Weight loss in achalasia is determined by its phenotype

Weight loss in achalasia is determined by its phenotype SUMMARY Patients with achalasia present with dysphagia, regurgitation, and varying degrees of weight loss. However, despite it being a disorder of the lower esophageal sphincter with functional obstruction in all patients, it is unclear why certain patients lose significantly more weight compared to others. The aims of this study are to assess demographic, clinical, and manometric characteristics of a large cohort of patients with achalasia to determine potential correlates of weight loss in this population. Patients with diagnosis of achalasia referred to our center between 2009 and 2016 were evaluated. Demographic and physiologic tests between those with and without weight loss were compared. The cohort of patients with initial self-reported weight loss were studied to determine change in weight after intervention (pneumatic dilation or myotomy). The Kruskal–Wallis test was used for comparison of continuous variables between groups and Pearson's χ2 test was used for comparison of categorical variables between groups. 138 patients with achalasia were evaluated. 35 patients were excluded due to lack of manometric data and 3 from lack of documented weight resulting in the study population of 100 patients with achalasia [51% male, median age: 56 years]. Weight loss was reported in 51/100 (51%) patients. BMI was lower in patients who reported weight loss (25 vs. 31, P < 0.001) with a median weight loss of 28 lbs (14–40 lbs). There were no significant differences in age at diagnosis, gender, or symptom presentation (dysphagia, regurgitation, or chest pain) between the groups. However, more patients with type II achalasia (63%) reported weight loss as compared to other sub-types (P = 0.013). 73% of type III achalasia denied having weight loss. Patients who denied weight loss had symptoms for longer duration (24 vs. 12 months, P < 0.001) and had lower mean residual LES pressure (20 vs. 30 mmHg, P = 0.006). Postintervention 42% of patients reported no weight regain despite appropriate therapy for achalasia with median follow-up of 22 months (range: 6–90 months). Type II achalasia patients are most likely and type III achalasia are least likely to have weight loss compared to type I achalasia. Given that no other demographic/physiologic parameters predicted weight loss, the role of underlying inflammatory cascade in achalasia phenotypes deserves special attention. INTRODUCTION Achalasia is one of the most studied motility disorders of the esophagus. It is characterized manometrically by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter (LES) during deglutition. The annual incidence is approximately 1/100,000 worldwide with an overall prevalence of 9–10/100,000.1–4 Diagnosis of achalasia is made on the basis of clinical presentation, esophagogastroduodenoscopy (EGD) to rule-out pseudoachalasia (from an obstructing mass), and high-resolution manometry (HRM), which is the current gold standard test. Phenotypically, achalasia can be categorized into three distinct types based on manometric patterns: type I (classic) with quiescent esophageal body, type II with intermittent periods of panesophageal pressurization, and type III (spastic) with premature or high amplitude distal esophageal contractions.5 These subtypes have treatment outcome implications with better treatment response to type I and II compared to type III.6 Achalasia is a heterogeneous disease with variable clinical presentation. Most patients (82–100%) report dysphagia to solids and liquids, as well as regurgitation (76–91%) of undigested food.7–10 Weight loss has been reported in 35–91% of patients during initial presentation.3,4 The degree of weight loss is widely variable with average weight loss of 20 ± 16 lbs.8 However, despite achalasia being a disorder of the LES with functional obstruction in all patients, it is unclear why certain patients report significantly more weight loss compared to others. One of the pioneer studies evaluating clinical response in achalasia with pneumatic dilatations in 1970s noted weight loss in approximately 91% of patients (N = 264) with 16 patients reporting > 20 kg and 18 patients reporting an average of 5 kg weight loss. However, a significant number of patients in this study had diagnostic latency with noted duration of symptoms ranging from 2 to > 20 years prior to diagnosis and treatment. Despite achalasia being initially described by Sir Thomas Willis in 1674, there are currently no studies that have evaluated correlates of weight loss and potential nutritional implications. The aims of this study are to 1) assess demographic, clinical, and manometric characteristics of a large cohort of patients with achalasia to determine potential correlates of weight loss in this population, and 2) evaluate postintervention weight trajectories after current gold standard treatment of pneumatic dilatation (PD) or Heller myotomy (HM). MATERIALS AND METHODS The study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice, and applicable regulatory requirements. The Vanderbilt Institutional Review Board approved this clinical trial (IRB # 140,375 and 161,769). Study design and patient population Our single center retrospective cohort study included adult patients (age ≥ 18 years) who were referred to the Esophageal Motility Center at Vanderbilt University Medical Center between 2009 and 2016 for evaluation and treatment of achalasia. For inclusion, patients were required to have a confirmed diagnosis of achalasia based on HRM and EGD. The Chicago Classification Criteria of esophageal motility disorders was employed to make the diagnosis of achalasia on HRM.11 Patients without confirmed manometry data or lack of weight measurement during clinic visit were excluded. Baseline patient characteristics recorded in the database included age, gender (male/female), and ethnicity (Caucasian, African American, Hispanic, or other). Primary covariates including age at diagnosis, BMI (kg/m2), symptom duration (months), degree of weight loss (lbs.), gastrointestinal symptoms (dysphagia, regurgitation, chest pain), and history of prior interventions for achalasia (HM, PD, Botox injections, or none) were obtained from chart review of the initial clinic encounter. Presence and degree of weight loss was self-reported