High- and low-compliance balloon dilators in patients with achalasia: a randomized prospective comparative trial

0016-5107/96/4404-039855.00 + 0 GASTROINTESTINAL ENDOSCOPY Copyright © 1996 by the American Society for Gastrointestinal Endoscopy

High- and low-compliance balloon dilators in patients with achalasia: a randomized prospective comparative trial Steffen M. Muehldorfer, MD, Eckhart G. Hahn, MD, Christian Ell, MD Erlangen, Germany

Background: Pneumatic dilation is the most effective nonsurgical method for treatment of achalasia. The most serious complication of this procedure is esophageal perforation, which occurs in about 5% of cases. We completed a randomized prospective comparative trial with a high-compliance latex balloon (HCB) mounted on an endoscope (40 mm maximum distension diameter, 6 psi inflation pressure) and a low-compliance balloon (LCB) (35 mm, 20 psi) with respect to efficacy and side effects. Methods: Twenty-five patients (13 treated with HCB, 12 treated with LCB) were included. The symptom score was assessed both before and after dilation, biannually, for up to 2 years, and complications were graded for severity. All dilations lasted for 3 minutes and were performed under direct endoscopic control. Patients were randomly assigned to the two different balloon types. Results: One perforation was observed in the LCB group (not significant between HCB and LCB). Superficial mucosal tears appeared in 40% of all dilations. Initial dilation treatment was successful in 20 of 25 (80%) patients (10 of 13 HCB, 10 of 12 LCB). There were no significant differences in the median pretreatment and post-treatment symptom scores. Three patients required repeated dilations during the observation period. They were treated with the competing balloon system and showed no difference compared with the initial posttreatment symptom score. Conclusions: No significant difference could be demonstrated between the HCB and LCB system as far as the complication rate and the clinical outcome are concerned. In consequence, both systems appear equally effective, although the endoscope-mounted system (HCB) can be handled more easily. (Gastrointest Endosc 1996;44:398-403.) At present, the underlying defect of achalasia cannot be reversed. Therefore, treatment aims to relieve functional obstruction at the gastroesophageal juncReceived December 18, 1995. For revision January 29, 1996. Accepted March 6, 1996. From the Department of Medicine, University of Erlangen-Nuremberg, Erlangen, Germany. Presented in part at the annual meeting of the American Society for Gastrointestinal Endoscopy, May 1995, San Diego, California (Gastrointest Endosc 1995;41:309). Reprint requests: Steffen M. Muehldorfer, MD, Medicine, University of Erlangen, Krankenhausstr. 12, 91054, Erlangen, Germany. 0016-5107/96/4000-000055.00 + 0 GASTROINTESTINAL ENDOSCOPY 37/1/73399 398

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tion. 1 The treatment options for achalasia include medications that relax smooth muscles, pneumatic dilation, and surgical myotomy. 2 Pneumatic balloon dilation is commonly considered the most effective nonsurgical treatment to relieve dysphagia. 2"4Pneumatic dilation has a relatively high success rate (mean 80%), is less expensive than surgery, 5 may be done on an outpatient basis,6 and has a low probability of postdilation gastroesophageal reflux. The most serious complication of this procedure is esophageal perforation, with a reported mean incidence of 5%. 2, 7 Other complications include bleeding, pleural effusions, and aspiration, s Despite widespread use, the current practice of pneumatic dilation has not been standardized. Many VOLUME 44, NO. 4, 1996

Figure 1. A, High-compliance latex balloon (HCB) mounted on an endoscope (Pentax FG-29X, 40 mm max distension diameter, 6 psi inflation pressure). B, Low-compliance balloon (LCB) (Microvasive Rigiflex ABD, 35 mm distension diameter, 20 psi inflation pressure). different types of dilators are being used. Generally t h e y can be classified as high-compliance (HCB) a n d low-compliance balloon (LCB) systems. LCBs are said to be safer a n d equally effective as HCBs, a l t h o u g h up to now no r a n d o m i z e d c o m p a r a t i v e trials proving this a s s u m p t i o n h a v e been published. 7, 9, 10 The following reports a r a n d o m i z e d prospective c o m p a r i s o n of LCB a n d H C B in p a t i e n t s with s y m p t o m a t i c achalasia.

