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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: 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]

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]

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 and Aim: Absent contractility (AC) and ineffective esophageal motility (IEM) are esophageal hypomotility disorders diagnosed using high‐resolution manometry (HRM). Patient characteristics and disease course of these conditions and differential diagnosis between AC and achalasia are yet to be elucidated. Methods: A multicenter study involving 10 high‐volume hospitals was conducted. Starlet HRM findings were compared between AC and achalasia. Patient characteristics including underlying disorders and disease courses were analyzed in AC and IEM. Results: Fifty‐three patients with AC and 92 with IEM were diagnosed, while achalasia was diagnosed in 1784 patients using the Chicago classification v3.0 (CCv3.0). The cut‐off integrated relaxation pressure (IRP) value at 15.7 mmHg showed maximum sensitivity (0.80) and specificity (0.87) for differential diagnosis of AC from type I achalasia. While most ACs were based on systemic disorders such as scleroderma (34%) and neuromuscular diseases (8%), 23% were sporadic cases. The symptom severity of AC was not higher than that of IEM. Regarding the diagnosis of IEM, the more stringent CCv4.0 excluded 14.1% of IEM patients than the CCv3.0, although patient characteristics did not change. In patients with the hypomotile esophagus, concomitance of reflux esophagitis was associated with low distal contractile integral and IRP values. AC and IEM transferred between each other, paralleling with the underlying disease course, although no transition to achalasia was observed. Conclusion: A successful determination of the optimal cut‐off IRP value was achieved using the starlet HRM system to differentiate AC and achalasia. Follow‐up HRM is also useful for differentiating AC from achalasia. Symptom severity may depend on underlying diseases instead of hypomotility severity. [ABSTRACT FROM AUTHOR]

Objectives: Patients with esophageal motility disorders (EMDs) including achalasia after gastric surgery have not been thoroughly characterized. Furthermore, the efficacy of peroral endoscopic myotomy (POEM) in this population should be clarified. Methods: In this retrospective multicenter study of 3707 patients with EMDs, 31 patients (0.8%) had a history of gastric surgery. Patient characteristics and POEM efficacy were compared between patients with and without previous gastric surgery. Results: In patients with EMD after gastric surgery, age at EMD diagnosis was higher (72.0 years), male sex was predominant (90.3%), and the American Society of Anesthesiologists physical status score was higher (≥II, 48.4%). High‐resolution manometry (HRM) findings did not reveal significant differences. In patients who underwent gastric surgery, atrophic gastritis was common (80.6%), and gastric cancer was the primary surgical indication (32.3%). Distal gastrectomy was performed in 28 patients (90.3%). POEM was effective (3.3% adverse events; 100% treatment success). The incidence rates of reflux esophagitis (RE) and symptomatic gastroesophageal reflux disease (GERD) were 60.0% and 16.7%, respectively, without significant intergroup differences, and severe RE was not observed in the long‐term follow‐up. Extended gastric myotomy was a risk factor for RE. Conclusion: Patients with gastric surgery often present severe disease manifestations; the surgical indication is mainly gastric cancer. HRM findings can be similarly used for diagnosis in patients with and without gastric surgery. POEM maintains safety and efficacy with acceptable RE and symptomatic GERD rates. To prevent RE, extended myotomy should be avoided. [ABSTRACT FROM AUTHOR]

Objectives: Indications for peroral endoscopic myotomy (POEM) and endoscopic submucosal dissection (ESD) in patients with achalasia concomitant with esophageal carcinoma (EC) are unclear. This study aimed to clarify the role of POEM in cases of achalasia concomitant with EC and to elucidate the indications for ESD and efficient surveillance for EC. Methods: We conducted a multicenter cohort study at 14 hospitals in Japan, including 3707 cases of achalasia‐related esophageal motility disorders (EMDs). Factors contributing to EC risk, the characteristics of EC, and clinical outcomes of POEM/ESD were analyzed. Results: In patients undergoing POEM, screening and surveillance endoscopy throughout a 1‐year period resulted in diagnosis of 72.1% new EC cases. Of 62 patients with 123 ECs, 40.3% had multiple or metachronous lesions within 37.5 months. EC was predominantly observed in the middle thoracic esophagus (58.5%) and posteriorly (73.2%). POEM had comparable safety and efficacy in cases of concomitant EC even after ESD. Endoscopic en bloc resection was performed in 95.8% and 89.3% of ECs diagnosed before and after POEM, respectively (P = 0.351); however, ESD on the POEM‐line was impaired by fibrosis. Multivariate analysis revealed risk factors for EC, including regular alcohol consumption, a history of smoking, advanced age, and extended disease duration. Alcohol intake and smoking had a synergistic effect on EC development. Conclusions: Screening and surveillance of POEM help in detecting EC. ESD is feasible in achalasia, although on the POEM‐line is challenging. Surveillance endoscopy for EC is recommended for cases with specific risks and a history of ECs. [ABSTRACT FROM AUTHOR]