by the patients during the initial clinic visit. All patients were evaluated and assessed by one provider (MV). Additional variables that were also recorded included marital status (single or married), smoking status (prior smoker, non-smoker, current smoker), and number of prescription medications listed on the initial clinic encounter. Postintervention We performed a phone interview using a standardized questionnaire on patients that had underwent PD or HM in the baseline cohort to assess their self-reported current weight (lbs.), whether they had gained weight post intervention (yes or no), and postintervention modified achalasia dysphagia score (MADS). MADS is a well-validated patient reported outcome measure that was specifically developed for use in patients with achalasia.12,13 It has strong developmental characteristics including content validity, reliability, and construct validity.14 MADS ranges from 0 to 100 with higher score corresponding to greater disease severity. It also evaluates for presence and severity of other symptoms such as heartburn and chest pain. Statistical analysis Data were collected and stored at the secure Web based Vanderbilt Digestive Disease Center REDCap (Research Electronic Data Capture) (1 UL1 RR024975 NCRR/NIH). There was strict control and supervision of the data entry and access for this study. Categorical variables were summarized using percentages and continuous variables were summarized using the median, 25th, and 75th percentiles. Demographic and physiologic tests between those with and without weight loss and those who were phone interviewed or not were compared. The Kruskal–Wallis test was used for comparison of continuous variables between groups and Pearson's Χ2 test was used for comparison of categorical variables between groups. Linear mixed effects regression was used to estimate the association of postintervention weight change with improvement in MADS score and subtype of achalasia or type of intervention. A random intercept was included in the mixed effects model to account for repeated measurements taken on the same subject over time. All analyses were conducted using the R statistical program at a 0.05 level of significance. RESULTS Demographics A total of 138 patients with achalasia were evaluated with 35 patients excluded due to lack of manometric data and 3 from lack of documented weight resulting in the study population of 100 patients (Fig. 1). Weight loss was reported in 51/100 (51%) patients with median (IQR) age of 54 years (37–66). Overall 53% of the patients with weight loss were female. Table 1 shows the clinical characteristics of patients with achalasia stratified based on weight loss. As expected, BMI was significantly lower in patients who reported weight loss (25 vs. 31, P < 0.001). Median weight loss was 28 lbs with IQR of 14–40 lbs. There were no significant differences in age at diagnosis, gender, symptom presentation (dysphagia, regurgitation, or chest pain), mean LES basal pressure or social factors (marital status) between the groups. There were also no differences in history of prior interventions (Heller myotomy, pneumatic dilatations, or botox injections) between the groups. Most of the patients in our cohort had no prior treatment (88% in the weight loss group and 80% in the no weight loss group). However, patients who reported no weight loss had symptoms for significantly longer duration (24 vs. 12 months, P < 0.001) and had lower mean residual LES pressure (20 vs. 30 mmHg, P = 0.006). Higher percentage of patients with weight loss had defective LES relaxation (integrated relaxation pressure of >15 mmHg) compared to patients without weight loss (91% vs. 73%, P = 0.04). Patients who reported no weight loss were more likely to be prior smokers (27% vs. 6%, P = 0.01) and had higher number of prescription medications on presentation (4 vs. 3, P = 0.04). Fig. 1 View largeDownload slide Patient flow diagram. Fig. 1 View largeDownload slide Patient flow diagram. Table 1 Clinical characteristics of patients with achalasia stratified to with and without weight loss. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, lower esophageal sphincter (LES) pressure, and # of prescription medications represent the median value (interquartile range). *Kruskal-Wallis and Pearson's X2 test Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 BMI, body mass index; LES, lower esophageal sphincter. View Large Table 1 Clinical characteristics of patients with achalasia stratified to with and without weight loss. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, lower esophageal sphincter (LES) pressure, and # of prescription medications represent the median value (interquartile range). *Kruskal-Wallis and Pearson's X2 test Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 BMI, body mass index; LES, lower esophageal sphincter. View Large Type of achalasia Patients who reported weight loss were significantly more likely to be subtype II achalasia (71%) compared to other subtypes (Fig. 2A. P = 0.01). When evaluating weight loss within phenotypes, patients with type II achalasia were also significantly more likely to report weight loss (63%) compared to other subtypes (Fig. 2B, P = 0.013). Furthermore, 73% of patients with type III achalasia reported no weight loss. Fig. 2 View largeDownload slide Percentage of patients stratified by reported history of weight loss (A, P = 0.01) and type of achalasia (B, P = 0.013). Fig. 2 View largeDownload slide Percentage of patients stratified by reported history of weight loss (A, P = 0.01) and type of achalasia (B, P = 0.013). Fig. 3 View largeDownload slide Relationship between postintervention modified achalasia dysphagia score (MADS) and weight change (pre to postintervention). Fig. 3 View largeDownload slide Relationship between postintervention modified achalasia dysphagia score (MADS) and weight change (pre to postintervention). Postintervention Overall, 32/100 patients agreed for a postintervention phone interview. Table 2 presents the clinical characteristics of patients stratified by phone interview. There were no baseline demographics or clinical differences between the two groups (age at diagnosis, BMI, gender, symptom duration, degree of weight loss, type of achalasia, weight prior to intervention, or type of intervention). Overall, 38% of patients who agreed to a phone interview had underwent pneumatic dilatation and 56% had underwent Heller myotomy. During the follow-up period of 22 months (range: 6–90 months), 43% of patients who had initially reported weight loss denied regaining their weight after undergoing therapy for achalasia. There were no differences in modified achalasia dysphagia score (MADS) between the patients who did and did not report weight gain postintervention (47 vs. 45, P = 0.66) suggesting no difference in dysphagia symptoms between the two groups. Figure 3 shows the relationship between postintervention MADS score and weight change (pre to postintervention). Table 2 Clinical characteristics of patients with achalasia who agreed to do the postintervention phone interview. