Incidence and risk factors of reflux esophagitis after peroral endoscopic myotomy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an effective and safe treatment for achalasia, but often leads to posttreatment gastroesophageal reflux disease. The aim of this study was to examine the incidence and severity of reflux esophagitis after POEM and to identify associated predictive factors. METHODS: Patients who underwent POEM between August 2011 and December 2022 were included. Multivariate logistic regression was used to assess predictive factors for reflux esophagitis after POEM. KEY RESULTS: In total, 252 patients were included; of which, 46% were female and age ranged between 18 and 87 years. Reflux esophagitis within 1 year after POEM was observed in 131 patients (52%), which was severe in 29 patients (LA grade C/D, 12%). Length of full-thickness myotomy (cm; OR 1.11, 95% CI 1.02-1.21), Eckardt scores before POEM (OR 0.84, 95% CI 0.74-0.96), previous pneumatic dilation (OR 0.51, 95% CI 0.29-0.91), and previous laparoscopic Heller myotomy (LHM; OR 0.44, 95% CI 0.23-0.86) were associated with reflux esophagitis after POEM. Alcohol use (none vs > 7 units per week; OR 3.51, 95% CI 1.35-9.11) and overweight (BMI ≥25 kg/m2; OR 2.67, 95% CI 1.17-6.09) were positive predictive factors and previous LHM (OR 0.13, 95% CI 0.02-0.95) was a negative predictive factor for severe reflux esophagitis after POEM (LA grade C/D). CONCLUSION: About half of the patients develop reflux esophagitis after POEM and 12% is graded as severe. Recognizing predictive factors of reflux esophagitis after POEM treatment leads to better patient selection before POEM and provides an opportunity to take preventive measures or start preemptive treatment.

Global trends in incidence and prevalence of achalasia, 1925-2021: A systematic review and meta-analysis.

BACKGROUND: Achalasia poses a significant socioeconomic burden, yet global trends remain undocumented. This study aims to describe the worldwide trends in the incidence and prevalence of achalasia from 1925 to 2021 and explore their correlation with various factors through a comprehensive systematic review. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases from inception to 30 June 2023, to identify studies reporting the incidence or prevalence of achalasia in the general population. This study utilized pooled estimates with 95% confidence intervals (CI) to estimate the incidence and prevalence of achalasia, and conducted various subgroup analyses. RESULTS: A total of 26 eligible studies covering approximately 269 million participants and 20,873 patients from 14 countries across five continents were included. Global pooled incidence and prevalence of achalasia were estimated to be 0.78 cases per 100,000 person-years (95% CI, 0.64-0.93; number of studies, 26; sample population, 269,315,171) and 10.82 cases per 100,000 person-years (95% CI, 8.15-13.48; number of studies, 14; sample population, 192,176,076), respectively. The incidence of achalasia was higher in Oceania (than Asia and Africa) and in adults (than children) after the introduction of the Chicago classification. Prevalence followed a similar pattern. The pooled incidence of achalasia showed an overall upward trend from 1925 to 2021 (1925-1999; 0.40 [0.32-0.49] vs. 2018-2021; 1.64 [1.33-1.95] cases per 100,000 person-years). CONCLUSIONS: The incidence and prevalence of achalasia have notably increased, particularly with advancements in diagnosis, and show significant variation worldwide, despite the large heterogeneity within the sample population. Further studies are necessary to accurately assess the global incidence and prevalence of achalasia.

Incidence, prevalence and clinical management of achalasia since the introduction of high-resolution manometry in Western Australia.