MATERIALS AND METHODS Twenty-five symptomatic patients (15 women, 10 men; median age 56 years, range 28 to 85) with a definite diagnosis of achalasia were enrolled in the study. Fourteen patients had been treated by balloon dilation in the past and reported a recurrence of their symptoms. The diagnosis of achalasia was made on the basis of esophageal manometry by aperistalsis of the esophageal body and incomplete or absent lower esophageal sphincter (LES) relaxation. 11 We used a radially oriented 6-lumen catheter (Mui, Mississauga, Canada) with a low-compliance hydraulic perfusion system (Mui) and a polygraph (Synectics, Irvine, Texas). Upper endoscopy was performed in all patients to exclude secondary causes of achalasia. A symptom score was established both before and after dilation, biannually, for up to 2 years. The symptom score for dysphagia, regurgitation, chest pain, and heartburn was calculated by multiplying the frequency of a symptom (0 = never, 1 = less than once a month, 2 = approximately once a month, 3 = approximately once a week, 4 = several times a week, 5 = daily) by the severity (1 = mild, 2 = moderate, 3 = severe, 4 = very severe) as proposed by Kim et al.12 The highest obtainable score for each symptom was 20. An excellent or good response to balloon dilationwas considered to be achieved when the symptom score decreased by 75% or more, or 50% or more, respectively. All pneumatic dilations were performed with either an HCB mounted on an endoscope (Pentax FG-29X, 40 mm maximum distension diameter, 6 psi inflation pressure) VOLUME 44, NO. 4, 1996

Figure 2. Radiogram of an inflated HCB (6 psi balloon pressure) showing a narrowed waist in the region of the lower esophageal sphincter.

(Pentax Precision Instrument Corp., Orangeburg, N.Y.), or with an LCB (Microvasive Rigiflex ABD, 35 mm, 20 psi)(Microvasive, Milford, Mass.) (Fig. 1). Patients were randomly assigned to the two different balloon types. A standard technique of pneumatic dilation was employed. We preferred to give a premedication with intravenous meperidine, diazepam, or midazolam to alleviate pain and to achieve amnesia. Every patient underwent a total of two dilation sessions performed on day one and day three. Balloon inflation pressure was 6 psi in the case of HCB, leaving a narrowed waist on the balloon at the diaphragmatic hiatus (Fig. 2). In LCB, inflation pressure was 20 psi with obliteration of the balloon waist. Balloon inflation was maintained for 3 minutes. I n case of dilation with the HCB, the balloon mounted on the endoscope was introduced and the correct dilation position then confirmed under direct endoscopic control from below by inversion of the endoscope. The LCB was passed over a guide wire, which had been previously introduced into the stomach through an endoscope. To avoid fluoroscopy we controlled the correct balloon position by inserting the endoscope again above the upper end of the balloon. After every dilation we checked for possible local lesions of the esophageal wall. Observed lesions were graded for severity (0 = none, 1 = superficial mucosal tears, 2 = mucosal G A S T R O I N T E S T I N A L E N D O S C O P Y 399

Table 1. Patient-specific data and clinical characteristics No. of patients Sex distribution Median age (y) Dysphagia--total Dysphagia--symptom score ->10 Regurgitation--total Regurgitation--symptom score ->10 Chest pain--total Chest pain--symptom score ->10 Heartburn--total Heartburn--symptom score ->10

HCB

LCB

13 8 F, 5 M 56 (range; 28-85) 13/13 (100%) 13/13 (100%) 12/13 (92%) 7/13 (54%) 9/13 (69%) 1/13 (8%) 5/13 (39%) 0/13 (0%)

12 7 F, 5 M 55 (range; 28-66) 12/12 (100%) 12/12 (100%) 12/12 (100%) 6/12 (50%) 8/12 (67%) 1/12 (8%) 5/12 (42%) 0/13 (0%)

HCB, High-compliance balloon; LCB, low-compliance balloon.