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, and weight prior to intervention represent the median value (interquartile range). *Kruskal–Wallis and Pearson's X2 test No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% BMI, body mass index. View Large Table 2 Clinical characteristics of patients with achalasia who agreed to do the postintervention phone interview. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, and weight prior to intervention represent the median value (interquartile range). *Kruskal–Wallis and Pearson's X2 test No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% BMI, body mass index. View Large We also evaluated postintervention weight trajectories based on type of achalasia (Fig. 4A) and intervention (Fig. 4B). In the phone interview group, there were no statistically significant differences, but patients with type 3 had negative postintervention weight trajectory compared to type I or II (Fig. 4A). Fig. 4 View largeDownload slide Postintervention weight trajectories based on type of achalasia (A) and intervention (B). HM, Heller myotomy; PD, pneumatic dilatation. Fig. 4 View largeDownload slide Postintervention weight trajectories based on type of achalasia (A) and intervention (B). HM, Heller myotomy; PD, pneumatic dilatation. DISCUSSION The diet of patients with achalasia has been overlooked with currently no published studies in this field of clinical practice. Treatment in this patient population has been focused primarily on improving physiology of the lower esophageal sphincter by disrupting the muscle fibers. Success for interventions has been defined using patient reported outcome measures such as the Eckardt symptom score or MADS score. Although the Eckardt score has a subcategory of weight loss and is widely used as a measure of achalasia severity, it has not been validated in postintervention patients. One retrospective cross-sectional study of patients with achalasia showed that 70% of the patients were overweight or obese (consistent with the general American population), yet, 26% were still at moderate or high nutrition risk based on results from the Malnutrition Universal Screening Tool (MUST).15 Thus, even though the Eckardt score is used to measure treatment efficacy, this score does not necessarily reflect nutritional status of patients with achalasia. Objective markers such as comparing pre-to postintervention body weight have not been used in clinical studies to evaluate treatment efficacy. Hence, it remains unknown why certain patients with achalasia report significantly more weight loss on presentation compared to others despite that all have mechanical obstruction. In a prospective study evaluating nutritional status in 19 patients with untreated achalasia, 80% reported having altered their dietary intake due to swallowing difficulties and 90% reported consuming less food than usual.16 In this unique cohort, we evaluated potential correlates of weight loss in patients with achalasia. We found that patients with achalasia had an average weight loss of 28 lbs on presentation (14–40 lbs). There were no differences in age at diagnosis, gender predominance, or symptom presentation (dysphagia, regurgitation, or chest pain) in patients with or without weight loss. Interestingly, patients with weight loss had symptoms for significantly shorter duration of time (12 vs. 24 months, P < 0.01), which suggest a lack of dietary adaptation early in the disease process. Furthermore, patients with type II achalasia were most likely (63%) and patients with type III achalasia were least likely to report weight loss (73%). It remains unclear why type II achalasia patients would report more weight loss. If dietary modification to accommodate swallowing difficulty is the primarily mechanism for weight loss in achalasia, then we would expect weight loss to occur in all types of achalasia. On the other hand, if LES physiology were the main driver of weight loss, we would expect patients’ to regain weight postintervention (pneumatic dilatation or Heller myotomy). In contrast, 43% of study patients reported not regaining weight after undergoing therapy for achalasia during a median follow-up of 22 months (range: 6–90 months). This suggests that it is unlikely that LES physiology is the sole etiology of weight loss in achalasia. One potential hypothesis could be that patients with type II achalasia might have a different proinflammatory response compared to other subtypes of achalasia that induces a higher catabolic state with alterations in gastrointestinal hormones that mediate energy homeostasis or suppress appetite. A recent cross-sectional study in which esophageal muscle tissue and peripheral blood was analyzed for systemic inflammatory patterns showed that achalasia tissue exhibited increased expression of proteins involved in extracellular matrix turnover, apoptosis, and proinflammatory, and profibrogenic cytokines.17 There was a significant increase in the percentage of circulating Th22/Th17/Th2/Th1 compared to healthy donors, with type III achalasia exhibiting the highest inflammatory response compared to types I and II.17 However, inflammatory response was not assessed based on the amount of weight loss. This is the first study to evaluate potential correlates of weight loss in patients with achalasia. However, we acknowledge that this study has several limitations. First, it is primarily a retrospective descriptive study, and thus, is designed to generate hypotheses. We did not have patient-reported outcome measures (the Eckardt or MADS score) or barium swallow on initial patient presentation to determine symptom and diseases