BACKGROUND: Epidemiological studies in achalasia and its clinical management in Australia are limited. AIMS: To determine the prevalence and trends in incidence rates and describe the types of treatment stratified by subtypes of achalasia. METHODS: A retrospective observational study was conducted at a single site that offers a state-wide high-resolution manometry (HRM) service in Western Australia (WA). Patients (aged ≥ 18 years) newly diagnosed with achalasia based on HRM findings between 2012 and 2021 were extracted from the HRM database. The crude incidence rate and age-standardised incidence rate (ASIR) along with the 2021-point prevalence were calculated. Trends were assessed by the Kendall τb test. The patients' initial and subsequent treatment modalities were described. RESULTS: A total of 296 new cases were identified, and the median age at diagnosis was 56 years. The patient's median age, sex and year of the first treatment did not vary significantly with the subtypes. The lowest and highest ASIR (cases/100 000 person-years) were 0.8 in 2012 and 2.1 in 2021, respectively. Only type 2 achalasia showed a significant increasing trend (P = 0.009). The 2021-point prevalence was 16.9 cases/100 000 people and increased with age. Pneumatic balloon dilatation (PBD) was the most common treatment for types 1 and 2, while laparoscopic Heller myotomy was most common for type 3. Peroral endoscopic myotomy (POEM) has become common in the past 5 years. CONCLUSION: The ASIR of type 2 achalasia significantly increased in WA. PBD was most commonly performed, although peroral endoscopic myotomy has recently increased as a preferred treatment option.

Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Using the Nationwide Veterans Affairs Achalasia Cohort.

INTRODUCTION: Achalasia is a postulated risk factor of esophageal cancer (EC); however, EC-associated risk in achalasia is understudied. We aimed to evaluate EC risk among individuals within the nationwide Veterans Affairs Achalasia Cohort. METHODS: We conducted a matched cohort study among US veterans aged 18 years or older from 1999 to 2019. Individuals with achalasia were age matched and sex matched 1:4 to individuals without achalasia. Follow-up continued from study entry until diagnosis with incident/fatal EC (primary outcome), death from non-EC-related causes, or end of the study follow-up (December 31, 2019). Association between achalasia and EC risk was examined using Cox regression models. RESULTS: We included 9,315 individuals in the analytic cohort (median age 55 years; 92% male): 1,863 with achalasia matched to 7,452 without achalasia. During a median 5.5 years of follow-up, 17 EC occurred (3 esophageal adenocarcinoma, 12 squamous cell carcinoma, and 2 unknown type) among individuals with achalasia, compared with 15 EC (11 esophageal adenocarcinoma, 1 squamous cell carcinoma, and 3 unknown type) among those without achalasia. EC incidence for those with achalasia was 1.4 per 1,000 person-years, and the median time from achalasia diagnosis to EC development was 3.0 years (Q1-Q3: 1.3-9.1). Individuals with achalasia had higher cumulative EC incidence at 5, 10, and 15 years of follow-up compared with individuals without achalasia, and EC risk was 5-fold higher (hazard ratio 4.6, 95% confidence interval: 2.3-9.2). DISCUSSION: Based on substantial EC risk, individuals with achalasia may benefit from a high index of suspicion and endoscopic surveillance for EC.

Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders.

BACKGROUND & AIMS: Achalasia has been assumed to be an autoimmune disease targeting esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes might be allergy-driven, caused by a form of eosinophilic esophagitis (EoE) in which activated eosinophils and/or mast cells infiltrating esophageal muscle release products that disrupt motility and damage myenteric neurons. To seek epidemiologic support for this hypothesis, we identified patients with achalasia in the Utah Population Database, and explored their frequency of having EoE and other allergic disorders. METHODS: We used International Classification of Diseases codes to identify patients with achalasia and allergic disorders including EoE, asthma, atopic dermatitis, contact dermatitis, allergic rhinitis, allergic conjunctivitis, hives/urticaria, and anaphylaxis. We calculated relative risk (RR) for each allergic disorder by comparing the number observed in patients with achalasia with the expected number in individuals matched for birthyear and sex, and we performed subanalyses for patients age ≤40 versus age >40 years. RESULTS: Among 844 patients with achalasia identified (55% female; median age at diagnosis, 58 years), 402 (47.6%) had ≥1 allergic disorder. Fifty-five patients with achalasia (6.5%) had EoE (1.67 EoE cases expected), for a RR of 32.9 (95% confidence interval, 24.8-42.8; P < .001). In 208 patients with achalasia age ≤40 years, the RR for EoE was 69.6 (95% confidence interval, 46.6-100.0; P < .001). RR also was increased significantly for all other allergic disorders evaluated (all greater than 3-fold higher than population rates). CONCLUSIONS: Achalasia is strongly associated with EoE and other allergic disorders. These data support the hypothesis that achalasia sometimes might have an allergic etiology.

PREVALENCE OF COMORBIDITIES IN PATIENTS WITH CHAGASIC MEGAESOPHAGUS.

