Health-related quality of life and physiological measurements in achalasia

Diseases of the Esophagus (2017) 30, 1 5 DOI: 10.1111/dote.12494 Original Article Health-related quality of life and physiological measurements in achalasia Daniel Ross, 1 Joel Richter, 2 Vic Velanovich 1 1 Division of General Surgery and 2 Gastroenterology, University of South Florida Morsani College of Medicine, Tampa, Florida, USA SUMMARY. The diagnosis of achalasia is generally made based on patient symptoms, the appearance of the esophagus on endoscopy and barium esophagogram, and esophageal manometry. In addition, timed barium esophagography (TBE) can give useful information on the clearance of liquid barium over a 10 minute period and the passage of a barium tablet. What is unclear is how well these physiological measurements of esophageal function correlate with patient-perceived health-related quality of life. Our aim was to assess whether objective physiological measurements of high-resolution manometry (HRM) and TBE will correlate with quantitative achalasia-related health-related quality of life (HRQoL) measurements. Patients referred for possible surgical treatment of achalasia were assessed preoperatively in the following manner. A gastroenterologist and surgeon clinically evaluated all patients. In addition to history and physical examination, patients underwent further testing with TBE, upper gastrointestinal endoscopy, and HRM. The diagnosis of achalasia was based on HRM. Prior to surgical treatment, patients completed the Measure of Achalasia Disease Severity (ADS) which is a validated instrument assessing the severity of achalasia-associated HRQoL. Hundred and twenty patients were included in this study. The mean ADS score was 24.9 ± 3.6. There was no statistically significant difference in score among the achalasia types: I, 24.0 ± 4.3; II, 25.4 ± 3.2; III, 24.3 ± 4.6. Using linear regression analysis, there was no statistically significant correlation between ADS scores and TBE column height or width at 1 and 5 minutes. There was no statistically significant difference between patients who could pass a 13 mm barium tablet (26.4 ± 3.4) and those who could not (24.9 ± 3.6). There was no statistically significant correlation between LES pressure and IRP with ADS scores. There is poor correlation between patient-perceived health-related quality of life and objective physiological measurements of achalasia. Therefore, the assessment of treatment outcomes of achalasia will need to require both an assessment of esophageal physiology as well as HRQoL. INTRODUCTION Achalasia is an esophageal motility disorder characterized by loss of coordinated esophageal peristalsis and failure of the lower esophageal sphincter (LES) to completely relax. 1 The typical constellation of clinical symptoms include dysphagia to solids and liquids, regurgitation, chest pain, heartburn, and sometimes progressive weight loss. 1,2 The diagnosis of achalasia is accomplished through evaluation of the patient s symptoms, radiologic imaging, upper gastrointestinal endoscopy, and esophageal manometry. 3 Physiologically, achalasia can be assessed radiographically or with manometry. Time barium esophagography (TBE) provides a real-time assessment of an individual s ability to clear solids and liquids through the esophagus. 4 This study not only provides Address correspondence to: Vic Velanovich, MD, Division of General Surgery, One Tampa General Circle, F145, Tampa, FL 33606, USA. Email: vvelanov@health.usf.edu a structural assessment of the esophagus, but also the time required for liquid passage and passage of a solid tablet (Fig. 1). High-resolution manometry (HRM) has become the standard for the assessment of esophageal motility. 5 HRM utilizes a catheter with multiple pressure sensitive probes spanning from the oropharynx to the stomach, allowing for the assessment of esophageal pressurization and LES relaxation (Fig. 2). HRM can classify achalasia into subtypes based on peristaltic dysfunction, according to the Chicago system. 6 Type II has been shown to be the more responsive to treatment, while type III is the most difficult to treat. 1,3,7 While HRM, TBE and endoscopy all provide objective assessments of achalasia, what is unclear is how well these physiological measurements of esophageal function correlate with patient-perceived health-related quality of life (HRQoL). 2,3,8 Therefore, our aim was to determine the extent of the correlation of patient-perceived HRQoL and objective physiological evidence of achalasia. C 2016 International Society for Diseases of the Esophagus 1