severity. Although the prevalence of chest pain, regurgitation, or dysphagia did not differ between patients with or without weight loss, we are unable to assess if symptom severity or disease severity (based on timed-barium swallow) might predict weight loss in the patients. We did find that the postintervention MADS score did not predict weight gain in this population, which might suggest that symptom severity might not correlate with weight loss in this population. Although we performed a phone interview to determine postintervention weight gain, the findings of this interview were limited by small sample size (32/100 patients) due to lack of response. Second, the postintervention weight was self-reported during the phone interview and not objectively measured, as most patients with achalasia are lost to follow-up postintervention. We attempted to minimize the selection bias by using a standardized questionnaire for postintervention interviews. Longitudinal studies evaluating the role of dietary adaptations and changes in objective markers of energy homeostasis and inflammatory patterns between the phenotypes of achalasia is much needed to understand the mechanism behind weight loss in achalasia. CONCLUSION Treatment in achalasia has primarily focused toward disrupting LES physiology using dilatation or myotomy. Despite achalasia being a disorder of the LES with functional obstruction in all patients, it is unclear why some patients lose significantly more weight compared to others. We found that type II achalasia patients are most likely and type III achalasia are least likely to have weight loss compared to type I achalasia. Given that no other demographic/physiologic parameters predicted weight loss, the role of underlying inflammatory cascade, or lack of dietary adaptation in achalasia phenotypes deserves special attention in research and clinical practice. Notes Disclosures and Conflicts of Interest: The authors declare that they have no conflict of interest. Specific author contributions: Study concept and design: Dhyanesh Patel, Michael Vaezi; Acquisition of data: Dhyanesh Patel, Rishi Naik, Tina Higginbotham, Michael Vaezi; Analysis and interpretation of data: Dhyanesh Patel, Michael Vaezi; Drafting of the manuscript: Dhyanesh Patel; Analysis of the data: James Slaughter; Study concept: Heidi Silver; Critical revisions of the manuscript: Heidi Silver, Michael Vaezi; Study supervision: Michael Vaezi. References 1 Farrukh A , DeCaestecker J , Mayberry J F . An epidemiological study of achalasia among the South Asian population of leicester, 1986–2005 . Dysphagia 2008 ; 23 : 161 – 4 . Google Scholar CrossRef Search ADS PubMed 2 Birgisson S , Richter J E . Achalasia in Iceland, 1952–2002: An epidemiologic study . Dig Dis Sci 2007 ; 52 : 1855 – 60 . Google Scholar CrossRef Search ADS PubMed 3 Sadowski D C , Ackah F , Jiang B , Svenson L W . Achalasia: incidence, prevalence and survival. A population-based study . Neurogastroenterol Motil 2010 ; 22 : e256 – 61 . Google Scholar CrossRef Search ADS PubMed 4 Enestvedt B K , Williams J L , Sonnenberg A . Epidemiology and practice patterns of achalasia in a large multi-centre database . Aliment Pharmacol Ther 2011 ; 33 : 1209 – 14 . Google Scholar CrossRef Search ADS PubMed 5 Kahrilas P J , Bredenoord A J , Fox M et al. The Chicago Classification of esophageal motility disorders, v3.0 . Neurogastroenterol Motil 2015 ; 27 : 160 – 74 . Google Scholar CrossRef Search ADS PubMed 6 Patel D A , Kim H P , Zifodya J S , Vaezi M F . Idiopathic (primary) achalasia: a review . Orphanet J Rare Dis 2015 ; 10 : 89 . Google Scholar CrossRef Search ADS PubMed 7 Vaezi M F , Richter J E . Current therapies for achalasia: comparison and efficacy . J Clin Gastroenterol 1998 ; 27 : 21 – 35 . Google Scholar CrossRef Search ADS PubMed 8 Fisichella P M , Raz D , Palazzo F , Niponmick I , Patti M G . Clinical, radiological, and manometric profile in 145 patients with untreated achalasia . World J Surg 2008 ; 32 : 1974 – 9 . Google Scholar CrossRef Search ADS PubMed 9 Sinan H , Tatum R P , Soares R V , Martin A V , Pellegrini C A , Oelschlager B K . Prevalence of respiratory symptoms in patients with achalasia . Dis Esophagus 2011 ; 24 : 224 – 8 . Google Scholar CrossRef Search ADS PubMed 10 Spechler S J , Souza R F , Rosenberg S J , Ruben R A , Goyal R K . Heartburn in patients with achalasia . Gut 1995 ; 37 : 305 – 8 . Google Scholar CrossRef Search ADS PubMed 11 Bredenoord A J , Fox M , Kahrilas P J et al. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography . Neurogastroenterol Motil 2012 ; 24 : 57 – 65 . Google Scholar CrossRef Search ADS PubMed 12 Urbach D R , Tomlinson G A , Harnish J L , Martino R , Diamant N E . A measure of disease-specific health-related quality of life for achalasia . Am J Gastroenterol 2005 ; 100 : 1668 – 76 . Google Scholar CrossRef Search ADS PubMed 13 Chrystoja C C , Darling G E , Diamant N E et al. Achalasia-specific quality of life after pneumatic dilation or laparoscopic heller myotomy with partial fundoplication: a multicenter, randomized clinical trial . Am J Gastroenterol 2016 ; 111 : 1536 – 45 . Google Scholar CrossRef Search ADS PubMed 14 Patel D A , Sharda R , Hovis K L et al. Patient-reported outcome measures in dysphagia: a systematic review of instrument development and validation . Dis Esophagus 2017 ; 30 : 1 – 23 . Google Scholar CrossRef Search ADS 15 Newberry C A , Vajravelu R K , Lynch K L . Obese achalasia patients are at significant nutritional risk . Gastroenterology 2017; 152 : S197 . CrossRef Search ADS 16 Zifodya J , Kim H P , Silver H J , Slaughter J C , Higginbotham T , Vaezi M . Nutritional status of patients with untreated achalasia . Gastroenterology 2015 ; 148 : S-819-S-820 . Google Scholar CrossRef Search ADS 17 Furuzawa-Carballeda J , Aguilar-Leon D , Gamboa-Dominguez A et al. Achalasia–an autoimmune inflammatory disease: a cross-sectional study . J Immunol Res 2015 ; 2015 : 1 – 18 . Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diseases of the Esophagus Oxford University Press

Weight loss in achalasia is determined by its phenotype

Loading next page...
 
/lp/ou_press/weight-loss-in-achalasia-is-determined-by-its-phenotype-54TPyf0Psx
Publisher
The International Society for Diseases of the Esophagus
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.
ISSN
1120-8694
eISSN
1442-2050
D.O.I.