•The study investigated the prevalence of certain comorbidities in patients with Chagas megaoesophagus compared to those without the condition, aiming to determine whether it serves as a protective or risk factor. •In the general group (546 patients), the three most prevalent comorbidities were hypertension (44.3%), dyslipidaemia (17.8%), and heart failure (15.2%). •In the older group (248 patients), similar to that in the general group, the most prevalent comorbidities were hypertension, dyslipidaemia, and heart failure. •The lower prevalence of diabetes mellitus and Alzheimer's disease in the patients with Chagas megaoesophagus suggests the association of enteric nervous system denervation and requires further investigation. Objective - This study aimed to evaluate the prevalence of some epidemiologically important comorbidities in patients with Chagas megaoesophagus in relation to the population without megaoesophagus, and whether this condition would be a protective or a risk factor for the conditions analysed. Methods - This observational descriptive study collected data from the medical records of patients with a previous diagnosis of megaoesophagus (timing: from 2005 to 2020). The patients were divided by age into a general (all ages) and an older group (aged 60 years or more). Associations were searched for four main areas/systems/involvements: cardiovascular, respiratory, endocrine and neurological. Results - The general group included 546 patients and the older group included 248 patients. As for the prevalence of comorbidities in the general group, the three most prevalent diseases were hypertension, with 44.3% (CI95%: 40.21-48.51%); dyslipidaemia, with 17.8% (CI95%: 14.79-21.19%); and heart failure, with 15.2% (CI95%: 12.43-18.45%). Similar to that in the general group, the most prevalent comorbidities in the group of older patients were hypertension, dyslipidaemia, and heart failure. Conclusion - Systemic arterial hypertension, dyslipidaemia, and heart failure were the most prevalent comorbidities in this population. The lower prevalence of diabetes mellitus and Alzheimer's disease suggests the association of enteric nervous system denervation and requires further investigation.

Can esophageal symptoms be associated with sleep disorders in esophageal rare diseases?. A prospective case-control study across achalasia, eosinophilic esophagitis and gastroesophageal reflux disease.

BACKGROUND: The association between sleep disorders and gastroesophageal reflux disease (GERD) has been the subject of several studies; however, quality of sleep has been under investigated in adult patients with eosinophilic esophagitis (EoE) and achalasia (Ach). This study aims to evaluate the prevalence of sleep disturbances in patients with EoE and Ach compared to GERD patients and their associations with esophageal symptoms. METHODS: Thirty Ach patients and 20 EoE patients were consecutively enrolled and compared to a control group of 46 GERD patients. All patients underwent a standardized questionnaire investigating the intensity-frequency scores (from 0 to 6) of esophageal symptoms, Pittsburgh Sleep Quality Index (PSQI) questionnaire to assess sleep quality, a SF-36 survey to investigate health-related quality of life (both physical (PCS) and mental (MCS) component scales), Beck Depression Inventory-II (BDI-II) and State Trait Anxiety Inventory (STAI) to assess the presence of depression and anxiety. RESULTS: The prevalence of sleep disturbances was 66.7% in Ach, 50% in EoE, and 60% in GERD patients (P=0.5). PCS and MCS significantly correlated with depression and anxiety levels. Ach patients showed significantly higher intensity-frequency scores of dysphagia for solids (Scheffè P<0.001) and liquids (Scheffè P<0.001) than EoE and GERD patients. No differences were found in the intensity-frequency scores of the esophageal symptoms among the three groups. There was a significant association between worst quality of sleep and higher intensity-frequency scores of regurgitation. CONCLUSIONS: Sleep disturbances are common with Ach and EoE, similar to GERD patients. Moreover, there is a significant association between regurgitation, a typical GERD symptom, and poor quality of sleep, independent from diagnosis.

Psychological burden of achalasia: Patients' screening rates of depression and anxiety and sex differences.

