphincter pressure; USD, U.S. dollars.
4
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 shortand 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
HAMDY ET AL.
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. 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. References
1. Vaezi MF, Pandolfi JE, Vela MF. ACG Clinical Guideline: Diagnosis and management of achalasia. Am J Gastroenterol 2013;108:1238–1249. 2. Campos GM, Vittinghoff E, Rabl C, Takata M, Gadenstatter M, Lin F, Ciovica R. Endoscopic and surgical treatments for achalasia: A systematic review and metaanalysis. Ann Surg 2009;249:45–47. 3. Patti MG, Pellegrini CA. Esophageal achalasia 2011: Pneumatic dilatation or laparoscopic myotomy? J Gastrointest Surg 2012;16:870–873.
MANAGEMENT OF EARLY-STAGE ACHALASIA
4. Stefanidis D, Richardson W, Timothy M, Farrell TM, Kohn GP, Augenstein V, Fanelli RD. SAGES guidelines for the surgical treatment of esophageal achalasia. Surg Endosc 2012;26:296–311. 5. Patti MP, Fisichella PM, Perretta S, Galvani C, Gorodner MV, Robinson T, Way LW. Impact of minimally invasive surgery on the treatment of esophageal achalasia: A decade of change. J Am Coll Surg 2003;196:698–703; discussion 703–705. 6. Vela MF, Richter JE, Khandwala F, Blackstone EH, Wachsberger D, Baker ME, Rice TW. The long-term efficacy of pneumatic dilatation and Heller myotomy for the treatment of achalasia. Clin Gastroenterol Hepatol 2006;4: 580–587. 7. Csendes A, Braghetto I, Burdiles P, Korn O, Csendes P, Henrı´quez A. Very late results of esophagomyotomy for patients with achalasia. Clinical, endoscopic, histologic, manometric, and acid reflux studies in 67 patients for a mean follow-up of 190 months. Ann Surg 2006;243:196–203. 8. Borges AA, Lemme EMO, Abrahao LJ, Madureira D, Andrade MS, Soldan M, Helman L. Pneumatic dilation versus laparoscopic Heller myotomy for the treatment of achalasia: Variables related to a good response. Dis Esophagus 2014;27:18–23. 9. Rebecchi F, Giaccone C, Farinella E, Campaci R, Morino M. Randomized controlled trial of laparoscopic Heller myotomy plus Dor fundoplication versus Nissen fundoplication for achalasia: Long-term results. Ann Surg 2008; 248:1023–1030. 10. Ferri LE, Feldman LS, Stanbridge D, Mayrand S, Fried GM. Has the introduction of laparoscopic Heller myotomy altered the treatment paradigm of achalasia? Can J Gastroenterol 2005;19:619–623. 11. Cuschieri A. Minimally invasive surgery: Hepatobiliarypancreatic and foregut. Endoscopy 2000;32:331–344. 12. Olsen AM, Holman CB, Andersen HA. The diagnosis of cardiospasm. Dis Chest 1953;23:477–498. 13. Richter JE. Achalasia: An update. J Neurogastroenterol Motil 2010;16:232–242. 14. Lake JM, Wong RK. Review article: The management of achalasia—A comparison of different treatment modalities. Aliment Pharmacol Ther 2006;24:909–918. 15. Yaghoobi M, Mayrand S, Martel M, Roshan-Afshar I, Bijarchi R, Barkun A. Laparoscopic Heller’s myotomy versus pneumatic dilation in the treatment of idiopathic achalasia: A meta-analysis of randomized, controlled trials. Gastrointest Endosc 2013;78:468–475. 16. Katzka DA, Castell DO. An analysis of the efficacy, perforation rates and methods used in pneumatic dilation for achalasia. Aliment Pharmacol Ther 2011;34:832–839.
