Predictors of Outcome of Pneumatic Dilation in Achalasia

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2004;2:389 394 Predictors of Outcome of Pneumatic Dilation in Achalasia KAVEH FARHOOMAND, JASON T. CONNOR, JOEL E. RICHTER, EDGAR ACHKAR, and MICHAEL F. VAEZI Department of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, Cleveland, Ohio Background & Aims: Graded pneumatic dilation (PD) is a widely accepted treatment for achalasia. We investigated the potential predictors of outcome in a large group of patients with achalasia and tested the hypothesis that graded PD may not be appropriate for all patients. Methods: Patients undergoing PD from 1992 to 2002 were evaluated retrospectively. Symptom scores (0 15) for dysphagia (0 5), regurgitation (0 5), and chest pain (0 5), as well as degree of esophageal emptying by timed barium swallow, were assessed for all patients. Failure was defined as the return of symptoms resulting in repeated PD or surgical myotomy. Clinical data assessed for short- and long-term predictors of response. Results: Seventy-five patients with achalasia without previous therapy constituted the studied population. Three-year success rates for PD using 3.0-cm, 3.0-cm followed by 3.5-cm, and 3.0-cm and 3.5-cm followed by 4.0-cm Rigiflex balloons were 37% (95% confidence interval [CI], 26 53), 76% (95% CI, 65 88), and 88% (95% CI, 80 97), respectively. Patient age and sex were important treatment outcome predictors. A Cox proportional hazards model of time to additional therapy on sex and 10-year increase in age showed that 3.0-cm PD was significantly (P 0.04) more likely to fail in younger men than older men (hazard ratio, 0.63; 95% CI, 0.41 0.98). In 25 of 68 patients (37%) initially treated with a 3.0-cm balloon, PD failed within 3 months. Twentytwo of 25 patients (88%) with early failure were men. Conclusions: (1) Young men have a greater failure rate with 3.0-cm PD than older men or women in general, and (2) graded PD in this group starting initially with the 3.0-cm balloon is more likely to fail. Achalasia is a rare primary esophageal motor disorder of unknown cause characterized by the absence of esophageal peristalsis and abnormal lower esophageal sphincter (LES) relaxation. 1 3 It commonly produces dysphagia, regurgitation of undigested food, and chest pain. The underlying pathological state is degeneration of the intrinsic inhibitory innervation of the esophagus, resulting in unopposed LES contraction. 4 6 Because the neuronal damage is irreversible, available treatment options are palliative and intended to reduce the pressure gradient across the LES, thus facilitating passive esophageal emptying by gravity. Currently, pneumatic dilation (PD) using Rigiflex (Microvasive, Natick, MA) balloon dilators is the most common and effective nonsurgical treatment for achalasia. 1 3 Treatment success varies from 50% to 93%. 1 This wide response range may be a function of inconsistent reported follow-up in treated patients. Only a few studies have addressed pretherapy predictors of success with PD. 7 9 Fellows et al. 7 studied 63 patients with achalasia treated with the old Rider Moeller bag and found that the need for repeated dilation was greater in patients 45 years than in older patients. In a later study using a larger sample size of 132 patients, the same group showed that patients 60 years experienced longer lasting improvement than younger patients. 8 Eckardt et al. 9 confirmed these findings and showed that young age and lower posttherapy LES pressure were predictors of good treatment outcome in patients treated with the Browne-McHardy dilator, which is no longer in use. Treatment with the Rigiflex dilator produces a 70% response with the 3.0-cm balloon and 93% success with the 3.5-cm balloon. 10 Despite the difference in treatment outcome between the 2 balloon sizes, the current guidelines recommend a graded approach in treating patients with achalasia; using a 3.0-cm balloon followed by a 3.5-cm and, subsequently, a 4.0-cm balloon in nonresponders. 