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Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results: DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1β and DOK1, IL-1β and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1β expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder. [ABSTRACT FROM AUTHOR]

Objectives: The endoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool used to evaluate lower esophageal sphincter (LES) function. EPSIS allows the measurement of intragastric pressure (IGP) during gastric insufflation through esophagogastroduodenoscopy (EGD) and records its pressure waveform. This study aimed to assess the usefulness and applicability of EPSIS as an adjunct diagnostic modality for achalasia. Methods: This case–control study was conducted using a database of patients who underwent EGD, barium swallow (BS), high‐resolution manometry (HRM), and EPSIS between January 2022 and December 2022. The achalasia (experimental) group (n = 35) consisted of patients with a definitive diagnosis of achalasia. The control group (n = 34) consisted of patients with no abnormalities in EGD, BS, or HRM and no abnormal acid reflux confirmed with 24‐h pH‐impedance monitoring. EPSIS findings were compared between the two groups and characterized by the waveform pattern (uphill or flat), maximum IGP (IGP‐Max), pressure difference, and the gradient of the waveform. Results: All patients in the achalasia group showed an uphill pattern, in contrast to 21 patients (61.8%) in the control group. IGP‐Max demonstrated the best diagnostic accuracy for achalasia, with a cut‐off value of 15.8 mmHg (100% sensitivity, 58.8% specificity, and area under the curve [AUC] 0.78). The pressure gradient also demonstrated good diagnostic accuracy, with a cut‐off value of 0.40 mmHg/s (80% sensitivity, 61.8% specificity, and AUC 0.76). Conclusion: This study demonstrated that EPSIS can be applied as a diagnostic modality in patients with achalasia. [ABSTRACT FROM AUTHOR]

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]

Endoscopic balloon dilatation is an established treatment for benign gastrointestinal strictures. In order to dilatate safely, it is necessary to dilatate gradually and preferably under direct endoscopic visualization. However, it is currently difficult to achieve dilatation widths of 20–30 mm with commercial products and of over 30‐mm with endoscopic visualization. Therefore, a safe and innovative application technique is needed for patients who need these 20‐mm or greater dilatation widths. We have developed two methods that enable more than 20‐mm dilatation under direct visualization. (i) Single‐barrel method: an endoscopic balloon dilatation catheter was fixed with grasping forceps at the tip of the endoscope and carried into the stomach. The balloon catheter was released from the endoscope to create a retroflexed view. The endoscope and balloon were positioned adjacent to each other at the gastric cardia. The balloon was inflated gradually and the esophagogastric junction was dilatated under direct visualization. (ii) Double‐barrel method: the same procedure was repeated with two balloons. Theoretically, we achieved a dilatation of >30‐mm in diameter. These modified methods may be helpful for esophagogastric junction strictures, such as esophageal achalasia (serving as an initial endoscopic balloon dilatation prior to using a 30‐mm achalasia balloon), or for functional strictures after Nissen fundoplication. In conclusion, our simple, modified method enables safe and gradual dilatation under direct endoscopic visualization. Additionally, combination of the sizes of one or two balloons can achieve various widths of dilatation. [ABSTRACT FROM AUTHOR]

Esophageal achalasia is a rare chronic debilitating disorder characterized by incomplete lower esophageal sphincter (LES) relaxation and abnormal peristalsis as a result of myenteric plexus degeneration. Although complex interactions among immunity, viruses and inheritance have been proposed, its causes remain unknown. MicroRNAs (miRs) play crucial roles in the regulation of gene expression during pathophysiological processes. Certain viruses such as herpes simplex virus (HSV) encode miRs derived from their own genomes. To determine the underlying relationship of miRNAs to achalasia, we analyzed the expression profile of miRNAs using biopsy samples obtained from LES muscle during peroral endoscopic myotomy. Peroral LES muscle biopsy sampling was uneventfully carried out in our case series of achalasia. Control biopsy tissues were also obtained from LES muscle of patients without symptoms relating to abnormal esophageal motility whose esophagogastric junction was surgically excised. RNA was extracted from biopsy specimens and analyzed using a microarray. Differentially expressed miRNAs in achalasia patients compared to controls were identified and analyzed using reverse transcription quantitative polymerase chain reaction. HSV‐1‐derived hsv1‐miR‐H1 and ‐H18 was significantly overexpressed in achalasia cohorts compared to controls. Correlations between the expression levels of viral miR and the patients' clinical characteristics including achalasia morphological type, dilatation grading, and disease duration were not identified. Further studies with a larger sample size are needed to replicate the current heuristic identification of neurotropic viral miRs and unravel their functional significance in order to provide new insight linking neurodegenerative etiology in achalasia. [ABSTRACT FROM AUTHOR]