OBJECTIVE: Achalasia is associated with reduced quality of life in affected patients but research regarding the psychological burden of achalasia in terms of depression and anxiety is scarce. The current study therefore aims to investigate rates of depression and anxiety in patients with achalasia in relation to prevalence rates in the general population and to examine the extent to which achalasia-related characteristics (time since diagnosis, symptom load, achalasia-related quality of life, treatment history) predict symptoms of depression and anxiety. METHODS: Using validated screening instruments, rates of depression and anxiety were assessed in a cross-sectional survey of a sample of 993 patients with achalasia and compared to population controls stratified by age and sex. Associations between depression and anxiety and achalasia-related factors were explored using linear regression. RESULTS: Compared to population controls, screening rates of female patients with achalasia were between 3.04 (p = .004) and 7.87 (p < .001) times higher for depression and 3.10 (p < .001) times higher for anxiety, respectively. No significant differences were found for male patients with achalasia. Both achalasia-related quality of life and symptom load were independently related to impaired mental health. CONCLUSION: Women appear to be specifically affected by the psychological burden of achalasia, pointing to sex-specific or gendered experiences of the disease. In addition to symptom reduction, psychological support may prove beneficial for improving the well-being of patients with achalasia.

Incidence, Morbidity, and Mortality of Achalasia: A Nationwide, Population-Based Cohort Study in South Korea.

Background/Aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). Conclusions: In this nationwide study, achalasia was associated with increased risk of mortality. Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.

Influence of Anxiety and Depression on the Symptoms of Achalasia Patients: A Retrospective Cohort Study in China during COVID-19.

BACKGROUND: Idiopathic achalasia (AC) may be affected by anxiety and/or depression; however, reliable evidence is still lacking. The present retrospective cohort study aimed to explore the influence of psycho-mental factors on the severity of AC. METHODS: All patients in the AC database of the Tianjin Medical University General Hospital from 2012 to 2020 were divided into two subgroups, intervention (n = 202) and medication (n = 84), according to previous treatments. Healthy people (n = 300) who underwent gastrointestinal endoscopy comprised the control group. The severity of symptoms and the anxiety and depression score of AC patients and controls were monitored by telephone and compared before and during COVID-19. In addition, the factors of AC symptoms during the COVID-19 were discussed by multiple linear regression. RESULTS: During COVID-19, the anxiety and depression levels of AC patients and healthy individuals were deteriorated. For AC patients, before and after COVID-19, symptoms, anxiety, and depression scores in the medication group were more serious than those in the intervention group. Furthermore, previous therapy, depression, and gender were found to be significantly related to the severity of AC symptoms during COVID-19. CONCLUSIONS: The outbreak of COVID-19 made AC patients and healthy people anxious and depressed. Depression rather than anxiety might worsen the AC symptoms. Interventional therapy might protect AC patients against psychological abnormalities during COVID-19.

Development and Validation of a National US Achalasia Cohort: The Veterans Affairs Achalasia Cohort (VA-AC).

BACKGROUND & AIMS: Achalasia is an esophageal motility disorder associated with significant morbidity, yet achalasia-associated risk factors and outcomes are not well-characterized. Our aim was to establish a national cohort of individuals with achalasia, utilizing Veterans Health Administration (VHA) data. METHODS: We iteratively developed combinations of International Classification of Diseases and Current Procedural Terminology code algorithms to validate an approach for identifying achalasia cases. We assessed algorithm accuracy for achalasia diagnosis through manual chart review of candidate achalasia cases and candidate non-achalasia controls. The prespecified end point chosen to establish algorithm performance success was achieving a 1-sided 95% confidence lower bound for a positive predictive value >85% for a random sample of 100 candidate achalasia cases. Once adequate performance was validated, we queried national VHA data to establish and characterize a cohort of individuals diagnosed with achalasia between 1999 and 2020. RESULTS: Three rounds of algorithm modification and validation were conducted to achieve the prespecified performance endpoint. In the final round, a combination of 3 or more International Classification of Diseases codes for achalasia in the subject's lifetime and a Current Procedural Terminology code for esophageal manometry achieved an observed 94% positive predictive value (1-sided 95% confidence lower bound of 88.5%) for identifying achalasia. Applying the algorithm to national VHA data identified a cohort of 2100 individuals with achalasia, with a median age 65 years and who were 93% male. CONCLUSIONS: Using a rigorous validation approach, we established a national cohort of 2100 individuals with achalasia within the VHA, one of the largest established to date. This cohort can be utilized to study risk factors for achalasia and outcomes over time.

Risk factors and long-term course of gastroesophageal reflux disease after peroral endoscopic myotomy: A large-scale multicenter cohort study in Japan.