3 Therefore, based on these studies, we hypothesized that graded PD for achalasia may not be well suited for all patients. Hence, the aim of this study is to determine factors that might predict outcome after PD using the Rigiflex balloon dilator and investigate the effectiveness of serial PDs in previously untreated patients with achalasia. Patients and Methods Patient Population All patients with achalasia evaluated at the Cleveland Clinic Foundation Center for Swallowing and Esophageal Dis- Abbreviations used in this paper: CI, confidence interval; LES, lower esophageal sphincter; PD, pneumatic dilation. 2004 by the American Gastroenterological Association 1542-3565/04/$30.00 PII: 10.1053/S1542-3565(04)00123-5

390 FARHOOMAND ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 5 orders (Cleveland, OH) who had undergone PD from 1992 to 2002 and those with adequate follow-up were potential participants in this retrospective study (N 116). Diagnostic criteria for achalasia were incomplete LES relaxation and esophageal aperistalsis on manometry and/or the presence of esophageal dilation, dysmotility, and narrowed LES on a timed barium esophagram. Patients previously treated by PD or surgical myotomy and those with inadequate follow-up were excluded. Therefore, the study population consisted of patients undergoing Rigiflex balloon dilation for the first time. Subjective Assessment All patients were interviewed before and after each Rigiflex dilation. The total symptom score, consisting of the sum of scores for dysphagia, regurgitation, and chest pain, was recorded. The frequency of each symptom was graded on a scale ranging from 0 to 5 (0 none, 1 1 time/mon, 2 1 time/wk, 3 2 4 times/wk, 4 1 time/d, and 5 several times per day). 11 Therefore, the maximum total score per patient was 15 points. Symptom improvement was assessed by comparing pre-pd and post-pd symptom scores. Symptom recurrence is defined as a total symptom score 3. Treatment failure is defined based on patients reports of return of their symptoms and/or the need for therapeutic intervention. Esophageal Manometry Esophageal manometry was performed before therapy in all patients by using a low-compliance pneumohydraulic water-infusion system (Arndorfer Medical Specialties, Milwaukee, WI) and an 8-lumen manometric catheter (Arndorfer Medical Specialties). The catheter had 4 proximal recording ports spaced at 5-cm intervals along its length and 4 more ports radially oriented at 90 near the tip. Recording sites were connected to an 8-channel polygraph (Synectics Medical AB, Stockholm, Sweden). All swallows were monitored by using an external microphone. LES pressure was measured by the station pull-through technique and recorded as the mean of 4 measurements at midrespiration. Completeness of LES relaxation (normal, 85%) was assessed as percentage of decrease from mean resting LES pressure to gastric baseline after wet swallows. Esophageal peristalsis was recorded 3, 8, 13, and 18 cm above the LES in response to 5-mL swallows of water at 30-second intervals. Manometry was not performed after therapy. PD All PDs were performed using the Rigiflex balloon dilator with fluoroscopic control. The first PD usually was performed with the 3.0-cm balloon, with progressive increases to 3.5-cm and 4.0-cm balloons if symptoms were not relieved. Patients fasted for at least 8 hours before the procedure. All patients were sedated with intravenous midazolam, meperidine, and topical anesthesia of the pharynx. After uppergastrointestinal endoscopy, the Rigiflex dilator was passed over a guidewire, and the balloon was positioned across the diaphragmatic hiatus using the radiopaque markers as guides or endoscopically. Correct location was verified fluoroscopically by observing the waist after minimal balloon inflation pressures of 3 5 psi. The balloon then was inflated for 30 60 seconds at 9 15 psi until obliteration of the waist. A Gastrografin swallow followed by a barium swallow was performed immediately after dilation to identify esophageal perforation. Barium