10.1093/dote/doy046
Publisher site
See Article on Publisher Site

Abstract

SUMMARY Patients with achalasia present with dysphagia, regurgitation, and varying degrees of weight loss. However, despite it being a disorder of the lower esophageal sphincter with functional obstruction in all patients, it is unclear why certain patients lose significantly more weight compared to others. The aims of this study are to assess demographic, clinical, and manometric characteristics of a large cohort of patients with achalasia to determine potential correlates of weight loss in this population. Patients with diagnosis of achalasia referred to our center between 2009 and 2016 were evaluated. Demographic and physiologic tests between those with and without weight loss were compared. The cohort of patients with initial self-reported weight loss were studied to determine change in weight after intervention (pneumatic dilation or myotomy). The Kruskal–Wallis test was used for comparison of continuous variables between groups and Pearson's χ2 test was used for comparison of categorical variables between groups. 138 patients with achalasia were evaluated. 35 patients were excluded due to lack of manometric data and 3 from lack of documented weight resulting in the study population of 100 patients with achalasia [51% male, median age: 56 years]. Weight loss was reported in 51/100 (51%) patients. BMI was lower in patients who reported weight loss (25 vs. 31, P < 0.001) with a median weight loss of 28 lbs (14–40 lbs). There were no significant differences in age at diagnosis, gender, or symptom presentation (dysphagia, regurgitation, or chest pain) between the groups. However, more patients with type II achalasia (63%) reported weight loss as compared to other sub-types (P = 0.013). 73% of type III achalasia denied having weight loss. Patients who denied weight loss had symptoms for longer duration (24 vs. 12 months, P < 0.001) and had lower mean residual LES pressure (20 vs. 30 mmHg, P = 0.006). Postintervention 42% of patients reported no weight regain despite appropriate therapy for achalasia with median follow-up of 22 months (range: 6–90 months). Type II achalasia patients are most likely and type III achalasia are least likely to have weight loss compared to type I achalasia. Given that no other demographic/physiologic parameters predicted weight loss, the role of underlying inflammatory cascade in achalasia phenotypes deserves special attention. INTRODUCTION Achalasia is one of the most studied motility disorders of the esophagus. It is characterized manometrically by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter (LES) during deglutition. The annual incidence is approximately 1/100,000 worldwide with an overall prevalence of 9–10/100,000.1–4 Diagnosis of achalasia is made on the basis of clinical presentation, esophagogastroduodenoscopy (EGD) to rule-out pseudoachalasia (from an obstructing mass), and high-resolution manometry (HRM), which is the current gold standard test. Phenotypically, achalasia can be categorized into three distinct types based on manometric patterns: type I (classic) with quiescent esophageal body, type II with intermittent periods of panesophageal pressurization, and type III (spastic) with premature or high amplitude distal esophageal contractions.5 These subtypes have treatment outcome implications with better treatment response to type I and II compared to type III.6 Achalasia is a heterogeneous disease with variable clinical presentation. Most patients (82–100%) report dysphagia to solids and liquids, as well as regurgitation (76–91%) of undigested food.7–10 Weight loss has been reported in 35–91% of patients during initial presentation.3,4 The degree of weight loss is widely variable with average weight loss of 20 ± 16 lbs.8 However, despite achalasia being a disorder of the LES with functional obstruction in all patients, it is unclear why certain patients report significantly more weight loss compared to others. One of the pioneer studies evaluating clinical response in achalasia with pneumatic dilatations in 1970s noted weight loss in approximately 91% of patients (N = 264) with 16 patients reporting > 20 kg and 18 patients reporting an average of 5 kg weight loss. However, a significant number of patients in this study had diagnostic latency with noted duration of symptoms ranging from 2 to > 20 years prior to diagnosis and treatment. Despite achalasia being initially described by Sir Thomas Willis in 1674, there are currently no studies that have evaluated correlates of weight loss and potential nutritional implications. The aims of this study are to 1) assess demographic, clinical, and manometric characteristics of a large cohort of patients with achalasia to determine potential correlates of weight loss in this population, and 2) evaluate postintervention weight trajectories after current gold standard treatment of pneumatic dilatation (PD) or Heller myotomy (HM). MATERIALS AND METHODS The study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice, and applicable regulatory requirements. The Vanderbilt Institutional Review Board approved this clinical trial (IRB # 140,375 and 161,769). Study design and patient population Our single center retrospective cohort study included adult patients (age ≥ 18 years) who were referred to the Esophageal Motility Center at Vanderbilt University Medical Center between 2009 and 2016 for evaluation and treatment of achalasia. For inclusion, patients were required to have a confirmed diagnosis of achalasia based on HRM and EGD. The Chicago Classification Criteria of esophageal motility disorders was employed to make the diagnosis of achalasia on HRM.11 Patients without confirmed manometry data or lack of weight measurement during clinic visit were excluded. Baseline patient characteristics recorded in the database included age, gender (male/female), and ethnicity (Caucasian, African American, Hispanic, or other). Primary covariates including age at diagnosis, BMI (kg/m2), symptom duration (months), degree of weight loss (lbs.), gastrointestinal symptoms (dysphagia, regurgitation, chest pain), and history of prior interventions for achalasia (HM, PD, Botox injections, or none) were obtained from chart review of the initial clinic encounter. Presence and degree of weight loss was self-reported by the patients during the initial clinic visit. All patients were evaluated and assessed by one provider (MV). Additional variables that were also recorded included marital status (single or married), smoking status (prior smoker, non-smoker, current smoker), and number of prescription medications listed on the