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17. Wong RKH, Maydonovitch C. Utility of parameters measured during pneumatic dilation as predictors of successful outcome.Am J Gastroenterol 1996;91:1126–1129. 18. Reynoso JF, Tiwari MM, Tsang AW, Oleynikov D. Does illness severity matter? A comparison of laparoscopic esophagomyotomy with fundoplication and esophageal dilation for achalasia. Surg Endosc 2011;25:1466–1471. 19. Gockel I, Junginger T, Bernhard G, Eckardt VF. Heller myotomy for failed pneumatic dilation in achalasia: How effective is it. Ann Surg 2004;239:371–377. 20. Ben-Meir A, Urbach DR, Khajanchee YS, Hansen PD, Swanstrom LL. Quality of life before and after laparoscopic Heller myotomy for achalasia. Am J Surg 2001;181:471–474. 21. Spechler SJ. American Gastroenterological Association medical position statement on treatment of patients with dysphagia caused by benign disorders of the distal esophagus. Gastroenterology 1999;117:229–232. 22. Yaghoobi M, Mikaeli J, Montazeri G, Nouri N, Sohrabi MR, Malekzadeh R. Correlation between clinical severity score and the lower esophageal sphincter relaxation pressure in idiopathic achalasia. Am J Gastroenterol 2003;98:278–283. 23. Boeckxstaens G, Annese V, Des Varannes SB, Chaussade S, Costantini M, Cuttitta A, Elizalde JI, Fumagalli U, Gaudric M, Rohof WO, Smout AJ, Tack J, Zwinderman AH, Zaninotto G, Busch OR. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med 2011;364:1807–1816. 24. Gockel I, Timm S, George G. Sgourakis GG, Musholt TJ, Rink AD, Lang H. Achalasia: If surgical treatment fails: Analysis of remedial surgery. J Gastrointest Surg 2010; 14(Suppl 1):S46–S57. 25. Bravi I, Nicita MT, Duca P, Grigolon A, Cantu P, Caparello C, Penagin R. Pneumatic dilation strategy in achalasia: prospective outcome and effects on esophageal motor function in the long term. Aliment Pharmacol Ther 2010;6: 658–665. 26. Vaezi MF, Baker ME, Achkar E, Richter JE. Timed barium esophagram: Better predictor of long term success after pneumatic dilation in achalasia than symptom assessment. Gut 2002;50:765–770.
Address correspondence to: Ayman El Nakeeb, MD Gastroenterology Surgical Center Mansoura University Jehan Street Mansoura, 50 Egypt E-mail: [email protected]
Full Report
Comparative Study Between Laparoscopic Heller Myotomy Versus Pneumatic Dilatation for Treatment of Early Achalasia: A Prospective Randomized Study Emad Hamdy, MD, Ayman El Nakeeb, MD, Ehab El Hanfy, MD, Mohamed El Hemaly, MD, Tarek Salah, MD, Hosam Hamed, MD, and Nabil Gad El Hak, MD
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.
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
Introduction
A
chalasia 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
Gastroenterology Surgical Center, Mansoura University, Mansoura, Egypt.
1
2
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 earlystage 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.
HAMDY ET AL.
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
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.
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.
Intervention
Follow-up
Laparoscopic esophageal cardiomyotomy and Dor fundoplication. The standard approach for performance of the
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.
Randomization
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
MANAGEMENT OF EARLY-STAGE ACHALASIA
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Table 1. Comparison of Preoperative Symptoms and Manometric Features Between the Laparoscopic Esophageal Myotomy Group and the Endoscopic Pneumatic Dilatation Group
Age (years) Sex (male:female) Dysphagia Mild Moderate Severe Heartburn Regurgitation Weight loss Manometry LESP % relaxation Simultaneous waves Nontransmitted waves
LEM
EPD
P value
32 8/17
30.8 5/20
.35 .33 .71
13 8 4 7/25 8/25 7/25
15 6 4 12/25 9/25 11/25
.15 .77 .24
39.8 68% 58.2% 35.2%
37.4 65.6% 59.2% 36.5%
.6 .82 .55 .78
EPD, endoscopic pneumatic dilatation; LEM, laparoscopic esophageal myotomy; LESP, lower esophageal sphincter pressure
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 presen-
tation 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). 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). 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
Table 2. Comparison of Postoperative Outcome Between the Laparoscopic Esophageal Myotomy Group and the Endoscopic Pneumatic Dilatation Group LEM Esophageal perforation Improvement of dysphagia after 3 months 1 year Developing reflux symptoms Recurrent symptoms after 1 year Manometeric features LESP % relaxation Simultaneous waves Nontransmitted waves Cost (USD) of the procedure
1/25 (4%) 24/25 22/25 7/25 2/24
(96%) (96%) (28%) (8.3%)
11.04 – 2.62 79.72 – 4.12% 44.4 – 4.56% 38.04 – 5.33% 580
EPD 2/25 (8%) 19/25 14/25 4/25 5/19
(76%) (56%) (16%) (26.3%)
16.01 – 2.88 75.08 – 4.31% 43.04 – 5.05% 41.3 – 6.78% 228
P value .55 .04 .01 .3 .1 .0001 .0001 .3 .67 .0001
EPD, endoscopic pneumatic dilatation; LEM, laparoscopic esophageal myotomy; LESP, lower esophageal sphincter pressure; USD, U.S. dollars.
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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 shortand 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
HAMDY ET AL.
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. 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. References
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Address correspondence to: Ayman El Nakeeb, MD Gastroenterology Surgical Center Mansoura University Jehan Street Mansoura, 50 Egypt E-mail: [email protected]