BACKGROUND : Gastroesophageal reflux disease (GERD) and reflux esophagitis remain problems after peroral endoscopic myotomy (POEM). This study aimed to elucidate the risk factors and long-term course of reflux esophagitis and symptomatic GERD after POEM. METHODS : This multicenter cohort study involved 14 high volume centers. Overall, 2905 patients with achalasia-related esophageal motility disorders treated with POEM were analyzed for reflux esophagitis, severe reflux esophagitis (Los Angeles classification C or D), and symptomatic GERD. RESULTS : Reflux esophagitis was diagnosed in 1886 patients (64.9 %). Age ≥ 65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy > 10 cm (RR 1.12), and gastric myotomy > 2 cm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5 %). Age ≥ 65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥ 7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy > 10 cm (RR 1.59) were factors associated with severe reflux esophagitis. Proton pump inhibitors (PPIs) were more effective for reflux esophagitis at 5-year follow-up (P = 0.03) than after 1 year (P = 0.08). Symptomatic GERD was present in 458 patients (15.9 %). Symptom duration ≥ 10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥ 26 (RR 0.60), and posterior myotomy (RR 0.80) were associated with symptomatic GERD. The incidence of symptomatic GERD was lower at 5-year follow-up compared with that after 1 year (P = 0.04), particularly in PPI users (P < 0.001). CONCLUSIONS : The incidence of severe reflux esophagitis was low after POEM, but excessive myotomy for older patients with previous treatments should be avoided. Early phase symptomatic GERD is non-acid reflux dependent and the natural course is favorable, basically supporting conservative treatment.

Autoimmune and viral risk factors are associated with achalasia: A case-control study.

BACKGROUND: Achalasia is a rare esophageal motility disorder of uncertain etiology. While past studies have indicated that autoimmune conditions and viral infections may be associated with development of achalasia, these associations are yet to be examined in large, population-based studies. METHODS: A matched case-control study was performed using administrative claim data from the IBM MarketScan Commercial Claims and Encounters Database between 2000 and 2019. A history of selected autoimmune conditions and viral infections was assessed using past medical claims. Multivariable conditional logistic regression was used to account for the matched nature of the study design and further control for confounding by demographic and clinical characteristics when reporting adjusted odds ratios (aORs). KEY RESULTS: Among 6769 cases and 27,076 controls, presence of any of the autoimmune conditions studied was associated with increased odds of achalasia (aOR = 1.26, 95% CI: 1.11, 1.42). Scleroderma or systemic sclerosis (aOR = 8.13, 95% CI: 3.34, 19.80) and Addison's disease (aOR = 3.83, 95% CI: 1.83, 8.04) had the strongest associations with achalasia. Presence of any of the viral infections studied was also associated with an increased risk of achalasia (aOR = 1.58, 95% CI: 1.23, 2.01). Varicella zoster virus (aOR = 3.84, 95% CI: 1.94, 7.62) and human papillomavirus (aOR = 1.77, 95% CI: 1.15, 2.73) both had strong relationships with achalasia. CONCLUSIONS AND INFERENCES: These findings suggest that achalasia may have autoimmune and viral components contributing to its etiology. Future mechanistic studies could target specific diseases and agents highlighted by this research.

The incidence of reintervention and reoperation following Heller myotomy across multiple indications.

INTRODUCTION: Achalasia is a debilitating primary esophageal motility disorder. Heller myotomy (HM) is a first-line therapy for the treatment of achalasia patients who have failed other modalities. Other indications for HM include diverticulum, diffuse esophageal spasm, and esophageal strictures. However, long-term outcomes of HM are unclear. This study aims to assess incidence of reintervention, either endoscopically or through minimally invasive or resectional procedures, in patients who underwent HM in New York State. METHODS: The Statewide Planning and Research Cooperative System (SPARCS) administrative longitudinal database identified 1817 adult patients who underwent HM between 2000 and 2008 for achalasia, esophageal diverticulum, diffuse esophageal spasm, and esophageal strictures, based on ICD-9 and CPT codes. Through the use of unique identifiers, patients requiring reintervention were tracked up to 2016 (for at least 8 years follow-up). Primary outcome was incidence of subsequent procedures following HM. Secondary outcomes were time to reintervention and risk factors for reintervention. RESULTS: Of the 1817 patients who underwent HM, 320 (17.6%) required subsequent intervention. Of the 320 patients, 234 (73.1%) underwent endoscopic reinterventions, 54 (16.9%) underwent minimally invasive procedures, and 32 (10%) underwent resectional procedures as their initial revisional intervention. Of the 234 patients who underwent endoscopic reintervention as their initial revisional procedure, only 40 (16.8%) required subsequent surgical procedures. Over a mean follow-up of 7.0 years, the mean time to a subsequent procedure was 4.3 ± 3.74 years. Reintervention rates after 10 years following HM for achalasia, diverticulum ,and other indication were 24.4%, 12.6%, and 37%, respectively. CONCLUSION: The majority of HM reinterventions were managed solely by endoscopic procedures (60.6%). Heller myotomy remains an excellent procedure to prevent surgical reintervention for achalasia and diverticulum.