Table 2. Excellent or good success (decrease of symptom score ->50%) for at least 6 months Dysphagia Regurgitation Chest pain Heartburn

HCB (n = 13)

LCB (n = 12)

10 (77%) 10 (77%) 5 (39%) 1 (8%)

10 (83%) 11 (92%) 4 (33%) 2 (17%)

HCB, High-compliance balloon; LCB, low-compliance balloon.

and submucosal tears, 3 = perforation). The grading was done by endoscopy and fluoroscopy as follows: Perforation. Fluoroscopically proven complete dissection of the esophageal wall with paravasation of water-soluble contrast media. Submucosal tear. Endoscopically confirmed tear of at least 1 cm length and 2 mm depth without complete dissection of the wall. Mucosal tear. Any other endoscopically confirmed superficial lesion. The inclusion criteria were as follows: definite diagnosis of achalasia, symptom score greater than 10, and written informed consent. Patients were excluded from the study if any of the following factors prevailed: a bleeding disorder or use of an anticoagulant agent, previous surgery involving the gastroesophageal junction, secondary achalasia, or large epiphrenic diverticula or hiatal hernia. Based on an expected efficacy of 85% in the HCB group and 90% in the LCB group and using a two-tailed test to achieve a statistical power of 80% and a 5% a error, we estimated that at least 900 patients in each group were needed. It is unlikely, therefore, that a clinical trial of a reasonable size can reach such a statistical power. We arbitrarily set a target of 25 patients and accepted a chance of type II error. The obtained data were analyzed by using the Wilcoxon rank-sum test. The study protocol was approved by the Erlangen University ethics board.

RESULTS The patient-specific data and clinical characteristics of all patients are shown in Table 1. In one patient 400 GASTROINTESTINAL ENDOSCOPY

the LES could not be entered by the manometric catheter. In the remaining 24 patients the median LES pressure before dilation was 34.5 m m Hg (range, 14 to 88). The median contraction amplitude in the tubular esophagus after wet swallows was 20 m m Hg (range, 5 to 65). We did not completely assess objective criteria such as manometry, barium swallow, or scintigraphy because they do not correlate very well with the subjective complaints of the patient. 12 However, we have included the data collected on m anom et ry and scintigraphy to demonstrate the effectiveness of the dilation procedure. The m ean resting LES pressure in 21 patients (mean basal pressure 35 m m Hg, range from 14 to 88) decreased significantly (p < 0.01) after dilation (mean basal pressure 16 m m Hg, range from 9 to 32). There were no significant differences in the mean p r e t r e a t m e n t and post-treatment pressure values between the balloon systems. In nine patients, esophageal scintigraphy was performed with liquid and solid swallows. From the dynamic study, condensed images were obtained and the m e a n transit time for liquid and solid boluses was calculated. Esophageal emptying of liquids and solid boluses improved significantly (p < 0.05) after pneumatic dilation with both systems by 64% and 46%, respectively. The results of balloon dilation are summarized in Table 2. In the HCB group only superficial mucosal tears were observed. In the LCB group one submucosal t ear and one perforation was detected (Fig. 3). Both patients were completely asymptomatic. The complications were detected endoscopically after the dilation procedure. Both complications could be managed conservatively and reached no statistical significance. Superficial mucosal tears appeared in 40% of all dilations (NS between HCB and LCB) (Fig. 4). There were no significant differences in the median p r e t r e a t m e n t and posttreatment symptom scores between the balloon systems. Pneumatic dilation provided significant relief of dysphagia in 20 of 25 (80%) symptomatic patients and VOLUME 44, NO. 4, 1996

A

HCB 35%

0%

65%

B

LCB

4~o/^ r%

4%

Figure 3. Postprocedural esophagram showing perforation of the distal esophagus. a significant decline in the symptom score 6 months (p < 0.001), 12 months (p < 0.01), and 18 months (p < 0.05) after dilation. Regurgitation also improved significantly after 6 (p < 0.01), 12 (p < 0.05), and 18 months (p < 0.05). On the other hand, chest pain and heartburn remained unchanged after treatment (Figs. 5 and 6). Three patients required repeated dilations during the observation period. They were treated with the alternative balloon system and showed no significant difference compared with the initial post-treatment symptom score. Two of these patients successfully underwent Heller myotomy and achieved resolution of their symptoms.