2 Diseases of the Esophagus METHODS Patients Patients with achalasia who were being evaluated for possible surgical intervention from January 1, 2012 to July 31, 2015 were included in the study. Preoperative evaluation included history, physical examination, upper gastrointestinal endoscopy, HRM and TBE. Other testing was done based on individual need. Patient with pseudo-achalasia as determined by upper endoscopy were excluded. Only patients with achalasia who completed HRM and TBE were included in the study. Fig. 1 Timed barium esophagogram at 1 minute. Column height and width are measured and the structure of the esophagus assessed. Physiological testing Timed barium esophagography With the patient upright, a 250 cc bolus of barium contrast fluid was swallowed, followed by chest radiogram. Height and width of the barium fluid column at 1, 5 and 10 minutes, as well as esophageal contour was evaluated. A 13 mm barium tablet was swallowed at 10 minutes to demonstrated passage of a solid bolus. The combination of esophageal shape and failure of Fig. 2 High-resolution manometry of the three major types of achalasia. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Correlating symptoms to testing in achalasia 3 immediate passage of liquid barium and the barium tablet is consistent with achalasia. 4 High-resolution manometry Esophageal motor function was studied with a 36-channel solid-state catheter system with high fidelity circumferential sensors at 1-cm intervals (Medtronic, Inc., Minneapolis, MN). Patients were given 10 15 five cc water swallows 30 s apart in the supine position. Data were analyzed using ManoView software in the high-resolution esophageal color topography mode to standardize data analysis. All pertinent HRM metrics including LES basal pressure, integrated relaxation pressure (IRP, normal <15 mm Hg), distal contractile integral (DCI), distal latency as well as percentage of wet swallows associated with panesophageal pressurization or failed swallows were measured to establish a diagnosis based on the Chicago classification of esophageal motility disorders. 6 Type I achalasia was defined as median IRP > 15 mm Hg and 100% failed peristalsis (DCI < 100 mm Hg s cm). Type II was defined as median IRP > 15 mm Hg and 100% failed peristalsis, with panesophageal pressurization in 20% of swallows. Type III was defined as median IRP > 15 mm Hg, no normal peristalsis, and premature (spastic contractions with DCI > 450 mm Hg s cm in 20% of swallows. If the catheter could not be positioned across the gastroesophageal junction due to anatomical issues or patient cooperation, such that an IRP could not be obtained, but all other diagnostic criteria for achalasia were meet, then these patients were classified as undetermined achalasia. Achalasia health-related quality of life assessment Before undergoing any operation, patients completed the Measure of Achalasia Disease Severity (ADS) questionnaire, which is a validated instrument assessing the effect of achalasia health-related quality of life designed by Urbach et al. 9 This 10 item survey (best score = 10 and worst score = 31) assessing dysphagia to both liquids and solids, specific types of food, other associated symptoms, and overall health in relation to achalasia. Although Urbach et al. 9 do have a table to recalibrate the raw 10 31 scores to an interval level 0 100 scale, we chose to keep the original scale because we feel that it is more precise and more responsive to the magnitude of change caused by an intervention. Statistical analysis Comparison of groups was done using analysis of variance. The relationship of ADS score to objective measurements was done using linear regression analysis. This included the correlation coefficient (r value) and the coefficient of determination (r 2 value). A P value of 0.05 was considered significant. Table 1 Linear regression analysis of ADS scores with TBE and HRM measurements P value R R 2 TBE Height 1 minute 0.87 0.016 0.0003 Width 1 minute 0.93 0.009 0.0001 Height 5 minutes 0.80 0.031 0.0009 Width 5 minutes 0.92 0.012 0.0001 HRM LES pressure 0.35 0.093 0.0087 IRP 0.25 0.125 0.0156 RESULTS Demographics A total of 120 patients were included in the study. Gender distribution was 64 male (53%) and 56 female (47%). The mean age, with standard deviation, was 55 ± 18 years (range: 18 85 years). Mean body mass index, with standard deviation, was 27.0 ± 6.1 kg/m 2. In general, patients with long standing achalasia have difficulty recalling exactly when their symptoms began, but the symptom length in our cohort ranged from 3 months to over 30 years. Distribution of achalasia types was type I 27 (22.5%), type II 60 (50%), type III 11 (9.2%) and undetermined 22 (18.3%). The mean, with standard deviation, ADS score was 24.9 ± 3.6. The distribution of treatments prior to evaluation by our group was no treatment 57 (47.5%), pneumatic and non-pneumatic dilation 40 (33.3%), botulinum toxin injection 6 (5%), dilation and botulinum toxin injection 10 (8.3%), Heller myotomy 4 (3.3%) and Heller myotomy and dilation 3 (2.5%). Comparison of ADS score with achalasia types The mean ADS with standard deviation for type I was 24.0 ± 4.3, for type II was 25.4 ± 3.2, for type III 24.3 ± 4.6, and for undetermined group 25.0 ± 3.2 (P = NS). Relationship of ADS score to TBE measurements Table 1 shows the results of the linear regression analysis to height and width at 1 and 5 minutes. There is no statistically significant relationship or correlations. There were 97 (80.8%) patients with no passage of the 13 mm barium tablet, 7 (5.8%) with passage, and 16 (13.3%) in whom it could not be determined if the pill passed or not. The ADS scores for each were 24.9 ± 3.6 for no passage, 26.4 ± 3.4 for passage, and 23.9 ± 3.7 for the undetermined group (P = NS). Relationship of ADS score to HRM measurements Table 1 shows the results of the linear regression analysis of ADS scores to LES pressure and IRP. There