Esophagram A timed barium esophagram 12 14 was performed before and 1 month after each dilation as an objective assessment of improvement in esophageal emptying in patients undergoing PDs after 1996. During the 6-year follow-up period, a repeated timed barium esophagram was performed in all patients with recurrence of symptoms. We have shown that a timed barium esophagram can be a useful as an objective means of assessing esophageal emptying after PD. 13 All patients fasted overnight before the barium esophagram. While standing, patients ingested a low-density barium sulfate suspension (45% weight in volume; E-Z PAQUE; E-Z- EM, Westbury, NY) over 30 45 seconds. They were instructed to drink the amount of barium they could tolerate (usually between 100 and 250 ml). With the patient upright in a slightly left posterior oblique position, radiographs (35 35 cm) of the esophagus were taken 1, 2, and 5 minutes after the last swallow of barium. The distance in centimeters from the distal esophagus (identified by the bird s beak appearance of the esophagogastric junction) to the top of a distinct barium column (barium height), as well as the maximal esophageal width, were measured. We used barium height at 5 minutes to determine completeness of emptying. This was based on our observations that most healthy individuals have barium emptied out of their esophagus by 1 minute, and in all individuals, by 5 minutes. 12 14 Statistical Methods Summary statistics for continuous variables are reported as mean SD, and categorical variables are reported as count and percent. Cox proportional hazards models were used to model the time until need for additional treatment. The proportional hazards assumption was checked for each model using the method described by Grambsch and Therneau. 15 Logistic regression was used to model the need for additional treatment, regardless of time of subsequent retreatment. Spearman correlation ( s ) coefficients were used to compare symptom scores with barium swallow measures. t tests were used to compare symptoms scores between groups. Statistical significance is defined as P 0.05. Results Study Population Between January 1992 and March 2002, a total of 116 patients underwent PD at the Cleveland Clinic Foun-

May 2004 ACHALASIA, PD, AND RESPONSE PREDICTORS 391 Table 1. Patient Characteristics at Study Entry Variable Follow-up (mo) 75 32.2 30.0 (1 121) Age (yr) 75 45.8 15.1 (17 78) Sex (men) 49 65% Prior medication 47 63% Prior bougie 50 33% LES pressure (mm Hg) 62 38.4 18.8 (11 101) Esophageal body amplitude 39 46.7 36.9 (5 188) Heartburn 38 51% Weight loss (lb) 42 23.9 16.6 (5 95) Dysphagia score 75 4.5 1.2 (0 5) Regurgitation score 75 3.2 1.9 (0 5) Chest pain score 75 1.5 1.9 (0 5) Total symptom score 75 9.1 3.2 (0 15) Ba 1 -Pre ht (cm) b 59 22.1 8.2 (0 39) Ba 1 -Pre wt (cm) c 56 5.5 2.5 (2.5 20) Ba 5 -Pre ht (cm) b 63 17.5 9.1 (0 38) Ba 5 -Pre wt (cm) c 60 4.8 2.3 (0 16) NOTE. Values expressed as mean SD (range) unless noted. LES, lower esophageal sphincter. a Number of patients with available parameters. b Barium height at 1 and 5 minutes, respectively, after ingestion before therapy. c Barium width at 1 and 5 minutes, respectively, after ingestion before therapy. dation and were potential candidates for this study. To avoid confounding factors, those with previous therapies were excluded: Heller s myotomy, 11 patients; previous PD, 15 patients. Fifteen patients lacked follow-up after repeated attempts to contact them, leaving 75 patients with achalasia in the study sample. Mean age (43.2 6.0 yr) and sex (9 men) in the 15 patients without follow-up were not different (P 0.9) from those for the 75 patients in the study. Twenty-two of the 75 patients had been treated previously with bougie dilation. Patient Demographics Table 1 lists demographic and baseline information for the cohort studied. The patient population included 26 women (35%) and 49 men (65%; mean age, 45.8 15.6 yr; mean follow-up, 32.2 30 mon; range, 1 121 mon). Seventy-five patients had undergone a total of 118 PDs (Figure 1): 3-cm balloon (n 68), 3.5-cm balloon (n 42), and 4.0-cm balloon (n 8), whereas in 7 patients, the 3.5-cm balloon was the initial balloon size. There were no perforations. Sixty patients required no additional therapy after serial dilations, whereas 15 patients subsequently required Heller s myotomy. Pretherapy mean dysphagia, regurgitation, and chest pain scores were 4.5 1.2, 3.2 1.9, and 1.5 1.9, for a mean total symptom score of 9.1 3.2. Forty-two patients (56%) reported weight loss. Average weight loss in this group was 23.9 16.6 lbs (range, 5 95 lbs). Mean 5-minute barium height before therapy was 17.5 9.1 cm. N a Dysphagia ( s 0.42; 95% confidence interval [CI ], 0.27 0.54; P 0.0001), regurgitation ( s 0.44; 95% CI, 0.30 0.56; P 0.0001), chest pain ( s 0.31; 95% CI, 0.15 0.44; P 0.0001), and total symptoms scores ( s 0.50; 95% CI, 0.37 0.61; P 0.0001) showed significant correlation to 5-minute barium height. Treatment Outcome A Kaplan Meier graph detailing the need for subsequent therapy as a function of balloon size is shown in Figure 2. Serial dilations offer clear improvement over treatment with the 3.0-cm balloon alone. Thirty-nine of 68 subjects (57.4%) undergoing 3.0-cm dilation required treatment later. The 3-year success rate for patients after 3.0-cm balloon dilation was only 37% (95% CI, 26 53). Three-year success rates for patients undergoing 3.0- plus 3.5-cm and 3.0- plus 3.5- plus 4.0-cm balloon dilations (Figure 2) were 76% (95% CI, 65 88) and 88% (95% CI, 80 97); respectively. There was a high early failure rate (37%; 95% CI, 28 54) within the first 3 months of therapy in those receiving 3.0-cm PD (sharp drop on the left side of graph; Figure 2). Of 25 patients who experienced early failure, 22 patients were men and 3 were women; mean Figure 1. Flow chart for patients and therapy. Seventy-five patients underwent Rigiflex balloon dilation; 68 patients began with a 3.0-cm balloon, of whom 34 patients required the larger 3.5-cm balloon, 29 patients required no further therapy, and 5 patients were referred to surgery (Heller myotomy). Seven patients started with the 3.5-cm balloon. Thus, combined with the 34 patients in whom pneumatic dilation (PD) failed with the 3.0-cm balloon, 41 subjects underwent dilation with the 3.5-cm balloon; 24 of these patients required no additional therapy, 9 patients underwent surgery, and the remaining 8 patients underwent PD with the 4.0-cm balloon. In 1 patient, the 4.0-cm balloon failed and the patient underwent surgery, whereas the remaining 7 patients underwent no additional therapy.

392 FARHOOMAND ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 5 Figure 2. Kaplan Meier curves for time to retreatment. Patients who underwent pneumatic dilation (PD) with the 3.0-cm balloon alone did poorly compared with those who underwent subsequent dilation with the larger sized balloons. The majority of failures for the 3.0-cm balloon occurred early after therapy. age was 43.3 16.2 years. Subsequently, 23 of these patients underwent repeated PD with the larger 3.5-cm balloon and 2 patients immediately opted for surgical myotomy (Figures 1 and 2). Mean total symptom score at the time of last follow-up after 3.0-cm PD (and before subsequent treatments) for the 39 subjects requiring additional treatment was 5.3 (maximum, 15; mean follow-up, 11 mon), whereas for the 29 subjects requiring no additional treatment, the symptom score was 1.0 (maximum, 7; mean follow-up, 12 mon). Mean dysphagia (2.9 vs. 0.5; P 0.0001) and regurgitation (1.2 vs. 0.1; P 0.01) scores were considerably higher in the group requiring additional treatment. There was a smaller difference in chest pain scores (1.2 vs. 0.4; P 0.04). Figure 3 shows changes in 5-minute barium height scores pretreatment and posttreatment for patients who did and did not require additional treatment. Mean barium height was reduced from 19.7 cm before therapy to 3.0 cm (85% reduction) in the group requiring no additional treatment and from 16.8 to 11.7 cm (30.4%) in the group requiring retreatment (P 0.0004). Fifteen of 23 patients (65%) requiring no additional therapy had complete emptying of barium after therapy; however, this was true in only 4 of 31 patients (13%) requiring additional treatment (P 0.0002). Treatment Outcome Predictors Univariate Cox proportional hazards models were used to predict time from the first 3.0-cm PD to repeated PD or Heller surgery (Table 2). Age, sex, previous bougie, and baseline 5-minute barium column heights were borderline or less than significant values at the 0.05 level. Older patients, those without previous bougie, and those with greater baseline 5-minute barium column heights had a longer interval between treatments. Additionally, the hazard ratio comparing men with women was 1.6, indicating male patients required subsequent treatment after 3.0-cm dilation earlier than women. The previous-bougie group (n 25) was similar with respect to age, sex, manometric findings, symptom scores, and barium height and width to those who did not have previous bougie before PD (n 53). A variety of multivariate Cox proportional hazards models and logistic regression models were constructed to identify potential causes for high early failure in those undergoing 3.0-cm PD. This analysis was performed in 2 ways: (1) in all patients with achalasia undergoing PD with or without previous bougie dilation (n 75), and (2) in patients with achalasia undergoing PD without previous bougie dilation (n 53). Multivariate models discovered a significant age-sex relationship in both groups. Younger men tended to require subsequent treatment much sooner than older men; the hazard ratio for a 10-year increase in age for men was 0.63 (95% CI, 0.41 0.98; P 0.04). However, women had approximately the same distribution of time length before subsequent treatment regardless of age; hazard ratio for a 10-year increase in age was 0.82 (95% CI, 0.49 1.34; P 0.43). Using a logistic regression fit, Figure 4 shows the probability of additional treatment for Figure 3. Barium column height change before and after dilation in patients requiring no additional therapy and those who were retreated. In patients who required no additional treatment, barium column height was reduced significantly after therapy, whereas this was not the case in those requiring treatment. Fifteen of 23 patients (65%) requiring no additional therapy had complete emptying of barium after therapy; however, this was true in only 4 of 31 patients (13%) requiring additional treatment (P 0.0001). The diamonds to the side of data points represent mean barium column heights.

May 2004 ACHALASIA, PD, AND RESPONSE PREDICTORS 393 Table 2. Univariate Cox Proportional Hazards Models Factor Hazard ratio 95% Confidence Interval Age (10-yr increase) 0.82 0.68 1.01 0.06 Age 40 yr 0.85 0.62 1.20 0.30 Male vs. female 1.65 0.81 3.33 0.10 Prior botox 1.36 0.41 4.50 0.61 Prior medication 1.17 0.61 2.24 0.63 Prior bougie 2.18 1.09 4.34 0.02 MLES pressure (10-unit increase) 1.00 0.82 1.21 0.97 BodyAmp (10-unit increase) 1.00 0.86 1.17 0.98 Dysphagia (1-point increase) 1.04 0.67 1.63 0.86 Regurgitation (1-point increase) 0.95 0.81 1.11 0.51 Chest pain (1-point increase) 0.98 0.84 1.16 0.85 Total (1-point increase) 0.97 0.87 1.08 0.60 Heartburn 0.95 0.50 1.80 0.88 Weight loss 1.48 0.76 2.86 0.25 1-Min barium height (5 cm) 0.91 0.74 1.12 0.36 1-Min barium width (1 cm) 1.07 0.96 1.18 0.23 5-Min barium height (5 cm) 0.80 0.66 0.97 0.02 5-Min barium width (1 cm) 1.08 0.95 1.22 0.26 P a older subjects, and (2) patients in whom posttherapy LES pressure was 10 mm Hg remained in remission for longer periods than those with higher values. Similarly, in 157 consecutive patients treated with the Witzel balloon, Ponce et al. 16 found that age 20 years, esophageal body diameter 3 cm, esophageal body basal pressure 15 mm Hg, LES pressure 30 mm Hg, and male sex were predictors of poor outcome. Using the more effective 1 Rigiflex dilator most commonly used in the United States, our data confirm these findings regarding age and extend these observation to suggest a