Abstract: Achalasia cardia (AC) is a frequently encountered motility disorder of the esophagus resulting from an irreversible degeneration of neurons. Treatment modalities are palliative in nature, and there is no curative treatment available for AC as of now. Significant advancements have been made in the management of AC over last decade. The introduction of high resolution manometry and per‐oral endoscopic myotomy (POEM) has strengthened the diagnostic and therapeutic armamentarium of AC. High resolution manometry allows for the characterization of the type of achalasia, which in turn has important therapeutic implications. The endoscopic management of AC has been reinforced with the introduction of POEM that has been found to be highly effective and safe in palliating the symptoms in short‐term to mid‐term follow‐up studies. POEM is less invasive than Heller's myotomy and provides the endoscopist with the opportunity of adjusting the length and orientation of esophageal myotomy according to the type of AC. The management of achalasia needs to be tailored for each patient, and the role of pneumatic balloon dilatation, POEM, or Heller's myotomy needs to be revisited. In this review, we discuss the important aspects of diagnosis as well as management of AC. The statements presented in the manuscript reflect the cumulative efforts of an expert consensus group. [ABSTRACT FROM AUTHOR]

Background and study aims: Detecting esophageal achalasia remains a challenge. We describe the diagnostic utility of corona appearance, a novel endoscopic finding specific to esophageal achalasia. Patients and methods: Corona appearance and seven conventional endoscopic findings were compared for sensitivity and consistency (κ-value) among 53 untreated esophageal achalasia patients who underwent endoscopy at our hospital. The following criteria had to be met during lower esophageal sphincter examination using the attached ST Hood short-type for positive corona appearance: A) congestion inside the hood, B) ischemic change around the hood, and C) palisade vessels outside the hood. Results: Corona appearance had the highest sensitivity (91%; κ-value, 0.71). Other findings in descending order of sensitivity included 1) functional stenosis of the esophagogastric junction (EGJ; 86%; κ-value, 0.58), 2) mucosal thickening and whitish change (71%; κ-value, 0.27), 3) abnormal contraction of the esophageal body (59%; κ-value, 0.32), 4) dilation of the esophageal lumen (58%; κ-value, 0.53), 5) liquid remnant (57%; κ-value, 0.51), 6) Wrapping around EGJ (49%; κ-value, 0.14), and 7) food remnant (30%; κ-value, 0.88). Even in 22 patients with poor (grade 1) intraluminal expansion, corona appearance had highest sensitivity (88%) compared to other endoscopic findings (κ-value, 0.63). Conclusions: Among endoscopic findings using a ST Hood short-type to diagnose esophageal achalasia, corona appearance had the highest sensitivity and its consistency (κ-value) among endoscopists was substantial compared to other endoscopic findings. Similar results were obtained for esophageal achalasia cases with poor expansion. Endoscopic diagnosis of esophageal achalasia with hood attached is useful. [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]

Esophageal achalasia is a benign esophageal motility disorder resulting from an impaired relaxation of the lower esophageal sphincter. The principles of treatment involve disruption of the sphincter at the esophagogastric junction. Treatment techniques include balloon dilatation, botulinum toxin injection, and surgical myotomy. In 2008, per-oral endoscopic myotomy ( POEM) was introduced by Inoue et al. as an endoscopic myotomy with no skin incision. The procedure has been well accepted and widely applied owing to its minimal invasiveness and high cure rates. Moreover, there have been discussions on wider indications for POEM and new technical developments have been reported. The present article reviews the historical background and present status of POEM, as well as future prospects for its application in the treatment of esophageal achalasia. [ABSTRACT FROM AUTHOR]

Background: Surgical Heller myotomy has high rates of successful long-term results, but failed cases still remain. Moreover, the treatment strategy in patients with surgical myotomy failure is controversial. Recently, peroral endscopic myotomy (POEM) was reported to be efficient and safe in primary treatment of achalasia. In this study, we aimed to evaluate the efficacy and safety of POEM for surgical myotomy failure as a rescue second-line treatment, and we discuss the treatment options adapted in achalasia recurrence. Study Design: A total of 315 consecutive achalasia patients received POEM from September 2008 to December 2012 in our hospital. Eleven (3.5%) patients who had persistent or recurrent achalasia and had received surgical myotomy as a first-line treatment from other hospitals were included in this study. Patient background, barium swallow studies, esophagogastroduodenoscopy (EGD), manometry, and symptom scores were prospectively evaluated. In principle, all patients in whom surgical myotomy failed received pneumatic balloon dilatation (PBD) as the first line “rescue” treatment, and only if PBD failed were patients considered for rescue POEM. Results: The PBD alone was effective in 1 patient, and in the remaining 10 patients, rescue POEM was performed successfully without complications. Three months after rescue POEM, significant reduction in lower esophageal sphincter (LES) resting pressures (22.1 ± 6.6 mmHg vs 10.9 ± 4.5 mmHg, p < 0.01) and Eckardt symptom scores (6.5 ± 1.3 vs 1.1 ± 1.3, p < 0.001) were observed. Conclusions: Short-term results of POEM for failed surgical myotomy were excellent. Long-term results are awaited. [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]