initial clinic encounter. Postintervention We performed a phone interview using a standardized questionnaire on patients that had underwent PD or HM in the baseline cohort to assess their self-reported current weight (lbs.), whether they had gained weight post intervention (yes or no), and postintervention modified achalasia dysphagia score (MADS). MADS is a well-validated patient reported outcome measure that was specifically developed for use in patients with achalasia.12,13 It has strong developmental characteristics including content validity, reliability, and construct validity.14 MADS ranges from 0 to 100 with higher score corresponding to greater disease severity. It also evaluates for presence and severity of other symptoms such as heartburn and chest pain. Statistical analysis Data were collected and stored at the secure Web based Vanderbilt Digestive Disease Center REDCap (Research Electronic Data Capture) (1 UL1 RR024975 NCRR/NIH). There was strict control and supervision of the data entry and access for this study. Categorical variables were summarized using percentages and continuous variables were summarized using the median, 25th, and 75th percentiles. Demographic and physiologic tests between those with and without weight loss and those who were phone interviewed or not were compared. The Kruskal–Wallis test was used for comparison of continuous variables between groups and Pearson's Χ2 test was used for comparison of categorical variables between groups. Linear mixed effects regression was used to estimate the association of postintervention weight change with improvement in MADS score and subtype of achalasia or type of intervention. A random intercept was included in the mixed effects model to account for repeated measurements taken on the same subject over time. All analyses were conducted using the R statistical program at a 0.05 level of significance. RESULTS Demographics A total of 138 patients with achalasia were evaluated with 35 patients excluded due to lack of manometric data and 3 from lack of documented weight resulting in the study population of 100 patients (Fig. 1). Weight loss was reported in 51/100 (51%) patients with median (IQR) age of 54 years (37–66). Overall 53% of the patients with weight loss were female. Table 1 shows the clinical characteristics of patients with achalasia stratified based on weight loss. As expected, BMI was significantly lower in patients who reported weight loss (25 vs. 31, P < 0.001). Median weight loss was 28 lbs with IQR of 14–40 lbs. There were no significant differences in age at diagnosis, gender, symptom presentation (dysphagia, regurgitation, or chest pain), mean LES basal pressure or social factors (marital status) between the groups. There were also no differences in history of prior interventions (Heller myotomy, pneumatic dilatations, or botox injections) between the groups. Most of the patients in our cohort had no prior treatment (88% in the weight loss group and 80% in the no weight loss group). However, patients who reported no weight loss had symptoms for significantly longer duration (24 vs. 12 months, P < 0.001) and had lower mean residual LES pressure (20 vs. 30 mmHg, P = 0.006). Higher percentage of patients with weight loss had defective LES relaxation (integrated relaxation pressure of >15 mmHg) compared to patients without weight loss (91% vs. 73%, P = 0.04). Patients who reported no weight loss were more likely to be prior smokers (27% vs. 6%, P = 0.01) and had higher number of prescription medications on presentation (4 vs. 3, P = 0.04). Fig. 1 View largeDownload slide Patient flow diagram. Fig. 1 View largeDownload slide Patient flow diagram. Table 1 Clinical characteristics of patients with achalasia stratified to with and without weight loss. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, lower esophageal sphincter (LES) pressure, and # of prescription medications represent the median value (interquartile range). *Kruskal-Wallis and Pearson's X2 test Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 BMI, body mass index; LES, lower esophageal sphincter. View Large Table 1 Clinical characteristics of patients with achalasia stratified to with and without weight loss. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, lower esophageal sphincter (LES) pressure, and # of prescription medications represent the median value (interquartile range). *Kruskal-Wallis and Pearson's X2 test Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 Weight loss No weight loss N = 51 N = 49 P-value* Age at diagnosis 54 (37, 66) 59 (43, 67) 0.36 BMI 25 (22, 31) 31 (27, 36) <0.001 Gender 47% M, 53% F 55% M, 45% F 0.42 Symptom duration (months) 12 (5.5, 12) 24 (12, 36) <0.001 Degree of weight loss (lbs.) 28 (14, 40) 0 <0.001 Dysphagia 100% 98% 0.30 Regurgitation 94% 87% 0.24 Chest pain 46% 35% 0.29 LES (mean residual) pressure (mmHg) 30 (19, 39) 20 (14, 31) 0.01 LES (mean) basal pressure (mmHg) 47 (26, 65) 33 (18, 66) 0.29 Defective LES relaxation (IRP > 15 mmHg) 91% 73% 0.04 Prior interventions:  Heller myotomy 6% 10%  Pneumatic dilatation 2% 0% 0.36  Botox injections 4% 10%  None 88% 80% Marital status:  Single 29%, 19% 0.22  Married 71% 81%, Smoking status:  Prior smoker 6% 27%  Non-smoker 75% 60% 0.01  Current smoker 20% 12% # of prescription medications 3 (1, 6) 4 (3, 7) 0.04 BMI, body mass index; LES, lower esophageal sphincter. View Large Type of achalasia Patients who reported weight loss were significantly more likely to be subtype II achalasia (71%) compared to other subtypes (Fig. 2A. P = 0.01). When evaluating weight loss within phenotypes, patients with type II achalasia were also significantly more likely to report weight loss (63%) compared to other subtypes (Fig. 2B, P = 0.013). Furthermore, 73% of patients with type III achalasia reported no weight loss. Fig. 2 View largeDownload slide Percentage of patients stratified by reported history of weight loss (A, P = 0.01) and type of achalasia (B, P = 0.013). Fig. 2 View largeDownload slide Percentage of patients stratified by reported history of weight loss (A, P = 0.01) and type of achalasia (B, P = 0.013). Fig. 3 View largeDownload slide Relationship between postintervention modified achalasia dysphagia score (MADS) and weight change (pre to postintervention). Fig. 3 View largeDownload slide Relationship between postintervention modified achalasia dysphagia score (MADS) and weight change (pre to postintervention). Postintervention Overall, 32/100 patients agreed for a postintervention phone interview. Table 2 presents the clinical characteristics of patients stratified by phone interview. There were no baseline demographics or clinical differences between the two groups (age at diagnosis, BMI, gender, symptom duration, degree of weight loss, type of achalasia, weight prior to intervention, or type of intervention). Overall, 38% of patients who agreed to a phone interview had underwent pneumatic dilatation and 56% had underwent Heller myotomy. During the follow-up period of 22 months (range: 6–90 months), 43% of patients who had initially reported weight loss denied regaining their weight after undergoing therapy for achalasia. There were no differences in modified achalasia dysphagia score (MADS) between the patients who did and did not report weight gain postintervention (47 vs. 45, P = 0.66) suggesting no difference in dysphagia symptoms between the two groups. Figure 3 shows the relationship between postintervention MADS score and weight change (pre to postintervention). Table 2 Clinical characteristics of patients with achalasia who agreed to do the postintervention phone interview. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, and weight prior to intervention represent the median value (interquartile range). *Kruskal–Wallis and Pearson's X2 test No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% BMI, body mass index. View Large Table 2 Clinical characteristics of patients with achalasia who agreed to do the postintervention phone interview. The ranges in parenthesis for age, BMI, symptom duration, degree of weight loss, and weight prior to intervention represent the median value (interquartile range). *Kruskal–Wallis and Pearson's X2 test No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% No phone interview Phone interview N = 68 N = 32 P-value* Age at diagnosis 58 (40, 67) 58 (39, 64) 0.64 BMI 27 (23, 35) 28 (26, 33) 0.69 Gender 51% M, 49% F 50% M, 50% F 0.89 Symptom duration (months) 12 (6, 24) 12 (10, 36) 0.095 Degree of weight loss (lbs) 9 (0, 30) 0 (0, 14) 0.39 Type of achalasia:  Type I 13% 22%  Type II 59% 53% 0.31  Type III 28% 22% Weight prior to intervention (kg) 85 (61, 102) 85 (71, 97) 0.9 Intervention:  Pneumatic dilatation 37% 38%  Myotomy 35% 56% 0.15  Botox injection 12% 6% BMI, body mass index. View Large We also evaluated postintervention weight trajectories based on type of achalasia (Fig. 4A) and intervention (Fig. 4B). In the phone interview group, there were no statistically significant differences, but patients with type 3 had negative postintervention weight trajectory compared to type I or II (Fig. 4A). Fig. 4 View largeDownload slide Postintervention weight trajectories based on type of achalasia (A) and intervention (B). HM, Heller myotomy; PD, pneumatic dilatation. Fig. 4 View largeDownload slide Postintervention weight trajectories based on type of achalasia (A) and intervention (B). HM, Heller myotomy; PD, pneumatic dilatation. DISCUSSION The diet of patients with achalasia has been overlooked with currently no published studies in this field of clinical practice. Treatment in this patient population has been focused primarily on improving physiology of the lower esophageal sphincter by disrupting the muscle fibers. Success for interventions has been defined using patient reported outcome measures such as the Eckardt symptom score or MADS score. Although the Eckardt score has a subcategory of weight loss and is widely used as a measure of achalasia severity, it has not been validated in postintervention patients. One retrospective cross-sectional study of patients with achalasia showed that 70% of the patients were overweight or obese (consistent with the general American population), yet, 26% were still at moderate or high nutrition risk based on results from the Malnutrition Universal Screening Tool (MUST).15 Thus, even though the Eckardt score is used to measure treatment efficacy, this score does not necessarily reflect nutritional status of patients with achalasia. Objective markers such as comparing pre-to postintervention body weight have not been used in clinical studies to evaluate treatment efficacy. Hence, it remains unknown why certain patients with achalasia report significantly more weight loss on presentation compared to others despite that all have mechanical obstruction. In a prospective study evaluating nutritional status in 19 patients with untreated achalasia, 80% reported having altered their dietary intake due to swallowing difficulties and 90% reported consuming less food than usual.16 In this unique cohort, we evaluated potential correlates of weight loss in patients with achalasia. We found that patients with achalasia had an average weight loss of 28 lbs on presentation (14–40 lbs). There were no differences in age at diagnosis, gender predominance, or symptom presentation (dysphagia, regurgitation, or chest pain) in patients with or without weight loss. Interestingly, patients with weight loss had symptoms for significantly shorter duration of time (12 vs. 24 months, P < 0.01), which suggest a lack of dietary adaptation early in the disease process. Furthermore, patients with type II achalasia were most likely (63%) and patients with type III achalasia were least likely to report weight loss (73%). It remains unclear why type II achalasia patients would report more weight loss. If dietary modification to accommodate swallowing difficulty is the primarily mechanism for weight loss in achalasia, then we would expect weight loss to occur in all types of achalasia. On the other hand, if LES physiology were the main driver of weight loss, we would expect patients’ to regain weight postintervention (pneumatic dilatation or Heller myotomy). In contrast, 43% of study patients reported not regaining weight after undergoing therapy for achalasia during a median follow-up of 22 months (range: 6–90 months). This suggests that it is unlikely that LES physiology is the sole etiology of weight loss in achalasia. One potential hypothesis could be that patients with type II achalasia might have a different proinflammatory response compared to other subtypes of achalasia that induces a higher catabolic state with alterations in gastrointestinal hormones that mediate energy homeostasis or suppress appetite. A recent cross-sectional study in which esophageal muscle tissue and peripheral blood was analyzed for systemic inflammatory patterns showed that achalasia tissue exhibited increased expression of proteins involved in extracellular matrix turnover, apoptosis, and proinflammatory, and profibrogenic cytokines.17 There was a significant increase in the percentage of circulating Th22/Th17/Th2/Th1 compared to healthy donors, with type III achalasia exhibiting the highest inflammatory response compared to types I and II.17 