DISCUSSION Pneumatic balloon dilation is commonly considered to be the most effective nonsurgical treatment to relieve dysphagia in patients with achalasia. 2-4 However, the technique of pneumatic dilation has not yet been standardized. Only one prospective randomized trial comparing LCB and HCB has been reported to date. 9 In this study, 20 patients were treated and followed-up for 6 months. During the course of this study 13 additional patients could not be randomized. In most cases this was caused by difficulties in placing VOLUME 44, NO. 4, 1996

Figure 4. A, Grading of esophageal lesions after dilation with HCB: 0 = none; 1 = superficial mucosal tears; 2 = mucosal and submucosal tears; 3 = perforation. B, Grading of esophageal lesions after dilation with LCB: 0 = none; 1 = superficial mucosal tears; 2 = mucosal and submucosal tears; 3 = perforation. the Brown-McHardy dilator in patients with tortuous esophagi. Therefore, a patient bias cannot be precluded in this study. The present study represents the second singlecenter comparison of an LCB and an HCB mounted on an endoscope. We were able to randomize 25 consecutive patients. All dilations were performed by skilled gastroenterologists. We maintained the inflated balloon for 3 minutes, in contrast to less than 30 seconds in some other reports, s' 13However, the exact duration for which the balloon should be kept inflated remains controversial. Even the need to perform a second inflation may also be questioned, but we preferred to do it in all our patients. 14 The advantage of the applied HCB system is its ease of use and its ability to be placed properly under endoscopic visualization, inasmuch as maintaining an accurate position of the inflated balloon is extremely important. We selected a wider diameter for the HCB G A S T R O I N T E S T I N A L E N D O S C O P Y 401

M e d i a n values of H C B vs, LCB: D y s p h a g i a 2O

LCB

l i ~,0.00, I ~ I ~'0.0, I~ I ~'0.0, ]

E o 10

~. E

HCB

6,5

5 Pre Rx

6 Mo Post

12 Mo Post

18 Mo Post

Figure 5. Median dysphagia scores (0-20) for patients treated with HCB and LCB at pretreatment evaluation and after dilation.

M e d i a n v a l u e s of H C B vs. LCB: Regurgitation

15

' ' .'°.°'

I I I p<°.°' II

I p'°.°' I I

8 lO

~5

~.)

2,5

0

0 Pre Rx

0

6 Mo Post

0111l '

12 Mo Post

N

0

18 Mo Post

Figure 6. Median regurgitation scores (0-20) for patients treated with HCB and LCB at pretreatment evaluation and after dilation.

because we observed a narrowed waist at the diaphragmatic hiatus, which in most cases was not obliterated at the maximum pressure of 6 psi for this balloon. This observation is supported by a recent study that found that the mean pressure to eliminate the waist of the balloon in patients with achalasia was 88 psi. 14 At present the most widely used LCB dilator is the Rigiflex balloon (Microvasive). The Rigiflex balloon dilator is usually placed over a guide wire under fluoroscopic control, which may be crucial in the patient with a markedly dilated esophagus. A hypothetic advantage of this balloon type is its low-compliance characteristic. This means that the balloon will inflate at maximum only to its designated diameter. Further inflation of the balloon will result in an increase in pressure within the lumen of the balloon without a resultant increase in its diameter. 14 In contrast, in high-compliance devices the balloon wall adapts its form more closely to the surrounding esophagus. Rabinovici et al. 7 argue that the law of Laplace can be applied to this esophagus balloon model. According to this law, the relation between pressure (P) and wall tension (T) in an elastic cylinder with a radius R and a wall thickness ~ is given by T = (P × R) / 8. According to this equation the esophageal wall tension, which is the critical determinant for 402