Epidemiologic and Economic Burden of Achalasia in the United States.

BACKGROUND & AIMS: Achalasia is a debilitating chronic condition of the esophagus. Currently there are no national estimates on the epidemiologic and economic burden of disease. We sought to estimate trends in incidence and prevalence of achalasia by age-sex strata, and to estimate the total direct medical costs attributed to achalasia in the United States. METHODS: We conducted a cohort study using two administrative claims databases: IBM MarketScan Commercial Claims and Encounters database (2001-2018; age <65) and a 20% sample of nationwide Medicare enrollment and claims (2007-2015; age ≥65). Point prevalence was calculated on the first day of each calendar year; the incidence rate captured new cases developed in the ensuing year. Utilization rates of healthcare services and procedures were reported. Mean costs per patient were calculated and standardized to the corresponding U.S. Census Bureau population data to derive achalasia-specific total direct medical costs. RESULTS: The crude prevalence of achalasia per 100,000 persons was 18.0 (95% CI, 17.4, 18.7) in MarketScan and 162.1 (95% CI, 157.6, 166.6) in Medicare. The crude incidence rate per 100,000 person-years was 10.5 (95% CI, 9.9, 11.1) in MarketScan and 26.0 (95% CI, 24.9, 27.2) in Medicare. Incidence and prevalence increased substantially over time in the Medicare cohort, and increased with more advanced age in both cohorts. Utilization of achalasia-specific healthcare was high; national estimates of total direct medical costs exceeded $408 million in 2018. CONCLUSIONS: Achalasia has a higher epidemiologic and economic burden in the US than previously suggested, with diagnosis particularly increasing in older patients.

Heller myotomy versus Heller myotomy with fundoplication in patients with achalasia: a systematic review and meta-analysis.

INTRODUCTION: Heller myotomy (HM) remains the gold standard procedure for achalasia. The addition of different types of fundoplication to HM has been debated in several studies. Given the contradictory reports, this meta-analysis was undertaken to compare different outcomes after HM and HM with fundoplication (HMF). METHODS: An electronic search was performed among five major databases (PubMed, Ovid, Scopus, Cochrane Library, Google Scholar) from inception to October 2019, identifying all randomised and non-randomised studies comparing HM with HMF. Two authors searched electronic databases using the keywords 'achalasia' AND 'dysphagia' AND 'gastroesophageal reflux' and all data were pooled for random-effects meta-analysis. The primary and secondary outcomes were gastroesophageal reflux and dysphagia, respectively. RESULTS: A total of six studies were included and involved 576 patients comparing HM and HMF. There was no statistically significant difference between gastroesophageal reflux in the HM vs HMF group (21.3% vs 22.9%, RR 1.32, 95% CI 0.60-2.88, p = 0.49). There was a slightly higher incidence of dysphagia observed in HM vs HMF (14.8% vs 10.8%, RR 1.54, 95% CI 0.98-2.41, p = 0.06). CONCLUSIONS: There was no statistically significant difference in long-term outcomes between a group of patients undergoing HM and a group who underwent HM with fundoplication.

Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). OBJECTIVE: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. METHODS: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. RESULTS: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics. CONCLUSION: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.

Robotic-assisted Heller Myotomy Is a Safe Operation.