Geriatric patients with existing studies on the safety and efficacy of peroral endoscopic myotomy (POEM) for achalasia involve small sample sizes and single institutions. However, multi-center, large-scale data analyses are lacking. The study aimed to clarify the characteristics of geriatric patients with esophageal motility disorders (EMDs) and determine the procedure-related outcomes and clinical course following POEM. This cohort study included 2,735 patients with EMDs who were treated at seven Japanese facilities between 2010 and 2019. The patients' characteristics and post-POEM clinical courses were compared between the geriatric (age ≥ 75 years; n  = 321) and non-geriatric (age < 75 years; n  = 2,414) groups. Compared with the non-geriatric group, the geriatric group had higher American Society of Anesthesiologists physical status scores; more recurrent cases; lower incidence of chest pain; and higher incidence of type III achalasia, distal esophageal spasm, and Jackhammer esophagus. Furthermore, the incidence of sigmoid esophagus was higher, although esophageal dilation was not severe in this group. POEM was safe and effective for geriatric patients with treatment-naïve and recurrent EMDs. Furthermore, compared with the non-geriatric group, the geriatric group had lower post-POEM Eckardt scores, fewer complaints of refractory chest pain, and a lower incidence rate of post-POEM reflux esophagitis. Geriatric patients are characterized by worse clinical conditions, more spastic disorders, and greater disease progression of EMDs, which are also the indications for minimally invasive POEM. POEM is more beneficial in geriatric patients as it has lowering symptom scores and incidence rates of reflux esophagitis. [ABSTRACT FROM AUTHOR]

Background and Aim: The perioperative management and clinical course of per‐oral endoscopic myotomy for patients receiving antithrombotic therapy remains unknown. This study aimed to clarify the status of antithrombotic therapy in per‐oral endoscopic myotomy and to determine its safety and efficacy. Methods: Patients treated with per‐oral endoscopic myotomy from 2010 to 2019 in seven high‐volume centers in Japan were retrospectively investigated. The patients' characteristics and antithrombotic agent management were analyzed; clinical outcomes were compared with those without antithrombotic agents. Results: Of 2752 patients who underwent per‐oral endoscopic myotomy, 120 patients on antithrombotic therapy (mean age 71.0 years, American Society of Anesthesiologists class II–IV [67.5%]) were identified. Antiplatelet, anticoagulant, and a combination of antithrombotic agents were used in 82, 30, and 8 patients, respectively. The perioperative management adhered to the therapeutic endoscopy guidelines published by the Japanese Society of Gastroenterological Endoscopy in most patients (88.3%). A poorer clinical baseline status (American Society of Anesthesiologists class II–IV; 67.0% vs 24.3%) and the sigmoid type (40.7% vs 22.3%) were more frequently observed in patients with achalasia on antithrombotic therapy. However, the clinical success (Eckardt score ≤ 3; 97.6% vs 94.6) and adverse event rates, such as bleeding and thromboembolic events (5.5% vs 4.7%), did not show inferiority. Conclusions: Per‐oral endoscopic myotomy on antithrombotic therapy is safe and effective. However, caution is required as patients on antithrombotic therapy tend to have poorer baseline health and achalasia statuses. Our experience should help establish perioperative management with antithrombotic therapy. [ABSTRACT FROM AUTHOR]

Background and Aim: Achalasia is a rare disease, with an incidence of one in 100 000. Genetic factors and autoimmune involvement have been reported in its etiology, and their involvement is strongly suspected, especially in patients with familial achalasia and those with comorbid hereditary or autoimmune diseases. However, these special types of achalasia are rare, and their frequency and clinical characteristics remain unclear. Methods: This retrospective, multicenter cohort study included Japanese patients with a diagnosis of achalasia, treated between 2010 and 2019 across six tertiary centers in Japan. The frequency and clinical characteristics of special types of achalasia, namely, familial achalasia, achalasia with a comorbid hereditary disease, and achalasia with a comorbid autoimmune disease, were retrospectively investigated using a large‐scale multicenter database. Results: During the study period, 1115 patients were treated for achalasia at six tertiary centers. Familial achalasia, achalasia with a comorbid hereditary disease, and achalasia with a comorbid autoimmune disease occurred in 7 (0.63%), 11 (0.99%), and 27 (2.4%) patients, respectively. Familial achalasia had a slightly younger age of onset (37.6 ± 12.1 years old) and a higher incidence in male patients (six patients; 85.7%). Down's syndrome was the most common hereditary comorbidity, and thyroid disease was the most common autoimmune comorbidity. Conclusions: We clarified the frequency and clinical characteristics of special types of achalasia. Although special types of achalasia are rare, these comorbidities should be considered when treating patients with achalasia. [ABSTRACT FROM AUTHOR]