combined age and sex effect. The reason for the poor outcome in younger men currently is unknown. One NOTE. P values in bold indicate significant or trend. MLES, mean LES pressure; BodyAmp, esophageal body amplitude. a P tests hypothesis that hazard ratio 0. men and women as a function of age in all patients with achalasia. Young men required repeated treatment more frequently after initial treatment than young women. However, this gap narrows with age until the effect between sexes is similar for patients 70 years. Excluding patients with previous bougie (n 25) further differentiated the effect between the sexes by age, showing a crossover after the age of 50 years. Discussion We found that serial PD is effective in previously untreated patients with achalasia, resulting in a 3-year success rate of 88%. However, this high rate of success was achieved predominantly because of the larger balloon sizes (3.5 and 4.0 cm). PD failed in 42% of patients within 3 months of therapy with 3.0-cm balloon dilation, requiring repeated dilation with the 3.5-cm balloons. Eighty-eight percent of these patients (22 of 25 patients) were men 45 years. Therefore, multivariate analysis of our data showed a significant age-sex relationship, suggesting that young men do not do well with 3.0-cm balloon compared with their older counterparts or women of the same age group (Figure 4). Our results are agree with and extend the findings of previous studies in identifying predictors of treatment outcome after PD. 9,16 In 54 patients newly diagnosed with achalasia, Eckardt et al. 9 performed PD using the old Browne McHardy dilator and found that: (1) patients 40 years had a significantly worse response to dilation than Figure 4. Probability of additional treatment after 3.0-cm balloon dilation by age and sex for (A) all patients with achalasia (n 75) and (B) those without previous bougie dilation (n 53). The solid bold line represents the probability of repeated dilation for men compared with the same probability for women of the same age. Initial dilation with the 3.0-cm balloon was more likely to fail in younger men, and they required repeated treatment for both analyses. The 2 probabilities approach each other for middle-aged patients in the analysis of patients without previous bougie and near the age of 70 years in the analysis involving all patients. M, male; F, female.

394 FARHOOMAND ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 5 possible explanation may be that the musculature in the LES region for this group of patients may be less susceptible to damage by forceful dilation; however, more focused studies to understand this phenomenon are needed. The 3-year success rate of 76% to 88% in our patients treated with serial PD (Figure 2) is in accord with previous publications showing efficacy ranging from 50% to 93%. 1 For example, in 72 patients with achalasia followed up for a mean of 6.5 years, PD was successful in 85%. 17 A cumulative analysis of multiple studies including 359 patients suggested that dilation with the 3.0-, 3.5-, and 4-cm balloon diameters resulted in good to excellent symptomatic relief in 74%, 86%, and 90%, respectively. 1 These data and the concern that larger balloon diameters may increase the risk for perforation are responsible for the currently recommended guideline of treating achalasia by the graded dilation approach. 3 However, our results suggest that PD is more likely to fail in young men with this graded approach, and they are less likely to need repeated dilation if they are treated initially with the 3.5-cm balloon. The efficacy of such an approach requires testing in a prospective trial. A potential shortcoming of this study results from its retrospective design. However, our data are strengthened because the majority of our patients had long-term follow-up of both subjective (symptoms) and objective (timed barium swallow) parameters. Additionally, our univariate analysis showed that patients with achalasia with previous bougie dilation tended to have a worse outcome post-pd