However, inflammatory response was not assessed based on the amount of weight loss. This is the first study to evaluate potential correlates of weight loss in patients with achalasia. However, we acknowledge that this study has several limitations. First, it is primarily a retrospective descriptive study, and thus, is designed to generate hypotheses. We did not have patient-reported outcome measures (the Eckardt or MADS score) or barium swallow on initial patient presentation to determine symptom and diseases severity. Although the prevalence of chest pain, regurgitation, or dysphagia did not differ between patients with or without weight loss, we are unable to assess if symptom severity or disease severity (based on timed-barium swallow) might predict weight loss in the patients. We did find that the postintervention MADS score did not predict weight gain in this population, which might suggest that symptom severity might not correlate with weight loss in this population. Although we performed a phone interview to determine postintervention weight gain, the findings of this interview were limited by small sample size (32/100 patients) due to lack of response. Second, the postintervention weight was self-reported during the phone interview and not objectively measured, as most patients with achalasia are lost to follow-up postintervention. We attempted to minimize the selection bias by using a standardized questionnaire for postintervention interviews. Longitudinal studies evaluating the role of dietary adaptations and changes in objective markers of energy homeostasis and inflammatory patterns between the phenotypes of achalasia is much needed to understand the mechanism behind weight loss in achalasia. CONCLUSION Treatment in achalasia has primarily focused toward disrupting LES physiology using dilatation or myotomy. Despite achalasia being a disorder of the LES with functional obstruction in all patients, it is unclear why some patients lose significantly more weight compared to others. We found that type II achalasia patients are most likely and type III achalasia are least likely to have weight loss compared to type I achalasia. Given that no other demographic/physiologic parameters predicted weight loss, the role of underlying inflammatory cascade, or lack of dietary adaptation in achalasia phenotypes deserves special attention in research and clinical practice. Notes Disclosures and Conflicts of Interest: The authors declare that they have no conflict of interest. Specific author contributions: Study concept and design: Dhyanesh Patel, Michael Vaezi; Acquisition of data: Dhyanesh Patel, Rishi Naik, Tina Higginbotham, Michael Vaezi; Analysis and interpretation of data: Dhyanesh Patel, Michael Vaezi; Drafting of the manuscript: Dhyanesh Patel; Analysis of the data: James Slaughter; Study concept: Heidi Silver; Critical revisions of the manuscript: Heidi Silver, Michael Vaezi; Study supervision: Michael Vaezi. References 1 Farrukh A , DeCaestecker J , Mayberry J F . An epidemiological study of achalasia among the South Asian population of leicester, 1986–2005 . Dysphagia 2008 ; 23 : 161 – 4 . Google Scholar CrossRef Search ADS PubMed 2 Birgisson S , Richter J E . Achalasia in Iceland, 1952–2002: An epidemiologic study . Dig Dis Sci 2007 ; 52 : 1855 – 60 . Google Scholar CrossRef Search ADS PubMed 3 Sadowski D C , Ackah F , Jiang B , Svenson L W . Achalasia: incidence, prevalence and survival. A population-based study . Neurogastroenterol Motil 2010 ; 22 : e256 – 61 . Google Scholar CrossRef Search ADS PubMed 4 Enestvedt B K , Williams J L , Sonnenberg A . Epidemiology and practice patterns of achalasia in a large multi-centre database . Aliment Pharmacol Ther 2011 ; 33 : 1209 – 14 . Google Scholar CrossRef Search ADS PubMed 5 Kahrilas P J , Bredenoord A J , Fox M et al. The Chicago Classification of esophageal motility disorders, v3.0 . Neurogastroenterol Motil 2015 ; 27 : 160 – 74 . Google Scholar CrossRef Search ADS PubMed 6 Patel D A , Kim H P , Zifodya J S , Vaezi M F . Idiopathic (primary) achalasia: a review . Orphanet J Rare Dis 2015 ; 10 : 89 . Google Scholar CrossRef Search ADS PubMed 7 Vaezi M F , Richter J E . Current therapies for achalasia: comparison and efficacy . J Clin Gastroenterol 1998 ; 27 : 21 – 35 . Google Scholar CrossRef Search ADS PubMed 8 Fisichella P M , Raz D , Palazzo F , Niponmick I , Patti M G . Clinical, radiological, and manometric profile in 145 patients with untreated achalasia . World J Surg 2008 ; 32 : 1974 – 9 . Google Scholar CrossRef Search ADS PubMed 9 Sinan H , Tatum R P , Soares R V , Martin A V , Pellegrini C A , Oelschlager B K . Prevalence of respiratory symptoms in patients with achalasia . Dis Esophagus 2011 ; 24 : 224 – 8 . Google Scholar CrossRef Search ADS PubMed 10 Spechler S J , Souza R F , Rosenberg S J , Ruben R A , Goyal R K . Heartburn in patients with achalasia . Gut 1995 ; 37 : 305 – 8 . Google Scholar CrossRef Search ADS PubMed 11 Bredenoord A J , Fox M , Kahrilas P J et al. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography . Neurogastroenterol Motil 2012 ; 24 : 57 – 65 . Google Scholar CrossRef Search ADS PubMed 12 Urbach D R , Tomlinson G A , Harnish J L , Martino R , Diamant N E . A measure of disease-specific health-related quality of life for achalasia . Am J Gastroenterol 2005 ; 100 : 1668 – 76 . Google Scholar CrossRef Search ADS PubMed 13 Chrystoja C C , Darling G E , Diamant N E et al. Achalasia-specific quality of life after pneumatic dilation or laparoscopic heller myotomy with partial fundoplication: a multicenter, randomized clinical trial . Am J Gastroenterol 2016 ; 111 : 1536 – 45 . Google Scholar CrossRef Search ADS PubMed 14 Patel D A , Sharda R , Hovis K L et al. Patient-reported outcome measures in dysphagia: a systematic review of instrument development and validation . Dis Esophagus 2017 ; 30 : 1 – 23 . Google Scholar CrossRef Search ADS 15 Newberry C A , Vajravelu R K , Lynch K L . Obese achalasia patients are at significant nutritional risk . Gastroenterology 2017; 152 : S197 . CrossRef Search ADS 16 Zifodya J , Kim H P , Silver H J , Slaughter J C , Higginbotham T , Vaezi M . Nutritional status of patients with untreated achalasia . Gastroenterology 2015 ; 148 : S-819-S-820 . Google Scholar CrossRef Search ADS 17 Furuzawa-Carballeda J , Aguilar-Leon D , Gamboa-Dominguez A et al. Achalasia–an autoimmune inflammatory disease: a cross-sectional study . J Immunol Res 2015 ; 2015 : 1 – 18 . Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Diseases of the EsophagusOxford University Press

Published: May 18, 2018

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off