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Background: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development. Methods: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia. Results: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media. Conclusions: In LES of patients with achalasia, hypophosphorylation of LC20, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) is standard treatment for achalasia. Gastroesophageal reflux disease (GERD) after POEM has been an important challenge since the early days of POEM implementation. The esophagogastric junction anti-reflux barrier consists of internal lower esophageal sphincter (LES) (i.e., intrinsic muscles of distal esophagus with sling fibers) and external LES (crural diaphragm and phrenoesophageal ligament anchors the distal esophagus to the crural diaphragm). During conventional POEM, the entire internal LES is unintentionally dissected. Preservation of the sling fiber may reduce post-POEM GERD, but its safety and effectiveness have been unclear. In this study, we investigated the safety and effectiveness of sling fiber preservation POEM (SP-POEM) for reducing severe post-procedural erosive esophagitis. Methods: We analyzed data of 236 patients who underwent POEM; of these, 203 patients underwent posterior myotomy without (Group 1) or with attempted (Group 2) sling fiber preservation. Group 1 (N = 79; sling fiber excision, N = 68) and Group 2 (N = 90; sling fiber preservation, N = 81) were compared. Post-procedural erosive esophagitis (Los Angeles classification) were assessed and the area (direction and length) of mucosal break was also investigated. The gastroesophageal flap valve was evaluated by Hill's classification. Results: Severe erosive esophagitis exceeding grade C (Los Angeles classification) occurred in 44.1% of patients (30/68) in Group 1 and in 18.5% of patients (15/81) in Group 2. In mapping of erosive esophagitis, mucosal breaks appeared widely in all directions in Group 1; they tended to be limited in Group 2 (especially in the 2 o'clock direction). Assessment using the Hill's classification showed that the gastroesophageal flap valve was preserved after SP-POEM. Conclusion: SP-POEM is safe and effective, with a success rate of 90%. The rate of severe erosive esophagitis can be decreased by preserving sling fibers. [ABSTRACT FROM AUTHOR]

Background: A new automated diagnostic program for high-resolution esophageal manometry (HREM) has been developed. This diagnostic program could detect locations of landmarks and could make final diagnoses automatically. However, the accuracy of the program is not known. The aim of this study was to evaluate the accuracy of the automated diagnostic program for HREM. Methods: A total of 445 studies were enrolled. An HREM system (Starlet®) was used, and esophageal motility was diagnosed using the Chicago classification v3.0. First, the locations of the upper esophageal sphincter, transition zone, lower esophageal sphincter, esophago-gastric junction, crural diaphragm and stomach were determined, and each swallow was checked manually. Then, the parameters of the Chicago classification were calculated using an analytic program of the Starlet, and diagnoses were made by three experts. Second, all study raw data were analyzed again by the automated diagnostic program. Diagnoses made by the program were compared to those made by experts to evaluate the accuracy of the diagnoses. Results: The new diagnostic program could identify the landmarks of each swallow, calculate the parameters and make a final diagnosis within 10 s. The diagnoses made by the automated diagnostic program were not matched to those made by experts in only 10 studies, and the overall accuracy of the new automated diagnostic program thus reached 97.8% (435/445). Conclusions: The new automated diagnostic program for HREM is clinically useful in terms of high diagnostic accuracy and time-saving. [ABSTRACT FROM AUTHOR]

Background: Achalasia is a rare esophageal motility disorder that is characterized by loss of peristalsis and failure of relaxation of the lower esophageal sphincter (LES), particularly during swallowing. This review focuses on the diagnosis of esophageal motility disorders as defined by the Chicago Classification ver 3.0, and presents management options with regard to per-oral endoscopic myotomy (POEM) as the treatment of choice.Methods: A concise review of literature was performed for articles related to the management of achalasia, and this was contrasted with our institution's current practice.Results: Achalasia is still incompletely understood, and management is focused on establishing a proper diagnosis, and relieving the obstructive symptoms.Conclusions: Achalasia should be considered when dysphagia is present, and not otherwise caused by an obstruction or inflammation, and when criteria is met as per the Chicago Classification ver 3.0. Lowering LES tone and disruption of LES can be accomplished by various methods, most notably pneumatic balloon dilatation and surgical myotomy. POEM has been gaining momentum as a first line therapy for achalasia symptoms, and can be considered an important tool for motility disorders of the esophagus. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Endoscopic balloon dilatation and laparoscopic myotomy are established treatments for achalasia. Recently, a new endoscopic technique for complete myotomy was described. Herein, we report the results of the first prospective trial of peroral endoscopic myotomy (POEM) in Europe.METHODS:POEM was performed under general anesthesia in 16 patients (male:female (12:4), mean age 45 years, range 26-76). The primary outcome was symptom relief at 3 months, defined as an Eckhard score ≤3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM.RESULTS:A 3-month follow-up was completed for all patients. Treatment success (Eckhard score ≤3) was achieved in 94% of cases (mean score pre- vs. post-treatment (8.8 vs. 1.4); P<0.001). Mean LES pressure was 27.2 mm Hg pre-treatment and 11.8 mm Hg post-treatment (P<0.001). No patient developed symptoms of gastro-esophageal reflux after treatment, but one patient was found to have an erosive lesion (LA grade A) on follow-up esophagogastroduodenoscopy. No patient required medication with proton pump inhibitors or antacids after POEM.CONCLUSIONS:POEM is a promising new treatment for achalasia resulting in short-term symptom relief in >90% of cases. Studies evaluating long-term efficacy and comparing POEM with established treatments have been initiated. [ABSTRACT FROM AUTHOR]