BACKGROUND: Surgical myotomy is the best therapeutic option for patients with achalasia. The minimally invasive technique is considered to be the preferred method for many surgeons. Robotic-assisted laparoscopic myotomy has several advantages over conventional laparoscopic surgery. These benefits include more accurate incisions that may result in a lower rate of intra-operative complications. OBJECTIVES: To describe our technique of performing robotic-assisted Heller myotomy and to review the initial results of this procedure. METHODS: All patients undergoing robotic-assisted Heller myotomy for achalasia between the years 2012-2018 at Rabin Medical Center were retrospectively reviewed from our institutional prospective database. RESULTS: Thirty patients underwent robotic-assisted Heller myotomy for achalasia. Mean operative time was 77 minutes (range 47-109 minutes) including docking time of the robotic system. There were no cases of conversion to laparoscopic or open surgery. There were no cases of intra-operative perforation of the mucosa. None of the patients had postoperative morbidity or mortality. Good postoperative results were achieved in 25 patients. Four patients required additional intervention (3 had endoscopic dilatations and 1 with known preoperative endstage achalasia had undergone esophagectomy). One patient was lost to follow-up. CONCLUSIONS: Robotic-assisted Heller myotomy is a safe technique with a low incidence of intra-operative esophageal perforation compared to the laparoscopic approach. We believe that robotic-assisted surgery should be the procedure of choice to treat achalasia.

Esophageal achalasia diagnosed in people previously diagnosed with an eating disorder: Epidemiological study using record-linkage.

OBJECTIVE: Occasionally, patients with eating disorders have been subsequently diagnosed with esophageal achalasia. We sought to establish whether eating disorders and achalasia coexisted more often than expected by chance alone. METHOD: National record-linkage study of hospital inpatients in England, between 2001 and 2017. Use of Cox proportional hazards to compare the occurrence of achalasia in cohorts of people with or without anorexia nervosa (AN), and with or without bulimia nervosa (BN), with adjustment of the comparisons for such confounders as age, sex, and year of admission. RESULTS: There were 18,500 people in the AN cohort, 11,300 in the BN cohort, and 8.7 million in the comparison cohort. The Cox regression hazard ratio, comparing the AN cohort with the reference cohort, was 3.4 (95% confidence interval 1.8-6.3) and that in the BN cohort was 4.2 (2.2-8.2). DISCUSSION: AN and achalasia, and BN and achalasia, were diagnosed in the same individuals, more often than expected by chance. Clinicians should be aware of the possible associations with achalasia because the treatment of eating disorders and achalasia is different.

Acalasia y su relación con el cáncer esofágico / Esophageal acalasia and its relationship with esophageal cancer

Resumen La acalasia es un trastorno motor primario de la musculatura lisa esofágica que se caracteriza por disfagia, pseudorregurgitación y baja de peso. El tratamiento puede ser endoscópico o quirúrgico. Sólo se conocen los resultados a largo plazo de la cirugía, mientras que los endoscópicos tienen aún un seguimiento muy corto y no permiten sacar conclusiones valederas. La acalasia es una lesión que tiene una probabilidad significativamente mayor de desarrollar un cáncer esofágico, ya sea de tipo epidermoide, por inflamación crónica y retención de comida en el esófago, o un adenocarcinoma, secundario a reflujo gastroesofágico, que aparece posterior a cualquier tratamiento. Las publicaciones muestran que alrededor de 3% a 4% de los pacientes presentan a largo plazo, sobre 10 a 15 años postratamiento, el desarrollo de un cáncer avanzado del esófago. Se concluye que es indispensable un seguimiento clínico y endoscópico en forma rutinaria a estos pacientes.

Achalasia is a primary motor disorder of the esophageal smooth muscle characterized by dysphagia, pseudoregurgitation, and weight loss. Treatment can be endoscopic or surgical. The long-term results are only known from surgery, while endoscopic results still have a very short follow-up and do not allow us to draw valid conclusions. Achalasia is a lesión that has a significantly higher probability of developing esophageal cancer, whether of the epidermoid type, due to chronic inflammation and food retention in the esophagus, or an adenocarcinoma, secondary to gastroesophageal reflux, which appears after any treatment. Publications show that about 3 to 4% of patients present in time, about 10 to 15 years after treatment, the development of advanced cancer of the esophagus. It is concluded that clinical and endoscopic follow-up is essential in these patients on a routine basis.