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Figure 7. The HCB adapts its form to the surrounding esophagus. According to the law of Laplace: T = (P x R) / ~. Since R2 > R1, it is concluded that T2 > ml. (R, radius; T, wall tension.) The LCB attaches to the esophageal wall only in the stenotic area and increases wall tension in this zone only (adapted from reference 7).

its rupture, will be significantly higher in the proximally widened esophagus as compared to the strictured area when using high-compliance balloons (Fig. 7). This proposition is confirmed by two case reports that showed longitudinal tears of the esophageal wall proximal to the stricture after dilation. 7 LCBs do not adapt to the form of the esophageal wall but rather apply direct radial forces to the strictured area only. Therefore, the risk of a more proximal perforation should be reduced. 7 Evidence supporting the safety of the LCB is provided in reported series in which no complications were observed. 9,13 However, in our randomized comparative trial only one patient (2%) in the LCB group exhibited esophageal perforation. No significant differences concerning the clinical outcome were noted between the HCB and the LCB system. Our data show that both balloon systems significantly alleviate dysphagia after pneumatic dilation in 80% of the symptomatic patients. This compares well with the success rates reported by other authors. Previous studies using HCBs that are now outdated or infrequently used showed excellent to good response rates ranging from 58% to 100%. 9,15-19 However, when using the LCB, the overall success rate ranged from 70% to 100% 4, 6, 9,13,14,20, 21 The only prospective randomized trial comparing LCB and HCB found a 70% success rate for the LCB and a 100% success rate for the HCB. 9 Additionally, we were able to confirm the data ofKim et al., 12 who showed that pneumatic dilation did not significantly improve other achalasia-related symptoms such as heartburn and chest pain. 12 VOLUME 44, NO. 4, 1996

T h e m o s t i m p o r t a n t f i n d i n g o f o u r s t u d y is t h a t t h e hypothesis stating that LCBs are safer than HCBs could not be confirmed because complications, such as deep submucosal tears and perforation, only occurred in the LCB group. Because of the small number of patients enrolled we cannot with certainty completely exclude an advantage of one of the two balloon s y s t e m s . H o w e v e r , no c l e a r t r e n d i n f a v o r o f o n e o f t h e systems could be observed. This result suggests that the biologic or anatomic characteristics of the patient are probably more important than the physical characteristics of the pneumatic dilator in determining the outcome and complications involved in the treatment of achalasia. I n s u m m a r y , o u r r e s u l t s i n d i c a t e t h a t t h e r e is n o significant difference between the HCB and LCB system concerning the complication rate and the clinical outcome. However, we believe that the endoscopem o u n t e d b a l l o o n d i l a t o r is t h e m o r e c o n v e n i e n t s y s tem, with an ideal endoscopic retrograde control of the balloon position. The disadvantage of our dilation-end o s c o p e is t h e l i m i t a t i o n o f i t s u s e s o l e l y to t h i s p r o c e d u r e . A c o m p a r a b l e , l e s s e x p e n s i v e s y s t e m is a v a i l a b l e t h a t c o n s i s t s of a n e x c h a n g e a b l e L C B ( W i t z e l B a l l o o n , Wimed, Berlin, Germany) fitting over a standard gast r o s c o p e . 22 REFERENCES 1. Wienbeck M, Barnert J. Therapie der Achalasie. Dtsch Med Wochenschr 1989;114:1971-3. 2. Katz P. Achalasia: two effective treatment options--let the patient decide. Am J Gastroenterol 1994;89:969-70. 3. Richter JE. Surgery or pneumatic dilatation for achalasia: a head-te-head comparison. Now are all the questions answered? Gastroenterology 1989;97:1340-1. 4. Abid S, Champion G, Richter JE, McEIvein R, Slaughter RL, Koehler RE. Treatment of achalasia: the best of both worlds. Am J Gastroenterol 1994;89:979-85. 5. Parkman HP, Reynolds JC, Ouyang A, Rosate EF, Eisenberg JM, Cohen S. Pneumatic dilatation or esophagomyotomy treatment for idiopathic achalasia: clinical outcomes and cost analysis. Dig Dis Sci 1993;38:75-85.

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