than those without previous bougie. At this time, the reason for this difference is not clear. The 2 groups were similar with respect to demographics and subjective and objective data parameters. Importantly, the age and sex factors discovered in our experiment were independent of this observation (Figure 4). Additionally, we found that the symptomatic response was dependent on improvement of esophageal emptying on timed barium esophagram after dilation (Figure 3). This is in agreement with our previous reports showing a strong correlation between symptomatic improvement and barium emptying in nearly 70% of patients with achalasia. 13 Additionally, we previously reported better long-term outcome in patients for whom there was concordance between symptomatic improvement and barium emptying after PD than those who have discordance between subjective and objective parameters. 14 In conclusion, the practice of serial PD for all patients with achalasia may need to be modified for young men. In this group, initial therapy with the 3.5-cm balloon would reduce the likelihood of repeated dilation. Serial PDs may be performed in women of any age and men 45 years. Future prospective studies assessing the reason for the sex and age differences in outcome are warranted. References 1. Vaezi MF, Richter JE. Current therapies for achalasia: comparison and efficacy. J Clin Gastroenterol 1998;27:21 35. 2. Birgisson S, Richter JE. Achalasia: what s new in diagnosis and treatment? Dig Dis 1997;15:1 27. 3. Vaezi MF, Richter JE. Diagnosis and management of achalasia. Am J Gastroenterol 1999;94:3406 3412. 4. Aggestrup S, Uddman R, Sundler F, Fahrenkrug J, Hankanson R, Sorensen HR, Hambragus G. Lack of vasoactive intestinal nerves in esophageal achalasia. Gastroenterology 1983;84:924 927. 5. Holloway RH, Dodds WJ, Helm JF, Hogan WJ, Dent J, Arndorger RC. Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia. Gastroenterology 1986;90:924 929. 6. Mearin F, Mourelle M, Guarner F, Salas A, Riveros-Moreno V, Moncada S, Malagelada JR. Patients with achalasia lack nitric oxide synthase in the gastroesophageal junction. Eur J Clin Invest 1993;23:724 728. 7. Fellows IW, Ogilvie AL, Atkinson M. Pneumatic dilation in achalasia. Gut 1983;24:1020 1023. 8. Robertson CS, Fellows IW, Mayberry JF, Atkinson M. Choice of therapy for achalasia in relation to age. Digestion 1988;40:244 250. 9. Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia treated by pneumatic dilation. Gastroenterology 1992;103:1732 1738. 10. Gelfand MD, Kozarek RA. An experience with polyethylene balloons for pneumatic dilation in achalasia. Am J Gastroenterol 1989;84:927 927. 11. Vaezi MF, Richter JE, Wilcox CM, Schroeder PL, Birgisson S, Slaughter RL, Koehler RE, Baker ME. Botulinum toxin vs pneumatic dilation in the treatment of achalasia: a randomized trial. Gut 1999;44:231 239. 12. De Oliveira JMA, Birgisson S, Doinoff C, Einstien D, Herts B, Davros W, Obuchowski N, Koehler RE, Richter JE, Baker ME. Timed-barium swallow: a simple technique for evaluating esophageal emptying in patients with achalasia. AJR Am J Roentgenol 1997;169:473 479. 13. Vaezi MF, Baker ME, Richter JE. Assessment of esophageal emptying post-pneumatic dilation: use of the timed barium esophagram. Am J Gastroenterol 1999;94:1802 1807. 14. Vaezi MF, Baker ME, Achkar E, Richter JE. Timed barium oesophagram: better predictor of long term success after pneumatic dilation in achalasia than symptom assessment. Gut 2002;50:765 770. 15. Grambsch P, Therneau T. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994;81:515 526. 16. Ponce J, Garrigues V, Pertejo V, Sala T, Berenguer J. Individual prediction of response to pneumatic dilation in patients with achalasia. Dig Dis Sci 1996;41:2135 2141. 17. Katz PO, Gilbert J, Castell DO. Pneumatic dilation is effective long-term treatment for achalasia. Dig Dis Sci 1998;38:75 85. Address requests for reprints to: Michael F. Vaezi, M.D., Ph.D., Department of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. e-mail: vaezim@ccf.org; fax: (216) 444-6302.