4 Diseases of the Esophagus were no statistically significant associations or correlations. DISCUSSION The presumed mechanism for symptoms in achalasia is the increased resistance to passage of food and liquid due to a combination of esophageal peristaltic failure and failure of the LES to relax. What this study shows is that the magnitude of symptom severity and health-related quality of life as experienced by the patient is independent of our present best physiologic measures of achalasia pathophysiology. This finding is consistent with other disease processes. Physiological and anatomic measures of gastroesophageal reflux disease and hiatal hernia also correlated poorly with patient-perceived symptoms. 10 It is also known that patient-perceived dyspnea severity correlates poorly with pulmonary function testing 11 and dysuria correlates poorly with urodynamic testing. 12 In achalasia, there seems to be a poor correlation between reflux symptoms and objective measures of reflux after laparoscopic Heller myotomy with Dor fundoplication. 13 It is not well understood why some patients perceived symptoms more severely than others. Many factors can influence how patients perceive symptoms that have nothing to do with the actual pathophysiology of the disease, 14 so this is probably true for achalasia as well. Other studies of achalasia, symptoms and physiologic testing have shown a variety, but overall similar, results to our study. Vaezi et al. 15 studied achalasia patients who had complete or near complete symptomatic relief to determine if TBE or symptomatic improvement better predicted long-term outcome. What they found was that the group with symptom relief, as measured by an ad hoc scoring scale, but poor TBE emptying were more likely to have recurrent symptoms after 1 year than those with good TBE emptying. Nicodeme et al. 16 studied 25 untreated and 25 treated patient with achalasia using TBE and HRM while assessing symptoms with the Eckardt score. Of the untreated group, they also found no correlation between objective physiological testing and symptom severity. In an interesting experiment, Lazarescu et al. 17 subjected healthy volunteers to pharmacologically induced esophageal hypomotility and assessed the perception of dysphagia to bolus transit. They found a poor correlation between patient-perceived difficulty of bolus passage and actual failed swallows. This was also true for gastroesophageal reflux disease patients with ineffective esophageal motility. Lin et al. 18 in a study of achalasia patients using the novel technology of high-resolution impedance manometry and the Impaction Dysphagia Questionnaire (IDQ) found that bolus flow time better correlated with IDQ score than IRP and TBE. However, it should be noted that they did not report if the IDQ was a validated instrument for achalasia, while the ADS is. Lastly, Patel et al. 19 studied a group of patients with achalasia who underwent Heller myotomy with Dor fundoplication using HRM and a global symptom scale and three achalasia specific questionnaires. They found that the degree of symptom improvement after Heller myotomy was best predicted by the severity of transit symptoms and IRP abnormality. Our study complements prior studies in that it is one of the largest cohorts of achalasia patient studies with the specific aim of determining the correlation of health-related quality of life and objective physiological testing using widely available techniques with are in use in clinical practice. We believe that this is the only study using Urbach s ADS instrument, and, therefore, it is worthy to note that using a variety of methods to assess symptom severity and quality of life lead to similar conclusions. Although this study was not designed to compare achalasia symptom severity/quality of life instruments, we would like to explain why we favor the ADS questionnaire as developed by Urbach et al. 9 over the Eckardt score. 20 When choosing a quality of life instrument certain principles need to be followed, namely, the conceptual and measurement model of the instrument, its validity, reliability, responsiveness to change, practicality and appropriateness. 21 Therefore, because of the ADS s rigorous psychometric testing and, in our opinion, superior face validity, we chose to employ it in our evaluation of achalasia patients. Specifically, the reliance on weight loss and chest pain, we feel, make the Eckardt score less responsive to symptomatic change caused by an intervention. In conclusion, there is poor correlation between HRQoL in achalasia patients and objective physiological assessment of achalasia. 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